Introduction to Biological Neurons

1.1 Introduction
After a century of research, our knowledge of the human brain is still very much incomplete.
Hundreds of different brain areas have been mapped out in various species. Neurons in these regions have
been classified, sub-classified, and reclassified based on anatomical details, connectivity, response
properties, and the channels, neuropeptides, and other markers they express. Hundreds of channels have
been quantitatively characterized, and the regulation and gating mechanisms are beginning to be
understood. Multi-electrode recordings reveal how hundreds of neurons in various brain areas respond to
stimuli. Despite this wealth of descriptive data, we still do not have a grasp on exactly how these
thousands of neurons are supposed to accomplish computation. To understand the minimal knowledge
about how brain is doing this enormous computation and signal processing we should have some basic
knowledge of biology, neuroscience, biochemistry, biophysics, signal& systems, networks and
information theory
A vast majority of neurons respond to sensory or synaptic inputs by generating a train of
stereotypical responses called action potentials or spikes. Deciphering the encoding process which
transforms continuous, analog signals (photon fluxes, acoustic vibrations, chemical concentrations and so
on) or outputs from other neurons into discrete, fixed-amplitude spike trains is essential to understand
neural information processing and computation, since often the nature of representation determines the
nature of computation possible. Researchers, however, remain divided on the issue of the neural code
used by neurons to represent and transmit information. Although there are many open problem in this area
but to model a problem analytically is still very much challenging.
The brain is a sophisticated and complex organ that nature has devised. In order to understand
brain function fairly, we must begin by learning how brain cells work individually and then see how they
are assembled to work together. There are mainly two types of cell in central nervous system: Neuron and
Glia. Although there are many neurons in the human brain (about 100 billion), glia outnumber neurons by
tenfold. However, neurons are more important cells for the major functions of the brain. It is the neurons
that sense changes in the environment, communicate these changes to other neurons, and command the
bodys responses to these sensations. Glia, or glial cells, are thought to contribute to brain function mainly
by insulating, supporting, and nourishing neighboring neurons.

1.2 Relevant Physiological Aspects
A typical neuron has four parts: (a) cell body or soma, (b) axon, (c) dendrites and (d) neuronal
membrane.


Fig1: Schematic of a neuron structure [1]
(a) Cell body or SOMA
20m diameter, watery fluid inside called cytosol and contains organelles like nucleus, rough ER,
smooth ER, mitochondria and golgi apparatus [1]. When signal from different dendrites propagate



towards axon hillock cellbody assumed to act as a conducting and it also performs the local energy
balancing.

Fig2: Cell Body [2]

(b) Axon
The axon, a structure found only in neurons that is highly specialized for the transfer of
information over distances in the nervous system. The axon begins with a region called the axon hillock,
which tapers to form the initial segment of the axon proper. It serves as the telegraph wire that sends
information over great distances. The end is called the axon terminal or terminal button. The terminal is a
site where the axon comes in contact with other neurons (or other cells) and passes information on to
them. This point of contact is called the synapse [1].
(c) Dendrite
It acts like a receiver for a neuron. The term dendrite is derived from the Greek for tree, as
these dendrites resemble the branches of a tree extended from the soma. The dendrites of a single neuron
are collectively called a dendritic tree. The branches are covered with thousands of synapses. The
dendritic membrane under the synapse (the postsynaptic membrane) has many specialized protein
molecules called receptors that detect the neurotransmitters in the synaptic cleft [1].
(d) Neuronal Membrane
The neuronal membrane serves as a barrier to enclose the cytoplasm inside the neuron and to
exclude certain substances that float in the fluid that bathes the neuron. The membrane is about 5 nm
thick and is studded with proteins. The protein composition of the membrane varies depending on
whether it is in the soma, the dendrites, or the axon. Neuronal membrane gives a neuron the remarkable
ability to transfer electrical signals throughout the brain and body [1].

1.3 Action Potential
The Action potential is an electrical signal that conveys information over distances in the nervous
system. The cytosol in the neuron at rest is negatively charged with respect to the extra-cellular fluid. The
action potential is a rapid reversal of this situation such that, for an instant, the inside of the membrane
becomes positively charged with respect to the outside. The action potential is also often called a spike, a
nerve impulse, or a discharge. The action potentials generated by a cell are all similar in size and duration,
and they do not diminish as they are conducted down the axon. The frequency and pattern of action
potentials constitute the code used by neurons to transfer information from one location to another. Action
potential has certain identifiable parts, called the rising phase, overshoot, falling phase, undershoot, after-
hyper-polarization [1].




Fig 3: Action potential [1]
1.4 Synapse
The junction between two neurons is called a synapse. With respect to a synapse, we refer to the
sending neuron as the pre-synaptic cell and to the receiving neuron as the postsynaptic cell. Most
synapses occur on the dendrites but some occur on the somas or the axons of other neurons. The most
common type of synapse in the (vertebrate) brain is the chemical synapse. For this type of synapse, the
axon comes very close to the postsynaptic neuron, leaving only a small gap of about 20-40 nanometers
across between pre and postsynaptic cell membranes, called the synaptic cleft. The pre-synaptic signal is
transmitted across the synaptic cleft by transformation from electrical signal into a chemical one and then
back into electrical signal on the postsynaptic side. The chemical signal is sent in the form of
neurotransmitter molecules. About 5,000 of these molecules are packaged in small spheres called synaptic
vesicles which reside in the pre-synaptic terminal [2].


Fig 4: Synapse [1]




Major Developments in Neuroscience and Neural
Information Theory

Review of recent literature [2, 3, 4] suggests that research on neuroscience may be classified in three
broad directions:

2.1 Experimental Neuroscience
Experimental neuroscience is an important discipline with an aim to understand the molecular,
cellular, physiological, structural and behavioral basis of normal function of the nervous system and its
diseases.

2.2 Theoretical Neuroscience
The task of understanding the principles of information processing in the brain poses, apart from
numerous experimental questions, challenging theoretical problems on all levels from molecules to
behavior. This Theoretical Neuroscience concentrates on modeling approaches on the level of neurons
and small populations of neurons, since one think that this is an appropriate level to address fundamental
questions of neuronal coding, signal transmission, or synaptic plasticity. Neuron is a dynamic element
that emits output pulses whenever the excitation exceeds some threshold. The resulting sequence of
pulses or spikes contains all the information that is transmitted from one neuron to the next. Signal
transmission and signal processing in neuronal systems need to be understood with the help of distributed
network consists of single neurons [3].

