Complex Network Analysis of Brain Connectivity: An Introduction
Transcript of Complex Network Analysis of Brain Connectivity: An Introduction
Complex Network Analysis of Brain Connectivity: An Introduction
LABREPORT 5
Fernando Ferreira-Santos
2012
Title: Complex Network Analysis of Brain Connectivity: An Introduction
Technical Report
Authors: Fernando Ferreira-Santos
University of Porto, Portugal and University College London, UK
Keywords: brain connectivity; network theory; graph theory.
Citation (APA 6th):
Ferreira-Santos, F. (2012). Complex network analysis of brain connectivity: An introduction
(LabReport No. 5). Porto: Laboratory of Neuropsychophysiology (University of Porto). Retrieved
from: http://www.fpce.up.pt/labpsi/data_files/09labreports/LabReport_5.pdf
LABREPORTS Series, Number 5
Scientific coordination:
João Marques-Teixeira, Fernando Barbosa, Pedro R. Almeida, Fernando Ferreira-Santos
This work is licensed under the Creative Commons Attribution 3.0 Unported License. To view a copy of this
licensed, visit http://creativecommons.org/licenses/by/3.0/ or send a letter to Creative Commons, 171
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Laboratory of Neuropsychophysiology Faculdade de Psicologia e de Ciências da Educação da Universidade do Porto Rua do Dr. Manuel Pereira da Silva, 4200-392 Porto PORTUGAL http://www.fpce.up.pt/labpsi/ http://www.fpce.up.pt/
2012 Complex Network Analysis of Brain Connectivity: An Introduction
Complex Network Analysis of Brain Connectivity:
An Introduction
Introduction 3 Network definition and properties 4 Network measures and types 6 Modelling brain connectivity and network inferences 9 Conclusions 11 References 11
Introduction
In the last decades there has been an exponential increase in human neuroscientific
research. This is in part due to the widespread availability of non-invasive techniques for
measuring brain structure and activity, such as neuroimaging (e.g., MRI, fMRI, DTI) and
neurophysiological recordings (e.g., EEG, MEG), which produce large datasets of spatiotemporal
data. In fact, the amount of data obtained from a single fMRI or high-density EEG experiment in
the present day would be computationally intractable a few decades ago and it is still fairly
common for researchers to analyze only a small subset of the whole data collected (e.g., analysing
only a few selected EEG electrodes from a high-density recording). Presently, one of the areas of
technical advancement that is raising significant interest is that of brain connectivity (Bullmore &
Sporns, 2009; Reijneveld, Ponten, Berendse, & Stam, 2007; Sporns, 2011; Stam & Reijneveld,
2007), and one of the promises of connectivity analyses is to make the most of the rich datasets
that neuroscientists collect, by analysing the spatiotemporal dynamics present in the data.
The purpose of the present report is to introduce the basic concepts of Network Theory1
(often enumerating different terms that are used to represent the same concept) and their
1 Network Theory is the part of Graph Theory (a branch of Mathematics) that is specifically concerned with modelling complex real-world systems (moving away from the classical objects of Graph Theoretical analysis, namely random and regular graphs, which are poor candidates for modelling many real-world phenomena; Strogatz, 2001). Earlier references to these methods in Neuroscience tend refer solely to “Graph Theory”, which is still technically correct.
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2012 Complex Network Analysis of Brain Connectivity: An Introduction application to the study of brain connectivity. Brain connectivity is a broad concept, but can be
generally divided into three subtypes: structural, functional, and effective connectivity (Friston,
1994; see Horwitz [2003] for a discussion of some conceptual caveats). Structural connectivity
refers to the anatomical connections between brain regions, typically corresponding to white
matter tracts. Functional connectivity corresponds to the temporal correlation in the activity of
two brain regions, regardless of whether they have direct anatomic links. Finally, effective
connectivity consists of directed causal influences one brain region produces in another (Rubinov
& Sporns, 2010). A common denominator to the different kinds of brain connectivity is the idea
that, in all instances, the system can be described as a (structural or functional) network. The idea
that the brain is a network-like system is far from being novel in neuroscience, but attempts to
examine these properties under formal mathematical network theories are a recent endeavour.
