2015 Book AdvancedModelsOfNeuralNetworks

Gerasimos G.
Rigatos
Advanced
Models
of Neural
Networks
Nonlinear Dynamics and Stochasticity in
Biological Neurons
Advanced Models of Neural Networks
Gerasimos G. Rigatos
Advanced Models of Neural

Networks
Nonlinear Dynamics and Stochasticity
in Biological Neurons
123
Gerasimos G. Rigatos
Unit of Industrial Automation
Industrial Systems Institute
Rion Patras
Greece
ISBN 978-3-662-43763-6 ISBN 978-3-662-43764-3 (eBook)

DOI 10.1007/978-3-662-43764-3
Springer Heidelberg New York Dordrecht London
Library of Congress Control Number: 2014947828
© Springer-Verlag Berlin Heidelberg 2015

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To Elektra
Preface
This book provides a complete study on neural structures exhibiting nonlinear

and stochastic dynamics. The book elaborates on neural dynamics by introducing
advanced models of neural networks. It overviews the main findings in the mod-
elling of neural dynamics in terms of electrical circuits and examines their stability
properties with the use of dynamical systems theory. Such electric circuit models
are characterized by attractors and fixed points while in certain cases they exhibit
bifurcations and chaotic dynamics. Moreover, solutions of the neural dynamics in
the form of travelling waves equations are derived. The dynamics of interconnected
neurons is analyzed with the use of forced oscillator and coupled oscillator models.
It is shown that by introducing stochastic uncertainty and variations in the previous
deterministic coupled oscillator model, stochastic coupled oscillator models can
be derived. Next, going into a more refined analysis level it is shown how neural
dynamics can be interpreted with the use of quantum and stochastic mechanics.
It is proven that the model of interacting coupled neurons becomes equivalent to
the model of interacting Brownian particles that is associated with the equations
and dynamics of quantum mechanics. It is shown that such neural networks with
dynamics compatible to quantum mechanics principles exhibit stochastic attractors.
Furthermore, the spectral characteristics of such neural networks are analyzed.
Additionally, a stochastic mechanics approach to stabilization of particle systems
with quantum dynamics is presented. It also shown that the eigenstates of the
quantum harmonic oscillator (QHO) can be used as activation functions in neural
networks. Moreover, a gradient-based approach to stabilization of particle systems
with quantum dynamics is provided. There are remarkable new results in the book
concerned with: (1) nonlinear synchronizing control of coupled neural oscillators,
(2) neural structures based on stochastic mechanics or quantum mechanics prin-
ciples, (3) nonlinear estimation of the wave-type dynamics of neurons, (4) neural
and wavelet networks with basis functions localized both in space and frequency,
(5) stochastic attractors in neural structures, and (6) engineering applications of
advanced neural network models.
This book aims at analyzing advanced models of neural networks, starting
with methods from dynamical systems theory and advancing progressively to
vii
viii Preface
stochasticity-based models and models compatible with principles of quantum

mechanics. Advanced models of neural networks enable on the one side to under-
stand patterns of neuronal activity seen in experiments in the area of neuroscience
and on the other side to develop neurocomputing methods in the area of information
sciences that remain consistent with physics principles governing biological neural
structures. The first chapters of the book (Chaps. 1–6) make use of dynamical
systems theory to explain the functioning of neural models. Dynamical systems and
computational methods are widely used in research to study activity in a variety
of neuronal systems. The dynamics of the neural structures are described with the
use of linear or nonlinear ordinary differential equations or with the use of partial
differential equations (PDEs). This approach to neural modelling focuses on the
following issues: (1) Modelling neural networks in terms of electrical circuits (The
Hodgin–Huxley equations. The FitzHugh–Nagumo equations. Ion channels) (2)
Elements of dynamical systems theory: The phase plane. Stability and fixed points.
Attractors, Oscillations. Bifurcations, Chaotic dynamics (3) Chaotic dynamics in
neural excitation. Travelling waves solutions to models of neural dynamics (4)
Neural oscillators (forced oscillators and coupled oscillator models).
The latter chapters of the book (Chaps. 7–13) analyze the significance of noise
and stochasticity in modelling of neuronal dynamics. The dynamics of neural struc-
tures are no longer described by linear or nonlinear ordinary differential equations
or by PDEs but are formulated in terms of stochastic differential equations. Neural
computation based on principles of quantum mechanics can provide improved
models of memory processes and brain functioning and is of primary importance
for the realization of quantum computing machines. To this end, the book studies
neural structures with weights that follow the model of the QHO. The proposed
neural networks have stochastic weights which are calculated from the solution of
Schrödinger’s equation under the assumption of a parabolic (harmonic) potential.
These weights correspond to diffusing particles, which interact with each other
as the theory of Brownian motion (Wiener process) predicts. The learning of the
stochastic weights (convergence of the diffusing particles to an equilibrium) is
analyzed. In the case of associative memories the proposed neural model results
in an exponential increase of patterns storage capacity (number of attractors). It
is also shown that conventional neural networks and learning algorithms based
on error gradient can be conceived as a subset of the proposed quantum neural
structures. Thus, the complementarity between classical and quantum physics can
be also validated in the field of neural computation. Furthermore, in continuation
to modelling of neural networks as interacting Brownian particles it is shown
how stabilization can be succeeded either for particle systems which are modelled
as coupled stochastic oscillators or for particle systems with quantum dynamics.
Finally, engineering applications of the previously described advanced models
of neural dynamics are provided. The book’s chapters are organized as follows:
(1) Modelling biological neurons in terms of electrical circuits, (2) Systems theory
for the analysis of biological neuron dynamics, (3) Bifurcations and limit cycles in
biological neurons, (4) Oscillatory dynamics in biological neurons, (5) Synchroniza-
tion of circadian neurons and protein synthesis control, (6) Wave dynamics in the
Preface ix
transmission of neural signals, (7) Stochastic models of biological neuron dynamics,

(8) Synchronization of stochastic neural oscillators using Lyapunov methods,
(9) Synchronization in coupled stochastic neurons using differential flatness theory,
(10) Attractors in associative memories with stochastic weights, (11) Spectral
analysis of neural models with stochastic weights, (12) Neural networks based
on the eigenstates of the QHO and engineering applications, (13) Gradient-based
feedback control for dynamical systems following the model of the QHO.
A summary of the chapters’ content is given in the following:
In Chap. 1, it is shown that the functioning of the cells membrane can be
represented as an electric circuit. To this end: (1) the ion channels are represented
as resistors, (2) the gradients of the ions concentration are represented as voltage
sources, (3) the capability of the membrane for charge storage is represented as
a capacitor. It is considered that the neurons have the shape of a long cylinder,
or of a cable with specific radius. The Hodgkin–Huxley model is obtained from
a modification of the cables PDE, which describes the change of the voltage
along dendrites axis. Cable’s equation comprises as inputs the currents which
are developed in the ions channels. Other models of reduced dimensionality that
describe voltage variations along the neuron’s membrane are the FitzHugh–Nagumo
model and the Morris–Lecar model. Cable’s equation is also shown to be suitable
for describing voltage variations along dendrites. Finally, the various types of ionic
channels across the neurons’ membrane are analyzed.
In Chap. 2, the main elements of systems theory are overviewed, thus providing
the basis for modelling of biological neurons dynamics. To understand oscillatory
phenomena and consequently the behavior of biological neurons benchmark exam-
ples of oscillators are given. Moreover, using a low order mathematical model of
biological neurons the following properties are analyzed: phase diagram, isoclines,
attractors, local stability, fixed points bifurcations, and chaos properties.
In Chap. 3, a systematic method is proposed for fixed point bifurcation analysis
in biological neurons using interval polynomials theory. The stages for performing
fixed point bifurcation analysis in biological neurons comprise (1) the computation
of fixed points as functions of the bifurcation parameter and (2) the evaluation of the
type of stability for each fixed point through the computation of the eigenvalues of
the Jacobian matrix that is associated with the system’s nonlinear dynamics model.
Stage (3) requires the computation of the roots of the characteristic polynomial
of the Jacobian matrix. This problem is nontrivial since the coefficients of the
characteristic polynomial are functions of the bifurcation parameter and the latter
varies within intervals. To obtain a clear view about the values of the roots of the
characteristic polynomial and about the stability features they provide to the system,
the use of interval polynomials theory and particularly of Kharitonov’s stability
theorem is proposed. In this approach the study of the stability of a characteristic
polynomial with coefficients that vary in intervals is equivalent to the study of the
stability of four polynomials with crisp coefficients computed from the boundaries
of the aforementioned intervals. The efficiency of the proposed approach for the
analysis of fixed point bifurcations in nonlinear models of biological neurons is
tested through numerical and simulation experiments.
x Preface
In Chap. 4, it is shown that the voltage of the neurons membrane exhibits

oscillatory variations after receiving suitable external excitation either when the
neuron is independent from neighboring neural cells or when the neuron is
coupled to neighboring neural cells through synapses or gap junctions. In the latter
case it is significant to analyze conditions under which synchronization between
coupled neural oscillators takes place, which means that the neurons generate the
same voltage variation pattern possibly subject to a phase difference. The loss
of synchronism between neurons can cause several neuro-degenerative disorders.
Moreover, it can affect several basic functions of the body such as gait, respiration,
and hearts rhythm. For this reason synchronization of coupled neural oscillators has
become a topic of significant research during the last years. It is also noted that
the associated results have been used in several engineering applications, such as
biomedical engineering and robotics. For example, synchronization between neural
cells can result in a rhythm generator that controls joints motion in quadruped, multi-
legged, and biped robots.
In Chap. 5, a new method is proposed for synchronization of coupled circadian
cells and for nonlinear control of the associated protein synthesis process using
differential flatness theory and the derivative-free nonlinear Kalman Filter. By
proving that the dynamic model of the synthesis of the FRQ protein (protein
extracted from the frq gene) is a differentially flat one its transformation to the linear
canonical (Brunovsky) form becomes possible. For the transformed model one can
find a state feedback control input that makes the oscillatory characteristics in the
concentration of the FRQ protein vary according to desirable setpoints. To estimate
the nonmeasurable elements of the state vector, a new filtering method named
Derivative-free nonlinear Kalman Filter is used. The Derivative-free nonlinear
Kalman Filter consists of the standard Kalman Filter recursion on the linearized
equivalent model of the coupled circadian cells and of computation of state and
disturbance estimates using the diffeomorphism (relations about state variables
transformation) provided by differential flatness theory. Moreover, to cope with
parametric uncertainties in the model of the FRQ protein synthesis and with stochas-
tic disturbances in measurements, the Derivative-free nonlinear Kalman Filter is
redesigned in the form of a disturbance observer. The efficiency of the proposed
Kalman Filter-based control scheme is tested through simulation experiments.
In Chap. 6, an analysis is given on wave-type PDEs that describe the transmission
of neural signals and proposes filtering for estimating the spatiotemporal variations
of voltage in the neurons’ membrane. It is shown that in specific neuron models the
spatiotemporal variations of the membrane’s voltage follow PDEs of the wave type
while in other models such variations are associated with the propagation of solitary
waves in the membrane. To compute the dynamics of the membrane PDE model
without knowledge of boundary conditions and through the processing of noisy
measurements, the Derivative-free nonlinear Kalman Filter is proposed. The PDE of
the membrane is decomposed into a set of nonlinear ordinary differential equations
with respect to time. Next, each one of the local models associated with the
ordinary differential equations is transformed into a model of the linear canonical
(Brunovsky) form through a change of coordinates (diffeomorphism) which is based
Preface xi
on differential flatness theory. This transformation provides an extended model of

the nonlinear dynamics of the membrane for which state estimation is possible by
applying the standard Kalman Filter recursion. The proposed filtering method is
tested through numerical simulation tests.
In Chap. 7, neural networks are examined in which the synaptic weights cor-
respond to diffusing particles and are associated with a Wiener process. Each
diffusing particle (stochastic weight) is subject to the following forces: (1) a
spring force (drift) which is the result of the harmonic potential and tries to
drive the particle to an equilibrium and (2) a random force (noise) which is the
result of the interaction with neighboring particles. This interaction can be in the
form of collisions or repulsive forces. It is shown that the diffusive motion of
the stochastic particles (weights update) can be described by Fokker–Planck’s,
Ornstein–Uhlenbeck, or Langevins equation which under specific assumptions are
equivalent to Schrödinger’s diffusion equation. It is proven that Langevin’s equation
is a generalization of the conventional gradient algorithms.
In Chap. 8, a neural network with weights described by the interaction of
Brownian particles is considered again. Each weight is taken to correspond to a
Brownian particle. In such a case, neural learning aims at leading a set of M
weights (Brownian particles) with different initial values on the 2D phase plane, to
a desirable final position. A Lyapunov function describes the evolution of the phase
diagram towards the equilibrium Convergence to the goal state is assured for each
particle through the negative definiteness of the associated Lyapunov function. The
update of each neural weight (trajectory in the phase diagram) is affected by (1) a
drift force due to the harmonic potential and (2) the interaction with neighboring
weights (particles). Using Lyapunov methods it is shown that the mean of the
particles converges to the equilibrium while using LaSalle’s theorem it is proven
that the individual particles remain within a small area encircling the equilibrium.
In Chap. 9, examples of chaotic neuronal dynamics are presented first, and
control of chaotic neuron model with the use of differential flatness theory is
explained. Moreover, a synchronizing control method is presented for neurons
described again as particle systems and modeled as coupled stochastic oscillators.
The proposed synchronization approach is flatness-based control. The kinematic
model of the particles is associated with the model of the QHO and stands for a
differentially flat system. It is also shown that after applying flatness-based control
the mean of the particle system can be steered along a desirable path with infinite
accuracy, while each individual particle can track the trajectory within acceptable
accuracy levels.
In Chap. 10, neural associative memories are considered in which the elements
of the weight matrix are taken to be stochastic variables. The probability density
function of each weight is given by the solution of Schrödinger’s diffusion equation.
The weights of the proposed associative memories are updated with the use of a
learning algorithm that satisfies quantum mechanics postulates. The learning rule
is proven to satisfy two basic postulates of quantum mechanics: (1) existence in
superimposing states and (2) evolution between the superimposing states with the
use of unitary operators. Therefore it can be considered as a quantum learning
xii Preface
algorithm. Taking the elements of the weight matrix of the associative memory
to be stochastic variables means that the initial weight matrix can be decomposed
into a superposition of associative memories. This is equivalent to mapping the
fundamental memories (attractors) of the associative memory into the vector spaces
which are spanned by the eigenvectors of the superimposing matrices and which
are related to each other through unitary rotations. In this way, it can be shown that
the storage capacity of the associative memories with stochastic weights increases
exponentially with respect to the storage capacity of conventional associative
memories.
In Chap. 11, spectral analysis of neural networks with stochastic weights (stem-
ming from the solution of Schrödinger’s diffusion equation) is performed. It is
shown that: (1) The Gaussian basis functions of the weights express the distribution
of the energy with respect to the weights’ value. The smaller the spread of the basis
functions is, the larger becomes the spectral (energy) content that can be captured
therein. Narrow spread of the basis functions results in wide range of frequencies of
a Fourier-transformed pulse (2) The stochastic weights satisfy an equation which is
analogous to the principle of uncertainty.
In Chap. 12, feedforward neural networks with orthogonal activation functions
(Hermite polynomials) which come from the solution of Schrödinger’s diffusion
equation are considered. These neural networks have significant properties: (1) the
basis functions are invariant under the Fourier transform, subject only to a change
of scale, (2) the basis functions are the eigenstates of the QHO and stem from
the solution of Schrödinger’s harmonic equation. The proposed neural networks
have performance that is equivalent to wavelet networks and belong to the general
category of nonparametric estimators. They can be used for function approximation,
image processing, and system fault diagnosis. The considered basis functions are
also analyzed with respect to uncertainty principles and the Balian–Low theorem.
In Chap. 13, the interest is in control and manipulation of processes at molecular
scale, as the ones taking place in several biological and neuronal systems. To this
end, a gradient method is proposed for feedback control and stabilization of particle
systems using Schrödinger’s and Lindblad’s descriptions. The eigenstates of the
quantum system are defined by the spin model. First, a gradient-based control
law is computed using Schrödinger’s description. Next, an estimate of state of the
quantum system is obtained using Lindblad’s differential equation. In the latter case,
by applying Lyapunov’s stability theory and LaSalle’s invariance principle one can
compute a gradient control law which assures that the quantum system’s state will
track the desirable state within acceptable accuracy levels. The performance of the
control loop is studied through simulation experiments for the case of a two-qubit
quantum system.
The book contains teaching material that can be used in several undergraduate
or postgraduate courses in university schools of engineering, computer science,
mathematics, physics, and biology. The book can be primarily addressed to final
year undergraduate students and to first years postgraduate students pursuing studies
in electrical engineering, computer science as well as in physics, mathematics, and
biology. The book can be also used as a main reference in upper level courses on
Preface xiii
machine learning, artificial intelligence, and computational intelligence as well as

a complementary reference in upper level courses on dynamical systems theory.
Moreover, engineers and researchers in the areas of nonlinear dynamical systems,
artificial and computational intelligence, and machine learning can get profit from
this book which analyzes advanced models of neural networks and which goes
beyond the common information representation schemes with the use of artificial
neural networks.
Acknowledgements
The author would like to thank research associates and colleagues who have con-
tributed to the preparation of this book either explicitly or implicitly. Discussions,
exchange of ideas, and reviewing of research work from people working in the field
have given the motivation for an in-depth analysis of the topic of Advanced Models
of Neural Networks and have provided a useful feedback while editing and revising
this book.
Athens, Greece Gerasimos G. Rigatos

October 2013
Contents
1 Modelling Biological Neurons in Terms of Electrical Circuits. . . . . . . . . 1

1.1 The Hodgkin–Huxley Equations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1.1 Nernst’s Equation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.1.2 The Goldman–Hodgkin–Katz Equation . . . . . . . . . . . . . . . . . . . 4
1.2 Equivalent Circuits of the Cell’s Membrane . . . . . . . . . . . . . . . . . . . . . . . . 5
1.2.1 The Electric Equivalent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.2.2 Membrane’s Time Constant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.3 Describing Membrane’s Voltage Dynamics
with Cable’s Equation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
1.4 The Hodgkin–Huxley Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.4.1 Derivation of the Hodgkin–Huxley Model . . . . . . . . . . . . . . . . 12
1.4.2 Outline of the Hodgkin–Huxley Equations. . . . . . . . . . . . . . . . 13
1.5 The FitzHugh–Nagumo Model of Neurons . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.6 The Morris–Lecar Model of Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.7 Modelling Dendrites in Terms of Electrical Circuits . . . . . . . . . . . . . . . 16
1.7.1 Dendrites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
1.7.2 Computing Cable’s Equation in Neurons. . . . . . . . . . . . . . . . . . 18
1.7.3 The Infinite Length Cable . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
1.8 Ion Channels and Their Characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
1.8.1 Types of Ion Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
1.8.2 Sodium Channels NaC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
1.8.3 Calcium Channels Ca2C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
1.8.4 Voltage-Gated Potassium Channels KC . . . . . . . . . . . . . . . . . . . 23
1.8.5 Voltage Sags . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
1.8.6 Currents and Concentration of Ions. . . . . . . . . . . . . . . . . . . . . . . . 24
1.8.7 Calcium-Dependent Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
1.9 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
xv
xvi Contents
2 Systems Theory for the Analysis of Biological Neuron Dynamics. . . . . 27

2.1 Characteristics of the Dynamics of Nonlinear Systems . . . . . . . . . . . . 27
2.2 Computation of Isoclines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2.3 Systems Theory and Neurodynamics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.3.1 The Phase Diagram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.3.2 Stability Analysis of Nonlinear Systems . . . . . . . . . . . . . . . . . . 34
2.3.3 Stability Analysis of the Morris–Lecar
Nonlinear Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
2.4 Phase Diagrams and Equilibria of Neuronal Models . . . . . . . . . . . . . . . 38
2.4.1 Phase Diagrams for Linear Dynamical Systems . . . . . . . . . . 38
2.4.2 Multiple Equilibria for Nonlinear Dynamical Systems . . . 40
2.4.3 Limit Cycles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
2.5 Bifurcations in Neuronal Dynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
2.5.1 Bifurcations of Fixed Points of Biological
Neuron Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
2.5.2 Saddle-Node Bifurcations of Fixed Points
in a One-Dimensional System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
2.5.3 Pitchfork Bifurcation of Fixed Points . . . . . . . . . . . . . . . . . . . . . 47
2.5.4 The Hopf Bifurcation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
2.6 Chaos in Neurons. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
2.6.1 Chaotic Dynamics in Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
2.6.2 Chaotic Dynamics in Associative Memories . . . . . . . . . . . . . . 51
2.7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
3 Bifurcations and Limit Cycles in Models of Biological Systems . . . . . . . 53
3.1 Outline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
3.2 Generalization of the Routh–Hurwitz Criterion
with Kharitonov’s Theorem. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
3.2.1 Application of the Routh Criterion to Systems
with Parametric Uncertainty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
3.2.2 An Application Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
3.3 Stages in Bifurcations Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
3.4 Bifurcation Analysis of the FitzHugh–Nagumo Neuron . . . . . . . . . . . 58
3.4.1 Equilibria and Stability
of the FitzHugh–Nagumo Neuron . . . . . . . . . . . . . . . . . . . . . . . . . 58
3.4.2 Condition for the Appearance of Limit Cycles. . . . . . . . . . . . 60
3.5 Bifurcation Analysis of Circadian Oscillators . . . . . . . . . . . . . . . . . . . . . . 61
3.5.1 Fixed Points Bifurcation Analysis Using
Kharitonov’s Theory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
3.5.2 Method to Detect Hopf Bifurcations
in the Circadian Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.6 Feedback Control of Bifurcations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
3.7 Simulation Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
3.8 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Contents xvii
4 Oscillatory Dynamics in Biological Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

4.1 Neural Oscillators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
4.2 Synaptic Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
4.3 Dynamics of the Synapses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
4.4 Study of the Glutamate Neurotransmitter . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
4.5 Study of the GABA Neurotransmitter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
4.6 Short- and Long-Term Plasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
4.7 Synchronization of Coupled FitzHugh–Nagumo
Neurons Using Differential Flatness Theory . . . . . . . . . . . . . . . . . . . . . . . . 83
4.7.1 The Problem of Synchronization of Coupled
Neural Oscillators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
4.7.2 Coupled Neural Oscillators as Coordinators
of Motion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
4.8 Differential Flatness Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
4.8.1 Definition of Differentially Flat Systems . . . . . . . . . . . . . . . . . . 86
4.8.2 Conditions for Applying Differential Flatness Theory . . . 87
4.8.3 Transformation of the Neurons’ Model into
the Linear Canonical Form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
4.9 Linearization of the FitzHugh–Nagumo Neuron . . . . . . . . . . . . . . . . . . . 89
4.9.1 Linearization of the FitzHugh–Nagumo
Model Using a Differential Geometric Approach . . . . . . . . . 89
4.9.2 Linearization of the FitzHugh–Nagumo
Model Using Differential Flatness Theory . . . . . . . . . . . . . . . . 91
4.10 Linearization of Coupled FitzHugh–Nagumo Neurons
Using Differential Geometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Using Differential Flatness Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
4.11.1 Differential Flatness of the Model
of the Coupled Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
4.11.2 Linearization of the Coupled Neurons Using
Differential Flatness Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
4.12 State and Disturbances Estimation
with the Derivative-Free Nonlinear Kalman Filter . . . . . . . . . . . . . . . . . 98
4.12.1 Kalman and Extended Kalman Filtering . . . . . . . . . . . . . . . . . . 98
4.12.2 Design of a Disturbance Observer
for the Model of the Coupled Neurons . . . . . . . . . . . . . . . . . . . . 100
4.12.3 Disturbances Compensation for the Model
of the Coupled Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
4.14 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
xviii Contents
5 Synchronization of Circadian Neurons and Protein

Synthesis Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
5.1 Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
5.2 Modelling of Circadian Oscillators Dynamics . . . . . . . . . . . . . . . . . . . . . . 109
5.2.1 The Functioning of the Circadian Oscillators . . . . . . . . . . . . . 109
5.2.2 Mathematical Model of the Circadian Oscillator . . . . . . . . . 111
5.3 Protein Synthesis Control Using Differential Geometry
Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
5.4 Protein Synthesis Control Using Differential Flatness Theory. . . . . 114
5.4.1 Differential Flatness of the Circadian Oscillator . . . . . . . . . . 114
5.4.2 Transformation into a Canonical Form . . . . . . . . . . . . . . . . . . . . 115
5.5 Robust Synchronization of Coupled Circadian
Oscillators Using Differential Geometry Methods . . . . . . . . . . . . . . . . . 118
Oscillators Using Differential Flatness Theory . . . . . . . . . . . . . . . . . . . . . 120
5.7 State Estimation and Disturbances Compensation
with the Derivative-Free Nonlinear Kalman Filter . . . . . . . . . . . . . . . . . 124
5.9 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
6 Wave Dynamics in the Transmission of Neural Signals . . . . . . . . . . . . . . . . 131
6.1 Outline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
6.2 Propagating Action Potentials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
6.3 Dynamics of the Solution of the Wave PDE . . . . . . . . . . . . . . . . . . . . . . . . 133
6.4 Myelinated Axons and Discrete Diffusion . . . . . . . . . . . . . . . . . . . . . . . . . . 133
6.4.1 Solitons in Neuron’s Dynamical Model . . . . . . . . . . . . . . . . . . . 135
6.4.2 Comparison Between the Hodgkin–Huxley
and the Soliton Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
6.5 Estimation of Nonlinear Wave Dynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
6.6.1 Evaluation Experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
6.6.2 Assessment of the Filter’s Performance . . . . . . . . . . . . . . . . . . . 145
6.7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
7 Stochastic Models of Biological Neuron Dynamics . . . . . . . . . . . . . . . . . . . . . 149
7.1 Outline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
7.2 Wiener Process and Its Equivalence to Diffusion . . . . . . . . . . . . . . . . . . . 150
7.2.1 Neurons’ Dynamics Under Noise . . . . . . . . . . . . . . . . . . . . . . . . . . 150
7.2.2 Wiener Walk and Wiener Process. . . . . . . . . . . . . . . . . . . . . . . . . . 151
7.2.3 Outline of Wiener Process Properties. . . . . . . . . . . . . . . . . . . . . . 152
7.2.4 The Wiener Process Corresponds
to a Diffusion PDE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
7.2.5 Stochastic Integrals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
7.2.6 Ito’s Stochastic Differential Equation . . . . . . . . . . . . . . . . . . . . . 153
Contents xix
7.3 Fokker–Planck’s Partial Differential Equation . . . . . . . . . . . . . . . . . . . . . . 154

7.3.1 The Fokker–Planck Equation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
7.3.2 First Passage Time . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
7.3.3 Meaning of the First Passage Time . . . . . . . . . . . . . . . . . . . . . . . . 155
7.4 Stochastic Modelling of Ion Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
7.5 Fokker–Planck Equation and the Integrate-and-Fire
Neuron Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
7.5.1 The Integrate-and-Fire Neuron Model . . . . . . . . . . . . . . . . . . . . . 157
7.5.2 Stochastic Integrate-and-Fire Neuron Model
and the Fokker–Planck Equation. . . . . . . . . . . . . . . . . . . . . . . . . . . 160
7.5.3 Rate of Firing for Neural Models . . . . . . . . . . . . . . . . . . . . . . . . . . 161
7.6 Stochasticity in Neural Dynamics and Relation
to Quantum Mechanics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
7.6.1 Basics of Quantum Mechanics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
7.6.2 Schrödinger’s Equation with Non-zero
Potential and Its Equivalence to Diffusion with Drift . . . . . 163
7.6.3 Study of the QHO Model Through
the Ornstein–Uhlenbeck Diffusion . . . . . . . . . . . . . . . . . . . . . . . . 164
7.6.4 Particle’s Motion Is a Generalization
of Gradient Algorithms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
7.7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
8 Synchronization of Stochastic Neural Oscillators Using
Lyapunov Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
8.1 Representation of the Neurons’ Dynamics as Brownian
Motion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
8.2 Interacting Diffusing Particles as a Model of Neural Networks . . . 171
8.2.1 Weights’ Equivalence to Brownian Particles . . . . . . . . . . . . . . 171
8.2.2 Stability Analysis for a Neural Model
with Brownian Weights . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
8.3 Convergence of the Stochastic Weights to an Equilibrium . . . . . . . . . 178
8.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
9 Synchronization of Chaotic and Stochastic Neurons Using
Differential Flatness Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
9.1 Chaotic Neural Oscillators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
9.1.1 Models of Chaotic Oscillators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
9.1.2 Differential Flatness of Chaotic Oscillators . . . . . . . . . . . . . . . 182
9.2 Stabilization of Interacting Particles Which
Are Modelled as Coupled Stochastic Oscillators . . . . . . . . . . . . . . . . . . . 184
9.3 Some Examples on Flatness-Based Control of Coupled
Oscillators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
9.4 Flatness-Based Control for the Multi-Particle System . . . . . . . . . . . . . 187
9.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
xx Contents
10 Attractors in Associative Memories with Stochastic Weights . . . . . . . . . 191

10.1 Weights Learning in Associative Memories Is a Wiener
Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
10.1.1 The Weights of Associative Memories Are
Equivalent to Brownian Particles . . . . . . . . . . . . . . . . . . . . . . . . . . 191
10.1.2 Mean Value and Variance of the Brownian Weights . . . . . . 193
10.1.3 Learning Through Unitary Quantum
Mechanical Operators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
10.2 Attractors in QHO-Based Associative Memories. . . . . . . . . . . . . . . . . . . 196
10.2.1 Decomposition of the Weight Matrix
into a Superposition of Matrices . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
10.2.2 Evolution Between the Eigenvector Spaces
via Unitary Rotations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
10.2.3 Applications of the Stochastic Associative
Memory Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
10.3 Attractors in Associative Memories with Stochastic Weights. . . . . . 200
10.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
11 Spectral Analysis of Neural Models with Stochastic Weights . . . . . . . . . 207
11.1 Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
11.2 Wavelet Basis Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
11.2.1 Wavelet Frames . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
11.2.2 Dyadic Grid Scaling and Orthonormal
Wavelet Transforms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
11.2.3 The Scaling Function and the Multi-resolution
Representation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
11.2.4 Examples of Orthonormal Wavelets . . . . . . . . . . . . . . . . . . . . . . . 211
11.2.5 The Haar Wavelet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
11.3 Spectral Analysis of the Stochastic Weights . . . . . . . . . . . . . . . . . . . . . . . . 214
11.3.1 Spectral Analysis of Wavelets. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
11.3.2 Energy Spectrum of the Stochastic Weights. . . . . . . . . . . . . . . 216
11.3.3 Stochastic weights and the Principle of Uncertainty . . . . . . 218
11.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
12 Neural Networks Based on the Eigenstates of the Quantum
Harmonic Oscillator. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
12.1 Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
12.2 Feed-Forward Neural Networks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
12.3 Eigenstates of the Quantum Harmonic Oscillator . . . . . . . . . . . . . . . . . . 224
12.4 Neural Networks Based on the QHO Eigenstates . . . . . . . . . . . . . . . . . . 225
12.4.1 The Gauss–Hermite Series Expansion. . . . . . . . . . . . . . . . . . . . . 225
12.4.2 Neural Networks Based on the Eigenstates
of the 2D Quantum Harmonic Oscillator . . . . . . . . . . . . . . . . . . 226
Contents xxi
12.5 Uncertainty Principles for the QHO-Based Neural Networks . . . . . 228

12.5.1 Uncertainty Principles for Bases
and the Balian–Low Theorem. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
12.5.2 Uncertainty Principles for Hermite Series . . . . . . . . . . . . . . . . . 229
12.6 Multiscale Modelling of Dynamical System . . . . . . . . . . . . . . . . . . . . . . . . 230
12.7 Applications to Image Compression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
12.8 Applications to Fault Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
12.8.1 Signals Power Spectrum and the Fourier Transform . . . . . . 242
12.8.2 Power Spectrum of the Signal Using
the Gauss–Hermite Expansion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
12.8.3 Detection of Changes in the Spectral Content
of the System’s Output . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
12.9 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
13 Quantum Control and Manipulation of Systems
and Processes at Molecular Scale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
13.1 Basics of Quantum Systems Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
13.2 The Spin as a Two-Level Quantum System . . . . . . . . . . . . . . . . . . . . . . . . . 252
13.2.1 Description of a Particle in Spin Coordinates . . . . . . . . . . . . . 252
13.2.2 Measurement Operators in the Spin State-Space. . . . . . . . . . 253
13.2.3 The Spin Eigenstates Define a Two-Level
Quantum System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
13.3 The Lindblad and Belavkin Description of Quantum Systems . . . . 254
13.3.1 The Lindblad Description of Quantum Systems . . . . . . . . . . 254
13.3.2 The Belavkin Description of Quantum Systems . . . . . . . . . . 255
13.3.3 Formulation of the Control Problem . . . . . . . . . . . . . . . . . . . . . . . 256
13.4 A Feedback Control Approach for Quantum System
Stabilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
13.4.1 Control Law Calculation Using Schrödinger’s
Equation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
13.4.2 Control Law Calculation Using Lindblad’s Equation. . . . . 258
13.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
Acronyms
FHN FitzHugh–Nagumo neurons

EEG Electroengephalogram
CPG Central pattern generators
GABA Gamma aminobutyric acid
KF Kalman filtering
EKF Extended Kalman filtering
DKF Derivative-free nonlinear Kalman filter
MIMO Multi input multi output
CDK Cycline dependent kinases
MRNA Messenger RNA
PDE Partial differential equations
QHO Quantum harmonic oscillator
CLT Central limit theorem
FNN Feedforward neural networks
FDI Fault detection and isolation
xxiii
Chapter 1
Modelling Biological Neurons in Terms
of Electrical Circuits
Abstract The functioning of the cells membrane can be represented as an electric

circuit. To this end: (1) the ion channels are represented as resistors, (2) the gradients
of the ions concentration are represented as voltage sources, (3) the capability of
the membrane for charge storage is represented as a capacitor. It is considered
that the neurons have the shape of a long cylinder, or of a cable with specific
radius. The Hodgkin–Huxley model is obtained from a modification of the cable’s
PDE, which describes the change of the voltage along dendrites axis. Cable’s
equation comprises as inputs the currents which are developed in the ions channels.
Other models of reduced dimensionality that describe voltage variations along the
neuron’s membrane are the FitzHugh–Nagumo model and the Morris–Lecar model.
Cable’s equation is also shown to be suitable for describing voltage variations along
dendrites. Finally, the various types of ionic channels across the neurons’ membrane
are analyzed.
1.1 The Hodgkin–Huxley Equations
In neural cells there is a voltage difference appearing between the inner and the
outer side of the membrane
VM D Vin Vout (1.1)
where Vin is the voltage at the inner part of the cell, Vout is the voltage at the outer
part of the cell, and VM is the membrane potential. The term “resting potential”
describes the membrane’s voltage when the cell is in rest and has an approximate
value of 70 mV.
In the neural cell two types of current are developed: The incoming current is
associated with the inflow of NaC ions and has as a result to raise the cell’s potential
(approaching to 0 mV). The outgoing current is associated with the outflow of KC
ions, or with the inflow of Cl ions and has as a result to reduce significantly the
cell’s potential.
G.G. Rigatos, Advanced Models of Neural Networks, 1

DOI 10.1007/978-3-662-43764-3__1, © Springer-Verlag Berlin Heidelberg 2015
2 1 Modelling Biological Neurons in Terms of Electrical Circuits
Fig. 1.1 Ionic currents in cell’s membrane: inflow of NaC and Cl and outflow of KC
The structural component of the membrane are lipids and proteins and based on
these an explanation of its conductivity features can be provided (Fig. 1.1). Lipids
prohibit current’s conduction whereas proteins enable ions to go through them, thus
forming ion channels.
There are two types of ion channels, the gated and the non-gated ones. The non-
gated ion channels are always open. The gated ion channels switch from the open to
the closed status according to a probability that depends on the membrane’s potential
(voltage-gated channels).
When the cell’s membrane is in rest the gated channels remain closed and the
associated resting potential of the membrane is due only to ions getting through
the non-gated channels. When specific gates in the membrane are open there is an
inflow of NaC and Cl and an outwards motion of KC . The inflow of ions continues
until an equilibrium condition is reached, i.e. until the concentration of positive ions
in the inner part of the membrane becomes equal to the concentration of ions to
the outer part of the membrane (equivalent is the equilibrium condition for negative
ions).
The balance mechanism in the inflow or outflow of ions is as follows: It is
assumed that there is an outflow of ions KC towards the outer part of the membrane.
In the inner part of the membrane there is a surplus of positive charges while in
the outer part of the membrane there is a surplus of negative charges (organic ions
A ). The outflow of the KC ions continues until there is an equalization of the
concentration of positive and negative charges in the inner and outer part of the
membrane.
1.1 The Hodgkin–Huxley Equations 3
The equilibrium in the inflow or outflow of charges is reached according to

Nernst’s conditions [16]:
C
ŒK in
EK D RT
zF
ln ŒK C (1.2)
out
where EK is the KC Nernst’s potential, ŒKC in is the concentration of the KC ions
in the inner part of the membrane, ŒKC out is the concentration of the KC ions in the
outer part of the membrane, R is a gas constant, F is the Faraday constant, z is the
valence of KC , and T is the absolute temperature in Kelvin.
When the neurons are at rest their membrane is permeable to ions of the KC ,
Na , and Cl type. In the equilibrium condition the number of open channels for
C
ions of the KC or Cl type is larger than the number of the open channels for ions
of the NaC type. The equilibrium potential of the neuron’s membrane depends on
the Nerst potential of the KC and Cl ions.
The exact relation that connects the membrane’s potential to ions concentrations
in its inner and outer part results from the Goldman–Hodgkin–Katz equation. The
inflow and outflow of ions continues until the associated voltage gradients become
zero (there is a voltage gradient for the positive ions NaC and KC and a voltage
gradient for the negative ions Cl ). Voltage gradients are also affected by ion
pumps, that is channels through which an exchange of specific ions takes place.
For example, the NaC -KC pump is a protein permeable by ions which enables the
exchange of 3NaC with 2KC . As long as there is a non-zero gradient due to the
concentration of KC in the inner and outer part of the membrane the outflow of
these ions continues.
For instance, when the concentration of positive ions KC in the outer part of the
membrane raises there is an annihilation of the gradient that forces the KC ions to
move outwards. This has as a result, an equilibrium condition to be finally reached.
1.1.1 Nernst’s Equation
The following notations are used next: ŒC x is the concentration of ions in the
membrane, V .x/ is the membrane’s potential at point x, along the membrane. Then
according to Fick’s diffusion law one has about the diffusive flux Jdiff [16, 65]
Jdiff D D @ŒC
@x

(1.3)
where D is the diffusion constant (cm2 /s) and ŒC in the concentration of molecules
(ions) N=cm3 . Moreover, there is a force that is responsible for the drift motion of
the molecules [16, 65]
Jdrift D zŒC @V
@x
(1.4)
where E D @V@x
is the electric field and z is the valence of the ion, that is ˙1; ˙2,
etc. and parameter is the so-called mobility and is measured in cm3 /V s. The
aggregate flow through the membrane is given by the relation
Jtotal D D @ŒC
@x

zŒC @V
@x
(1.5)
The diffusion coefficient that appears in the aforementioned equations is given by
DD kT
q
(1.6)
where k is the Boltzmann constant, T denotes the absolute temperature, and q is the
electric charge (measured in Coulombs). Therefore the aggregate flux can be written
as
@ŒC
Jtotal D kT
q @x
zŒC @V
@x (1.7)
Multiplying this current flux with the valence and Faraday’s constant and using
RT=F in place of kT=q one has [16, 65]

I D zRT @ŒC
@x

z 2
F ŒC @V
@x
(1.8)
This is the Nernst–Planck equation describing current flow through the membrane.
Nernst’s equation is obtained setting the current in Nernst–Planck equation to be
equal to zero (I D 0). That is, at equilibrium condition of the diffusion and electric
effects is reached. Thus, after intermediate operations one has the Nernst potential
equation

ŒCin
Veq D Vin Vout D RT
zF
ln ŒCout
(1.9)
1.1.2 The Goldman–Hodgkin–Katz Equation
Under the assumption that the electric field across the lipid membrane remains
constant one has [16, 65]
E D VlM and dV
dx
D VM
l
(1.10)
The mobility of ions across the membrane is denoted by u . The aqueous concen-
tration of ions is denoted by ŒC and the concentration of ions on the membrane is
denoted as ˇŒC . The Nernst–Planck equation for current flow across the membrane
becomes
I D u z2 FˇŒC VlM u zRTˇ ddx

ŒC
0<x<l (1.11)
1.2 Equivalent Circuits of the Cell’s Membrane 5
with boundary conditions ŒC .0/ D ŒC in and ŒC .l/ D ŒC out . Using these
boundary conditions the solution for the Nernst–Planck equation becomes

u z2 F VM ˇ ŒC out e ŒC in
I D l e l
(1.12)
where D zVM F
RT
. By defining the membrane’s permeability as
ˇu RT
P D lF
(1.13)
one obtains that the current’s equation through the membrane becomes

ŒC out e ŒC in
I D P zF e 1
(1.14)
It is assumed now that there is flow of a large number of ions, e.g. KC , NaC , and
Cl . At the equilibrium condition, the current through the membrane drops to zero,
i.e. it holds
I D IK C INa C ICl D 0 (1.15)
The potential of the membrane for which the zeroing of the current I takes place is
n o
PK ŒKC out CPNa ŒNaC out CPCl ŒClin
VM D RT
F
ln PK ŒKC in CPNa ŒNaC in CPCl ŒClout
(1.16)
where variables PK , PNa , and PCl denote the associated permeabilities. Equa-
tion (1.16) is the Goldman–Hodgkin–Katz and the associated voltage is measured
in mV.
1.2 Equivalent Circuits of the Cell’s Membrane
1.2.1 The Electric Equivalent
The functioning of the cell’s membrane can be represented as an electric circuit.

To this end: (1) the ion channels are represented as resistors, (2) the gradients of
the ions’ concentration are represented as voltage sources, (3) the capability of the
membrane for charge storage is represented as a capacitor (Fig. 1.2). This is depicted
in the following diagram:
For the charge that is stored in the membrane it holds
q D C M VM (1.17)
Fig. 1.2 Electric equivalent of the cell’s membrane
Fig. 1.3 Equivalent circuit of cell’s membrane
Voltage VM is computed from the Goldman–Hodgkin–Katz equation and CM is

the membrane’s capacity. The normalized membrane capacity (capacity per cm2 ) is
noted as cM . Considering the equivalent circuit of Fig. 1.3 it holds that
dq
I D dt
(1.18)
and
IOk D VM Ek
Rk
)IOk D gO k .VM Ek / (1.19)
where gO k is the conductance normalized per unit of surface.

The above holds for one channel of ions. Assume now that there are Nk channels
of ions. The aggregate resistance of the circuit is Nk Rk D rk . Then the current
through the ions’ channel is written as
1.2 Equivalent Circuits of the Cell’s Membrane 7
Fig. 1.4 Electric circuit consisting of ion channels in cell’s membrane
VM Ek
Ik D rk (1.20)
By applying Kirchhoff’s law in the loop, in the transient stage, one gets [16, 65]
.VM Ek /
Icapac C Ik )cM dVdtM C rk
D0 (1.21)
that is
cM dVdtM D VMrE
k
k
D gk .VM Ek / (1.22)
For example, in the case of N D 3 ion channels of the Cl, K and Na type it holds
that the aggregate ions current is
Iion D VMRE
Cl
Cl
VM EK
RK
VM ENa
RNa (1.23)
or using the normalized conductance coefficients gCl , gK , and gNa and the normal-
ized capacitance cM one has
Iion D gCl .VM ECl / gK .VM EK / gNa .VM ENa / (1.24)
Equivalently, assuming an external input current I (normalized per surface of the

membrane), it holds that [16, 65]
I.t/
cM d VdtM D gCl .VM ECl / gK .VM EK / gNa .VM ENa / C A
(1.25)
where A denoted membrane’s surface (Fig. 1.4). Using the notation

ER D .gCl ECl C gK EK C gNa ENa /rM (1.26)

1
rM D (1.27)
gCl C gK C gNa
it holds that
cM d VdtM D .VMrE
M
R/
C I.t/
A
(1.28)
Considering that the conductance coefficients are constants and that the currents
have reached their steady state one obtains
gCl ECl CgK EK CgNa ENa CI =A

Vss D gCl CgK CgNa (1.29)
Therefore, in case that there is no external current, the membrane’s voltage VM in

the steady state is the weighted sum of the equilibrium potentials ECl , EK , and ENa
(according to Nernst’s equation) for the three ionic channels.
1.2.2 Membrane’s Time Constant
It is assumed that the external current applied to the membrane is I.t / D I0 between
time instant t D 0 and t D T . Assuming that the cell’s shape is approximated by a
sphere with surface A D 42 , the normalized (over surface and time unit) current
is
(
I0
I.t / if 0t < T
IM .t / D D 42 (1.30)
42 0 otherwise
Using Eq. (1.28) and considering ER D 0 for the membrane’s potential, the
following partial differential equation holds
cM dVdtM D VrMM C IM .t / (1.31)
Solving the differential equation with respect to VM .t / one obtains the change in
time of the membrane’s potential which is described by Eq. (1.32) and is depicted
in Fig. 1.5
( t
rM I0
.1 e m / for 0 < t < T
VM .t / D 42
t
(1.32)
VM .T /e M for t > T
1.3 Describing Membrane’s Voltage Dynamics with Cable’s Equation 9
0.16
0.14
0.12
0.1
VM
0.08
0.06
0.04
0.02
0
10 20 30 40 50 60 70 80
time
Fig. 1.5 Diagram of membrane’s voltage variation
1.3 Describing Membrane’s Voltage Dynamics with Cable’s

Equation
The previous analysis has considered that the neurons have a spherical shape. This
assumption does not hold for neurons’ axon and in the case of neurons’ dendrites
where the neurons’ shape is better approximated by a cylinder. In the latter case it
is considered that the neurons have the shape of a long cylinder or cable, or cable of
radius a as depicted in Fig. 1.6.
The equation of the membrane’s voltage according to the cable’s model is a
partial differential equation that describes the voltage’s spatiotemporal variation
VM .x; t /. Voltage VM .x; t / depends also on the coaxial currents IL that pass
through the cell [21].
The aggregate resistance of the cable, for radius a and length x is given by
RL D rL x
˛ 2
(1.33)
where rL is a special resistance. According to Ohm’s law, for the change of voltage
along the cables’s axis holds [16, 65]
VM .x C x; t / VM .x; t / D IL .x; t /RL D IL .x; t / x r

˛2 L
(1.34)
Fig. 1.6 Cable equivalent circuit of the neuron’s membrane
Fig. 1.7 Currents of the membrane at point x
Therefore, for x !0 it holds

2
IL .x; t / D ˛
rL
@VM
@x
.x; t / (1.35)
Assuming that along the cable (dendrite) there are parallel ion channels, which are
noted by the resistance RM , for the variation of the current along the neuron’s axis
it holds (see Fig. 1.7).
IL .x C x; t / D IL .x; t / Iion .x; t / Icap .x; t / (1.36)

1.3 Describing Membrane’s Voltage Dynamics with Cable’s Equation 11
or equivalently
Icap .x; t / C Iion .x; t / D IL .x C x; t / C IL .x; t / (1.37)
out of which one obtains [16, 65]

@VM
.2 ˛x/cM C .2 ˛x/iion
@t
˛ 2 @VM ˛ 2 @VM
D .x C x; t / .x; t / (1.38)
rL @x rL @x
After dividing both sides of the equation with 2 ˛x and taking x)0 cable’s
equation is produced
˛ @2 VM
cM @V@tM D 2rL @x 2
iion (1.39)
VM .x;t/
Setting iion D rM
one gets
˛ @2 VM
cM @V@tM D 2rL @x 2
VM
rM
(1.40)
Cable’s equation for the neural cell is formulated as follows [16, 65]
2
M @V@tM D 2 @@xVM
2 VM (1.41)
q
where D ar M
2rL
and M D cM rM .
Next, it is assumed that the neural cell has the form of a semi-infinite cable
for x > 0, in which a step current IM .0/ D I0 is injected, while the associated
boundary condition is VM .0/. The solution of the partial differential equation given
in Eq. (1.41) provides the spatiotemporal variation of the voltage V .x; t /.
By examining the solution of the PDE in steady state, i.e. when @V@tM D 0, the
partial differential equation becomes an ordinary differential equation of the form
2
2 ddxV2ss Vss D 0 (1.42)
2
From Eq. (1.35), using that I0 D ˛
rL
@VM
@x
one obtains the boundary condition
dV ss
dx
.0/ D ˛
rL
2 I0 (1.43)
while another boundary condition is that V tends to 0 as x!1. The solution of the
steady state (spatial component) of the cable equation is finally written as
rL I0 x
Vss .x/ D ˛ 2
e (1.44)
Time constant affects the variation of voltage.

Fig. 1.8 Membrane’s circuit

currents
1.4 The Hodgkin–Huxley Model
1.4.1 Derivation of the Hodgkin–Huxley Model
The Hodgkin–Huxley model is obtained from a modification of the cable’s PDE,

which describes the change of the voltage V .x; t / along dendrites’ axis. It holds
that [15, 39]
IL D Icap C Iion (1.45)
Cable’s equation comprises as inputs the currents which are developed in the ions’
channels
˛ @2 VM
2rL @2 x 2
D cM @V@tM C IK C INa C IL (1.46)
which can be also written in the following form
˛ @2 VM
cM @V@tM D 2rL @2 x 2
gK .VM EK / gN .VM ENa / gL .VM EL / (1.47)
where gk is the conductance of the KC channel, gNa is the conductance of the NaC
channel, and gL is the conductance of the leakage channel (Fig. 1.8).
Through an identification procedure, Hodgkin and Huxley derived specific
relations for the conductances in the ionic channels KC and NaC .
gK D gN K n4 gNa D gN Na m3 h (1.48)
where gN K and gN Na are the maximum values for the conductances and n, m, h
are gating variables which take values between 0 and 1. Thus, n4 represents the
probability channel KC to be open. Moreover, m3 represents the probability that the
sodium activation gate is open, and h is the probability that the sodium inactivation
1.4 The Hodgkin–Huxley Model 13
gate is open. It is noted that independently from the model derived by Hodgkin and
Huxley it is possible to obtain the values of the parameters of the neuron membrane’s
model through nonlinear estimation and Kalman Filtering methods [84, 99, 175].
The change in time of parameters m, h, and n in time is given by
dn
dt
D an .V /.1 n/ ˇn .V /n D .n1 .V / n/=n .V /
dm
dt
D am .V /.1 m/ ˇm .V /m D .m1 .V / m/=m .V / (1.49)
dh
dt
D ah .V /.1 h/ ˇh .V /h D .h1 .V / h/=h .V /
For the boundary conditions of the aforementioned differential equations one has
(denoting the general variable X D n, m or h) that
ax .V /
X1 .V / D ax .V /Cˇx .V /
X .V / D 1
ax .V /Cˇx .V / (1.50)
Moreover, the following parameter values have been experimentally used [16]
gN Na D 120 mS/cm3 gN K D 36 mS/cm3 gN L D 0:3 mS/cm3

ENa D 50 mV EK D 77 mV EL D 54:4 mV
an .V / D 0:01.V C 55/=.1 exp..V C 55/=10//

ˇn .V / D 0:125exp..V C 65/=80/ (1.51)
am .V / D 0:1.V C 40/=.1 exp..V C 40/=10//
ˇm .V / D 4exp..V C 65/=18/
ah .V / D 0:07exp..V C 65/=20/
ˇh .V / D 1=.1 C exp..V C 35/=10//
1.4.2 Outline of the Hodgkin–Huxley Equations
By considering that there is no spatial variation of V .x; t /, i.e. that @V @t

.x;t/
D 0, and
moreover that the conductances gN k , gN Na , and gN L vary in time, the Hodgkin–Huxley
equation becomes an ordinary differential equation
cM dV
dt
D gN Na m3 h.V ENa / gN K n4 .V EK / gN L .V EL /
dn
dt
D
Œan .V /.1 n/ ˇn .V /n
(1.52)
dm
dt
D
Œam .V /.1 m/ ˇm .V /m
dh
dt
D
Œah .V /.1 h/ ˇh .V /h
Coefficient
varies with the system’s temperature according to the relation

D Q10 .T Tbase /=10 where Tbase D 6:3ı C and Q10 D 3 (1.53)
If the currents IL ; IK ; INa which are applied to the membrane are lower than a
specific threshold, then the variation of the membrane’s potential returns fast to
the equilibrium. If the currents IL ; IK ; INa which are applied to the membrane are
greater than a specific threshold, then the variation of the membrane’s potential
exhibits oscillations.
1.5 The FitzHugh–Nagumo Model of Neurons
The FitzHugh–Nagumo model is a two-dimensional simplified form of the

Hodgkin–Huxley model and in several cases represents efficiently the membrane’s
voltage dynamics in neurons [16, 55]. The model captures all the qualitative
properties of the Hodgkin–Huxley dynamics, in the sense that it results in the same
bifurcation diagram (loci of fixed points with respect to model’s parameters). In
Eq. (1.54) variable V stands for the membrane’s voltage, while variable w is known
as recovery variable and is associated with the ionic currents of the membrane.
Finally, variable I is an external input current.
The FitzHugh–Nagumo model comprises two differential equations
dV
dt
D V .V a/.1 V / w C I
(1.54)
dw
dt
D .V w/
where typically 0 < a < 1, > 0, and 0. The FitzHugh–Nagumo model is
equivalent to Van Der Pol oscillator, the latter being described by
dV
C D F .V / J (1.55)
dt
dJ
L DV (1.56)
dt
As shown in Fig. 1.9 the model of the FitzHugh–Nagumo neuron, for specific
values of its parameters or suitable feedback control input I may exhibit sustained
oscillations in its state variables and in such a case limit cycles will also appear in
the associated phase diagram. The detailed stability analysis of models of biological
neurons will be given in Chap. 3.
1.6 The Morris–Lecar Model of Neurons
The dynamics of a neuron (cell’s membrane and the associated potential) can
be also studied using not cable’s equation for the Hodgkin–Huxley model but a
simpler model that is called Morris–Lecar model [16,112]. The Morris–Lecar model
1.6 The Morris–Lecar Model of Neurons 15
a 1 b 0.4
0.5 0.3
Vm
0.2
0
0.1
−0.5
0 5 10 15 20 25 30 35 40
x2
0
time (sec)
0.4
−0.1
0.2
−0.2
w
−0.3
−0.2
−0.4 −0.4
0 5 10 15 20 25 30 35 40 −0.4 −0.2 0 0.2 0.4 0.6
time (sec) x1
Fig. 1.9 (a) State variables of the FitzHugh–Nagumo neuron exhibiting sustained oscillations, (b)
limit cycles in the phase diagram of the FitzHugh–Nagumo neuron
examines the variation of the membrane’s potential in a neuron as a function of the

conductances of the associated ionic channels and contains also a second differential
equation which expresses the probability an ionic channel to be open. The model’s
equations are:
CM dV
dt
D Iapp gL .V EL / gk .V Ek / gCa m1 .V /.V ECa /
D Iapp Iion .V; n/ (1.57)
d
dt
D
. 1 .V / /= .V /
where
h i
m1 .V / D 1
2
1 C tanh V VV
2
1
.V / D 1
(1.58)
hcosh..V V1 /=2V
4 / i
m1 .V / D 12 1 C tanh V VV 4
3
Here, parameters Vi ; i D 1; ; 4 are chosen to fit data obtained from an identi-

fication procedure. Although it is more simple comparing to the Hodgkin–Huxley
model (the latter expressed either in a PDE or set of ODEs form), the Morris–Lecar
model captures efficiently several properties of the biological neurons.
Fig. 1.10 (a) Real structure a

of a dendrite, (b)
representation of a dendrite
through its segmentation in
smaller parts, each one
characterized by uniform
potential
1.7 Modelling Dendrites in Terms of Electrical Circuits
1.7.1 Dendrites
The greater part of the cumulative surface of the membrane in neural cells is
occupied by dendrites. Dendrites permit the creation of connections between
different neurons. Moreover, dendrites direct signals of a specific voltage amplitude
from the neighboring neurons to the soma of a particular neuron. The dendrites, as
parts of the membrane, have ionic channels which open or close according to the
change of the membrane’s potential [16, 65]. As a final result, dendrites define the
response of the neurons to synaptic inputs (voltages V .x; t /; Fig. 1.10).
For the study of the voltage dynamics in dendrites, an established approach is to
partition their tree-like structure in smaller parts which are characterized by spatially
uniform voltage potential, i.e. @V@x.x;t/
D 0. It is considered that there exist differences
in the value and distribution of the voltage V .x; t /, in different parts of the dendrites
(Fig. 1.11).
For each smaller part in the dendrite that is characterized by spatially uniform
potential, the major parameters are: the cylinder’s radius ˛i , the length Li , the
membrane’s potential Vi , the capacitance (normalized per unit of surface) ci , and
the resistance of the membrane (normalized per unit of surface) rLi . It is assumed
that in each compartment there is an electrode to which external current Ielectrode is
applied.
From the analysis of the circuit of the elementary part of the dendrite one has
i
Icap C Iion
i
D Ilong
i
C Ielectrode
i
(1.59)
i i
where Icap and Iion are the capacitance and ionic currents per unit area of membrane
for segment i , and additionally
i
Icap D Ci dV
dt
i i
; Iion D Vi
i
rM (1.60)
1.7 Modelling Dendrites in Terms of Electrical Circuits 17
Fig. 1.11 Electric circuit of local segment of a dendrite
Fig. 1.12 Segments of the membrane
Next, two interconnected elementary parts of the dendrite are examined (Fig. 1.12).
The associated longitudinal resistance Rlong is equal to the sum of the resistances of
two successive semi-cylinders
Rlong D rL L1
2 ˛ 2
C rL L2
2 ˛ 2
(1.61)
Defining the conductances of the two elementary parts
˛1 ˛22
g1;2 D (1.62)
rL L1 .a22 L1 C a12 L2 /
˛2 ˛12
g2;1 D (1.63)
rL L1 .a22 L1 C a12 L2 /
the associated currents in the two segments are (there is longitudinal voltage
variation while the membrane’s potential in the i -th segment is spatially unchanged)
1
Ilong D g1;2 .V2 V1 /
(1.64)
2
Ilong D g2;1 .V1 V2 /
The current of the i -th electrode is
i
ielectrode D Ielectrode
Ai (1.65)
with Ai D 2˛i L denoting the surface of segment i . Thus, one arrives at a set of
coupled differential equations
1
Ielectrode
c1 dVdt1 C V1
rm 1
D g1;2 .V2 V1 / C A1
1
Ielectrode
(1.66)
c2 dVdt2 C V2
rm 2
D g2;1 .V1 V2 / C A2
or equivalently
V2 V1
c1 dVdt1 C V1
r M1
D r1
C i1
V1 V2 (1.67)
c2 dVdt2 C V2
r M2
D r2
C i2
Next, it is assumed that the current is injected in only one out of the two cylinders,
that is i2 D 0. It is assumed that r1 D r2 D r and rM1 D rM2 D rM . From
Eqs. (1.66) and (1.67) it holds
V1 CV2
c1 dVdt1 C c2 dVdt2 C rM
D i1 (1.68)
Thus, finally about the segment’s resistance one has

rM .rCrM /
V1
i1
D rC2rM
(1.69)
while the variation of voltage V at the i -th segment is generalized as follows

dV j V P Vk Vj
Cj dt
D Rjj C k;j Rjk
C Ij (1.70)
where Rkj denotes the resistance of the connection between the k-th and the j -th
segment.
1.7.2 Computing Cable’s Equation in Neurons
It is assumed that the cable is defined in the interval .0; l/ and that its cross-section
is circular with diameter d.x/. The cable is segmented in n-parts and the distance
from the origin is defined as xj D j h, where h D nl is the elementary length. Each
part has surface equal to Aj D dj h where dj D d.xj / is the diameter and the
d2
associated surface of the cross-section is equal to 4j . It is assumed that the special
resistance and the capacitance of the membrane are cM and rM , respectively, while
1.7 Modelling Dendrites in Terms of Electrical Circuits 19
the longitudinal resistance is rL . By ignoring the final points, the voltage varies
according to the following relation [16, 65]
dV j V Vj C1 Vj Vj 1 Vj
cM Aj dt
D rM =A
j
j
C 4rL h=.dj2C1 /
C 4rL h=.dj2C1 / (1.71)
Dividing by h the two last terms (coupling terms) one obtains

V Vj 2 Vj Vj 1

h
dj2C1 j C1
4rL h
d j 4rL h
(1.72)
As h!0 one obtains the diffusion operator

@
4rL @x
.d 2 .x/ @V
@x
/ (1.73)
Moreover, by dividing both members of Eq. (1.71) with dx, cable’s equation comes
to the form
cM @V
@t
D rVM C 1 @
4rL d.x/ @x
.d 2 .x/ @V
@x
/ (1.74)
dj2 .Vj 1 Vj /

