Focal Brain Lesions to Critical Locations Cause Widespread Disruption of the Modular Organization of the Brain

Although it is generally assumed that brain damage predominantly affects only the function of the damaged region, here we show that focal damage to critical locations causes disruption of network organization throughout the brain. Using resting state fMRI, we assessed whole-brain network structure in patients with focal brain lesions. Only damage to those brain regions important for communication between subnetworks (e.g., “connectors”)—but not to those brain regions important for communication within sub-networks (e.g., “hubs”)—led to decreases in modularity, a measure of the integrity of network organization. Critically, this network dysfunction extended into the structurally intact hemisphere. Thus, focal brain damage can have a widespread, nonlocal impact on brain network organization when there is damage to regions important for the communication between networks. These findings fundamentally revise our understanding of the remote effects of focal brain damage and may explain numerous puzzling cases of functional deficits that are observed following brain injury.

[1]  Linda Douw,et al.  Local polymorphic delta activity in cortical lesions causes global decreases in functional connectivity , 2013, NeuroImage.

[2]  Biyu J. He,et al.  Breakdown of Functional Connectivity in Frontoparietal Networks Underlies Behavioral Deficits in Spatial Neglect , 2007, Neuron.

[3]  Aric Hagberg,et al.  Exploring Network Structure, Dynamics, and Function using NetworkX , 2008 .

[4]  R. Guimerà,et al.  Functional cartography of complex metabolic networks , 2005, Nature.

[5]  M P Young,et al.  On imputing function to structure from the behavioural effects of brain lesions. , 2000, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[6]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[7]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[8]  Keith A. Johnson,et al.  Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease , 2009, The Journal of Neuroscience.

[9]  Andreas Kleinschmidt,et al.  Functional interactions between intrinsic brain activity and behavior , 2013, NeuroImage.

[10]  O. Sporns,et al.  Identification and Classification of Hubs in Brain Networks , 2007, PloS one.

[11]  Karl J. Friston,et al.  Dynamic Diaschisis: Anatomically Remote and Context-Sensitive Human Brain Lesions , 2001, Journal of Cognitive Neuroscience.

[12]  S. Slobounov,et al.  Alteration of Cortical Functional Connectivity as a Result of Traumatic Brain Injury Revealed by Graph Theory, ICA, and sLORETA Analyses of EEG Signals , 2010, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[13]  Gordon Worley,et al.  Diffuse reduction of white matter connectivity in cerebral palsy with specific vulnerability of long range fiber tracts , 2013, NeuroImage: Clinical.

[14]  Chu Timone How do brain tumors alter functional connectivity? A magnetoencephalography study , 2006 .

[15]  N. Geschwind Disconnexion syndromes in animals and man. II. , 1965, Brain : a journal of neurology.

[16]  G. Frisoni,et al.  Functional network disruption in the degenerative dementias , 2011, The Lancet Neurology.

[17]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[18]  Fernando Maestú,et al.  Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury. , 2010, Brain : a journal of neurology.

[19]  C. Stam,et al.  Alzheimer's disease: connecting findings from graph theoretical studies of brain networks , 2013, Neurobiology of Aging.

[20]  G. Fink,et al.  Cortical connectivity after subcortical stroke assessed with functional magnetic resonance imaging , 2008, Annals of neurology.

[21]  Raymond J. Dolan,et al.  Network reconfiguration and working memory impairment in mesial temporal lobe epilepsy , 2013, NeuroImage.

[22]  Edward T. Bullmore,et al.  Modular and Hierarchically Modular Organization of Brain Networks , 2010, Front. Neurosci..

[23]  M. Farah Neuropsychological inference with an interactive brain: A critique of the "locality" assumption. , 1994 .

[24]  M. Hallett,et al.  Multimodal imaging of brain reorganization in motor areas of the contralesional hemisphere of well recovered patients after capsular stroke. , 2006, Brain : a journal of neurology.

[25]  Edward T. Bullmore,et al.  Neuroinformatics Original Research Article , 2022 .

[26]  John Duncan,et al.  Global Increase in Task-related Fronto-parietal Activity after Focal Frontal Lobe Lesion , 2013, Journal of Cognitive Neuroscience.