Network definition and properties
In Network Theoretical terms, a network (or graph) is a mathematical model that
represents of a collection of nodes (or vertices) and links (or edges, or connections) between pairs
of nodes (Newman, 2003; Rubinov & Sporns, 2010) (Figure 1). Note that a complex network is an
abstract model and can be used to represent the brain systems at different levels (from small
ensembles of neurons and synaptic connections to macroanatomical regions connected by white
matter bundles)2.
Figure 1. Graphical representation of a network (or graph).
The characteristics of the links define the network properties. In the simplest case of
unweighted undirected networks, each link has the same strength or length (and, as such, existing
links are represented by 1 whereas the absence of a link is represented by 0) and links are
bidirectional (meaning the in a link connecting nodes A and B information can travel from A to B
and from B to A). If a network is weighted, this means that the links may differ from each other,
with some being stronger than others. The strength or length of each link is represented by its
2 In fact, networks have been used to model complex systems across disciplines from physics to the social sciences (Newman, 2003).
node
link
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2012 Complex Network Analysis of Brain Connectivity: An Introduction specific weight. Finally, a network may be directed if its links are unidirectional (in a directed link
connecting nodes A and B information can travel from A to B but not from B to A) (Figure 2).
Figure 2. Graphical representation of four networks illustrating the possible combinations of different properties.
As seen in Figures 1 and 2 above, networks can be graphically represented by plotting the
nodes and links according to the network properties, but the most computationally useful format
to represent networks in matrix form. The adjacency matrix is a n-by-n square matrix (n being the
number of nodes in the network). Usually the adjacency matrix is indicated by A and an individual
link is indicated as Ai,j. For visualization, the adjacency matrix can be coded in greyscale values
(0=black up to 1=white) or with other colour maps.
Figure 3. Graphical representation of three networks (top row) and the corresponding adjacency matrices, coded with a greyscale colour map (bottom row). The nodes are indicated by letters both in the graphical representation and in the adjacency matrix. For weighted networks the width of the links indicates connection strength. For directed networks the arrows indicate the direction of the information flow. Note that the adjacency matrices of undirected networks are necessarily symmetrical whereas for directed networks this is not the case.
WeightedUnweighted (binary)
Undirected(symmetrical)
Directed(asymmetrical)
B
D
C
A
E B
D
C
A
E
WeightedUnweighted (binary)Undirected (symmetrical)
A B C D E
A 0 1 1 1 0
B 1 0 1 1 0
C 1 1 0 1 0
D 1 1 1 0 1
E 0 0 0 1 0
A B C D E
A 0 0.8 0.5 1 0
B 0.8 0 0.2 0.5 0
C 0.5 0.2 0 0.8 0
D 1 0.5 0.8 0 0.8
E 0 0 0 0.8 0
B
D
C
A
E
Directed (asymmetrical)
A B C D E
A 0 1 1 1 0
B 0 0 1 1 0
C 0 0 0 1 0
D 1 0 0 0 1
E 0 0 0 1 0
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2012 Complex Network Analysis of Brain Connectivity: An Introduction
Network measures and types
The main advantage of formal Network Theoretical analysis is the precise quantification of
network parameters (or measures, or metrics) that allow examining the network topology and
efficiency. There are many measures which can be calculated for a network (for a detailed review
see Appendix 1 of Rubinov & Sporns, 2010), but only the core measures of networks will be
detailed below (Stam & Reijneveld, 2007)3 – Figure 4 provides examples of some of the core
measures of networks.
Set of nodes in a network (N) and size (n): the size of a network is the number of nodes (n) in it. It
corresponds to the number of rows of the adjacency matrix (or columns, given that it is a square
matrix). For a network of size n, he maximum number of possible links is (n– 1)n/2 for undirected
networks and (n– 1)n for directed networks (excluding the possibility of self-connections). The set
of all nodes in the network is usually represented by N.
Degree (k) and Degree Distribution: the degree (sometimes referred to as strength) of a node
consists of the number of links which connect to it, which is also the number of neighbour nodes
(i.e. nodes directly connected to it). The degree distribution consists of the degrees of all the
nodes in the network, and can be defined analytically as the probability of k as a function of k. The
mean degree of the network is a measure of the density or wiring cost of the network (the larger
the degree then the larger the number of connections).