It is noted that the term 4rL h
has current dimensions and at the limit h!0 it
2
corresponds to longitudinal current IL D d4rL.x/ @V
@x
.
If d.x/ D d is the constant diameter of the segment, then it is possible to multiply
the two segments with rM , and this leads to the linear cable equation
2
@V
@t
D V C 2 @@xV2 (1.75)
q
d
where D 4rrML is the space constant and D rM cM is the time constant.
Considering that as x!1 the voltage of the membrane approaches zero, then
x
the steady-state solution of the cable’s equation takes the form V .x/ D Ae .
1.7.3 The Infinite Length Cable
The relation given in Eq. (1.75) is modified in case of an infinite length cable.
Including an excitation current to the previous equation
2
@V
@t
C V .x; t / 2 @@xV2 D rM I.x; t / (1.76)
where 1 < x < C1 and V .x; 0/ D V0 .x/. The current I.x; t / has units
A=cm2 . For this linear differential equation of the 1st order, the solution is [16,65]
.1C 2 k 2 /t Rt 2 2 .t s/
VO .k; t / D e VO0 .k/ C . rM / 0 e .1C k / IO.; s/ds (1.77)
where
R C1
VO .k; t / D 1 e ikx V .x; t /dx
R C1 ikx
VO0 D 1 e Vo .x/dx (1.78)
R C1
O
I .k; t / D 1 e ikx I.x; t /dx
Using the definition of the inverse Fourier transform one has

R
1 C1 ikx O
V .x; t / D 2 1
e V .k; t /dk (1.79)
one finds that the solution V .x; t / is given by

R C1 R t R C1
V .x; t / D 1 G.x y; t /Vo .y/dy C rM
0 1 G.x y; t s/I.y; s/dyds
(1.80)
where the Green function G.x; t / is defined as

t 2 =. 4 2 t
G.x; t / D q 1 e e x /
(1.81)
4 2 t

If the membrane is in rest state at time instant 0, i.e. V0 .x/ D 0 and for I.x; t / D
I0 ı.x/ı.t /, then

tx 2
t
V .x; t / D rp
M I0
e 4 2 e . / (1.82)
4 t
If I.x; t / D Io u.x/, i.e. a step input is applied at position x, then

h x p q x
p q i
x x
V .x; t / D rM4Io e erf c 2 p
t
t

e erf c p C
2 t
t

(1.83)
R 1 y 2
where erf c D p2
x
e dy, while in steady-state the solution becomes
rM I0 jxj
Vss .x/ D 4
e (1.84)
1.8 Ion Channels and Their Characteristics
1.8.1 Types of Ion Channels
In the set of equations that constitute the Hodgkin–Huxley model one can
distinguish the KC and NaC ion channels, whereas in the Morris–Lecar model
one can distinguish the CaC model. However, there may be more ion channels
across the neuron’s membrane which are described as follows [16, 60, 65].
1.8 Ion Channels and Their Characteristics 21
According to the Hodgkin–Huxley formulation, the aggregate current that goes

through an ion channel is given by a relation that has the generic form:
Ichannel D mp hq Idrive .V / (1.85)
where m and h are variables taking values between 0 and 1, p and q are non-negative
integers, and V is the membrane’s potential. In general, the more the membrane’s
potential grows, the more parameter h gets smaller (inactivation) and the more
parameter m grows (activation). Sodium channels of the Hodgkin–Huxley model
have both activation and inactivation.
Channel KC of the Hodgkin–Huxley model, and channels Ca2C and KC of the
Morris–Lecar model do not exhibit inactivation. In general, the drive current can
take the following form
Ilin D gmax .V Vmax /

zVF
(1.86)
2F 2 ŒC in ŒC out e
Icfe D
RT
Pmax z RT V zVF
1e RT
where the units of gmax are Siemens/cm2 and cf e means constant field equation. In
the equation about the channel’s current Eq. (1.85), the variation of parameters m
and h is given by differential equations of the form
dx
dt
D ax .1 x/ bx x
(1.87)
dx
dt
D .x1 x/=x
while for the voltage-dependent parameters ax and bx , as well as for parameters x1

and x the functions which approximate them have the form
Fe .V; A; B; C / D Ae .V B/=C
A.V B/
Fl .V; A; B; C / D 1e .V B/=C (1.88)
Fh .V; A; B; C / D A=.1 C e .V B/=C /
whereas parameters x1 and x are described by
x1 .V / D 1
.1Ce .V VT /=K / (1.89)
x .V / D min C amp =cosh. V V max /
A key parameter for the appearance and density of voltage pulses is the leak
potential EL . According to the value of this parameter, at points of the membrane,
the variation of the voltage V in time may take the form of spikes or bursts.
1.8.2 Sodium Channels NaC
Sodium channels are distinguished into (1) transient or fast sodium current channels,
(2) persistent or slow sodium channel currents. As an example of persistent sodium
channel currents one can consider the ones appearing in the so-called pre-Bötzinger
complex, that is neurons that coordinate respiration pulses. The associated model
has the form described in Eq. (1.52) of the Hodgkin–Huxley dynamics and is
given by
Cm dV
dt
D gL .V EL / gk n4 .V Ek /
gNa m1 .V / .1 /.V ENa / gNap w1 .V /h.V ENa /
3
(1.90)
d
dt
D .n1 .V / /= .V /
dh
dt
D .h1 .V / h/= .V /
The leak potential EL is a key parameter for introducing bursting in such a model.
1.8.3 Calcium Channels Ca2C
The equation of the current of the associated channel is given by the constant
field equation, given in Eq. (1.86). Calcium channels are distinguished in two large
categories:
1. T-type calcium currents ICa;T which exhibit inactivation with respect to parame-
ter h in the current equation IChannel D mp hq Idrive .V /.
2. L-type calcium currents ICa;L which do not exhibit inactivation with respect to
parameter h in the current equation IChannel D mp hq Idrive .V /.
T -currents exhibit bursts and subthreshold oscillations. They are described by a set
of equations of the form
C dV
dt
D Io gL .V EL / IT
dh
dt
D .h1 .V / h/=h .V /
IT D m1 .V /2 hI cf e.V; ŒCao ; ŒCai /
(1.91)
m1 .V / D 1=.1 C exp..V C 59/=6:2//
h1 .V / D 1=.1 C exp..V C 83/=4//
h .V / D 22:7 C 0:27=Œexp..V C 48/=4/ C exp..V C 407=50//
The response of this model depends on the activation variable m and on the
deactivation variable h.
1.8.4 Voltage-Gated Potassium Channels KC
These are ion channels which open or close depending on the value of the
membrane’s potential V .
1.8.4.1 A-Current
The transient sodium current and the delayed rectifier current are similar to those
of the Hodgkin–Huxley model, although in the present case they are faster. To this
model an additional potassium current is introduced.
An example about the voltage gated channel comes from a model which has the
form
IA D gA a3 b.V EA / (1.92)
The activation variable a increases as current increases. The de-activation variable

b decreases as current increases. Steady-state current is almost zero.
IA;ss D gA ˛1 .V /3 b.1/.V /.V EA / (1.93)
The conductivity variable gA affects the number of spikes that the membrane may
exhibit and is defined by the relation gA C gK D gtotal D 67:7, where a typical value
for parameter gK is gK D 20.
1.8.4.2 M-Current
These are slow KC currents which may affect the firing rate (spiking) of the
membrane. The M current and the associated with it slow currents KC can inhibit
neurons’ firing. Apart from slowing down the neuron’s firing rate the M current
affects also the steady-state value of the neuron’s voltage [140].
If there is no M-current (gm very small), then the model may exhibit bifurcations
on limit cycles. As gm grows then Hopf bifurcations may appear.
With reference to the dynamic model of Eq. (1.90) in the present model one
should consider to introduce the following input currents [16]
IM D gN M p.V Ek /
dp
dt
D .1 .V / /=p .V /
(1.94)
1 .V / D 1Ce.V1C35/=100
p .V / D 3:5Ce.V C35=20/
mac
Ce .V C35=20/
1.8.4.3 Inward Rectifier
This current appears when the neuron becomes hyperpolarized. The current’s
equation has the form
IKin D gKin h.V /.V Ek /

(1.95)
h.V / D 1=Œ1 C exp..V Vth /=K/
Typical values of the parameters appearing in the above model are Vth D 85 mV
and K D 5 mV. Considering the existence of a leak current, the steady-state current
becomes
I D gL .V EL / C gKin h.V /.V EK / (1.96)
Differentiating with respect to V gives
dI
dt
D gL C gKin h.V / C gKin h0 .V /.V EK / (1.97)
1.8.5 Voltage Sags
After hyperpolarization of the neuron takes place then an inward current appears
with values between 43 and 0 mV. The current dynamics is [16]
Ih D gh y.V C 43/
dy
dt
D .y1 .V / y/=y .V /
(1.98)
y1 .V / D 1=Œ1 C exp..V Vth /=K/
y .V / D to sech..V Vm /=b/
1.8.6 Currents and Concentration of Ions
The assumption that the concentration of ions in the inner and outer part of the
membrane remains constant is in general acceptable, apart from the case of Ca2C
ions. The concentration of Ca2C ions in the inner part of the membrane is very
small (of the order of 104 mM) and a small inflow of Ca2C suffices to change this
concentration significantly. Due to this, cascading reactions in the internal part of
the cell are caused.
Similarly, the concentration of ions KC in the outer part of the membrane is very
small and in case that several neurons fire simultaneously then this concentration
may change.
1.8.7 Calcium-Dependent Channels
Modelling of channels where there is transfer of Ca2C is important because the

concentration of these ions affects several signaling mechanisms. The two most
important channels of this type are: (1) IK,Ca which is the calcium dependent
potassium channel, and (2) Ican which is the inward calcium-dependent current. The
first current appears in several neurons and is responsible for low hyperpolarization
(AHP) and spike-frequency adaptation. It is known as AHP current.
1. Calcium-dependent potassium channel—the afterhyperpolarization
A typical model for the IK,Ca current comes from [140] and is given by
IK,Ca D gK,Ca m2 .V Ek /
dm
dt
D .m1 .c/ m/=m .c/
2 (1.99)
m1 .c/ D k 2cCc 2
m .c/ D max.min ; o =.1 C .c=k/2 //
Typical values for the parameters of the above model are k D 0:0025 mM, min D
0:1 ms, o variable. The firing rate f is affected by the value of the current IK,Ca
according to the relation
df F 0 .I agf /
dI
D 1CagF 0 .I /agf /
(1.100)
and for large F 0 this relation is written approximately as

df
dI
D 1
ag (1.101)
A solution which has been also proposed about the firing rate is f .I / D C
p
2 C A2 I , where D A2 ag=2. Moreover about the voltage spikes that appear
in the calcium-dependent potassium channel it holds
C dV
dt
D I Ifast gz.V Ek /
(1.102)
dz
dt
D Œq.V /.1 z/ z
2. Calcium-activated nonspecific cation current

This case is concerned with the inwards calcium current ICAN . This is
described by the relations
p
ICAN D gCAN mCAN .V ECAN / (1.103)
where the gate parameter mCAN varies according to the dynamic model
dmCAN
dt
D .g.c/.1 mCAN / mCAN /=CAN (1.104)
where g.c/ is a monotonous function of the concentration of Ca2C . According to

the model of Destexhe–Paré it holds
ICAN D gCAN mC .V C 20/

(1.105)
dmc
dt
D 0:005ŒCa2C 2 .1 mc / mc =3000
The rate of the voltage spikes in a membrane characterized by calcium-activated

nonspecific cation (CAN) current increases each time calcium stimuli arrives.
1.9 Conclusions
In this chapter it has been shown that the functioning of the cells membrane can
be represented as an electric circuit. To this end: (1) the ion channels have been
represented as resistors, (2) the gradients of the ions concentration have been
represented as voltage sources, (3) the capability of the membrane for charge storage
has been represented as a capacitor. An assumption made was that the neurons have
the shape of a long cylinder, or of a cable with specific radius.The Hodgkin–Huxley
model was derived from a modification of the cable’s PDE, which describes
the change of the voltage along dendrites axis. It has been shown that cables’
equation comprises as inputs the currents which are developed in the ions channels.
Additional models of reduced dimensionality that describe voltage variations along
the neurons membrane have been introduced. These were the FitzHugh–Nagumo
model and the Morris–Lecar model. It has been also demonstrated that cable’s
equation is also shown to be suitable for describing voltage variations along
dendrites. Finally, the various types of ionic channels and ion currents across the
neurons membrane have been analyzed.
Chapter 2
Systems Theory for the Analysis of Biological
Neuron Dynamics
Abstract The chapter analyzes the basics of systems theory which can be used in
the modelling of biological neurons dynamics. To understand the oscillatory behav-
ior of biological neurons benchmark examples of oscillators are given. Moreover,
using as an example, the model of biological neurons the following properties are
analyzed: phase diagram, isoclines, attractors, local stability, bifurcations of fixed
points, and chaotic dynamics.
2.1 Characteristics of the Dynamics of Nonlinear Systems
Main features characterizing the stability of nonlinear dynamical systems are

defined as follows [92, 209]:
1. Finite escape time: It is the finite time within which the state-vector of the
nonlinear system converges to infinity.
2. Multiple isolated equilibria: A linear system can have only one equilibrium
to which converges the state vector of the system in steady-state. A nonlinear
system can have more than one isolated equilibria (fixed points). Depending on
the initial state of the system, in steady-state the state vector of the system can
converge to one of these equilibria.
3. Limit cycles: For a linear system to exhibit oscillations it must have eigenvalues
on the imaginary axis. The amplitude of the oscillations depends on initial condi-
tions. In nonlinear systems one may have oscillations of constant amplitude and
frequency, which do not depend on initial conditions. This type of oscillations is
known as limit cycles.
4. Sub-harmonic, harmonic, and almost periodic oscillations: A stable linear sys-
tem under periodic input produces an output of the same frequency. A nonlinear
system, under periodic excitation can generate oscillations with frequencies
which are several times smaller (subharmonic) or multiples of the frequency
of the input (harmonic). It may also generate almost periodic oscillations with

28 2 Systems Theory for the Analysis of Biological Neuron Dynamics
Fig. 2.1 Pendulum

performing oscillations
frequencies which are not necessarily multiples of a basis frequency (almost

periodic oscillations).
5. Chaos: A nonlinear system in steady-state can exhibit a behavior which is not
characterized as equilibrium, periodic oscillation, or almost periodic oscillation.
This behavior is characterized as chaos. As time advances the behavior of
the system changes in a random-like manner, and this depends on the initial
conditions. Although the dynamic system is deterministic, it exhibits randomness
in the way it evolves in time.
6. Multiple modes of behavior: It is possible the same dynamical system to exhibit
simultaneously more than one of the aforementioned characteristics (1)–(5).
Thus, a system without external excitation may exhibit simultaneously more
than one limit cycles. A system receiving a periodic external input may exhibit
harmonic or subharmonic oscillations, or an even more complex behavior in
steady state which depends on the amplitude and frequency of the excitation.
Example 1. Oscillations of a pendulum (Fig. 2.1).
The equation of the rotational motion of the pendulum under friction is given by
ml 2 R D mgsin. /l klv )
ml 2 R D mgsin. /l kl 2 P ) (2.1)
mlR D mgsin. / klP
By defining the state variables x1 D and x2 D P one has the state-space

description
xP 1 D x2
(2.2)
xP 2 D gl sin.x1 / k
x
m 2
2.1 Characteristics of the Dynamics of Nonlinear Systems 29
Fig. 2.2 Tunnel diode circuit
To compute the equilibrium one has
xP 1 D xP 2 D 0)
(2.3)
x2 D 0 and x1 D n n D 0; ˙1; ˙2;
Indicative forms of oscillations for the pendulum are defined as follows:

(a) The effect of friction is neglected, therefore one has
xP 1 D x2
(2.4)
xP 2 D gl sin.x1 /
(b) An external torque T is applied to the pendulum
xP 1 D x2
(2.5)
xP 2 D gl sin.x1 / mk x2 C 1
ml2
T
Example 2. Tunnel diode circuit (Fig. 2.2).

The following equations hold
1 dV c .t /
Vc D Ic .s/)Ic .s/ D sC Vc .s/)Ic .t / D C (2.6)
sC dt
dI L .t /
VL .s/ D sLIL .s/)VL .t / D L (2.7)
dt
IL .s/ D IC C IR (2.8)
IR .s/ D h.VR / (2.9)
The following state variables are defined x1 D VC and x2 D iL . From Eq. (2.8) it
holds
IL IC IR D 0)IC D IL IR )IC D x2 h.x1 / (2.10)
Moreover, it holds
IL R E C VL C VC D 0)E D VL C VC C iL R)E D L dIdtL C VC C IL R)

E D LxP 2 C VC C x2 R)xP 2 D L1 ŒVC Rx2 C E)xP 2 D L1 Œx1 Rx2 C u
(2.11)
where u D E. Additionally, from Eq. (2.6) it holds
dV c .t/
dt
D 1
I .t /
C c
(2.12)
By replacing Eqs. (2.10) into (2.12) one obtains

dV c .t/
dt
D 1
C
Œx2 h.x1 / (2.13)
From Eqs. (2.11) and (2.13) one has the description of the system is state-space form
xP 1 D C1 Œx2 h.x1 /
(2.14)
xP 2 D L1 Œx1 Rx2 C u
The associated equilibrium is computed from the condition xP 1 D 0 and xP 2 D 0

which gives
h.x1 / C x2 D 0
(2.15)
x1 Rx2 C u D 0
which gives
h.x1 / C Ex1
R
D0
(2.16)
x2 D Ex1
R
Therefore, finally the equilibrium point is computed from the solution of the relation
h.x1 / D E
R
R1 x1 (2.17)
Example 3. Spring-mass system (Fig. 2.3).

It holds that
mxR D F Ff Fsp )
(2.18)
mxR D F b xP kx
2.1 Characteristics of the Dynamics of Nonlinear Systems 31
Fig. 2.3 Spring-mass system
One can also consider a model with nonlinear spring dynamics given by
g.x/ D k.1 a2 x 2 /x jaxj < 1 model of softening spring

(2.19)
g.x/ D k.1 C a2 x 2 /x x > xthres model of hardening spring
The combination of a hardening spring, a linear viscous damping term and of a

periodic external force F D Acos.!t / results into the Duffing oscillator
mxR C c xP C kx C ka2 x 3 D Acos.!t / (2.20)
The combination of a linear spring, a linear viscous damping term, a dry friction
term and of a zero external force generates the following oscillator model
mxR C kx C c xP C .x; x/
P D0 (2.21)
where
8
< k mgsign.x/P if jxP > 0j
P D
.x; x/ kx if jxj
P D 0 and jxjs mg=k (2.22)
:
s mgsign.x/ if xP D 0 and jxj > s mg=k
By defining the state variables x1 D x and x2 D xP one has
xP 1 D x2
(2.23)
xP 2 D mk x1 mc x2 1
m
P
.x; x/
For x2 D xP > 0 one obtains the state-space description
xP 1 D x2
(2.24)
xP 2 D m x1 mc x2
k
k g
For x2 D xP < 0 one obtains the state-space description
xP 1 D x2
(2.25)
xP 2 D mk x1 mc x2 C k g
2.2 Computation of Isoclines
An autonomous second order system is described by two differential equations of

the form
xP 1 D f1 .x1 ; x2 /
(2.26)
xP 2 D f2 .x1 ; x2 /
The method of the isoclines consists of computing the slope (ratio) between f2 and
f1 for every point of the trajectory of the state vector .x1 ; x2 /.
f2 .x1 ;x2 /
s.x/ D f1 .x1 ;x2 / (2.27)
The case s.x/ D c describes a curve in the x1 x2 plane along which the trajectories
xP 1 D f1 .x1 ; x2 / and xP 2 D f2 .x1 ; x2 / have a constant slope.
The curve s.x/ D c is drawn in the x1 x2 plane and along this curve one also
draws small linear segments of length c. The curve s.x/ D c is known as isocline.
The direction of these small linear segments is according to the sign of the ratio
f2 .x1 ; x2 /=f1 .x1 ; x2 /.
Example 1. The following simplified pendulum equation is considered
xP 1 D x2
(2.28)
xP 2 D sin.x1 /
The slope s.x/ is given by the relation
f2 .x1 ;x2 / 2/
s.x/ D f1 .x1 ;x2 /
)s.x/ D sin.x
x2 (2.29)
Setting s.x/ D c it holds that the isoclines are given by the relation
x2 D 1c sin.x1 / (2.30)
For different values of c one has the following isoclines diagram depicted in Fig. 2.4.
2.2 Computation of Isoclines 33
Fig. 2.4 Isoclines diagram 5

sin.x /
for s.x/ D x2 1 4
c=−1/4
c=−1/3
c=−1/2
3 c=−1.0
c=1.0
2 c=1/2
c=1/3
1 c=1/4
2
0
x
−1
−2
−3
−4
−5
−5 0 5
x
1
Fig. 2.5 Isoclines diagram 5

0:5x2 sin.x1 /
for s.x/ D x2 4
c1=−3/4
c2=−5/6
c3=−1
3 c4=−3/2
c5=1/2
2 c6=0
c7=−1/6
1 c8=−1/4
x2
−1
−2
−3
−4
−5
−5 0 5
x
1
Example 2. The following oscillator model is considered, being free of friction and
with state-space equations
xP 1 D x2
(2.31)
xP 2 D 0:5x2 sin.x1 /
To compute isoclines one has
s.x/ D 0:5x2xsin.x 1/
D c) 0:5x2 sin.x1 / D cx2 )
2 (2.32)
.0:5 C c/x2 D sin.x1 /)x2 D 0:5Cc1
sin.x1 /
For different values of parameter c the isoclines are depicted in Fig. 2.5.
2.3 Systems Theory and Neurodynamics
Basic features that are important in the study of neurodynamics are (1) equilibria
(fixed points), (2) limit cycles, (3) phase diagrams, (4) periodic orbits, and (5)
bifurcations of fixed points [92, 209]. The definition of these features will be given
through examples in the case neuron models.
2.3.1 The Phase Diagram
One can consider the Morris–Lecar model with the two state variables, V and .
The dynamics of the Morris–Lecar model can be written as
dV
dt
D f .V; t /
d (2.33)
dt
D g.V; /
The phase diagram consists of the points on the trajectories of the solution of the
associated differential equation, i.e. .V .tk /; .tk //.
At a fixed point or equilibrium it holds f .VR ; R / D 0 and g.VR ; R / D 0.
The closed trajectories are associated with periodic solutions. If there are closed
trajectories, then 9T > 0 such that .V .tk /; .tk // D .V .tk C T /; .tk C T //.
Another useful parameter is the nullclines. The V -nullcline is characterized by
the relation VP D f .V; / D 0. The -nullcline is characterized by the relation
P D g.V; / D 0. The fixed points (or equilibria) are found on the intersection of
nullclines.
2.3.2 Stability Analysis of Nonlinear Systems
2.3.2.1 Local Linearization
A manner to examine stability in nonlinear dynamical systems is to perform local

linearization around an equilibrium. Assume the nonlinear system xP D f .x; u/ and
f .x0 ; u/ D 0 that is x0 is the local equilibrium. The linearization of f .x; u/ with
respect to u round x0 (Taylor series expansion) gives the equivalent description
xP D Ax C Bu (2.34)
2.3 Systems Theory and Neurodynamics 35
where
0 @f1 @f1 @f1 1
@x1 @x2
@xn
B @f2 @f2 @f2 C
B @x1 @x2 C
A D rx f D B @xn C jxDx (2.35)
@ A 0
@fn @fn
@x1 @x2
@f
@xn
n
and
0 @f1 @f1 @f1 1
@u1 @u2
@un
B @f2 @f2 @f2 C
B @u1 @u2 C
B D ru f D B @un C jxDx (2.36)
@ A 0
@fn @fn
@u1 @u2
@f
@un
n
The eigenvalues of matrix A define the local stability features of the system:
Example 1. Assume the nonlinear system
d 2x
dt2
C 2x dx
dt
C 2x 2 4x D 0 (2.37)
By defining the state variables x1 D x, x2 D xP the system can be written in the

following form
xP 1 D x2
(2.38)
xP 2 D 2x1 x2 2x12 C 4x1
It holds that xP D 0 if f .x/ D 0 that is .x1;1 ; x2;1 / D .0; 0/ and .x1;2 ; x2;2 / D .2; 0/.
Round the first equilibrium .x1;1 ; x2;1 / D .0; 0/ the system’s dynamics is written as

01 xP 1 01 x1
A D rx f D or D (2.39)
40 xP 2 40 x2
The eigenvalues of the system are 1 D 2 and 2 D 2. This means that the fixed
point .x1;1 ; x2;1 / D .0; 0/ is an unstable one.
Next, the fixed point .x1;2 ; x2;2 / D .2; 0/ is analyzed. The associated Jacobian
matrix is computed again. It holds that

0 1
A D rx f D (2.40)
4 4
The eigenvalues of the system are 1 D 2 and 2 D 2. Consequently, the fixed
point .x1;2 ; x2;2 / D .2; 0/ is a stable one.
Fig. 2.6 Global stability and global asymptotic stability
2.3.2.2 Lyapunov Stability Approach
The Lyapunov method analyzes the stability of a dynamical system without the need
to compute explicitly the trajectories of the state vector x D Œx1 ; x2 ; ; xn T .
Theorem. The system described by the relation xP D f .x/ is asymptotically stable
in the vicinity of the equilibrium x0 D 0 if there is a function V .x/ such that
(i) V .x/ to be continuous and to have a continuous first order derivative at x0
(ii) V .x/ > 0 if x¤0 and V .0/ D 0
(iii) VP .x/ < 0, 8x¤0.
The Lyapunov function is usually chosen to be a quadratic (and thus positive)
energy function of the system; however, there in no systematic method to define it.
Assume now, that xP D f .x/ and x0 D 0 is the equilibrium. Then the system is
globally asymptotically stable if for every > 0, 9ı./ > 0, such that if jjx.0/jj < ı
then jjx.t /jj < , 8t 0.
This means that if the state vector of the system starts in a disc of radius ı then
as time advances it will remain in the same disc, as shown in Fig. 2.6. Moreover, if
limt!1 jjx.t /jj D x0 D 0, then the system is globally asymptotically stable.
Example 1. Consider the system
xP 1 D x2
(2.41)
xP 2 D x1 x32
The following Lyapunov function is defined
V .x/ D x12 C x22 (2.42)

2.3 Systems Theory and Neurodynamics 37
The equilibrium point is .x1 D 0; x2 D 0/. It holds that V .x/ > 0 8 .x1 ; x2 /¤.0; 0/
and V .x/ D 0 for .x1 ; x2 / D .0; 0/. Moreover, it holds
VP .x/ D 2x1 xP 1 C 2x2 xP 2 D 2x1 x2 C 2x2 .x1 x23 /)

(2.43)
VP .x/ D 2x24 < 0 8 .x1 ; x2 /¤.0; 0/
Therefore, the system is asymptotically stable and limt!1 .x1 ; x2 / D .0; 0/.
Example 2. Consider the system
xP 1 D x1 .1 C 2x1 x22 /

(2.44)
xP 2 D x13 x2
The following Lyapunov function is considered
V .x/ D 12 x12 C x22 (2.45)
The equilibrium point is x1 D 0; x2 D 0. It holds that
VP .x/ D x1 xP 1 C 2x2 xP 2 D x12 .1 C 2x1 x22 C 2x2 .x13 x2 //)

(2.46)
VP .x/ D x12 < 0 8 .x1 ; x2 /¤.0; 0/
Therefore, the system is asymptotically stable and limt!1 .x1 ; x2 / D .0; 0/.
2.3.3 Stability Analysis of the Morris–Lecar Nonlinear Model
Local stability of the Morris–Lecar model can be studied round the associated
equilibria. Local linearization can be performed round equilibria. Using the set
of differential equations that describe the Morris–Lecar neuron that was given
in Eq. (1.57) and performing Taylor series expansion, that is xP D h.x/)xP D
h.x0 /jx0 C rx h.x x0 / C one obtains the system’s local linear dynamics.
The Morris–Lecar neuron model has the generic form

xP 1 f .x1 ; x2 /
D (2.47)
xP 2 g.x1 ; x2 /
where f .x1 ; x2 / D Iapp gL .V EL / gk .V Ek / gCa m1 .V /.V ECa / D

Iapp Iion .V; n/ and g.x1 ; x2 / D
. 1 .V / /= .V /. The fixed points of this
model are computed from the condition xP 1 D 0 and xP 2 D 0. The Jacobian matrix
rx h D M is given by
@f @f
!
.VR ; R / .VR ; R /
M D @V
@g
@
@g (2.48)
@V
.VR ; R / @
.VR ; R /
which results into the matrix

@Iion
.VR ; R /=CM gk .VR Ek /=CM
J D @V (2.49)

01 = .VR /
= .VR /
The eigenvalues of matrix M define stability round fixed points (stable or

unstable fixed point). To this end, one has to find the roots of the associated
characteristic polynomial that is given by det. I J / D 0 where I is the identity
matrix.
2.4 Phase Diagrams and Equilibria of Neuronal Models
2.4.1 Phase Diagrams for Linear Dynamical Systems
The following autonomous linear system is considered
xP D Ax (2.50)
The eigenvalues of matrix A define the system dynamics. Some terminology

associated with fixed points is as follows.
A fixed point for the system of Eq. (2.50) is called hyperbolic if none of the
eigenvalues of matrix A has zero real part. A hyperbolic fixed point is called a
saddle if some of the eigenvalues of matrix A have real parts greater than zero and
the rest of the eigenvalues have real parts less than zero. If all of the eigenvalues
have negative real parts, then the hyperbolic fixed point is called a stable node or
sink. If all of the eigenvalues have positive real parts, then the hyperbolic fixed point
is called an unstable node or source. If the eigenvalues are purely imaginary, then
one has an elliptic fixed point which is said to be a center.
Case 1: Both eigenvalues of matrix A are real and unequal, that is 1 ¤ 1 ¤0.
For 1 < 0 and 2 < 0 the phase diagram for z1 and z2 is shown in Fig. 2.7:
In case that 2 is smaller than 1 , the term e 2 t decays faster than e 1 t .
For 1 > 0 > 2 the phase diagram of Fig. 2.8 is obtained:
In the latter case there are stable trajectories along eigenvector v1 and unstable
trajectories along eigenvector v2 of matrix A. The stability point .0; 0/ is said to be
a saddle point.
When 1 > 2 > 0 then one has the phase diagrams of Fig. 2.9:
2.4 Phase Diagrams and Equilibria of Neuronal Models 39
Fig. 2.7 Phase diagram of 10

initial state variables x1 , x2 of
8
a second order linear
autonomous system with 6
negative eigenvalues, where
4
1 < 2 < 0
2
x2
0
−2
−4
−6
−8
−10
−15 −10 −5 0 5 10 15
x1

initial state variables x1 , x2 of
a second order linear 1.5
autonomous system with real

1
eigenvalues, where
1 > 0 > 2
0.5
x2
−0.5
−1
−1.5
−2
−30 −20 −10 0 10 20 30
x1
Case 2: Complex eigenvalues:
Typical phase diagrams in the case of stable complex eigenvalues are given in
Fig. 2.10.
Typical phase diagrams in the case of unstable complex eigenvalues are given in
Fig. 2.11.
Typical phase diagrams in the case of imaginary eigenvalues are given in
Fig. 2.12.
Case 3: Matrix A has non-zero eigenvalues which are equal to each other. The
associated phase diagram is given in Fig. 2.13.

state variables x1 , x2 of a
second order linear
2
autonomous system with real
eigenvalues 1 > 2 > 0
1
x2
0
−1
−2
−3
−30 −20 −10 0 10 20 30
x
1

second order linear
10
autonomous system with
complex stable eigenvalues
5
X2
−5
−10
−15
−10 −5 0 5 10
X1
2.4.2 Multiple Equilibria for Nonlinear Dynamical Systems
A nonlinear system can have multiple equilibria as shown in the following example.
Consider, for instance, the model of a pendulum under friction
xP 1 D x2
(2.51)
xP 2 D gl sin.x1 / K
x
m 2
The associated phase diagram is designed for different initial conditions and is
given in Fig. 2.14.
For the previous model of the nonlinear oscillator, local linearization round
equilibria with the use of Taylor series expansion enables analysis of the local
Fig. 2.11 Phase diagram of x 10

10
1
second order linear 0.8
autonomous system with
0.6
complex unstable eigenvalues
0.4
0.2
x2
0
−0.2
−0.4
−0.6
−0.8
−1
−8 −6 −4 −2 0 2 4 6 8
9
x x 10
1

20
second order linear
imaginary eigenvalues
10
5
x2
−5
−10
−15
−20
−25
−15 −10 −5 0 5 10 15
x1
stability properties of nonlinear dynamical systems
xP 1 D f1 .x1 ; x2 /
(2.52)
xP 2 D f2 .x1 ; x2 /
which gives
xP 1 D f1 .p1 ; p2 / C ˛11 .x1 p1 / C ˛12 .x2 p2 / C h.o.t

(2.53)
xP 2 D f2 .p1 ; p2 / C ˛21 .x1 p1 / C ˛22 .x2 p2 / C h.o.t

8
second order linear
identical stable eigenvalues
4
x2
0
−2
−4
−6
−8
−10
−15 −10 −5 0 5 10 15
x1

second order nonlinear
4
oscillator that exhibits
multiple equilibria
2
x2
−2
−4
−6
−30 −20 −10 0 10 20 30
x1
where
@f1 .x1 ;x2 / @f1 .x1 ;x2 /
˛11 D @x1
jx1 Dp1 ;x2 Dp2 ˛12 D @x2
jx1 Dp1 ;x2 Dp2
@f2 .x1 ;x2 / @f2 .x1 ;x2 / (2.54)
˛21 D @x1
jx1 Dp1 ;x2 Dp2 ˛22 D @x2
jx1 Dp1 ;x2 Dp2
For the equilibrium it holds:
f1 .p1 ; p2 / D 0
(2.55)
f2 .p1 ; p2 / D 0
Next, by defining the new variables y1 D x1 p1 and y2 D x2 p2 one can rewrite

the state-space equation
yP1 D xP 1 D ˛11 y1 C ˛12 y2 C h.o.t.

(2.56)
yP2 D xP 2 D ˛21 y1 C ˛22 y2 C h.o.t.
By omitting the higher order terms one can approximate the initial nonlinear system
with its linearized equivalent
yP1 D ˛11 y1 C ˛12 y2

(2.57)
yP2 D ˛21 y1 C ˛22 y2
which in matrix form is written as
yP D Ay (2.58)
where
@f1 @f1
!
˛11 ˛12 @x1 @x2 @f
AD D @f2 @f2
jxDp D j
@x xDp
(2.59)
˛21 ˛22 @x1 @x2
Matrix A D @f @x
is the Jacobian matrix of the system that is computed at point
.x1 ; x2 / D .p1 ; p2 /. It is anticipated that the trajectories of the phase diagram of the
linearized system in the vicinity of the equilibrium point will be also close to the
trajectories of the phase diagram of the nonlinear system.
Therefore, if the origin (equilibrium) in the phase diagram of the linearized
system is (1) a stable node (matrix A has stable linear eigenvalues), (2) a stable focus
(matrix A has stable complex eignevalues), (3) a saddle point (matrix A has some
eigenvalues with negative real part while the rest of the eigenvalues have positive
real part), then one concludes that the same properties hold for phase diagram of the
nonlinear system.
Example. A nonlinear oscillator of the following form is considered:
xP D f .x/)
(2.60)
xP 1 x2
D
xP 2 sin.x1 / 0:5x2
The associated Jacobian matrix is

@f 0 1
D (2.61)
@x cos.x1 / 0:5
There are two equilibrium points .0; 0/ and .; 0/. The linearization round the
equilibria gives

0 1 0 1
A1 D A2 D
1 0:5 1 0:5
(2.62)
with eigenvalues with eigenvalues
1;2 D 0:25˙j 0:97 1 D 1:28 2 D 0:78
Consequently, the equilibrium .0; 0/ is a stable focus (matrix A1 has stable complex
eignevalues) and the equilibrium .; 0/ is a saddle point (matrix A2 has an unstable
eigenvalue).
2.4.3 Limit Cycles
A dynamical system is considered to exhibit limit cycles when it admits the

nontrivial periodic solution
x.t C T / D x.t / 8 t 0 (2.63)
for some T > 0 (the trivial periodic solution is the one associated with x.t / =
constant). An example about the existence of limit cycles is examined in the case of
the Van der Pol oscillator (actually this is a model that approximates the functioning
of neural oscillators such as Central Pattern Generators). The state equations of the
oscillator are
xP 1 D x2
(2.64)
xP 2 D x1 C .1 xŠ2 /x2
Next the phase diagram of the Van der Pol oscillator is designed for three different
values of parameter , namely D 0:2, D 1, and D 5:0. In Figs. 2.15 and 2.16,
it can be observed that in all cases there is a closed trajectory to which converge all
curves of the phase diagram that start from points far from it.
To study conditions under which dynamical systems exhibit limit cycles, a
second order autonomous nonlinear system is considered next, given by

xP 1 f1 .x1 ; x2 /
D (2.65)
xP 2 f2 .x1 ; x2 /
Next, the following theorem defines the appearance of limit cycles in the phase
diagram of dynamical systems [92, 209].
Fig. 2.15 Phase diagram of 2.5

the Van der Pol oscillator for
2
D 0:2
1.5
0.5
x2
0
−0.5
−1
−1.5
−2
−2.5
−2.5 −2 −1.5 −1 −0.5 0 0.5 1 1.5 2 2.5
x
1

the Van der Pol oscillator for
D1
2
1
x2
−1
−2
−3
−2.5 −2 −1.5 −1 −0.5 0 0.5 1 1.5 2 2.5
x
1
Theorem 1 (Poincaré–Bendixson). If a trajectory of the nonlinear system of

Eq. (2.65) remains in a finite region ˝, then one of the following is true: (i) the
trajectory goes to an equilibrium point, (ii) the trajectory tends to a limit cycle, (iii)
the trajectory is itself a limit cycle.
Moreover, the following theorem provides a sufficient condition for the nonexis-
tence of limit cycles:
Theorem 2 (Bendixson). For the nonlinear system of Eq. (2.65), no limit cycle can
exist in a region ˝ of the phase plane in which @f
@x1
1
C @f
@x2
2
does not vanish and does
not change sign.
2.5 Bifurcations in Neuronal Dynamics
2.5.1 Bifurcations of Fixed Points of Biological Neuron

Models
As the parameters of the nonlinear model of the neuron are changed, the stability
of the equilibrium point can also change and also the number of equilibria may
vary. Values of these parameters at which the locus of the equilibrium (as a function
of the parameter) changes and different branches appear are known as critical or
bifurcation values. The phenomenon of bifurcation has to do with quantitative
changes of parameters leading to qualitative changes of the system’s properties
[36, 54, 76, 97, 113].
Another issue in bifurcation analysis has to do with the study of the segments
of the bifurcation branches in which the fixed points are no longer stable but either
become unstable or are associated with limit cycles. The latter case is called Hopf
bifurcation and the system’s Jacobian matrix has a pair of complex imaginary
eigenvalues.
2.5.2 Saddle-Node Bifurcations of Fixed Points

in a One-Dimensional System
The considered dynamical system is given by xP D x 2 . The fixed points of the

p
system result from the condition xP D 0 which for > 0 gives x D ˙ . The
p p
first fixed point x D is a stable one whereas the second fixed point x D
is an unstable one. The phase diagram of the system is given in Fig. 2.17. Since
there is one stable and one unstable fixed point the associated bifurcation (locus of
the fixed points in the phase plane) will be a saddle-node one.
The bifurcations diagram is given next. The diagram shows how the fixed points
of the dynamical system vary with respect to the values of parameter . In the above
case it represents a parabola in the x plane as shown in Fig. 2.18.
p
For > 0 the dynamical system has two fixed points located at ˙ . The
one fixed point is stable and is associated with the upper branch of the parabola.
The other fixed point is unstable and is associated with the lower branch of the
parabola. The value D 0 is considered to be a bifurcation value and the point
.x; / D .0; 0/ is a bifurcation point. This particular type of bifurcation where one
branch is associated with fixed points and the other branch is not associated with
any fixed points is known as saddle-node bifurcation.
2.5 Bifurcations in Neuronal Dynamics 47
Fig. 2.17 Phase diagram and fixed points of the system xP D x 2 . Converging arrows denote
a stable fixed point
Fig. 2.18 Saddle-node bifurcation diagram
2.5.3 Pitchfork Bifurcation of Fixed Points
In pitchfork bifurcations the number of fixed points varies with respect to the values
of the bifurcation parameter. The dynamical system xP D x. x 2 / is considered.
The associated fixed points are found by the condition xP D 0. For < 0 there is
one fixed point at zero which is stable. For D 0 there is still one fixed point at
zero which is still stable. For > 0 there are three fixed points, one at x D 0,
Fig. 2.19 Phase diagram and fixed points of a system exhibiting pitchfork bifurcations. Converg-
ing arrows denote a stable fixed point
Fig. 2.20 Pitchfork bifurcation diagram
p p
one at x D C which is stable, and one at x D which is also stable. The
associated phase diagrams and fixed points are presented in Fig. 2.19.
2.5 Bifurcations in Neuronal Dynamics 49
2.5.4 The Hopf Bifurcation
Bifurcation of the equilibrium point means that the locus of the equilibrium on the
phase plane changes due to variation of the system’s parameters. Equilibrium x is
a hyperbolic equilibrium point if the real parts of all its eigenvalues are non-zero.
A Hopf bifurcation appears when the hyperbolicity of the equilibrium point is
lost due to variation of the system parameters and the eigenvalues become purely
imaginary. By changing the values of the parameters at a Hopf bifurcation, an
oscillatory solution appears [131].
The stages for finding Hopf bifurcations in nonlinear dynamical systems are
described next. The following autonomous differential equation is considered:
dx
dt
D f1 .x; / (2.66)
where x is the state vector x2Rn and 2Rm is the vector of the system parameters.
In Eq. (3.15) a point x satisfying f1 .x / D 0 is an equilibrium point. Therefore
from the condition f1 .x / D 0 one obtains a set of equations which provide
the equilibrium point as function of the bifurcating parameter. The stability of
the equilibrium point can be evaluated by linearizing the system’s dynamic model
around the equilibrium point and by computing eigenvalues of the Jacobian matrix.
The Jacobian matrix at the equilibrium point can be written as
@f1 .x/
Jf1 .x / D @x
jxDx (2.67)
and the determinant of the Jacobian matrix provides the characteristic equation
which is given by
det.i In Jf1 .x / / D n1 C ˛1 n1

i C C ˛n1 i C ˛n D 0 (2.68)
where In is the nn identity matrix, i with i D 1; 2; ; n denotes the eigenvalues

of the Jacobian matrix Df1 .x /. From the requirement the eigenvalues of the
system to be purely imaginary one obtains a condition, i.e. values that the bifurcating
parameter should take, for the appearance of Hopf bifurcations.
As example, the following nonlinear system is considered:
xP 1 D x2 xP 2 D x1 C .m x12 /x1 (2.69)
Setting xP 1 D 0 and xP 2 D 0 one obtains the system’s fixed points. For m1 the
system has the fixed point .x1 ; x2 / Dp.0; 0/. For m > 1 the system p has the fixed
points .x1 ; x2 / D .0; 0/, .x1 ; x2 / D . m 1; 0/, .x1 ; x2 / D . m 1; 0/. The
system’s Jacobian is

0 1
J D (2.70)
1 C m 3x1 0
2
Fig. 2.21 Phase diagram and 2

fixed points of a system
exhibiting Hopf bifurcations 1.5
0.5
x1−x2
0
−0.5
−1
−1.5
−2
−2 −1.5 −1 −0.5 0 0.5 1 1.5 2 2.5
time
Fig. 2.22 Hopf bifurcation 4

diagram
3
0
x
−1
−2
−3
−4
1 2 3 4 5 6 7 8 9 10 11
m
If m1, the eigenvalues of the Jacobian at the fixed point .x1 ; x2 / D .0; 0/ will
be imaginary. Thus the system exhibits Hopf bifurcations, as shown in Fig. 2.21. If
m > 1, then the fixed point .x1 ; x2 / D .0; 0/ is an unstable one. On the p
other hand,

if m > 1, the eigenvalues
p of the Jacobian at the fixed points .x1 ; x2 / D . m 1; 0/
and .x1 ; x2 / D . m 1; 0/ will be imaginary and the system exhibits again Hopf
bifurcations.
2.7 Conclusions 51
2.6 Chaos in Neurons
2.6.1 Chaotic Dynamics in Neurons
Nonlinear dynamical systems, such as neurons, can exhibit a phenomenon called

chaos, by which it is meant that the system’s output becomes extremely sensitive
to initial conditions. The essential feature of chaos is the unpredictability of the
system’s output. Even if the model of the chaotic system is known, the system’s
response in the long run cannot be predicted. Chaos is distinguished from random
motion. In the latter case, the system’s model or input contain uncertainty and as a
result, the time variation of the output cannot be predicted exactly (only statistical
measures can be computed). In chaotic systems, the involved dynamical model
is deterministic and there is little uncertainty about the system’s model, input,
and initial conditions. In such systems, by slightly varying initial conditions or
parameters values, a completely different phase diagram can be produced [214,216].
Some known chaotic dynamical systems are the Van der Pol oscillator which
as explained in Sect. 1.5. is equivalent to the model of the FitzHugh–Nagumo
neuron [207, 224]. Other chaotic models are the Duffing oscillator which is
considered to be equivalent to variants of the FitzHugh–Nagumo neuron and which
has been proposed to model the dynamics of neuronal groups recorded by the
Electroengephalogram (EEG).
2.6.2 Chaotic Dynamics in Associative Memories
The variations of the parameters of associative memories (elements of the weight

matrix) within specific ranges can result in the appearance of chaotic attractors or in
the appearance of limitcycles. The change in the branches of the locus where these
attractors reside, which is due to changes in the values of the dynamic model’s
parameters, is also noted as bifurcation. An example about chaotic dynamics
emerging in Hopfield associated memories is shown in Fig. 2.23.
2.7 Conclusions
In this chapter, the main elements of systems theory are overviewed, thus providing
the basis for modelling of biological neurons dynamics. To explain oscillatory phe-
nomena and consequently the behavior of biological neurons benchmark examples
a b
2 100
1 50
x2
x3
0 0
−1 −50
−2 −100
−2 0 2 −2 0 2
x1 x1
c d
100 6
Lyapunov exponent
50 4
x3
0 2
−50 0
−100 −2
−2 0 2 −20 −10 0
x2 p
Fig. 2.23 (a)–(c) Phase diagrams showing limit cycles of the Hopfield model, (d) Lyapunov
exponents vs varying parameters
of oscillators have been given. Moreover, using mathematical models of oscillators

and biological neurons the following properties have been analyzed: phase diagram,
isoclines, attractors, local stability, bifurcations of fixed points, and chaos properties.
Chapter 3
Bifurcations and Limit Cycles in Models
of Biological Systems
Abstract The chapter proposes a systematic method for fixed point bifurcation
analysis in circadian cells and similar biological models using interval polynomials
theory. The stages for performing fixed point bifurcation analysis in such biological
systems comprise (i) the computation of fixed points as functions of the bifurcation
parameter and (ii) the evaluation of the type of stability for each fixed point through
the computation of the eigenvalues of the Jacobian matrix that is associated with the
system’s nonlinear dynamics model. Stage (ii) requires the computation of the roots
of the characteristic polynomial of the Jacobian matrix. This problem is nontrivial
since the coefficients of the characteristic polynomial are functions of the bifurcation
parameter and the latter varies within intervals. To obtain a clear view about the
values of the roots of the characteristic polynomial and about the stability features
they provide to the system, the use of interval polynomials theory and particularly
of Kharitonov’s stability theorem is proposed. In this approach the study of the
stability of a characteristic polynomial with coefficients that vary in intervals is
equivalent to the study of the stability of four polynomials with crisp coefficients
computed from the boundaries of the aforementioned intervals. The efficiency of the
proposed approach for the analysis of fixed points bifurcations in nonlinear models
of biological neurons is tested through numerical and simulation experiments.
3.1 Outline
The chapter analyzes the use of interval polynomial theory for the study of fixed
point bifurcations and the associated stability characteristics in circadian cells
and similar biological models. The bifurcation parameter is usually one of the
coefficients of the biological system or a feedback control gain that is used to modify
the system’s dynamics. The bifurcation parameter varies within intervals; therefore,
assessment of the stability features for all fixed points of the system (each fixed
point depends on a different value of the bifurcation parameter) requires extended
computations. Therefore, it is significant to develop methods that enable to draw

54 3 Bifurcations and Limit Cycles in Models of Biological Systems
a conclusion about the stability features of larger sets of fixed points where each set
is associated with an interval from which the bifurcation parameter takes its values.
A solution to this problem can be obtained from interval polynomials theory and
Kharitonov’s theorem [162, 192].
Aiming at understanding how the dynamics of neurons is modified due to exter-
nal stimuli and parametric variations the topic of fixed point bifurcations in such
biological models has been extensively studied during the last years [116, 204, 214].
Similar results and methods have been extended to artificial neural networks, such
as Hopfield associative memories [76, 178]. Additionally, studies on bifurcations
appearing in biological models such as circadian cells show how the dynamics
and the stability of such models can be affected by variations of external inputs
and internal parameters [128, 193]. A subject of particular interest has been also
the control of bifurcations appearing in biological systems which is implemented
with state feedback and which finally succeeds to modify the biological oscillator’s
dynamics and its convergence to attractors [49, 50, 54, 131, 132, 199, 205].
In this chapter, as a case study, bifurcations of fixed points in two particular types
of biological models will be examined. The first model is the FitzHugh–Nagumo
neuron. The voltage of the neurons membrane exhibits oscillatory variations after
receiving suitable external excitation either when the neuron is independent from
neighboring neural cells or when the neuron is coupled to neighboring neural cells
through synapses or gap junctions, as shown in Chap. 1. The FitzHugh–Nagumo
model of biological neurons is a simplified model (second order) of the Hodgkin–
Huxley model (fourth order), where the latter is considered to reproduce efficiently
in several cases the neuron’s dynamics. The FitzHugh–Nagumo model describes the
variations of the voltage of the neuron’s membrane as a function of the ionic currents
that get through the membrane and of an external current that is applied as input to
the neuron [5, 16, 161, 220]. The second model is that of Neurospora circadian cells.
Circadian cells perform protein synthesis within a feedback loop. The concentration
of the produced proteins exhibits periodic variations in time. The circadian cells
regulate the levels of specific proteins’ concentration through an RNA transcription
and translation procedure [102, 104, 189]. Circadian neurons in the hypothalamus
are also responsible for synchronization and periodic functioning of several organs
in the human body.
Typically, the stages for analyzing the stability features of the fixed points that
lie on bifurcation branches comprise (i) the computation of fixed points as functions
of the bifurcation parameter and (ii) the evaluation of the type of stability for each
fixed point through the computation of the eigenvalues of the Jacobian matrix that
is associated with the system’s nonlinear dynamics model. Stage (ii) requires the
computation of the roots of the characteristic polynomial of the Jacobian matrix.
This problem is nontrivial since the coefficients of the characteristic polynomial
are functions of the bifurcation parameter and the latter varies within intervals [36,
113, 129]. To obtain a clear view about the values of the roots of the characteristic
polynomial and about the stability features they provide to the system the use of
interval polynomials theory and particularly of Kharitonov’s stability theorem is
proposed [162, 192]. In this approach the study of the stability of a characterized
3.2 Generalization of the Routh–Hurwitz Criterion with Kharitonov’s Theorem 55
polynomial with coefficients that vary in intervals is equivalent to the study of the
stability of four polynomials with crisp coefficients computed from the boundaries
of the aforementioned intervals.
3.2 Generalization of the Routh–Hurwitz Criterion

with Kharitonov’s Theorem
3.2.1 Application of the Routh Criterion to Systems

with Parametric Uncertainty
The following characteristic polynomial is considered
p. / D cn n C cn1 n1 C C c1 C c0 (3.1)
The polynomial’s coefficients vary within intervals, that is
cimin ci ci max i D 0; 1; 2; ; n (3.2)
The study of the stability of the above characteristic polynomial is now transferred
to the study of the stability of four Kharitonov polynomials, where each polynomial
is written as
pi . / D cni n C cn1
i
n1 C C c1i C c0i i D 1; ; 4 (3.3)
The associated coefficients are written as
i
c2k i
; c2kC1 k D m; m 1; ; 0; 1 (3.4)
where m D n=2 if n is an even number and m D .n 1/=2 if n is an odd number.

For the first Kharitonov polynomial p1 .s/ D cn1 s n C cn1
1
s n1 C C c11 s C c01
the coefficients are
1
c2k D c2k
max 1
if k is an even number; c2kC1 D c2kC1
max
if k is an even number
(3.5)
c2k D c2k if k is an odd number; c2kC1 D c2kC1
1 min 1 min
if k is an odd number
For the second Kharitonov polynomial p2 .s/ D cn2 s n C cn1

2
2
c2k D c2k
min 2
min
(3.6)
2 max 2 max
For the third Kharitonov polynomial p3 .s/ D cn3 s n C cn1

3
s n1 C C c13 s C c03 the
coefficients are
3
c2k D c2k
min 3
max
(3.7)
3 max 3 min
For the fourth Kharitonov polynomial p4.s/ D cn4 s n C cn1

4
4
c2k D c2k
max 4
min
(3.8)
4 min 4 max
3.2.2 An Application Example
As an example the following characteristic polynomial is considered p. / D 3 C

.a C b/ 2 C ab C K with parametric uncertainty given by K2Œ8; 12, a2Œ2:5; 3:5,
b2Œ3:8; 4:2. The coefficients of the characteristic polynomial have the following
variation ranges: c3 D 1, c2 D .a C b/2Œ6:3; 7:7, c1 D ab2Œ9:5; 14:7 and c0 D
K2Œ8; 12. The associated Kharitonov polynomials are
p1 . / D 12 C 14:7 C 6:3 2 C 3
p2 . / D 8 C 14:7 C 7:7 2 C 3
(3.9)
p3 . / D 8 C 9:5 C 7:7 2 C 3
p4 . / D 12 C 9:5 C 6:3 2 C 3
Next, Routh–Hurwitz criterion is applied for each one of the four Kharitonov
polynomials. For polynomial p1 . /
3 j1 14:7
2 j 6:3 12
(3.10)
1 j 12:795 0
0 j 12
Since there is no change of sign in the first column of the Routh matrix it can be
concluded that polynomial p1 . / has stable roots. For polynomial p2 . /
3 j 1 14:7
2 j 7:7 8
(3.11)
1 j 13:6610 0
0 j 8
3.3 Stages in Bifurcations Analysis 57
3 j1 9:5
2 j 7:7 8
(3.12)
1 j 8:4610 0
0 j8
3 j1 9:5
2 j 6:3 12
(3.13)
1 j 7:5952 0
0 j 12
concluded that polynomial p4 . / has stable roots.
Using that all four Kharitonov characteristic polynomials p i . / have stable
roots it can be concluded that the initial characteristic polynomial p. / has stable
roots when its parameters vary in the previously defined ranges. Equivalently, the
computation of the four Kharitonov characteristic polynomials can be performed as
follows:
p1 . / D c0max C c1max C c2min 2 C c3min 3 C c4max 4 C c5max 5 C c6min 6 C

p2 . / D c0min C c1min C c2max 2 C c3max 3 C c4min 4 C c5min 5 C c6max 6 C
p3 . / D c0min C c1max C c2max 2 C c3min 3 C c4min 4 C max
5 C c6 C
5 max 6
p4 . / D c0max C c1min C c2min 2 C c3max 3 C c4max 4 C c5min 5 C c6min 6 C

(3.14)
while an equivalent statement of Kharitonov’s theorem is as follows [162, 192]:
Theorem. Each characteristic polynomial in the interval polynomials family p. /
is stable if and only if all four Kharitonov polynomials pi . /; i D 1; ; 4 are
stable.
3.3 Stages in Bifurcations Analysis
The classification of fixed points according to their stability features has been given
in Sect. 2.4. Here the classification of fixed points’ bifurcations is overviewed. Bifur-
cation of the equilibrium point means that the locus of the equilibrium on the plane
(having as horizontal axis the bifurcation parameter and as vertical axis the fixed
point variable) changes due to variation of the system’s parameters. Equilibrium
x is a hyperbolic equilibrium point if the real parts of all its eigenvalues are
non-zero. One can have stable or unstable bifurcations of hyperbolic equilibria. A
saddle-node bifurcation occurs when there are eigenvalues of the Jacobian matrix
with negative real part and other eigenvalues with non-negative real part. A Hopf
bifurcation appears when the hyperbolicity of the equilibrium point is lost due to
variation of the system parameters and the eigenvalues become purely imaginary. By
changing the values of the parameters at a Hopf bifurcation, an oscillatory solution
appears.
The stages for finding bifurcations in nonlinear dynamical systems are described
next. The following autonomous differential equation is considered:
dx
dt
D f1 .x; q/ (3.15)
where x is the state vector x2Rn and q2Rm is the vector of the system parameters.
In Eq. (3.15) a point x satisfying f1 .x / D 0 is an equilibrium point. Therefore
from the condition f1 .x / D 0 one obtains a set of equations which provide
the equilibrium point as function of the bifurcating parameter. The stability of
the equilibrium point can be evaluated by linearizing the system’s dynamic model
around the equilibrium point and by computing eigenvalues of the Jacobian matrix.
The Jacobian matrix at the equilibrium point can be written as
@f1 .x/
Jf1 .x / D @x
jxDx (3.16)
and the determinant of the Jacobian matrix provides the characteristic equation
which is given by
det. i In Jf1 .x / / D cn n1 C cn1 n1

i C C c1 i C c0 D 0; (3.17)
where In is the nn identity matrix, i with i D 1; 2; ; n denotes the eigenvalues

of the Jacobian matrix Jf1 .x / . Using the above characteristic polynomial one can
formulate conditions for the system to have stable or unstable fixed points or saddle-
node fixed points. From the requirement the eigenvalues of the system to be purely
imaginary one obtains a condition, i.e. values that the bifurcating parameter should
take, so as Hopf bifurcations to appear.
3.4 Bifurcation Analysis of the FitzHugh–Nagumo Neuron

3.4.1 Equilibria and Stability of the FitzHugh–Nagumo
Neuron
The model of the dynamics of the FitzHugh–Nagumo neuron is considered
dV
dt
D V .V a/.1 V / w C I
(3.18)
dw
dt
D .V w/
3.4 Bifurcation Analysis of the FitzHugh–Nagumo Neuron 59
By defining the state variables x1 D w, x2 D V and setting current I as the external

control input one has
dx1
dt
D x1 C x2
dx2
dt
D x2 .x2 a/.1 x2 / x1 C u
(3.19)
y D h.x/ D x1
Equivalently one has

xP 1 x1 C x2 0
D C u
xP 2 x2 .x2 a/.1 x2 / x1 1
(3.20)
y D h.x/ D x1
Next, the fixed points of the dynamic model of the FitzHugh–Nagumo neuron are
computed. It holds that
xP 1 D x1 C x2
(3.21)
xP 2 D x2 .x2 ˛/.1 x2 / x1 C I
Setting I D 0, and setting xP 1 D 0 and xP 2 D 0 (nullclines), the associated fixed

points are found
x2 D x1
(3.22)
x1 . 3 x12 C .a 2 C 2 /x1 ˛ 1/ D 0
The numerical values of the parameters are taken to be D 0:2 and a D 7. Then by
substituting the relation for x2 from the first row of Eq. (3.22) into the second row
one obtains
x1 Œ 3 x12 C 2 .1 C a/x1 C .a 1/ D 0 (3.23)
From the above conditions one has the first fixed point
x1;1 D 0 x2;1 D 0 (3.24)
whereas, since the determinant D 4 .1 C a/ 2a 4 4 3 / < 0 no other real

valued solutions for .x1 ; x2 / can be found and consequently no other fixed points
can be considered.
Next, the type of stability that is associated with the fixed point x1;1 D 0; x2;1 D
0 is examined. The Jacobian matrices of the right-hand side of Eq. (3.21) are
computed and the associated characteristic polynomials are found
!
@f1 @f1

J D @x1
@f2
@x2
@f2 D (3.25)
@x1 @x2
1 3x22 C 2.1 C a/x2 a
Stability at the fixed point x1 D 0 and x2 D 0: Substituting the values of x1 and x2

in Eq. (3.27) the obtained characteristic polynomial is p. / D 2 C .a C / C
.˛ C /.
Next, it is considered that a2Œamin ; amax D Œ6:8; 7:2, whereas D 1:5 and
D 0:2 are crisp numerical values. Then for the coefficients of the characteristic
polynomial p.s/ D 2 C k1 C k2 one has k1 D .a C / 2 Œ7:1; 7:5 and
k2 D .a / C 2 Œ3:54; 3:66.
The application of the Routh–Hurwitz criterion gives
2 j 1 k2
1 j k 1 0 (3.26)
0 j k2
Since k1 > 0 and k2 > 0 there is no change of sign in the first column of the Routh
matrix and the roots of the characteristic polynomial p. / are stable. Therefore, the
equilibrium .0; 0/ is a stable one.
3.4.2 Condition for the Appearance of Limit Cycles
Finally, it is noted that the appearance of the limit cycles in the FitzHugh–Nagumo
neuron model is possible. For instance, if state feedback is implemented in the form
I D qx2 , then .x1 ; x2 / D .0; 0/ is again a fixed point for the model while the
Jacobian matrix J at .x1 ; x2 / becomes

J D (3.27)
1 3x2 C 2.1 C a/x2 a q
2
The characteristic polynomial of the above Jacobian matrix is p. / D 2 C .a C

q C C .q C //. Setting the feedback gain q D a the characteristic
polynomial becomes p. / D 2 C. 2 2 C˛ /. Then, the condition .˛ / >
0 with a > 0, > 0 and > 0 suffices for the appearance of imaginary eigenvalues.
In such a case the neuron model exhibits sustained oscillations (limit cycles).
3.5 Bifurcation Analysis of Circadian Oscillators 61
3.5 Bifurcation Analysis of Circadian Oscillators
3.5.1 Fixed Points Bifurcation Analysis Using

Kharitonov’s Theory
The model of the circadian cells is given by
Kin x1
xP 1 D vs vm (3.28)
C x3n
Kin Km C x 1
x2
xP 2 D vd K 1 x 2 C K2 x 3 C x 1 Ks (3.29)
Kd C x 2
xP 3 D K1 x2 K2 x3 (3.30)
The model’s parameters are defined as follows: vs denotes the rate of transcription
of the frq gene into FRQ protein inside the nucleus. Ki represents the threshold
constant beyond which nuclear FRQ protein inhibits transcription of the frq gene. n
is the Hill coefficient showing the degree of cooperativity of the inhibition process,
vm is the maximum rate of frq mRNA degradation, KM is the Michaelis constant
related to the transcription process. Parameter Ks defines the rate of FRQ synthesis
and stands for the control input to the model. Parameter K1 denotes the rate of
transfer of FRQ protein from the cytoplasm to the nucleus and K2 denotes the
rate of transfer of the FRQ protein from the nucleus into the cytoplasm. Parameter
vd denotes the maximum rate of degradation of the FRQ protein and Kd is the
Michaelis constant associated with this process.
Fixed points are computed from the nullclines xP 1 D 0, xP 2 D 0, and xP 3 D 0.
From Eq. (3.28) one has
x3 D K1
x
K2 2 (3.31)
By substituting Eq. (3.31) and after intermediate operations one obtains x1 also as a
function of x2 that is
K2 .vd CK1 Kd /x2 CK1 K2 Kd x22 .K2 Kd CK2 x2 /K1 x2

x1 D K2 .Ks Kd CKs x2 /
(3.32)
By substituting Eqs. (3.31) and (3.32) into Eq. (3.28) and after intermediate
operations one obtains the equation
vm k12 .kd 1/x23 C Œvm Kin K1 K2 Kd vm Kin K1 K2 C vm K1 vd vs Kin K1 K2 Kd

Cvs Kin K1 K2 x22 C Œvm Kin K2 vd vs Kin Km Ks K2 vs K1n K2 .vd C K1 Kd / C vs
CKin K1 K2 Kd x2 vs Kin Km K2 Ks Kd
(3.33)
a 25 b 14
12
20
10
8
15
x2
x2
6
10
4
2
5
0
0 −2
0.4 0.5 0.6 0.7 0.8 0.9 1 −100 −80 −60 −40 −20 0 20
Kd c2
Fig. 3.1 (a) Bifurcation of fixed point x2;2 (blue line) and x2;3 (red line) of the circadian
oscillators under variation of the Michaelis parameter Kd , (b) Bifurcation of fixed point x2;2 (blue
line) and x2;3 (red line) of the circadian oscillators under state feedback with gain c2
The control input of the circadian oscillator is taken to be zero, that is Ks D 0.