I ntegrate-and-Fire Model of the Neurons
The leaky integrate-and-fire model (LIF) [5] is one of the most elementary spiking
models and has been widely used to gain a better understanding of information processing in
neurons. In this model, the sub-threshold membrane potential of a neuron is governed by a first-
order linear differential equation




( ) - v ( )
( ) = C +
rest
in
v t dv t
i t
dt R
(1)

which corresponds to the circuit in Fig. 5 below [5]:



Fig 5: Equivalent circuit for leaky integrate-and-fire neuron [2]

In this model, the membrane time constant is = RC
m
t . The value of
m
t is typically 8
20 ms. A solution of above equation is

0
0
1 1
(t-t ) (t- )
0
1
( ) v + e ( ( ) v ) + e ( )
m m
t
rest rest in
t
v t v t i d
C

t t


=
}
(2)


By redefining the voltage reference, we can instead consider ( ) v
rest
v t . Replacing
( ) v
rest
v t by ( ) v t , we have for
0
t t >

0
0
1 1
(t-t ) (t- )
0
1
( ) e ( ) + e ( )
m m
t
in
t
v t v t i d
C

t t


=
}



| )
0
0 0 ,
1
( ) 1 ( ) + ( ) ( ) * h(t)
in t
i t t v t t t
C
o

| |
=
|
\ .
.(3)

Where
| )
0
1
t
,
h(t) e 1 ( )
m
t
t
t

= and * denotes convolution. This is true as long as ( ) v t is

less than the threshold. When a neuron has just output a spike at time
0
t 0 =
, we will assume that
the membrane potential is reset to
0
( ) 0 v t = . Then,
1
= * h
in
v i
C
. (4)



as long as < T v where T is the threshold function. In the above notation, we assume that
in
i

is causal; that is, for. Of course, the function h defined above is also causal. Suppose we let

m
t . Then,
| )
0
,
h(t) 1 ( )
t
t

= . This is called the perfect / leakless integrator model. As a

generalization of the leaky integrate-and fire model, we will allow h to be any decaying causal
function and use (4) to define the membrane potential. Note that
in
i is a result of incoming spike
train [2, 3, 5].

Refractory Period
Output spikes from a neuron are usually well separated. Even with strong input, it is
virtually impossible to excite a second spike during or immediately after a first one. This
minimal distance between two spikes is defined as the absolute refractory period of the neuron.
The typical length of this period is about 24 ms. The absolute refractory period is followed by a
state of relative refractoriness during which it is difficult, but not impossible to generate an
action potential. The relative refractory period may last around 1020ms. Both of these
refractory phases can be modeled in the IF-model by using a decaying threshold function.
Immediately after a spike is generated, we may assume that the threshold is large (possible
infinite), and hence it is impossible for the membrane potential to built up and reach the value of
the threshold in a short amount of time. Using decaying threshold implies that as time passes, the
threshold will be at a lower value and hence it is easier to generate a spike [2].

Energy Consumption
Another important fact is that our nervous system consumes a lot of energy. Human
brains consume 20% of energy consumption for adults and 60% for infant .When we block the
neural signaling by anesthesia, the brains energy consumption is halved. This suggests that
about 50% of the energy is used to drive signals along axons and across synapses. In 1996, Levy
and Baxter included the amount of energy expended by neuron in their study, initiating
theoretical studies of energy-efficient coding in nervous systems [6].

2.3 Neural Information Theory or Living Information Theory [8]
Information theory, the most rigorous way to quantify neural code reliability, is an aspect
of probability theory that was developed in the 1940s as a mathematical framework for
quantifying information transmission in man-made communication systems. The theorys rigor
comes from measuring information transfer precision by determining the exact probability
distribution of outputs given any particular signal or input. Moreover, because of its
mathematical completeness, information theory has fundamental theorems on the maximum
information transferrable in a particular communication channel. In engineering, information
theory has been highly successful in estimating the maximal capacity of communication channels
and in designing codes that take advantage of it. In neural coding, information theory can be used
to precisely quantify the reliability of stimulusresponse functions, and its usefulness in this



context was recognized early. One can argue that this precise quantification is also crucial for
determining what is being encoded and how. In this respect, researchers have recently taken
greater advantage of information-theoretic tools in three ways-
First, the maximum information that could be transmitted as a function of firing rate has been
estimated and compared to actual information transfer as a measure of coding efficiency.
Second, actual information transfer has been measured directly, without any assumptions about
which stimulus parameters are encoded, and compared to the necessarily smaller estimate
obtained by assuming a particular stimulusresponse model. Such comparisons permit
quantitative evaluation of a models quality[10].
Third, researchers have determined the limiting spike timing precision used in encoding, that
is, the minimum time scale over which neural responses contain information.

I nformation Theory in Living Systems
While applying information theory in living systems we should keep in mind that, basic
concepts and methods of classical information theory developed by Shanon and his fellow
researchers , which is very much effective for man-made communication systems may not be
always applicable to the long standing mysteries of nature. One must think critically before
applying information theoretic concept for analysis of information processing abilities of neurons
and hence our brain. One should always remember two things-
Judicious application of Shannons fundamental concepts of entropy, mutual information,
channel capacity is crucial to gaining an elevated understanding of how living systems handle
sensory information what is the capacity of a single neuron channel [8, 10].
Living systems have little if any need for the elegant block and convolutional coding theorems
and techniques of information theory because, organisms have found ways to perform their
information handling tasks in an effectively Shannon- optimum manner without having to
employ coding in the information-theoretic sense of the term [8, 10].

2.4. Comments on Outstanding Research Issues
1. Proposed models in literature do not consider complete signal flow from axon to axon
terminal and axon terminal to synaptic cleft and synaptic cleft to dendrites or cell body
and dendrite or cell body to axon hillock.
2. All the signals that reach dendrite or cell body, do not cross threshold and generate action
potential. What happen to these signals? Will they act as jitter for next action potential???
How local energy balancing takes place???
3. Neocortex is known to exhibit memory and a functional element of neocortex is a neuron.
It is not clear from the available literature if there is any memory trace in a single neuron.
Modeling of a single neuron is still an active area of research [1, 3].