Clustering coefficient (C): this is the main measure of local structure of a network which can be
calculated for individual nodes or for the entire network. The clustering coefficient ci of node i
with degree ki can be defined as the ratio of the actual number of links between neighbours of i
(ei), and the maximum possible number of links between those neighbours (neighbours of i are
nodes directly connected to node i).
𝑐𝑖 =2𝑒𝑖
𝑘𝑖(𝑘𝑖 − 1) (1)
The clustering coefficient C of the network is the average of all individual clustering coefficients:
3 In Network Theory notation there is a tendency to use capital letters to indicate network measures and lower case letters to denote node measures, although there are sometimes exceptions to this. The present report follows this convention.
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2012 Complex Network Analysis of Brain Connectivity: An Introduction
𝐶 =
1𝑁�𝑐𝑖
𝑁
𝑖=1
(2)
Clustering coefficients vary between 0 and 1. High clustering coefficients means that neighbouring
nodes are well interconnected. This suggests redundancy in connections, which protects the
network against random error, i.e. the loss of an individual node will have little impact on the
structure of the network.
Characteristic path length (L): this is a network measure indicates how integrated a network is and
how easy can information flow within the network. The path length or distance (or geodesic path)
di,j between two nodes i and j is the smallest number of links that connect i to j. The characteristic
path length L of a network is the average of distances between all pairs of nodes:
𝐿 =1
𝑁(𝑁 − 1)� 𝑑𝑖,𝑗
𝑖,𝑗∈𝑁,𝑖≠𝑗
(3)
Figure 4. Core network measures for two networks. The k and c values indicate the degree and clustering coefficient for each individual node (A to E), respectively. Note that differences in the density of connections, which in this example can be appreciated visually, are reflected by the value of the mean degree and lead to different degree distributions. The distance matrices indicate the distance d for each pair of nodes. The top network shows more interconnections between neighbouring nodes than the bottom network, leading to a higher C and a lower L.
A B C D E c
A 0 1 1 1 0 1
B 1 0 1 1 0 1
C 1 1 0 1 0 1
D 1 1 1 0 1 0.5
E 0 0 0 1 0 0
A B C D E c
A 0 1 1 1 0 0.3
B 1 0 0 0 0 0
C 1 0 0 1 0 1
D 1 0 1 0 1 0.3
E 0 0 0 1 0 0
C = 0.70
C = 0.33
L = 1.3
L = 1.6
A B C D E
A 0 1 1 1 2
B 1 0 1 1 2
C 1 1 0 1 2
D 1 1 1 0 1
E 2 2 2 1 0
A B C D E
A 0 1 1 1 2
B 1 0 2 2 3
C 1 2 0 1 2
D 1 2 1 0 1
E 2 3 2 1 0
Distance matrix
B
D
C
A
EA B C D E k
A 0 1 1 1 0 3
B 1 0 1 1 0 3
C 1 1 0 1 0 3
D 1 1 1 0 1 4
E 0 0 0 1 0 1
Mean k = 2.8
B
D
C
A
EA B C D E k
A 0 1 1 1 0 3
B 1 0 0 0 0 1
C 1 0 0 1 0 2
D 1 0 1 0 1 3
E 0 0 0 1 0 1
Mean k = 2.0
00.20.40.60.8
1
0 1 2 3 4
P(k)
Degree (k)
Degree distributionAdjacency matrixNetwork
00.20.40.60.8
1
0 1 2 3 4
P(k)
Degree (k)
Degree Clust. Coef.
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Based on the core measures presented so far, different types of networks can be
distinguished4 (Stam & Reijneveld, 2007 – Figure 5):
Ordered (regular or latice-like) networks: in these networks every node is connected to its k
neighbours, leading to an ordered connectivity structure. The degree of all nodes in such a
network is the same. This leads to a high clustering coefficient C (high resilience to random error)
and a high characteristic path length L (poor transmission of information).