It is assumed that the bifurcating parameter is Kd (Michaelis constant). By substi-
tuting the numerical values of the parameters of the model into the characteristic
polynomial one obtains
x2 f0:3750.kd 1/x22 C .0:2913Kd C 0:7587/x2 C .0:0039Kd 0:8196/g D 0

(3.34)
A first fixed point is located at
.x1;1 ; x2;1 ; x3;1 / D .0; 0; 0/ (3.35)
For the binomial appearing in the above equation the determinant is D

0:0791Kd2 C 1:6773Kd 0:6536 which is positive for Kd 0:3891. In such a case
there are two more fixed points at
q
.0:2913Kd C 0:7587/ C 0:0791Kd2 C 1:6773Kd 0:6538
x2 D (3.36)
0:75.Kd 1/
q
.0:2913Kd C 0:7587/ 0:0791Kd2 C 1:6773Kd 0:6538
x2 D (3.37)
0:75.Kd 1/
The bifurcation diagram of the fixed points considering as bifurcation parameter

the Michaelis constant Kd is given in Fig. 3.1a. Next, the Jacobian matrix of the
dynamic model of the system is computed, which is given by
0 K n nx n1
1
vm .K KCx
M
2 0 .Kin Cx3 n /2
B M 1/ i 3 C
J D@ 0 Kd
.KvdCx 2 K1 K2 A (3.38)
d 2/
0 K1 K2
The associated characteristic polynomial is
p. / D 3 C Œ Kvdd C K1 C K2 C KvmM 2 C Œ KK2 dvd C KvMM . Kvdd / C K1 C K2 C KvMM KK2 dvd :

(3.39)
The variation ranges for parameter Kd are taken to be Kd 2ŒKdmin ; Kdmax D
Œ0:4; 0:9. Then the variation ranges of the rest of the parameters of the characteristic
polynomial are: c2 D Œ Kvdd C K1 C K2 C KvMM 2Œ3:59; 5:54, c1 D KK2 dvd C KvMM . Kvdd / C
K1 C K2 2Œ3:42; 6:41 and c0 D KvMM KK2 dvd 2Œ0:88; 1:97.
Next, the four Kharitonov polynomials are computed as follows:
p1 . / D c0max C c1max C c2min 2 C c3min 3

p2 . / D c0min C c1min C c2max 2 C c3max 3
(3.40)
p3 . / D c0min C c1max C c2max 2 C c3min 3
p4 . / D c0max C c1min C c2min 2 C c3max 3
which take the values
p1 . / D 1:97 C 6:41 C 3:59 2 C 3

p2 . / D 0:88 C 3:42 C 5:54 2 C 3
(3.41)
p3 . / D 0:88 C 6:41 C 5:54 2 C 3
p4 . / D 1:97 C 3:42 C 3:59 2 C 3
The Routh criterion is applied for each characteristic polynomial pi . / i D

1; ; 4. For polynomial p1 . / it holds
3 j 1 6:41
2 j 3:59 1:97
(3.42)
1 j 5:86 0
0 j 1:97
concluded that the characteristic polynomial is a stable one. For polynomial p2 . /
it holds
3 j 1 3:42
2 j 5:54 0:88
(3.43)
1 j 3:26 0
0 j 0:88
it holds
3 j 1 6:41
2 j 5:54 0:88
(3.44)
1 j 6:25 0
0 j 0:88
it holds
3 j 1 3:42
2 j 3:59 1:97
(3.45)
1 j 2:87 0
0 j 1:97
concluded that the characteristic polynomial is a stable one. Consequently, the fixed
point .x1;1 ; x2;1 ; x3;1 / D .0; 0; 0/ is a stable one (sink) for the considered variations
of Kp .
3.5.2 Method to Detect Hopf Bifurcations

in the Circadian Cells
Using the characteristic polynomial of the linearized equivalent of the biological

model, it is possible to formulate conditions for the emergence of Hopf bifurcations.
The whole procedure makes again use of the Routh–Hurwitz criterion.
Consider the characteristic polynomial computed at a fixed point
P . / D cn n C cn1 n1 C cn2 n2 C C c1 C c0 (3.46)
The coefficients ci ; i D 0 ; n are functions of the bifurcating parameter, which is

denoted as .
The following matrix is introduced
0 1
cn1 cn 0 0 0 0
B C
B cn3 cn2 cn1 0 0 0 C
B C
j D B cn5 cn4 cn3 cn2 0 0 C
B C
@ A
cn.2j 1/ cn.2j 2/ cn.2j 3/ cn.2j 4/ cn.2j nC1/ cn.2j n/
(3.47)
where coefficients cn.2j m/ with j D 1; 2; ; n and m D 1; 2; ; n become

zero if n .2j m/ < 0 or if n .2j m/ > n.
The Routh–Hurwitz determinants show the existence of eigenvalues which are
conjugate imaginary numbers. A series of matrices containing the coefficients cj
are defined as follows:
1 D cn1

cn1 cn
2 D
cn3 cn2
(3.48)
0 1
cn1 cn 0
3 D @cn3 cn2 cn1 A
cn5 cn4 cn3
and so on. Each matrix j ; j D 1; ; n 1 is square and the first column contains
every other coefficient of the characteristic polynomial cn1 ; cn3 ; . The roots of
the characteristic polynomial p. / have negative real parts if and only if det.j / >
0 for j D 1; ; n. The following two remarks can be made:
(i) Since det.n / D c0 det.n1 / this means that a necessary condition for the
roots of p. / to have negative real part is c0 > 0. If c0 D 0, then there is a zero
eigenvalue.
(ii) If det.j / > 0 for all j D 1; 2; ; n 2 and det.n1 / D 0, then
the characteristic polynomial contains imaginary roots. Provided that the rest
of the roots of the characteristic polynomial have negative real part then
Hopf bifurcations appear. An additional condition for the appearance of Hopf
bifurcations is that the derivative of the determinant det.n1 / D 0 with respect
to the bifurcating parameter is not zero. That is dd
det.n1 / ¤ 0.
According to the above criteria (i) and (ii) one can determine where possible saddle-
node bifurcations (eigenvalue 0) and Hopf bifurcations (imaginary eigenvalues)
appear. Therefore, one can formulate conditions about the values of the bifurcating
parameter that result in a particular type of bifurcations.
Equivalently, conditions about the appearance of Hopf bifurcations can be
obtained from the Routh table according to Sect. 3.2. The zeroing of certain rows
of the Routh table gives an indication that the characteristic polynomial contains
imaginary conjugate eigenvalues. By requiring the elements of these rows of the
Routh matrix to be set equal to zero one finds the values of the bifurcating parameter
that result in the appearance of Hopf bifurcations.
For the previous characteristic polynomial of the circadian cells one has
p. / D 3 C Œ Kvdd C K1 C K2 C KvMM 2 C Œ KK2 dvd C KvMM . Kvdd C K1 C K2 / C KvMM KK2 dvd

(3.49)
which after the substitution of numerical values for its parameters becomes
p. / D 3 C Œ K
1:4
d
C 2:0375 2 C Œ 2:1525
Kd
C 1:0313 C 0:7875
Kd (3.50)
Using the Routh–Hurwitz determinants one has
1 D c1 D 1:4
Kd
C 2:0375 (3.51)
For 1 > 0 it should hold Kd < 0:6871 which is not possible since Kd is a
positive parameter.
For the determinant of 2 to be zero, where
!
c1 c0
1:4
C 2:0375 1
2 D D Kd
(3.52)
c3 c2 0:7875
Kd
2:1525
Kd
C 1:0313
one obtains the relation 3:0135

Kd2
C 5:0420
Kd
C 2:1013 D 0 which in turn gives Kd D
1:2722, Kd D 1:1273. Again, these values are not acceptable since Kd > 0.
Therefore, no Hopf bifurcations can appear at the fixed point .x1;1 ; x2;1 ; x3;1 / D
.0; 0; 0/, under the existing set of parameters’ values.
At the same conclusion one arrives if the Routh–Hurwitz matrix is used, that is
3 j 1 2:1525
Kd
j Kd C 2:0375
2 1:4 0:7875
Kd
(3.53)
1 j 3:0135
K 2 5:0420
Kd
2:1013 0
d
0 j 0:7875
Kd
1:4
For the first coefficient of the second row of the matrix it holds K d
C2:0375 > 0. To
obtain zero coefficients at the line associated with 1 (so as imaginary eigenvalues
to appear in the characteristic polynomial of the preceding line) one has again the
relation 3:0135
Kd2
C 5:0420
Kd
C 2:1013 D 0 which in turn gives Kd D 1:2722, Kd D
1:1273. As mentioned, these values are not acceptable since Kd > 0. Therefore,
no Hopf bifurcations can appear at the fixed point .x1;1 ; x2;1 ; x3;1 / D .0; 0; 0/,
under the existing set of parameters’ values.
3.6 Feedback Control of Bifurcations
Next, it is considered that input Ks is a feedback control term of the form Ks D

c2 x2 . Then the dynamics of the circadian oscillator becomes
Kn
xP 1 D vs K n Cx
i
n vm K Cx
m
x1
1
i 3
xP 2 D vd KdxCx
2
2
K 1 x 2 C K 2 x 3 C c2 x 1 x 3 (3.54)
xP 3 D K1 x2 K2 x3
3.6 Feedback Control of Bifurcations 67
Feedback can change the oscillation characteristics of the circadian model. It can
change the type of stability characterizing the system’s fixed points. Additionally
fixed points bifurcations can be altered through state feedback control. The previ-
ously analyzed Eq. (3.33) is considered again for computing fixed points
vm k12 .Kd 1/x23 C Œvm Kin K1 K2 Kd vm Kin K1 K2 C vm K1 vd vs Kin K1 K2 Kd

Cvs Kin K1 K2 x22 C Œvm Kin K2 vd vs Kin Km Ks K2 vs K1n K2 .vd C K1 Kd /
Cvs Kin K1 K2 Kd x2 vs Kin Km K2 Ks Kd
(3.55)
Next, the nominal value of Kd will be considered known and will be substituted
in the characteristic polynomial, while the input Ks will be considered equal to the
feedback law of the form Ks D c2 x2 . In such a case the equation for computing x2
becomes
vm k12 .Kd 1/x23

CŒvm Kin K1 K2 Kd vm Kin K1 K2 C vm K1 vd vs Kin K1 K2 Kd C vs Kin K1 K2
vs Kin Km c2 K2 x22 C Œvm Kin K2 vd vs K1n K2 .vd C K1 Kd / C vs Kin K1 K2 Kd
vs Kin Km K2 c2 Kd x2
(3.56)
Substituting numerical values for the model’s parameters and taking Kd D 1:4 the
equation for computing x2 becomes
x2 f0:15x22 C .1:1665 C 0:0126c2 /x2 C .0:8157 C 0:0176c2 /g D 0 (3.57)
The fixed points for the model of the circadian cells are found to be:
First fixed point: .x1;1 ; x2;1 ; x3;1 / D .0; 0; 0/ whereas from the computation
of the associated determinant one obtains D ..1:6665 C 0:0126c2 /2 C
0:6.0:8157 C 0:0176c2 // which is positive if c2 takes values in the intervals
c2 < 251:15 and c2 > 82:39. Thus, for > 0 one has the fixed points
expressed as functions of the feedback gain c2
Second fixed point:
K1 .Kd 1/x2 ;2 Cvd

x1;2 D c2 .kd C1/
p
.1:665C0:0126c2 /C 1:58104 c22 C0:0527c2 C3:2694
x2;2 D 0:3
(3.58)
x3;2 D K1
x ;2
K2 2
Third fixed point:
K1 .Kd 1/x2 ;3 Cvd

x1;3 D c2 .kd C1/
p (3.59)
.1:665C0:0126c2 / 1:58104 c22 C0:0527c2 C3:2694
x2;3 D 0:3
x3;3 D K1
x ;3
K2 2
The bifurcation diagram of the fixed points considering as bifurcating parameter the
feedback control gain c2 is given in Fig. 3.1b. Next, from the right part of Eq. (3.54)
the system’s Jacobian is computed
0 1
Kin nx3n1
vm .KmKCx
m
0 vs
B 1/
2
.Kin Cx3n /2 C
J DB
@ c2 x 2 vd .K KCx
d
2 K 1 C c2 x 1 K2
C
A (3.60)
d 2/
0 K1 K2
From the system’s Jacobian a generic form of the characteristic polynomial is

computed at the fixed point .x1 ; x2 ; x2 /. After intermediate operations one obtains
nh i h io
kd Km
det. I J / D 3 C k2 C K vdCx 2 K1 c2 x1 C vm C 2
nh i h ih i o
2
d 2 K m Cx 1
kd Km Kd vs Kin nx3n1
C .K vdCx 2 K1 K1 K2 C vm C K2 C .KvdCx 2 K1 c2 x1 .K n
Cx n 2
nh i h i o
2
d 2 / .Km Cx 1 / d 2 / i 3 /
Km vd Kd vs Kin nx3n1 vd Kd
C vm C K Cx 2 K c2 x1 K1 K2 .K n Cx n /2 K Cx 2 C K1 c2 x2
.Kd Cx2 /2 1
m 1 i 3 d 2
(3.61)
or equivalently
det. I J / D 3 C cf2 2 C cf1 C cf0 (3.62)
where

Km vd Kd
cf0 D vm C K 1 c x
2 1 K K
1 2
Km C x 1 2 .Kd C x2 /2

vs Kin nx3n1 vd Kd
C K 1 c x
2 2 (3.63)
.Kin C x3n /2 Kd C x2 2

vd kd Km
cf 1 D K1 K1 K2 C vm C
.Kd C x2 /2 .Km C x1 /2

vd Kd vs Kin nx3n1
K2 C K 1 c2 x 1 (3.64)
.Kd C x2 /2 .Kin C x3n /2
3.6 Feedback Control of Bifurcations 69

vd kd Km
cf 2 D k2 C K1 c2 x1 C vm C (3.65)
Kd C x 2 2 Km C x 1 2
The associated Routh matrix is
3 j 1 cf1
2 j cf 2 cf 0
(3.66)
1 j c f 0 c f 1 c f 2 0
0 j cf 0
The condition for obtaining Hopf bifurcation is cf2 > 0 and cf0 cf1 cf2 D 0. It can
be confirmed that for the fixed point .x1;2 ; x2;2 ; x3;2 / and for the previously used set
of values of the parameters of the circadian oscillator model, solutions c2 obtained
from the condition cf0 cf1 cf2 D 0 result in cf2 < 0, therefore Hopf bifurcations
do not appear.
The bifurcation diagram of Fig. 3.1b shows the limit values of c2 beyond which
x2;2 remains positive. Such a value is c2 < 45:2. It is examined next if for
specific range of variations of parameter c2 the fixed point .x1;2 ; x2;2 ; x3;2 / is a
stable or an unstable one. To this end Kharitonov’s theorem will be used again. For
c2 2Œ60:2; 50:2 it holds that cf2 2Œ31:31; 31:91, while cf1 2Œ68:33; 70:39 and
cf0 2Œ23:27; 23:67. The associated four Kharitonov polynomials take the values
p1 . / D 23:67 C 70:39 C 31:31 2 C 3

p2 . / D 23:27 C 68:33 C 31:91 2 C 3
(3.67)
p3 . / D 23:27 C 70:39 C 31:91 2 C 3
p4 . / D 23:67 C 68:33 C 31:31 2 C 3
The Routh table for Kharitonov polynomial p1 . / is
3 j 1 70:39
2 j 31:31 23:67
(3.68)
1 j 69:63 0
0 j 23:67
Since there is no change of sign of the coefficients of the first column of the Routh
table it can be concluded that the characteristic polynomial p1 . / is a stable one.
The associated Routh table for the second Kharitonov polynomial p2 . / is
3 j 1 68:33
2 j 31:91 23:27
(3.69)
1 j 67:59 0
0 j 23:27
Since there are no changes of sign in the coefficients of the first column of the Routh
table it can be concluded that polynomial p2 . / is also stable. The associated Routh
table for Kharitonov polynomials p3 . / and p4 . / are
3 j 1 70:39
2 j 31:91 23:27
(3.70)
1 j 69:66 0
0 j 23:27
Since there is no change of sign of the coefficients of the first column of the Routh
table it can be concluded that the characteristic polynomial p3 . / is a stable one.
Finally, the associated Routh table for the fourth Kharitonov polynomial p4 . / is
3 j 1 68:33
2 j 31:31 23:67
(3.71)
1 j 67:57 0
0 j 23:67
Since there are no changes of sign in the coefficients of the first column of the
Routh tables it can be concluded that polynomial p4 . / is stable. From the previous
analysis it can be seen that all Kharitonov polynomials have stable roots therefore
the fixed point .x1;2 ; x2;2 ; x3;2 / of the circadian oscillator under feedback gain
c2 2Œ60:2; 50:2 is a stable one.
Next, the case that the feedback gain c2 2 Œ270:2; 260:2 is examined. In such
a case the variation ranges for the coefficients of the characteristic polynomial are
cf2 2 Œ58:52; 55:12, cf1 2Œ175:03; 163:82 and cf0 2 Œ88:17; 84:13. The
four Kharitonov polynomials of the system are:
p1 . / D 84:13 163:82 58:52 2 C 3

p2 . / D 88:17 175:03 55:12 2 C 3
(3.72)
p3 . / D 88:17 163:82 55:12 2 C 3
p4 . / D 84:13 175:03 58:12 2 C 3
The associated Routh table for the first Kharitonov polynomial p1 . / is
3 j 1 163:82
2 j 58:52 84:14
(3.73)
1 j 165:25 0
0 j 84:14
Since there is change of sign of the coefficients of the first column of the Routh table
it can be concluded that the characteristic polynomial p1 . / is an unstable one. The
associated Routh table for Kharitonov polynomial p1 . / and p2 . / are
3.7 Simulation Tests 71
3 j 1 175:03
2 j 55:12 88:17
(3.74)
1 j 176:63 0
0 j 88:17
From the changes of sign of the coefficients of the first column of the Routh tables
it can be concluded that polynomial p2 . / is unstable. The associated Routh table
for the third Kharitonov polynomial p3 . / is
3 j 1 163:82
2 j 55:12 88:17
(3.75)
1 j 165:42 0
0 j 88:17
Since there is change of sign of the coefficients of the first column of the Routh
table it can be concluded that the characteristic polynomial p3 . / is an unstable one.
Finally, the associated Routh table for the fourth Kharitonov polynomial p4 . / is
3 j 1 175:03
2 j 58:12 84:13
(3.76)
1 j 176:48 0
0 j 84:13
From the changes of sign of the coefficients of the first column of the Routh tables
it can be concluded that the characteristic polynomial p4 . / is unstable. From the
previous analysis it can be seen that all Kharitonov polynomials have unstable roots;
therefore, the fixed point .x1;2 ; x2;2 ; x3;2 / of the circadian oscillator under feedback
gain c2 2Œ270:2; 260:2 is an unstable one.
3.7 Simulation Tests
The following example is concerned with bifurcations of the fixed point of

the FitzHugh–Nagumo neuron. Assuming zero external current input and
known parameters of the model it has been found the associated fixed point is
.x1;1 ; x2;1 ; x2;1 / D .0; 0; 0/. As confirmed by the results given in Fig. 3.2 this fixed
point is a stable one. The nominal values of the model’s parameters were D 1:5,
D 0:1, and a D 7.
Next, examples on the stability of fixed points in the circadian oscillator model
are given under variation of specific parameters of the dynamical model. The
nominal values of the model’s parameters were: vs D 0:02, Ki D 0:9, vm D 1:5,
Km D 1:6, Ks D 1, vd D 1:4, K1 D 0:5, K2 D 0:6, n D 4, while Kd
a 2 b 3
1.5 2.5
x1−x*1
1
2
0.5
0 1.5
x2−x*2
0 5 10 15 20
time
1
3
2 0.5
x2−x*2
1
0
0
−1 −0.5
0 5 10 15 20 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8
time x1−x*1
Fig. 3.2 The fixed point of the FitzHugh–Nagumo neuron is a stable one: (a) diagrams of the state
variables, (b) phase diagrams
a 20 b 20
x1−x*1
15
10
x2−x*2
10
0
0 5 10 15 20 5
time
20 0
0 2 4 6 8 10 12
x2−x*2
10 x1−x*1
15
0
0 5 10 15 20
time 10
x3−x*3
20
x3−x*3
5
10
0 0
0 5 10 15 20 0 5 10 15 20
time x2−x*2
Fig. 3.3 The first fixed point of the circadian oscillator becomes a stable one for parameter
Kd 2Œ0:3; 0:9: (a) diagrams of the state variables, (b) phase diagrams
was an uncertain parameter. It was assumed that the Michaelis constant parameter
varies within intervals, that was Kd 2Œ0:4; 0:9 and based on this interval the ranges
of variation of the Jacobian matrix of the model computed at the fixed point
.x1;1 ; x2;1 ; x2;1 / D .0; 0; 0/ were found. By applying Kharitonov’s theorem it was
possible to show that conditions about the stability of the fixed point were satisfied.
The associated results are depicted in Fig. 3.3.
Moreover, the case of state feedback was considered in the form Ks D c2 x2 and
using parameter c2 as feedback gain. The variation range of c2 was taken to be the
interval Œ60:2; 50:2 and based on this the ranges of variation of the coefficient
of the characteristic polynomial of the system’s Jacobian matrix were computed.
Stability analysis followed, using Kharitonov’s theorem. First, it was shown that by
choosing 60:2 < c2 < 50:2 e.g. c2 D 55 then the fixed point .x1;2 ; x2;2 ; x3;2 /
remained stable.
Next, it was shown that by setting 270:2 < c2 < 260:2 e.g. c2 D 265
the fixed point became unstable. Indeed in the first case, that is when c2 D 55
3.8 Conclusions 73
a 2 b 3
x1−x*1
2
1
x2−x*2
1
0
0 5 10 15 20 0
time
5 −1
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8
x2−x*2
0 x1−x*1
4
−5
0 5 10 15 20
2
time
x3−x*3
5
0
x3−x*3
0 −2
−5 −4
0 5 10 15 20 −0.5 0 0.5 1 1.5 2 2.5
time x2−x*2
Fig. 3.4 The second fixed point of the circadian oscillator is stable for feedback gain value
c2 2Œ60:2; 50:2: (a) diagrams of the state variables, (b) phase diagrams
a 1.4
b 2.8
2.6
x1−x1
*
1.2
x2−x*2
2.4
1
0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16 2.2
time
3 2
1 1.05 1.1 1.15 1.2 1.25 1.3 1.35 1.4
x2−x2
x1−x*1
*
2.5
6
2
0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16
time 5
x3−x3
*
6
x3−x3
*
4
4
2 3
0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16 2 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8
time x −x*
2 2
Fig. 3.5 The second fixed point of the circadian oscillator is unstable one for feedback gain value
c2 2Œ270:2; 260:2: (a) diagrams of the state variables, (b) phase diagrams
the roots of the characteristic polynomial that is associated with the Jacobian of the
system are 1 D 29:49, 2 D 1:52, and 3 D 0:42, which means that the
fixed point is a stable one. In the second case, that is for c2 D 265 the roots of the
characteristics polynomial became 1 D 59:5, 2 D 2:21, and 3 D 0:65 which
means that the fixed point is an unstable one. The associated results are depicted in
Figs. 3.4 and 3.5.
3.8 Conclusions
The chapter has studied bifurcations in biological models, such as circadian cells.
It has been shown that the stages for analyzing the stability features of the fixed
points that lie on bifurcation branches comprise (i) the computation of fixed points
as functions of the bifurcation parameter and (ii) the evaluation of the type of
stability for each fixed point through the computation of the eigenvalues of the
Jacobian matrix that is associated with the system’s nonlinear dynamics model.
Stage (ii) requires the computation of the roots of the characteristic polynomial
of the Jacobian matrix. This problem is nontrivial since the coefficients of the
characteristic polynomial are functions of the bifurcation parameter and the latter
varies within intervals. To obtain a clear view about the values of the roots of
the characteristic polynomial and about the stability features they provide to the
system, the use of interval polynomials theory and particularly of Kharitonov’s
stability theorem has been proposed. In this approach the study of the stability of a
characteristic polynomial with coefficients that vary in intervals is equivalent to the
study of the stability of four polynomials with crisp coefficients computed from the
boundaries of the aforementioned intervals. The method for fixed points stability
analysis was tested on two different biological models: (1) the FitzHugh–Nagumo
neuron model, (2) a model of circadian cells which produce proteins out of an RNA
transcription and translation procedure. The efficiency of the proposed stability
analysis method has been confirmed through numerical and simulation tests.
Chapter 4
Oscillatory Dynamics in Biological Neurons
Abstract The voltage of the neurons membrane exhibits oscillatory variations after
receiving suitable external excitation either when the neuron is independent from
neighboring neural cells or when the neuron is coupled to neighboring neural cells
through synapses or gap junctions. In the latter case it is significant to analyze
conditions under which synchronization between coupled neural oscillators takes
place, which means that the neurons generate the same voltage variation pattern
possibly subject to a phase difference. The loss of synchronism between neurons
can cause several neurodegenerative disorders. Moreover, it can affect several basic
functions of the body such as gait, respiration, and heart’s rhythm. For this reason
synchronization of coupled neural oscillators has become a topic of significant
research during the last years. The associated results have been also used in several
engineering applications, such as biomedical engineering and robotics. For example,
synchronization between neural cells can result in a rhythm generator that controls
joints motion in quadruped, multi-legged, and biped robots.
4.1 Neural Oscillators
Neurons exhibit complicated activation functions, denoted as spiking and bursting.

This activation mechanism is characterized by a silent stage (resting) and a stage
with intensive spike-like oscillations. Bursting activity appears in specific thalamic
cells (this affects, for example, the phases of sleep in people with parkinsonian
tremor and in such a case increased bursting activity appears in neurons which
are found in basal ganglia). Moreover, bursting activity appears in cells which
coordinate breath’s rhythm, inside the so-called pre-Botzinger complex.
There is need for two biophysical mechanisms to generate bursting: (1) a
mechanism for the generation of the bursting oscillations, (2) a mechanism for the
switching between the silent phase and the bursting phase.
Spikes are voltage oscillations which are generated by the interaction of an
incoming NaC current and an outgoing KC current. The slow phase is due to an ionic

76 4 Oscillatory Dynamics in Biological Neurons
current which is activated or deactivated at a slower pace than the rest of the currents.
A slow current which forms the basis for the slow modulation phase is the calcium-
dependent potassium current IKCa . Ions of Ca2C enter the cell’s membrane during
the active spiking phase and this results in raise (activation) of the current IKCa
(outward current). When the outward current becomes sufficiently large the cell can
no longer produce the spiking activity and the active phase is terminated. During the
silent phase, there is an outflow of Ca2C from the cell’s membrane and the calcium
channels close.
A generic mathematical model of the bursting activity is described by a set of
differential equations which evolve at multiple scales
dx
dt
D f .x; y/
dy (4.1)
dt
D g.x; y/
where > 0 takes a small positive value. In the above set of equations x2Rn are fast
variables which are responsible for spikes generation, and y2Rm are slow variables
which are responsible for the slow modulation of the silent and active phases.
There are different types of bursting which are different in the amplitude and
frequency of oscillations that the neuron’s membrane performs during the active
phase. These are [3, 16, 49, 65]:
1. square-wave bursting: This form of bursting was first observed in pancreatic ˇ-
cells. In square-wave bursting the amplitude of the membrane’s voltage variation
remains practically unchanged, whereas the frequency of spiking slows down
during the active phase.
2. elliptic bursting: In elliptic bursting one can notice small amplitude oscillations
during the silent phase, and progressively the amplitude of the oscillations
increases and remains unchanged for a long time interval. During the active
phase the frequency of spikes initially increases and subsequently drops. Elliptic
bursting appears in models of thalamic neurons, and particularly in neurons of
the basal ganglia.
3. parabolic bursting: In parabolic bursting there are no oscillations during the silent
phase and there is an abrupt transition to the active phase which consists of
oscillations of large amplitude. The values of the parameters of the dynamic
model of the neuron are the ones which define which type of bursting will finally
appear.
Indicative diagrams of biological neurons under spiking activity are given in
Fig. 4.1. Moreover, representative diagrams of neurons under bursting activity are
shown in Fig. 4.2.
It is noted that by changing the parameters of the dynamic model, the neuron
bursting can exhibit chaotic characteristics which have to do with the number of
spikes during the active phase, the frequency under which bursts appear and the
transition from bursting to spiking [88].
4.2 Synaptic Channels 77
a 0.1 b 0.06
0.05 0.058
0.056
Vm
0.054
−0.05
0.052
−0.1
0 20 40 60 80 100
2
0.05
x
time (sec)
0.06 0.048
0.055 0.046
w
0.05 0.044
0.045 0.042
0.04 0.04
0 20 40 60 80 100 −0.1 −0.05 0 0.05 0.1
time (sec) x
1
Fig. 4.1 (a) State variables of the FitzHugh–Nagumo neuron model under spiking activity, (b) The
associated phase diagram
a 0.2 b 0.8
0.1
0.6
Vm
0
0.4
−0.1
−0.2 0.2
0 20 40 60 80 100
x2
time (sec)
1 0
0.5 −0.2
w
0 −0.4
−0.5 −0.6
0 20 40 60 80 100 −0.2 −0.15 −0.1 −0.05 0 0.05 0.1 0.15 0.2
time (sec) x1
Fig. 4.2 (a) State variables of the FitzHugh–Nagumo neuron model under bursting activity,
(b) The associated phase diagram
4.2 Synaptic Channels
In the isolated neurons studied up to now, ion-gated and voltage-gated channels have
been studied, i.e. channels which allow the passage of specific ions (KC , NaC , and
Ca2C ) and which open or close if the value of the membrane’s potential exceeds
a threshold or if the concentration of ions also exceeds a certain threshold. There
are also other channels, among which the most important are the synaptic channels
[16, 26, 65].
The events which lead to opening of synaptic channels include several stages.
The wave-type spatiotemporal variation of the membrane’s potential V .x; t / travels
along the membrane of the axon and arrives at pre-synaptic areas which are called
synaptic terminals. These terminals contain ions, such as Ca2C . When the terminals
get depolarized Ca2C ions are released. A protein (vesicle) binds the Ca2C ions,
transfers them through the synapse, and releases them at a post-synaptic site.
Actually, the neurotransmitter is diffused through the synapse and once reaching
Fig. 4.3 Neurotransmitter

for neurons connected
through a synapse
the post-synaptic neuron it is attached to various receptors (usually on the so-called

protuberances, which are part of dendrites known as spines).
In their turn, these receptors open channels which either hyperpolarize or
depolarize the neuron according to the type of the neurotransmitter. The presence
of other chemical substances in the presynaptic channel may facilitate or inhibit
the binding of ions by the vesicle. Moreover, the binding or release of ions by
the vesicle can be performed in a stochastic manner. Additionally, the presynaptic
excitation can lead to activation of more proteins-transmitters which means that a
larger quantity of ions will be transferred and released at the post-synaptic neuron.
This increase of ion transfer is called potentiation or facilitation. There is also the
inverse phenomenon, in which after several presynaptic spikes, the transfer and
release of ions at the post-synaptic neuron decreases. This is known as depression
(Fig. 4.3).
4.3 Dynamics of the Synapses
The following cases of synapses dynamics are examined: (1) the glutamate: it
stimulates the post-synaptic cell and open channels [16, 65], (2) the aminobutyric
acid, also known as GABA: it inhibits the postsynaptic cell and closes channels.
The synaptic currents which are developed in such a case depend on a conduc-
tivity parameter and on the difference between the membrane’s voltage and voltage
threshold value.
Isyn D g.t /.Vpost Vrev / (4.2)
A common assumption made is that conductivity is a sum of constant functions

which depend only on the time instances in which the presynaptic cell has given a
spike.
4.3 Dynamics of the Synapses 79
Fig. 4.4 Model of the

variation of synaptic 1.6
conductances in the case of a
single pre-synaptic spike: (a) 1.4
AMPA (blue) and (b) GABAA
1.2
(red)
1
sa−sb
0.8
0.6
0.4
0.2
0
0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16 0.18 0.2
time (sec)
P
g.t / D gN k a.t tk / D gz.t
N / (4.3)
where
a.t / D ad ar
ar ad
.e ad t e ar t / (4.4)
or a.t / D ad2 e ad t . As far as parameter z.t / is concerned its variation in time is
given by the differential equation
z00 C .ar C ad /z0 C ar ad z D 0 (4.5)
Another manner for modelling conductivity in the synapse is to use
g.t / D gs.t
N / (4.6)
where s.t / denotes the fraction of the open channel which satisfies the relation
ds
dt
D ar ŒT .1 s/ ad s (4.7)
where ŒT is the concentration of the transmitter coming from the pre-synaptic

neuron and released at the post-synaptic neuron (Fig. 4.4).
The time is set at t D t0 . Then the concentration ŒT becomes equal to Tmax and
at time instant t1 it returns to zero. Then
s.t t0 / D s1 C .s.t0 / s1 /e .tt0 /=t0 (4.8)

for t0 < t < t1 where
s1 D ar Tmax
ar Tmax Cad (4.9)
and
s D 1
ar Tmax Cad (4.10)
After the pulse of the transmitter has gone, s.t / decays as
s.t / D s.t1 /e ad .tt1 / (4.11)
A model about the concentration of the transmitter at the pre-synaptic neuron is
ŒT .Vpre / D Tmax
1Cexp..Vpre VT =KCp// (4.12)
4.4 Study of the Glutamate Neurotransmitter
Glutamate neurotransmitter activates two different types of receptors: (1)

AMPA/Kainate which is vary fast, (2) NMDA which is associated with memory.
Both receptors lead to activation of the post-synaptic neuron [16, 65].
(a) AMPA/Kainate
The current associated with the neuro-transmitter is
IAMPA D gN AMPA .V VAMPA / (4.13)
The responses of AMPA synapses can be very fast, for example in the case of
acoustic neurons they can have rise and decay times of the order of milliseconds.
Similarly, in the case of cortical neurons the rise and decay time can be of the
order of 0.4–0.8 ms. AMPA synapses exhibit intensive depression in case of
subsequent spikes. Each time that a spike is generated the amplitude of the
AMPA current at the post-synaptic neuron drops.
(b) NMDA
The NMDA receptor is also sensitive to glutamate with a response that lasts
longer than the one of AMPA. Under normal conditions the NMDA receptor
is partially found blocked by Mg2C ions. One of the basic types of ions that
is transferred by the NMDA current is Ca2C which is responsible for many
long-term changes in neurons. This ion is considered to affect significantly the
mechanism of short-term memory.
4.5 Study of the GABA Neurotransmitter 81
The NMDA current is modelled as
INMDA D gN NMDA sB.V /.V VNMDA / (4.14)
where s is given by the previous relation
ds
dt
D ar ŒT .1 s/ ad s (4.15)
and
B.V / D 1
1Ce 0:062V ŒMg2C =3:57
(4.16)
4.5 Study of the GABA Neurotransmitter
GABA is the main inhibitory neurotransmitter in the cortex and can be distinguished
into two types, i.e. GABAA and GABAB [16, 65].
(a) GABAA
The neurotransmitter GABAA is responsible for inhibiting the stimulation
of the post-synaptic neuron and as in the case of AMPA and NMDA this
neurotransmitter is activated by a spike.
The associated current equation is
IGABAA D GN GABAA s.V VGABAA / (4.17)
(b) GABAB
At the postsynaptic neuron a receptor protein binds the neurotransmitter and
activates an intracellular circuit (G-protein). Next a KC channel is activated
which polarizes the membrane of the post-synaptic neuron. The equations of
current associated with the GABAB neurotransmitter are as follows:
n
IGABAB D gN GABAB KdCs
s
n .V Ek /
dr
dt
D ar ŒT .1 r/ br r (4.18)
ds
dt
D k3 r k d s
(c) Permanent connections between neurons (Gap or electrical junctions)

There are connections between neurons which do not depend on a neurotrans-
mitter (vesicle). The associated current is
Igap D gN gap .Vpost Vpre / (4.19)
where ggap denotes conductivity. This model is usually met in neurons of the
cerebral cortex.
a b
Fig. 4.5 (a) Synaptic depression: decrease in the amplitude of the post-synaptic current (b) synap-
tic facilitation: increase in the amplitude of the post-synaptic current
4.6 Short- and Long-Term Plasticity
Short-term plasticity is distinguished from long-term plasticity and denotes a

change in the amplitude of the current appearing at the post-synaptic neuron, as
a consequence of spikes generated at the pre-synaptic neuron. An example is given
in the diagram of Fig. 4.5 and shows connection between cortical excitatory cells
(RS) and cortical fast synaptic units (FS) [16, 65].
Next, it is explained how a pre-synaptic current affects the amplitude of the post-
synaptic current. One defines
M.t / D q.t /f .t / (4.20)
where q.t /2.0; 1/ is the depression factor having as resting value q0 and f .t /2.0; 1/
is the facilitating factor having as resting value f0 . The variation of f and q is
given by
df
f dt
D f0 f; d dq
dt
D d0 q (4.21)
4.7 Synchronization of Coupled FitzHugh–Nagumo Neurons Using. . . 83
Each time a spike occurs f .t / increases by .1 f / and q.t / decreases by ad d .

There are also more detailed models about the change of f; q, given by
df f0 f P
D f
C j ı.t j /af .1 f/
dt
P (4.22)
dq
dt
D d0q
d
j ı.t j /ad q
Moreover, there are different models to describe the variation of f and q, which do
not include the spiking times. For example,
dq d0 q
dt
D d
ad .V /q
(4.23)
ad.V / D a
1Ce k.V Vthr /
Neurons plasticity affects memory. A basic assumption in neuroscience is that

memories are stored in the strength of the synaptic connections (Hebbian Learning).
Hebb rules enforce or weaken a synapse, depending on whether presynaptic or post-
synaptic neurons are active. If both neurons are active, then one has enforcement of
the neural synapse, otherwise the synapse is weakened (for both neurons to be active
it is necessary the potential of each neuron’s membrane to have a high value. The
potential can be computed by the solution of the differential equations describing
the propagation of the membrane’s potential).
4.7 Synchronization of Coupled FitzHugh–Nagumo Neurons

Using Differential Flatness Theory
4.7.1 The Problem of Synchronization of Coupled Neural

Oscillators
The voltage of the neuron’s membrane exhibits oscillatory variations after receiving
suitable external excitation either when the neuron is independent from neighboring
neural cells or when the neuron is coupled to neighboring neural cells through
synapses or gap junctions [16, 98, 182]. In the latter case it is significant to analyze
conditions under which synchronization between coupled neural oscillators takes
place, which means that the neurons generate the same voltage variation pattern
subject to a phase difference. The loss of synchronism between neurons can
cause several neuro-degenerative disorders. Moreover, it can affect several basic
functions of the body such as gait, respiration, and heart’s rhythm. For this reason
synchronization of coupled neural oscillators has become a subject of significant
research during the last years. The associated results have been also used in several
engineering applications, such as biomedical engineering and robotics. For example,
synchronization between neural cells can result in a rhythm generator that controls
joints motion in quadruped, multi-legged, and biped robots.
Dynamical models of coupled neural oscillators can serve as Central Pattern
Generators (CPGs) [70, 212]. This means that they stand for higher level control
elements in a multi-layered control scheme which provide the activation frequency
and rhythm for controllers operating at the lower level, e.g. controllers that provide
motion to robot’s joints. CPG methods have been used to control various kinds of
robots, such as crawling robots and legged robots and various modes of locomotion
such as basic gait control, gait transitions control, dynamic adaptive locomotion
control, etc. [85]. CPG models have been used with hexapod and octopod robots
inspired by insect locomotion [11]. CPGs have been also used for controlling swim-
ming robots, such as lamprey robots [40]. Quadruped walking robots controlled with
the use of CPGs have been studied in [62]. Models of CPGs are also increasingly
used for the control of biped locomotion in humanoid robots [79].
The problem of synchronization of coupled neural oscillators becomes more
difficult when there is uncertainty about the parameters of the dynamical model
of the neurons [8]. Thus, it is rather unlikely that coupled neurons will have
identical dynamical models and that these models will be free of parametric
variations and external disturbances. To synchronize neurons subject to model
uncertainties and external disturbances several approaches have been proposed.
In [130] by using the Lyapunov function method and calculating the largest
Lyapunov exponent, respectively, a sufficient condition and a necessary condition
of the coupling coefficient for achieving self-synchronization between two coupled
FitzHugh–Nagumo neurons are established. In [5] matrix inequalities on the basis
of Lyapunov stability theory are used to design a robust synchronizing controller
for the model of the coupled FitzHugh–Nagumo neurons. In [217] robust control
system combining backstepping and sliding mode control techniques is used to
realize the synchronization of two gap junction coupled chaotic FitzHugh–Nagumo
neurons under external electrical stimulation. In [207] a Lyapunov function-based
control law is introduced, which transforms the FitzHugh–Nagumo neurons into
an equivalent passive system. It is proved that the equivalent system can be
asymptotically stabilized at any desired fixed state, namely, synchronization can be
succeeded. In [144] synchronizing control for coupled FitzHugh–Nagumo neurons
is succeeded using a Lyapunov function approach. The control signal is based on
feedback of the synchronization error between the master and the slave neurons.
Finally, the use of differential geometric methods in the modelling and control of
FitzHugh–Nagumo neuron dynamics has been studied in [47, 220].
In this chapter, differential flatness theory has been proposed for the synchro-
nization of coupled nonlinear oscillators of the FitzHugh–Nagumo type. Differential
flatness theory is currently a main direction in nonlinear dynamical systems and
enables linearization for a wider class of systems than the one succeeded with Lie-
algebra methods [157, 173, 177]. To find out if a dynamical system is differentially
flat, the following should be examined: (1) the existence of the so-called flat output,
i.e. a new variable which is expressed as a function of the system’s state variables.
The flat output and its derivatives should not be coupled in the form of an ordinary
4.7 Synchronization of Coupled FitzHugh–Nagumo Neurons Using. . . 85
differential equation (ODE), (2) the components of the system (i.e., state variables
and control input) should be expressed as functions of the flat output and its
derivatives [58, 101, 101, 109, 125, 172]. In certain cases the differential flatness
theory enables transformation to a linearized form (canonical Brunovsky form) for
which the design of the controller becomes easier. In other cases by showing that a
system is differentially flat one can easily design a reference trajectory as a function
of the so-called flat output and can find a control law that assures tracking of this
desirable trajectory [58, 200].
This chapter is concerned with proving differential flatness of the model of
the coupled FitzHugh–Nagumo neural oscillators and its resulting description in
the Brunovksy (canonical) form [125]. By defining specific state variables as flat
outputs an equivalent description of the coupled FitzHugh–Nagumo neurons in the
Brunovksy (linear canonical) form is obtained. It is shown that for the linearized
model of the coupled neural oscillators it is possible to design a feedback controller
that succeeds their synchronization. At a second stage, a novel Kalman Filtering
method, the Derivative-free nonlinear Kalman Filter, is proposed for estimating the
non-directly measurable elements of the state vector of the linearized system. With
the redesign of the proposed Kalman Filter as a disturbance observer, it becomes
possible to estimate disturbance terms affecting the model of the coupled FitzHugh–
Nagumo neurons and to use these terms in the feedback controller. By avoiding
linearization approximations, the proposed filtering method improves the accuracy
of estimation and results in smooth control signal variations and in minimization of
the synchronization error [158, 159, 170].
4.7.2 Coupled Neural Oscillators as Coordinators of Motion
Coupled neural oscillators can provide as output signals that maintain a specific
phase difference and which can be used for the coordination of robot’s motion.
These coupled neural oscillators are also known as CPGs and can synchronize
the motion performed by the legs of quadruped and biped robots. The concept of
CPGs comes from biological neurons, located at the spinal level, and which are able
of generating rhythmic commands for the muscles. CPGs receive commands from
higher levels of the central nervous system and also from peripheral afferents. Thus
their functioning is the result of the interaction between central commands and local
reflexes.
Neuronal mechanisms in the brain select which CPGs will be activated at
every time instant. The basal ganglia play an important role in this. Under resting
conditions the output layer of the basal ganglia (the pallidum) maintains different
CPG neurons under inhibition. To achieve CPG activation, striatial neurons, the
input layer of the basal ganglia, inhibit cells in the pallidum which keep under
inhibition the CPG neurons. The striatial neurons can, in turn, be activated from
either neocortex or directly from the thalamus. The responsiveness of striatial
neurons to activation can be facilitated by dopaminergic inputs (Fig. 4.6). On
Fig. 4.6 Biological mechanism of activation of coupled neural oscillators (Central Patterns
Generators)
the other hand, deficiencies or enhanced levels of dopaminergic inputs result in

movements distortion and malfunction of the locomotion system [70, 212].
Coupled neuron models which have been used as CPGs are Hodkin–Huxley
neurons and FitzHugh–Nagumo neurons (Fig. 4.7). CPG methods have been used
to control various kinds of robots, such as crawling robots and legged robots and
various modes of locomotion such as basic gait control, gait transitions control,
dynamic adaptive locomotion control, etc. [85].
4.8 Differential Flatness Theory
4.8.1 Definition of Differentially Flat Systems
The main principles of differential flatness theory are as follows [58, 177, 200]:
A finite dimensional system is considered. This can be written in the general form
P w;
of an ODE, i.e. Si .w; w; R ; w.i/ /; i D 1; 2; ; q. The term w denotes the
system variables (these variables are, for instance, the elements of the system’s
state vector and the control input) while w.i/ , i D 1; 2; ; q are the associated
derivatives. Such a system is said to be differentially flat if there is a collection
of m functions y D .y1 ; ; ym / of the system variables and of their time-
4.8 Differential Flatness Theory 87
Fig. 4.7 Models of coupled neural oscillators in engineering: FitzHugh–Nagumo neurons for
controlling robot’s motion
derivatives, i.e. yi D
.w; w; P w;
R ; w.˛i / /; i D 1; ; m satisfying the following
two conditions [58, 157, 200]: (1) There does not exist any differential relation of
the form R.y; y; P ; y .ˇ/ / D 0 which implies that the derivatives of the flat output
are not coupled in the sense of an ODE, or equivalently it can be said that the flat
output is differentially independent, (2) All system variables (i.e., the elements of
the system’s state vector w and the control input) can be expressed using only the
flat output y and its time derivatives wi D i .y; y; P ; y .i / /; i D 1; ; s.
4.8.2 Conditions for Applying Differential Flatness Theory
The following generic class of nonlinear systems is considered
xP D f .x; u/ (4.24)
Such a system can be transformed to the form of an affine in the input system by
adding an integrator to each input [25]
P
xP D f .x/ C miD1 gi .x/ui (4.25)
If the system of Eq. (4.25) can be linearized by a diffeomorphism z D

.x/ and
a static state feedback u D ˛.x/ C ˇ.x/v into the following form
zPi;j D ziC1;j for 1j m and 1i vj 1

(4.26)
zPvi;j D vj
P
with m j D1 vj D n, then yj D z1;j for 1j m are the 0-flat outputs which can
be written as functions of only the elements of the state vector x (when the flat
output of a system is only function of its states x, then this is called 0-flat). To
define conditions for transforming the system of Eq. (4.25) into the canonical form
described in Eq. (4.26) the following theorem holds [25].
Theorem. For the nonlinear systems described by Eq. (4.25) the following vari-
ables are defined: (i) G0 D spanŒg1 ; ; gm , (ii) G1 D spanŒg1 ; ; gm ;
j
adf g1 ; ; adf gm , (k) Gk D spanfadf gi for 0j k; 1i mg (where adif g
stands for a Lie Bracket). Then, the linearization problem for the system of Eq. (4.25)
can be solved if and only if: (1). The dimension of Gi ; i D 1; ; k is constant for
x2X Rn and for 1i n 1, (2). The dimension of Gn1 is of order n, (3). The
distribution Gk is involutive for each 1kn 2.
4.8.3 Transformation of the Neurons’ Model into the Linear

Canonical Form
It is assumed now that after defining the flat outputs of the initial multi-input multi-
output (MIMO) nonlinear system (this approach will be also shown to hold for the
neuron model), and after expressing the system state variables and control inputs
as functions of the flat output and of the associated derivatives, the system can be
transformed in the Brunovsky canonical form:
xP 1 D x2

xP r1 1 D xr1
Pp
xP r1 D f1 .x/ C j D1 g1j .x/uj C d1
xP r1 C1 D xr1 C2
(4.27)
xP p1 D xp
Pp
xP p D fp .x/ C j D1 gpj .x/uj C dp
y1 D x1

yp D xnrp C1
4.9 Linearization of the FitzHugh–Nagumo Neuron 89
where x D Œx1 ; ; xn T is the state vector of the transformed system (according to

the differential flatness formulation), u D Œu1 ; ; up T is the set of control inputs,
y D Œy1 ; ; yp T is the output vector, fi are the drift functions, and gi;j ; i; j D
1; 2; ; p are smooth functions corresponding to the control input gains, while dj
is a variable associated with external disturbances. It holds that r1 Cr2 C Crp D n.
Having written the initial nonlinear system into the canonical (Brunovsky) form it
holds
.ri / Pp
yi D fi .x/ C j D1 gij .x/uj C dj (4.28)
Next the following vectors and matrices can be defined f .x/DŒf1 .x/; ; fn .x/T ,
g.x/ D Œg1 .x/; ; gn .x/T with gi .x/ D Œg1i .x/; ; gpi .x/T , A D
diagŒA1 ; ; Ap ; B D diagŒB1 ; ; Bp , C T D diagŒC1 ; ; Cp ; d D
Œd1 ; ; dp T , where matrix A has the MIMO canonical form, i.e. with block-
diagonal elements
0 1
01 0
B0 0 0C
B C
B :: C
Ai D B ::: ::: :C
B C
@0 0 1A
(4.29)
0 0 0 r r
i i

BiT D 0 0 0 1 1r

i
CiT D 1 0 0 0 1r
i
Thus, Eq. (4.28) can be written in state-space form
xP D Ax C Bv C B dQ
(4.30)
y D Cx
where the control input is written as v D f .x/ C g.x/u.
4.9 Linearization of the FitzHugh–Nagumo Neuron
4.9.1 Linearization of the FitzHugh–Nagumo Model Using

a Differential Geometric Approach
The model of the dynamics of the FitzhHugh Nagumo neuron is considered
dV
dt
D V .V a/.1 V / w C I
(4.31)
dw
dt
D .V w/
By defining the state variables x1 D w, x2 D V and setting current I as the external

control input one has
dx1
dt
D x1 C x2
dx2
dt
D x2 .x2 a/.1 x2 / x1 C u
(4.32)
y D h.x/ D x1
Equivalently one has

xP 1 x1 C x2 0
D C u
xP 2 x2 .x2 a/.1 x2 / x1 1
(4.33)
y D h.x/ D x1
The state variable z1 D h1 .x/ D x1 is defined. It holds that
@h1 @h2
z2 D Lf h1 .x/ D f1 C f2 D 1f1 C 0f2 D f1 (4.34)
@x1 @x2
L2f h1 .x/ D @x
@z2
1
f1 C @x
@z2
2
f2 D @x@1 . x1 C x2 /f1 C @x@2 . x1 C x2 /f2 )
Lf h1 .x/ D . /f1 C f2 )
2
L2f h1 .x/ D . x1 C x2 / C Œx2 .x2 a/.1 x2 / x1

(4.35)
Moreover, it holds
@h1 @h2
Lg h1 .x/ D g1 C g2 D 0g1 C 1g2 D g2 D 1 (4.36)
@x1 @x2
Lg Lf h1 .x/ D @x
@z2
1
g1 C @x
@z2
2
g2 D @x@1 . x1 C x2 /g1 C @x@2 . x1 C x2 /g2 )
Lg Lf h1 .x/ D g1 C g2 )Lg Lf h1 .x/ D . /0 C 1)Lg Lf h1 .x/ D
(4.37)
It holds that
zP1 D z2
(4.38)
zP2 D L2f h1 .x/ C Lg Lf h1 .x/u
or equivalently
zP1 D z2
(4.39)
zP2 D f x1 C x2 C Œx2 .x2 a/.1 x2 / x1 g C u
4.9 Linearization of the FitzHugh–Nagumo Neuron 91
which can be also written in the matrix canonical form

zP1 01 z1 0
D C v (4.40)
zP2 00 z2 1
Next, the relative degree of the system is computed. It holds that Lg h1 .x/ D 0,
whereas
Lg Lf h1 .x/ D @f 1
@x1 1
g C @f 1
@x2 2
g )
(4.41)
Lg Lf h1 .x/ D 0 C 1 D ¤0
f h1 .x/¤0 for n D 2. Therefore, the relative degree of the system is

and Lg Ln1
n D 2.
4.9.2 Linearization of the FitzHugh–Nagumo Model Using

Differential Flatness Theory
Next, the FitzHugh–Nagumo model is linearized with the use of the differential
flatness theory. The flat output of the system is taken to be y D h.x/ D x1 . It holds
that yP D xP 1 . From the first row of the state space equation of the neuron given in
Eq. (4.33) one gets
xP 1 Cx1 P
yCy
x2 D
)x2 D
(4.42)
Moreover, from the second row of Eq. (4.33) one gets
u D xP 2 x2 .x2 ˛/.1 x2 / C x1 (4.43)
and since x1 , x2 are functions of the flat output and its derivatives one has that the
control input u is also a function of the flat output and its derivatives. Therefore, the
considered neuron model stands for a differentially flat dynamical system.
From the computation of the derivatives of the flat output one obtains
yP1 D xP 1 D f1 (4.44)
yR1 D fP1 D @x@1 . x1 C x2 /xP 1 C @x@1 . x1 C x2 /xP 2 )

yR1 D xP 1 C xP 2 )yR1 D . x1 C x2 /CŒx2 .x2 a/.1 x2 / x1 C u:
(4.45)
By denoting as v D xP 1 C xP 2 )yR1 D . x1 C x2 / C Œx2 .x2 a/.1

x2 /x1 Cu, one arrives again at a state space description of the system in the linear
canonical form. Thus setting z1 D y1 and z2 D yP1 D y2 one gets Eq. (4.40)

zP1 01 z1 0
D C u (4.46)
zP2 00 z2 1
For the linearized neuron model one can define a feedback control signal using that
yR D v.
v D yR d kd .yP yPd / kp .y yd /) (4.47)
and using that L2f h.x/ C Lg Lf h.x/u D v one has
u D .v L2f h.x//=Lg Lf h.x/ (4.48)

Using Differential Geometry
The following system of coupled neurons is considered
dV 1
dt
D V1 .V1 ˛/.1 V1 / w1 C g.V1 V2 / C I1
dw1
dt
D .V1 w1 /
(4.49)
dV 2
dt
D V2 .V2 ˛/.1 V2 / w2 C g.V2 V1 / C I2
dw2
dt
D .V2 w2 /
The following state variables are defined x1 D w1 , x2 D V , x3 D w2 , x4 D

V2 , u1 D I1 and u2 D I2 (Fig. 4.8). Thus, one obtains the following state-space
description
dx1
dt
D x1 C x2
dx2
dt
D x2 .x2 a/.1 x2 / x1 C g.x2 x1 / C u1
(4.50)
dx3
dt
D x3 C x4
dx4
dt
D x4 .x4 a/.1 x4 / x3 C g.x4 x2 / C u2
while the measured output is taken to be
y1 D h1 .x/ D x1
(4.51)
y2 D h2 .x/ D x3
4.10 Linearization of Coupled FitzHugh–Nagumo Neurons Using Differential. . . 93
Fig. 4.8 Equivalent circuit diagram of coupled FitzHugh–Nagumo neurons
Equivalently, the state-space description of the system is given by

0 1 0 1 0 1
xP 1 x1 C x2 00

BxP 2 C Bx2 .x2 a/.1 x2 / x1 C g.x2 x4 /C B1 0C u1
B CDB CCB C (4.52)
@xP 3 A @ x3 C x4 A @0 0A u2
xP 4 x4 .x4 ˛/.1 x4 / x3 C g.x4 x2 / 01

y1 h1 .x/ x1
D D (4.53)
y2 h2 .x/ x3
It holds that
z11 D h1 .x/ D x1
z12 D Lf h1 .x/ D @h 1
@x1 1
f C @h 1
f C @h
@x2 2
1
f C
@x3 3
@h1
f)
@x4 4 (4.54)
z2 D f1 )z2 D x1 C x2
1 1
Moreover, it holds that
@z1 @z1 @z1 @z1

zP12 D L2f h1 .x/ D @x21 f1 C @x22 f2 C @x23 f3 C @x24 f4 )
zP12 D f1 C f2 )Pz12 D (4.55)
D . /. x1 C x2 / C Œx2 .x2 ˛/.1 x2 / x1 C g.x2 x4 /
In a similar manner one computes
Lg1 h1 .x/ D @h 1
g C @h
@x1 11
1
g C @h
@x2 12
1
g C @h
@x3 13
1
g )
@x4 14 (4.56)
Lg1 h1 .x/ D 1g11 C 0g12 C 0g13 C 0g14 )Lg1 h1 .x/ D 0
and
Lg1 h1 .x/ D @h2

g C @h
@x1 21
2
g C @h
@x2 22
2
g C @h
@x3 23
2
g )
@x4 24 (4.57)
Similarly one gets
@z1 @z1 @z1 @z1

Lg1 Lf h1 .x/ D @x21 g11 C @x22 g12 C @x23 g13 C @x24 g14 )
Lg1 Lf h1 .x/ D . /g11 C g12 C 0g13 C 0g14 ) (4.58)
Lg1 Lf h1 .x/ D . /0 C 1 C 00 C 00)Lg1 Lf h1 .x/ D
and
@z1 @z1 @z1 @z1
Lg2 Lf h1 .x/ D . /g21 C g22 C 0g23 C 0g24 ) (4.59)
Lg2 Lf h1 .x/ D . /0 C 0 C 00 C 00)Lg1 Lf h1 .x/ D 0
Moreover, it holds
z21 D h2 .x/ D x3 (4.60)
and
z22 D Lf h2 .x/ D @h 2
f C @h
@x1 1
2
f C @h
@x2 2
2
f C
@x3 3
@h2
f)
@x4 4 (4.61)
z2 D f3 )z2 D x3 C x4
2 2
Additionally, one has
@z1 @z1 @z1 @z1

zP22 D L2f h2 .x/ D @x21 f1 C @x22 f2 C @x23 f3 C @x24 f4 )
zP22 D 0f1 C 0f2 f3 C f4 ) (4.62)
zP2 D . x3 C x4 / C Œx4 .x4 a/.1 x4 / x3 C g.x4 x2 /
2
Moreover one computes
Lg1 h2 .x/ D @h2

g C @h
@x1 11
2
g C @h
@x2 12
2
g C @h
@x3 13
2
g )
@x4 14
Lg1 h2 .x/ D 0g11 C 0g12 C 1g13 C 0g14 )Lg1 h2 .x/ D g13 )Lg1 h2 .x/ D 0
(4.63)
and
Lg2 h2 .x/ D @h 2
g C @h
@x1 21
2
g C @h
@x2 22
2
g C @h
@x3 23
2
g )
@x4 24 (4.64)
Equivalently
@z2 @z2 @z2 @z2

Lg1 Lf h2 .x/ D 0g11 C 0g12 g13 C g14 ) (4.65)
Lg1 Lf h2 .x/ D 00 C 01 0 C 0)Lg1 Lf h2 .x/ D 0
and
@z2 @z2 @z2 @z2
Lg2 Lf h2 .x/ D 0g11 C 0g12 g23 C g24 (4.66)
Lg2 Lf h2 .x/ D 00 C 00 0 C 1)Lg2 Lf h2 .x/ D
Therefore, it holds
zP11 D z12
zP12D h1 .x/ C Lg1 Lf h1 .x/u1 C Lg2 Lf h1 .x/u2
L2f
(4.67)
zP21 D z22
zP2 D Lf h2 .x/ C Lg1 Lf h2 .x/u1 C Lg2 Lf h2 .x/u2
2 2
or equivalently,
zR12 D L2f h1 .x/ C Lg1 Lf h1 .x/u1 C Lg2 Lf h1 .x/u2

(4.68)
zR22 D L2f h2 .x/ C Lg1 Lf h2 .x/u1 C Lg2 Lf h2 .x/u2
which can be also written in matrix form

1 !
zR2 L2f h1 .x/ Lg1 Lf h1 .x/ Lg2 Lf h1 .x/ u1
D C (4.69)
or
zR D Dm C Gm u (4.70)
Denoting
v1 D L2f h1 .x/ C Lg1 Lf h1 .x/u1 C Lg2 Lf h1 .x/u2

one also has

1
zR1 v1
2 D (4.71)
zR1 v2
where the control inputs v1 and v2 are chosen as v1 D zR11d kd1 .Pz11d Pz11 /kp1 .z11d z11 /
and v2 D zR21d kd2 .Pz21d zP21 / kp1 .z21d z21 /.
1
Therefore, the associated control signal is u D Gm .v Dm .x//.