Top-Down and Bottom-Up Approach in Neuroscience

Computational neuroscience is used to bridge the gap between the mathematical
neuroscience and experimental neuroscience. Hodgkin and Huxley combined their experiments
with a mathematical description [5], which they used for simulations on one of the early
computers. One of the central tasks of computational neuroscience is to bridge the different
levels of description by simulation and mathematical theory. The bridge can be built in two
different ways - Bottom-up models and Top-down models. Bottom-up models integrate what is
known on a lower level to explain phenomena observed on a higher level. Top-down models, on
the other hand, start with known cognitive functions of the brain (e.g., working memory), and try
to predict how neurons or group of neurons should behave in order to achieve that function.
Some examples of the top-down approach are theories of associative memory, reinforcement
learning, and sparse coding [11].

3.1. Bottom-Up Approach
The brain contains billions of neurons that generate short electrical pulses, called action
potentials or spikes to communicate with each other. Hodgkin and Huxleys description of
neuronal action potentials [5] is widely used framework for biophysical neuron models. In these
models, cell membrane of a neuron is described by a number of ion channels, with specific time
constants and gating dynamics that control the momentary state (open or closed) of a channel
(Fig. 6C). By a series of mathematical steps and approximations, theory has sketched a
systematic bottom-up path from such biophysical models of single neurons to macroscopic
models of neural activity [11].
In the first step, biophysical models of spike generation are reduced to integrate-and-fire
models where spikes occur whenever the membrane potential reaches the threshold (Fig. 6B).
In the next step, the population activity A(t)defined as the total number of spikes
emitted by a population of interconnected neurons in a short time windowis predicted from the
properties of individual neurons using mean-field methods known from physics. Each neuron
receives input from many others, it is sensitive only to their average activity (mean field) but
not to the activity patterns of individual neurons [11].
Instead of the spike based interaction among thousands of neurons, network activity can
therefore be described macroscopically as an interaction between different populations Such
macroscopic descriptionsknown as population models, neural mass models, or, in the
continuum limit, neural field models (Fig. 6A)help researchers to gain an intuitive and more
analytical understanding of the principal activity patterns in large networks. Although the
transition from microscopic to macroscopic scales relies on purely mathematical arguments,
simulations are important to add aspects of biological realism (such as heterogeneity of neurons
and connectivity, adaptation on slower time scales, and variability of input and receptive fields)



that are difficult to treat mathematically. However, the theoretical concepts and the essence of
the phenomena are often robust with respect to these aspects [11].


Fig6: Bottom up approach in nervous system [11]

3.2. Decision-Making: Combines Top-Down and Bottom-Up
Often we have to take a decision between two alternatives (A or B), such as Should I do
it or not?. Psychometric measures of performance and reaction times for two alternative forced-
choice decision-making paradigms can be explained by a phenomenological drift-diffusion
model. This model consists of a diffusion equation describing a random variable that
accumulates noisy sensory data until it reaches one of two boundaries corresponding to a specific
choice (Fig. 7A). Although this model able to describe reaction time distribution, it suffers from
a crucial disadvantage, namely the difficulty in assigning a biological meaning to the model
parameters [11].
Recently, neurophysiological experiments have begun to reveal neuronal correlates of
decision making, in tasks involving visual patterns of moving random dots or vibrotactile or
auditory frequency comparison. Computational neuroscience offers a framework to bridge the
conceptual gap between the cellular and the behavioral level. Explicit simulations of microscopic
models based on local networks with large numbers of spiking neurons can reproduce and
explain both the neurophysiological and behavioral data. These models describe the interactions
between two groups of neurons coupled through mutually inhibitory connections (Fig. 7C).
Suitable parameters are inferred by studying the dynamical regimes of the system and choosing



parameters consistent with the experimental observations of decision behavior. Thus, the pure
bottom-up model is complemented by the top-down insights of target functions that the network
needs to achieve [11].



Fig 7: Decision making in nervous system [11]

3.3. Large-scale brain networks and cognition
Much of our current knowledge of cognitive brain function has come from the modular
paradigm, in which brain areas are postulated to act as independent processors for specific
complex cognitive functions [15]. Recent research shows that this paradigm has serious
limitations and might in fact be misleading. Even the functions of primary sensory areas of the
cerebral cortex, once thought to be pinnacles of modularity, are being redefined by recent
evidence of cross-modal interactions. A new paradigm is emerging in cognitive neuroscience
that suggests instead of working in a modular way for a cognitive function brain areas are
working conjointly as a large scale networks [12, 13, 15] .

Large-scale structural brain networks
The neuroanatomical structure of large-scale brain networks give us an idea of connected
brain areas that facilitates signaling along a particular pathway for the service of specific
cognitive functions. It is important to identify the brain areas that constitute structural network
nodes and the connecting paths that serve as structural network edges to know which
configurations of interacting areas are possible. In the past, large-scale structural brain networks



were often schematized by two-dimensional wiring diagrams, with brain areas connected by
lines or arrows representing pathways. Currently, more sophisticated network visualization and
analysis schemes are being developed and used. Principal methods to define structural nodes and
edges in the brain is described first. Some of possible functional consequences of the structural
organization of large-scale brain networks is described then [15].

Nodes
The nodes of large-scale structural brain networks are typically brain areas defined by: (i)
cytoarchitectonics; (ii) local circuit connectivity; (iii) output projection target commonality; and
(iv) input projection source commonality. A brain area can be described as a subnetwork of a
large-scale network; this subnetwork consists of neuron populations (nodes) and connecting
pathways (edges). Despite the complex internal structure of each node, it is often convenient,
particularly in network modeling research, to treat them as unitary neural masses that serve as
spatially undifferentiated (lumped) nodes in large-scale networks. The definition of nodes are
changing time to time as new methods are developed and understanding of structure function
relations in the brain evolves .Techniques used in recent years to determine structural nodes from
neuroanatomical data include: (i) anatomical parcellation of the cerebral cortex using the
Brodmann atlas; (ii) parcellation in standardized Montreal Neurological Institute (MNI) space
using macroscopic landmarks in structural magnetic resonance imaging (sMRI) data; (iii)
subject-specific automated cortical parcellation based on gyral folding patterns; (iv) quantitative
cytoarchitectonic maps; and (v) neurochemical maps showing neurotransmitter profiles .Diverse
tradeoffs arise in the use of these techniques [15]. Classical, but still popular Brodmaan mapping
scheme is used for analysis. (Details are given in appendix - 1)