Random networks: these are the opposite of ordered networks, as the links between nodes are
completely random. This leads to low C and low L (i.e., information travels easily, but the network
is vulnerable to the loss of single nodes).
Small-world networks: the small-world topology resembles an ordered network with a few
randomly rewired links. This means that small-world networks have high C, making them resilient,
but also low L, making them effective. A popularized idea related to the concept of small-world
networks is that of the “six degrees of separation” – according to this idea, a person is only six
acquaintances (or, in some versions, handshakes) away from any other person in the world
(http://en.wikipedia.org/wiki/Six_degrees_of_separation). This illustration captures the
interesting properties of small-world networks: most people have shaken hands with other
people from their community (high C). But a few people from that community, e.g. public figures
or politicians, will have shaken hands with several other people from other communities. These
“long-range” links mean that the distance (in handshakes) to other people is dramatically reduced
because of this specific person who functions as a hub in the network.
Small-worldness can be calculated via the following formula (Humphries & Gurney, 2008):
𝑆 =𝐶/𝐶rand𝐿/𝐿rand
(4)
Small-world networks often have S > 1. Note that C and Crand are the clustering coefficients,
and L and Lrand are the characteristic path lengths of the tested network and a random null
network, respectively (see section ‘Modelling brain connectivity and network inferences’ below).
4 Scale-free networks are an additional type of networks that will not be addressed in the present report. The degree distribution of scale-free networks follows a power law, i.e., the network grows by preferential attachment. For details see Stam & Reijneveld (2007).
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Figure 5. Reprinted with permission from Stam & Reijneveld (2007, p. 6): “Three basic network types in the model of Watts and Strogatz. The leftmost graph is a ring of 16 vertices (N=16), where each vertex is connected to four neighbours (k=4). This is an ordered graph which has a high clustering coefficient C and a long path length L. By choosing an edge at random, and reconnecting it to a randomly chosen vertex, graphs with increasingly random structure can be generated for increasing rewiring probability p. In the case of p=1, the graph becomes completely random, and has a low clustering coefficient and a short path length. For small values of p so-called small-world networks arise, which combine the high clustering coefficient of ordered networks with the short path length of random networks.”
Modelling brain connectivity and network inferences
When considering brain networks, the network nodes should ideally represent meaningful
brain regions. The use of EEG/MEG sensors as nodes is a common practice, but such results
should be carefully interpreted as the electromagnetic signals picked up are likely to show spatial
overlap. Regarding the network links, these may represent structural or functional associations. In
structural networks, links should represent the anatomical connections between brain regions,
and different weights may represent the size, amount or coherence of fibre tracts. For functional
and effective networks, links represent some measure correlation or causal influence
(respectively) between the activity of the nodes they connect (Rubinov & Sporns, 2010).
The first step of a network analysis is to extract a network model from the raw brain
connectivity data. From the raw data, one must produce a connectivity matrix that captures the
strengths of the connections between the nodes under analysis (which are usually represented
using continuous numeric scales). In a structural connectivity analysis this matrix could represent
white matter integrity (e.g., by considering anisotropy measures of brain structures); in a
functional connectivity analysis the connectivity matrix will show some measure of association
between channels or regions (e.g., temporal correlation, coherence); and in an effective
connectivity analysis the connectivity matrix will be populated by measures of causal influence
(e.g. Granger-causality, directed transfer function). The second step is to produce the adjacency
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2012 Complex Network Analysis of Brain Connectivity: An Introduction matrix. In weighted networks models, the adjacency matrix would simply be this connectivity
matrix (or a normalized version of it). However, it is more common to convert the connectivity
matrix to a binary (unweighted) adjacency matrix by retaining only the links that are above a
certain threshold. This leads to a binary network model, where the links above the threshold are
represented by 1 (presence of link) and those below it by 0 (absence of link). Finally, having
produced the adjacency matrix, one can calculate all relevant network measures, as described in
sections above.