Using Differential Flatness Theory
4.11.1 Differential Flatness of the Model of the Coupled

Neurons
It can be proven that the model of the coupled FitzHugh–Nagumo neurons described
in Eq. (4.50) is a differentially flat one. The following flat outputs are defined
y1 D h1 .x/ D x1
(4.72)
y2 D h2 .x/ D x3
From the first row of the dynamical model of the coupled neurons one has
yP1 Cy1
yP1 D y1 C x2 )x2 D
(4.73)
Similarly, from the third row of the dynamical model of the coupled neurons one has
yP2 Cy2
yP2 D y2 C x4 )x4 D
(4.74)
Thus all state variables xi ; i D 1; ; 4 can be written as functions of the flat

outputs and their derivatives.
From the second row of the dynamical model of the coupled neurons one has
u1 D xP 2 x2 .x2 a/.1 x2 / C x1 g.x2 x1 /)u1 D f1 .y1 ; yP1 :y2 ; yP2 /

(4.75)
Similarly, from the second row of the dynamical model of the coupled neurons
one has
u2 D xP 4 x4 .x4 a/.1 x4 / C x3 g.x4 x2 /)u2 D f2 .y1 ; yP1 :y2 ; yP2 /

(4.76)
Consequently, all state variables xi ; i D 1; ; 4 and all control inputs ui i D 1; 2

of the model of the coupled FitzHugh–Nagumo neurons can be written as functions
of the flat outputs yi i D 1; 2 and their derivatives. Therefore, the model of the
coupled neurons is a differentially flat one.
4.11.2 Linearization of the Coupled Neurons Using

Differential Flatness Theory
The problem of linearization and decoupling of the interconnected FitzHugh–

Nagumo neural oscillators can be efficiently solved using differential flatness theory.
For the model of the coupled FitzHugh–Nagumo neurons described in Eq. (4.50) the
flat outputs y1 D h1 .x/ D x1 and y2 D h2 .x/ D x2 have been defined. It holds that
yP1 D xP 1 )yP1 D f1 )yP1 D x1 C x2 (4.77)
and
yR1 D @f 1
xP C @f
@x1 1
1
@x2 2
xP C @f 1
xP C @f
@x3 3
1
xP )
@x4 4
yR1 D . /xP 1 C xP 2 C 0xP 3 C 0xP 4 )
yR1 D . /f1 C .f2 C u1 /)
yR1 D . /. x1 C x2 / C Œx2 .x2 a/.1 x2 / x1 C g.x2 x4 / C u1 )
(4.78)
or equivalently
yR1 D L2f h1 .x/ C Lg1 Lf h1 .x/u1 C Lg2 Lf h1 .x/u2 (4.79)
where
L2f h1 .x/ D . /. x1 C x2 / C Œx2 .x2 a/.1 x2 / x1 C g.x2 x4 /

Lg1 Lf h1 .x/ D Lg2 Lf h1 .x/ D 0
(4.80)
Equivalently, one computes
yP2 D xP 3 )yP2 D f3 )yP2 D x3 C x4 (4.81)
and
yR2 D @f 3
xP C @f
@x1 1
3
@x2 2
xP C @f 3
@x3 3
xP C @f 3
@x4 4
xP )
yR2 D 0xP 1 C 0xP 2 C . /xP 3 C xP 4 )
yR2 D . /f3 C .f4 C u2 /)
yR2 D . /. x3 C x4 / C Œx4 .x4 a/.1 x4 / x3 C g.x4 x2 / C u2 )
yR2 D L2f h2 .x/ C Lg1 Lf h2 .x/u1 C Lg2 Lf h2 .x/u2
(4.82)
where
L2f h2 .x/ D . /. x3 C x4 / C Œx4 .x4 a/.1 x4 / x3 C g.x4 x2 /

Lg1 Lf h2 .x/ D 0 Lg2 Lf h2 .x/ D
(4.83)
By defining the state variables z11 D y1 , zP11 D yP1 , z21 D y2 and zP21 D yP2 one obtains a
description of the coupled neurons in the state-space form
1 !
2 D C (4.84)
zR2 2
Lf h2 .x/ Lg1 Lf h2 .x/ Lg2 Lf h2 .x/ u2
zR D Dm C Gm u (4.85)
Denoting

one also has

1
zR1 v
D 1 (4.86)
zR21 v2
where the control inputs v1 and v2 are chosen as v1 D zR11d kd1 .Pz11d Pz11 /kp1 .z11d z11 /
and v2 D zR21d kd2 .Pz21d zP21 / kp1 .z21d z21 /.
1
Therefore, the associated control signal is u D Gm .v Dm .x//.
4.12 State and Disturbances Estimation

with the Derivative-Free Nonlinear Kalman Filter
4.12.1 Kalman and Extended Kalman Filtering
It will be shown that a new nonlinear filtering method, the so-called Derivative-
free nonlinear Kalman Filter, can be used for estimating wave-type dynamics
in the neuron’s membrane. This can be done through the processing of noisy
measurements and without knowledge of boundary conditions. Other results on the
application of Kalman Filtering in the estimation of neuronal dynamics can be found
in [77, 99, 134, 161]
An overview of Kalman and Extended Kalman Filtering is given first. In the
discrete-time case a dynamical system is assumed to be expressed in the form of a
discrete-time state model [166]:
4.12 State and Disturbances Estimation with the Derivative-Free Nonlinear. . . 99
x.k C 1/ D A.k/x.k/ C B.k/u.k/ C w.k/

(4.87)
z.k/ D Cx.k/ C v.k/
where the state x.k/ is a m-vector, w.k/ is an m-element process noise vector,
and A is an m m real matrix. Moreover the output measurement z.k/ is a p-
vector, C is a pm-matrix of real numbers, and v.k/ is the measurement noise.
It is assumed that the process noise w.k/ and the measurement noise v.k/ are
uncorrelated. The process and measurement noise covariance matrices are denoted
as Q.k/ and R.k/, respectively. Now the problem is to estimate the state x.k/ based
on the measurements z.1/; z.2/; ; z.k/. This can be done with the use of Kalman
Filtering. The discrete-time Kalman filter can be decomposed into two parts: (1)
time update (prediction stage), and (2) measurement update (correction stage).
Measurement update:
K.k/ D P .k/C T ŒC P .k/C T C R1

O
x.k/ D xO .k/ C K.k/Œz.k/ C xO .k/ (4.88)
P .k/ D P .k/ K.k/CP .k/
Time update:
P .k C 1/ D A.k/P .k/AT .k/ C Q.k/
(4.89)
xO .k C 1/ D A.k/x.k/
O C B.k/u.k/
Next, the following nonlinear state-space model is considered:
x.k C 1/ D
.x.k// C L.k/u.k/ C w.k/
(4.90)
z.k/ D .x.k// C v.k/
The operators
.x/ and .x/ are
.x/ D Œ
1 .x/;
2 .x/; ,
m .x/T , and .x/ D
Œ1 .x/; 2 .x/; ; p .x/T , respectively. It is assumed that
and are sufficiently
smooth in x so that each one has a valid series Taylor expansion. Following a
linearization procedure, about the current state vector estimate x.k/ O the linearized
version of the system is obtained:
x.k C 1/ D
.x.k//
O C J
.x.k//Œx.k/
O x.k/
O C w.k/
(4.91)
z.k/ D .xO .k// C J .xO .k//Œx.k/ xO .k/ C v.k/
O
where J
.x.k// O
and J .x.k// are the associated Jacobian matrices of
and ,
respectively. Now, the EKF recursion is as follows [157].
Measurement update. Acquire z.k/ and compute:
K.k/ D P .k/JT .xO .k//ŒJ .xO .k//P .k/JT .xO .k// C R.k/1
O
x.k/ D xO .k/ C K.k/Œz.k/ .xO .k// (4.92)
P .k/ D P .k/ K.k/J .xO .k//P .k/
Time update. Compute:
P .k C 1/ D J
.x.k//P
O O
.k/J
T .x.k// C Q.k/

(4.93)
xO .k C 1/ D
.x.k//
O C L.k/u.k/
4.12.2 Design of a Disturbance Observer for the Model

of the Coupled Neurons
Using Eq. (4.69), the nonlinear model of the coupled neurons can be written in the
MIMO canonical form that was described in Sect. 4.8, that is
0 1 0 10 1 0 1
zP1 0 1 0 0 z1 0 0

BzP2 C B0 0 0 C B C
0C Bz2 C B1 B 0C
B CDB C C v1 (4.94)
@zP3 A @0 0 1 0A @z3 A @0 0A v2
zP4 0 0 0 0 z4 0 1
where z1 D y1 , z2 D yP1 , z3 D y2 and z4 D yP2 , while v1 D L2f h1 .x/ C

Lg1 Lf h1 .x/u1 C Lg2 Lf h1 .x/u2 and v2 D L2f h2 .x/ C Lg1 Lf h2 .x/u1 C
Lg2 Lf h2 .x/u2 . Thus one has a MIMO linear model of the form
zP D Az C Bv
(4.95)
zm D C z
where z D Œz1 ; z2 ; z3 ; z4 T and matrices A,B,C are in the MIMO canonical form
0 1 0 1 0 1
0 1 0 0 0 0 10
B0 0 0 0C B1 0C B C
ADB CBDB C C T D B0 0 C (4.96)
@0 0 1 0A @0 0A @0 1 A
0 0 0 0 01 00
Assuming now the existence of additive input disturbances in the linearized model
of the coupled neurons described in Eq. (4.69) one gets
1 !
zR2 L2f h1 .x/
D
zR22 L2f h2 .x/
(4.97)
Lg1 Lf h1 .x/ Lg2 Lf h1 .x/ u1 C d1
C
Lg1 Lf h2 .x/ Lg2 Lf h2 .x/ u2 C d2
These disturbances can be due to external perturbations affecting the coupled

neurons and can also represent parametric uncertainty for the neurons’ model. It
can be assumed that the additive disturbances di ; i D 1; 2 are described by the
4.12 State and Disturbances Estimation with the Derivative-Free Nonlinear. . . 101
n-th order derivatives of di and the associated initial conditions. Without loss of
generality it will be considered that n D 2. This means
dR1 D fa .y1 ; yP1 ; y2 ; yP2 /

(4.98)
dR2 D fb .y1 ; yP1 ; y2 ; yP2 /
By defining the additional state variables z5 D d1 , z6 D dP1 , z7 D d2 , z8 D dP2 one

has zP1 D z2 , zP2 D v1 C d1 , zP3 D z4 , zP4 D v2 C d2 , zP5 D z6 , zP6 D fa , zP7 D z8 and
zP8 D fb . Thus, in the case of additive input disturbances the state-space equations
of the model of the coupled neurons can be written in the following matrix form
zP D Az C Bv
(4.99)
zm D Cz
where the state vector is z D Œz1 ; z2 ; z3 ; z4 ; z5 ; z6 ; z7 ; z8 T , the control input vector is

u D Œv1 ; v2 ; fa ; fb T , and the measured output is zm D Œz1 ; z3 T , while matrices A,
B, and C are defined as
0 1 0 1
0 1 0
00000 0000
B0 0 1 0 0 0C
0 0 B1 0 0 0 C
B C B C
B0 C B0 0 0 0 C
B 0 0 0 0 0C
0 1 B C
B C B C
B0 0 0 0 1 0C
0 0 B0 1 0 0 C
ADB C BDB C (4.100)
B0 0 0 1 0 0C
0 0 B0 0 0 0 C
B C B C
B0 0 0 0 0 0C
0 0 B0 0 1 0 C
B C B C
@0 0 0 0 0 1A
0 0 @0 0 0 0 A
0 0 0
00000 0001

10000000
C D (4.101)
00100000
The associated disturbance observer is
zPO D Ao zO C Bo u C K.zm zOm /

(4.102)
zOm D Co zO
where Ao D A, Co D C and

01000000
BoT D (4.103)
00010000
where now u D Œu1 ; u2 T .

4.12.3 Disturbances Compensation for the Model

of the Coupled Neurons
For the aforementioned model, and after carrying out discretization of matrices Ao ,
Bo , and Co with common discretization methods one can perform Kalman filtering
[157–159, 166, 169, 170]. This is Derivative-free nonlinear Kalman filtering which,
unlike EKF, is performed without the need to compute Jacobian matrices and does
not introduce numerical errors due to approximative linearization with Taylor series
expansion.
In the design of the associated disturbances’ estimator one has the dynamics
defined in Eq. (5.85), where K2R82 is the state estimator’s gain and matrices Ao ,
Bo , and Co have been defined in Eqs. (4.100) and (4.101). The discrete-time equiv-
alents of matrices Ao , Bo , and Co are denoted as AQd , BQ d , and CQ d , respectively, and
are computed with the use of common discretization methods. Next, a Derivative-
free nonlinear Kalman Filter can be designed for the aforementioned representation
of the system dynamics [157, 158]. The associated Kalman Filter-based disturbance
estimator is given by the recursion [159, 166, 169].
Measurement update:
K.k/ D P .k/CQ dT ŒCQ d P .k/CQ dT C R1

zO.k/ D zO .k/ C K.k/ŒCQ d z.k/ CQ d zO .k/ (4.104)
P .k/ D P .k/ K.k/CQ d P .k/
Time update:
P .k C 1/ D AQd .k/P .k/AQTd .k/ C Q.k/

(4.105)
zO .k C 1/ D AQd .k/Oz.k/ C BQ d .k/Qv.k/
To compensate for the effects of the disturbance inputs it suffices to use in the control
loop the estimates of the disturbance terms that is zO5 D d1 and zO7 D d2 and the
modified control input vector
!
v1 fOa v1 zO5
vD or v D (4.106)
v2 fOPb v2 zO7
Results on the synchronization between the master and the slave FitzHugh–Nagumo
neuron are provided for three different cases, each one associated with difference
disturbance and uncertainty terms affecting the neuron model as well as with
different setpoints for the state vector elements of the coupled neurons’ model.
a 6 b 60
5 50
40
4
30
3
20
x2−x4
x1−x3
2
10
1
0
0
−10
−1 −20
−2 −30
0 5 10 15 20 25 30 35 40 0 5 10 15 20 25 30 35 40
time (sec) time (sec)
Fig. 4.9 Synchronization in the model of the two coupled FitzHugh–Nagumo neurons (a) between
state variables x1 (master neuron) and x3 (slave neuron), (b) between state variables x2 (master
neuron) and x4 (slave neuron)
a b
5 1 0.2
z5 − z1est
z6 − z2est
x2
0 0 0
−5 −1 −0.2
−1.5 −1 −0.5 0 0.5 1 1.5 10 20 30 40 10 20 30 40

x1 time (sec) time (sec)
4
5 0.5
2
z7 − z3est
z8 − z4est
x4
0 0 0
−2 −0.5
−5
−4
−1.5 −1 −0.5 0 0.5 1 1.5 10 20 30 40 10 20 30 40
x3
Fig. 4.10 Phase diagrams of the synchronized FitzHugh–Nagumo neurons (a) between state
variables x1 –x2 (master neuron) and between x3 –x4 (slave neuron), (b) estimation of disturbances
affecting the master neuron (state variables z5 and z6 ) and the slave neuron (state variables z7 and
z8 )
The results obtained in the first test case are shown in Figs. 4.9 and 4.10. The results
obtained in the second case are shown in Figs. 4.11 and 4.12. Finally, the results
obtained in the third case are shown in Figs. 4.13 and 4.14.
In Figs. 4.9a, 4.11a, and 4.13a it is shown how the proposed Kalman Filter-
based feedback control scheme succeeded the convergence of state variable x1 of
the master neuron to state variable x3 of the second neuron. Similarly, in Figs. 4.9b,
4.11b, and 4.13b it is shown how the proposed Kalman Filter-based feedback control
scheme succeeded the convergence of state variable x2 of the master neuron to state
variable x3 of the second neuron. In Figs. 4.10a, 4.12a, and 4.14a the phase diagrams
between the state variables x1 , x2 of the master neuron and the phase diagrams
between the state variables x3 , x4 of the slave neuron are presented. The phase
diagrams for the master and slave neuron become identical and this is an indication
a 6 b 60
5 50
4
40
3
30
2
20
x1−x3
x2−x4
1
10
0
0
−1
−2 −10
−3 −20
−4 −30
0 5 10 15 20 25 30 35 40 0 5 10 15 20 25 30 35 40
Fig. 4.11 Synchronization in the model of the two coupled FitzHugh–Nagumo neurons (a)
between state variables x1 (master neuron) and x3 (slave neuron), (b) between state variables x2
(master neuron) and x4 (slave neuron)
a 30 b 0.4
20 1 0.2
z5 − z1est
z6 − z2est
10
x2
0 0 0
−10
−1 −0.2
−20
−30 −0.4
−4 −3 −2 −1 0 1 2 3 4 10 20 30 40 10 20 30 40
30 4
20
2 0.5
z7 − z3est
z8 − z4est
10
x4
0 0 0
−10
−2 −0.5
−20
−30 −4
−4 −3 −2 −1 0 1 2 3 4 10 20 30 40 10 20 30 40
z8 )
about the succeeded synchronization. Finally, in Figs. 4.10b, 4.12b, and 4.14b the
estimates of the disturbances terms affecting the neurons’ model are provided. It
can be noticed that the Kalman Filter-based observer provides accurate estimates
about the non-measurable disturbances and this information enables the efficient
compensation of the perturbations’ effects.
4.14 Conclusions 105
a 8 b 80
6 60
40
4
20
2
x2−x4
x1−x3
0
0
−20
−2
−40
−4 −60
−6 −80
0 5 10 15 20 25 30 35 40 0 5 10 15 20 25 30 35 40
Fig. 4.13 Synchronization in the model of the two coupled FitzHugh–Nagumo neurons (a)
between state variables x1 (master neuron) and x3 (slave neuron), (b) between state variables x2
(master neuron) and x4 (slave neuron)
a b
50 1 0.2
z5 − z1est
z6 − z2est
x2
0 0 0
−1 −0.2
−50
−8 −6 −4 −2 0 2 4 6 8 10 20 30 40 10 20 30 40
50
2 0.5
z7 − z3est
z8 − z4est
x4
0 0 0
−2 −0.5
−50
−8 −6 −4 −2 0 2 4 6 8 10 20 30 40 10 20 30 40
z8 )
4.14 Conclusions
A new method for robust synchronization of coupled neural oscillators has been
developed. The model of the FitzHugh–Nagumo neural oscillators has been con-
sidered which represents efficiently voltage variations on the neuron’s membrane,
due to ionic currents and external activation currents. It was pointed out that
synchronism between the coupled neurons is responsible for rhythm generation
and control of several functions in living species such as gait, breathing, heart’s
pulsing, etc. Moreover, models of synchronized neurons can be used in several
robotic applications to control locomotion of multilegged, quadruped, and biped
robots.
With the application of differential geometric methods and differential flatness

theory it was shown that the nonlinear model of the FitzHugh–Nagumo neuron
can be written in the linear canonical form. It was also shown that by applying
differential geometric methods and by computing Lie derivatives exact linearization
of the model of the coupled FitzHugh–Nagumo neurons (connected through a gap
junction) can be succeeded. Moreover, it was proven that the model of the coupled
FitzHugh–Nagumo neuron is a differentially flat one and by defining appropriate flat
outputs it can be transformed to the MIMO linear canonical form. For the linearized
representation of the coupled neuron’s model the design of a feedback control is
possible and synchronization between the two neurons can be attained.
Next, the problem of synchronization of the coupled neurons under external
perturbations and parametric uncertainties was examined. To obtain simultaneous
state and disturbances estimation a disturbance observer based on the Derivative-
free nonlinear Kalman Filter has been used. The Derivative-free nonlinear Kalman
Filter consists of the standard Kalman Filter recursion on the linearized equivalent
model of the coupled neurons and on computation of state and disturbance estimates
using the diffeomorphism (relations about state variables transformation) provided
by differential flatness theory. After estimating the disturbance terms in the neurons’
model their compensation has become possible.
The performance of the synchronizing control loop has been tested through
simulation experiments. It was shown that the proposed method assures that the
neurons will remain synchronized, despite parametric variations and uncertainties in
the associated dynamical model and despite the existence of external perturbations.
The method can be extended to multiple interconnected neurons, thus enabling to
succeed more complicated patterns in robot’s motion.
Chapter 5
Synchronization of Circadian Neurons
and Protein Synthesis Control
Abstract The chapter proposes a new method for synchronization of coupled

circadian cells and for nonlinear control of the associated protein synthesis process
using differential flatness theory and the derivative-free nonlinear Kalman Filter. By
proving that the dynamic model of the FRQ protein synthesis is a differentially
flat one its transformation to the linear canonical (Brunovsky) form becomes
possible. For the transformed model one can find a state feedback control input
that makes the oscillatory characteristics in the concentration of the FRQ protein
vary according to desirable setpoints. To estimate nonmeasurable elements of the
state vector the Derivative-free nonlinear Kalman Filter is used. The Derivative-
free nonlinear Kalman Filter consists of the standard Kalman Filter recursion on
the linearized equivalent model of the coupled circadian cells and on computation
of state and disturbance estimates using the diffeomorphism (relations about state
variables transformation) provided by differential flatness theory. Moreover, to
cope with parametric uncertainties in the model of the FRQ protein synthesis
and with stochastic disturbances in measurements, the Derivative-free nonlinear
Kalman Filter is redesigned in the form of a disturbance observer. The efficiency
of the proposed Kalman Filter-based control scheme is tested through simulation
experiments.
5.1 Overview
The chapter studies synchronization of networks of circadian oscillators and control

of the protein synthesis procedure performed by them. Circadian oscillators are
cells performing protein synthesis within a feedback loop. The concentration of
the produced proteins exhibits periodic variations in time. In humans, circadian
oscillators are neural cells which are found in the suprachiasmatic nucleus of the
hypothalamus and which are coupled through the exchange of neurotransmitters.
There are also peripheral circadian oscillators which are responsible for rhyth-
micity in the functioning of various organs in the human body. The peripheral

108 5 Synchronization of Circadian Neurons and Protein Synthesis Control
Fig. 5.1 Coupled circadian neurons at the hypothalamus and synchronization of circadian oscilla-
tors in peripheral organs
circadian oscillators are controlled by the circadian neurons through messages

sent by the latter, in the form of hormones (ACTH, cortisol, etc.), metabolites,
inputs from the sympathetic neural system, or variations in body temperature
[61, 67, 68, 104] (see Fig. 5.1). Circadian rhythms affect cell cycle apoptosis and
DNA repair, drug metabolism, and detoxification, as well as angiogenesis. The
disruption of periodicity and synchronism in circadian oscillators is known to be
responsible for the appearance of malignancies [32,33,105,106]. On the other hand,
pharmacological treatment of tumors when taking into account the variations of
proteins concentration controlled by the circadian oscillators can be more efficient.
Mathematical models of circadian oscillators consist of sets of ordinary differential
equations describing the feedback loop of the generation of proteins in the circadian
cells. The main stages of these feedback loops are transcription of genes into mRNA,
translation of mRNA into proteins, and inhibition of the transcription stage by the
generated protein. The number of ordinary differential equations in such models is
moderate in simple organisms (e.g., neurospora and drosophila) whereas it becomes
elevated in the case of mammals. In this chapter the model of the neurospora
circadian oscillators will be considered for testing the method of feedback control
and synchronization of the circadian cells. However, the method is generic and can
be applied to more elaborated and increased order models of circadian oscillators.
5.2 Modelling of Circadian Oscillators Dynamics 109
Previous results on the control of circadian oscillators have been presented

in [14, 53, 102, 142, 182, 188–190, 219]. It appears that this control problem is
a nontrivial one when taking into account uncertainty and stochasticity of the
oscillators model. Up to now the problem of robust synchronization of coupled
circadian oscillators has not been solved efficiently. The approach followed in this
chapter for succeeding control of the protein synthesis procedure in the circadian
cells as well as for synchronizing coupled circadian cells when performing such
processes is based on transformation of the dynamical model of the circadian
oscillators into the linear canonical (Brunovsky) form. This transformation makes
use of differential flatness theory [58, 101, 109, 172].
The problem of synchronization of coupled circadian oscillators becomes more
difficult when there is uncertainty about the parameters of the dynamical model of
the circadian cells and when the parameters of the dynamical models of these cells
are uneven. This chapter is concerned with proving differential flatness of the model
of the coupled circadian oscillators and its resulting description in the Brunovksy
(canonical) form [125]. By defining specific state variables as flat outputs an
equivalent description of the coupled circadian oscillators in the Brunovksy (linear
canonical) form is obtained. It is shown that for the linearized model of the
coupled oscillators it is possible to design a feedback controller that succeeds their
synchronization. At a second stage, the novel Kalman Filtering method proposed in
Chap. 4, that is the Derivative-free nonlinear Kalman Filter, is used as a disturbance
observer, thus making possible to estimate disturbance terms affecting the model of
the coupled oscillators and to use these terms in the feedback controller. By avoiding
linearization approximations, the proposed filtering method improves the accuracy
of estimation and results in smooth control signal variations and in minimization of
the synchronization error [158, 159, 170].
5.2 Modelling of Circadian Oscillators Dynamics
5.2.1 The Functioning of the Circadian Oscillators
Circadian neurons are a small cluster of 2104 neurons in the ventral hypothalamus
and provide the body with key time-keeping signals, known as circadian rhythms.
Circadian neurons mainly receive input from the retina, can be coupled through
neurotransmitters, and can stimulate other cells in the body also exhibiting an
oscillatory behavior that provides time keeping for other functions of the body.
Circadian oscillators affect cell division. A model that describes the cell cycle is
given in [32]. The model comprises several stages of the cell division cycle each one
denoted by a different index i (1i I ), whereas the primary variable is denoted as
i D i .t; a/ and represents the density of cells of age a in phase i at time instant t .
During each phase, the density of cells varies either due to spontaneous death rate
di D di .t; a/ or due to a transition rate KiC1;i .t; a/ from phase i to phase i C 1.
Actually, the transition rate KiC1;i stands for a control input to the cells proliferation
model and is dependent on excitation received from circadian oscillators.
The PDE model of the cell cycle is given by
@
C @a@
Œvi .a/ i C Œdi C Ki;iC1 i D 0
@t i R
vi .0/ i .t; a D 0/ D a0 Ki1;i .t; a/ i1 .t; a/da 2i I (5.1)
R
1 .t; a D 0/2 a0 KI;1 .t; a/ I .t; a/da
P R
where IiD1 a0 i .t; a/da D 1, vi .a/ denotes a speed function of age a in phase
i with respect to time t and Ki;iC1 .t; a/ D i .t /1faai g .a/. The transition rates
i .t /1faai g .a/ have the following significance: a minimum age ai must be spent in
phase i , and a dynamic control t ! i .t / is exerted on the transition from phase i to
phase i C1. Functionals i are dependent on physiological control, that is hormonal
or circadian, as well as on pharmacological factors. From the above, it is concluded
that circadian oscillators indeed affect the cells’ cycle. They may also have an effect
on cell’s cycle through the death rate di .
It has been verified that the cells’s growth is controlled by proteins known as
cyclines and cycline-dependent kinases (CDK) and in turn the concentration of
cyclines is controlled by circadian oscillators. Cyclines and CDKs, apart from
circadian control can be pharmacologically controlled. Anticancer drugs, such as
alcylating agents act by damaging DNA and thus triggering p53 protein which
provokes cell cycle arrest. It has been shown that p53 protein, on the one hand,
and many cellular drug detoxification mechanisms (such as reduced glutathione),
on the other hand, are dependent on the cell circadian clock, showing 24 h
periodicity. Consequently, the circadian neurons affect cell cycle’s transitions in
both physiological and pathological conditions. By disrupting the circadian clock
cells’ proliferation and tumor development can be triggered. Moreover, by infusing
anticancer drugs in time periods which are in-phase with high levels of proteins
which arrest the cell cycle and which are controlled by the circadian mechanism
one can anticipate a more efficient anticancer treatment. Finally, altering the period
of the oscillations of the circadian cells with disruptive inputs from cytokines and
drugs is an approach to improving the efficacy of chemotherapy [106].
It is also known that light through the retino-hypothalamic tract modulates
equally for all neurons. A higher risk of cancer is related with circadian disruption
induced by dark/light rhythm perturbations. Disruptive inputs can be due to
circulating molecules such as cytokines (e.g., interferon and interleukin) either
secreted by the immune system in the presence of cancer cells or delivered by
therapy. These inputs are known to have a disruptive effect on circadian neurons
mostly at the central pacemaking revel. It is also known that elevated levels of
cytokines are associated with fatigue.
Finally a note is given about transmission pathways from central to peripheral
circadian cells. These pathways maybe provided by the autonomic nervous system,
neurohormonal ways using the hypothalamocorticosurrenal axis. In a simple way
communication between circadian neurons may be based on intercentral, hormonal,
such as adrenocorticotropic hormone (ACTH) and peripheral tissue terminal inputs
(such as cortisol).
5.2 Modelling of Circadian Oscillators Dynamics 111
5.2.2 Mathematical Model of the Circadian Oscillator
The considered model of the circadian oscillator comes from Neurospora Crassa
(fungus), which is a benchmark biological system. This is a third order oscillator
model. Oscillator models of higher order describe the functioning of human
circadian neurons.
The considered state variables are: x1 : describing the concentration of mRNA,
x2 : describing the concentration of the FRQ (frequency) protein outside the nucleus,
and x3 : describing the concentration of the FRQ protein inside the nucleus. The
Neurospora oscillator model is described by a set of three differential equations:
Kin x1
xP 1 D vs vm (5.2)
C x3n
Kin KM C x 1
x2
xP 2 D Ks x1 vd K 1 x 2 C K2 x 3 (5.3)
Kd C x 2
xP 3 D K1 x2 K2 x3 (5.4)
This model describes the molecular mechanism of circadian rhythms in Neurospora.

The molecular mechanism is based on a negative feedback loop that regulates the
synthesis of FRQ protein which is extracted from the frq gene. Transcription of the
frq gene produces messenger RNA (mRNA). Transcription occurs in the nucleus.
At a next step, the translation of the mRNA produces FRQ protein in the cytoplasm.
Once translation process takes place in the cytoplasm, the generated FRQ protein is
transferred in the nucleus and this has as a result to inhibit further transcription of
the frq gene into mRNA. This completes the feedback loop.
The rest of the model’s parameters are defined as follows: vs denotes the rate of
transcription of the frq gene into FRQ protein inside the nucleus. Ki represents the
threshold constant beyond which nuclear FRQ protein inhibits transcription of the
frq gene (Fig. 5.2). n is the Hill coefficient showing the degree of cooperativity of
the inhibition process, vm is the maximum rate of frq mRNA degradation, KM is
the Michaelis constant related to the transcription process. Parameter Ks defines the
rate of FRQ synthesis and stands for the control input to the model. Parameter K1
denotes the rate of transfer of FRQ protein from the cytoplasm to the nucleus and K2
denotes the rate of transfer of the FRQ protein from the nucleus into the cytoplasm.
Parameter vd denotes the maximum rate of degradation of the FRQ protein and Kd
is the Michaelis constant associated with this process.
Typical values for the aforementioned parameters are: vs D 1:6nMh1 , Ki D
1nM, n D 4, vm D 0:7nMh1 , KM D 0:4nM, ks D 1h1 (when no control is
exerted to the protein synthesis), vd D 4nMh1 , Kd D 1:4nM, k1 D 0:3h1 , and
k2 D 0:15h1 .
Fig. 5.2 Feedback loop of FRQ protein synthesis in circadian oscillators
5.3 Protein Synthesis Control Using Differential

Geometry Methods
It will be shown that using a differential geometric approach and the computation
of Lie derivatives one can arrive into the linear canonical form for the dynamical
model of the circadian oscillator.
First, the nonlinear model of the circadian oscillator is written in the following
state-space form:
0 1 0 Kin
1 0 1
n vm K Cx
x1
xP 1 vs K n Cx 0
@xP 2 A D B C @ A
i 3 m 1
@vd K xCx
2
K x
1 2 C K x
2 3 A C x 1 Ks (5.5)
d 2
xP 3 K1 x 2 K2 x 3 0
Next, the state variable z1 D h1 .x/ D x1 is defined. Next, the variable z2 D

Lf h1 .x/ is computed. It holds that
z2 D Lf h1 .x/ D @h1
f
@x1 1
C @h1
f
@x2 2
C @h1
f)
@x3 3
Kin (5.6)
z2 D Lf h1 .x/ D f1 )Lf h1 .x/ D vs K n Cx n vm KmxCx
1
1
i 3
Equivalently
z3 D L2f h1 .x/ D Lf z2 )z3 D @x @z2

f1 C @x
@z2
f2 C @x@z2
f3 )
h n
1i
n
2
n1
3
(5.7)
Ki Ki nx3
z3 D vm .Km Cx1 /2 vs K n Cx n vm Km Cx1 vs .K n Cx n /2 .K1 x2 K2 x3 /
Km x1
i 3 i 3
5.3 Protein Synthesis Control Using Differential Geometry Methods 113
For the derivative of z3 with respect to time it holds
zP3 D L3f h1 .x/ C Lg L2f h1 .x/u (5.8)
For the computation of L3f h1 .x/ one has
L3f h1 .x/ D @z3

f
@x1 1
C @z3
f
@x2 2
C @z3
f
@x3 3 (5.9)
which gives
L3f nh1 .x/ oh i

Km 2.Km Cx1 / Kin x1 Km Km Kin x1
D vm .K Cx 4 Œvs K n Cx n vm K Cx C vm .K Cx /2 vm .K Cx /2 v s n
Cx n vm
Cx
n m 1 / oh i 3 m 1 im n1 m 1 K i 3 K m 1
K n nxn1 Kin nx3n1
vs .Kin Cx3 n /2 K1 vd KdxCx 2
K 1 x 2 C K 2 x 3 C v m
Km
Cx 2 vs .K n Cx n /2
i 3 2 .K m 1 / i 3o
K n n.n1/x3n2 .Kin Cx3n /Kin nx3n1 2.Kin Cx3n / K n nx n1
vs i .K n Cx n /4
.K1 x2 K2 x3 / C vs .Kin Cx3 n /2 K2 ŒK1 x2 K2 x3
i 3 i 3
(5.10)
For the computation of Lg L2f h1 .x/ one has
Lg L2f h1 .x/ D @z3

g
@x1 1
C @z3
g
@x2 2
C @z3
g
@x3 3 (5.11)
which gives
n o
K n nx n1
Lg L2f h1 .x/ D vs .Kin Cx3 n /2 K1 x1 (5.12)
i 3
It can be noticed that L3f h1 .x/ computed in Eq. (5.37) is the same as function
P computed using Eq. (5.24), while Lg L2f h1 .x/ computed in Eq. (5.12) is
f .y; y/
the same as function g.y; y/P that was computed using Eq. (5.25).
Finally, the relative degree of the system is computed. It holds that Lg h1 .x/ D
0 and Lg Lf h1 .x/ D 0, while as shown above in Eq. (5.12) it holds that
Lg L2f h1 .x/¤0. Therefore, the relative degree of the system is n D 3. This confirms
the appearance of the control input in the equation obtained after computing the third
order derivative of x1 with respect to time.
Next, by defining the new control variables z1 D h1 .x/, z2 D Lf h1 .x/, and
z3 D L2f h1 .x/ and using the relation zP3 D L3f h1 .x/ C Lg L2f h1 .x/u D v one
arrives at a description of the circadian oscillator dynamics in the linear canonical
form, that is
0 1 0 10 1 0 1
zP1 010 z1 0
@zP2 A D @0 0 1A @z2 A C @0A v (5.13)
zP3 000 z3 1
and the associated measurement equation is

0 1

z1
z m D 1 0 0 @z 2 A (5.14)
z3
For the linearized model of the circadian oscillator dynamics the control law is
computed using Eqs. (5.31) and (5.32), as in the case of differential flatness theory.
5.4 Protein Synthesis Control Using Differential

Flatness Theory
5.4.1 Differential Flatness of the Circadian Oscillator
Considering the model of the circadian oscillator described in Eqs. (5.2)–(5.4) the
flat output is taken to be y D x1 .
From Eq. (5.2) it holds
Kn y
yP D vs K n Cx
i
n vm K Cy )
n i 3
Mh io
.Km Cy/Kin y
x3 n D .Km Cy/ P my
yCv
vs vm Km Cy
yP ) (5.15)
n n
h io1=n
.Km Cy/Ki
x3 D .Km Cy/ P my
yCv
vs vm KmyCy yP
Therefore, state variable x3 is a function of the flat output and its derivatives that is
x3 D f1 .y; y/.
P
From Eq. (5.4) one obtains
xP 3 D k1 x2 k2 x3 )
(5.16)
x2 D K11 ŒxP 3 C k2 x3
Therefore, state variable x2 is a function of the flat output and its derivatives that is
x2 D f3 .y; y/.
P
From Eq. (5.3) it holds
xP 2 D Ks x1 vd KdxCx2
K 1 x 2 C K2 x 3 )
2 (5.17)
Ks D x1 ŒxP 2 vd Kd Cx2 K1 x2 K2 x3
1 x2
Taking into account that x1 D y, x3 D f1 .y; y/, P and x2 D f2 .y; y/ P one obtains
that the control input Ks is also a function of the flat output y and of the associated
derivatives, that is Ks D f3 .y; y/.
P
5.4 Protein Synthesis Control Using Differential Flatness Theory 115
Consequently, all state variables and the control input of the system are written
as functions of the flat output and its derivatives and this proves that the model of
the circadian oscillator is a differentially flat one.
5.4.2 Transformation into a Canonical Form
From Eq. (5.2) it holds that
Kn
xP 1 D vs K n Cx
i
n vm K Cx
M
x1
1
(5.18)
i 3
Deriving the aforementioned relation with respect to time one has
Kin nxn1
xR 1 D vs 3
xP 3 vm .K KCx
M
xP 1 (5.19)
.Kin Cx3n /2 M 1/
2
Substituting xP 2 from Eq. (5.3) and xP 3 from Eqs. (5.4) into (5.19) one has

Kin nxn1 Kn
xR 1 D vs 3
.K1 K2 k2 x3 / vm .K KCx
M i
vs K n Cx n vm K Cx
x1
(5.20)
.Kin Cx3n /2 M
2
1/ i 3 m 1
which can be also written as
Kin nxn1 Kin nxn1

xR 1 D vs 3
K x vs
2 1 2
3
K2 x 3
.Kin C x3n / .Kin C x3n /2
KM Kin KM x1
vm v
2 s
C vm v
2 mK C x
(5.21)
.KM C x1 / KinC x3n .KM C x1 / m 1
By deriving once more with respect to time one obtains
.3/ ŒKin n.n 1/x3n2 .Kin C x3n /2 C Kin nx3n1 2.Kin C x3n /
x1 D vs xP 3 K1 x2
.Kin C x3n /4
Kin nx3n1
Cvs K1 xP 2
.Kin C x3n /2
ŒKin n.n 1/x3n2 .Kin C x3n /2 C Kin nx3n1 2.Kin C x3n /
vs xP 3 K2 x3
.Kin C x3n /4
Kin nx3n1
vs K2 xP 3
.Kin C x3n /2
ŒKm 2.Km C x1 / Kin
vm P
x 1 vs
.Km C x1 /4 Kin C x3n
Km Kin nx3n1 ŒKm 2.Km C x1 / x1

vm vs P 3 vm
n 2x xP 1 vm
.Km C x1 / .Ki C x3 /
2 n
.Km C x1 / 4 Km C x 1
Km Km
Cvm vm xP 1 (5.22)
.Km C x1 /2 .Km C x1 /2
By substituting the relations about the derivatives xP 1 , xP 2 , and xP 3 and after performing
intermediate operations one finally obtains

.3/ Km 2.Km C x1 / Kin x1
x1 D vm v s vm
.Km C x1 /4 Kin C x3n Km C x 1

Km Km Kin
Cvm vm vs
.Km C x1 /2 .Km C x1 /2 Kin C x3n

x1 K n nxn1 x2
vm vs ni 3 n 2 K1 vd K 1 x 2 C K2 x 3
Km C x 1 .Ki C x3 / Kd C x 2

Km K n nx n1
C vm vs ni 3n 2
.Km C x1 / .Ki C x3 /
2
Kin n.n 1/x3n2 .Kin C x3n / Kin nx3n1 2.Kin C x3n /

vs .K1 x2 K2 x3 /
.Kin C x3n /4

K n nx n1
Cvs ni 3 n 2 K2 ŒK1 x2 K2 x3
.Ki C x3 /

K n nx n1
vs ni 3 n 2 K1 x1 Ks (5.23)
.Ki C x3 /
By defining the control input u D Ks and the following two functions
n h i oh i
Km 2.Km Cx1 / Kin x1 Kin
f .x/ D vm .K m Cx1 /
vs K n Cx n vm
Cx
C vm .KmKCx m Km
2 vm .K Cx /2 vs K n Cx n
ni 3 n n1 oh i
4 K /
m 1 1 m 1 i 3
Ki nx3
vm KmxCx 1
v s n
Cx n 2 K1 v d
x2
Cx
K 1 x 2 C K 2 x 3
1 .K ni 3 / K d 2
Kin nx3n1
C vm .KmKCx m
1 /2 vs .K n Cx n /2
i 3
Kin n.n1/x3n2 .Kin Cx3n /Kin nx3n1 2.Kin Cx3n /
vs .Kin Cx3n /4 o
.K1 x2 K2 x3 /
Kin nx3n1
Cvs .K n Cx n /2 K2 ŒK1 x2 K2 x3
i 3
(5.24)

Kin nx3n1
g.x/ D vs K1 x1 (5.25)
.Kin C x3n /2
5.4 Protein Synthesis Control Using Differential Flatness Theory 117
one has the dynamics of the circadian oscillator in the form
x .3/ D f .x/ C g.x/u (5.26)
or equivalently
y .3/ D f .y; y/
P C g.y; y/u
P (5.27)
where function f .y; y/P comprises all terms in the right part of Eq. (5.23) that do not
multiply the control input Ks , whereas function g.y; y/ P comprises those terms in
the right part of Eq. (5.23) that multiply the control input Ks .
After transforming the circadian oscillator in the form y .3/ D f .y; y/Cg.y;
P P
y/u
and by defining the new control input v D f .y; y/ P C g.y; y/u
P one has the dynamics
y .3/ D v (5.28)
Next, by defining the new state variables z1 D y, z2 D y, P and z3 D yR one obtains

the following state-space description for the circadian oscillator
0 1 0 10 1 0 1
zP1 010 z1 0
@zP2 A D @0 0 1A @z2 A C @0A v (5.29)
zP3 000 z3 1
and the associated measurement equation is

0 1

z1
z m D 1 0 0 @z 2 A (5.30)
z3
Knowing that zP3 D y .3/ D v the control law for the synthesis of the FRQ protein
and consequently the control law of the circadian rhythms is
.3/
y .3/ D v D yd K1 .yR yRd / K2 .yP yPd / K3 .y yd / (5.31)
Since v D f .y; y/
P C g.y; y/u,P the control input that is finally applied to the model
of the circadian oscillator is
u D g 1 .y; y/Œv
P f .y; y/
P (5.32)
The above control law assures that limt!1 y.t / D yd .t / which implies
limt!1 x1 .t / D x1;d .t / (concentration of frq mRNA), limt!1 x2 .t / D x2;d .t /
(concentration of FRQ protein in cytoplasm), and limt!1 x3 .t / D x3;d .t /
(concentration of FRQ protein in nucleus).

Oscillators Using Differential Geometry Methods
The nonlinear state-space model of the coupled circadian oscillators is given by
0 1 0 Kn 0 1 1
n vm
i x1
xP 1 vs K n Cx KM Cx1 0 0
BxP C B C B
i 3
B 2C B vd KdxCx
2
K1 x2 C K2 x3 C Kc .x2 x5 /C Bx1 0C C
B C B 2 C B C
BxP 3 C B
B K1 x 2 K 2 x 3 C B0
CCB 0 C u1
B CDB Kin C B0 C
BxP 4 C B vs K n Cx n vm KM Cx4
x4
C B 0 C u2
B C B C C
@xP 5 A @v x5 K1 x5 C K2 x6 C Kc .x5 x2 /A @ 0 x4 A
i 6
d Kd Cx5
xP 6 K x K x 0 0
1 5 2 6
(5.33)
The following two functions are defined: z1 D h1 .x/ D x1 and z4 D h2 .x/ D x4 . It
holds that
Kin x1
z2 D Lf h1 .x/ D v3 n vm (5.34)
Ki C x 3
n
KM C x 1
K n nxn1
z3 D L2f h1 .x/ D v3 .K niCx3n /2 .K1 x2 K2 x3 /
i n3 (5.35)
Ki
vm .KMKCxm
1 /2 vs K n Cx n vm K Cx
m
x1
1
i 3
Moreover, it holds that
zP3 D L3f h1 .x/ C Lg1 L2f h1 .x/u1 C Lg2 L2f h1 .x/u2 (5.36)
where
n h i
m 2.Km Cx1 / Kin
L3f h1 .x/ D vm K.K m Cx1 / o h
4 v s n
Ki Cx3 n vm
x1
Km Cx1i
Kin
Cvm .Km Cx1 /2 vm .Km Cx1 /2 vs K n Cx n vm KmxCx
Km Km 1
n n n1
oh i 3 1 i
K nx
vs .Kin Cx3 n /2 K1 vd KdxCx2
K 1 x 2 C K 2 x 3 C K c .x 2 x 5 /
i 3 n 2
(5.37)
K n nx n1
C vm .Km Cx1 /2 vs .K ni Cx3n /2
Km
i 3
vs .Kin Cx3n /4 o
.K1 x2 K2 x 3 /
Kin nx3n1
i 3
.n1/
Kin nx3
Lg1 L2f h1 .x/ D vs K1 x 1 (5.38)
.Kin C x3n /2
Lg2 L2f h2 .x/ D 0 (5.39)
5.5 Robust Synchronization of Coupled Circadian Oscillators Using. . . 119
Equivalently, it holds that
zP6 D L3f h2 .x/ C Lg1 L2f h2 .x/u1 C Lg2 L2f h2 .x/u2 (5.40)
where
n h i o
m 2.Km Cx1 / Kin
L3f h2 .x/ D vm K.K m Cx4 /
4 vs n
Khi Cx6n v m
x4
Kim Cx4
C vm
Km
.Km Cx4 /2 vm
Km
.Km Cx4 /2
Kin
vs K n Cx n
n oh i 6 i
Kin nxn1
vm Km Cx4 vs .K n Cx n /2 K1 vd Kd Cx5 K1 x5 C K2 x6 C Kc .x5 x2 /
x4 3 x5
i 6 n
Kin nx6n1
C vm .KmKCx m
4/
2 vs .K n Cx n /2
i 6
vs .Kin Cx6n /4 o
.K1 x5 K2 x 6 /
Kin nx6n1
i 6
(5.41)
Lg1 L2f h2 .x/ D 0 (5.42)
.n1/
Kin nx6
Lg2 L2f h2 .x/ D vs K1 x 4 (5.43)
.Kin C x6n /2
Therefore, for the system of the coupled circadian neurons one obtains an input
output linearized form given by
! ! !
.3/
z1 L3f h1 .x/ Lg1 L2f h1 .x/ Lg2 L2f h1 .x/ u1
.3/ D C (5.44)
z4 L3f h2 .x/ Lg1 L2f h2 .x/ Lg2 L2f h2 .x/ u2
The new control inputs are defined as
v1 D L3f h1 .x/ C Lg1 L2f h1 .x/u1 C Lg2 L2f h1 .x/u2

(5.45)
v2 D L3f h2 .x/ C Lg1 L2f h2 .x/u1 C Lg2 L2f h2 .x/u2
Therefore, the system’s dynamics becomes
.3/
x1 D v1
.3/ (5.46)
x4 D v2
By defining the new state variables z1 D x1 , z2 D x2 , z3 D x3 , z4 D x4 , z5 D x5 , and

z6 D x6 one obtains a description for the system of the coupled circadian oscillators
in the linear canonical (Brunovsky) form
0 1 0 10 1 0 1
zP1 0 1 0 0 0
z1 0 00
BzP C B0 B
0C Bz2 C B0 0C
C C B
B 2C B 0 1 0 0 C
B C B CB C B C
BzP3 C B0 0 0C Bz3 C B1 0C v1
0 0 0
B CDB CB C C B C (5.47)
BzP4 C B0 0 0C Bz4 C B0 0C v2
0 0 1
B C B CB C B C
@zP5 A @0 0 1A @z5 A @0 0A
0 0 0
zP6 0 0 0 0 0
z6 0 01
0 1
z1
Bz C
B 2C
B
C
zm1 1 0 0 0 0 0 Bz3 C
D B C (5.48)
zm2 0 0 0 1 1 0 Bz4 C
B C
@z5 A
z6
The control law that allows FRQ protein concentration converge to desirable levels
is given by
.3/
v1 D x1;d K11 .xR 1 xR 1d / K21 .xP 1 xP 1d / K31 .x1 x1d /
.3/ (5.49)
By knowing the control inputs .v1 ; v2 /T one can compute the control inputs .u1 ; u2 /T
that are finally applied to the system of the coupled circadian neurons. By setting
! !
Q L3f h1 .x/ Lg1 L2f h1 .x/ Lg2 L2f h1 .x/
f D GQ D (5.50)
L3f h2 .x/ Lg1 L2f h2 .x/ Lg2 L2f h2 .x/

Oscillators Using Differential Flatness Theory
In case that there is coupling between circadian oscillators (neurons) it is also

possible to find a linearizing and decoupling control law based on differential
flatness theory. Without loss of generality the model of two coupled circadian
neurons is considered. The state vector of this model now comprises the following
state variables: x1 : mRNA concentration for the first neuron, x2 : concentration of the
FRQ protein in the cytoplasm of the first neuron, x3 : concentration of FRQ protein
in the nucleus of the first neuron, x4 : concentration of mRNA of the second neuron,
x5 : concentration of the FRQ protein in the cytoplasm of the second neuron, x6 :
concentration of FRQ protein in the nucleus of the second neuron.
Kin x1
xP 1 D vs n vm (5.51)
Ki C x 3
n
KM C x 1
x2
xP 2 D Ks1 x1 vd K1 x2 C K2 x3 C Kc .x2 x5 / (5.52)
Kd C x 2
xP 3 D K1 x2 K2 x3 (5.53)
Kn x4
xP 4 D vs n i n vm (5.54)
Ki C x 6 KM C x 4
x5
xP 5 D Ks2 x4 vd K1 x5 C K2 x6 C Kc .x5 x2 / (5.55)
Kd C x 5
xP 6 D K1 x5 K2 x6 (5.56)
It can be proven that the model of the coupled circadian neurons is differentially
flat. The flat output is defined as
y D Œy1 ; y2 D Œx1 ; x4 (5.57)
As it has been shown in Eq. (5.51) in the case of the independent circadian oscillator
it holds
n h io1=n
.Km Cy1 /Kin
x3 D .Km Cy1 /yCv
P m y1
vs vm KmyCy
1
1
P
y 1 (5.58)
therefore it holds x3 D f1 .y1 ; yP1 ; y2 ; yP2 /. Moreover from Eq. (5.53) it holds
xP 3 D K1 x2 K2 x3 )x2 D 1
ŒxP
K1 3
C K2 x 3 (5.59)
therefore it holds x2 D f2 .y1 ; yP1 ; y2 ; yP2 /. Additionally, from Eq. (5.54) it holds
n h io1=n
.Km Cy2 /Kin
x6 D .Km Cy2 /yP2 Cvm y2
vs vm KmyCy
2
2
P
y 2 (5.60)
therefore it holds x6 D f3 .y1 ; yP1 ; y2 ; yP2 /. Furthermore, from Eq. (5.56) one obtains
xP 5 D K1 x5 K2 x6 )x5 D 1
ŒxP
K1 6
C K2 x 6 (5.61)
therefore it holds x5 D f4 .y1 ; yP1 ; y2 ; yP2 /. Next, using Eq. (5.52) one finds
h i
Ks1 D 1
x1
xP 2 vd KdxCx
2
2
C K 1 x 2 K 2 x 3 K c .x 2 x 5 / (5.62)
Since, x1 , x2 , x3 , and x5 are functions of the flat output and of its derivatives it holds
that Ks1 D f5 .y1 ; yP1 ; y2 ; yP2 /. Similarly, from Eq. (5.55) one obtains for the second
control input
h i
Ks2 D 1
x4
xP 5 vd KdxCx
5
5
C K 1 x 5 K 2 x 6 K c .x 5 x 2 / (5.63)
Since x2 , x4 , x5 , and x6 are functions of the flat output and of its derivatives it holds
that Ks2 D f6 .y1 ; yP1 ; y2 ; yP2 /.
From the above analysis, for the model of the coupled circadian oscillators it
holds that all state variables and the control inputs are functions of the flat output
and of its derivatives. Therefore, this system is a differentially flat one.
As in the case of the isolated circadian neuron here it holds
Kn
xP 1 D v3 K n Cx
i
n vm
x1
KM Cx1 (5.64)
i 3
and deriving with respect to time gives
Kin nxn1
xR 1 D v3 3
.K1 x2 K2 x3 /
.Kin C x3n /2

Km Kin x1
vm vs n vm (5.65)
.KM C x1 /2 Ki C x3n Km C x 1
.3/
while the relation for x1 is modified by including in it the coupling term Kc .x2
x5 / which appears now in xP 2 as described in Eq. (5.52). This results into
.3/
x1 D fA .y1 ; yP1 ; y2 ; yP2 /
CgA1 .y1 ; yP1 ; y2 ; yP2 /u1 C gA2 .y1 ; yP1 ; y2 ; yP2 /u2 (5.66)
u1 D Ks1 and u2 D Ks2 . For fA .y1 ; yP1 ; y2 ; yP2 /, gA1 .y1 ; yP1 ; y2 ; yP2 /, and
gA2 .y1 ; yP1 ; y2 ; yP2 / one has
n 1 ; yP1 ; y2 ; yP2 / h
fA .y i o
m 2.Km Cx1 / Kin
D vm K.K vs n n vm
x1
C v m
Km
v m
Km
h m Cx1 / iKi Cx3 Km Cx1 .Km Cx1 / .Km Cx1 /
4 2 2
Kin
n vm
x1
vs K n Cx
n i n3 n1 KmoCx h1 i
Ki nx3
vs .K n Cx n /2 K1 vd KdxCx 2
K 1 x 2 C K 2 x 3 C K c .x 2 x 5 / (5.67)
n i 3 2
Kin nx3n1
C vm .KmKCx m
1/
v
2 s .K n Cx n /2
i 3
vs n n 4 .K1 x2 K2 x 3 /
o .Ki Cx3 /
Kin nx3n1
i 3
.n1/
Kin nx3
gA1 .y1 ; yP1 ; y2 ; yP2 / D vs K1 x 1 (5.68)
.Kin C x3n /2
gA2 .y1 ; yP1 ; y2 ; yP2 / D 0 (5.69)
Similarly, for the second neuron one has

.3/
x4 D fB .y1 ; yP1 ; y2 ; yP2 / C gB1 .y1 ; yP1 ; y2 ; yP2 /u1 C gB2 .y1 ; yP1 ; y2 ; yP2 /u2 (5.70)
u1 D Ks1 and u2 D Ks2 . For fB .y1 ; yP1 ; y2 ; yP2 /, gB1 .y1 ; yP1 ; y2 ; yP2 /, and
gB2 .y1 ; yP1 ; y2 ; yP2 / one has
fB n.y1 ; yP1 ; y2 ; yP2 / h i o

m 2.Km Cx1 / Kin
D vm K.K vs n n vm
x4
C v m
Km
v m
Km
h m Cx4 / iKi Cx6 Km Cx4 .Km Cx4 / .Km Cx4 /
4 2 2
Kin
n vm K Cx
x4
vs K n Cx
n i n6 n1 oh 4
m i
Ki nx3
vs .K n Cx n /2 K1 vd KdxCx 5
K 1 x 5 C K 2 x 6 C K c .x 5 x 2 / (5.71)
n i 6 5
Kin nx6n1
C vm .KmKCx m
4/
v
2 s .K n Cx n /2
i 6
vs n n 4 .K1 x5 K2 x 6 /
o .Ki Cx6 /
Kin nx6n1
i 6
gB1 .y1 ; yP1 ; y2 ; yP2 / D 0 (5.72)

.n1/
Kin nx6
gB2 .y1 ; yP1 ; y2 ; yP2 / D vs K1 x 4 (5.73)
.Kin C x6n /2
Therefore, the system of the coupled circadian neurons can be written in the input–
output linearized form
!
.3/
x1 fA .y1 ; yP1 ; y2 ; yP2 / g .y ; yP ; y ; yP / g .y ; yP ; y ; yP / u1
.3/ D C A1 1 1 2 2 A2 1 1 2 2
x4 fB .y1 ; yP1 ; y2 ; yP2 / gB1 .y1 ; yP1 ; y2 ; yP2 / gB2 .y1 ; yP1 ; y2 ; yP2 / u2
(5.74)
The new control inputs are defined as
v1 D fA .y1 ; yP1 ; y2 ; yP2 / C gA1 .y1 ; yP1 ; y2 ; yP2 /u1 C gA2 .y1 ; yP1 ; y2 ; yP2 /u2
(5.75)
v2 D fB .y1 ; yP1 ; y2 ; yP2 / C gB1 .y1 ; yP1 ; y2 ; yP2 /u1 C gB2 .y1 ; yP1 ; y2 ; yP2 /u2
Therefore, the system’s dynamics becomes
.3/
x1 D v1
.3/ (5.76)
x4 D v2
By defining the new state variables z1 D x1 , z2 D x2 , z3 D x3 , z4 D x4 , z5 D x5 , and

z6 D x6 one obtains a description for the system of the coupled circadian oscillators
in the linear canonical (Brunovsky) form
0 1 0 10 1 0 1
zP1 0 10 0 0
z1 0 00
BzP C B0 B
0C Bz2 C B0 0C
C C B
B 2C B 0 1 0 0 C
B C B CB C B C
BzP3 C B0 00C Bz3 C B1 0C v1
0 0 0
B CDB CB C C B C (5.77)
BzP4 C B0 00C Bz4 C B0 0C v2
0 0 1
B C B CB C B C
@zP5 A @0 01A @z5 A @0 0A
0 0 0
zP6 0 00 0 0
z6 0 01
0 1
z1
Bz C
B 2C
B
C
zm1 1 0 0 0 0 0 Bz3 C
D B C (5.78)
zm2 0 0 0 1 1 0 Bz4 C
B C
@z5 A
z6
The control law that allows FRQ protein concentration converge to desirable levels
is given by
.3/
.3/ (5.79)
By knowing the control inputs .v1 ; v2 /T one can compute the control inputs .u1 ; u2 /T
that are finally applied to the system of the coupled circadian neurons. By setting

