Directed Functional Networks in Alzheimer's Disease: Disruption of Global and Local Connectivity Measures

Techniques available in graph theory can be applied to signals recorded from human brain. In network analysis of EEG signals, the individual nodes are EEG sensor locations and the edges correspond to functional relations between them that are extracted from EEG time series. In this paper, we study EEG-based directed functional networks in Alzheimer's disease (AD). To this end, directed connectivity matrices of 25 AD patients and 26 healthy subjects are processed and a number of meaningful graph theory metrics are studied. Our data show that functional networks of AD brains have significantly reduced global connectivity in alpha and beta bands (P < 0.05). The AD brains have significantly higher local connectivity than healthy controls in alpha and beta bands. This decreased profile in global connectivity can be linked to compensatory increased local connectivity as a result of wide-spread decline in the long-range connections. We also study resiliency of brain networks against targeted attack to hub nodes and find that AD networks are less resilient than healthy brains in alpha and beta bands.

[1]  Daniel L. Rubin,et al.  Network Analysis of Intrinsic Functional Brain Connectivity in Alzheimer's Disease , 2008, PLoS Comput. Biol..

[2]  G. Schwarz Estimating the Dimension of a Model , 1978 .

[3]  Massimo Marchiori,et al.  Economic small-world behavior in weighted networks , 2003 .

[4]  Patrick R Hof,et al.  Life and death of neurons in the aging cerebral cortex. , 2007, International review of neurobiology.

[5]  Hualou Liang,et al.  Short-window spectral analysis of cortical event-related potentials by adaptive multivariate autoregressive modeling: data preprocessing, model validation, and variability assessment , 2000, Biological Cybernetics.

[6]  Alan C. Evans,et al.  Structural Insights into Aberrant Topological Patterns of Large-Scale Cortical Networks in Alzheimer's Disease , 2008, The Journal of Neuroscience.

[7]  M. Jalili,et al.  Synchronizability of EEG-Based Functional Networks in Early Alzheimer's Disease , 2012, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[8]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[9]  Klaus Lehnertz,et al.  Assessing directed interactions from neurophysiological signals—an overview , 2011, Physiological measurement.

[10]  M. Filippi,et al.  Structural and functional network connectivity breakdown in Alzheimer’s disease studied with magnetic resonance imaging techniques. , 2011, Journal of Alzheimer's disease : JAD.

[11]  Steven L. Bressler,et al.  Foundational perspectives on causality in large-scale brain networks. , 2015, Physics of life reviews.

[12]  Edward T. Bullmore,et al.  Efficiency and Cost of Economical Brain Functional Networks , 2007, PLoS Comput. Biol..

[13]  P. Pietrini,et al.  Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease. , 2001, Brain : a journal of neurology.

[14]  C. Stam,et al.  Small-world networks and functional connectivity in Alzheimer's disease. , 2006, Cerebral cortex.

[15]  Katarzyna J. Blinowska,et al.  Directed Transfer Function is not influenced by volume conduction—inexpedient pre-processing should be avoided , 2014, Front. Comput. Neurosci..

[16]  O. Sporns,et al.  The economy of brain network organization , 2012, Nature Reviews Neuroscience.

[17]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[18]  G. Sandini,et al.  Graph theoretical analysis of magnetoencephalographic functional connectivity in Alzheimer's disease. , 2009, Brain : a journal of neurology.

[19]  P. Nunez,et al.  Source analysis of EEG oscillations using high-resolution EEG and MEG. , 2006, Progress in brain research.

[20]  Ali Mahloojifar,et al.  Disorganization of Equilibrium Directional Interactions in the Brain Motor Network of Parkinson's disease: New Insight of Resting State Analysis Using Granger Causality and Graphical Approach , 2013, Journal of medical signals and sensors.

[21]  Kuncheng Li,et al.  Altered functional connectivity in early Alzheimer's disease: A resting‐state fMRI study , 2007, Human brain mapping.

[22]  C. Granger Investigating causal relations by econometric models and cross-spectral methods , 1969 .

[23]  W. M. van der Flier,et al.  Functional neural network analysis in frontotemporal dementia and Alzheimer's disease using EEG and graph theory , 2009, BMC Neuroscience.

[24]  Mahdi Jalili,et al.  Resiliency of EEG-Based Brain Functional Networks , 2015, PloS one.

[25]  M. Perc Evolution of cooperation on scale-free networks subject to error and attack , 2009, 0902.4661.

[26]  Mahdi Jalili,et al.  Error and attack tolerance of small-worldness in complex networks , 2011, J. Informetrics.

[27]  V Latora,et al.  Efficient behavior of small-world networks. , 2001, Physical review letters.

[28]  Richard S. Frackowiak,et al.  Evolution of source EEG synchronization in early Alzheimer's disease , 2013, Neurobiology of Aging.

[29]  Reto Meuli,et al.  Topography of EEG multivariate phase synchronization in early Alzheimer's disease , 2010, Neurobiology of Aging.

[30]  S. Rombouts,et al.  Loss of ‘Small-World’ Networks in Alzheimer's Disease: Graph Analysis of fMRI Resting-State Functional Connectivity , 2010, PloS one.

[31]  Mahdi Jalili,et al.  Diagnosis of Early Alzheimer's Disease Based on EEG Source Localization and a Standardized Realistic Head Model , 2013, IEEE Journal of Biomedical and Health Informatics.

[32]  Udo Rüb,et al.  Vulnerability of cortical neurons to Alzheimer's and Parkinson's diseases. , 2006, Journal of Alzheimer's disease : JAD.

[33]  Olaf Sporns,et al.  The Human Connectome: A Structural Description of the Human Brain , 2005, PLoS Comput. Biol..

[34]  Mahdi Jalili,et al.  Constructing brain functional networks from EEG: partial and unpartial correlations. , 2011, Journal of integrative neuroscience.

[35]  G K Wilcock,et al.  Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer disease. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[36]  J. Durbin,et al.  Testing for serial correlation in least squares regression. II. , 1950, Biometrika.

[37]  O. Sporns,et al.  Mapping the Structural Core of Human Cerebral Cortex , 2008, PLoS biology.

[38]  Yong Liu,et al.  Disrupted Small-World Brain Networks in Moderate Alzheimer's Disease: A Resting-State fMRI Study , 2012, PloS one.

[39]  Matjaz Perc,et al.  The Matthew effect in empirical data , 2014, Journal of The Royal Society Interface.

[40]  Richard S. Frackowiak,et al.  Properties of functional brain networks correlate with frequency of psychogenic non-epileptic seizures , 2012, Front. Hum. Neurosci..

[41]  Katarzyna J. Blinowska,et al.  A new method of the description of the information flow in the brain structures , 1991, Biological Cybernetics.

[42]  Karl J. Friston Functional and effective connectivity in neuroimaging: A synthesis , 1994 .

[43]  Wei Liao,et al.  Nonlinear connectivity by Granger causality , 2011, NeuroImage.

[44]  O. Sporns Networks of the Brain , 2010 .

[45]  W. Hesse,et al.  The use of time-variant EEG Granger causality for inspecting directed interdependencies of neural assemblies , 2003, Journal of Neuroscience Methods.

[46]  Karl J. Friston Functional and Effective Connectivity: A Review , 2011, Brain Connect..