Problem in node selection
A major problem being that of anatomical specificity versus extent of coverage across the
brain. This problem is particularly acute for the cerebral cortex because the borders of most
cortical regions cannot be reliably detected using macroscopic features from sMRI. The choice
of spatial scale for nodal parcellation has important consequences for the determination of
network connectivity [15].
Although newer methods offer a tighter link with the functional architecture of the brain,
but still coverage exists for only a small set of cortical regions and a wide area of human
prefrontal and temporal cortices have not yet been adequately mapped. Most anatomical
parcellation studies have focused on the cerebral cortex. Less attention has been paid to
subcortical structures such as the basal ganglia and the thalamus, which have only been
demarcated at a coarse level using sMRI. Brainstem systems mediating motivation, autonomic
function and arousal have been poorly studied because they are very difficult to identify using in
vivo techniques. Nonetheless, it is important to identify these structures because they
significantly influence cortical signaling and thus affect cognitive function [15].






Fig 8: Structural nodes of cerebral cortex [15]
Edges
The edges connecting brain areas in large-scale structural networks are long-range axon
pathways. Network edges are directed because axon fiber pathways have direction from the
somata to the synapses, and can be bidirectional when axon pathways run in both directions
between particular brain areas. Each brain area has a unique connection set of other areas with
which it is interconnected. Network edges have variable weights based on the number and size of
axons in the pathways, and the number and strengths of functioning synapses at the axon
terminals [15].
Three main approaches are currently used to trace axon pathways, and thus determine
structural network edges.
The first is autoradiographic tracing in experimental animals. In the macaque monkey,
this technique has provided a rudimentary map of anatomical links between major cortical areas
and more recently has successfully detailed rostrocaudal and dorsalventral connectivity
gradients between major prefrontal and parietal cortical areas [15].
The second approach uses diffusion-based magnetic resonance imaging methods, such as
diffusion tensor imaging (DTI) and diffusion spectrum imaging (DSI), to determine major fiber
tracts of the human brain in vivo by identifying the density of connections between brain areas
[15]. (Fig .9)
The third approach to mapping of network edges uses anatomical features such as local
cortical thickness and volume to measure anatomical connectivity. In this approach, which has
evolved during the same recent time period as DTI technology, interregional covariation in
cortical thickness and volume across subjects is used to estimate connectivity [15].







Problem in edge selection
In autoradiographic tracing however it is difficult, to extrapolate from macaque
connectional neuroanatomy to that of the human brain because the degree of pathway homology
between macaque and human brains is not well understood.
Diffusionbased tractography of the entire human brain is still in its early days, but rapidly
evolving techniques are providing reliable estimates of the anatomical connectivity of several
hundred cortical nodes [12, 13]. With additional anatomical constraints on seeds and targets
in diffusion- based tractography, it is increasingly possible to make closer links between
projection zones and cytoarchitectonic maps [15].
In the third method edges that are identified might not actually reflect axonal pathways
and precaution is required in interpreting the results. Nevertheless, networks identified using this
approach have revealed stable graph-theoretic properties [15].

Comments on Structural Nodes and Edges
Recent studies have combined both node and edge detection to identify structural
networks, either across the whole brain or within specific brain systems. At the whole-brain
level, network nodes are determined by one of the parcellation methods described above, and
then network edges are determined by DTI or DSI. If, however, structural network nodes are
inferred from DTI or DSI patterns of convergence and divergence, nodes and edges cannot be
independently identified. Within specific functional systems, such as for language or working
memory, the nodes are constrained to lie within the system and then the edges are identified by
diffusion-based tractography . The use of cytoarchitectonic boundaries to define the nodes allows
aspects of brain connectivity that are more closely linked to the underlying neuronal organization
to be uncovered in parallel [12-15].

Large-scale functional brain networks
Human brain has evolved to provide survival strategy to human in a way that one can
survive in a wide varity of ambience changes, act differently in different condition depending on
the situtiation. At each moment certain set of conditions must be analyzed by human brain with
the help of perception. The set of perception along with the learned concepts produce an
immediate solution to the immediate problem and act accordingly. It is reasonable to assume that
a set of interconnected brain areas act in tandem to provide these solutions, as well as
corresponding behavior and that they interact dynamically to achieve an action. A large-scale
functional network can therefore be defined as a collection of interconnected brain areas that
interact to perform circumscribed functions. The topological form of functional networks
changes throughout an individuals lifespan and is uniquely shaped by maturational and learning
processes within the large-scale neuroanatomical connectivity matrix for each individual [13-15].






Nodes
The characterization of functional networks in the brain requires identification of
functional nodes. However, there is no commonly agreed definition of what constitutes a
functional node in the brain. Since the advent of advanced functional electrophysiological and
neuroimaging methods, additional methodologies to define functional network nodes have
become available. A network node can be a circumscribed brain region displaying elevated
metabolism in positron emission tomography (PET) recordings, elevated blood perfusion in
functional magnetic resonance imaging (fMRI) recordings, or synchronized oscillatory activity
in local field potential (LFP) recordings. Participation of a brain area in a large-scale functional
network is commonly inferred from its activation or deactivation in relation to cognitive
function. A group of brain areas jointly and uniquely activated or deactivated during cognitive
function with respect to a baseline state can represent the nodes of a large-scale network for that
function [15].

Problem of selection of Functional nodes
A major challenge is to determine how functional network nodes defined by different
recording modalities are related, and how they relate to structural network nodes. From the
network perspective, cognitive functions are carried out in real time by the operations of
functional networks comprised of unique sets of interacting network nodes. For a brain area to
qualify as a functional network node, it must be demonstrated that, in combination with a
particular set of other nodes, it is engaged in a particular class of cognitive functions. Although it
is not yet known how the various definitions of large-scale functional network nodes derived
from different recording modalities are related, a possible scenario is that the elevated
excitability of neurons within an area leads to elevated metabolic activity, which in turn causes
an increase in local blood oxygen availability. The elevated excitability could also cause
increased interactions between neurons within the area. Interactions between different
populations can produce oscillatory activity and can have important functional consequences if,
for example, the interactions lead to increased sensitivity of neurons within the area to the inputs
that they receive [15].
Much of the work in the field of functional neuroimaging uses the fMRI blood-oxygen-level-
dependent (BOLD) signal to identify the nodes of large-scale functional networks by relating the
joint activation of brain areas to different cognitive functions. fMRI BOLD activation has
revealed network nodes that are involved in such cognitive functions as attention [58], working
memory, language, emotion, motor control and time perception [15].