Q fA .y1 ; yP1 ; y2 ; yP2 / Q gA1 .y1 ; yP1 ; y2 ; yP2 / gA2 .y1 ; yP1 ; y2 ; yP2 /
f D GD (5.80)
fB .y1 ; yP1 ; y2 ; yP2 / gB1 .y1 ; yP1 ; y2 ; yP2 / gB2 .y1 ; yP1 ; y2 ; yP2 /
It holds v D fQ C Gu)u
Q D GQ 1 .v fQ/.
5.7 State Estimation and Disturbances Compensation

with the Derivative-Free Nonlinear Kalman Filter
The parametric uncertainty terms and the external disturbance terms affecting
x .3/ D v or y .3/ D v are denoted with variable dQ . In that case the dynamics of
the coupled circadian oscillators takes the form
y1 D v1 C dQ1 y2 D v2 C dQ2
.3/ .3/
(5.81)
It is also assumed that the dynamics of the disturbance and model uncertainty terms
is described by the associated n-th order derivative, where without loss of generality
here it is assumed that n D 3
5.7 State Estimation and Disturbances Compensation with the Derivative-Free. . . 125
P dQ2 D fd2 .y; y/

dQ1 D fd1 .y; y/
.3/ .3/
P (5.82)
The state vector of the circadian oscillator is extended by including in it state

variables that describe the disturbance’s variations. Thus one has z1 D y1 , z2 D yP1 ,
z3 D yR1 , z4 D y2 , z5 D yP2 , z6 D yR2 , z7 D dQ1 , z8 D dPQ1 , and z9 D dRQ1 , z10 D dQ2 ,
z11 D dPQ2 , and z12 D dRQ2 . The associated description of the system in the form of
state-space equations becomes
zPe D Aze C Bue

z m D Ce z e (5.83)
where ze is the extended state vector ze D Œz1 ; ; z12 T , ve D Œv1 ; v2 ; fd1 ; fd2 T , is
the extended control input vector, and matrices Ae , Be , and Ce are defined as
0 1 0 1 0 1
010000000000 0000 10
B0 0 1 0 0 0 0 0 0 0 0 0 C B0 0 0 0C B0 0C
B C B C B C
B C B C B C
B0 0 0 0 0 0 1 0 0 0 0 0 C B1 0 0 0C B0 0C
B C B C B C
B0 0 0 0 1 0 0 0 0 0 0 0 C B0 0 0 0C B0 1C
B C B C B C
B0 0 0 0 0 1 0 0 0 0 0 0 C B0 0 0 0C B0 0C
B C B C B C
B0 0 0 0 0 0 0 0 0 1 0 0 C B0 1 0 0C T B C
Ae D B C Be D B C C D B0 0C (5.84)
B0 0 0 0 0 0 0 1 0 0 0 0 C B0 0 0 0C e B0 0C
B C B C B C
B0 0 0 0 0 0 0 0 1 0 0 0 C B0 0 0 0C B0 0C
B C B C B C
B C B C B C
B0 0 0 0 0 0 0 0 0 0 0 0 C B0 0 1 0C B0 0C
B C B C B C
B0 0 0 0 0 0 0 0 0 0 1 0 C B0 0 0 0C B0 0C
B C B C B C
@0 0 0 0 0 0 0 0 0 0 0 1 A @0 0 0 0A @0 0A
000000000000 0001 00
The associated disturbance observer is
zPO D Ao zO C Bo u C K.zm zOm /

(5.85)
zOm D Co zO
where Ao D A, Co D C , and

001000000000
BoT D (5.86)
000001000000
where now u D Œu1 ; u2 T . For the aforementioned model, and after carrying out
discretization of matrices Ao , Bo , and Co with common discretization methods one
can perform Kalman filtering [157, 169]. This is Derivative-free nonlinear Kalman
filtering. As explained in Chap. 4, unlike EKF, the filtering method is performed
without the need to compute Jacobian matrices and does not introduce numerical
errors due to approximative linearization with Taylor series expansion.
The design of a disturbance observer based on the Derivative-free nonlinear

Kalman Filter enables simultaneous estimation of the nonmeasurable elements of
the state vector, that is y2 , y3 and y5 , y6 and estimation of the disturbance term
dQ1 D z7 and dQ2 D z10 . For the compensation of the disturbance term the control
input that is applied to the circadian oscillator model is modified as follows:
v1 .k/ D v.k/ dOQ1 .k/ or

v1 .k/ D v.k/ zO7 .k/
(5.87)
v2 .k/ D v.k/ dOQ2 .k/ or
v2 .k/ D v.k/ zO10 .k/
In the design of the associated disturbances’ estimator one has the dynamics defined
in Eq. (5.85), where K2R121 is the state estimator’s gain and matrices Ao , Bo , and
Co have been given in Eqs. (5.84)–(5.86). The discrete-time equivalents of matrices
Ao , Bo , and Co are denoted as AQd , BQ d , and CQ d respectively, and are computed
with the use of common discretization methods. Next, a Derivative-free nonlinear
Kalman Filter can be designed for the aforementioned representation of the system
dynamics [157, 158]. The associated Kalman Filter-based disturbance estimator is
given by the recursion [166, 169]
Measurement update:
K.k/ D P .k/CQ dT ŒCQ d P .k/CQ dT C R1

zO.k/ D zO .k/ C K.k/ŒCQ d z.k/ CQ d zO .k/ (5.88)
P .k/ D P .k/ K.k/CQ d P .k/
Time update:
P .k C 1/ D AQd .k/P .k/AQTd .k/ C Q.k/

(5.89)
zO .k C 1/ D AQd .k/Oz.k/ C BQ d .k/Qv.k/
The nonlinear dynamical model of the coupled circadian oscillators has been
described in Eqs. (5.51)–(5.56). Using the canonical form model control law for the
FRQ protein synthesis was computed according to the stages described in Sect. 5.6.
The Derivative-free nonlinear Kalman Filter used for model uncertainty, measure-
ment noise, and external disturbances compensation was designed according to
Sect. 5.7.
Results on the synchronization between a primary and a secondary circadian cell
are provided for six different cases, each one associated with different disturbance
a b 5 2
5
z7 − z7est
z8 − z8est
x1 − x4
0 0
0 −5 −2
5 10 15 20 25 30 35 40 0 20 40 0 20 40
time time time
0.5 1
z10 − z10est
5
z − z est
x2 − x5
9
0 0
9
0 −0.5 −1
5 10 15 20 25 30 35 40 0 20 40 0 20 40
time time time
0.2 0.05
− z est
z12 − z12est
5
x3 − x6
11
0 0
11
0
z
−0.2 −0.05
5 10 15 20 25 30 35 40 0 20 40 0 20 40
time time time
Fig. 5.3 Test 1: (a) Synchronization of state variables xi (i D 1; 4: frq mRNA concentration,
i D 2; 5: FRQ protein concentration in cytoplasm, i D 3; 6: FRQ protein concentration in nucleus)
between the two circadian cells (red continuous line denotes concentration in cell 1 whereas the
dashed blue line denotes concentration in cell 2) (b) Estimation of disturbance inputs and of their
derivatives (blue lines) with the use of the Derivative-free nonlinear Kalman Filter
a 10
b 5 5
z − z est
z − z est
x1 − x4
8
5 0 0
7
8
0 −5 −5
5 10 15 20 25 30 35 40 0 10 20 30 40 0 10 20 30 40
time time time
1 1
− z est
10
z − z est
x2 − x5
10
9
5 0 0
10
9
0
z
−1 −1
5 10 15 20 25 30 35 40 0 10 20 30 40 0 10 20 30 40
time time time
0.5 0.1
z11 − z11est
− z est
10
x3 − x6
12
5 0 0
12
0
z
−0.5 −0.1
5 10 15 20 25 30 35 40 0 10 20 30 40 0 10 20 30 40
time time time
and uncertainty terms affecting the cell as well as with different setpoints for the
state vector elements of the coupled circadian cell model. The results obtained
are shown in Figs. 5.3a, 5.4a, 5.5a, 5.6a, 5.7a, and 5.8a. It can be observed that
the proposed control scheme that was based on linearization and decoupling of
the circadian’s oscillator model with the use of differential flatness theory enabled
complete synchronization between the state variables of the first cell (xi ; i D 1; 2; 3
denoted with the continuous red line) and the state variables of the second cell
(xi ; i D 4; 5; 6 denoted with the dashed blue line).
a b 5 5
z − z est
z8 − z8est
4
x −x
10
7
0 0
1
7
0 −5 −5
5 10 15 20 25 30 35 40 0 10 20 30 40 0 10 20 30 40
time time time
1 2
z10 − z10est
z − z est
x2 − x5
9
0 0
9
0 −1 −2
5 10 15 20 25 30 35 40 0 10 20 30 40 0 10 20 30 40
time time time
1 0.5
− z est
z12 − z12est
x3 − x6
11
0 0
11
0
z
−1 −0.5
5 10 15 20 25 30 35 40 0 10 20 30 40 0 10 20 30 40
time time time
a 10
b 5 2
z7 − z7est
z8 − z8est
4
x −x
5 0 0
1
0 −5 −2
5 10 15 20 25 30 35 40 0 10 20 30 40 0 10 20 30 40
time time time
4 1 z10 − z10est 2
z9 − z9est
x2 − x5
2 0 0
0 −1 −2
5 10 15 20 25 30 35 40 0 10 20 30 40 0 10 20 30 40
time time time
0.5 0.2
− z est
z12 − z12est
4
x3 − x6
11
2 0 0
11
0
z
−0.5 −0.2
5 10 15 20 25 30 35 40 0 10 20 30 40 10 20 30 40
time time time
In Figs. 5.3b, 5.4b, 5.5b, 5.6b, 5.7b, and 5.8b the estimates of the disturbance
inputs affecting the model of the coupled circadian oscillators are presented. The
real value of the disturbance variable is denoted with the red line while the estimated
value is denoted with the blue line. The disturbance terms affecting the inputs of the
model are variables z7 and z10 . Their first and second order derivatives are variables
z8 , z9 and z11 , z12 , respectively. It can be noticed that the Kalman Filter-based
observer provides accurate estimates about the non-measurable disturbances and
this information enables the efficient compensation of the perturbations’ effects.
5.9 Conclusions 129
a b 5 5
z7 − z7est
z − z est
x1 − x4
20
8
0 0
8
0 −5 −5
5 10 15 20 25 30 35 40 0 20 40 0 20 40
time time time
1 1
− z est
z9 − z9est
4
x2 − x5
10
2 0 0
10
z
0 −1 −1
5 10 15 20 25 30 35 40 0 20 40 0 20 40
time time time
0.5 0.05
− z est
− z est
4
x3 − x6
11
12
2 0 0
11
12
z
z
0 −0.5 −0.05
5 10 15 20 25 30 35 40 0 20 40 0 20 40
time time time
a 4
b 5 5
z7 − z7est
z − z est
x1 − x4
8
2 0 0
8
0 −5 −5
5 10 15 20 25 30 35 40 0 20 40 0 20 40
time time time
1 1
1 − z est
z9 − z9est
x2 − x5
10
0.5 0 0
10
0
z
−1 −1
5 10 15 20 25 30 35 40 0 20 40 0 20 40
time time time
0.2 0.05
z11 − z11est
z12 − z12est
1
x3 − x6
0.5 0 0
0 −0.2 −0.05
5 10 15 20 25 30 35 40 0 20 40 0 20 40
time time time
5.9 Conclusions
The problem of robust synchronization of coupled circadian oscillators and the

problem of the nonlinear control of the associated protein synthesis has been
studied. Control of the periodic variations of protein levels in circadian cells is
important because it affects several functions performed by living organisms. When
the periodicity of circadian cells is disrupted pathological situations such as tumor
growth may appear. On the other hand, knowing the effect of the circadian cycle on
the variation of proteins levels can help in administering more efficiently anticancer
treatment. The chapter has proposed a synchronizing control method for coupled
circadian cells using differential flatness theory and the Derivative-free nonlinear
Kalman Filter.
With the application of differential geometric methods and differential flatness
theory it was shown that the nonlinear model of the coupled circadian cells can be
written in the linear canonical form. It was also shown that by applying differential
geometric methods and by computing Lie derivatives exact linearization of the
model of the coupled circadian cells can be succeeded. Moreover, it was proven
that the model of the coupled circadian cells is a differentially flat one and by
defining appropriate flat outputs it can be transformed to the MIMO (multi-input
multi-output) linear canonical form. For the linearized representation of the coupled
neuron’s model the design of a feedback control is possible and synchronization
between the two neurons can be attained.
Next, the problem of synchronization of the coupled circadian cells under
external perturbations and parametric uncertainties was examined. As explained,
synchronization of coupled circadian oscillators becomes more difficult when there
is uncertainty about the parameters of the dynamical model of the circadian cells
and when the parameters of the dynamical models of these cells are uneven. To
obtain simultaneous state and disturbances estimation, a disturbance observer based
on the Derivative-free nonlinear Kalman Filter has been used. The Derivative-
free nonlinear Kalman Filter consists of the standard Kalman Filter recursion
on the linearized equivalent model of the coupled cells and on computation of
state and disturbance estimates using the diffeomorphism (relations about state
variables transformation) provided by differential flatness theory. After estimating
the disturbance terms in the model of the coupled circadian cells their compensation
has become possible.
The performance of the synchronizing control loop has been tested through
simulation experiments. It was shown that the proposed method assures that
the circadian cells will remain synchronized, despite parametric variations and
uncertainties in the associated dynamical model and despite the existence of external
perturbations. Robust synchronizing control of biological oscillators is a developing
research field while the application of elaborated control and estimation methods in
biological models is anticipated to give nontrivial results for further advancements
in the fields of biophysics and biomedical engineering.
Chapter 6
Wave Dynamics in the Transmission of Neural
Signals
Abstract The chapter analyzes wave-type partial differential equations (PDEs) that
describe the transmission of neural signals and proposes filtering for estimating the
spatiotemporal variations of voltage in the neurons’ membrane. It is shown that
in specific neuron models the spatiotemporal variations of the membrane’s voltage
follow PDEs of the wave type while in other models such variations are associated
with the propagation of solitary waves in the membrane. To compute the dynamics
of the membrane PDE model without knowledge of initial conditions and through
the processing of noisy measurements, a new filtering method, under the name
Derivative-free nonlinear Kalman Filtering, is proposed. The PDE of the membrane
is decomposed into a set of nonlinear ordinary differential equations with respect
to time. Next, each one of the local models associated with the ordinary differential
equations is transformed into a model of the linear canonical (Brunovsky) form
through a change of coordinates (diffeomorphism) which is based on differential
flatness theory. This transformation provides an extended model of the nonlinear
dynamics of the membrane for which state estimation is possible by applying the
standard Kalman Filter recursion. The proposed filtering method is tested through
numerical simulation tests.
6.1 Outline
As explained in Chap. 1, spatiotemporal variations of voltage in neurons’ membrane

are usually described by partial differential equations (PDEs) of the wave or cable
type [1, 38, 176, 185, 194]. Certain models of the voltage dynamics consider also
the propagation of solitary waves through the membrane. Thus, voltage dynamics in
the membrane can be viewed as a distributed parameters system [23, 211]. State
estimation in distributed parameter systems and in infinite dimensional systems
described by PDEs is a much more complicated problem than state estimation
in lumped parameter systems [46, 72, 74, 174, 213, 218]. Previous results on state
estimation of wave-type nonlinear dynamics can be found in [29, 81, 201, 208].

132 6 Wave Dynamics in the Transmission of Neural Signals
To compute the dynamics of the membrane’s PDE model without knowledge of

initial conditions and through the processing of noisy measurements, the following
stages are followed: Using the method for numerical solution of the PDE through
discretization the initial PDE is decomposed into a set of nonlinear ordinary
differential equations with respect to time [139]. Next, each one of the local
models associated with the ordinary differential equations is transformed into a
model of the linear canonical (Brunovsky) form through a change of coordinates
(diffeomorphism) which is based on differential flatness theory. This transformation
provides an extended model of the nonlinear system for which state estimation is
possible by application of the standard Kalman Filter recursion [122, 200]. Unlike
other nonlinear estimation methods (e.g., Extended Kalman Filter) the application
of the standard Kalman Filter recursion to the linearized equivalent of the nonlinear
PDE does not need the computation of Jacobian matrices and partial derivatives and
does not introduce cumulative numerical errors [157–160, 170].
6.2 Propagating Action Potentials
The Hodgkin–Huxley equation, in the cable PDE form, is re-examined. It holds that:
2
Cm @V
@t
D 4d @ V
Ri @x 2
Iion C I
(6.1)
@
@t
D ˛ .V /.1 / ˇ .V /
where D m; h; , that is parameters that affect conductivity and consequently

the input currents of the membrane. If c is the velocity of propagation of the wave
solution, then one can use the notation
V .x; ct; t / D VO .x/ (6.2)
By performing a change of coordinates D x ct one has

2
Cm @V
@t
D Cm c @V
@
C 4d @ V
Ri @ 2
C I Iion
(6.3)
@
@t
D c @ C ˛ .V /.1 / ˇ .V /
@
where again D m; h; . The following boundary condition holds V . D ˙1/ D

Vrest . Equation (6.3) is decomposed into a set of equivalent ordinary differential
equations
dV
d
DU
dU
d
D 4d
Ri
.Iion I cCm U / (6.4)
d
d
D .˛Gamma .V /.1 / ˇ .V / /=c
6.4 Myelinated Axons and Discrete Diffusion 133
where D m; h; . The solution should satisfy the following boundary conditions
.V; U; m; h; n/.˙1/ D .Vrest ; 0; m1 .Vrest /; h1 .Vrest /; n1 .Vrest // (6.5)
6.3 Dynamics of the Solution of the Wave PDE
Neurons communicate over long distances and this is succeeded by electric

signals (action potentials) which are transmitted along the neuron’s axis. Diffusion
phenomena describing nonlinear flow of ions across the membrane generate changes
in the potential of the membrane which are transmitted on its longitudinal axis. The
transmitted potential takes the form of a traveling wave. In several cases the wave
equation is computed from the solution of a reaction-diffusion PDE. The model
of propagating action potential in the form of a wave equation holds both for the
neuron’s membrane and for dendrites.
For example, the neuron described by FitzHugh–Nagumo equation can be
considered to have dynamics of the Shilnikov type that is
2
@V
@t
D @@xV2 C f .V / w C I
(6.6)
@w
@t
D .v kw/
where f .w/ D v.1 v/.v a/ with 0 < a < 1, > 0 and k0. If > 0 is
sufficiently small, then the wave differential equation has a solution (homoclinic
orbit). In particular, if f .v; w/ D I v C H.v a/ w where H is a Heaviside
function, then the so-called McKean model is obtained.
The dynamics of the neuron described by Eq. (6.6) is called type-II neuron
dynamics. There is also the type-I neuron dynamics described by the diffusion PDE
@2 V
@V
@t
D @x 2
C f .V / (6.7)
where f .v/ is a periodic function of period 2.
6.4 Myelinated Axons and Discrete Diffusion
It is assumed that the membrane’s axis that is covered by myelin (a fatty substant
which one the one side serves as insulator of the axis and on the other side reduces
the capacitance of the membrane). It is also assumed that in regular intervals, known
as Ranvier nodes, the axis contacts the extracellular mean, and additionally that there
is high density of NaC channels (Fig. 6.1).
The diameter of the axis is denoted as a1 , while the diameter of the myelinated
axis is denoted as a2 .
Fig. 6.1 Myelinated axis
The capacitance due to myelination is defined from the following relation

ln.a2 =a1 /
1
cm
D 2Cm dm L
(6.8)
where L is the length of the myelinated area, Cm is the capacitance of the material,
and dm is the thickness of the cellular wall. The potential on the myelinated
membrane satisfies a diffusion PDE of the form
4a12 @2 V
cm @V
L @t
D RL @t 2
(6.9)
where RL is the transmembrane resistivity. The above diffusion equation can be also
written as
2
@V
@t
D D @@tV2 (6.10)
4a2 L
where D D cm R1 1 . It holds that the transmembrane conductance and the capacitance
of the myelinated areas is about 1,000 times smaller comparing to unmyelinated
areas. The membrane’s potential varies linearly between the nodes
.Vn Vn1 /x
V .x/ D Vn1 C L
(6.11)
The current at the node is proportional to the gradient of the voltage at the
myelinated segments. Thus, at node n voltage satisfies the relation
ACm ddtVn D AIionic .Vn / C In In1 (6.12)
where A is the area of the membrane which corresponds to the node and the
longitudinal current is
4a2 @V Vn1 /
In D Rl1 @x
D 4a12 .Vn R 1L
(6.13)
Area A is the surface of the membrane emerging at the node and is the length of
the node. By dividing with surface A Eq. (6.12) becomes
6.4 Myelinated Axons and Discrete Diffusion 135
Cm ddtVn D Iionic .Vn / C D.VnC1 2Vn C Vn1 / (6.14)
where D D R4a 1
l L
. Thus the PDE of the voltage along the myelinated axis is turned
into a system of equivalent ordinary differential equations.
Cm dV
dt
D DŒV .t C / 2V .t / C V .t / Iionic .V; w; /
(6.15)
dw
dt
D g.V; w/
where parameter w represents gating variables, calcium, etc.

It can be set f .V / D Iionic .V / and it can be assumed that f .V / has three
roots, Vrest , Vthr , and Vex , which mean resting state, threshold, and excited state,
respectively. As boundary conditions, one can assume V .1/ D Vex and V1 D
Vex . Using the approximation about the second derivative with respect to time
2 V 00 D V .t C / 2V .t / C V .t / (6.16)
one arrives at the ordinary differential equation
2 4a1 00
Cm V 0 D f .V / C L R1
V (6.17)
p
L
where is the discretization step. By performing the change of variables D
the wave equation is written as
p
L
Cm
V D f .V / C 4a1
V
Rl
(6.18)
Assume that c p
is the velocity of the wave traveling along the myelinated axis. It
holds that c D L , and consequently for the myelinated part it holds
q
cmyelin D L

' L

c (6.19)
For the values D 1 m, L D 100 m one obtains cmyelin ' 10c.
6.4.1 Solitons in Neuron’s Dynamical Model
In the following approach of modelling for the neuron’s membrane dynamics, the
neuron’s axon is considered to be a one-dimensional cylinder with lateral excitations
moving along the coordinate x. The dynamics of this cylinder is described by a
wave-type equation [10, 80, 86, 103]
@2 A
2@
@t 2
D @
@x
c @x A (6.20)
where A D Ap 0A is the charge in the area of the membrane as a function of
x and t and c D 1=.sA A / is the density-dependent velocity of the wave. Here,
0A is the density of the membrane at physiological conditions. To the extent that the
compressibility is independent of the density and the amplitude of the propagating
density wave A << 0A the wave’s velocity is approximately constant (c D c0 ).
Thus, the wave equation is simplified in the form
@2 2
@t 2
A D c02 @x
@
2
A (6.21)
The compressibility sA depends on temperature and on density of the lipid

membranes. The lipids of the membrane can change from the liquid to the gel
state. At densities near the phase transition, where the two phases co-exist, a small
increase in pressure can cause a significant increase in density by converting lipids
from liquid to gel. Near this phase transition, the compression modulus becomes
significantly smaller. In the latter case, the wave’s velocity is approximated by
c2 D 1
A sA
D c02 C pA C q.A /2 (6.22)
with p < 0 and q > 0.

A more complicated form of the wave’s propagation in the nerve is obtained by
including the term h@4 A =@x 4 with h > 0. This term shows that compressibility
decreases at higher frequencies and leads to a propagation velocity which increases
with increasing frequency. The term also shows a linear dependence on frequency
of the pulse propagation velocity. Changes in coefficient h affect the spatial size of
the solitary waves but not their functional form. Substituting Eqs. (6.22) in (6.21)
and including also the abovementioned compressibility factor h@4 A =@x 4 , the
equation describing the wave propagation becomes
@2 4
@t 2
A D @
@x
fŒc02 C pA C q.A /2 @x
@
A g h @x
@
4
A (6.23)
In the above equation A is the change in lateral density of the membrane A D
A 0A , A is the lateral density of the membrane, 0A is the equilibrium lateral
density of the membrane, c0 is the velocity of small amplitude wave, p and q are
parameters defining the dependence of the wave velocity on the membrane’s density.
Equation (6.23) is closely related to Boussinesq equation.
6.4.2 Comparison Between the Hodgkin–Huxley

and the Soliton Model
In the following, some major features of the two neuron models (the
Hodgkin–Huxley model and the soliton model) are summarized [10, 80].
6.5 Estimation of Nonlinear Wave Dynamics 137
The Hodgkin–Huxley model is exclusively of electric nature: (1) The action

potential is based on the electric cable theory in which the pulse is a consequence of
voltage and time-dependent changes of the conductance for sodium and potassium,
(2) The nerve pulse consists of a voltage signal that changes both in space and time
and this change is driven by the flow of ions, through channels formed by proteins,
(3) The model is consistent with the channel-blocking effects of several poisons,
such as tetrodotoxin, but does not provide an explication of anesthesia (4) Reversible
changes in heat and mechanical changes are not explicitly addressed, and according
to this model heat generation should be expected.
The soliton model is of both electric and mechanical nature: (1) The propagation
of solitons is a consequence of the nonlinearity of the elastic constants close to
the melting transition of the lipid’s membrane, (2) The model does not consider an
explicit role of protein and ion channels, (3) The propagating pulse is associated
with changes in all variables of the membrane including temperature, lateral
pressure, thickness, and length (4) In accordance with experimental findings, the
propagating pulse in this model does not dissipate heat, (5) the model provides an
explanation of the mechanism of anesthesia.
6.5 Estimation of Nonlinear Wave Dynamics
It will be shown that the new nonlinear filtering method, the so-called Derivative-
free nonlinear Kalman Filter, can be used for estimating wave-type dynamics
in the neuron’s membrane. This can be done through the processing of noisy
measurements and without knowledge of boundary conditions. Previous results on
the application of Kalman Filtering in the estimation of neuronal dynamics can be
found in [77, 134, 208]
The following nonlinear wave equation is considered
@2
2
@t 2
D K @@x
2 C f .
/ (6.24)
Using the approximation for the partial derivative
@2

i C1 2
i C
i 1
@x 2
' D x 2
(6.25)
and considering spatial measurements of variable

along axis x at points x0 C
ix; i D 1; 2; ; N one has
@2
i
@t 2
D K

x 2 iC1
2K

x 2 i
C 1

x 2 i1
C f .
i / (6.26)
By considering the associated samples of

given by
0 ;
1 ; ;
N ;
N C1 one has
@2
1
@t 2
D K

x 2 2
2K

x 2 1
C K

x 2 0
C f .
1 /
@2
2
@t 2
D K

x 2 3
2K

x 2 2
C K

x 2 1
C f .
2 /
@2
3
@t 2
D K

x 2 4
2K

x 2 3
C K

x 2 2
C f .
3 /
(6.27)

@2
N 1
@t 2
D K

x
x 2 N
2K
2
N 1 C K

x 2 N 2
C f .
N 1 /
@2
N
@t 2
D K

x 2 N C1
2K

x 2 N
C K

x 2 N 1
C f .
N /
By defining the following state vector

x T D
1 ;
2 ; ;
N (6.28)
one obtains the following state-space description
xR 1 D K
x
x 2 2
2K
x
x 2 1
C K

x 2 0
C f .x1 /
xR 2 D K
x
x 2 3
2K
x
x 2 2
C K
x
x 2 1
C f .x2 /
xR 3 D K
x
x 2 4
2K
x
x 2 3
C K
x
x 2 2
C f .x3 /
(6.29)

xR N 1 D K
x x
x 2 N
2K
2 xN 1 C x
K
2 xN 2 C f .xN 1 /
xR N D K

x 2 N C1
x
2K
2 xN C x 2 xN 1 C f .xN /
K
Next, the following state variables are defined
y1;i D xi
(6.30)
y2;i D xP i
and the state-space description of the system becomes as follows
yP1;1 D y2;1
yP2;1 D K
y
x 2 1;2
x2K
2 y1;1 C x 2
0 C f .y1;1 /
K
yP1;2 D y2;2
yP2;2 D xK
2 y1;3 x 2 y1;2 C x 2 y1;1 C f .y1;2 /
2K K
yP1;3 D y2;3
yP2;3 D x 2 y1;4 x
K 2K
2 y1;3 C x 2 y1;2 C f .y1;3 /
K
(6.31)

yP1;N 1 D y2;N 1
yP2;N 1 D x K
2 y1;N x 2 y1;N 1 C x 2 y1;N 2 C f .y1;N 1 /
2K K
yP1;N D y2;N
yP2;N D x 2
N C1 x
K 2K
2 y1;N C x 2 y1;N 1 C f .y1;N /
K
6.5 Estimation of Nonlinear Wave Dynamics 139
The dynamical system described in Eq. (6.31) is a differentially flat one with flat
output defined as the vector yQ D Œy1;1 ; y1;2 ; ; y1;N . Indeed all state variables can
be written as functions of the flat output and its derivatives.
Moreover, by defining the new control inputs
v1 D xK
2 y1;2 x 2 y1;1 C x 2
0 C f .y1;1 /
2K K
v2 D x 2 y1;3 x 2 y1;2 C x 2 y1;1 C f .y1;2 /

K 2K K
v3 D xK
2 y1;4 x 2 y1;3 C x 2 y1;2 C f .y1;3 /
2K K
(6.32)

vN 1 D x 2 y1;N x 2 y1;N 1 C x
K 2K K
2 y1;N 2 C f .y1;N 1 /
vN D x 2
N C1 x 2 y1;N C x 2 y1;N 1 C f .y1;N /
K 2K K
the following state-space description is obtained

0 1 0 1
0 1 0 0 0 0 0 0 0 0 0 0 0
0
yP1;1
1 B C0 y 1 B C
B 0 0 0 0 0 0 0 0 C 1;1 B1 0 0 0 0C
B yP2;1 C B 0 0 0 1 0 0 0 0 C B y2;1 C B 0 0 0 0 0 C
B C B
C0 1
B C B B C B
B yP C B 0 0 0 0 0 0 0 0 C B C
C B y1;2 C B 0 1 0 0 0 C B
C v1
B 1;2 C B v2 C
B yP C B 0 0 0 0 0 0 0 0 C CB C B0 0 0 0 0C CB C
B 2;2 C B C B y2;2 C B B C B C
B C B B C B v C
B C D B 0 0 0 0 0 0 0 0 C B C C B 0 0 1 0 0C
3
C B C B C
B C B B C B C
ByP1;N 1 C B C
C By1;N 1 C B
B C
C B C
B C B B C @
C N 1 A
ByP2;N 1 C B 0 0 0 0 0 1 0 0 C C By2;N 1 C B
B 0 0 0 0 0 C
v
B C
@ yP1;N A B CB C B C vN
B 0 0 0 0 0 0 0 0 C @ y1;N A B 0 0 0 1 0 C
B C B C
yP2;N @ 0 0 0 0 0 0 0 1 A y2;N @0 0 0 0 0A
0 0 0 0 0 0 0 0 0 0 0 0 1
(6.33)
By selecting measurements from a subset of points xj j 2Œ1; 2; ; m, the

associated observation (measurement) equation becomes
0 1
0 1 y1;1
0 1 1 0 0 0 0 B C
B y2;1 C
z1 B0 0 0 0 0CBy C
B z2 C B C B 1;2 C
B CDB CB C
C B y2;2 C
@ A B
B CB C
(6.34)
@0 0 0 1 0AB C
zm B C
0 0 0 0 0 @y1;N A
y2;N
Thus, in matrix form one has the following state-space description of the system
yQP D AyQ C Bv
(6.35)
zQ D C yQ
Denoting a D Dx K
2 and b D Dx 2 , the initial description of the system given in
2K
Eq. (6.33) is rewritten as follows:
0 1 0 1
0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 1Bb 0 a 0 0 0 0 0 0 0 0 0 0C 0 1 B1 0 0 0 0C
yP1;1 B C y1;1 B C
B yP2;1 C B B 0 0 0 1 0 0 0 0 0 0 0 0 0
CB
C y C B
B 0 0 0 0 0
C0
C 1
B C B C B 2;1 C B
B yP C B a 0 b 0 a 0 0 0 0 0 0 0 0C B y C B0 1 0 0 0C CB
v1
B 1;2 C B CB 1;2 C
C B C v2 C
B yP
B 2;2 C B
C CBB C B0 0 0 0 0CB C
B C B
0 0 0 0 0 1 0 0 0 0 0 0 0 CB y 2;2
C B
B
C B v3 C C
B C B
B C D B0 0 a 0 b 0 a 0 0 0 0 0 0C B C C B 0 0 1 0 0 C B C C
B C B B C B C
ByP1;N 1 C B CC By1;N 1 C B
B CB
C C
B C B B C @
C N 1 A
ByP2;N 1 C B 0 0 0 0 0 0 0 0 0 0 1 0 0 C C By2;N 1 C B
B 0 0 0 0 0 C
v
B C
@ yP1;N A B CB C B C vN
B0 0 0 0 0 0 0 a 0 b 0 a 0C @ y1;N A B 0 0 0 1 0 C
B C B C
yP2;N @ 0 0 0 0 0 0 0 0 0 0 0 0 1 A y2;N @0 0 0 0 0A
0 0 0 0 0 0 0 0 0 a 0 b 0 0 0 0 0 1
(6.36)
The associated control inputs are now defined as
v1 D x
K
2
0 C f .y1;1 /
v2 D f .y1;2 /
v3 D f .y1;3 /
(6.37)

vN 1 D f .y1;N 1 /
vN D xK
2
N C1 C f .y1;N /
By selecting measurements from a subset of points xj j 2Œ1; 2; ; m, the

associated observation (measurement) equation remains as in Eq. (6.34), i.e.
0 1
0 1 y1;1
0 1 1 0 0 0 0 B C
B y2;1 C
z1 B0 0 0 0 0CBy C
B z2 C B C B 1;2 C
B CDB B
CB C
C B y2;2 C (6.38)
@ A B CB C
@0 0 0 1 0AB C
zm B C
0 0 0 0 0 @y1;N A
y2;N
For the linear description of the system in the form of Eq. (6.35) one can perform
estimation using the standard Kalman Filter recursion. The discrete-time Kalman
filter can be decomposed into two parts: (1) time update (prediction stage), and (2)
measurement update (correction stage).
The discrete-time equivalents of matrices A, B, C in Eq. (6.36) and Eq. (6.38)
are computed using common discretization methods. These are denoted as Ad , Bd ,
and Cd respectively. Then the Kalman Filter recursion becomes:
Fig. 6.2 Grid points for

measuring
.x; t /
Measurement update:
K.k/ D P .k/CdT ŒCd P .k/CdT C R1

O
y.k/ D yO .k/ C K.k/Œz.k/ Cd yO .k/ (6.39)
P .k/ D P .k/ K.k/Cd P .k/
Time update:
P .k C 1/ D Ad .k/P .k/ATd .k/ C Q.k/

(6.40)
yO .k C 1/ D Ad .k/y.k/
O C Bd .k/u.k/
Therefore, by taking measurements of

.x; t / at time instant t at a small number of
measuring points, as shown in Fig. 6.2, j D 1; ; n1 it is possible to estimate the
complete state vector, i.e. to get values of
in a mesh of points that covers efficiently
the variations of
.x; t /. By processing a sequence of output measurements of the
system, one can obtain local estimates of the state vector y. O The measuring points
can vary in time provided that the observability criterion for the state-space model
of the PDE holds.
Remark. The proposed derivative-free nonlinear Kalman Filter is of improved pre-
cision because unlike other nonlinear filtering schemes, e.g. the Extended Kalman
Filter it does not introduce cumulative numerical errors due to approximative
linearization of the system’s dynamics. Besides it is computationally more efficient
(faster) because it does not require to calculate Jacobian matrices and partial
derivatives.
6.6.1 Evaluation Experiments
The proposed filtering scheme was tested in estimation of the dynamics of a

wave equation of the form of Eq. (6.24) under unknown boundary and initial
conditions. It has been shown that it is possible to obtain voltage measurements from
dendritic trees using, for example, laser-based scanning techniques [69, 84, 202].
In the simulation experiments the following wave-type dynamics in the neuron’s
membrane was considered
O t/
Fig. 6.3 Test case 1: (a) spatiotemporal variation of the wave function
.x; t /. (b) estimate
.x;
of the wave function provided by the derivative-free nonlinear Kalman Filter
@2
@t 2
D @
@x
fŒc02 C
C q
2 @
@x
g)
(6.41)
@2
2
@t 2
D . C 2q
/. @
@x
/2 C Œc02 C
C q
2 @@x
2
By denoting f .
/ D . C 2q
/. @
@x
/2 and K.x; t / D Œc02 C
C q
2 , one finally
obtains the following description for the wave-type dynamics of the membrane
@2
2
@t 2
D K.x; t / @@x
2 C f .
/ (6.42)
The estimator was based on the Derivative-free nonlinear Kalman Filter as analyzed
in Sect. 6.5 and made use of a grid of N D 50 points, out of which n D 25 were
measurement points. At each measurement point a value of the state variable x1 D
.x; t / was obtained. In Fig. 6.3 the estimate of the wave function provided by the
distributed filtering algorithm is compared to the real wave function dynamics. Due
to boundary conditions set at points x D 0 and x D 10 of the x-axis wave type
dynamics .x; t / is generated and propagates in time. The nonlinear Kalman Filter
estimates the wave-type dynamics without knowledge of the initial conditions of the
PDE. As it can be noticed the derivative-free nonlinear Kalman Filter approximates
closely the real wave function. Indicative results about the estimation obtained at
local grid points is given in Figs. 6.4, 6.5, and 6.6.
The evaluation tests were repeated for different values in the parameters of
the wave function coefficient K.x; t /. In Fig. 6.7 a new value of gain K.x; t / is
considered and the estimate of the wave function provided by the distributed filtering
algorithm is compared again to the real wave function dynamics. Additional results
about the accuracy of estimation obtained in local grid points, when using different
coefficients c0 , , and q in the computation of K.x; t / are given in Figs. 6.8, 6.9,
and 6.10. As it can be observed again, the derivative-free nonlinear Kalman Filter
resulted in very accurate estimates of the wave-type dynamics.
a 400 b 120
100
300
80
200
60
yi − y−esti
yi − y−esti
100 40
0 20
0
−100
−20
−200
−40
−300 −60
0 5 10 15 20 0 5 10 15 20
t t
Fig. 6.4 Test case 1: estimate (dashed green line) and real value (red continuous line) (a) of
.x1 ; t / at grid point 1 (b) of

.x2 ; t / at grid point 2
a 100 b 80
80 60
60 40
yi − y−esti
yi − y−esti
40 20
20 0
0 −20
−20 −40
−40 −60
0 5 10 15 20 0 5 10 15 20
t t

a 40 b 40
30 30
20 20
10 10
yi − y−esti
yi − y−esti
0 0
−10 −10
−20 −20
−30 −30
−40 −40
−50 −50
0 5 10 15 20 0 5 10 15 20
t t
.x1 5; t / at grid point 15 (b) of

O t/
Fig. 6.7 Test case 2: (a) spatiotemporal variation of the wave function
.x; t / (b) estimate
.x;
of the wave function provided by the derivative-free nonlinear Kalman Filter
a 300 b 150
250
100
200
150 50
100
yi − y−esti
yi − y−esti
0
50
−50
0
−50 −100
−100
−150
−150
−200 −200
0 5 10 15 20 0 5 10 15 20
t t

a 80 b 60
60
40
40
20
yi − y−esti
yi − y−esti
20
0
0
−20
−20
−40
−40
−60 −60
0 5 10 15 20 0 5 10 15 20
t t

a 50 b 50
40 40
30 30
20 20
10 10
yi − y−esti
yi − y−esti
0 0
−10 −10
−20 −20
−30 −30
−40 −40
−50 −50
0 5 10 15 20 0 5 10 15 20
t t
.x1 5; t / at grid point 15 (b) of

6.6.2 Assessment of the Filter’s Performance
6.6.2.1 Stability of the Filtering Method
The stability and convergence conditions for the proposed filtering algorithm are
those of the standard Kalman Filter, which means that the filter converges if the
system’s model in its linearized canonical form satisfies obvervability (detectability)
criteria. About the method for solution of a PDE through its decomposition into
a set of local ODEs, numerical stability conditions have been provided and these
are related to the step of spatio-temporal discretization of the initial PDE [139].
The method converges and remains numerically stable if the discretization steps
2 2
are taken to be sufficiently small. For the basic wave-type PDE @@t y2 D K @@xy2 the
2 1 where Dt and Dx are the discretization steps in
Dt
convergence condition is 2K Dx
space and time [139].
6.6.2.2 Implementation Stages and Advantages of the Filtering Method
The first stage of the filter’s design is to analyze the PDE that describes the
system’s dynamics into a set of ordinary differential equations. Actually, at each
iteration of the algorithm in time, a numerical solution of the PDE is computed at
a spatial grid of N points and at each point of the grid the system’s dynamics is
described by a nonlinear ODE. At a second stage differential flatness theory and
a diffeomorphism (change of coordinates) is used to transform the local nonlinear
ODEs into linear ODEs which in turn can take the form of a linear state space
equation in the canonical (Brunovsky) form. The Derivative-free nonlinear Kalman
Filter consists of the standard Kalman Filter recursion on the linearized equivalent
model of the valve and on computation of state and disturbance estimates using
the diffeomorphism (relations about state variables transformation) provided by

differential flatness theory.
Comparing to other nonlinear filtering approaches that could have been used,
the proposed filtering approach exhibits significant advantages: (1) it is based on
an exact linearization of the local ODEs thus avoiding numerical errors due to
approximative linearization, (2) in terms of computation it is faster than other
nonlinear filtering approaches, (3) it exhibits the optimality properties of the
standard Kalman Filter recursion for estimation under measurement noise.
6.6.2.3 Methods for Real-Time Monitoring of Neuron’s Membrane

Dynamics
An established method for recording neuron’s activity at low spatial resolution is

based on the use of multi-electrode arrays. Monitoring of the neurons’ activity at
low resolution can be also obtained with the use of positron emission tomography.
This technique involves usage of radioactive tracers which bind to receptors. The
tracers emit rays which are detected by a scanning device and reflect the dynamics
of the binding sites. It has been also shown that it is possible to obtain voltage
measurements at high resolution from dendritic trees using fMRI techniques and
optical imaging. fMRI is a special case of magnetic resonance imaging. It is based
on the different magnetization features between oxygenated and non-oxygenated
tissue. fMRI provides recording of the activity of the neuron’s membrane with high
spatial resolution (of the order of tens of m) and high sampling rate.
Optical methods are the most suitable for measuring voltage variations in neuron
membranes at high resolution. This can be succeeded, for example, through the
monitoring of molecules called chromophores or voltage sensitive dyes that change
their color according to voltage levels in the membrane. More recently, the use of
quantum dots as voltage signaling nanoparticles has enabled to further improve
the spatial resolution of optical imaging techniques. The resolution of the optical
imaging methods is at the m-scale and enables to obtain a sufficient number of
measurements for filtering and state estimation purposes [123–138].
6.6.2.4 Practical Applications of the Proposed Filtering Method
The proposed filtering method for distributed parameter systems has a wide range of
applications: (1) Estimation of the dynamics of the neuron’s membrane with the use
of a small number of measurements. Due to practical constraints the spatiotemporal
variations of the membrane’s voltage have to be performed using only a limited
measurements set. Moreover, knowledge about initial and boundary conditions
of the system is in most cases unknown. To estimate the dynamics of this type
of distributed parameter system the use of the proposed filtering method that is
based on the Derivative-free nonlinear Kalman Filter is of great importance, (2)
Estimation of the parameters of the models that describe the dynamics of biological
6.7 Conclusions 147
neurons. Actually, one has to do with a dual identification problem, that is estimation
of the non-measurable elements of the state vector of the biological neuron
and estimation of the unknown model parameters. The proposed Derivative-free
nonlinear Kalman Filter can offer an efficient solution to this problem (3) Change
detection about the parameters of the model that describes the neuron’s dynamics.
This is a fault diagnosis problem and can result in efficient method of medical
diagnosis of neurological diseases. The filter can be parameterized to reproduce
the dynamics of the healthy neuron. By comparing real measurements from the
neuron against measurements obtained from the filter and by performing statistical
processing for the associated differences (residuals) one can diagnose deviation of
the neuron’s functioning from the normal ranges. This can be particularly useful for
diagnosis of neurological diseases related to neurons decay, at their early stages.
Moreover, it is possible to perform fault isolation, which means to find which is the
distorted parameter in the neuron’s model that is responsible for deviation from the
healthy functioning. This can be particularly useful for developing more efficient
medical treatments of neurological diseases (4) More efficient modelling of brain
functioning and of the nervous system. By detecting changes in the parameters of
neurons’ model one can find out how the response and adaptation of the neurons’
functioning is associated with external stimuli and medication (pharmaceutical
treatment).
6.7 Conclusions
This chapter has analyzed wave-type PDEs that appear in the transmission of neural
signals and has proposed filtering for estimating the dynamics of the neurons’
membrane. It has been shown that in specific neuron models the spatiotemporal
variations of the membrane’s voltage follow PDEs of the wave-type while in other
models such variations are associated with the propagation of solitary waves through
the membrane. To compute the dynamics of the membrane’s PDE model without
knowledge of initial conditions and through the processing of a small number of
measurements, a new filtering method, under the name Derivative-free nonlinear
Kalman Filtering, has been proposed.
The method is based into decomposition of the initial wave-type PDE that
describes the dynamics of the distributed parameter system, into a set of nonlinear
ordinary differential equations. Next, with the application of a change of coordinates
(diffeomorphism) that is based on differential flatness theory, the local nonlinear
differential equations are turned into linear ones. This enables to describe the wave
dynamics with a state-space equation that is in the linear canonical (Brunovsky)
form. For the linearized equivalent of the wave system dynamics it is possible to
perform state estimation with the use of the standard Kalman Filter recursion. The
efficiency of the derivative free nonlinear Kalman Filter has been confirmed through
numerical simulation experiments.
Chapter 7
Stochastic Models of Biological Neuron
Dynamics
Abstract The chapter examines neural networks in which the synaptic weights
correspond to diffusing particles. Each diffusing particle (stochastic weight) is
subject to the following forces: (1) a spring force (drift) which is the result of the
harmonic potential and tries to drive the particle to an equilibrium and (2) a random
force (noise) which is the result of the interaction with neighboring particles. This
interaction can be in the form of collisions or repulsive forces. It is shown that the
diffusive motion of the stochastic particles (weights’ update) can be described by
Fokker–Planck’s, Ornstein–Uhlenbeck, or Langevin’s equation which under specific
assumptions are equivalent to Schrödinger’s diffusion equation. It is proven that
Langevin’s equation is a generalization of the conventional gradient algorithms.
7.1 Outline
Conventional neural networks may prove insufficient for modelling memory and
cognition, as suggested by effects in the functioning of the nervous system, which
lie outside classical physics [19, 48, 59, 73, 75, 136, 168]. One finds ample support
for this in an analysis of the sensory organs, the operation of which is quantized at
levels varying from the reception of individual photons by the retina, to thousands
of phonon quanta in the auditory system. Of further interest is the argument that
synaptic signal transmission has a quantum character, although the debate on this
issue has not been conclusive. For instance, it has been mentioned that superposition
of quantum states takes place in the microtubules of the brain and that memory recall
is the result of quantum measurement [73]. Moreover, it has been argued that human
cognition must involve an element inaccessible to simulation on classical neural
networks and this might be realized through a biological instantiation of quantum
computation.
To evaluate the validity of the aforementioned arguments, neural structures
with weights that follow the model of the quantum harmonic oscillator (QHO)
will be studied in this chapter. Connectionist structures which are compatible with

150 7 Stochastic Models of Biological Neuron Dynamics
the theory of quantum mechanics and demonstrate the particle-wave nature of

information have been analyzed in [34, 120, 127, 133]. The use of neural networks
compatible with quantum mechanics principles can be found in [6, 135, 137, 145],
while the relation between random oscillations and diffusion equations has been
studied in [66, 179]. Other studies on neural models with quantum mechanical
properties can be found in [143, 149, 167, 198].
In this chapter it is assumed that the weights of neural networks are stochastic
variables which correspond to diffusing particles, and interact to each other as
the theory of Brownian motion (Wiener process) predicts. Brownian motion is the
analogous of the QHO, i.e. of Schrödinger’s equation under harmonic (parabolic)
potential. However, the analytical or numerical solution of Schrödinger’s equation
is computationally intensive, since for different values of the potential V .x/ it is
required to calculate the modes k .x/ in which the particle’s wave-function .x/ is
decomposed. Moreover, the solution of Schrödinger’s equation contains non-easily
interpretable terms such as the complex number probability amplitudes which are
associated with the modes k .x/, or the path integrals that constitute the particle’s
trajectory. On the other hand, instead of trying to solve Schrödinger’s equation for
various types of V .x/ one can study the time evolution of the particle through an
equivalent diffusion equation, assuming probability density function depending on
QHO’s ground state, i.e. 0 .x/ D j 0 .x/j2 [56].
This chapter extends the results on neural structures compatible with quantum
mechanics principles presented in [163, 165]. Moreover, the chapter extends the
results on quantum neural structures, where the basic assumption was that the neural
weights correspond to diffusing particles under Schrödinger’s equation with zero
or constant potential [149]. The diffusing particle (stochastic weight) is subject to
the following forces: (1) a spring force (drift) which is the result of the harmonic
potential and tries to drive the particle to an equilibrium and (2) a random force
(noise) which is the result of the interaction with neighboring particles. This
interaction can be in the form of collisions or repulsive forces. It is shown that
the diffusive motion of the stochastic particles (weights’ update) can be described
by Langevin’s equation which is a stochastic linear differential equation [56, 66].
Following the analysis of [22, 52, 93] it is proven that Langevin’s equation is a
generalization of the conventional gradient algorithms. Therefore neural structures
with crisp numerical weights can be considered as a subset of NN with stochastic
weights that follow the QHO model.
7.2 Wiener Process and Its Equivalence to Diffusion
7.2.1 Neurons’ Dynamics Under Noise
Up to now, neuronal dynamics has been expressed in a deterministic manner.

However, stochastic terms such as noise may also be present in the neurons’
7.2 Wiener Process and Its Equivalence to Diffusion 151
dynamic model. Reasons for the appearance of noise in neurons are: (1) randomness
in the opening or closing of the ion channels, (2) randomness in the release of
transmitters which in turn leads to random charging and discharging of the neuron’s
membrane [121, 196, 197]. The main effects of the noise in neurons are as follows:
(1) firing of the neurons even under sub-threshold inputs, (2) increase of the pattern
storage capacity.
A basic tool for studying the stochastic dynamics of neurons is a stochastic
differential equation known as Langevin’s equation:
dx D A.x; t /dt C B.x; t /dW.t / (7.1)
For the numerical solution of Langevin’s equation usually the following solution is
used
p
x.n C 1/ D x.n/ C hA.x.n/; tn / C B.x.n/; tn / hNO .0; 1/ (7.2)
where h is the discretization step, and NO .0; 1/ is a vector of independent, identically

distributed variables.
7.2.2 Wiener Walk and Wiener Process
The Wiener walk and the Wiener process are essential mathematical tools for
describing the stochastic neuron dynamics. Wiener walk will be analyzed and the
Wiener process will be derived as a limit case of the walk [37,90]. The Wiener walk
describes a simple symmetric random walk. Assume 1 ; ; n a finite sequence of
independent random variables, each one of which takes the values ˙1 with the same
probability. The random walk is the sequence
sk D 1 C 2 C C k ; 0kn (7.3)
The n-step Wiener walk is considered in the time interval Œ0; T , where the time step
t is associated with the particle’s displacement x
w.tk / D 1 x C C k x (7.4)
The random function that is described by Eq. (7.4) is the Wiener walk [56]. A sample
of the Wiener walk in depicted in Fig. 7.1a.
The Wiener walk is an important topic in the theory of stochastic processes,
is also known as Brownian motion and it provides a model for the motion of a
particle under the effect of a potential. The Wiener process is the limit of the
Wiener walk for n!1, and using the central limit theorem (CLT) it can be shown
that the distribution of the Wiener process is Gaussian. Indeed, since the random
variable w.tk / of Eq. (7.4) is the sum of an infinitely large number of increments
a 15 b 1
0.9
10
0.8
5 0.7
Wiener walk w(k)
0.6
0
f(x)
0.5
−5
0.4
−10 0.3
0.2
−15
0.1
−20 0
0 200 400 600 800 1000 1200 1400 1600 1800 2000 −8 −6 −4 −2 0 2 4 6
x
k (iterations)
Fig. 7.1 (a) Wiener random walk (b) Solution of Schrödinger’s equation: Shifted Gaussians that
give the probability density function of a stationary diffusion process (continuous curves) and the
approximation of the p.d.f. by symmetric triangular possibility distributions (dashed lines)
(or decrements), then according to the CLT it must follow a Gaussian distribution.
Thus one obtains:
Efw.t /g D 0 while EŒw.t / Efw.t /g2 D 2 t (7.5)
7.2.3 Outline of Wiener Process Properties
Wiener’s process is a stochastic process that satisfies the following conditions:

1. w.0/ D 0
2. The distribution of the stochastic variable w.t / is a Gaussian one with a p.d.f.
.x; t / which satisfies the following relation
@.x;t/ 2 @2 .x;t/
@t
D 2 @x 2
; .x; 0/ D ı.x/ (7.6)
For a limited number of time instants t1 < t2 < < tn the stochastic variables
w.tj / w.tj 1 / are independent.
3. It holds that Efw.t /g D 0 and EfŒw.t / w.s/2 D 2 .t s/g for all 0st .
4. w.t / is a continuous process
The standard Wiener process evolves in time according to the following relation
p
w.t C h/ D w.t / C hN.0; 1/ (7.7)
The Wiener process actually describes a diffusion phenomenon and the associated
p.d.f. of stochastic variable is given by
x 2
.x; t / D p1 e 2t (7.8)
2 t
7.2 Wiener Process and Its Equivalence to Diffusion 153
7.2.4 The Wiener Process Corresponds to a Diffusion PDE
It has been shown that the limit of the Wiener walk for n!1 is the Wiener process,
which corresponds to the partial differential equation of a diffusion [56]. For t > 0,
function .x; t / is defined as the probability density function (p.d.f.) of the Wiener
process, i.e.
Z C1
EŒf .w.t // D f .x/.x; t /dx (7.9)
1
As explained in Eq. (7.6), the p.d.f. .x; t / is a Gaussian variable with mean value
equal to 0 and variance equal to 2 t which satisfies a diffusion p.d.e of the form
@ 1 @2
D 2 2 (7.10)
@t 2 @t
which is the simplest diffusion equation (heat equation). The generalization of the
Wiener process in an infinite dimensional space is the Ornstein–Uhlenbeck process,
where the joint probability density function is also Gaussian [17, 56]. In that case
there are n Brownian particles, and each one performs a Wiener walk, given by
wi .tk /; i D 1; ; n of Eq. (7.4).
7.2.5 Stochastic Integrals
For the stochastic variable w.t / the following integral is computed

Rt
I D t0 G.s/dw.s/ (7.11)
or
Pn
Sn D j D1 G.j /Œw.tj / w.tj 1 / (7.12)
where G.t / is a piecewise continuous function. To compute the stochastic integral

the selection of sample points j is important. If j D tj 1 , then one has the Itô
calculus. If j D .tj 1 C tj /=2, then one has the Stratonovic calculus.
7.2.6 Ito’s Stochastic Differential Equation
From the relation about the standard Wiener process given in Eq. (7.7), and
considering that the variance of noise is equal to 1, it holds that
EŒ.w.t C h/ w.t //2 D hEŒN.0; 1/2 D h (7.13)

Using Langevin’s equation one has
dx D ˛.x; t /dt C w.t / (7.14)
Assume that function y D f .x/ where f is twice differentiable. It holds that
dy D f .x C dx/ f .x/ D f 0 .x/dx C 12 f 00 .x/dx2 C D

f .x/Œ˛.x; t /dt C b.x; t /dw.t / C 12 f 00 .x/b 2 .x; t /.dw.t //2 C D
0
Œf 0 .x/˛.x; t / C 12 f 00 .x/b 2 .x; t /dt C f 0 .x/b.x; t /dw.t / C

(7.15)
The relation

1
df Œx.t / D f 0 .x/˛.x; t / C f 00 .x/b 2 .x; t / dt
2
Cf 0 .x/b.x; t /dw.t / (7.16)
is Itô’s formula and can be generalized to the multi-dimensional case.
7.3 Fokker–Planck’s Partial Differential Equation
7.3.1 The Fokker–Planck Equation
Fokker–Planck’s equation stands for a basic tool for the solution of stochastic
differential equation. Instead of attempting an analytical solution of the
stochastic differential equation one can attempt to find the equivalent solution
of Fokker–Planck equation which stands for a partial differential equation.
It is assumed that .x; t / denotes the probability density function the stochastic
variable X to take the value x at time instant t . One can obtain the Fokker–Planck
equation after a series of transformations applied to Langevin’s equation, thus con-
firming that the two relations are equivalent. Thus one starts from a Langevin-type
equation
dx D f .x; t /dt C g.x; t /dt (7.17)
Next the transformation y D h.x/ is introduced, where h is an arbitrary function

that is twice differentiable. It holds that
dh.x/ D h0 .x/f .x; t /dt C h00 g 2 .x; t /=2dt C h0 .x/gdw (7.18)
By computing mean values one gets
d
dt
Efh.x/g D Efh0 .x/f .x; t /g C Efh00 .x/g 2 .x; t /=2g (7.19)
7.3 Fokker–Planck’s Partial Differential Equation 155
Assume that .x; t / is the probability density function for the stochastic variable x.
It is noted that
R
EfU.x; t /g D U.x; t /.x; t /dx (7.20)
Using Taylor series expansion one gets

R R
d
dt
h.x/.x; t /dx D Œh0 .x/f .x; t / C h00 g 2 .x; t /=2.x; t /dx (7.21)
which is also written as

R R
d
dt
h.x/.x; t /dx D Œ.f .x; t /.x; t //0 C .g 2 .x; t /=2.x; t //00 h.x/dx (7.22)
and since the relation described in Eq. (7.22) should hold for all h.x/ one gets
@
@t
D @
@x
Œf .x; t /.x; t / C 1 @
2 @x
Œg 2 .x; t /.x; t / (7.23)
This is Fokker–Planck equation.
7.3.2 First Passage Time
This is a parameter which permits to compute the firing rate of the neurons. In such
a case, the aim is to compute the statistical distribution that is followed by the time
instant T in which stochastic variable x exits the interval Œa; b (Fig. 7.2).
The probability for x to belong in the interval Œa; b at time instant t is denoted
as G.x; t /. Thus if t is the time instant at which x exits the interval Œa; b, then
G.x; t / D prob.T t /.
In the case of neurons, the first passage time corresponds to the time instant where
the membrane’s potential exceeds a threshold and a spike is generated. It holds that
G.x; t / satisfies Fokker–Planck equation, that is
@G.x;t/ 2 @2 G.x;t/
@t
D f .x; t / @G.x;t/
@x
C 2 @x 2
(7.24)
Regarding boundary conditions it holds that G.x; 0/ D 1 if ax < b.
7.3.3 Meaning of the First Passage Time
In biological neuron models, such as the Morris–Lecar model, a spike is generated

N One can write the complete Fokker–Planck
if variable w.t / exceeds a threshold w.
equations for a wide domain, compute the outgoing flux (rate in time that the voltage
exceeded certain boundaries) and thus compute the firing rate.
Fig. 7.2 First passage time for a wiener process
For example, in case of a 2D neuron model one has
dV D f .V; w/dt C dw
dw D g.V; w/dt (7.25)
and the associated Fokker–Planck equation is written as

2 @2 P
@P
@t
D 2 @V
Œf .V; w/P V Œg.V; w/P w (7.26)
Assume that the stationary solution of the Fokker–Planck equation is computed,

denoted as P .V; w/. This variable defines the probability distribution for the values
of V and w. Then one has firing of a spike if w exceeds threshold w. N The firing rate
is computed as
RV
F D V12 Jw .V; w/dV
N (7.27)
where Jw .V; w/ D g.V; w/P .V; w/.
7.4 Stochastic Modelling of Ion Channels
By introducing stochastic dynamics to the neurons’ model (i.e, to the Morris–Lecar

model), one obtains equations of the Fokker–Planck or Langevin type. Assume that
the number of ion channels in the membrane is N , ˛ is the transition rate from open
7.5 Fokker–Planck Equation and the Integrate-and-Fire Neuron Model 157
to close, ˇ is the transition rate from closed to open. Moreover it is assumed that the
number of open channels in the membrane is o.
Then N o is the number of closed channels at time instant t , r1 D ˛.N o/ is
the total rate of transitions from open to closed, and r2 D ˇo is the total number of
transitions from closed to open. The aggregate rate for all events is r D r1 C r2 .
Denoting X1 2.0; 1/ the probability of appearance of an event until time instant
tnew (under exponential waiting time) one has
X1 D e rtnew )tnew D 1r ln.X1 / (7.28)
Regarding the Morris–Lecar neuron model the following may hold: (1) opening of
a calcium channel, (2) closing of a calcium channel, (3) opening of a potassium
channel, (4) closing of a potassium channel. It has been shown that the rate of
opening or closing of the channels is associated with the voltage of the membrane
which is described by the relation
Cn dV
dt
D I gl .V El / .gk w=Nw /.VEk / gC a .M=Nm /.V EC a / (7.29)
where W is the total number of open ion channels KC , M is the total number of
total ion channels C a2C . Equation (7.29) is written also as
dV
dt
D .V1 V /g (7.30)
where V1 and g are functions of the parameters W and M .