Once the model has been specified and its parameters calculated, one is typically
interested in drawing inferences. In network analysis, this is usually done by comparing the
measures of the tested network with those of a similar but random network, which constitutes
the null network against which inferences are drawn. Randomization can take place at different
steps of the modelling process (Zalesky, Fornito, & Bullmore, 2012), but it is usually accomplished
by randomly shuffling the cells of the connectivity matrix prior to thresholding (Stam & Reijneveld,
2007). The random null network will be similar to the network under study in several dimensions
(e.g., it will have the same mean degree), thus ensuring that inferences about specific measures
are correctly drawn. As illustrated in Figure 4 above, differences in the mean degree of the
network will affect the clustering coefficient and path length, suggesting that only when degree is
controlled for, can meaningful interpretations of the other measures emerge. Figure 6
summarizes the process described.
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Figure 6. Reprinted with permission from Stam & Reijneveld (2007, p. 12): “Schematic illustration of graph analysis applied to multi channel recordings of brain activity (fMRI, EEG or MEG). The first step (panel A) consists of computing a measure of correlation between all possible pairs of channels of recorded brain activity. The correlations can be represented in a correlation diagram (panel B, strength of correlation indicated with black white scale). Next a threshold is applied, and all correlations above the threshold are considered to be edges connecting vertices (channels). Thus, the correlation matrix is converted to a unweighted graph (panel C). From this graph various measures such as the clustering coefficient C and the path length L can be computed. For comparisons, random networks can be generated by shuffling the cells of the original correlation matrix of panel B. This shuffling preserves the symmetry of the matrix, and the mean strength of the correlations (panel D). From the random matrices graphs are constructed, and graph measures are computed as before. The mean values of the graph measures for the ensemble of random networks are determined. Finally, The ratio of the graph measures of the original network and the mean values of the graph measures of the random networks can be determined (panel F).”
Conclusions
The present report has provided a basic introduction to the main concepts of complex
network analysis of brain connectivity data. A future report will focus on technical issues and
review software tools to conduct such studies. Readers interested in learning more about this
topic are referred to the works cited for additional information.
References Bullmore, E., & Sporns, O. (2009). Complex brain networks: Graph theoretical analysis of structural and
functional systems. Nature Reviews Neuroscience, 10(3), 186-198. doi:10.1038/nrn2575
LABREPORT 5 -- Fernando Ferreira-Santos 11
2012 Complex Network Analysis of Brain Connectivity: An Introduction Friston, K. J. (1994). Functional and effective connectivity in neuroimaging: A synthesis. Human Brain
Mapping, 2(1-2), 56-78. doi:10.1002/hbm.460020107
Horwitz, B. (2003). The elusive concept of brain connectivity. NeuroImage, 19(2), 466-470.
doi:10.1016/S1053-8119(03)00112-5
Humphries MD, Gurney K (2008) Network ‘Small-world-ness’: A quantitative method for determining
canonical network equivalence. PLoS ONE, 3(4), e0002051. doi:10.1371/journal.pone.0002051
Newman, M. E. J. (2003). The Structure and function of complex networks. SIAM Review, 45(2), 167-256.
doi:10.1137/S003614450342480
Reijneveld, J. C., Ponten, S. C., Berendse, H. W., & Stam, C. J. (2007). The application of graph theoretical
analysis to complex networks in the brain. Clinical Neurophysiology, 118(11), 2317-2331.
doi:10.1016/j.clinph.2007.08.010
Rubinov, M., & Sporns, O. (2010). Complex network measures of brain connectivity: uses and
interpretations. NeuroImage, 52(3), 1059-1069. doi:10.1016/j.neuroimage.2009.10.003
Sporns, O. (2011). Networks in the brain. Cambridge, MA: MIT Press.
Stam, C. J., & Reijneveld, J. C. (2007). Graph theoretical analysis of complex networks in the brain. Nonlinear
Biomedical Physics, 1(3), 1-19. doi:10.1186/1753-4631-1-3
Zalesky, A., Fornito, A., & Bullmore, E. (2012). On the use of correlation as a measure of network
connectivity. NeuroImage, 60(4), 2096-2106. Elsevier Inc. doi:10.1016/j.neuroimage.2012.02.001
Abbreviations used: DTI Diffusion tensor imaging EEG Electroencephalography fMRI Functional magnetic resonance imaging MEG Magnetoencephalography MRI Magnetic resonance imaging
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