Edges
The identification of functional network edges comes from different forms of functional
interdependence (or functional connectivity) analysis, which assesses functional interactions
among network nodes. The identification of network edges, like that of network nodes, is highly
dependent on the monitoring methodology. Functional interdependence analysis can identify



network edges from time series data in the time (e.g. cross-correlation function) or frequency
(e.g., spectral coherence or phase synchrony measures) domain. In either domain, the analysis
can use a symmetric measure, in which case significant interdependences are represented as
undirected edges, or an asymmetric measure, in which case they are represented as directed
edges. Methods using directional measures include Granger causality analysis and dynamic
causal modeling. Functional interdependences must be statistically significant for them to
represent the edges of large-scale functional networks. Determination of thresholds for
significance testing of network edges is often fraught with difficulty, and the particular method
used for threshold determination can have an appreciable impact on the resulting large-scale
network. Certain graph-theoretic measures, however, do not suffer from this problem because
they take into account the full weight structure of the network. Fluctuations in neuronal
population activity at different time scales can control the time-dependent variation of
engagement and coordination of areas in large-scale functional networks. Network edges are
possibly best represented by the correlation of time series fluctuations at different time scales,
reflecting different functional network properties. The correlation of slow fluctuations at rest in
fMRI BOLD signals possibly reflects slow interactions necessary to maintain the structural and
functional integrity of networks, whereas the correlation of fast fluctuations could reflect fast
dynamic coupling required for information exchange within the network [12-15].
Functional interdependence has been observed across a range of time scales from
milliseconds to minutes. Recent evidence suggests that slow intracranial cortical potentials are
related to the fMRI BOLD signal. It is possible that functional networks are organized according
to a hierarchy of temporal scales, with structural edges constraining slow functional edges, which
in turn constrain progressively faster network edges. Studies in both monkeys and humans
support the existence of hierarchical functional organization across time scales [15].

Intrinsic functional brain networks
Functional interdependence analysis has often been used to investigate interactions
between brain areas during task performance. Although task-based analyses have enhanced our
understanding of dynamic context-dependent interactions, they often have not contributed to a
principled understanding of functional brain networks. By focusing on task-related interactions
between specific brain areas, they have tended to ignore the anatomical connectivity and
physiological processes that underlie these interactions. Intrinsic interdependence analysis of
fMRI data acquired from subjects at rest and unbiased by task demands has been used to identify
intrinsic connectivity networks (ICNs) in the brain. ICNs identified in the resting brain include
networks that are also active during specific cognitive operations, suggesting that the human
brain is intrinsically organized into distinct functional networks. One key method for identifying
ICNs in resting-state fMRI BOLD data is independent component analysis (ICA), which has
been used to identify ICNs involved in executive control, episodic memory, autobiographical
memory, self-related processing and detection of salient events. ICA has revealed a sensorimotor
ICN anchored in bilateral somatosensory and motor cortices, a visuospatial attention network
anchored in intra-parietal sulci and frontal eye fields, a higher-order visual network anchored in



lateral occipital and inferior temporal cortices, and a lower-order visual network. This technique
has allowed intrinsic, as well as task-related, fMRI activation patterns to be used for
identification of distinct functionally coupled systems, including a central-executive network
(CEN) anchored in dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC),
and a salience network anchored in anterior insula (AI) and anterior cingulate cortex (ACC) [15].
A second major method of ICN identification is seedbased functional interdependence
analysis. Like ICA, this technique has been used to examine ICNs associated with specific
cognitive processes such as visual orienting attention, memory and emotion. First, a seed region
associated with a cognitive function is identified. Then, a map is constructed of brain voxels
showing significant functional connectivity with the seed region. This approach has
demonstrated that similar networks to those engaged during cognitive task performance are
identifiable at rest, including dorsal and ventral attention systems and hippocampal memory
systems. It has also revealed distinct functional circuits within adjacent brain regions: functional
connectivity maps of the human basolateral and centromedial amygdal [15].
Graph-theoretic studies of resting-state fMRI functional connectivity results have
suggested that human large-scale functional brain networks are usefully described as small-
world. Other graph-theoretic metrics such as hierarchy have been useful in characterizing
subnetwork topological properties, but a consistent view of hierarchical organization in large-
scale functional networks has yet to emerge [15]


















Problem Formulation and Methodology
In our work we have hypothised human nervous system according the following tree.

Graphical representation of human nervous system is given below-

Fig 12: Human Nervous System(HNS), Graphical representation




Problem#1
Model human nervous system(HNS) as a large distributed network and try to predict some of the
cognitive behavior from this network mathematically.




Appendix-1(Brodmaan Area)


Areas Broad Parts Location in Brain Functions Remarks
Area- 3, 2, 1 Primary Somatosensory
Cortex
The lateral postcentral gyrus
is a prominent structure in
the parietal lobe of the
human brain and an
important landmark. It is the
location of the primary
somatosensory cortex
The main sensory receptive area for
the sense of touch

Area- 4 Primary Motor Cortex It is located in the posterior
portion of the frontal lobe.
is about the same as the
precentral gyrus.
The borders of this area are:
the precentral sulcus in front
(anteriorly), the medial
longitudinal fissure at the
top (medially), the central
sulcus in back (posteriorly),
and the lateral sulcus along
the bottom (laterally).

Plan and execute movements.
Area- 5 Somatosensory Association
Cortex
Part of the parietal cortex in
the human brain.
It is situated immediately
posterior to the primary
somatosensory areas
(Brodmann areas 3, 1, and
2), and anterior to
Brodmann area 7.
It is involved in somatosensory
processing and association.(The
somatosensory system is a diverse
sensory system comprising the
receptors and processing centres to
produce the sensory modalities such
as touch, temperature, proprioception
(body position), and nociception
(pain). The sensory receptors cover
the skin and epithelia, skeletal
muscles, bones and joints, internal
organs, and the cardiovascular
system.)