When introducing stochastic models to describe the change of the membrane’s
voltage then either a Fokker–Planck or a Langevin equation follows, that is
dx D Œ˛.1 x/ C ˇxdt C x dW.t / (7.31)
˛.1x/Cˇx
where the standard deviation is approximated by x2 D N
(standard
deviation).
7.5 Fokker–Planck Equation and the Integrate-and-Fire

Neuron Model
7.5.1 The Integrate-and-Fire Neuron Model
A simple model of the neuron’s dynamics (apart from the elaborated model of
the FitzHugh–Nagumo, Hodgkin–Huxley, or Morris–Lecar neuron) is that of the
integrate and fire neuron, and this is given by
dV D .I aV /dt C dW t (7.32)
Fig. 7.3 The

integrate-and-fire biological
neuron model is represented
as a resistance–capacitance
circuit
which in discrete form is written as

p
VnCh D Vn C h.In aVn / C hNO .0; 1/ (7.33)
By integrating Langevin’s equation in time one obtains

Rt Rt
x.t / D x.t0 / C t0 a.x.s/; s/ds C t0 b.x.s/; s/dW.s/ (7.34)
In the integrate-and-fire model the neuron dynamics is described as an electric

circuit, as shown in Fig. 7.3 [45, 75]. This is in accordance with the simplified
Hodgkin–Huxley model in which spatial variation of the voltage is not taken into
account. The state variable is taken to be the membrane’s potential V
P
C VP D i Ii .t / (7.35)
where C is the neuron membrane capacitance, V is the neuron membrane voltage,

and Ii is a current (flow of charge) associated with the membrane. The equivalent
circuit representation of the integrate-and-fire neuron is a resistance–capacitance
(RC) circuit.
In Fig. 7.4 it is shown how the parts of the biological neuron are modeled by
the local RC circuits and how spikes are generated. The neuron’s membrane is
activated by input current s.t /. The membrane’s capacitance Cm is in parallel to
the membrane’s resistance Rm (or equivalently to the membrane’s conductance gm )
and is driven by the synaptic current s.t /. The synaptic current s.t / is affected by the
synapse’s resistance Rsyn and the synapse’s capacitance Csyn . When the membrane’s
(capacitor Cm ) voltage V exceeds threshold VT a spike occurs and the voltage is
reset to VR . The integrate-and-fire model of the neuron dynamics can be extended
to the case of multiple interconnected neurons, as shown in Fig. 7.5.
Currents s.t / are considered to be due to the inflow and outflow of ions such as
KC , Cl , NaC , or CaC . The membrane potential was shown to be associated with
the concentration of electric charges. Currents s.t / which appear in the previous
7.5 Fokker–Planck Equation and the Integrate-and-Fire Neuron Model 159
Fig. 7.4 Correspondence of the integrate-and-fire neuron model to the biological neuron
Fig. 7.5 Model of the biological associative memory
neuron model represent a continuous flow of charge. Considering both ionic currents
and synaptic currents excitation Eq. (7.35) can be written as
C VP D gL .VL V / C s.t / (7.36)
where gL is the membrane’s (ion’s channel) conductance, VL is an equilibrium

potential, and s.t / is the synaptic current input. Spiking is modeled as a threshold
process, i.e. once membrane potential V exceeds a threshold value VT , a spike is

assumed and the membrane potential is reset to VR where VR VL VT . An even
more elaborated integrate-and-fire neuron model has been proposed, which takes
the form
VP D 1
C
ŒgL .VL V / C s.t / C ˛.VR V /ˇ (7.37)
The spiking period T varies according to

2
TP D 1 ˛TH.V /; ˇ D exp 2
T
2
(
1 V VT (7.38)
H.V / D
0 V < VT
The integration of Eq. (7.36) provides also the spiking period of the neuron
R VT R
C
VR gL .VL V /Cs.t/ dV D dT D T (7.39)
When s.t / is deterministic then the neuron spikes with a specific period. On the
other hand, when the input s.t / of the neuron is a stochastic variable then the
neuron spikes with a random period. In stochastic neurons there are stochastic flows
of charges and stochastic currents s.t / which cause spiking at a random rate. The
models of Eqs. (7.35) and (7.37) can be also extended to include various types of
ion-channel dynamics, and to model accordingly spike-rate adaptation and synaptic
transmission [75].
7.5.2 Stochastic Integrate-and-Fire Neuron Model

and the Fokker–Planck Equation
The dynamics of the previously described integrate-and-fire stochastic neuron can

be associated with Fokker–Planck equation [75]. Now, input s.t / to the neuron’s
model is a random variable (e.g., there is randomness in the flow of ions and
randomness in the associated currents).
As a consequence, the spiking period in the stochastic neuron cannot be
analytically defined [see Eq. (7.36)], but is sampled from a probability distribution
[88]. Using the stochastic input s.t / in the equations of neuron dynamics, i.e.
Eqs.(7.35) and (7.37), the spatio-temporal variations of the neuron’s voltage will no
longer be associated with deterministic conditions, but will be given by a probability
density function .x; t /. In [75] it has been proposed to associate ions density
function .x; t / with a Fokker–Planck equation (or an advection-diffusion equation)
of the form
7.6 Stochasticity in Neural Dynamics and Relation to Quantum Mechanics 161
@ @u.x/ 2 @2
D C (7.40)
@t @x 2 @x 2
where u.x/ is an external potential function (drift function) and 2 is a diffusion

constant. This is in accordance with the Fokker–Planck equation and can be used to
describe the stochastic neuron dynamics [149, 156].
7.5.3 Rate of Firing for Neural Models
Most of the integrate-and-fire neural models activate a reset condition when the
voltage of the membrane exceeds a specific threshold denoted as Vspike . Since
voltage is reset when the threshold value is reached, from that point on the
probability to detect this voltage level at the neuron’s membrane becomes zero.
What can be detected instead is the generated current.
A generic scalar model of the voltage of the neuron’s membrane is used first
dV D f .V; t /dt C dw.t / (7.41)
When the voltage V .t / reaches the threshold value Vspike then it is reset to the initial
value Vreset . If f .V; t / D ˛V C I , then one has the leaky integrate-and-fire model
of the neuron. If f .V; t / D ˛V 2 C I , then one has the quadratic integrate-and-fire
neuron’s model.
As explained in the previous subsections, to compute the mean firing rate one
should compute the solution of the Fokker–Planck equation in steady state, that is
@G.x;t/ 2 @2 G.x;t/
@t
D f .x; t / @G.x;t/
@x
C 2 @x 2
(7.42)
7.6 Stochasticity in Neural Dynamics and Relation

to Quantum Mechanics
7.6.1 Basics of Quantum Mechanics
In quantum mechanics the state of an isolated quantum system Q is represented by

a vector j .t / > in a Hilbert space. This vector satisfies Schrödinger’s diffusion
equation [34, 133]
d
i„ j .t / >D H .t / (7.43)
dt
where H is the Hamiltonian operator that gives the total energy of a particle
p2
(potential plus kinetic energy) H D 2m C V .x/. Equation (7.43) denotes that the
particle with momentum p and energy E is diffused in the wave with a probability
density proportional to j .x; t /j2 . Equivalently, it can be stated that j .x; t /j2
denotes the probability for the particle to be at position x at time t . The external
p2
potential V is defined as V D 2m C E where E is the eigenvalue (discrete energy
level) of the Hamiltonian H . For V D 0 or constant, the solution of Eq. (7.43) is a
superposition of plane waves of the form
i.pxEt/
j .x; t / >D e „ (7.44)
where i is the imaginary unit, x is the position of the particle, and „ is Planck’s
constant. These results can be applied to the case of an harmonic potential if only
the basic mode was taken into account.
The probability to find the particle between x and x C dx at the time instant t
is
R1 given by P .x/dx D j .x; t /j2 dx. The total probability should equal unity, i.e.
1 j .x; t /j dx D 1. The average position x of the particle is given by
2
Z 1 Z 1
< x >D P .x/xdx D . x /dx (7.45)
1 1
where is the conjugate value of . Now, the wave function .x; t / can be
analyzed in a set of orthonormal eigenfunctions in a Hilbert space
1
X
.x; t / D cn n (7.46)
nD1
The coefficients cn are an indication of the probability to describe the particle’s

position x at time t by the eigenfunction
R 1 n and thanks to the orthonormality of
the n ’s, the cn ’s are given by cn D 1 n dx. Moreover, the eigenvalues and
eigenvectors of the quantum operator of position x can be defined as x n D an n ,
where n is the eigenvector and an is the associated eigenvalue. Using Eqs. (7.45)
and (7.46) the average position of the particle is found to be
1
X
< x >D jjcn jj2 an (7.47)
nD1
with jjcn jj2 denoting the probability that the particle’s position be described by the
eigenfunction n . When the position x is described by n the only measurement
of x that can be taken is the associated eigenvalue an . This is the so-called filtering
problem, i.e. when trying to measure a system that is initially in the state
P D
1
c
nD1 n n the measurement effect on state is to change it to an eigenfunction
n with measurable value only the associated eigenvalue an . The eigenvalue an is
chosen with probability P / jjcn jj2 .
7.6.2 Schrödinger’s Equation with Non-zero Potential

and Its Equivalence to Diffusion with Drift
In Sect. 7.2 the equivalence between Wiener process and the diffusion process was
demonstrated. Next, the direct relation between diffusion and quantum mechanics
will be shown [56]. The basic equation of quantum mechanics is Schrödinger’s
equation, i.e.
@
i D H .x; t / (7.48)
@t
where j .x; t /j2 is the probability density function of finding the particle at position
x at time instant t , and H is the system’s Hamiltonian, i.e. the sum of its kinetic and
potential energy, which is given by H D p 2 =2m C V , with p being the momentum
of the particle, m the mass and V an external potential. It holds that
p2
D 12 m„ @x
@2
2m 2
(7.49)
thus the Hamiltonian can be also written as
H D 12 m„ @x
2
2 C V:
@ (7.50)
The solution of Eq. (13.1) is given by [34]
.x; t / D e iH t .x; 0/ (7.51)
A simple way to transform Schrödinger’s equation into a diffusion equation is

to substitute variable i t with t . This transformation enables the passage from
imaginary time to real time. However in the domain of non-relativistic quantum
mechanics there is a closer connection between diffusion theory and quantum
theory. In stochastic mechanics, the real time of quantum mechanics is also the
real time of diffusion and in fact quantum mechanics is formulated as conservative
diffusion [56]. This change of variable results in the diffusion equation
2
@ 1
D @x V .x/
2
(7.52)
@t 2 @2
Equation (7.52) can be also written as @ @t

D H, where H is the associated
Hamiltonian and the solution is of the form .x; t / D e tH .x/, and variable
2 is a diffusion constant. The probability density function satisfies also the
Fokker–Planck partial differential equation

@ 1 2 @2 @
D u.x/ (7.53)
@t 2 @x 2 @x
where u.x/ is the drift function, i.e. a function related to the derivative of the external
potential V . In that case Eq. (7.53) can be rewritten as
@
D HO (7.54)
@t
h i
where HO D 1 2 @2
2
@x 2 @
@x
u.x/ , while the probability density function .x; t / is
found to be
O
.x; t / D e H .x/ (7.55)
It has to be noted that the Fokker–Planck equation is equivalent to Langevin’s

equation and can be also used for the calculation of the mean position of the diffused
particle, as well as for the calculation of its variance [66].
Now, P the solution .x/ is a wave-function for which holds .x/ D j .x/j2 with
.x/ D N iD1 ck k .x/, where k .x/ are the associated eigenfunctions [34, 127]. It
can be assumed that 0 .x/ D j 02 .x/j, i.e. the p.d.f. includes only the basic mode,
while higher order modes are truncated, and the drift function u.x/ of Eq. (7.53) is
taken to be [56]
1 2 1 @0 .x/
u.x/ D (7.56)
2 0 .x/ @x
Thus it is considered that the initial probability density function is .x/ D 0 .x/,
which is independent of time, thus from Eq. (7.54) one has HO 0 D 0, which means
that the p.d.f. remains independent of time and the examined diffusion process is a
stationary one, i.e. .x; t / D 0 .x/ 8t . A form of the probability density function
for the stationary diffusion is that of shifted, partially overlapping Gaussians, which
is depicted in Fig. 7.1b. In place of Gaussian p.d.f., symmetric triangular possibility
distributions have been also proposed [163]. The equation that describes the shifted
Gaussians is (Fig. 7.1b)
1 2 !2 .xa/2 1 !
C C 2 e 2 .xCa/
2
0 .x/ D C e (7.57)
2 2
7.6.3 Study of the QHO Model Through

the Ornstein–Uhlenbeck Diffusion
The Ornstein–Uhlenbeck diffusion is a model of the Brownian motion [17]. The

particle tries to return to position x.0/ under the influence of a linear force vector,
i.e. there is a spring force applied to the particle as a result of the potential V .x/. The
corresponding phenomenon in quantum mechanics is that of the QHO [34, 66]. In
the QHO the motion of the particle is affected by the parabolic (harmonic) potential
a 8
b 5
7 4
3
6
drift function u(x)

2
5
1
V(k)− λ 0
4
0
3
−1
2
−2
1
−3
0 −4
−1 −5
0 20 40 60 80 100 120 140 160 180 200 0 20 40 60 80 100 120 140 160 180 200
x x
Fig. 7.6 (a) Diagram of V .x/ 0 where V .x/ is the harmonic potential of the QHO and 0 is
the associated eigenvalue (b) Linear drift force applied to the diffused particle as a result of the
harmonic potential V .x/
1 !2 2
V .x/ D x (7.58)
2 2
It is known that the ground mode of the QHO of Eq. (7.48) is a Gaussian function
[56, 164], i.e.
!x 2
0 .x/ D Ce 2 2 (7.59)
while it can be proved easily that the associated eigenvalue is 0 D 12 !. A diagram

of V .x/ 0 is given in Fig. 7.6a.
For the diffusion constant holds 2 D m„ where „ is Planck’s constant and
finally gives V .x/ D 12 m! 2 x 2 . Assuming the stationary p.d.f. of Eq. (7.57)
!x 2
.x/ D 0 .x/
2
D C 2e 2 2 (7.60)
the force applied to the particle due to the harmonic potential V .x/ is given by
Eq. (7.56), and is found to be
@ 0 .x/
u.x/ D 2 1
0 .x/ @x
) u.x/ D !x (7.61)
which means that the drift is a spring force applied to the particle and which aims at
leading it to an equilibrium position. The drift force is depicted in Fig. 7.6b.
7.6.4 Particle’s Motion Is a Generalization of Gradient

Algorithms
As analyzed, the Wiener process describes the Brownian motion of a particle. In this
section, this motion is also stated in terms of equations of Langevin’s equation. The
stochastic differential equation for the position of the particle is [56]:
dx.t / D u.x.t //dt C dw.t / (7.62)
where u.x.t // is the so-called drift function, and is usually given in the form of a
spring force, i.e. u.x/ D kx which tries to bring the particle to the equilibrium
x D 0 and is the result of a parabolic potential applied to the particle, i.e. V .x/ D
kx 2 . The term w.t / denotes a random force (due to interaction with other particles,
e.g. collision) and follows a Wiener walk. For each continuous random path w.t /, a
continuous random path x.t / is also generated, which can be written in the form
Z t
x.t / D x.0/ C u.x.s//ds C w.t / (7.63)
0
The integration of Langevin’s equation and certain assumptions about the

noise w.t /, for instance white noise, dichotomic noise (also known as
Ornstein–Uhlenbeck noise), etc., enable the calculation of the mean position of
the particle Efxg and also to find its variance Efx Efxgg2 [66].
Knowing that the QHO model imposes to the particle the spring force of
Eq. (7.61), the kinematic model of the diffusing particle becomes
dx.t / D !x.t /dt C dw.t / (7.64)
with initial condition x.0/ D 0. The first term in the right part is the drift, i.e. the
spring forces that makes the particle return to x.0/, while the second term is the
random diffusion term (noise).
The extension of Langevin’s equation gives a model of an harmonic oscillator,
driven by noise. Apart from the spring force, a friction force that depends on
the friction coefficient and on the velocity of the particle is considered. The
generalized model of motion of the particle can then be also written as [13, 66]:
d 2x dx
2
C 2 C ! 2 x D .t/ (7.65)
dt dt
Thus an equation close to electrical or mechanical oscillators is obtained [163,195].

Equation (7.64) can be also written as
7.7 Conclusions 167
dx.t /
D h.x.t // C .t /)dx.t / D h.x.t //dt C w.t / (7.66)
dt
where h.x.t // D ˛ @V@t.x/ , with ˛ being a learning gain, V .x/ being the harmonic
potential, and .t / being a noise function. Equation (7.64) is a generalization of
gradient algorithms based on the ordinary differential equation (ODE) concept,
where the gradient algorithms are described as trajectories towards the equilibrium
of an ODE [22, 52]. Indeed, conventional gradient algorithms with diminishing step
are written as
dx.t / D h.x.t //dt (7.67)
The comparison of Eqs. (7.64) and (7.67) verifies the previous argument. The update
of the neural weights that follow the model of the QHO given by Eq. (7.64). The
force that drives x.t / to the equilibrium is the derivative of the harmonic potential,
and there is also an external noisy force w.t / which is the result of collisions
or repulsive forces due to interaction with neighboring particles. Similarly, in the
update of neural weights with a conventional gradient algorithm, the weight is driven
towards an equilibrium under the effect of a potential’s gradient (where the potential
is usually taken to be a quadratic error cost function).
7.7 Conclusions
In this chapter, neural structures with weights which are stochastic variables and
which follow the model of the QHO have been studied. The implications of
this assumptions for neural computation were analyzed. The neural weights were
taken to correspond to diffusing particles, which interact to each other as the
theory of Wiener process (Brownian motion) predicts. The values of the weights
are the positions of the particles and the probability density function j .x; t /j2
that describes their position is derived by Schrödinger’s equation. Therefore the
dynamics of the neural network is given by the time-dependent solution of
Schrödinger’s equation under a parabolic (harmonic) potential.
However, the time-dependent solution of Schrödinger’s equation is difficult to
be computed, either analytically or numerically. Moreover, this solution contains
terms which are difficult to interpret, such as the complex number probability
amplitudes associated with the modes k .x/ of the wave-function .x/ (solu-
tion of Schrödinger’s equation), or the path integrals that describe the particles’
motion. Thus in place of Schrödinger’s equation the solution of a stationary
diffusion equation (Ornstein–Uhlenbeck diffusion) with drift was studied, assuming
probability density function that depends on the QHO’s ground state 0 .x/ D
j 0 .x/j2 .
It was shown that in neural structures with weights that follow the QHO model,
the weights update is described by Langevin’s stochastic differential equation. It
was proved that conventional gradient algorithms are a subcase of Langevin’s
equation. It can be also stated that neural networks with crisp numerical weights
and conventional gradient learning algorithms are a subset of neural structure
with weights based on the QHO model. In that way the complementarity between
classical and quantum physics was also validated in the field of neural computation.
Chapter 8
Synchronization of Stochastic Neural Oscillators
Using Lyapunov Methods
Abstract A neural network with weights described by the position of interacting

Brownian particles is considered. Each weight is taken to correspond to a Gaussian
particle. Neural learning aims at leading a set of M weights (Brownian particles)
with different initial values on the 2-D phase plane, to the desirable final position.
A Lyapunov function describes the evolution of the phase diagram towards the
equilibrium Convergence to the goal state is assured for each particle through the
negative definiteness of the associated Lyapunov function. The update of the weight
(trajectory in the phase plane) is affected by (1) a drift force due to the harmonic
potential, and (2) the interaction with neighboring weights (particles). It is finally
shown that the mean of the particles will converge to the equilibrium while using
LaSalle’s theorem it is shown that the individual particles will remain within a small
area encircling the equilibrium.
8.1 Representation of the Neurons’ Dynamics as Brownian

Motion
It will be shown that the model of the interacting coupled neurons becomes
equivalent to the model of interacting Brownian particles, and that each weight is
associated with a Wiener process. In such a case, the neural network proposed by
Hopfield can be described by a set of ordinary differential equations of the form
Pn
Ci xP i .t / D R1i xi .t / C j D1 Tij gj .xj .t // C Ii 1i n (8.1)
Variable xi .t / represents the voltage at the membrane of the i -th neuron and Ii is
the external current input to the i -th neuron. Each neuron is characterized by an
input capacitance Ci and a transfer function gi .u/ which represents connection to
neighboring neurons. The connection matrix element Tij has a value 1=Rij when
the output of the j -th neuron is connected to the input of the i -th neuron through
a resistance Rij , and a value 1=Rij when the inverting output of the j -th neuron

170 8 Synchronization of Stochastic Neural Oscillators Using Lyapunov Methods
is connected to the input of the i -th neuron through a resistance Rij . The nonlinear
function that describes connection between neurons gi .u/ is a sigmoidal one. By
defining the parameters
Tij
bi D 1
Ci Ri
˛ij D Ci
ci D Ii
Ci
(8.2)
Thus, Eq. (8.1) can be rewritten as

Pn
xP i .t / D bi xi .t / C j D1 ˛ij gj .xj .t // C ci 1i n (8.3)
which can be also written in matrix form as
P / D Bx.t / C Ag.x.t // C C
x.t (8.4)
where
x.t / D .x1 .t /; ; xn .t //T B D diag.b1 ; ; bn / A D .aij /nn

(8.5)
C D .c1 ; ; cn / T
g.x/ D .g1 .x1 /; ; gn .xn // T
One can consider the case

Pn
bi D j D1 j˛ij j > 0; ci 0 1i n (8.6)
Moreover, by assuming a symmetric network structure it holds
˛ij D ˛ji 1i j n (8.7)
which means that A is a symmetric matrix. It is also known that neural networks are
subjected to noise. For example, if every external input Ii is perturbed in the way
Ii !Ii Ci wi .t /, where wi .t / is white noise, then the stochastically perturbed neural
network is described by a set of stochastic differential equations (Wiener processes)
of the form
dx.t / D ŒBx.t / C Ag.x.t // C C dt C 1 d w1 .t / (8.8)
where 1 D .1 =C1 ; ; n =Cn /T . Moreover, if the connection matrix element Tij

is perturbed in the way Tij !Tij C ij wP 2 .t /, where w2 .t / is another white noise
independent of w1 .t /, then the stochastically perturbed neural network can be
described as
dx.t / D ŒBx.t / C Ag.x.t // C C dt C 1 d w1 .t / C 2 g.x.t //dw2 .t / (8.9)
where 2 D .ij =Ci /nn . In general one can describe the stochastic neural network
by a set of stochastic differential equations of the form
8.2 Interacting Diffusing Particles as a Model of Neural Networks 171
dx.t / D ŒBx.t / C Ag.x.t // C C dt C dw.t / (8.10)
In the above relation w.t / D Œw1 .t /; ; wm .t /T is an m-dimensional Brownian

motion defined on a probability space .˝; F; P / with a natural filtration fFt0 g, i.e.
Ft D fw.s/ W 0st g and W Rn ! Rm i.e. .x/ D .ij .x//nm which is called
the noise intensity matrix.
8.2 Interacting Diffusing Particles as a Model of Neural

Networks
8.2.1 Weights’ Equivalence to Brownian Particles
An equivalent concept of a neural network with weights described by interacting

Brownian particles can be also found in [83, 87]. Here, a neural structure of M
neurons is considered, e.g. an associative memory (Fig. 8.1). For the weight w, the
P is defined, where e denotes the distance of the weight from the
error vector Œe; e
desirable value w and eP the rate of change of e. Thus, each weight can be mapped
to the 2-D plane using the notation Œx; y D Œe; e.
P Moreover, each weight is taken to
correspond to a Brownian particle. The particles are considered to have mechanical
properties, that is to be subjected to acceleration due to forces. The objective of
learning is to lead a set of M weights (Brownian particles) with different initial
values on the 2-D plane, to the desirable final position Œ0; 0.
Each particle (weight) is affected by the rest of the M 1 particles. The cost
function that describes the motion of the i -th particle towards the equilibrium is
2
denoted as V .x i / W Rn ! R, with V .x i / D 12 e i [147, 150–152]. Convergence to
the goal state should be succeeded for each particle through the negative definiteness
of the associated Lyapunov function, i.e. it should hold VP i .x i / D eP i .t / e i .t / < 0
T
[92].
As already mentioned, in the quantum harmonic oscillator (QHO) model of the
neural weights the update of the weight (motion of the particle) is affected by (1) the
drift force due to the harmonic potential, and (2) the interaction with neighboring
weights (particles). The interaction between the i -th and the j -th particle is [64]:
g.x i x j / D .x i x j /Œga .jjx i x j jj/ gr .jjx i x j jj/ (8.11)
where ga ./ denotes the attraction term and is dominant for large values of jjx i x j jj,
while gr ./ denotes the repulsion term and is dominant for small values of jjx i x j jj.
Function ga ./ can be associated with an attraction potential, i.e.
rxi Va .jjx i x j jj/ D .x i x j /ga .jjx i x j jj/ (8.12)

Fig. 8.1 The model of a Hopfield associative memory with feedback weights
Function gr ./ can be associated with a repulsion potential, i.e.
rxi Vr .jjx i x j jj/ D .x i x j /gr .jjx i x j jj/ (8.13)
A suitable function g./ that describes the interaction between the weights is given
by [150]
jjx i x j jj2
g.x i x j / D .x i x j /.a be 2 / (8.14)
where the parameters a, b, and c may also be subjected to stochastic variations and
noise terms. It holds that ga .x i x j / D a, i.e. attraction has a linear behavior
(spring-mass system) jjx i x j jjga .x i x j /. Moreover,
jjx i x j jj2
gr .x i x j / D be 2 (8.15)
which means that gr .x i x j /jjx i x j jj b is bounded. For the i -th particle with
unit mass mi D 1 holds
xP i D vi ; mi vP i D U i (8.16)
where the aggregate force is U i D f i CF i . The term f i D Kv vi denotes friction,

while the term F i is the propulsion. Assuming zero acceleration vP i D 0 one gets
F i D Kv vi , which for Kv D 1 and mi D 1 gives F i D vi . Thus an approximate
kinematic model is
xP i D F i (8.17)
The propulsion F i is equal to the derivative of the total potential of each particle
(drift term), i.e.
PM PM
F i D rx i fV i .x i / C 1
2 iD1 j D1;j ¤i ŒVa .jjx
i
x j jj C Vr .jjx i x j jj/g )
PM
F i D rx i fV i .x i /g C j D1;j ¤i Œrx i Va .jjx
i
x j jj/ rx i Vr .jjx i x j jj/ )
PM
F i D rx i fV i .x i /g C j D1;j ¤i Œ.x
i
x j /ga .jjx i x j jj/ .x i x j /gr .jjx i x j jj/ )
PM
F i D rx i fV i .x i /g j D1;j ¤i g.x
i
xj /
Taking also into account that the force F i which excites the particles’ motion
(weights variation in time) may be subjected to stochastic perturbations and noise,
that is
PM
F i D rx i fr.x i / j D1;j ¤i g.x
i
x j / C i g (8.18)
one has finally that the particles’ motion is a stochastic process. Next, substituting
in Eq. (8.17) one gets Eq. (8.31), i.e.
PM
x i .t C 1/ D x i .t / C i .t /Œrx i V i .x i / C e i .t C 1/ j D1;j ¤i g.x
i
xj /
i D 1; 2; ; M; with i .t / D 1;
(8.19)
which verifies that the kinematic model of a multi-particle system is equivalent to a

distributed gradient search algorithm.
8.2.2 Stability Analysis for a Neural Model with Brownian

Weights
The stability of the system consisting of Brownian particles is determined by the

behavior of its center (mean position of the particles x i ) and of the position of each
particle with respect to this center. The center of the multi-particle system is given
by
PM PM
xN D E.x i / D 1
M iD1 x
i
) xPN D
P i ) xPN
iD1 x
1
M
P h PM i (8.20)
D M1 MiD1 rx i V .x /
i i
j D1;j ¤i .g.x i
x j
//
From Eq. (8.14) it can be seen that g.x i x j / D g.x j x i /, i.e. g./ is an odd
function. Therefore, it holds that
0 1
1 @ X
M
g.x i x j /A D 0 (8.21)
M
j D1;j ¤i
1 X
M
xPN D Œrx i V i .x i / (8.22)
M iD1
Denoting the goal position by x , and the distance between the i -th particle and
the mean position of the multi-particle system by e i .t / D x i .t / xN the objective
of the learning algorithm for can be summarized as follows: (i) limt!1 xN D x ,
i.e. the center of the multi-particle system converges to the goal position, (ii)
limt!1 x i D x, N i.e. the i -th particle converges to the center of the multi-particle
system, (iii) limt!1 xPN D 0, i.e. the center of the multi-particle system stabilizes at
the goal position. If conditions (i) and (ii) hold then, limt!1 x i D x . Furthermore,
if condition (iii) also holds, then all particle will stabilize close to the goal position
[64, 108, 150, 152].
To prove the stability of the multi-particle system the following simple Lyapunov
function is considered for each particle:
1 iT i 1
Vi D e e ) Vi D jjei jj2 (8.23)
2 2
Thus, one gets
VP i D ehi eP i ) VP i D .xP i x/e

PN i )
T
PM PM i
VP D rx i V .x / j D1;j ¤i g.x i x j / C
i i i 1
M j D1 rx j V
j
.x j / e i :
Substituting g.x i x j / from Eq. (8.14) yields

2
X
M
VPi D 4rx i V i .x i / .x i x j /a
j D1;j ¤i
3
X
M
1 XM
C .x i x j /gr .jjx i x j jj/ C rx j V j .x j /5 e i
M j D1
j D1;j ¤i
which gives
2 3
X
M
VPi D a 4 .x i x j /5 e i
j D1;j ¤i
2 3T
X
M
1 X M
C gr .jjx i x j jj/.x i x j /T e i 4rx i V i .x i / rx j V j .x j /5 e i :
M j D1
j D1;j ¤i
It holds that
PM PM
j D1 .x
i
x j / D M x i M M1 j D1 x
j
D M x i M xN D M.x i x/
N D M ei
therefore
X
M
VPi D aMjje i jj2 C gr .jjx i x j jj/.x i x j /T e i
j D1;j ¤i
2 3T
1 XM
4rx i V i .x i / rx j V j .x j /5 e i (8.24)
M j D1
It assumed that for all x i there is a constant N such that
jjrx i V i .x i /jj N (8.25)
Equation (8.25) is reasonable since for a particle moving on a 2-D plane, the gradient
of the cost function rx i V i .x i / is expected to be bounded. Moreover it is known that
the following inequality holds:
PM P PM
j D1;j ¤i gr .x
i
x j /T e i Mj D1;j ¤i be j D1;j ¤i bjje jj:
i i
Thus the application of Eq. (8.24) gives:

PM
VP i aMjje i jj2 C j D1;j ¤i gr .jjx
i
x j jj/jjx i x j jj jje i jj
PM
Cjjrx i V i .x i / 1
M j D1 rx j V j .x j /jjjje i jj
) VP i aMjje i jj2 C b.M 1/jje i jj C 2N jje i jj
where it has been taken into account that

PM P
j D1;j ¤i gr .jjx
i
x j jj/T jje i jj M
j D1;j ¤i bjje jj D b.M 1/jje jj;
i i
and from Eq. (8.25)

P
jjrx i V i .x i / M1 M j D1 rx i V .x /jjjjrx i V .x /jj
j j i i
P
C M1 jj M j D1 rx i V .x /jj
j j
N C M1 M N 2N :
Thus, one gets

h i
VP i aMjje i jj jje i jj b.M 1/
aM
N
2 aM (8.26)
The following bound is defined:
b.M 1/ 2N 1
D C D .b.M 1/ C 2N / (8.27)
aM aM aM
Thus, when jje i jj > , VPi will become negative and consequently the error e i D
x i xN will decrease. Therefore the error e i will remain in an area of radius , i.e.
the position x i of the i -th particle will stay in the cycle with center xN and radius .
8.2.2.1 Stability in the Case of a Quadratic Cost Function
The case of a convex quadratic cost function is examined, for instance
A i A
V i .x i / D jjx x jj2 D .x i x /T .x i x / (8.28)
2 2
where x D 0 and xP D 0 defines a minimum point (attractor) for which holds

V i .x i D x / D 0. The weights error is expected to converge to x . The stochastic
weights (particles) will follow different trajectories on the 2-D plane and will end at
the attractor.
Using Eq.(8.28) yields rx i V i .x i / D A.x i x /. Moreover, the assumption
rx i V i .x i / N can be used, since the gradient of the cost function remains
bounded. The particles will gather round xN and will stay in a radius given by
Eq. (8.27). The motion of the mean position xN of the particles is
PM
xPN D M1 iD1 rx i V
i
.x i / ) xPN D M
A
.x i x / )
xPN xP D M x C
A i A
M
x ) xPN xP D A.xN x /:
The variable e D xN x is defined, and consequently
eP D Ae ) .t / D c1 e At C c2 ; with c1 C c2 D e .0/ (8.29)
Equation (8.29) is an homogeneous differential equation, which for A > 0 results

into
N / D x
limt!1 e .t / D 0; thus limt!1 x.t
It is left to make more precise the position to which each particle converges.
Fig. 8.2 LaSalle’s theorem:

C : invariant set, E C :
invariant set which satisfies
VP .x/ D 0, M E: invariant
set, which satisfies
VP .x/ D 0, and which
contains the limit points of
x.t / 2 E, LC the set of limit
points of x.t / 2 E
8.2.2.2 Convergence Analysis Using La Salle’s Theorem
It has been shown that limt!1 x.t N / D x and from Eq. (8.26) that each particle
will stay in a cycle C of center xN and radius given by Eq. (8.27). The Lyapunov
function given by Eq. (8.23) is negative semi-definite, therefore asymptotic stability
cannot be guaranteed. It remains to make precise the area of convergence of each
particle in the cycle C of center xN and radius . To this end, La Salle’s theorem can
be employed [64, 92].
La Salle’s Theorem: Assume the autonomous system xP D f .x/ where f W D !
Rn . Assume C D a compact set which is positively invariant with respect to
xP D f .x/, i.e. if x.0/ 2 C ) x.t / 2 C 8 t . Assume that V .x/ W D ! R is a
continuous and differentiable Lyapunov function such that VP .x/ 0 for x 2 C , i.e.
V .x/ is negative semi-definite in C . Denote by E the set of all points in C such that
VP .x/ D 0. Denote by M the largest invariant set in E and its boundary by LC , i.e.
for x.t / 2 E W limt!1 x.t / D LC , or in other words LC is the positive limit set of
E (see Fig. 8.2b). Then every solution x.t / 2 C will converge to M as t ! 1.
La Salle’s theorem is applicable to the case of the multi-particle system and helps
to describe more precisely the area round xN to which the particle trajectories x i
will converge. A generalized Lyapunov function is introduced which is expected to
verify the stability analysis based on Eq. (8.26). It holds that
PM PM PM
V .x/ D iD1 V
i
.x i / C 1
2 iD1 j D1;j ¤i fVa .jjx
i
x j jj Vr .jjx i x j jj/g )
PM PM PM
V .x/ D iD1 V
i
.x i / C 1
2 iD1 j D1;j ¤i fajjx
i
x j jj Vr .jjx i x j jj/ and
PM PM PM
rx i V .x/ D Œ iD1 rx i V
i
.x i / C 1
2 iD1 j D1;j ¤i rx i fajjx
i
x j jj Vr .jjx i x j jj/g )
PM PM
i
.x i / C j D1;j ¤i .x
i
x j /fga .jjx i x j jj/ gr .jjx i x j jj/g )
PM PM
i
.x i / C j D1;j ¤i .x
i
x j /fa gr .jjx i x j jj/g
and using Eq. (8.19) with i .t / D 1 yields rx i V .x/ D xP i , and
X
M X
M
VP .x/ D rx V .x/T xP D rx i V .x/T xP i ) VP .x/ D jjxP i jj2 0 (8.30)
iD1 iD1
Therefore, in the case of a quadratic cost function it holds V .x/ > 0 and VP .x/0
and the set C D fx W V .x.t // V .x.0//g is compact and positively invariant.
Thus, by applying La Salle’s theorem one can show the convergence of x.t / to the
set M C; M D fx W VP .x/ D 0g ) M D fx W xP D 0g.
8.3 Convergence of the Stochastic Weights to an Equilibrium
To visualize the convergence of the stochastic weights to an attractor, the interaction

between the weights (Brownian particles) can be given in the form of a distributed
gradient algorithm, as described in Eq. (8.19):
2 3
X
M
x i .tC1/ D x i .t/C i .t/ 4h.x i .t// C i .t/ C g.x i x j /5 ; i D 1; 2; ; M
j D1;j ¤i
(8.31)
The term h.x.t /i / D rx i V i .x i / indicates a local gradient algorithm, i.e. motion in
T
the direction of decrease of the cost function V i .x i / D 12 e i .t / e i .t /. The term i .t /
i
is the algorithms step while the stochastic
P disturbance e .t / enables the algorithm to
escape from local minima. The term M j D1;j ¤i g.x i
x j / describes the interaction
between the i -th and the rest M 1 Brownian particles (feedback from neighboring
neurons as depicted in Figs. 10.1 and 7.5).
In the conducted simulation experiments the multi-particle set consisted of ten
particles (weights) which were randomly initialized in the 2-D field Œx; y D Œe; e. P
The relative values of the parameters a and b that appear in the potential of
Eq. (8.14) affected the trajectories of the individual particles. For a > b the cohesion
8.3 Convergence of the Stochastic Weights to an Equilibrium 179
a b
10 10
5 5
Y
0
Y
−5 −5
−10 −10
−10 −5 0 5 10 −10 −5 0 5 10
X X
Fig. 8.3 (a) Convergence of the individual neural weights that follow the QHO model to an
attractor (b) Convergence of the mean of the weights position to the attractor Œx ; y D Œe D
0; eP D 0
a b
Fig. 8.4 (a) Lyapunov function of the individual stochastic weights (Brownian particles) in a 2D-
attractors plane without prohibited regions (obstacle-free) and (b) Lyapunov function of the mean
of the stochastic weights (multi-particle system) in a 2D-attractors plane without prohibited regions
(obstacle-free)
of the particles was maintained and abrupt displacements of the particles were
avoided (Fig. 8.3).
For the learning of the stochastic weights without constraints (i.e., motion of the
Brownian particles in a 2D-attractors plane without prohibited areas), the evolution
of the aggregate Lyapunov function is depicted in Fig. 8.4a. The evolution of the
Lyapunov function corresponding to each stochastic weight (individual particle) is
depicted in Fig. 8.4b.
8.4 Conclusions
Stochasticity in neuronal model was considered and neural weights with dynamics
described by Brownian motion were studied. Convergence of learning of stochastic
neural weights to attractors (equilibriums) was proved using Lyapunov stability
analysis. The convergence of the weights is affected by a drift (elastic) term that is
imposed by the potential (that is a function associated with the square of the weights’
distance from the equilibrium) and a random term that is imposed by interaction
with neighboring weights. Thus a proof has been given about the convergence
(stability) of learning in models of stochastic neurons.
Chapter 9
Synchronization of Chaotic and Stochastic
Neurons Using Differential Flatness Theory
Abstract This chapter presents a control method for neuron models that have the
dynamics of chaotic oscillators. The proposed chaotic control method makes use
of a linearized model of the chaotic oscillator which is obtained after transforming
the oscillators dynamic model into a linear canonical form through the application
of differential flatness theory. The chapter also analyzes a synchronizing control
method (flatness-based control) for stochastic neuron models which are equivalent
to particle systems and which can be modeled as coupled stochastic oscillators. It is
explained that the kinematic model of the particles can be derived from the model of
the quantum harmonic oscillator (QHO). It is shown that the kinematic model of the
particles is a differentially flat system. It is also shown that after applying flatness-
based control the mean of the particle system can be steered along a desirable path
with infinite accuracy, while each individual particle can track the trajectory within
acceptable accuracy levels.
9.1 Chaotic Neural Oscillators
9.1.1 Models of Chaotic Oscillators
Chaotic systems exhibit dynamics which are highly dependent on initial conditions.
Since future dynamics are defined by initial conditions the evolution in time of
chaotic systems appears to be random. The output or the state vector of a chaotic
oscillator has been used to model the dynamics of biological neurons. For example,
the Duffing oscillator has been used to model the EEG signal received that is
from brain neuronal groups, as well as to describe the dynamics of variants of
the FitzHugh–Nagumo neuron [63, 181, 184, 207, 214, 216]. Main types of chaotic
oscillators are described in the sequel:

182 9 Synchronization of Chaotic and Stochastic Neurons Using Differential Flatness. . .
1. Duffing’s chaotic system:
xP 1 .t / D x2 .t /
(9.1)
xP 2 .t / D 1:1x1 .t / x13 .t / 0:4x2 .t / C 1:8cos.1:8t /
2. The Genesio-Tesi chaotic system:
xP 1 .t / D x2 .t /
xP 2 .t / D x3 .t / (9.2)
xP 3 .t / D cx1 .t / bx2 .t / ˛x3 .t / C x12 .t /
where a, b, and c are real constants. When at least one of the system’s Lyapunov
exponents is larger than zero the system is considered to be chaotic. For example,
when a D 1:2, b D 2:92, and c D 6 the system behaves chaotically.
3. The Chen chaotic system
xP 1 .t / D a.x1 .t / x2 .t //
xP 2 .t / D .c a/x1 .t / C cx2 .t / x1 .t /x3 .t / (9.3)
xP 3 .t / D x1 .t /x2 .t / bx3 .t /
where a, b, and c are positive parameters. When at least one of the system’s
Lyapunov exponents is larger than zero the system is considered to be chaotic.
For example, when a D 40, b D 3, and c D 3 the system behaves chaotically.
The evolution in time of the phase diagram of the Duffing oscillator and of the
Genesio-Tesi chaotic system are shown in Fig. 9.1. Other dynamical systems that
exhibit chaotic behavior are Lorenz’s system, Chua’s system, and Rössler’s system.
It will be shown that for chaotic dynamical systems exact linearization is possible,
through the application of a diffeomorphism that enables their description in new
state space coordinates. As an example, the Duffing oscillator will be used, while it
is straightforward to apply the method to a large number of chaotic oscillators.
9.1.2 Differential Flatness of Chaotic Oscillators
1. Differential flatness of Duffing’s oscillator:

By defining the flat output y D x1 one has x1 D y, x2 D yP and
u D 1:8cos.1:8t / D yR 1:1y C y 3 C 0:4y. P Thus all state variables and the
control input of the Duffing oscillator are expressed as functions of the flat
output and its derivatives, and differential flatness of the oscillator is proven.
Moreover, by defining the new control input v D yR 1:1y C y 3 C 0:4yP or
v D 1:1x1 x13 0:4x2 C u, and the new state variables y1 D y and y2 D yP
9.1 Chaotic Neural Oscillators 183
a Duffing chaotic oscillator b Genesio−Tesi chaotic oscillator

4 10
3 8
6
2
4
1 2
x2
x2
0 0
−1 −2
−4
−2
−6
−3 −8
−4 −10
−3 −2 −1 0 1 2 3 −4 −2 0 2 4 6
x1 x1
Fig. 9.1 Phase diagram of typical chaotic oscillators (a) Duffing’s oscillator (b) Genesio-Tesi’s
oscillator
a description of the oscillator’s dynamics in the linear canonical (Brunovsky’s)

form is obtained

yP1 01 y1 0
D C v (9.4)
yP2 00 y2 1
2. Differential flatness of Genesio-Tesi’s oscillator:

By defining the flat output y D x1 one has x1 D y, x2 D y, P x3 D yR and
y .3/ D xP 3 D cy b yP ayR C y 2 . Thus all state variables of the Genesio-Tesi
oscillator are expressed as functions of the flat output and its derivatives, and
differential flatness of the oscillator is proven. Moreover, by defining as new
control input v D cy b yP ayR C y 2 , and the new state variables y1 D y,
y2 D y, P and y3 D yR a description of the oscillator’s dynamics in the linear
canonical (Brunovsky’s) form is obtained
0 1 0 10 1 0 1
yP1 010 y1 0
@yP2 A D @0 0 1A @y2 A C @0A v (9.5)
yP3 000 y3 1
3. Differential flatness of Chen’s oscillator:

By defining the flat output y D x1 one has x1 D y, x2 D a1 .yP Cay/, and x3 D
yC.ac/
R P
y.2aca 2 /y
ay
(for y¤0). From the third row of the associated state-space
equations and after intermediate computations one obtains y .3/ D .a c C 1 C
ab b/yR Œ2.2aca2 /Ca2 b.aCc/yP .aCc/ y
yP 2 ay 2 .yP Cay/a2 b.2aca2 /y.
Thus all state variables of the Chen oscillator are expressed as functions of the
flat output and its derivatives, and differential flatness of the oscillator is proven.
Moreover, by defining as new control input v D .ac C1Cab b/yR Œ2.2ac
a2 /Ca2 b.a Cc/yP .aCc/
y
yP 2 ay 2 .yP Cay/a2 b.2ac a2 /y, and the new state
variables y1 D y, y2 D y, P and y3 D yR a description of the oscillator’s dynamics
in the linear canonical (Brunovsky’s) form is obtained
0 1 0 10 1 0 1
yP1 010 y1 0
@yP2 A D @0 0 1A @y2 A C @0A v (9.6)
yP3 000 y3 1
It is noted that differential flatness can be proven for several other types
of chaotic oscillators, such as Lorenz’s system, Rössler’s system, and Chua’s
system. By expressing all state variables and the control input of such systems
as functions of the flat output and their derivatives it is possible to obtain again a
description in the linear canonical (Brunovsky) form.
Having written the chaotic oscillator in the linearized canonical form
y .n/ D v (9.7)
Then it suffices to apply a feedback control of the form

.n/ .n1/
v D yd v k1 .y .n1/ yd / kn1 .yP yPd / kn .y yd / (9.8)
to make the oscillator’s output y.t / convergence to the desirable setpoint yd .t /.

Considering that v D f .y; y;
P ; yP .r/ /Cu the control input that is finally applied
to the system is u D v f .y; y; P ; yP .r/ /. Using the control input u all state
vector elements xi of the chaotic oscillator will finally converge to their own
setpoints.
9.2 Stabilization of Interacting Particles Which

Are Modelled as Coupled Stochastic Oscillators
It will be shown that it is possible to succeed synchronizing control of models of

stochastic neural oscillators, which are equivalent to interacting diffusing particles
[35, 57, 124]. To this end one can consider either open-loop or closed-loop control
approaches. Open-loop control methods are suitable for controlling micro and
nano systems, since the control signal can be derived without need for on-line
measurements [12, 28, 41, 102]. A different approach would be to apply closed-
loop control using real-time measurements, taken at micro or nano-scale. The next
sections of this chapter are concerned with open-loop control for particle systems.
The proposed control approach is flatness-based control [58, 126, 153, 172].
A multi-particle system that consists of N particles is considered. It is assumed
that the particles perform diffusive motion, and interact to each other as the theory of
Brownian motion predicts. As explained, Brownian motion is the analogous of the
quantum harmonic oscillator (QHO), i.e. of Schrödingers equation under harmonic
(parabolic) potential [56]. Moreover, it has been shown that the diffusive motion
of the particles (kinematic model of the particles) can be described by Langevin’s
equation which is a stochastic linear differential equation [56, 66].
9.3 Some Examples on Flatness-Based Control of Coupled Oscillators 185
Next, it will be also shown that the kinematic model of each individual particle is
a differentially flat system and thus can be expressed using a flat output and its
derivatives. It will be proven that flatness-based control can compensate for the
effect of external potentials, and interaction forces, thus enabling the position of the
multi-particle formation to follow the reference path. When flatness-based control
is applied, the mean position of the formation of the N diffusing particles can be
steered along any desirable position in the 2D plane, while the i -th particle can track
this trajectory within acceptable accuracy levels.
9.3 Some Examples on Flatness-Based Control of Coupled

Oscillators
Flatness-based control of N linear coupled oscillators has been analyzed in [172].

The generalized coordinates zi are considered and n oscillators are taken. The
oscillators can be coupled through an interaction term fi .z1 ; z2 ; ; zN / and through
the common control input u. This means that the general oscillator model can be
written as
d2
z
dt2 i
D .!i /2 zi C fi .z1 ; z2 ; ; zN / C bi u; (9.9)
i D 1; ; N . For fi .z1 ; z2 ; ; zN / D 0 one obtains
d2
z
dt2 i
D .!i /2 zi C bi u; i D 1; ; N (9.10)
The terms !i > 0 and bi ¤0 are constant parameters, while T > 0 and D¤0 are
also defined. The objective is to find open-loop control Œ0; T with t !u.t / steering
the system from an initial to a final state. In [172] it has been shown that such control
can be obtained explicitly, according to the following procedure: using the Laplace
transform of Eq. (9.10) and the notation s D dt d
one has
.s 2 C .!i /2 /zi D bi u; i D 1; ; N: (9.11)
Then the system can be written in the form [110]:

P
zi D Qi .s/y; u D Q.s/y; with y D N kD1 ck zk
bi QN
Qi .s/ D .!i /2 kD1 .1 C . !k / / for k¤i;
s 2
(9.12)
Q
Q.s/ D N kD1 .1 C . !k / /; ck D Qk .j !k / 2 R
s 2 1
The real coefficients qki and qk are defined as follows [172]:

P 1 i 2k
Qi .s/ D N q s
PNkD0 k 2k (9.13)
Q.s/ D kD0 qk s
This enables to express both the system’s state variables x.t / and the control
input u.t / as functions of the flat output y.t /, i.e.
Pn1 Pn
xi .t / D i .2k/
kD0 qk y .t /; v.t / D kD0 qk y
.2k/
.t / (9.14)
Additionally, any piecewise continuous open-loop control u.t /; t 2 Œ0; T

steering from the steady-state zi .0/ D 0 to the steady-state zi .T / D .!bii/2 D can
be written as
PN
u.t / D kD0 qk y
.2k/
.t /; (9.15)
for all functions y.t / such that y.0/ D 0, y.T / D D, 8 i f1; ; 2n1g, y .i/ .0/ D
y .i/ .T / D 0. The results can be extended to the case of an harmonic oscillator with
damping. In that case Eq. (9.10) is replaced by
d 2 zi
dt2
D !i 2 zi 2i !i zPi C bi u; i D 1; ; n (9.16)
where the damping coefficient is i 0 [172]. Thus, one obtains
zi D Qi .s/y; u D Q.s/y

Q
Qi .s/ D .!bii/2 nkD1 1 C 2k !sk C !s2 k¤i
2 k (9.17)
Qn
Q.s/ D kD1 1 C 2k !sk C !sk
which proves again that the system’s parameters (state variables) and the control
input can be written as functions of the flat output y and its derivatives. In that case
the flat output is of the form
Pn
yD kD1 ck zk C dk szk (9.18)
where s D dtd and the coefficients ck and dk can be computed explicitly. According
to [110] explicit descriptions of the system parameters via an arbitrary function y
(flat output) and its derivatives are possible for any controllable linear system of
finite dimension (controllability is equivalent to flatness).
The desirable setpoint for the flat output is
PN
yd D d
kD1 ck zk C dk szdk (9.19)
Using this in Eq. (9.15) enables to compute the open-loop control law that steers
the system’s state variables along the desirable trajectories.
9.4 Flatness-Based Control for the Multi-Particle System 187
9.4 Flatness-Based Control for the Multi-Particle System
First, the motion of particles is considered, i.e. it is assumed that no external control
affects the particle’s motion. The particles move on the 2D-plane only under the
influence of an harmonic potential. The kinematic model of the particles is as
described in Sect. 8.2.
xP i D F i
P PM
F i D rx i fV i .x i / C 12 M
iD1 j D1;j ¤i ŒVa .jjx x jj C Vr .jjx x jj/g
i j i j
(9.20)
The interaction between the i -th and the j -th particle is
g.x i x j / D .x i x j /Œga .jjx i x j jj/ gr .jjx i x j jj/ (9.21)
where ga ./ denotes the attraction term and is dominant for large values of jjx i x j jj,
while gr ./ denotes the repulsion term and is dominant for small values of jjx i x j jj.
From Eq. (9.21) it can be seen that g.x i x j / D g.x j x i /, i.e. g./ is an odd
function. Therefore, for the center of the multi-particle system holds that
PM
1
M
. j D1;j ¤i g.x
i
x j // D 0 and
(9.22)
PM
xPN D 1
M
i i
iD1 Œrx i V .x /
According to the Lyapunov stability analysis and application of LaSalle’s

theorem given in Chap. 8, it has been shown that the mean of the multi-particle
system will converge exactly to the goal position Œx ; y D Œ0; 0 while each
individual particle will remain in a small bounded area that encircles the goal
position [64, 92, 150, 152].
Next, flatness-based control for the multi-particle system will be analyzed. The
equivalent kinematic model of the i -th particle is given in Eq. (9.20) and can be
written in the form:
xP i D !x i C ui C i (9.23)
where !x i is the drift term due to the harmonic potential, ui is the external control,
and i is a disturbance term due to interaction with the rest N 1 particles, or due
to the existence of noise. Then it can be easily shown that the system of Eq. (9.23)
is differentially flat, while an appropriate flat output can be chosen to be y D x i .
Indeed all system variables, i.e. the elements of the state vector and the control input
can be written as functions of the flat output y, and thus the model that describes
the i -th particle is differentially flat.
An open-loop control input that makes the i -th particle track the reference
trajectory yri is given by
ui D !xri C xP ri C uic ; (9.24)
where xir is the reference trajectory for the i -th particle, and xP ir is the derivative of
the i -th desirable trajectory. Moreover uic D i stands for an additional control
term which compensates for the effect of the noise i on the i -th particle. Thus, if
the disturbance i that affects the i th-particle is adequately approximated it suffices
to set uic D i . The application of the control law of Eq. (9.24) to the model of
Eq. (9.23) results in the error dynamics
xP i D xP ri !x i C !xri C i uic )
xP i xP ri C !.xi xir / D i C uc ) (9.25)
eP i C !e i D i C uc :
Thus, if uc D i , then limt!1 D 0.

Next, the case of the N interacting particles will be examined. The control law
that makes the mean of the multi-particle system follow a desirable trajectory Efxri g
can be derived. The kinematic model of the mean of the multi-particle system is
given by
EfxP i g D !Efx i g C Efui g C Ef i g (9.26)
i D 1; ; N , where Efx i g is the mean value of the particles’ position, EfxP i g

is the mean velocity of the multi-particle system, Ef i g is the average of the
disturbance signal, and Efui g is the control input that is expected to steer the mean
of the multi-particle formation along a desirable path. The open-loop controller is
selected as:
Efui g D !Efx i gr C EfxPi gr Ef i g (9.27)
where Efx i gr is the desirable trajectory of the mean. From Eq. (9.27) it can be
seen that the particle’s control consists of two parts: (1) a part that compensates for
the interaction between the particles and, (2) a part that compensates for the forces
which are due to the harmonic external potential (slowing down of the particles’
motion).
Assuming that for the mean of the particles’ system holds Ef i g D 0, then the
control law of Eq. (9.27) results in the error dynamics for the mean position of the
particles
EfeP i g C !Efe i g D 0; (9.28)
which assures that the mean position of the particles will track the desirable
trajectory, i.e.
limt!1 Efe i g D 0: (9.29)

a b
Fig. 9.2 (a) Particles following reference trajectory (i), (b) associated control input
For non-constant acceleration, the generalized model of the harmonic oscillator

will be used and the results of Sect. 9.3 will be applied. Thus, the common control
inputPu.t / can be selected as u D Q.s/y, where y is the flat output, defined as
y D nkD1 ck zk C dk szk .
The particles (interacting weights) were initialized at arbitrary positions on the 2D-
plane. Trajectory tracking under flatness-based control is examined. The following
reference trajectories have been tested:
xr .t / D 5sin. 2T t /
(9.30)
yr .t / D 5cos. 2T t /
xr .t / D 5sin. 2T t /
(9.31)
yr .t / D 1:5cos. 2T t / C 1:5sin. 4T t / C 1:5sin. 8T t /
Open-loop flatness-based control has been applied, which means that the control
signal consisted of the reference trajectory and its derivatives, while measurements
about the position and the velocity of the particles have not been used. It can be
observed that under flatness-based control the mean of the particle system can be
steered along a desirable path with infinite accuracy, while each individual particle
can track the trajectory within acceptable accuracy levels.
The top left diagram in Figs. 9.2 and 9.3 shows the trajectories followed by the
particles when a separate control law was designed for each particle, while the
bottom diagram shows the trajectories followed by the particles when the average
control input was applied to each one of them. The right plot in Figs. 9.2 and 9.3
a b
Fig. 9.3 (a) Particles following reference trajectory (ii), (b) associated control input
shows the control input along the x (top) and y axis (bottom) (continuous line:
average control, dashed line: control designed individually for the i -th particle).
9.6 Conclusions
The chapter has presented first a control method for neuron models that have the
dynamics of chaotic oscillators. The proposed chaotic control method makes use
of a linearized model of the chaotic oscillator which is obtained after transforming
the oscillators dynamic model into a linear canonical form through the application
of differential flatness theory. Moreover, flatness-based control was applied to
motion control of a multi-particle system. A set of M particles (stochastic weights)
in a 2D-plane was considered and it was assumed that the interaction between
the particles was given by forces as the ones that appear in Brownian motion.
The multi-particle formation corresponds to an ensemble of coupled harmonic
oscillators. The kinematic model of the particles comprised a drift term that was
due to the harmonic potential, a disturbance term that was due to interaction with
the rest of the particles and a term that stands for the control input. Next, by applying
flatness-based control it was shown that the mean of the multi-particle formation can
follow the reference trajectory with infinite accuracy, while each individual particle
can be steered along the desirable trajectory within satisfactory accuracy ranges.
Chapter 10
Attractors in Associative Memories
with Stochastic Weights
Abstract Neural associative memories are considered in which the elements of

the weight matrix are taken to be stochastic variables. The probability density
function of each weight is given by the solution of Schrödinger’s diffusion equation.
The weights of the proposed associative memories are updated with the use of a
learning algorithm that satisfies quantum mechanics postulates. This learning rule
is proven to satisfy two basic postulates of quantum mechanics: (a) existence in
superimposing states, (b) evolution between the superimposing states with the use
of unitary operators. Taking the elements of the weight matrix of the associative
memory to be stochastic variables means that the initial weight matrix can be
decomposed into a superposition of associative memories. This is equivalent to
mapping the fundamental memories (attractors) of the associative memory into
the vector spaces which are spanned by the eigenvectors of the superimposing
matrices and which are related to each other via unitary rotations. In this way, it
can be shown that the storage capacity of the associative memories with stochastic
weights increases exponentially with respect to the storage capacity of conventional
associative memories.
10.1 Weights Learning in Associative Memories Is a Wiener

Process
10.1.1 The Weights of Associative Memories Are Equivalent

to Brownian Particles
In Sect. 8.2 a neural network with weights that follow the QHO model was
presented and stability of learning was analyzed. Interacting Brownian particles
stood in place of the neural weights. Now, it will be shown that this model is a
generalization of known associative memories, and since this model is compatible
with quantum mechanics postulates it can be considered as a quantum associative

192 10 Attractors in Associative Memories with Stochastic Weights
Fig. 10.1 A connectionist associative memory
memory. Moreover, it will be shown that the considered associative memory with
stochastic weights exhibits an exponential increase in the number of attractors,
comparing to conventional associative memories [83, 91, 156].
Suppose that a set of p N -dimensional vectors ( fundamental memories) are to
be stored in a Hopfield associative memory of N neurons, as the one depicted in
Fig. 10.1. The output of neuron j is given by sj D sgn.vj /; j D 1; 2; ; N and
P
the input vj is given by vj D N iD1 wji si j j D 1; 2; ; N , where si are the
outputs of the neurons connected to the j -th neuron, j is the threshold, and wji ’s
are the associated weights [78, 82].
The weights of the associative
Pp memory are selected using Hebb’s postulate
j
of learning, i.e. wji D N1 kD1 xk xki ; j ¤ i and wji D 0; j D i , where
i; j D 1; 2; ; N . The above can be summarized in the network’s correlation
weight matrix which is given by
1X T
p
W D xk xk (10.1)
N
kD1
From Eq. (10.1) it can be easily seen that in the case of binary fundamental
memories the weights learning is given by Hebb’s rule
j
wji .n C 1/ D wji .n/ C sgn.xkC1 xkC1
i
/ (10.2)
10.1 Weights Learning in Associative Memories Is a Wiener Process 193
i j
where k denotes the k-th fundamental memory. The increment sgn.xkC1 xkC1 / may
have the values C1 or 1. Thus, the weight wji is increased or decreased by 1 each
time a new fundamental memory is presented to the network. The maximum number
of fundamental memories p that can be retrieved successfully from an associative
memory of N neurons (error probability < 1 %) is given by pmax D 2lnNN
[7]. Thus,
for N D 16 the number of fundamental memories should not be much larger than
2.
The equivalence between Eqs. (7.4) and (10.2) is obvious and becomes more
j i
clear if in place of sgn.xkC1 xkC1 /, the variable kC1 D ˙1 is used, and if kC1
is also multiplied with the (step) increment x. Thus the learning of the weights
of an associative memory is a Wiener process. Consequently, the weights can
be considered as Brownian particles and their mean value and variance can be
calculated using the Central Limit Theorem (CLT) as in Sect. 7.2.2.
10.1.2 Mean Value and Variance of the Brownian Weights
The eigenvalues and the eigenvectors of the weight matrix W give all the informa-
tion needed to interpret the storage capacity of a neural associative memory [7].
The eigenvalues i i D 1; 2; ; N of the weight matrix W are calculated from
the solution of f . / D jW I j D 0. The eigenvectors q of matrix W satisfy
W x D q ) .W I /q D 0. Then according to the spectral theorem one gets
[78]:
X
M
W D QQT ) W D i qN i qN iT (10.3)
iD1
where i is the i -th eigenvalue of matrix W and qi is the associated N 1

eigenvector. Since the weight matrix W is symmetric, all the eigenvalues are real
and the eigenvectors will be orthogonal [78]. The input vector x which is presented
to the Hopfield P network can be written as a linear combination of the eigenvectors
qi , i.e. x D M iD1 i qi . Due to the orthogonality of the eigenvectors the convergence
of
PN the Hopfield network to its fundamental memories (attractors) PN xN gives xN D
iD1 i i qi . The memory vectors N
x are given by the sum iD1 i i qi , which
means that the eigenvectors of the symmetric matrix W consist of an orthogonal
basis of the subspace which is spanned by the memory vectors x. N
It can be shown that the memory vectors become collinear to the eigenvectors
of matrix W , thus constituting an orthogonal basis of the space V if the following
two conditions are satisfied: (a) the number of neurons N of the Hopfield network is
large (high dimensional spaces), and (b) the memory vectors are chosen randomly.
The following lemmas give sufficient conditions for the fundamental memory
vectors (attractors) to coincide with the eigenvectors of the weight matrix W :
Lemma 1. If the fundamental memory vectors (attractors) of the associative

memory are chosen to be orthogonal, then they are collinear to the eigenvectors
of matrix W [165].
Proof. The fundamental memory vectors xN are taken to be orthogonal to each other,
i.e. xN i xN jT D ı.i j /, where i; j D 1; 2; ; N . The weight matrix W is given by
Eq. (10.1).Thus, the following holds
Pp Pp
W xN kT D 1
N
f iD1 xN iT xN i gxN kT D 1
N
f iD1 xN iT .xN i xN kT /g ) W xN kT D 1
N
xN kT (10.4)
From Eq. (10.4) it can be concluded that if the memory vectors are orthogonal then
they are collinear to the eigenvectors of the matrix W .
Lemma 2. If the memory vectors of an associative memory are chosen randomly
and the number of neurons N is large, then there is high probability for them to be
orthogonal [165].
Proof. The normalized internal product of the memory vectors xi and xk is
considered
1X j j Xx x X
N N j j N
1 i k
xi xkT D xi xk D D Yj (10.5)
N N j D1 j D1
N j D1
j j
For large N and xi , xk randomly chosen from the discrete set f1; 1g it holds that
the mathematical expectation of Yj , denoted by E.Yj /, is E.Yj / D 0 and E.Yj
P 1 PN 1 1 PN
YNj /2 D N1 N N 2 j j
j D1 .Yj Yj / D N j D1 Yj D N N 2
2
.x x /2 . Assuming binary
j j j 2 PN j D1 j i j k2
patterns i.e. xi 2 f1; 1g then .xi xk / D 1, i.e. j D1 .xi xk / D N , thus
1 1 1
E.Yj YNj /2 D N ) E.Yj YNj /2 D 2 (10.6)
N N2 N
Therefore E.Yj / D 0 and E.Yj YNj /2 D N12 . The Central Limit Theorem is applied
here. This states:
“Consider fYk g” a sequence of mutually independent random variables fYk g
which follow a common distribution. It is assumed
P that Yk has mean and variance
2 , and let Y D Y1 C Y2 C C YN D N iD1 Yi . Then as N approaches infinity
the probability distribution of the sum random variable Y approaches a Gaussian
distribution”
.Y N i /
p \ N.0; 1/ (10.7)
N
According to CLT
PNthe probability distribution of the sum random variable
1 PN j j
N j D1 x i x k D j D1 Yj follows a Gaussian distribution of center D N 0
and variance 2 D N N12 D N1 . Therefore for large number of neurons N , i.e.
10.1 Weights Learning in Associative Memories Is a Wiener Process 195
Fig. 10.2 Partition of the real

axis x 2 R into an infinite
number of symmetric
triangular possibility
distributions (fuzzy sets)
for high dimensional spaces N1 ! 0 and the vectors xi and xk will be practically
orthogonal.
Thus, taking into account the orthogonality of the fundamental memories xN k and
Lemma 1, it can be concluded that memory patterns in high dimensional spaces
practically coincide with the eigenvectors of the weight matrix W .
10.1.3 Learning Through Unitary Quantum Mechanical

Operators
As already mentioned, the update of the weights wij of the associative memories is
performed according to Eq. (10.2), which implies that the value of wij is increased
by or decreased as indicated by sgn.x i x j /. If the weight wij is assumed to be a
stochastic variable, which is described by the probability (possibility) distribution
j
of Fig. 7.1b, then the term sgn.xki xk / of Hebbian learning can be replaced by a
stochastic increment.
A way to substantiate this stochastic increment is to describe variable wij
in terms of a possibility distribution (fuzzy sets). To this end, the real axis x,
where the wij takes its values, is partitioned in triangular possibility distributions
(fuzzy sets) A1 ; A2 ; ; An1 ; An (see Fig. 10.2). These approximate sufficiently
the Gaussians depicted in Fig. 7.1b. Then, the increase of the fuzzy (stochastic)
weight is performed through the possibility transition matrix Rni which results into
An D Rni ıAn1 , with ı being the max–min operator. Similarly, the decrease of
the fuzzy weight is performed through the possibility transition matrix Rnd , which
results into An1 D Rni ıAn [163, 195].
It has been shown that update of the weights based on the increase and decrease
operators satisfies two basic postulates of quantum mechanics, i.e.: (a) existence of
the stochastic weights wij in a superposition of states, (b) evolution of the weights
with the use of unitary operators, i.e. Rni ıRnd D Rnd ıRni D I [149, 165]. Moreover,
it has been shown that the aforementioned operators are equivalent to quantum
addition and quantum subtraction, respectively [163, 165].
10.2 Attractors in QHO-Based Associative Memories
10.2.1 Decomposition of the Weight Matrix

into a Superposition of Matrices
Taking the weights wij of the weight matrix W to be stochastic variables with
p.d.f. (or possibility distribution) as the one depicted in Fig. 7.1b means that W
can be decomposed into a superposition of associative memories (Fig. 10.3). The
equivalence of using probabilistic or possibilistic (fuzzy) variables in the description
of uncertainty has been analyzed in [51].
Following the stochastic (fuzzy) representation of the neural weights, the overall
associative memory WPequals a weighted averaging of the individual weight
matrices WN i , i.e. W D m N
iD1 i Wi , where the nonnegative weights i indicate the
contribution of each local associative memory WN i to the aggregate outcome [165].
Without loss of generality, a 3 3 weight matrix of a neural associative memory
is considered. It is also assumed that the weights wij are stochastic (fuzzy) variables
and that quantum P learning has been used for the weights update. The weights satisfy
the condition N iD1 Ai .wij / D 1 (strong fuzzy partition). Thus, the following
combinations of membership values of the elements of the matrices WN i are possible:
WN 1 W 12 13 23 WN 5 W 1 12 13 23

WN 2 W 12 13 1 23 WN 6 W 1 12 13 1 23
WN 3 W 12 1 13 23 WN 7 W 1 12 1 13 23
WN 4 W 12 1 13 1 23 WN 8 W 1 12 1 13 1 23
The decomposition of matrix W into a set of superimposing matrices WN i gives

80 1 0 Ai Ai 19
< l 12 13 0 a12 a13 =
WN 1 D @12 23 A ; @a12
Ai
0 a23Ai A
: Ai Ai ;
13 23 a13 a23 0
80 1 0 19
ˆ
< l 12 13 0 a12 Ai Ai
a13 >
=
B C
WN 2 D @12 1 23 A ; @a12 0 a23 A
A A C1
i i
:̂ Ai Ai C1 >
;
13 1 23 a13 a23 0
10.2 Attractors in QHO-Based Associative Memories 197
Fig. 10.3 Decomposition of an associative memory with stochastic weights into a superposition
of weight matrices, each one having its own attractors
80 1 0 19
ˆ
< l 12 1 13 0 a12 Ai
a13i C1 >
A
=
B C
WN 3 D @ 12 23 A ; @a12 0
A i A
a23i C1 A
:̂ 1 >
;
13 23 Ai Ai C1
a13 a23 0
80 1 0 19
ˆ
< l 12 1 13 0 Ai
a12
A
a13i C1 =>
B Ai C
WN 4 D @ 12 1 23 A ; @ a12
A
0 a23i C1 A
:̂ 1 >
;
13 1 23 A
a13i C1
A
a23i C1 0
80 1 0 19
ˆ
< l 1 12 13
A
0 a12i C1 a13 Ai >
=
B Ai C1 Ai C
WN 5 D @1 12 23 A ; @a12 0 a23 A
:̂ >
13 23 Ai
a13 Ai
a23 0 ;
80 1 0 19
ˆ
< l 1 12 13
A
0 a12i C1 a13 Ai >
=
B A Ai C
WN 6 D @1 12 1 23 A ; @a12i C1 0 a23 A
:̂ >
;
13 1 23 Ai
a13
A
a23i C1 0
80 1 0 19
ˆ
< l 1 12 1 13 0 a12 Ai Ai C1 >
a13 =
B A Ai C
WN 7 D @ 1 12 23 A ; @a12i C1 0 a23 A
:̂ 1 >
;
13 23 A Ai
a13i C1 a23 0
80 1 0 19
ˆ
< l 1 12 1 13 0 a12i C1 a13i C1 >
A A
=
B A C
WN 8 D @1 12 1 23 A ; @a12i C1 0 a23i C1 A
A
:̂ 1 1 >
;
13 23 A A
a13i C1 a23i C1 0
where Ai and AiC1 are the two adjacent fuzzy sets to which the weight wij belongs,
with centers c Ai and c Ai C1 , respectively (Fig. 10.2). The diagonal elements of the
matrices WN i are taken to be 0 (no self-feedback in neurons is considered), and
denotes that the membership value of the element wi i ; i D 1; ; 3 is indifferent.
The matrices which have as elements the membership values of the weights wij
are denoted by Mi and the associated jjL1 jj are calculated. Each L1 norm is divided
by the number of the non-diagonal elements of the matrices Mi . This results to
0 0 1
Ai Ai 1 Ai Ai
0 a12 a13 0 a12 a13
B Ai C
W D 12 C313 C23 @a12 Ai A
C 12 C13323 C1 @a12
Ai A
0 a23 0 a23i C1 A
aAi aAi 0 Ai Ai C1
a013 a23 0
0 13 23 A 1 A
1
Ai
Ai
0 a12 a13 i C1
0 a12 a13i C1
B Ai Ai C C2 B Ai C
C 12 133C23 C1 @ a12 0 a23 A C 12 133 23 @ a12
A
0 a23i C1 A
Ai C1 Ai Ai C1 Ai C1
a13 a23 0
0 1 a013 a23 0 1
A A Ai
0 a12i C1 a13 Ai
0 a12i C1 a13
B Ai C1 Ai C C 12 C13 23 C2 B Ai C1 C
C 12 C133 C23 C1 @a12 0 a23 A 3 @a12
A
0 a23i C1 A
Ai Ai Ai Ai C1
0 a13 aA23 0A 1 0a13 a23 A 0
A
1
i C1 i C1
0 a12 a13 0 a12 a13i C1
i C1
B Ai C1 Ai C C3 B A C
C 12 133 C23 C2 @a12 0 a23 A C 12 133 23 @a12i C1 0 a23i C1 A
A
A Ai A A
a13i C1 a23 0 a13i C1 a23i C1 0
The following lemma holds [165]:

P PN
Lemma 3. The jjL1 jj of the matrices Mi (i.e. N iD1 j D1 jij j) divided by the
number of the non-diagonal elements , i.e. N.N 1/ and by 2N 1 , where N is
the number of neurons, equals unity.
1 XN X N
jij j D 1 (10.8)
N.N 1/2N 1 iD1 j D1
Proof. There are 2N 1 couples of matrices Mi . Due to the strong fuzzy partition
there are always two matrices Mi and Mj with complementary elements, i.e. .wij /
and 1 .wij /. Therefore the sum of the corresponding L1 norms jjMi jj C jjMj jj
normalized by the number of the non-zero elements (i.e., N.N 1/) equals
unity. Since there are 2N 1 couples of L1 norm sums jjMi jj C jjMj jj it holds
1 P2N
2N 1 iD1 jjMi jj D 1. This normalization procedure can be used to derive the
membership values of the weight matrices WN i .
Remark 1. The decomposition of the matrix W into a group of matrices WN i reveals
the existence of non-observable attractors. According to Lemmas 1 and 2 these
attractors coincide with the eigenvectors vi of the matrices WN i . Thus the patterns
10.2 Attractors in QHO-Based Associative Memories 199
that can be recalled from an associative memory are more than the ones associated
with the initial matrix W . For an associative memory of N neurons, the possible
patterns become N 2N .
10.2.2 Evolution Between the Eigenvector Spaces via Unitary

Rotations
It will be shown that the transition between the vector spaces which are associated
with matrices WN i ’s is described by unitary rotations. This is stated in the following
theorem [165]:
Theorem 2. The rotations between the spaces which are spanned by the eigenvec-
tors of the weight matrices WN i are unitary operators.
Proof. Let xi ; yi ; zi and xj ; yj ; zj be the unit vectors of the bases which span
the spaces associated with the matrices WN i and WN j , respectively. Then a memory
vector p can be described in both spaces as: p D .pxi ; pyi ; pzi /T and p D
.pxj ; pyj ; pzj /T . Transition from the reference system WN i ! fxi ; yi ; zi g to the
reference system WNj ! fxj ; yj ; zj g is expressed by the rotation matrix R, i.e.
pWN i D RpWN j . The inverse transition is expressed by the rotation matrix Q, i.e.
pWN j D QpWN i .
Furthermore it is true that
0 1 0 10 1
pxi xi xj xi yj xi zj pxj
@py A D @yi xj yi yj yi zj A @pyj A (10.9)
i
pzi zi xj zi yj zi zj pzj
Thus, using Eq. (10.9) the rotation matrices R and Q are given by
0 1 0 1
x i xj xi yj xi zj xj xi xj yi xj zi
R D @yi xj yi yj yi zj A ; Q D @yj xi yj yi yj zi A (10.10)
zi xj zi yj zi zj zj xi zj yi zj zi
It holds that
pWN i D RpWN j and pWN j D QpWN i )

pWN i D RQpWN i and pWN j D QRpWN j ) (10.11)
QR D RQ D I )Q D R1
Moreover, since “dot products” are commutative, from Eq. (10.10) one obtains
Q D RT . Therefore it holds Q D R1 D RT , and the transition from the reference
system WN i to the reference system WN j is described by unitary operators, i.e. QR D
RT R D R1 R D I .
10.2.3 Applications of the Stochastic Associative Memory

Model
The proposed stochastic associative memory model has also practical signifi-
cance:
1. Stochastic neuron models enable the study and understanding of probabilistic
decision making [31].
2. Stochastic neuron models can explain instabilities in short-term memory and
attentional systems. These become particularly apparent when the basins of
attraction become shallow or deep (in terms of an energy profile) and have
been related to some of the symptoms of neurological diseases. The approach
thus enables predictions to be made about the effects of pharmacological agents
[43, 44, 75, 114, 115, 171].
3. Stochastic neuron models can improve neural computation towards the direction
of quantum computation [137, 165].
10.3 Attractors in Associative Memories with Stochastic

Weights
It will be examined how the concept of weights that follow the QHO model affects
the number of attractors in associative memories. The storage and recall of patterns
in quantum associative memories will be tested through a numerical example and
simulation tests.
1. Superposition of weight matrices:
Assume that the fundamental memory patterns are the following binary vectors
s1 D Œ1; 1; 1, s2 D Œ1; 1; 1, s3 D Œ1; 1; 1, which are linearly independent
but not orthogonal. Orthogonality should be expected in high dimensional vector
spaces if the elements of the memory vectors are chosen randomly. In this example,
to obtain orthogonality of the memory vectors, Gramm–Schmidt orthogonalization
is used according to
X
k1
uj sk
uk D sk uj (10.12)
u uT
j D1 j j
This gives the orthogonal vectors u1 D Œ1; 1; 1, u2 D Œ 23 ; 23 ; 4

3
,u3 D Œ1; 1; 0.
The weight matrix which results from Hebbian learning asymptotically becomes a
Wiener process. Matrix W is W D 13 ŒuT1 u1 C uT2 u2 C uT3 u3 , i.e.
10.3 Attractors in Associative Memories with Stochastic Weights 201
Fig. 10.4 Partition of the fuzzy universe of discourse
0 1
0:8141 0:1481 0:0369
W D @0:1481 0:8141 0:0369A
(10.13)
0:0369 0:0369 0:9247
It can be easily shown that W u1 D u1 , W u2 D u2 , W u3 D u3 , i.e. u1 , u2 ,

u3 are stable states (attractors) of the network. The eigenvalues of matrix W are
1 D 0:667, 2 D 0:888, and 3 D 1:0. The associated eigenvectors of W
are v1 D Œ0:7071; 0:7071; 0T , v2 D Œ0:4066; 0:4066; 0:8181T , and v3 D
Œ0:5785; 0:5785; 0:5750T . It can be observed that v1 is collinear to u3 , v2 is collinear
to u2 , and v3 is collinear to u1 . That was expected from Lemma 1, in Sect. 10.1.
Next, the elements of the weight matrix W are considered to be stochastic
variables, with p.d.f. (possibility distribution) as the one depicted in Fig. 7.1b and
thus matrix W , given by Eq. (10.13), can be decomposed into a superposition
of weight matrices WN i . Assume that only the non-diagonal elements of W are
considered and that the possibility distribution of the stochastic variables wij is
depicted in Fig. 10.4.
Then, the weight matrix W is decomposed into a superposition of weight
matrices WN i , i D 1; ; 8:
80 1 0 19
< 0:405 0:155 0 0:14 0:02 =
W D @0:405 0:155A ; @0:14 0 0:02A
: ;
0:155 0:155 0:02 0:02 0
80 1 0 19
< 0:405 0:155 0 0:14 0:02 =
C @0:405 0:845A ; @0:14 0 0:04A
: ;
0:155 0:845 0:02 0:04 0
80 1 0 19
< 0:405 0:845 0 0:14 0:04 =
C @0:405 A @
0:155 ; 0:14 0 0:02A
: ;
0:845 0:155 0:04 0:02 0
80 1 0 19
< 0:405 0:845 0 0:14 0:04 =
C @0:405 0:845A ; @0:14 0 0:04A
: ;
0:845 0:845 0:04 0:04 0
80 1 0 19
< 0:595 0:155 0 0:16 0:02 =
C @0:595 A @
0:155 ; 0:16 0 0:02A
: ;
0:155 0:155 0:02 0:02 0
80 1 0 19
< 0:595 0:155 0 0:16 0:02 =
C @0:595 0:845A ; @0:16 0 0:04A
: ;
0:155 0:845 0:02 0:04 0
80 1 0 19
< 0:595 0:845 0 0:16 0:04 =
C @0:595 A @
0:155 ; 0:16 0 0:02A
: ;
0:845 0:155 0:04 0:02 0
80 1 0 19
< 0:595 0:845 0 0:16 0:04 =
C @0:595 0:845A ; @0:16 0 0:04A
: ;
0:845 0:845 0:04 0:04 0
Using Lemma 3, the membership i of each matrix WN i is taken to be the norm

jjL1 jj of the matrix with elements the membership values of the weights wij ,
PN PN
j D1 j.w N ij /j/. According to Sect. 10.2.1 this gives W D
1
i.e. N .N 1/2N 1 . iD1
1 W1 C 2 W2 C C 8 W8 , where the membership i are: 1 D 0:0596,
2 D 0:1171, 3 D 0:1171, 4 D 0:1746, 5 D 0:0754, 6 D 0:1329,
7 D 0:1329, and 8 D 0:1904. By calculating the eigenvectors of matrices WN i ,
the associated memory patterns can be found. These are non-observable attractors
different from the attractors u1 , u2 , and u3 of the initial weight matrix W . Thus, the
number of memory patterns is increased by a factor 2N D 8.
The eigenstructure analysis of matrix WN 1 gives: 1 D 0:14, 2 D 0:1455,
N N
3 D 0:0055, with associated eigenvectors v1W1 D Œ0:7071; 0:7071; 0T , v2W1 D
N
Œ0:6941; 0:6941; 0:1908T , and v3W1 D Œ0:1349; 0:1349; 0:9816T .
N
3 D 0:1519, with associated eigenvectors v1W2 D Œ0:6921; 0:7143; 0:1041T ,
N N
v2W2 D Œ0:2648; 0:1176; 0:9572T , and v3W2 D Œ0:6715; 0:6900; 0:2701T .
N
3 D 0:1519, with associated eigenvectors are v1W3 D Œ0:7143; 0:6921; 0:1041T ,
N N
v2W3 D Œ0:1170; 0:2648; 0:9572T , and v3W3 D Œ0:6715; 0:6900; 0:2701T .

N N
N
Œ0:6667; 0:6667; 0:3333T , and v3W4 D Œ0:2357; 0:2357; 0:9428T .
N N
N
Œ0:6969; 0:6969; 0:1691T , and v3W5 D Œ0:1196; 0:1196; 0:9856T .
N
N N
v2W6 D Œ0:2353; 0:1071; 0:9660T , and v3W6 D Œ0:6787; 0:6933; 0:2421T .
N
The eigenstructure analysis of matrix W7 gives: 1 D 0:1613, 2 D 0:0093,
N
N N
v2W7 D Œ0:1071; 0:2353; 0:9660T , and v3W7 D Œ0:6993; 0:6787; 0:2421T .
N N
N
Œ0:6739; 0:6739; 0:3029T , and v3W8 D Œ0:2142; 0:2142; 0:9530T .
Remark 2. In neural structures with weights that follow Schrödinger’s equation
with zero or constant potential (see the analysis in [165]), the probability to recall
N
the pattern vkWi ; i D 1; ; 8; k D 1; ; 3 is proportional to the membership
i of the matrix WN i , i.e. P / .WN i /. The superimposing matrices WN i ’s describe a
distributed associative memory [96].
Remark 3. The difference of the neural structures that follow the quantum harmonic
oscillator (QHO) model comparing to neural structures that follow Schrödinger’s
equation with zero or constant potential is that convergence to an attractor is
controlled by the drift force imposed by the harmonic potential [124]. Convergence
to an attractor, as the results of Chap. 8 indicate, can be steered through the drift
force, which in turn is tuned by the parameters a and b of Eq. (8.14).
2. Unitarity of the rotation operators
Here the analysis of second part of Sect. 10.2 will be verified. Matrix R of
Eq. (10.10) which performs a rotation from the basis defined by the eigenvectors
.WN / .WN / .WN / .WN / .WN / .WN /
v1 1 ; v2 1 ; v3 1 , to the basis defined by the vectors v1 2 ; v2 2 ; v3 2 is calculated
.WN 1 / .WN 1 /
as follows: v1 D Œ0:7071; 0:7071; 0T , v2 D Œ0:6941; 0:6941; 0:1908T and
N .WN /
v3W1 D Œ0:1349; 0:1349; 0:9816T , while v1 2 D Œ0:6921; 0:7143; 0:1041T ,
.WN / .WN /
v2 2 D Œ0:2648; 0:1176; 0:9972T , and v3 2 D Œ0:6715; 0:6900; 0:2701T .
The rotation matrix R is given by
0 .WN 1 / .WN 2 / .WN 1 / .WN 2 / .WN 1 / .WN 2 /
1 0 1
v1 v1 v1 v2 v1 v3 0:9945 0:1041 0:0131
B .WN 1 / .WN 2 / .WN 1 / .WN 2 / .WN / .WN / C
RD @v2 v1 v2 v2 v2 1 v3 2 A D @ 0:0045 0:0752 0:9966 A
.WN / .WN / .WN / .WN / .WN / .WN / 0:1052 1:0304 0:0815
v3 1 v1 2 v3 1 v2 2 v3 1 v3 2
(10.14)
Fig. 10.5 (a) input pattern 1 (b) recalled pattern 1
It holds
0 1 0 1
1:000 0:0008 0:0037 100
RR D @0:0008 0:9989 0:0042A ) RR ' @0 1 0A
T T
(10.15)
0:0037 0:0042 1:0794 001
Thus, matrix R represents a unitary rotation from the vector space

.WN / .WN / .WN / .WN / .WN / .WN /
v1 1 ; v2 1 ; v3 1
to the vector space v1 2 ; v2 2 ; v3 2 .
3. Simulation tests
Simulation tests have been carried out for the recognition of images stored in
an associative memory. Two binary images were considered (see Figs. 10.5b and
10.7b). Both images consisted of 8 8 pixels. The images were selected, so as to
reduce cross pattern interference [180].
The correlation weight matrix W 2 R6464 was found. The images of Figs. 10.5a,
10.6a, 10.7a, 10.8a were given as input to the weight matrix W . The recalled patterns
are given in Fig. 10.5b, 10.6b, 10.7b, 10.8b, respectively. This simulation test
demonstrates the known error-correcting capability of neural associative memories.
When the randomly distorted patterns were presented to the associative memory
then after a number of iterations the associative memory converged to the stored
images.
Next, the weight matrix W was viewed as an associative memory with stochastic
weights. The superimposed weight matrices WN i ; i D 1; 2; ; 264 were considered
and the associated rotation matrices Ri ’s were calculated. The decomposition of
W into the superposition of weight matrices WN i followed the analysis presented
in Sect. 10.2.1. The calculation of the rotation matrices Ri followed the analysis
presented in Sect. 10.2.2. The patterns of Figs. 10.9a and 10.10a were generated
by applying the stored images of Figs. 10.5b and 10.7b to two different rotation
matrices Ri , respectively. Then by applying the patterns of Figs. 10.9a and 10.10a
as input to the matrices RiT recall of the initial patterns could be observed. This
simulation test demonstrates that the rotation matrices Ri result in 264 different
perceptions of the initial memory patterns.

Fig. 10.9 Eigenspace of matrix Wi (a) Rotated pattern 1 (b) Retrieved pattern 1
Fig. 10.10 Eigenspace of matrix Wi (a) Rotated pattern 2 (b) Retrieved pattern 2
10.4 Conclusions
Neural associative memories have been considered in which the elements of the
weight matrix were taken to be stochastic variables. The probability density function
of each weight was given by the solution of Schrödinger’s equation under harmonic
potential (quantum harmonic oscillator). Weights that follow the QHO model give
to associative memories significant properties: (a) the learning of the stochastic
weights is a Wiener process, (b) the update of weights can be described by
unitary operators as the principles of quantum mechanics predict, (c) the number of
attractors increases exponentially comparing to conventional associative memories.
The above theoretical findings were further analyzed through simulation tests. The
convergence of the QHO-driven weights to an equilibrium was observed and the
existence of non-observable attractors in QHO-based associative memories was
demonstrated.
Chapter 11
Spectral Analysis of Neural Models
with Stochastic Weights
Abstract Spectral analysis of neural networks with stochastic weights (stemming

from the solution of Schrödinger’s diffusion equation) has shown that: (a) The
Gaussian basis functions of the weights express the distribution of the energy with
respect to the weights’ value. The smaller the spread of the basis functions is, the
larger becomes the spectral (energy) content that can be captured therein. Narrow
spread of the basis functions results in wide range of frequencies of the Fourier
transformed pulse, (b) The stochastic weights satisfy an equation which is analogous
to the principle of uncertainty.
11.1 Overview
The energy spectrum of the stochastic weights that follow the quantum harmonic
oscillator (QHO) model is studied. To this end, previous results on wavelets’ energy
spectrum are used [2,42,149,168]. Spectral analysis of the stochastic weights shows
that: (a) The Gaussian membership functions of the weights express the distribution
of energy with respect to the weights’ value. The smaller the spread of the basis
functions is, the larger becomes the spectral (energy) content that can be captured
therein (b) The stochastic weights satisfy an equation which is analogous to the
principle of uncertainty. Moreover, simulation and numerical results were provided
to support the argument that the representation of the basis functions in the space
and in the frequency domain cannot be, in both cases, too sharply localized.

208 11 Spectral Analysis of Neural Models with Stochastic Weights
11.2 Wavelet Basis Functions
11.2.1 Wavelet Frames
The continuous time wavelet is defined at scale a and b as

1 xb
a;b .x/ D p (11.1)
a ˛
It will be shown that a continuous time signal f .x/ can be expressed as a series
expansion of discrete wavelet basis functions. The discrete wavelet has the form
[2, 187, 191, 225]

1 x nb0 ˛0m
m;n .x/ Dp m (11.2)
˛0 ˛0m
The wavelet transform of a continuous signal f .x/ using discrete wavelets of the
form of Eq. (11.2) is given by
Z C1
1 x nb0 ˛0m
Tm;n D f .x/ p m dx (11.3)
1 ˛0 ˛0m
which can be also expressed as the inner product Tm;n D< f .x/; m;n >. For the
discrete wavelet transform, the values Tm;n are known as wavelet coefficients. To
determine how good the representation of a signal is in the wavelet space one can
use the theory of wavelet frames. The family of wavelet functions that constitute
a frame are such that the energy of the resulting wavelet coefficients lies within a
certain bounded range of the energy of the original signal
C1
X C1
X
AE jTm;n j2 BE (11.4)
mD1nD1
where Tm;n are the discrete wavelet coefficients, A and B are the frame bounds, and
R C1
E is the energy of the signal given by E D 1 jf .x/j2 dt D jjf .x/jj2 . The values
of the frame bounds depend on the parameters ˛0 and b0 chosen for the analysis and
the wavelet function used. If A D B, the frame is known as tight and has a simple
reconstruction formula given by the finite series
C1 C1
1 X X
f .x/ D Tm;n m;n .x/ (11.5)
A mD1nD1
A tight frame with A D B > 1 is redundant, with A being a measure of the

redundancy. When A D B D 1 the wavelet family defined by the frame forms
11.2 Wavelet Basis Functions 209
an orthonormal basis. Even if A¤B a reconstruction formula of f .x/ can be

obtained in the form:
C1
X C1X
2
f 0 .x/ D Tm;n m;n .x/ (11.6)
A C B mD1nD1
where f 0 .x/ is the reconstruction which differs from the original signal f .x/ by
an error which depends on the values of the frame bounds. The error becomes
acceptably small for practical purposes when the ratio B=A is near unity. The closer
this ratio is to unity, the tighter the frame.
11.2.2 Dyadic Grid Scaling and Orthonormal Wavelet

Transforms
The dyadic grid is perhaps the simplest and most efficient discretization for practical
purposes and lends itself to the construction of an orthonormal wavelet basis.
Substituting ˛0 D 2 and b0 D 1 into Eq. (11.2) the dyadic grid wavelet can be
written as

1 x n2m
m;n D p (11.7)
2m 2m
or more compactly
m
m;n .t / D 2 2 .2m x n/ (11.8)
Discrete dyadic grid wavelets are commonly chosen to be orthonormal. These

wavelets are both orthogonal to each other and normalized to have unit energy. This
is expressed as
Z C1
1 if m D m0 ; and n D n0
m;n .x/ m0 ;n0 .x/dx D (11.9)
1 0 otherwise
Thus, the products of each wavelet with all others in the same dyadic system are
zero. This also means that the information stored in a wavelet coefficient Tm;n is
not repeated elsewhere and allows for the complete regeneration of the original
signal without redundancy. In addition to being orthogonal, orthonormal wavelets
are normalized to have unit energy. This can be seen from Eq. (11.9), as using
m D m0 and n D n0 the integral gives the energy of the wavelet function equal to
unity. Orthonormal wavelets have frame bounds A D B D 1 and the corresponding
wavelet family is an orthonormal basis. An orthonormal basis has components
which, in addition to being able to completely define the signal, are perpendicular
to each other.
Using the dyadic grid wavelet of Eq. (11.7) the discrete wavelet transform is
defined as
Z C1
Tm;n D x.t / m;n .x/dt (11.10)
1
By choosing an orthonormal wavelet basis m;n .x/ one can reconstruct the original
signal f .x/ in terms of the wavelet coefficients Tm;n using the inverse discrete
wavelet transform:
C1
X C1
X
f .x/ D Tm;n m;n .x/ (11.11)
mD1nD1
requiring the summation over all integers m and n. In addition, the energy of the
signal can be expressed as
Z C1 C1
X C1
X
jf .x/j2 dx D jTm;n j2 (11.12)
1 mD1nD1
11.2.3 The Scaling Function and the Multi-resolution

Representation
Orthonormal dyadic discrete wavelets are associated with scaling functions and their
dilation equations. The scaling function is associated with the smoothing of the
signal and has the same form as the wavelet

m;n .x/ D 2m=2
.2m x n/ (11.13)
The scaling functions have the property

Z C1

0;0 .x/dx D 1 (11.14)
1
where
0;0 .x/ D
.x/ is sometimes referred as the father scaling function or father
(mother) wavelet. The scaling function is orthogonal to translations of itself, but
not to dilations of itself. The scaling function can be convolved with the signal to
produce approximation coefficients as follows:
Z C1
Sm;n D f .x/
m;n .x/dx (11.15)
1
One can represent a signal f .x/ using a combined series expansion using both the
approximation coefficients and the wavelet (detail) coefficients as follows:
C1
X X
m0 C1
X
f .x/ D Sm0 ;n
m0 ;n C Tm;n m;n .x/ (11.16)
nD1 mD1nD1
It can be seen from this equation that the original continuous signal is expressed as
a combination of an approximation of itself, at arbitrary scale index m0 added to
a succession of signal details form scales m0 down to negative infinity. The signal
detail at scale m is defined as
C1
X
dm .x/ D Tm;n m;n .x/ (11.17)
nD1
and hence one can write Eq. (11.16)
X
m0
f .x/ D fm0 .t / C dm .x/ (11.18)
mD1
From this equation it can be shown that
fm1 .x/ D fm .x/ C dm .x/ (11.19)
which shows that if one adds the signal detail at an arbitrary scale (index m) to
the approximation at that scale he gets the signal approximation at an increased
resolution (at a smaller scale index m 1). This is the so-called multi-resolution
representation.
11.2.4 Examples of Orthonormal Wavelets
The scaling equation (or dilation equation) describes the scaling function
.x/ in
terms of contracted and shifted versions of itself as follows [2, 119]:
X

.x/ D ck
.2x k/ (11.20)
k
where
.2x k/ is a contracted version of
.t / shifted along the time axis by an
integer step k and factored by an associated scaling coefficient ck . The coefficient
of the scaling equation should satisfy the condition
X
ck D 2 (11.21)
k
X
2 if k 0 D 0
ck ckC2k 0 D (11.22)
0 otherwise
k
This also shows that the sum of the squares of the scaling coefficients is equal to
2. The same coefficients are used in reverse with alternate signs to produce the
associated wavelet equation
X
.x/ D .1/k c1k
.2x k/ (11.23)
k
This construction ensures that the wavelets and their corresponding scaling func-
tions are orthogonal. For wavelets of compact support, which have a finite number
of scaling coefficients Nk the following wavelet function is defined
X
.x/ D .1/k cNk 1k
.2x k/ (11.24)
k
This ordering of scaling coefficients used in the wavelet equation allows for our
wavelets and their corresponding scaling equations to have support over the same
interval Œ0; Nk1 . Often the reconfigured coefficients used for the wavelet function
are written more compactly as
bk D .1/k cNk 1k (11.25)
where the sum of all coefficients bk is zero. Using this reordering of the coefficients
Eq. (11.24) can be written as
k 1
NX
.x/ D bk
.2x k/ (11.26)
kD0
From the previous equations and examining the wavelet at scale index m C 1 one
can see that for arbitrary integer values of m the following holds
X
1 2t
2.mC1/=2
n D 2m=2 21=2 ck
2n k (11.27)
2mC1 22m
k
which may be written more compactly as
1 X

mC1;n .x/ D p ck
m;2nCk .x/ (11.28)
2 k
That is the scaling function at an arbitrary scale is composed of a sequence of

shifted functions at the next smaller scale each factored by their respective scaling
coefficients. Similarly, for the wavelet function one obtains
1 X
mC1;n .x/ Dp bk
m;2nCk .x/ (11.29)
2 k
a b
Fig. 11.1 (a) (i) The Haar scaling function in terms of shifted and dilated versions of itself, (ii)
The Haar wavelet in terms of shifted and dilated versions of its scaling function, (b) (i) Three
consecutive scales shown from the Haar wavelet family specified on a dyadic grid, e.g. from the
bottom m;n .x/, mC1;n .x/, mC2;n .x/, (ii) Three Haar wavelets at three consecutive scales on a
dyadic grid, iii) Three Haar wavelets at different scales. This time the Haar wavelets are not defined
on a dyadic grid and are hence not orthogonal to each other
11.2.5 The Haar Wavelet
The Haar wavelet is the simplest example of an orthonormal wavelet. Its scaling
equation contains only two non-zero scaling coefficients and is given by

.x/ D
.2x/ C
.2x 1/ (11.30)
that is, its scaling coefficients are c0 D c1 D 1. These values can be obtained from
Eqs. (11.21) and (11.22). The solution of the Haar scaling equation is the single
block pulse defined as

1 0x < 1

.x/ D (11.31)
0 elsewhere
Using this scaling function, the Haar wavelet equation is
.x/ D
.2x/
.2x 1/ (11.32)
The Haar wavelet is finally found to be

8 1
< 1 0x < 2
.x/ D 1 2 x < 1
1
(11.33)
:
0 elsewhere
The mother wavelet for the Haar wavelet system .x/ D 0;0 .x/ is formed from
two dilated unit block pulses placed next to each other on the time axis, with one
of them inverted. From the mother wavelet one can construct the Haar system of
wavelets on a dyadic grid m;n .x/ (Fig. 11.1).
2 2 5 5
4 4
1 1
3 3
0 0
2 2
−1 −1 1 1
−2 −2 0 0
−50 0 50 −50 0 50 0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
(a) (b) (a) (b)
2 2 5 5
4 4
1 1
3 3
0 0
2 2
−1 −1
1 1
−2 −2 0 0
−50 0 50 −50 0 50 0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
(c) (d) (c) (d)
a b
Fig. 11.2 (i) Real (continuous) and imaginary (dashed) part of Morlet wavelets for various
frequencies: (a) f0 D 0:1 Hz (b) f0 D 0:3 Hz (c) f0 D 0:5 Hz, (d) f0 D 0:7 Hz (ii) Energy
spectrum of the Morlet wavelet of Fig. 11.2c for central frequency f0 D 0:5 Hz and different
variances: (a) 2 , (b) 4 2 , (c) 8 2 , (d) 16 2
11.3 Spectral Analysis of the Stochastic Weights
Spectral analysis of associative memories with weights described by interacting

Brownian particles (quantum associative memories) will be carried out following
previous studies on wavelets power spectra [2, 42, 149, 168]. Spectral analysis in
quantum associative memories shows that the weights wij satisfy the principle of
uncertainty.
11.3.1 Spectral Analysis of Wavelets
11.3.1.1 The Complex Wavelet
The study of the energy spectrum of wavelets will be used as the basis of the
spectral analysis of quantum associative memories. The Morlet wavelet is the most
commonly used complex wavelet and in a simple form is given by

1 .2f0 /2 x 2
.x/ D 4 e i2f0 x e 2 e 2 (11.34)
This wavelet is simply a complex wave within a Gaussian envelope. The complex
sinusoidal waveform is contained in the term e i2f0 x D cos.2f0 x/Ci sin.2f0 x/.
The real and the imaginary part of the Morlet wavelet for various central frequencies
are depicted in Fig. 11.2a.
11.3 Spectral Analysis of the Stochastic Weights 215
It can be seen that the real and the imaginary part of the wavelet differ in phase
1
by a quarter period. The 4 term is a normalization factor which ensures that the
wavelet has unit energy.
11.3.1.2 Spectral Decomposition and Heisenberg Boxes
The Fourier transform of the Morlet wavelet is given by

p
O .f / D 14 1
2e 2 .2f 2f0 /
2
(11.35)
which has the form of a Gaussian function displaced along the frequency axis by
f0 . The energy spectrum (the squared magnitude of the Fourier transform) is given
by [2]
j O .f /j2 D 2 2 e .2f 2f0 /

1 2
(11.36)
which is a Gaussian centered at f0 . The integral of (11.36) gives the energy of the
Morlet wavelet. The energy spectrum of the Morlet wavelet depicted in diagram (c)
of Fig. 11.2(i), for different values of the variance 2 is given in Fig. 11.2b.
The central frequency f0 is the frequency of the complex sinusoid and its value
determines the number of significant sinusoidal waveforms contained within the
envelope. The dilated and translated Morlet wavelet . xb a
/ is given by

xb 1 xb
/ e 12 . xb
2
D 4 e i2f0 . a a / (11.37)
a
The Heisenberg boxes in the x-frequency plane for a wavelet at different scales
are shown in Fig. 11.3a. To evaluate frequency composition a sample of a long
region of the signal is required. If instead, a small region of the signal is measured
with accuracy, then it becomes very difficult to determine the frequency content
of the signal in that region. That is, the more accurate the temporal measurement
(smaller x ) is, the less accurate the spectral measurement (larger f ) becomes, and
vice-versa [119].
The Morlet central frequency f0 sets the location of the Heisenberg box in the
x-frequency plane. If the x-length of the wavelets remains the same, then no matter
the change of the central frequency f0 the associated Heisenberg boxes will have
the same dimensions. This is depicted in Fig. 11.3b.
Finally, in Fig. 11.4a are shown the Heisenberg boxes in the x-frequency plane
for a number of wavelets with three different spectral frequencies (low, medium,
and high). The confining Gaussian windows have the same dimensions along the x
axis. Therefore, altering the central frequency of the wavelet shifts the Heisenberg
box up and down the x-frequency plane without altering its dimensions.
a b
Fig. 11.3 (a) Heisenberg boxes in the x-frequency plane for a wavelet at various scales f1 ,f2 ,f3
and of different length x along the x-axis. x is the standard deviation of the squared wavelet
function .x/2 ; f is the standard deviation of the spectrum around the mean spectral components
f1 , f2 , and f3 (b) Heisenberg boxes in the x-frequency plane for wavelet at various scales f1 , f2 ,
f3 and of the same length x along the x-axis. Changes of the central frequency f0 do not affect
the size of the Heisenberg boxes
11.3.2 Energy Spectrum of the Stochastic Weights
The following theorem holds [148, 149]:

Theorem 1. The Gaussian basis functions of the weights wij of a quantum asso-
ciative memory express the distribution of energy with respect to the value of wij .
The smaller the spread of the basis functions is, the larger becomes the spectral
(energy) content that can be captured therein.
p f2
Proof. The Fourier transform of g.x/ D I0 e ax is G.f / D I0 a e 4a .
2
Consequently for < wij > described by shifted overlapping Gaussians, i.e.
1
X 2
1 .wij kc/
< wij >D e 2 2 ak (11.38)
kD1
it holds that the associated Fourier transform is:

11.3 Spectral Analysis of the Stochastic Weights 217
a b
Fig. 11.4 (a) Heisenberg boxes in the x-frequency plane for a number of superimposing wavelets
of the same length x along the x-axis and at three different spectral frequencies set to low,
medium, and high value. (b) Heisenberg boxes in the x-frequency plane for a number of Gaussian
basis functions which have the same variance and which are shifted on the x axis
1
( ) 1
X 1 .wij kc/
2 X p
e 2 2 ak
1 2 2
G D .kc/e ifkc 2e 2 f
kD1 kD1
where ˛k D kc; with c being the distance between the centers of two adjacent
fuzzy basis functions. If only the real part of G.f / is kept, then one obtains
( 1
) 1
X 12
.wij kc/2 X p 1 2 2
G e 2 ak D .kc/ cos.fkc/ 2e 2 f (11.39)
kD1 kD1
If the weight wij is decomposed in the x domain into shifted Gaussians of the
same variance 2 then, in the frequency domain, wij is analyzed in a superposition
of filters, which have a shape similar to the one given in Fig. 11.4b.
Rayleigh’s theorem states that the energy of a signal f .x/ x 2 Œ1; C1 is
R C1
given by 1 f 2 .x/dx. Equivalently, using the Fourier transform F .s/ of f .x/, the
R C1
energy is given by 1 F 2 .s/ds. The energy distribution of a particle is proportional
to the probability j .wij /j2 of finding the particle between wij and wij C wij .
Therefore, the energy of the particle will be given by the integral of the squared
Fourier transform j O .f /j2 . The energy spectrum of the weights of the quantum
associative memories is depicted in Fig. 11.4b.
11.3.3 Stochastic weights and the Principle of Uncertainty
The significance of Eq. (11.39) is that the product between the information in the
space domain g.wij / and the information in the frequency domain G.s/ cannot be
wij 2
smaller than a constant. In the case of a Gaussian function g.wij / D e 2 2 with
1 2 2
Fourier transform G.s/ D e 2 s it can be observed that: (a) if is small, then
g.wij / has a pick at wij D 0 while G.s/ tends to become flat, (b) if is large, then
g.wij / is flat at wij D 0 while G.s/ makes a peak at s D 0.
w2ij

This becomes more clear if the dispersion of function g.wij / D e round 2 2
wij D 0 is used [139]. The dispersion of g.wij / and of its Fourier transform G.s/
becomes
w2ij
R C1 21
1 w2ij e 2 d wij
D.g/ D w2
D 12 2
R C1 2 ij2
1 e d wij (11.40)
R C1 2 2 s ds
1 2 2
1 s e
D.G/ D R C1 1 s 2 2 D 1
2 2
1 e ds
2
which results into the uncertainty principle for the weights of quantum associative
memories
1
D.g/D.G/ D : (11.41)
4
Equation (11.41) means that the accuracy in the calculation of the weight wij
is associated with the accuracy in the calculation of its spectral content. When
the spread of the Gaussians of the stochastic weights is large (small) then their
spectral content is poor (rich). Equation (11.41) is an analogous of the quantum
mechanics uncertainty principle, i.e. xp „, where x is the uncertainty in the
measurement of particle’s position, p is the uncertainty in the measurement of the
particle’s momentum, and „ is Planck’s constant.
It should be noted that (11.41) expresses a general property of the Fourier
transform and that similar relations can be found in classical physics. For instance,
in electromagnetism it is known that it is not possible to measure with arbitrary
precision, at the same time instant, the variation of a wave function both in the
time and frequency domain. What is really quantum in the previous analysis is the
association of a wave function with a particle (stochastic weight) and the assumption
that the wave length and the momentum of the particle satisfy the relation p D „k
with jkj D 2
.
11.4 Conclusions
Spectral analysis of the weights of that follow the QHO model was based on previ-
ous studies of wavelets’ energy spectrum. Spectral analysis of quantum associative
memories has shown that: (a) The Gaussian basis functions of the weights express
the distribution of the energy with respect to the weights’ value. The smaller the
spread of the basis functions is, the larger becomes the spectral (energy) content that
can be captured therein. Narrow spread of the basis functions results in wide range
of frequencies of the Fourier transformed pulse, (b) The stochastic weights satisfy an
equation which is analogous to the principle of uncertainty. Through numerical and
simulation tests it has been confirmed that the representation of the basis functions
in the space and in the frequency domain cannot be, in both cases, two sharply
localized.
Chapter 12
Neural Networks Based on the Eigenstates
of the Quantum Harmonic Oscillator
Abstract The chapter introduces feed-forward neural networks where the hidden
units employ orthogonal Hermite polynomials for their activation functions. These
neural networks have some interesting properties: (a) the basis functions are
invariant under the Fourier transform, subject only to a change of scale, (b) the
basis functions are the eigenstates of the quantum harmonic oscillator (QHO),
and stem from the solution of Schrödinger’s harmonic equation. The proposed
neural networks have performance equivalent to wavelet networks and belong to
the general category of nonparametric estimators. They can be used for function
approximation, system modelling, image processing and fault diagnosis. These
neural networks demonstrate the particle-wave nature of information and give the
incentive to analyze significant issues related to this dualism, such as the principle
of uncertainty and Balian–Low’s theorem.
12.1 Overview
Feed-forward neural networks (FNN) are the most popular artificial neural struc-
tures due to their structural flexibility, good representational capabilities, and
availability of a large number of training algorithms. The hidden units in an FNN
usually have the same activation functions and are often selected as sigmoidal
functions or Gaussians. This chapter presents FNN that use orthogonal Hermite
polynomials as basis functions. The proposed neural networks have some interesting
properties: (a) the basis functions are invariant under the Fourier transform, subject
only to a change of scale (b) the basis functions are the eigenstates of the quantum
harmonic oscillator (QHO), and stem from the solution of Schrödinger’s diffusion
equation. The proposed neural networks belong to the general category of nonpara-
metric estimators and are suitable for function approximation, image processing,
and system fault diagnosis. Two-dimensional QHO-based neural networks can be
also constructed by taking products of the one-dimensional basis functions.

222 12 Neural Networks Based on the Eigenstates of the Quantum Harmonic Oscillator
FNN that use the eigenstates of the quantum harmonic oscillator (Hermite
basis functions) demonstrate the particle-wave nature of information as described
by Schrödinger’s diffusion equation [34, 186]. Attempts to enhance connectionist
neural models with quantum mechanics properties can be also found in [96, 135–
137]. The proposed FNNs extend previous results on neural structures compatible
with quantum mechanics postulates, given in [149, 163, 164, 168].
Through the analysis given in this chapter, it is shown that the input variable x
of the neural network can be described not only by crisp values (particle equivalent)
but also by the normal modes of a wave function (wave equivalent). Since the
basis functions of the proposed FNN are the eigenstates of the quantum
Pn harmonic
oscillator, the FNN’s output will be the weighted sum .x/ D iD1 wk k .x/,
where j .x/j2 is the probability that the input of the neural network (quantum
particle equivalent) is found between x and x C x. Thus, the weight wk provides
a measure of the probability to find the input on the neural network in the region
associated with the eigenfunction k .x/.
Furthermore, issues related to the uncertainty principle are examined in case
of the QHO-based neural network. An expression of the uncertainty principle for
Hermite basis functions is given. The uncertainty principle is a measure of the
time-frequency localization of the activation functions in the QHO-based neural
network and evaluates the degradation of localization when successive elements of
these orthonormal basis functions are considered. It is shown that the Hermite basis
functions as well as their Fourier transforms cannot be uniformly concentrated in
the time-frequency plane [89, 141]. Simulation results support this argument.
12.2 Feed-Forward Neural Networks
FNN serve as powerful computational tools, in a diversity of applications including

function approximation, image compression, and system fault diagnosis. When
equipped with procedures for learning from measurement data they can generate
models of unknown systems. FNN are the most popular artificial neural structures
due to their structural flexibility, good representational capabilities, and availability
of a large number of training algorithms.
The idea of function approximation with the use of FNN comes from generalized
Fourier series. It is known that any function .x/ in an L2 space can be expanded
in a generalized Fourier series in a given orthonormal basis, i.e.
1
X
.x/ D ck k .x/; axb (12.1)
kD1
12.2 Feed-Forward Neural Networks 223
a b
Fig. 12.1 (a) Feed-forward neural network (b) Quantum neural network with Hermite basis
functions
Truncation of the series yields in the sum
X
M
SM .x/ D ak k .x/ (12.2)
kD1
If the coefficients ak are taken to be equal to the generalized Fourier coefficients,

Rb
i.e. when ak D ck D a .x/ k .x/dx, then Eq. (12.2) is a mean square optimal
approximation of .x/.
Unlike generalized Fourier series, in FNN the basis functions are not necessarily
orthogonal. The hidden units in an FNN usually have the same activation functions
and are often selected as sigmoidal functions or gaussians. A typical feed-forward
neural network consists of n inputs xi ; i D 1; 2; ; n, a hidden layer of m neurons
with activation function h W R ! R and a single output unit (see Fig. 12.1a). The
FNN’s output is given by
!
X
n X
n
.x/ D cj h wji xi C bj (12.3)
j D1 iD1
The root mean square error in the approximation of function .x/ by the FNN
is given by
v
u
u1X N
ERMS Dt . .x k / O .x k //2 (12.4)
N
kD1
where x k D Œx1k ; x2k ; ; xnk is the k-th input vector of the neural network. The
activation function is usually a sigmoidal function h.x/ D 1Ce1 x while in the case
of radial basis functions networks it is a Gaussian [78]. Several learning algorithms
for neural networks have been studied. The objective of all these algorithms is to
find numerical values for the network’s weights so as to minimize the mean square
error ERMS of Eq. (12.4). The algorithms are usually based on first and second order
gradient techniques. These algorithms belong to: (a) batch-mode learning, where to
perform parameters update the outputs of a large training set are accumulated and
the mean square error is calculated (back-propagation algorithm, Gauss–Newton
method, Levenberg–Marquardt method, etc.), (b) pattern-mode learning, in which
training examples are run in cycles and the parameters update is carried out each
time a new datum appears (Extended Kalman Filter algorithm).
12.3 Eigenstates of the Quantum Harmonic Oscillator
FNN with Hermite basis functions (see Fig. 12.1b) show the particle-wave nature of
information, as described by Schrödinger’s diffusion equation, i.e.
„ 2
i„@ .x;t/
@t
D 2m r 2 .x; t / C V .x/ .x; t / ) i „ @ .x;t/
@t
D H .x; t / (12.5)
where „ is Planck’s constant, H is the Hamiltonian, i.e. the sum of the potential
„2 2 „2 @2
V .x/ and of the Laplacian 2m r D 2m @x 2
. The probability density function
j .x; t /j2 gives the probability at time instant t the input x of the neural network
(quantum particle equivalent) to have a value between x and x C x. The general
solution of the quantum harmonic oscillator, i.e. of Eq. (12.5) with V .x/ being a
parabolic potential, is [34, 186]:
D Hk .x/e x e i.2kC1/t k D 0; 1; 2;
2 =2
k .x; t / (12.6)
where Hk .x/ are the associated Hermite polynomials. In case of the quantum har-
monic oscillator, the spatial component X.x/ of the solution .x; t / D X.x/T .t / is
Xk .x/ D Hk .x/e x
2 =2
k D 0; 1; 2; (12.7)
Eq. (12.7) satisfies the boundary condition limx!˙1 X.x/ D 0. From the above
x2
it can be noticed that the Hermite basis functions Hk .x/e 2 are the eigenstates of
the quantum harmonic oscillator (see Fig. 12.2). The general relation for the Hermite
polynomials is
d .k/
e x
2 2
Hk .x/ D .1/k e x .k/
(12.8)
dx
12.4 Neural Networks Based on the QHO Eigenstates 225
a b
Hermite basis functions 2D Hermite basis function
1
0.8
0.6 1
0.4
0.5
0.2
Basis 2
0
H(x)
−0.2 −0.5
−0.4
−1
10
−0.6
5 10
−0.8 0 5
−5 0
−1 −5
−10 −8 −6 −4 −2 0 2 4 6 8 10 y −10 −10 x
x
Fig. 12.2 (a) First five one-dimensional Hermite basis functions (b) 2D Neural Network based on
the QHO eigenstates: basis function B1;2 .x; ˛/
According to Eq. (12.8) the first five Hermite polynomials are:
H0 .x/ D 1 for D 1; a1 D a2 D 0; H1 .x/ D 2x for D 3; a0 D a3 D 0

H2 .x/ D 4x 2 2 for D 5; a1 ; a4 D 0; H3 .x/ D 8x 3 12x for D 7; a0 ; a5 D0
H4 .x/ D 16x 4 48x 2 C 12 for D 9; a1 ; a6 D 0
It is known that Hermite polynomials are orthogonal [186]. Other polynomials

with the property of orthogonality are: Legendre polynomials, Chebychev polyno-
mials, and Laguerre polynomials [215, 217].
12.4 Neural Networks Based on the QHO Eigenstates
12.4.1 The Gauss–Hermite Series Expansion
The following normalized basis functions can now be defined [143]:
1 1 x2
k .x/ D Œ2k 2 kŠ 2 Hk .x/e 2 ; k D 0; 1; 2; (12.9)
where Hk .x/ is the associated Hermite polynomial. To succeed multi-resolution

analysis Hermite basis functions of Eq. (12.9) are multiplied with the scale coeffi-
cient ˛. Thus the following basis functions are derived
1
ˇk .x; ˛/ D ˛ 2 k .˛
1
x/ (12.10)
where ˛ is a characteristic scale. The abovementioned basis functions have an input

range from 1 to C1. The basis functions of Eq. (12.10) also satisfy orthogonality
condition, i.e.
R C1
1 ˇm .x; ˛/ˇk .x; ˛/dx D ımk ; (12.11)
where ımk is the Kronecker delta symbol [143]. Any continuous function f .x/; x 2
R can be written as a weighted sum of the above orthogonal basis functions, i.e.
1
X
f .x/ D ck ˇk .x; ˛/ (12.12)
kD0
The expansion of f .x/ using Eq. (12.12) is a Gauss–Hermite series. It holds

that the Fourier transform of the basis function k .x/ of Eq. (12.9) satisfies the
relation [143]
k .s/ D j n k .s/ (12.13)
while for the basis functions ˇk .x; ˛/ of Eq. (12.10), it holds that the associated
Fourier transform is
Bk .s; ˛/ D j n ˇk .s; ˛ 1 / (12.14)
Therefore, it holds
P1 F P
f .x/ D kD0 ck ˇk .x; ˛/ F .s/ D 1 n 1
kD0 ck j ˇk .s; ˛ / (12.15)
!
which means that the Fourier transform of Eq. (12.12) is the same as the initial
function , subject only to a change of scale.
12.4.2 Neural Networks Based on the Eigenstates

of the 2D Quantum Harmonic Oscillator
FNN with Hermite basis functions of two variables can be constructed by taking
products of the one-dimensional basis functions Bk .x; ˛/ [143]. Thus, setting x D
Œx1 ; x2 T one can define the following basis functions
1
Bk1 ;k2 .x; ˛/ D Bk .x1 ; ˛/Bk2 .x2 ; ˛/ (12.16)
˛ 1
12.4 Neural Networks Based on the QHO Eigenstates 227
a 2D Hermite basis function b 2D Hermite basis function
1 1
0.5 0.5
Basis 11
Basis 13
0 0
−0.5 −0.5
−1 −1
10 10
5 10 5 10
5 5
0 0
0 0
y −5 y −5
−5 −5 x
x
−10 −10 −10 −10
Fig. 12.3 2D Neural Network based on the QHO eigenstates: (a) basis function B3;3 .x; ˛/ (b)
basis function B4;1 .x; ˛/
These two-dimensional basis functions are again orthonormal, i.e. it holds

Z
d 2 xBn .x; ˛/Bm .x; ˛/ D ın1 m1 ın2 m2 (12.17)
The basis functions Bk1 ;k2 .x/ are the eigenstates of the two-dimensional harmonic
oscillator, which is a generalization of Eq. (12.5). These basis functions form
a complete basis for integrable functions of two variables. A two-dimensional
function f .x/ can thus be written in the series expansion:
1
X
f .x/ D ck Bk1 ;k2 .x; ˛/ (12.18)
k1 ;k2
The choice of an appropriate scale coefficient ˛ and of the maximum order

k1max ; k2max is a practical issue. Indicative basis functions B1;2 .x; ˛/, B3;3 .x; ˛/ and
B4;1 .x; ˛/ of a 2D feed-forward quantum neural network are depicted in Fig. 12.2b,
and Fig. 12.3a,b, respectively.
Remark. The significance of the results of Sect. 12.4 is summarized in the sequel:
(i) Orthogonality of the basis functions and invariance under the Fourier trans-
form, (subject only to a change of scale): this means that the energy distribution
in the proposed neural network can be estimated without moving to the
frequency domain. The values of the weights of the neural network provide
a measure of how energy is distributed in the various modes ˇk .x; ˛/ of the
signal that is approximated by the neural network.
(ii) The basis functions of the neural network are the eigenstates of the quantum
harmonic oscillator: this means that the proposed neural network can capture
the particle-wave nature of information. The input variable x is viewed not
only as a crisp value (particle equivalent) but is also distributed to the normal
modes of a wave function (wave equivalent).
(iii) The basis functions of the neural network have different frequency charac-
teristics, which means that the QHO-based neural network is suitable for
multi-resolution analysis.
12.5 Uncertainty Principles for the QHO-Based Neural

Networks
12.5.1 Uncertainty Principles for Bases and the Balian–Low

Theorem
Overcoming limitations of existing image processing approaches is closely related

to the harnessing of uncertainty principle [94]. A brief description of Heisenberg’s
principle of uncertainty is first given. The position of a quantum particle, i.e. of a
particle the motion of which is subject to Schrödinger’s equation is defined by x
while its momentum is denoted by p. As explained in Chap. 11, it holds
xp„ (12.19)
where „ is Planck’s constant. The interpretation of Eq. (12.19) is as follows: it is

impossible to define at a certain time instant both the position and the momentum
of the particle with arbitrary precision. When the limit imposed by Eq. (12.19) is
approached, the increase of the accuracy of the position measurement (decrease of
x) implies a decrease in the accuracy of the momentum measurement (increase of
p) and vice-versa.
The uncertainty principle in harmonic analysis is a class of theorems which state
that a function and its Fourier transform cannot be both too sharply localized. The
uncertainty principle can be seen not only as a statement about the time-frequency
localization of a single function but also as a statement on the degradation of
localization when one considers successive elements of a set of basis functions [71].
This means that the elements of a basis as well as their Fourier transforms cannot
be uniformly concentrated in the time-frequency plane [24, 111].
First, a formulation of the uncertainly principle in the case of Gabor frames will
be given, through the Balian–Low theorem. A Gabor function gnm ; n; m 2 Z is
defined as (see, for instance, Fig. 11.2b):
gmn .x/ D e imf0 x g.x nb0 /; n; m; 2 Z (12.20)

12.5 Uncertainty Principles for the QHO-Based Neural Networks 229
A Gabor frame is a set of functions gmn .x/ that can be a basis of the L2 space.
The Gabor frame depends on two positive and bounded numbers b0 and f0 and on a
function g, which has compact support is contained in an interval of length 2 [191].
P f0
If there exist two real constants C1 and C2 such that 0 < C1 jg.x nb0 /j C2 <
2
1, then the family of Gabor functions gmn ; n; m; 2Z is a frame in L2 .R/, with

bounds 2 Cf0
1
and 2 C
f0
2
.
The Balian–Low theorem describes the behavior of Gabor frames at the critical
frequency f0 defined by b0 f0 D 2. The theorem is a key result in time-frequency
analysis. It expresses the fact that time-frequency concentration and non-redundancy
are incompatible properties for Gabor frames of Eq. (12.20). Specifically, if for some
˛ > 0 and g2L2 .R/ the set fe 2lx=˛ g.x k˛/gk;l2Z 2 is an orthonormal basis for
L2 .R/, then
Z Z
jxg.x/j2 dx jf g.f
O /j2 df D1 (12.21)
R R
This means thatRfor a Gabor frame which is contracted from the function g.x/ one
has necessarily
R x 2 jg.x/j2 dx D 1 (which means not fine localizaton on the space
axis x) or f 2 jg.f
O /j2 df D 1 (which means not fine localization on the frequency
axis f ).
In Sect. 11.3 a practical view of the application of the uncertainty principles to
wavelets (which generalize Gabor functions) has been presented.
12.5.2 Uncertainty Principles for Hermite Series
For a function k .x/2L2 .R/ the mean . k/ and the variance 2 . k/ are defined
as follows [89]:
R R
. k/ D xj k .x/j
2
dx; 2 . k/ D jx . k /j
2
j k .x/j
2
dx (12.22)
The Hermite basis functions k .x/ were defined in Eq. (12.6), while the Her-
mite polynomials Hk .x/ were given in Eq. (12.8). The Hermite functions are an
orthonormal basis for L2 .R/. It was also shown that Hermite functions are the
eigenfunctions of the solution of Schrödinger’s equation, and remain invariant
under Fourier transform, subject only to a change of scale as given in Eq. (12.13),
i.e. k .s/ D j n k .s/. Furthermore, the mean-dispersion principle provides an
expression of the uncertainty principle for orthogonal series [89]. This states that
there does not exist an infinite orthonormal sequence f k g1kD0 L , such that all
2
four of . k /, .k /, . k / and .k / are uniformly bounded.