Area- 6 Premotor cortex and
Supplementary Motor Cortex
(Secondary Motor
Cortex)(Supplementary motor
area)
It is part of the frontal
cortex in the human brain.
Situated just anterior to the
primary motor cortex
(BA4), it is composed of the
premotor cortex and,
medially, the supplementary
motor area, or SMA.
This large area of the frontal cortex is
believed to play a role in the planning
of complex, coordinated movements.
Brodmann area 6 is
also called agranular
frontal area 6 in
humans because it
lacks an internal
granular cortical
layer (layer IV).
Area- 7 Somatosensory Association
Cortex
Part of the parietal cortex in
the human brain. Situated
posterior to the primary
somatosensory cortex
(Brodmann areas 3, 1 and
2), and superior to the
occipital lobe
This region is believed to play a role
in visuo-motor coordination.
area 7 along with area 5 has been
linked to a wide variety of high-level
processing tasks, including activation
in association with language use.This
function in language has been
theorized to stem from how these two
regions play a vital role in generating
conscious constructs of objects in the
world.




Area- 8 Includes Frontal eye fields Part of the frontal cortex in
the human brain. Situated
just anterior to the premotor
cortex (BA6)
Believed to play an important role in
the control of eye movements.

Area- 9 Dorsolateral prefrontal cortex Part of the frontal cortex in
the human brain.
DLPFC serves as the highest cortical
area responsible for motor planning,
organization, and regulation.
It plays an important role in the
integration of sensory and mnemonic
information and the regulation of
intellectual function and action,
especially in relation to impulse
control.
It is also involved in working
memory.
However, DLPFC is not exclusively
responsible for the executive
functions. All complex mental activity
requires the additional cortical and
subcortical circuits with which the
DL-PFC is connected.

Area- 10 Anterior prefrontal cortex
(most rostral part of superior
and middle frontal gyri)
It is the anterior-most
portion of the Prefrontal
cortex in the human brain.
One of the least well understood
regions of the human brain".

Present research suggests that it is
involved in strategic processes in
memory recall and various executive
functions.
During human
evolution, the
functions in this
area resulted in its
expansion relative
to the rest of the
brain
Area- 11 Orbitofrontal area (orbital and
rectus gyri, plus part of the
rostral part of the superior
frontal gyrus)
It is a prefrontal cortex
region in the frontal lobes in
the brain
It is involved in the cognitive
processing of decision-making.

Area- 12 Orbitofrontal area (used to be
part of BA11, refers to the
area between the superior
frontal gyrus and the inferior
rostral sulcus)
It occupies the most rostral
portion of the frontal lobe.
Not known
Area- 13, 14 Insular cortex In each hemisphere of the
mammalian brain the insular
cortex (often called insula,
insulary cortex or insular
lobe) is a portion of the
cerebral cortex folded deep
within the lateral sulcus (the
fissure separating the
temporal lobe from the
parietal and frontal lobes).
The insulae are believed to be
involved in consciousness and play a
role in diverse functions usually
linked to emotion or the regulation of
the body's homeostasis. These
functions include perception, motor
control, self-awareness, cognitive
functioning, and interpersonal
experience. In relation to these it is
involved in psychopathology.
Area -14 for non-
human primates.
Area- 15 Anterior Temporal Lobe Subdivisions of the cerebral
cortex in the brain.
Area 15 was defined
by Brodmann in the
guenon monkey, but
he found no
equivalent structure
in humans.
Area- 17 Primary visual cortex (V1) Part of the cerebral cortex It
is located in the occipital
lobe, in the back of the
brain.
Responsible for processing visual
information.




Area- 18 Secondary visual cortex (V2) It is part of the occipital
cortex in the human brain.
is the second major area in
the visual cortex, and the
first region within the visual
association area.
It receives strong feedforward
connections from V1 (direct and via
the pulvinar) and sends strong
connections to V3, V4, and V5. It also
sends strong feedback connections to
V1.

Area- 19 Associative visual cortex
(V3,V4,V5)
It is part of the occipital
lobe cortex in the human
brain.
Area 19 has been noted to receive
inputs from the retina via the superior
colliculus and pulvinar, and may
contribute to the phenomenon of
blindsight.
In patients blind
from a young age,
the area has been
found to be
activated by
somatosensory
stimuli.
Area- 20 Inferior temporal gyrus It is placed below the
middle temporal gyrus, and
is connected behind with the
inferior occipital gyrus; it
also extends around the
infero-lateral border on to
the inferior surface of the
temporal lobe, where it is
limited by the inferior
sulcus.
This region believed to play a part in
high-level visual processing and
recognition memory.
It may also be involved in face
perception, and in the recognition of
numbers.

Area- 21 Middle temporal gyrus Middle temporal gyrus is a
gyrus in the brain on the
Temporal lobe. It is located
between the superior
temporal gyrus and inferior
temporal gyrus
Its exact function is unknown, but it
has been connected with processes as
different as contemplating distance,
recognition of known faces, and
accessing word meaning while
reading.

Area- 22 Superior temporal gyrus, of
which the caudal part is
usually considered to contain
the Wernicke's area
The superior temporal gyrus
is one of three (sometimes
two) gyri in the temporal
lobe of the human brain,
which is located laterally to
the head, situated somewhat
above the external ear. The
superior temporal gyrus is
bounded by: the lateral
sulcus above; the superior
temporal sulcus (not always
present or visible) below; an
imaginary line drawn from
the preoccipital notch to the
lateral sulcus posteriorly.
On the left side of the brain this area
helps with generation and
understanding of individual words. On
the right side of the brain it helps to
discriminate pitch and sound intensity,
both of which are necessary to
perceive melody and prosody.
Researchers believe this part of the
brain is active in processing language.

Area- 23 Ventral posterior cingulate
cortex
The posterior cingulate
cortex is the backmost part
of the cingulate cortex, lying
behind the anterior cingulate
cortex. This is the upper part
of the "limbic lobe". The
cingulate cortex is made up
of an area around the
midline of the brain.
Surrounding areas include
the retrosplenial cortex and
the precuneus.
The posterior cingulate cortex forms a
central node in the "default mode"
network of the brain. It has been
shown to communicate with various
brain networks simultaneously and is
involved in various functions. Along
with the precuneus, the posterior
cingulate cortex has been implicated
as a neural substrate for human
awareness in numerous studies of both
the anesthesized and vegetative
(coma) state. Imaging studies indicate
a prominent role for the posterior
cingulate cortex in pain and episodic
memory retrieval. It has also been
revealed that increased size of
posterior ventral cingulate cortex is
related to the working memory
performance decline. Furthermore, the




posterior cingulate may be involved in
the capacity to understand what other
people believe.
Area- 24 Ventral anterior cingulate
cortex.
The anterior cingulate
cortex (ACC) is the frontal
part of the cingulate cortex,
surrounding the frontal part
of the corpus callosum.
It appears to play a role in a wide
variety of autonomic functions, such
as regulating blood pressure and heart
rate, as well as rational cognitive
functions, such as reward anticipation,
decision-making, empathy, impulse
control,and emotion.