Using Eq. (12.22) for the Hermite basis functions one obtains . k / D .k / D
0, and 2 . k / D 2 .k / D 2kC1 4
which quantifies the results of the mean-
dispersion principle and formulates an uncertainty principle for Gauss–Hermite
basis functions (Fig. 12.4).
a b
1st Hermite basis functions 2nd Hermite basis functions 3 3
1 1
2 2
0.5 0.5 1 1
0 0
H(x)
H(x)
0 0
−1 −1
−0.5 −0.5 −2 −2
−3 −3
−1 −1 0 50 100 150 200 0 50 100 150 200
−10 −5 0 5 10 −10 −5 0 5 10
x x (a) (b)
3rd Hermite basis functions 4th Hermite basis functions

3 3
1 1
2 2
0.5 0.5
1 1
H(x)
H(x)
0 0 0 0
−1 −1
−0.5 −0.5
−2 −2
−1 −1 −3 −3
−10 −5 0 5 10 −10 −5 0 5 10 0 50 100 150 200 0 50 100 150 200
x x (c) (d)
Fig. 12.4 (a) The first four modes of the Hermites series expansion (b) Fourier transform of the
basic mode of the Hermite expansion assuming the following variances: (a) 3 2 , (b) 5 2 , (c) 10 2 ,
(d) 25 2
12.6 Multiscale Modelling of Dynamical System
The performance of neural networks that use the eigenstates of the quantum
harmonic oscillator as basis functions is compared to the performance of one hidden
layer FNN with sigmoidal basis functions (OHL-FNN), as well as to Radial Basis
Function (RBF) neural networks with Gaussian activation functions. It should be
noted that the sigmoidal basis functions
.x/ D 1Cexp.x/ 1
in OHL-FNN and
the Gaussian basis functions in RBF do not satisfy the property of orthogonality.
Unlike this, neural networks with Hermite basis functions use the orthogonal
eigenfunctions of the quantum harmonic oscillator which are given in Eq. (12.10).
In the sequel neural networks with Hermite basis functions, one hidden layer
FNN with sigmoidal basis functions and RBF neural networks with Gaussian
functions are used to approximate function yk D f .xk / C vk , where vk is a noise
sequence, independent from xk ’s. The obtained results are depicted in Fig. 12.5
to Fig. 12.14. The training pairs were xk ; ykd . Root mean square error, defined as
q
P d 2
RMSE D N1 N k1 .yk yk / , gives a measure of the performance of the neural
networks.
In the case of RBF and of neural networks with Hermite basis functions, training
affects only the output weights, and can be performed with second order gradient
algorithms. However, since the speed of convergence is not the primary objective
of this study, the LMS (Least Mean Square) algorithm is sufficient for training. In
the case of the OHL-FNN with sigmoidal basis functions, training concerns weights
of both the hidden and output layer and is carried out using the back-propagation
12.6 Multiscale Modelling of Dynamical System 231
2
y, yd
−2
−4
−6
−8
−10 −8 −6 −4 −2 0 2 4 6 8 10
x
Fig. 12.5 Approximation of the test function of Eq. (12.23) (dashed line), using a feed-forward
neural network with Hermite basis functions
2
f(x)
−2
−4
−6
−8
−10 −8 −6 −4 −2 0 2 4 6 8 10
iterations
Fig. 12.6 Approximation of the test function of Eq. (12.23) (dashed line), using a one hidden layer
FNN with sigmoidal basis functions
algorithm [78]. Alternatively, second order (Newton) training methods can be used
[118].
The following test functions are examined (dashed red lines):
2
y, yd
−2
−4
−6
−8
−10 −8 −6 −4 −2 0 2 4 6 8 10
x
Fig. 12.7 Approximation of the test function of Eq. (12.23) (dashed line), using an RBF neural
network with Gaussian basis functions
0.6
0.4
0.2
0
y, yd
−0.2
−0.4
−0.6
−0.8
−10 −8 −6 −4 −2 0 2 4 6 8 10
x
1. Test function 1 given in Eq. (12.23) over the domain D D Œ10; 10:
f .x/ D 0:5 cos.x=2/ C 0:3 sin.x=2/ (12.23)
0.6
0.4
0.2
0
f(x)
−0.2
−0.4
−0.6
−0.8
−10 −8 −6 −4 −2 0 2 4 6 8 10
iterations
Fig. 12.9 Approximation of the test function of Eq. (12.24) (dashed line), using a one hidden layer
FNN with sigmoidal basis functions
0.6
0.4
0.2
0
y, yd
−0.2
−0.4
−0.6
−0.8
−10 −8 −6 −4 −2 0 2 4 6 8 10
x
f .x/ D
2:186x 12:864; 10x < 2
(12.24)
4:246x; 2x < 0
10e .0:05xC0:5/ sinŒ.0:001x C 0:05/x; 0x10
10
2
y, yd
−2
−4
−6
−8
−10
−10 −8 −6 −4 −2 0 2 4 6 8 10
x
10
2
f(x)
−2
−4
−6
−8
−10
−10 −8 −6 −4 −2 0 2 4 6 8 10
iterations
Fig. 12.12 Approximation of the test function of Eq. (12.25) (dashed line), using a one hidden
layer FNN with sigmoidal basis functions
f .x/ D 20:5e .0:3jxj/ sin.0:03x/ cos.0:7x/ (12.25)
4. Test function 4 given in Eq. (12.26) over the domain D D Œ10; 10 Œ10; 10:
f .x; y/ D sin.0:3x/ sin.0:3y/e .0:1jyj/ (12.26)
The approximation results for the 2D function of Eq. (12.26), obtained by an

NN with Hermite basis functions are shown in Fig. 12.15. The approximation
10
2
y, yd
−2
−4
−6
−8
−10
−10 −8 −6 −4 −2 0 2 4 6 8 10
x
1.5
0.5
f(x,y)
−0.5
−1
−1.5
10
5 10
0 5
y 0
−5 x
−5
−10 −10
Fig. 12.14 Test function of Eq. (12.26)
of the test function obtained by a one hidden layer FNN with sigmoidal basis
functions is shown in Fig. 12.16. Finally the approximation achieved by RBF
neural network with Gaussian activation functions is depicted in Fig. 12.17.
5. Test function 5 given in Eq. (12.27) over the domain D D Œ10; 10 Œ10; 10
(Fig. 12.18):
2 0:02y 2 /
f .x; y/ D 1:9e .0:02x tanh.0:3y/ (12.27)
The approximation results for the 2D function of Eq. (12.27), obtained by an

NN with Hermite basis functions, are depicted in Fig. 12.19. The approximation
1.5
0.5
f(x,y)
−0.5
−1
−1.5
10
5 10
5
0
0
−5
−5
y −10 −10 x
Fig. 12.15 Approximation of the test function of Eq. (12.26), using a feed-forward neural network
with Hermite basis functions
1.5
0.5
f(x,y)
−0.5
−1
−1.5
10
5 10
5
0
0
y −5
−5
x
−10 −10
Fig. 12.16 Approximation of the test function of Eq. (12.26), using a one hidden layer FNN with
sigmoidal basis functions
obtained by a one hidden layer FNN with sigmoidal basis functions is shown in
Fig. 12.20. Finally the approximation achieved by an RBF neural network with
Gaussian activation functions is given in Fig. 12.21.
1.5
0.5
f(x,y)
−0.5
−1
−1.5
10
5 10
5
0
0
y −5
−5
x
−10 −10
Fig. 12.17 Approximation of the test function of Eq. (12.26), using an RBF neural network with
Gaussian basis functions
0.8
0.6
0.4
0.2
f(x,y)
−0.2
−0.4
−0.6
−0.8
10
5 10
5
0
0
y −5
−5
x
−10 −10
Fig. 12.18 Test function of Eq. (12.27)
Table 12.1 demonstrates the final RMSE values, succeeded by neural networks
with Hermite basis functions (Hermite-FNN), the one hidden layer FNN with
sigmoidal basis functions (OHL-FNN) and the RBF with Gaussian activation
functions, after 50 epochs.
From Table 12.1, it is observed that in function approximation problems, neural
networks with Hermite basis functions perform at least as well as one hidden layer
FNN with sigmoidal activation functions (OHL-FNN) and RBF with Gaussian
activation functions. As expected, the number of nodes of the hidden layer of the
OHL-FNN and the variance of the Gaussian basis functions of the RBF affect the
quality of function approximation. In the case of 1D functions Hermite-based neural
0.8
0.6
0.4
0.2
f(x,y)
−0.2
−0.4
−0.6
10
5 10
5
0
0
y −5
−5 x
−10 −10
Fig. 12.19 Approximation of the test function of Eq. (12.27), using a feed-forward neural network
with Hermite basis functions
0.8
0.6
0.4
0.2
f(x,y)
−0.2
−0.4
−0.6
10
5 10
5
0
0
y
−5
−5
x
−10 −10
Fig. 12.20 Approximation of the test function of Eq. (12.27), using a one hidden layer FNN with
sigmoidal basis functions
networks and OHL-FNN succeed better approximation than RBF. In the case of
the 2D functions, the performance of OHL-FNN improved when more nodes were
added to the hidden layer, while the performance of RBF improved when the spread
of the gaussians was increased.
12.7 Applications to Image Compression 239
0.8
0.6
0.4
0.2
f(x,y)
−0.2
−0.4
−0.6
−0.8
10
5 10
5
0
y 0
−5
−5
x
−10 −10
Fig. 12.21 Approximation of the test function of Eq. (12.27), using an RBF neural network with
Gaussian basis functions
Table 12.1 Evaluation of Function FNN type Num nodes RMSE

NN with Hermite basis
functions Hermite 6 0.613
Eq. (12.23) OHL-FNN 6 0.187
RBF 6 0.223
Hermite 6 0.034
Eq. (12.24) OHL-FNN 6 0.059
RBF 6 0.373
Hermite 6 0.726
Eq. (12.25) OHL-FNN 6 0.339
RBF 6 1.565
Hermite 16 0.047
Eq. (12.26) OHL-FNN 16 0.121
RBF 16 0.050
Hermite 16 0.032
Eq. (12.27) OHL-FNN 16 0.117
RBF 16 0.028
12.7 Applications to Image Compression
The suitability of NN based on the QHO eigenstates for function approximation

and system modelling has been evaluated in [164], using the benchmark tests
given in [221]. Here, the image compression capabilities of FNN with Hermite
basis functions will be evaluated. Regarding the structure of FNN used for image
compression, the hidden layer has fewer nodes than the input layer, and the hidden
layer output values are considered as the compressed image (see Fig. 12.22a). In
order to reconstruct the compressed image, the weights between the nodes of the
hidden and the output layer are also transmitted. If the number of the output values
Fig. 12.22 (a) A one hidden layer FNN for image compression, having n neurons at the input and
output layer and m neurons at the hidden layer (m < n) (b) Image compression using a one hidden
layer FNN: the image is divided into square blocks that become input training patterns to the NN
for all the nodes of the hidden layer, plus the weights between the hidden and the
output layer, is less than the total number of pixels of the image, compression is
achieved. The fewer the number of units in the middle layer, the higher the degree
of compression [117, 118].
In FNN-based image compression, an image of size L L pixels is first divided
L2
into P square blocks of equal size Mb Mb . The total number of blocks is P D M 2.
b
Each square block is then arranged into a vector of dimension n 1, i.e. n D Mb2 ,
that is fed to the neural network as an input training pattern. All such vectors are
12.7 Applications to Image Compression 241
Fig. 12.23 (a) Lena image used in image compression tests (b) Reconstructed Lena image
achieved by a one hidden layer FNN with sigmoidal basis functions
Fig. 12.24 (a) Reconstructed Lena image achieved by an FNN with Hermite basis functions,
(b) Boats image used in image compression tests
put together to form a training matrix X of size n P . The target matrix D for the
training of the neural net is considered to be the same as the input matrix X . The
structure of an FNN for image compression is depicted in Fig. 12.22b. To quantify
the quality of the reconstructed image, the compression ratio can be used, which
in a simple form is expressed as:
LL
D (12.28)
mP Cmn
Fig. 12.25 (a) Reconstructed Boats image achieved by a one hidden layer FNN with sigmoidal
basis functions, (b) Reconstructed Boats image achieved by an FNN with Hermite basis functions
where the first term in the denominator is the number of outputs of the hidden layer
with respect to all input patterns, and the second term is the number of the output
weights.
In the sequel the image compression performed by FNN with Hermite basis
functions is compared to the compression achieved by an FNN with sigmoidal
activation functions. The hidden layer nodes of the FNN with Hermite basis
functions contains the first 4 eigenstates of the quantum harmonic oscillator given
in Eq. (12.10). Both neural structures consist of 16 nodes at the input layer, 4 nodes
at the hidden layer, and 16 nodes at the output layer.
Tests are performed on two benchmark images, Lena and Boats. Both images are
of size 512512 pixels and the block size is selected as 44. Using Eq. (12.28), the
compression ratio achieved by the examined neural structures is found to be '4.
The reconstructed Lena images are depicted in Fig 12.23a,b and in Fig. 12.24a.
The reconstructed Boats images are depicted in Fig 12.24b and in Fig. 12.25a,b,
respectively.
12.8 Applications to Fault Diagnosis
12.8.1 Signals Power Spectrum and the Fourier Transform
It will be shown that neuronal networks using as activation functions the QHO
eigenstates can be also used in fault diagnosis tasks. Apart from time-domain
approaches to fault diagnosis, one can use frequency-domain methods to find out
12.8 Applications to Fault Diagnosis 243
the existence of a fault in a system under monitoring [17,222,223]. Thus to conclude

if a dynamical system has been subjected to fault of its components, information
coming from the power spectrum of its outputs can be processed. To find the spectral
density of a signal .t / with the use of its Fourier transform .j!/, the following
definition is used:
R C1 R
1 C1
R C1
E D . .t //2 dt D 2 .t /. 1 .j!/e j!t d!/dt i.e.
1 R
1 C1
1 (12.29)
E D 2 1 .j!/ .j!/d!
Taking that .t / is a real signal it holds that .j!/ D .j!/ which is the
signal’s complex conjugate. Using this in Eq. (12.29) one obtains
R
1 C1
E D 2 1 R .j!/ .j!/d! or
C1 (12.30)
E D 2 1
1 j .j!/j d!
2
1
This means that the energy of the signal is equal to 2 times the integral over
frequency of the square of the magnitude of the signal’s Fourier transform. This
is Parseval’s theorem. The integrated term j .j!/j2 is the energy density per unit
of frequency and has units of magnitude squared per Hertz.
12.8.2 Power Spectrum of the Signal Using

the Gauss–Hermite Expansion
As shown in Eqs. (12.11) and (12.17) the Gauss–Hermite basis functions satisfy the
orthogonality property, i.e. for these functions it holds
Z C1
1 if m D k
m .x/ k .x/dx D
1 0 if m¤k
Therefore, using the definition of the signal’s energy one has

R C1 R C1 PN
ED 1 . .t //2 dt D 1 Œ kD1 ck
2
k .t / dt (12.31)
and exploiting the orthogonality property one obtains

PN
ED 2
kD1 ck (12.32)
Therefore the square of the coefficients ck provides an indication of the distribution

of the signal’s energy to the associated basis functions. One could arrive at the
same results using the Fourier transformed description of the signal and Parseval’s
theorem. It has been shown that the Gauss–Hermite basis functions remain invariant
under the Fourier transform subject only to a change of scale. Denoting by .j!/
the Fourier transformed signal of .t / and by k .j!/ the Fourier transform of the
k-th Gauss–Hermite basis function one obtains
PN
.j!/ D kD1 ck k .j!/ (12.33)
and the energy of the signal is computed as

R
1 C1
E D 2 1
j .j!/j2 d! (12.34)
Substituting Eqs. (12.33) into (12.34) one obtains

R
1 C1 PN
E D 2 1
j kD1 ck k .j!/j2 d! (12.35)
and using the invariance of the Gauss–Hermite basis functions under Fourier
transform one gets
R
1 C1 PN 1
E D 2 1
j kD1 ck ˛ 2 k .˛
1
j!/j2 d! (12.36)
while performing the change of variable !1 D ˛ 1 ! it holds that

R
1 C1 PN 1
E D 2 1
j kD1 ck ˛ 2 k .j!1 /j
2
d !1 (12.37)
Next, by exploiting the orthogonality property of the Gauss–Hermite basis functions

one gets that the signal’s energy is proportional to the sum of the squares of the
coefficients ck which are associated with the Gauss–Hermite basis functions, i.e. a
relation of the form
P
E D N 2
kD1 ck (12.38)
12.8.3 Detection of Changes in the Spectral Content

of the System’s Output
The thermal model of a system, i.e. variations of the temperature output signal, has
been identified considering the previously analyzed neural network with Gauss–
Hermite basis functions. As shown in Figs. 12.26 and 12.27, thanks to the multi-
frequency characteristics of the Gauss–Hermite basis functions, such a neural model
can capture with increased accuracy spikes and abrupt changes in the temperature
profile [164, 167, 169, 221]. The RMSE (Root Mean Square Error) of training the
Gauss–Hermite neural model was of the order of 4 103 .
The update of the output layer weights of the neural network is given by a
gradient equation (LMS-type) of the form
wi .k C 1/ D wi .k/ e.k/
T .k/ (12.39)
12.8 Applications to Fault Diagnosis 245
a
100
90
80
estimated vs real output (C )
o
70
60
50
40
30
20
5 10 15 20
time (h)
b
100
90
estimated vs real output (Co)
80
70
60
50
40
30
20
10 20 30 40 50 60 70
time (h)
Fig. 12.26 Approximation of the system’s temperature output (red line) by a neural network with
Hermite polynomial basis functions (blue-line) (a) temperature’s time variation—profile 1 (b)
temperature’s time variation—profile 2
where e.k/ D y.k/ yd .k/ is the output estimation error at time instant k and
T .k/ is the regressor vector having as elements the values

.x.k// of the Gauss–
Hermite basis functions for input vector x.k/.
To approximate the temperature–signal’s variations described in a data set
consisting of 870 quadruplets of input–output data, a feed-forward neural network
with 3-D Gauss–Hermite basis functions has been used. The neural network
contained 64 nodes in its hidden layer.
a
100
90
80
70
60
50
40
30
20
10 20 30 40 50 60 70
time (h)
b
100
90
80
70
60
50
40
30
20
10 20 30 40 50 60 70
time (h)
Fig. 12.27 Approximation of the system’s temperature output (red line) by a neural network with
Hermite polynomial basis functions (blue-line) (a) temperature’s time variation—profile 3 (b)
temperature’s time variation—profile 4
The spectral components of the temperature signal for both the fault-free and
the under-fault operation of the system have been shown in Figs. 12.28, 12.29,
12.30, 12.31. It can be noticed that after a fault has occurred the amplitude of the
aforementioned spectral components changes and this can be a strong indication
about failure of the monitored system.
Obviously, the proposed spectral decomposition of the monitored signal, with
series expansion in Gauss–Hermite basis functions can be used for fault detection
tasks. As it can be seen in Figs. 12.28, 12.29, 12.30, 12.31, in case of failure,
the spectral components of the monitored signal differ from the ones which are
obtained when the system is free of fault. Moreover, the fact that certain spectral
components exhibit greater sensitivity to the fault and change value in a more abrupt
manner is a feature which can be exploited for fault isolation. Specific failures can
be associated with variations of specific spectral components. Therefore, they can
provide indication about the appearance of specific types of failures and specific
malfunctioning components.
a 1.4 b 0.4
difference in HST spectral components amplitude

0.35
1.2
HST spectral components amplitude
0.3
1
0.25
0.8 0.2
0.6 0.15
0.1
0.4
0.05
0.2
0
0 −0.05
0 10 20 30 40 50 60 0 10 20 30 40 50 60
q q
Fig. 12.28 Temperature’s time variation—profile 1: (a) Amplitude of the spectral components of
the temperature signal in the fault free case (red bar line) and when a fault had taken place (yellow
bar line) (b) differences in the amplitudes of the spectral components between the fault-free and
the faulty case (green bar line)
a 1.5 b 0.1
0.05
−0.05
1
−0.1
−0.15
−0.2
0.5
−0.25
−0.3
−0.35
0 −0.4
0 10 20 30 40 50 60 0 10 20 30 40 50 60
q q
Fig. 12.29 Temperature time variation—profile 2: (a) Amplitude of the spectral components of
12.9 Conclusions
In this chapter FNN that use the eigenstates of the quantum harmonic oscillator as
basis functions have been studied. The proposed neural networks have some inter-
esting properties: (a) the basis functions are invariant under the Fourier transform,
a 1.4 b 0.05

1.2 0
−0.05
1
−0.1
0.8
−0.15
0.6
−0.2
0.4
−0.25
0.2 −0.3
0 −0.35
0 10 20 30 40 50 60 0 10 20 30 40 50 60
q q
a 1.4 b 0.05
1.2 0
1 −0.05
0.8 −0.1
0.6 −0.15
0.4 −0.2
0.2 −0.25
0 −0.3
0 10 20 30 40 50 60 0 10 20 30 40 50 60
q q
subject only to a change of scale (b) the basis functions are the eigenstates of the
quantum harmonic oscillator, and stem from the solution of Schrödinger’s diffusion
equation. The proposed FNN belong to the general category of nonparametric
estimators and are suitable for function approximation, system modelling, and
image processing.
FNN that use Hermite basis functions demonstrate the particle-wave nature of
information as described by Schrödinger’s diffusion equation. It is considered that
the input variable x of the neural network can be described not only by crisp
values (particle equivalent) but also by the normal modes of a wave function (wave
equivalent). Since the basis functions are the eigenstates of the quantum harmonic
oscillator, thisP
means that the output of the proposed neural network is the weighted
sum .x/ D m kD1 wk k .x/ where j .x/j is the probability that the input of the
2
neural network (quantum particle equivalent) is found between x and x C x. The
weight wk provides a measure of the probability to find the input on the neural
network in the region of the patterns space associated with the eigenfunction k .x/.
Issues related to the uncertainty principle have been studied for the case of the
QHO-based neural networks. The uncertainty principle was presented first through
the Balian–Low theorem and next an expression of the uncertainty principle for
Hermite basis functions has been given. It was shown that the Gauss–Hermite basis
functions as well as their Fourier transforms cannot be uniformly concentrated in
the time-frequency plane.
In the simulation tests, FNN with Hermite basis functions were evaluated in
image compression problems. In this task the performance of FNN with Hermite
basis functions was satisfactory and comparable to the compression succeeded by
other neural structures, such as MLP or RBF networks. The fact that the basis
functions of the QHO-based neural networks contain various frequencies makes
them suitable for multi-resolution analysis.
Additionally, the use of FNN comprising as basis functions the eigenstates of
the QHO was tested in the problem of fault diagnosis. Faults could be diagnosed
by monitoring changes in the spectral content of a system and these in turn were
associated with the values of the weights of the neural network.
Chapter 13
Quantum Control and Manipulation of Systems
and Processes at Molecular Scale
Abstract Biological systems, at molecular level, exhibit quantum mechanical

dynamics. A question that arises is if the state of such systems can be controlled
by an external input such as an electromagnetic field or light emission (e.g., laser
pulses). The chapter proposes a gradient method for feedback control and stabi-
lization of quantum systems using Schrödinger’s and Lindblad’s descriptions. The
eigenstates of the quantum system are defined by the spin model. First, a gradient-
based control law is computed using Schrödinger’s description. Next, an estimate
of state of the quantum system is obtained using Lindblad’s differential equation.
In the latter case, by applying Lyapunov’s stability theory and LaSalle’s invariance
principle one can compute a gradient control law which assures that the quantum
system’s state will track the desirable state within acceptable accuracy levels. The
performance of the control loop is studied through simulation experiments for the
case of a two-qubit quantum system.
13.1 Basics of Quantum Systems Control
Recently, evidence has emerged from several studies that quantum coherence is
playing an important role in certain biological processes [95, 100, 107]. In [183] the
quantization of systems in the quantum theory and their functional roles in biology
has been analyzed. In [146] it has been shown that the electron clouds of nucleic
acids in a single strand of DNA can be modeled as a chain of coupled quantum
harmonic oscillators with dipole–dipole interaction between nearest neighbors.
Finally it has been shown that the quantum state of a single base (A, C.G. or T)
contains information about its neighbor, questioning the notion of treating individual
DNA bases as independent bits of information. The next question that arises is if the
state of such systems exhibiting quantum mechanical dynamics can be controlled
by an external input, such as electromagnetic field or light emission (e.g., laser
pulses). To this end this chapter analyzed the basics of quantum systems control and
proposes a systematic method for assuring stability in quantum control feedback
loops.

252 13 Quantum Control and Manipulation of Systems and Processes at Molecular Scale
The main approaches to the control of quantum systems are: (a) open-loop
control and (b) measurement-based feedback control [210]. In open-loop control,
the control signal is obtained using prior knowledge about the quantum system
dynamics and assuming a model that describes its evolution in time. Some open-
loop control schemes for quantum systems have been studied in [153,154]. Previous
work on quantum open-loop control includes flatness-based control on a single
qubit gate [41]. On the other hand, measurement-based quantum feedback control
provides more robustness to noise and model uncertainty [30]. In measurement-
based quantum feedback control, the overall system dynamics are described by
the estimation equation called stochastic master equation or Belavkin’s equation
[20]. An equivalent approach can be obtained using Lindblad’s differential equation
[210]. Several researchers have presented results on measurement-based feedback
control of quantum systems using the stochastic master equation or the Lindblad
differential equation, while theoretical analysis of the stability for the associated
control loop has been also attempted in several cases [18, 124, 203].
In this chapter, a gradient-based approach to the control of quantum systems
will be examined. Previous results on control laws which are derived through the
calculation of the gradient of an energy function of the quantum system can be
found in [4, 9, 155, 163]. Convergence properties of gradient algorithms have been
associated with Lyapunov stability theory in [22]. The chapter considers a quantum
system confined in a cavity that is weakly coupled to a probe laser. The spin model is
used to define the eigenstates of the quantum system. The dynamics of the quantum
model are described by Lindblad’s differential equation and thus an estimate of the
system’s state can be obtained. Using Lyapunov’s stability theory a gradient-based
control law is derived. Furthermore, by applying LaSalle’s invariance principle
it can be assured that under the proposed gradient-based control the quantum
system’s state will track the desirable state within acceptable accuracy levels. The
performance of the control loop is studied through simulation experiments for the
case of a two-qubit quantum system.
13.2 The Spin as a Two-Level Quantum System
13.2.1 Description of a Particle in Spin Coordinates
As explained in Chap. 7, the basic equation of quantum mechanics is Schrödinger’s

equation, i.e.
@
i D H .x; t / (13.1)
@t
where j .x; t /j2 is the probability density function of finding the particle at position
x at time instant t , and H is the system’s Hamiltonian, i.e. the sum of its kinetic
13.2 The Spin as a Two-Level Quantum System 253
and potential energy, which is given by H D p 2 =2m C V , with p being the

momentum of the particle, m the mass, and V an external potential. The solution
of Eq. (13.1) is given by .x; t / D e iHt .x; 0/ [34].
However, cartesian coordinates are not sufficient to describe the particle’s
behavior in a magnetic field and thus the spin variable taking values in SU(2)
has been introduced. In that case the solution of Schrödinger’s equation can
be represented in the basis jr; > where r is the position vector and is the
spin’s value which belongs in f 12 ; 12 g (fermion). Thus vector which appears in
P R equation can be decomposed in the vector space jr; > according to
Schrödinger’s
j >D d 3 rjr; >; < r; j >. The projection of j > in the coordinates
system r; is denoted as < r; j >D .r/. Equivalently one has C .r/ D<
r; Cj > and .r/ D< r; j >. Thus one can write .r/ D Œ C .r/; .r/T .
13.2.2 Measurement Operators in the Spin State-Space
It has been proven that the eigenvalues of the particle’s magnetic moment are ˙ 12
or ˙„ 12 . The corresponding eigenvectors are denoted as jC > and j >. Then the
relation between eigenvectors and eigenvalues is given by
z jC >D C.„=2/jC >

(13.2)
z j >D C.„=2/j >
which shows the two possible eigenvalues of the magnetic moment [34]. In general
the particle’s state, with reference to the spin eigenvectors, is described by
j >D ˛jC > Cˇj > (13.3)
with j˛j2 C jˇj2 D 1 while matrix z has the eigenvectors jC >D Œ1; 0 and j >D
Œ0; 1 and is given by

„ 1 0
z D (13.4)
2 0 1
Similarly, if one assumes components of magnetic moment along axes x and z, one
obtains the other two measurement (Pauli) operators

„ 01 „ 0 i
x D ; y D (13.5)
2 10 2 i 0
13.2.3 The Spin Eigenstates Define a Two-Level

Quantum System
The spin eigenstates correspond to two different energy levels. A neutral particle
is considered in a magnetic field of intensity Bz . The particle’s magnetic moment
M and the associated kinetic moment are collinear and are related to each other
through the relation
M D (13.6)
The potential energy of the particle is
W D Mz Bz D Bz z (13.7)
Variable !0 D Bz is introduced, while parameter z is substituted by the spin’s

measurement operator Sz .
Thus the Hamiltonian H which describes the evolution of the spin of the
particle due to field Bz becomes H0 D !0 Sz , and the following relations between
eigenvectors and eigenvalues are introduced:
H jC >D C „!2 0 jC >; H j >D „!2 0 j > (13.8)
Therefore, one can distinguish 2 different energy levels (states of the quantum
system)
EC D C „!2 0
(13.9)
E D „!2 0
By applying an external magnetic field the probability of finding the particle’s

magnetic moment at one of the two eigenstates (spin up or down) can be changed.
This can be observed, for instance, in the Nuclear Magnetic Resonance (NMR)
model and is the objective of quantum control [34].
13.3 The Lindblad and Belavkin Description of Quantum

Systems
13.3.1 The Lindblad Description of Quantum Systems
It will be shown that the Lindblad and the Belavkin equation can be used in place
of Schrödinger’s equation to describe the dynamics of a quantum system. These
equations use as state variable the probability density matrix D j >< j,
13.3 The Lindblad and Belavkin Description of Quantum Systems 255
associated with the probability of locating the particle at a certain eigenstate.

The Lindblad and Belavkin equations are actually the quantum analogous of
the Kushner–Stratonovich stochastic differential equation which denotes that the
change of the probability of the state vector x to take a particular value depends
on the difference (innovation) between the measurement y.x/ and the mean value
of the estimation of the measurement EŒy.x/. It is also known that the Kushner–
Stratonovich SDE can be written in the form of a Langevin SDE [155]
dx D ˛.x/dt C b.x/dv (13.10)
which finally means that the Lindblad and Belavkin description of a quantum system
are a generalization of Langevin’s SDE for quantum systems [210]. For a quantum
system with state vector x and eigenvalues .x/2R, the Lindblad equation is written
as [27, 210]
„P D i ŒHO ; C DŒc

O (13.11)
where is the associated probability density matrix for state x, i.e. it defines the
probability to locate the particle at a certain eigenstate of the quantum system and
the probabilities of transition to other eigenstates. The variable HO is the system’s
Hamiltonian, operator ŒA; B is a Lie bracket defined as ŒA; B D AB BA, the
vector cOPD .cO1 ; ; cOL /T is also a vector of operators, variable D is defined as
O D L
DŒc lD1 DŒcOl , and finally „ is Planck’s constant.
13.3.2 The Belavkin Description of Quantum Systems
The Lindblad equation (also known as stochastic master equation), given in

Eq. (13.11), is actually a differential equation which can be also written in the form
of a stochastic differential equation that is known as Belavkin equation. The most
general form of the Belavkin equation is:
O c C HŒi HO dt C dzC .t /c

„dc D dtDŒc O c (13.12)
Variable H is an operator which is defined as follows:
O C rO C TrŒr
O D r
HŒr O C rO C (13.13)
Variable HO stands for the Hamiltonian of the quantum system. Variable cO is

an arbitrary operator obeying cO C cO D R, O where RO is an hermitian operator.
The infinite dimensional complex variables vector dz is defined as dz D
.dz1 ; ; dzL /T , and in analogy to the innovation dv of the Langevin equation
(see Eq. (13.10)), variable dz expresses innovation for the quantum case. Variable
dzC denotes the conjugate-transpose .dz /T . The statistical characteristics of dz are
dzdzC D „Hc dt; dzdzT D „Y dt. In the above equations matrix Y is a symmetric
complex-valued matrix. Variable Hc is defined as m1 D fHc D diag.n1 ; ; nL / W
8l; nl 2Œ0; 1g, where nl can be interpreted as the possibility of monitoring the
l-th output channel. There is also a requirement for matrix U to be positive semi-
definite. As far as the measured output of the Belavkin equation is concerned one
has an equation of complex currents J T dt D< cH O c C cO C Y >c CdzT , where
<> stands for the mean value of the variable contained in it [210]. Thus, in the
description of the quantum system according to Belavkin’s formulation, the state
equation and the output equation are given by Eq. (13.14).
O c C HŒi HO dt C dzC .t /c

„d c D dtDŒc O c
C (13.14)
J dt D< cO Hc C cO Yc > dt C dz
T T T
where c is the probability density matrix (state variable) for remaining at one of
the quantum system eigenstates, and J is the measured output (current).
13.3.3 Formulation of the Control Problem
The control loop consists of a cavity where the multi-particle quantum system is
confined and of a laser probe which excites the quantum system. Measurements
about the condition of the quantum system are collected through photodetectors and
thus the projections of the probability density matrix of the quantum system are
turned into weak current. By processing this current measurement and the estimate
of the quantum system’s state which is provided by Lindblad’s or Belavkin’s
equation, a control law is generated which modifies a magnetic field applied to the
cavity. In that manner, the state of the quantum system is driven from the initial
value .0/ to the final desirable value d .t / (see Fig. 13.1).
When Schrödinger’s equation is used to describe the dynamics of the quantum
system the objective is to move the quantum system from a state , that is associated
with a certain energy level, to a different eigenstate associated with the desirable
energy level. When Lindblad’s or Belavkin’s equation is used to describe the
dynamics of the quantum system, the control objective is to stabilize the probability
density matrix .t / on some desirable quantum state d .t /2C n , by controlling the
intensity of the magnetic field. The value of the control signal is determined by
processing the measured output which in turn depends on the projection of .t /
defined by TrfP.t /g.
13.4 A Feedback Control Approach for Quantum System Stabilization 257
Fig. 13.1 Feedback control loop for quantum systems
13.4 A Feedback Control Approach for Quantum

System Stabilization
13.4.1 Control Law Calculation Using Schrödinger’s Equation
It is assumed that the dynamics of the controlled quantum system is described by a

Schrödinger equation of the form
i „ P .t / D ŒH0 C f .t /H1 .t / .t / 2 C n (13.15)
where H0 is the system’s Hamiltonian, H1 is the control Hamiltonian, and f .t / is

the external control input. The following Lyapunov function is then introduced [9]
C
V. / D . Z Z d /2 (13.16)
where C stands for the transposition and complex conjugation, Z is the quantum
system’s observable and is associated with the energy of the system. The term
C
Z denotes the observed mean energy of the system at time instant t and
Zd is the desirable energy value. The first derivative of the Lyapunov function of
Eq. (13.16) is
VP . / D 2Œ C
Z Zd Œ P C Z C C
Z P (13.17)
while from Eq. (13.15) it also holds P .t / D „i ŒH0 C f .t /H1 .t /, which results
into
VP . / D 2i
„
. C
Z Zd / C
fH0 Z ZH0 C f .H1 Z ZH1 /g (13.18)
Choosing the control signal f .t / to be proportional to the gradient with respect to

f of the first derivative of the Lyapunov function with respect to time (velocity
gradient), i.e.
f .t / D krf fVP . /g (13.19)
C C
and for Z such that H0 Z D ZH0 (e.g. Z D H0 ) one obtains
2i C C
f .t / D . Z Zd / .H1 Z ZH1 / (13.20)
„
Substituting Eqs. (13.20) into (13.18) provides
2i 2i
VP . / D k . C
Z Zd / C
Œ . C
Z Zd / C
„ „
.H1 Z ZH1 / .H1 Z ZH1 / (13.21)
and finally results in the following form of the first derivative of the Lyapunov
function
4
VP . / D k 2 .
Z Z d /2 C2
.H1 Z ZH1 /2 2
0 (13.22)
„
which is non-positive along the system trajectories. This implies stability for the
quantum system and in such a case La Salle’s principle shows convergence not to
an equilibrium but to an area round this equilibrium, which is known as invariant
set [92].
Consequently, from Eq. (13.22) and LaSalle’s theorem, any solution of the
system .t / remains in the invariant set M D f W VP . / D 0g.
13.4.2 Control Law Calculation Using Lindblad’s Equation
Next, it will be shown how a gradient-based control law can be formulated using the
description of the quantum system according to Lindblad’s equation. The following
bilinear Hamiltonian system is considered (Lindblad equation)
P / D i ŒH0 C f .t /H1 ; .t /

.t (13.23)
13.4 A Feedback Control Approach for Quantum System Stabilization 259
where H0 is the interaction Hamiltonian of the quantum system, H1 is the control

Hamiltonian of the quantum system, and f .t / is the real-valued control field for the
quantum system. The control problem consists of calculating the control function
f .t / such that the system’s state (probability transition matrix .t /) with initial
conditions .0/ D 0 converges to the desirable final state d for t !1. It is
considered that the initial state 0 and the final state d have the same spectrum
and this is a condition needed for reachability of the final state through unitary
evolutions.
Because of the existence of the interaction Hamiltonian H0 it is also considered
that the desirable target state also evolves in time according to the Lindblad
equation, i.e.
Pd .t / D i ŒH0 ; d .t / (13.24)
The target state is considered to be stationary if it holds ŒH0 ; d .t / D 0, therefore

in such a case it also holds Pd .t / D 0. When ŒH0 ; d .t /¤0 then one has Pd ¤0 and
the control problem of the quantum system is a tracking problem. The requirement
.t /!d .t / for t !1 implies a trajectory tracking problem, while the requirement
.t /!O.d /.t / for t !1 is an orbit tracking problem.
It will be shown that the calculation of the control function f .t / which assures
that .t / converges to d .t / can be performed with the use of the Lyapunov method.
To this end, a suitable Lyapunov function V .; d / will be chosen and it will be
shown that there exists a gradient-based control law f .t / such that VP .; d /0.
The dynamics of the state of the quantum system, as well as the dynamics of the
target state are jointly described by
P / D i ŒH0 C f .t /H1 ; .t /

.t
(13.25)
Pd .t / D i ŒH0 ; d .t /
A potential Lyapunov function for the considered quantum system is taken to be
V D 1 Tr.d / (13.26)
It holds that V > 0 if ¤d . The Lyapunov function given in Eq. (13.26) can
be also considered as equivalent to the Lyapunov function V . ; d / D 1 j <
d .t /j .t / > j , which results from the description of the quantum system with
2
the use of Schrödinger’s equation given in Eq. (13.1). The term < d .t /j .t / >
expresses an internal product which takes value 1 if d .t / and .t / are aligned.
The first derivative of the Lyapunov function defined in Eq. (13.26) is
VP D Tr.Pd / Tr.d /
P (13.27)
One can continue on the calculation of the first derivative of the Lyapunov function
VP D Tr.Pd / Tr.d /)

P
VP D Tr.Œi H0 ; d / Tr.d Œi H0 ; / f .t /Tr.d Œi H1 ; /)
VP D Tr.Œi H0 d Cd i H0 /Tr.d Œi H0 Ci H0 /f .t /Tr.d Œi H1 ; /)
VP D Tr.i H0 d C d i H0 d i H0 C d i H0 / f .t /Tr.d Œi H1 ; /
(13.28)
Using that Tr.i H0 d / D Tr.d i H0 / one obtains
VP D f .t /Tr.d Œi H1 ; / (13.29)
The control signal f .t / is taken to be the gradient with respect to f of the first
derivative of the Lyapunov function, i.e. f .t / D krf VP .t /, which gives
f .t / D kTr.d Œi H1 ; / k > 0 (13.30)
and which results in a negative semi-definite Lyapunov function VP 0. Choosing the
control signal f .t / according to Eq. (13.30) assures that for the Lyapunov function
of the quantum system given by Eq. (13.26) it holds
V > 0 8 .; d /¤0

(13.31)
VP 0
and since a negative semi-definite Lyapunov function is examined, LaSalle’s

theorem is again applicable [92].
Again according to LaSalle’s theorem, explained in Chap. 8, the state
..t /; d .t // of the quantum system converges to the invariant set M D
f.; d /jVP ..t /; d .t // D 0g. Attempts to define more precisely the convergence
area for the trajectories of .t / when applying La Salle’s theorem can be found in
[203, 206].
Simulation tests about the performance of the gradient-based quantum control loop
are given for the case of a two-qubit (four-level) quantum system. Indicative results
from two different simulation experiments are presented, each one associated with
different initial conditions of the target trajectory and different desirable final state.
The Hamiltonian of the quantum system was considered to be ideal, i.e. H0 2C 4
was taken to be strongly regular and H1 2C 4 contained non-zero non-diagonal
elements. The two-qubit quantum system has four eigenstates which are denoted as
1 D .1000/, 2 D .0100/, 3 D .0010/, and 4 D .0001/. For the first case, the
desirable values of elements iid ; i D 1; ; 4 corresponding to quantum states 1
a 0.4
evolution of the target state of the quantum system b 0.4
evolution of the state of the quantum system
0.35 0.35
0.3 0.3
matrix ρd
matrix ρ
0.25 0.25
0.2 0.2
0.15 0.15
0.1 0.1
0 50 100 150 200 0 50 100 150 200
t (sec) t (sec)
Fig. 13.2 (a) Desirable quantum states in the first test case, (b) Actual quantum states in the first
test case
a evolution of the target state of the quantum system b evolution of the state of the quantum system
0.4 0.4
0.35 0.35
0.3 0.3
matrix ρd
matrix ρ
0.25 0.25
0.2 0.2
0.15 0.15
0.1 0.1
0 50 100 150 200 0 50 100 150 200
t (sec) t (sec)
Fig. 13.3 (a) Desirable quantum states in the second test case, (b) Actual quantum states in the
second test case
to 4 are depicted in Fig. 13.2a, while the convergence of the actual values ii ; i D
1; ; 4 towards the associated desirable values is shown in Fig. 13.2b. Similarly,
for the second case, the desirable values of elements iid ; i D 1; ; 4 are shown
in Fig. 13.3a, while the associated actual values are depicted in Fig. 13.3b. It can be
observed that the gradient-based control calculated according to Eq. (13.30) enabled
convergence of ii to iid , within acceptable accuracy levels. Figure 13.4 presents the
evolution in time of the Lyapunov function of the two simulated quantum control
systems. It can be noticed that the Lyapunov function decreases, in accordance
with the negative semi-definiteness proven in Eq. (13.31). Finally, in Fig. 13.5, the
control signals for the two aforementioned simulation experiments are presented.
The simulation tests verify the theoretically proven effectiveness of the proposed
gradient-based quantum control scheme. The results can be extended to the case of
control loops with multiple control inputs fi and associated Hamiltonians Hi ; i D
1; ; n.
a 0.7396
evolution of the Lyapunov function of the control loop b 0.746
evolution of the Lyapunov function of the control loop
0.7394 0.745
0.744
0.7392
Lyapunov function V
Lyapunov function V
0.743
0.739
0.742
0.7388
0.741
0.7386
0.74
0.7384 0.739
0.7382 0.738
0 50 100 150 200 0 50 100 150 200
t (sec) t (sec)
Fig. 13.4 (a) Lyapunov function of the first test case, (b) Lyapunov function of the second test
case
a 0.1
evolution of the control in input b evolution of the control in input
0.3
0.08 0.2
0.1
0.06
control input
control input
0
0.04
−0.1
0.02
−0.2
0 −0.3
−0.02 −0.4
0 50 100 150 200 0 50 100 150 200
t (sec) t (sec)
Fig. 13.5 (a) Control input of the first test case, (b) Control input of the second test case
13.6 Conclusions
The chapter has presented a gradient-based approach to feedback control of

quantum systems. Different descriptions of the quantum system dynamics were
formulated using Schrödinger’s and Lindblad’s differential equations, as well as
Belavkin’s stochastic differential equation. When Scrödinger’s equation is used to
describe the dynamics of the quantum system the objective is to move the quantum
system from an eigenstate associated with a certain energy level to a different
eigenstate associated with the desirable energy level. When Lindblad’s or Belavkin’s
equations are used to describe the dynamics of the quantum system the control
objective is to stabilize the probability density matrix on some desirable quantum
state d 2C n by controlling the intensity of the magnetic field. The control input
is calculated by processing the measured output, which in turn depends on the
projection of the probability density matrix , as well as on processing of the
estimate of provided by Lindblad’s or Belavkin’s equation. It was shown that
using either the Schrödinger or the Lindblad description of the quantum system a
gradient-based control law can be formulated which assures tracking of the desirable
quantum state within acceptable accuracy levels. The convergence properties of the
gradient-based control scheme were proven using Lyapunov stability theory and
LaSalle’s invariance principle. Finally, simulation experiments for the case of a two-
qubit (four-level) quantum system verified the theoretically established efficiency of
the proposed gradient-based control approach.
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Index
Aminoboutyric acid, 78 Circadian cells, 61, 111

Circadian rhythm, 110
Circadian rhythm Neurospora, 111
A-current, 23 Cortical excitatory cells, 82
Advection-diffusion equation, 160 Cortical fast synaptic inputs, 82
Alcylating agents, 110 Coupled circadian oscillators, 118
AMPA / Kainate, 80 Cycline dependent kinases, 110
Anticancer drugs, 110 Cytoplasm, 111
Asymptotic stability, 36
Attractors, 51, 179, 191, 200
Dendrites, 9, 16
Depression of synapses, 78
Balian-Low theorem, 229, 249 Derivative-free nonlinear Kalman Filter, 85,
Basal ganglia neurons, 75 98, 126, 130, 132
Belavkin’s SDE, 252, 254–256 Diffeomorphism, 88, 106
Bendixson’s theorem, 45 Differential flatness theory, 84, 86, 91, 115,
Bifurcations of fixed points, 46 120, 181
Binding or release of ions, 78 Differential geometry, 92, 112, 118
Brownian motion, 150, 151, 166, 169 Diffusing particle, 150, 166
Brunovsky canonical form, 85, 88, 119, 123 Distributed gradient algorithm, 173
Bursting activity, 75 Distributed parameter systems, 131
Disturbance observer, 101, 125
Drift function, 161, 164
Cable’s PDE, 1, 9 Duffing chaotic oscillator, 182
Calcium activated cation current, 25
Calcium activated potassium channel, 25
Calcium ion channels, 22 Elliptic bursting, 76
Cell circadian clock, 110 Energy of signal, 208
Cell nucleus, 107 Extended Kalman Filter, 98, 132
Central Limit Theorem, 152, 194
Central pattern generators, 84
Chaos, 28, 51, 181 Fault diagnosis, 242
Chaotic dynamics, 51 Feed-forward neural networks, 222
Chaotic oscillators, 181 Feedback control of bifurcations, 66
Characteristic polynomial, 54–56, 58 Feedback control of quantum systems, 257
Chen chaotic oscillator, 182 Finite escape time, 27

DOI 10.1007/978-3-662-43764-3, © Springer-Verlag Berlin Heidelberg 2015
274 Index
First passage time, 155 Kalman Filter, 98

FitzHugh–Nagumo model, 1, 14, 51, 58, 89, Kharitonov’s stability theorem, 54, 55, 63
92, 133 Kushner-Stratonovich SDE, 255
Flatness-based control, 84, 86, 87, 91, 96, 114,
120, 185, 187
Fokker–Planck’s PDE, 154, 155, 161, 163 Langevin’s SDE, 150, 151, 154, 157, 166, 255
Fourier transform, 215, 216, 218, 226, 242, LaSalle’s theorem, 177, 178, 258, 260
244 Laser probe, 256
FRQ protein synthesis, 61, 111, 117 Lie derivatives, 106
Fundamental memory patterns, 192, 194, Limit cycles, 27, 34, 44, 51, 60
200 Lindblad differential equation, 254, 255, 258,
259
Lipids and proteins, 2
Gabor frames, 228 Local linearization, 34
Gap junctions, 83, 84, 106 Long term plasticity, 82
Gated ion channels, 2 Lyapunov stability, 36, 169, 171, 174, 175,
Gauss-Hermite series, 225 177, 179, 251, 252, 257–259
Gaussian envelope, 214
Generalized Fourier coefficients, 223
Generalized Fourier series, 222 M-current, 23
Genesio-Tesi chaotic oscillator, 182 Magnetic moment, 253
Global asymptotic stability, 36 Mean-dispersion principle, 229
Glutamate neurotransmitter, 80 Michaelis constant, 61, 111
Goldman-Hodgkin-Katz equation, 3, 5 Momentum of particle, 162, 253
Gradient control, 258, 259 Morlet wavelet, 214
Green function, 20 Morris-Lecar model, 1, 15, 20
mRNA transcription, 61, 111
mRNA translation, 61, 111
Haar wavelet, 213 Multi-input multi-output nonlinear system, 88
Hamiltonian operator, 162, 163, 224, 252, 254, Multi-particle system confined in cavity, 252
255, 259, 260 Multi-resolution function representation, 210,
Harmonic potential, 162, 167 211, 225
Hebbian learning, 195, 200 Multi-scale modelling of dynamical systems,
Heisenberg boxes, 215 230
Hermite basis functions, 224, 225, 229, 242, Multiple isolated equilibria, 27
243 Myelinated axons, 133
Hodgkin-Huxley model, 1, 12, 20, 137
Hopf bifurcations, 49, 50, 58, 64
Hyperbolic equilibrium point, 38, 49 Nernst potential equation, 4
Nernst’s conditions, 3
Network of circadian cells, 109
Image compression, 222, 239 Neural synapses, 78
Integrate and fire neuron, 157, 160 Neurons bursting phase, 75
Interval polynomial, 54, 55, 63 Neurons silent phase, 75
Invariance under Fourier transform, 221, 229, Neurospora circadian cells, 54, 61, 111
244 Neurotransmitter, 81
Inverse wavelet transform, 210 Neurotransmitters, 77, 80
Inward calcium-dependent current, 25 NMDA receptor, 80
Ion channels, 1 Non-gated ion channels, 2
Isoclines, 32 Non-observable attractors, 198
Ito’s SDE, 153 Nonlinear estimation methods, 132
Nuclear Magnetic Resonance, 254
Number of attractors in associative memories,
Jacobian matrix, 35, 37, 43, 58–60, 62, 68 200
Index 275
Open-loop control of quantum systems, 252 Spin eigenvectors, 253

Ornstein–Uhlenbeck diffusion, 153, 164, 167 Square-wave bursting, 76
Orthonormal wavelet basis, 209 Stabilization of quantum systems, 251
Stochastic integrals, 153
Stochastic process, 152
Parabolic bursting, 76 Stochastic weight, 149
Parseval’s theorem, 243 Stochastic weights, 150, 179, 218
Phase diagram, 34, 38, 76, 104 Stratonovic calculus, 153
Photodetectors, 256 Striatial neurons, 85
Pitchfork bifurcations, 47 Sub-harmonic and harmonic oscillation, 28
Poincaré-Bendixson’s theorem, 45 Superposition of associative memories, 196
Potentiation of synapses, 78 Synaptic channels, 77
Power spectral density, 243 Synaptic terminals, 77
Power spectrum of signal, 243 Synchronization of circadian oscillators with
Probabilistic decision making, 200 differential flatness theory, 120
Probability density matrix, 254 Synchronization of circadian oscillators with
Protein synthesis control with differential differential geometry, 118
flatness theory, 114 Synchronization of FitzHugh–Nagumo
Protein synthesis control with differential neurons, 84, 102
geometry, 112 Synchronization of neural oscillators, 84, 102
Quantum harmonic oscillator, 149, 150, 164, Thalamic cells, 75

167, 181, 184, 222, 224, 228, 230, 242, Time-frequency localization of a function, 222
257 Two-qubit quantum system, 252, 260
Type-I neuron dynamics, 23, 133
Type-II neuron dynamics, 133
Random oscillations, 150
Random spiking, 160
Rayleigh’s theorem, 217 Uncertainty principle, 218
Reaction-diffusion PDE, 133 Uncertainty principle for Hermite basis
Receptors, 78 functions, 222, 229
Resting potential, 1 Uncertainty principle in harmonic analysis,
Routh-Hurwitz criterion, 55 228
Unitary rotation operators, 196, 199, 204
Saddle-node bifurcation, 46, 58

Schödinger’s equation eignestates, 229 Van der Pol oscillator, 14, 44
Schrödinger’s diffusion equation, 150, 161, Velocity gradient control, 258
163, 167, 221, 222, 224, 228, 248, 253, Vesicle, 77
254, 257, 259 Voltage sags, 24
Schrödinger’s equation eigenstates, 230 Voltage-gated potassium ion channels, 23
Short term plasticity, 82
Short-term memory, 80, 200
Sodium ion channels, 22 Wave-type differential equations, 135
Solitary waves, 131, 136 Wavelet basis functions, 208
Spectral analysis of neurons, 207, 214, 246 Wavelet transform, 208
Spiking, 75, 76, 160 Wiener walk, 151

2015 Book AdvancedModelsOfNeuralNetworks

Uploaded by

2015 Book AdvancedModelsOfNeuralNetworks

Uploaded by

Gerasimos G.

Advanced Models of Neural

ISBN 978-3-662-43763-6 ISBN 978-3-662-43764-3 (eBook)

© Springer-Verlag Berlin Heidelberg 2015

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

This book provides a complete study on neural structures exhibiting nonlinear

stochasticity-based models and models compatible with principles of quantum

transmission of neural signals, (7) Stochastic models of biological neuron dynamics,

In Chap. 4, it is shown that the voltage of the neurons membrane exhibits

on differential flatness theory. This transformation provides an extended model of

machine learning, artificial intelligence, and computational intelligence as well as

Athens, Greece Gerasimos G. Rigatos

1 Modelling Biological Neurons in Terms of Electrical Circuits. . . . . . . . . 1

2 Systems Theory for the Analysis of Biological Neuron Dynamics. . . . . 27

4 Oscillatory Dynamics in Biological Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

5 Synchronization of Circadian Neurons and Protein

7.3 Fokker–Planck’s Partial Differential Equation . . . . . . . . . . . . . . . . . . . . . . 154

10 Attractors in Associative Memories with Stochastic Weights . . . . . . . . . 191

12.5 Uncertainty Principles for the QHO-Based Neural Networks . . . . . 228

FHN FitzHugh–Nagumo neurons

Abstract The functioning of the cells membrane can be represented as an electric

1.1 The Hodgkin–Huxley Equations

VM D Vin Vout (1.1)

G.G. Rigatos, Advanced Models of Neural Networks, 1

The equilibrium in the inflow or outflow of charges is reached according to

1.1.1 Nernst’s Equation

The diffusion coefficient that appears in the aforementioned equations is given by

1.1.2 The Goldman–Hodgkin–Katz Equation

I D u z2 FˇŒC VlM u zRTˇ ddx

I D IK C INa C ICl D 0 (1.15)

1.2 Equivalent Circuits of the Cell’s Membrane

1.2.1 The Electric Equivalent

The functioning of the cell’s membrane can be represented as an electric circuit.

Fig. 1.2 Electric equivalent of the cell’s membrane

Fig. 1.3 Equivalent circuit of cell’s membrane

Voltage VM is computed from the Goldman–Hodgkin–Katz equation and CM is

where gO k is the conductance normalized per unit of surface.

Fig. 1.4 Electric circuit consisting of ion channels in cell’s membrane

Iion D gCl .VM ECl / gK .VM EK / gNa .VM ENa / (1.24)

Equivalently, assuming an external input current I (normalized per surface of the

where A denoted membrane’s surface (Fig. 1.4). Using the notation

ER D .gCl ECl C gK EK C gNa ENa /rM (1.26)

gCl ECl CgK EK CgNa ENa CI =A

Therefore, in case that there is no external current, the membrane’s voltage VM in

1.2.2 Membrane’s Time Constant

cM dVdtM D VrMM C IM .t / (1.31)

Fig. 1.5 Diagram of membrane’s voltage variation

1.3 Describing Membrane’s Voltage Dynamics with Cable’s

VM .x C x; t / VM .x; t / D IL .x; t /RL D IL .x; t / x r

Fig. 1.6 Cable equivalent circuit of the neuron’s membrane

Fig. 1.7 Currents of the membrane at point x

Therefore, for x !0 it holds

IL .x C x; t / D IL .x; t / Iion .x; t / Icap .x; t / (1.36)

Icap .x; t / C Iion .x; t / D IL .x C x; t / C IL .x; t / (1.37)

out of which one obtains [16, 65]

Time constant affects the variation of voltage.

Fig. 1.8 Membrane’s circuit

1.4 The Hodgkin–Huxley Model

1.4.1 Derivation of the Hodgkin–Huxley Model

The Hodgkin–Huxley model is obtained from a modification of the cable’s PDE,

IL D Icap C Iion (1.45)

which can be also written in the following form

gN Na D 120 mS/cm3 gN K D 36 mS/cm3 gN L D 0:3 mS/cm3

an .V / D 0:01.V C 55/=.1 exp..V C 55/=10//

1.4.2 Outline of the Hodgkin–Huxley Equations

By considering that there is no spatial variation of V .x; t /, i.e. that @V @t

1.5 The FitzHugh–Nagumo Model of Neurons

The FitzHugh–Nagumo model is a two-dimensional simplified form of the

1.6 The Morris–Lecar Model of Neurons

examines the variation of the membrane’s potential in a neuron as a function of the

Here, parameters Vi ; i D 1; ; 4 are chosen to fit data obtained from an identi-

Fig. 1.10 (a) Real structure a

1.7 Modelling Dendrites in Terms of Electrical Circuits

Fig. 1.11 Electric circuit of local segment of a dendrite

Fig. 1.12 Segments of the membrane

VM .x C x; t / VM .x; t / D IL .x; t /RL D IL .x; t / x r

Therefore, for x !0 it holds

IL .x C x; t / D IL .x; t / Iion .x; t / Icap .x; t / (1.36)

Icap .x; t / C Iion .x; t / D IL .x C x; t / C IL .x; t / (1.37)

dj2 .Vj 1 Vj /

whereas parameters x1 and x are described by

By defining the state variables x1 D and x2 D P one has the state-space