Area- 25 Subgenual area (part of the
Ventromedial prefrontal
cortex
It is an area in the cerebral
cortex of the brain
This region is extremely rich in
serotonin transporters and is
considered as a governor for a vast
network involving areas like
hypothalamus and brain stem, which
influences changes in appetite and
sleep; the amygdala and insula, which
affect the mood and anxiety; the
hippocampus, which plays an
important role in memory formation;
and some parts of the frontal cortex
responsible for self-esteem

Area- 26 Ectosplenial portion of the
retrosplenial region of the
cerebral cortex
It is the retrosplenial region
of the cerebral cortex. It is a
narrow band located in the
isthmus of cingulate gyrus
adjacent to the fasciolar
gyrus internally. It is
bounded externally by the
granular retrolimbic are
Not known
Area- 28 Ventral entorhinal cortex Located in the medial
temporal lobe
Functioning as a hub in a widespread
network for memory and
navigation.He EC-hippocampus
system plays an important role in
autobiographical/declarative/episodic
memories and in particular spatial
memories including memory
formation, memory consolidation, and
memory optimization in sleep. The
EC is also responsible for the pre-
processing (familiarity) of the input
signals in the reflex nictitating
membrane response of classical trace
conditioning, the association of
impulses from the eye and the ear
occurs in the entorhinal cortex.
The EC is the main
interface between
the hippocampus
and neocortex.
Area- 29 Retrosplenial cingulate cortex In the human it is a narrow
band located in the isthmus
of cingulate gyrus.(The
cingulate cortex is a part of
the brain situated in the
medial aspect of the cerebral
cortex. It includes the cortex
of the cingulate gyrus,
which lies immediately
above the corpus callosum,
and the continuation of this
in the cingulate sulcus. The
cingulate cortex is usually
considered part of the limbic
lobe.)
It receives inputs from the thalamus
and the neocortex, and projects to the
entorhinal cortex via the cingulum. It
is an integral part of the limbic
system, which is involved with
emotion formation and processing,
learning, and memory. The
combination of these three functions
makes the cingulate gyrus highly
influential in linking behavioral
outcomes to motivation (e.g. a certain
action induced a positive emotional
response, which results in learning). It
also plays a role in executive function
and respiratory control.
cingulate cortex
highly important in
disorders such as
depressionand
schizophrenia.
Area- 30 Part of cingulate cortex In the human it is a narrow
band located in the isthmus




of cingulate gyrus.
Area- 31 Dorsal Posterior cingulate
cortex
In the human it occupies
portions of the posterior
cingulate gyrus and medial
aspect of the parietal lobe.
Approximate boundaries are
the cingulate sulcus dorsally
and the parieto-occipital
sulcus caudally. It partially
surrounds the subparietal
sulcus, the ventral
continuation of the cingulate
sulcus in the parietal lobe.
Cytoarchitecturally it is
bounded rostrally by the
ventral anterior cingulate
area 24, ventrally by the
ventral posterior cingulate
area 23, dorsally by the
gigantopyramidal area 4 and
preparietal area 5 and
caudally by the superior
parietal area 7

Area- 32 Dorsal anterior cingulate
cortex
In the human it forms an
outer arc around the anterior
cingulate gyrus. The
cingulate sulcus defines
approximately its inner
boundary and the superior
rostral sulcus (H) its ventral
boundary; rostrally it
extends almost to the
margin of the frontal lobe.
Cytoarchitecturally it is
bounded internally by the
ventral anterior cingulate
area 24, externally by
medial margins of the
agranular frontal area 6,
intermediate frontal area 8,
granular frontal area 9,
frontopolar area 10, and
prefrontal area 11

Area- 33 Part of anterior cingulate
cortex
It is a narrow band located
in the anterior cingulate
gyrus adjacent to the
supracallosal gyrus in the
depth of the callosal sulcus,
near the genu of the corpus
callosum.
Cytoarchitecturally it is
bounded by the ventral
anterior cingulate area 24
and the supracallosal gyrus

Area- 34 Dorsal entorhinal cortex (on
the Parahippocampal gyrus)
Area 28
Area- 35 Perirhinal cortex (in the rhinal
sulcus)
Perirhinal cortex is a
cortical region in the medial
temporal lobe
It receives highly-processed sensory
information from all sensory regions,
and is generally accepted to be an
important region for memory.

Area- 36 Ectorhinal area, now part of
the perirhinal cortex (in the
It is located in temporal
region of cerebral cortex.
With its medial boundary




rhinal sulcus) corresponding
approximately to the rhinal
sulcus it is located primarily
in the fusiform gyrus.
Cytoarchitecturally it is
bounded laterally and
caudally by the inferior
temporal area 20, medially
by the perirhinal area 35 and
rostrally by the
temporopolar area 38
Area- 37 Fusiform gyrus The fusiform gyrus is part of
the temporal lobe and
occipital lobe
There is still some dispute over the
functionalities of this area, but there is
relative consensus on the following:
processing of color information face
and body recognition (see Fusiform
face area) word recognition (see
Visual word form area)within-
category identification

Area- 38 Temporopolar area (most
rostral part of the superior and
middle temporal gyri)
It is part of the temporal
cortex in the human brain.
BA 38 is at the anterior end
of the temporal lobe, known
as the temporal pole.
The functional significance of this
area TG is not known, but it may bind
complex, highly processed perceptual
inputs to visceral emotional responses
is unique to humans
Area- 39 Angular gyrus, considered by
some to be part of Wernicke's
area
The angular gyrus is a
region of the brain in the
parietal lobe, that lies near
the superior edge of the
temporal lobe, and
immediately posterior to the
supramarginal gyrus
It is involved in a number of processes
related to language, number
processing and spatial cognition,
memory retrieval, attention, and
theory of mind.

Area- 40 Supramarginal gyrus
considered by some to be part
of Wernicke's area
It is part of the parietal
cortex in the human brain.
The inferior part of BA40 is
in the area of the
supramarginal gyrus, which
lies at the posterior end of
the lateral fissure, in the
inferior lateral part of the
parietal lobe.
It is probably involved with language
perception and processing, and lesions
in it may cause Receptive aphasia or
transcortical sensory aphasia

Area- 41, 42 Auditory cortex The auditory cortex is the
part of the cerebral cortex
that processes auditory
information in humans and
other vertebrates. It is
located bilaterally, roughly
at the upper sides of the
temporal lobes in humans
on the superior temporal
plane, within the lateral
fissure and comprising parts
of Heschl's gyrus and the
superior temporal gyrus,
including planum polare and
planum temporale
A part of the auditory system, it
performs basic and higher functions in
hearing.

Area- 43 Primary gustatory cortex Defined in the postcentral
region of cerebral cortex. It
occupies the postcentral
gyrus and the precentral
gyrus between the
ventrolateral extreme of the
central sulcus and the depth
of the lateral sulcus at the
Not known



insula.
Area- 44 Pars opercularis, part of
Broca's area
n the human, this region
occupies the triangular part
of the inferior frontal gyrus
and, surrounding the
anterior horizontal limb of
the lateral sulcus, a portion
of the orbital part of the
inferior frontal gyrus.
Bounded caudally by the
anterior ascending limb of
the lateral sulcus, it borders
on the insula in the depth of
the lateral sulcus.
Recent neuroimaging studies show
BA44 involvement in selective
response suppression in go/no- go
tasks and is therefore believed to play
an important role in the suppression of
response tendencies.Neuroimaging
studies also demonstrate that area 44
is related to hand movements.

Area- 45 Pars triangularis Broca's area Brodmann area 45 (BA45),
is part of the frontal cortex
in the human brain. Situated
on the lateral surface,
inferior to BA9 and adjacent
to BA46.
Together with BA 44, it comprises
Broca's area, a region that is active in
semantic tasks, such as semantic
decision tasks (determining whether a
word represents an abstract or a
concrete entity) and generation tasks
(generating a verb associated with a
noun).

Area- 46 Dorsolateral prefrontal cortex Brodmann area 46, or
BA46, is part of the frontal
cortex in the human brain. It
is between BA10 and BA45.
BA46 is known as middle
frontal area 46. In the
human brain it occupies
approximately the middle
third of the middle frontal
gyrus and the most rostral
portion of the inferior
frontal gyrus. Brodmann
area 46 roughly corresponds
with the dorsolateral
prefrontal cortex (DLPFC)
The DLPFC plays a role in sustaining
attention and working memory.
Lesions to the DLPFC impair short-
term memory and cause difficulty
inhibiting responses. Lesions may also
eliminate much of the ability to make
judgements about what's relevant and
what's not as well as causing problems
in organization. The DLPFC has
recently been found to be involved in
exhibiting self-control.

Area- 47 pars orbitalis, part of the
inferior frontal gyrus
Brodmann area 47, or
BA47, is part of the frontal
cortex in the human brain.
Curving from the lateral
surface of the frontal lobe
into the ventral (orbital)
frontal cortex. It is below
areas BA10 and BA45, and
beside BA11.
This area is also known as
orbital area 47. In the
human, on the orbital
surface it surrounds the
caudal portion of the orbital
sulcus (H) from which it
extends laterally into the
orbital part of inferior
frontal gyrus
BA47 has been implicated in the
processing of syntax in oral and sign
languages, and more recently in
musical syntax.

Area- 48 Retrosubicular area (a small
part of the medial surface of
the temporal lobe)
In the human it is located on
the medial surface of the
temporal lobe.
Not known
Area- 49 Parasubicular area in a rodent
























Area- 52 Parainsular area (at the
junction of the temporal lobe
and the insula)
It is located in the bank of
the lateral sulcus on the
dorsal surface of the
temporal lobe. Its medial
boundary corresponds
approximately to the
junction between the
temporal lobe and the
insula.
Not known



References

[1] M.F.Bear, B.W.Connors, M.A.Paradiso, Neuroscience: Exploring the Brain, Lippincott Williams &
Wilkins, 2007

[2] Gerstner and Kistler. Spiking Neuron Models. Single Neurons, Populations, Plasticity.Cambridge
University, 2002.

[3] P.Dayan and L.F. Abbott, Theoretical Neuroscience: Computational and Mathematical Modeling of
Neural Systems. The Mit Press, 2001

[4] R.B. Stein. Some models of neuronal variability. Biophysical Journal, 7:3768, 1967.

[5] A. L. Hodgkin and A. F. Huxley, A quantitative description of membrane current and its application to
conduction and excitation in nerve. Journal of Physiology, 117:500544, 1952.

[6] William B Levy and Robert A. Baxter, Energy-efficient neuronal computation via quantal synaptic
failures. Journal of Neuroscience, 22(11):4746 4755, June 2002.

[7] Thomas M. Cover and Joy A. Thomas. Elements of Information Theory. Wiley Series in
Telecommunications. John Wiley & Sons, New York, 1991.

[8] T. Berger, Living information theory: The 2000 Shannon lecture. IEEE Information Theory Society
Newsletter, 53:1,619, 2003.

[9] Claude E. Shannon, A mathematical theory of communication. The Bell System Technical Journal,
27:379423 and 623656, July and October 1948.

[10] A. Borst and F. E. Theunissen, Information theory and neural coding .Nature Neuroscience, 2:947
957, 1999.

[11] W. Gerstner and H. Sprekeler and G. Deco , Theory and Simulation in Neuroscience . Science
338:60-65, 2012

[12] Goldman-Rakic, P.M. Topography of cognition: parallel distributed networks in primate association
cortex. Annu. Rev. Neurosci. 11, 137156, 1988

[13] Hagmann, P. et al. Mapping the structural core of human cerebral cortex. PLoS Biol. 6, e159, 2008

[14] Bullmore, E. and Sporns, O. Complex brain networks: graph theoretical analysis of structural and
functional systems. Nat. Rev. Neurosci. 10, 186198, 2009

[15] Steven L. Bressler and Vinod Menon. Large-scale brain networks in cognition: emerging methods
and principles. Trends in Cognitive Sciences Vol.14, No.6, 277-290, 2010