[27]  Leon Danon,et al.  Comparing community structure identification , 2005, cond-mat/0505245.

[28]  Mark D'Esposito,et al.  Neurology of Cognitive and Behavioral Disorders , 2001 .

[29]  N. Geschwind Disconnexion syndromes in animals and man. I. , 1965, Brain : a journal of neurology.

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

[31]  E. Bullmore,et al.  Hierarchical Organization of Human Cortical Networks in Health and Schizophrenia , 2008, The Journal of Neuroscience.

[32]  Fabrice Bartolomei,et al.  Graph theoretical analysis of structural and functional connectivity MRI in normal and pathological brain networks , 2010, Magnetic Resonance Materials in Physics, Biology and Medicine.

[33]  Monica Fabiani,et al.  Frontoparietal Traffic Signals: A Fast Optical Imaging Study of Preparatory Dynamics in Response Mode Switching , 2013, Journal of Cognitive Neuroscience.

[34]  B. Biswal,et al.  The resting brain: unconstrained yet reliable. , 2009, Cerebral cortex.

[35]  Daniel L. Schacter,et al.  Intrinsic Architecture Underlying the Relations among the Default, Dorsal Attention, and Frontoparietal Control Networks of the Human Brain , 2013, Journal of Cognitive Neuroscience.

[36]  Desmond J. Higham,et al.  Network analysis detects changes in the contralesional hemisphere following stroke , 2011, NeuroImage.

[37]  Anthony Randal McIntosh,et al.  Towards a network theory of cognition , 2000, Neural Networks.

[38]  K. Worsley,et al.  Impaired small-world efficiency in structural cortical networks in multiple sclerosis associated with white matter lesion load. , 2009, Brain : a journal of neurology.

[39]  Rafael Ruiz-Cruces,et al.  Massed sentence repetition training can augment and speed up recovery of speech production deficits in patients with chronic conduction aphasia receiving donepezil treatment , 2014 .

[40]  Olaf Sporns,et al.  Modeling the Impact of Lesions in the Human Brain , 2009, PLoS Comput. Biol..

[41]  Stephen M Smith,et al.  Correspondence of the brain's functional architecture during activation and rest , 2009, Proceedings of the National Academy of Sciences.

[42]  Karen Sage,et al.  A clinical study of the combined use of bromocriptine and speech and language therapy in the treatment of a person with aphasia , 2014 .

[43]  M. Corbetta,et al.  Resting interhemispheric functional magnetic resonance imaging connectivity predicts performance after stroke , 2009, Annals of neurology.

[44]  Bruce R. Rosen,et al.  Connectivity alterations assessed by combining fMRI and MR-compatible hand robots in chronic stroke , 2009, NeuroImage.

[45]  M. Berthier,et al.  Foreign accent syndrome: A multimodal evaluation in the search of neuroscience-driven treatments , 2013, Neuropsychologia.

[46]  Caterina Gratton,et al.  Double dissociation of two cognitive control networks in patients with focal brain lesions , 2010, Proceedings of the National Academy of Sciences.

[47]  M E J Newman,et al.  Finding and evaluating community structure in networks. , 2003, Physical review. E, Statistical, nonlinear, and soft matter physics.

[48]  Jonathan D. Power,et al.  Evidence for Hubs in Human Functional Brain Networks , 2013, Neuron.

[49]  Karl J. Friston,et al.  Statistical parametric mapping , 2013 .

[50]  Alan C. Evans,et al.  Uncovering Intrinsic Modular Organization of Spontaneous Brain Activity in Humans , 2009, PloS one.

[51]  Linda Douw,et al.  Disturbed functional brain networks and neurocognitive function in low-grade glioma patients: a graph theoretical analysis of resting-state MEG , 2009, Nonlinear biomedical physics.

[52]  Toru Nakamura,et al.  Resting Network Plasticity Following Brain Injury , 2009, PloS one.

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

[54]  J. H. Steiger Tests for comparing elements of a correlation matrix. , 1980 .

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

[56]  Jennifer T. Crinion,et al.  Anterior temporal lobe connectivity correlates with functional outcome after aphasic stroke , 2009, Brain : a journal of neurology.

[57]  J. Baron,et al.  Motor imagery after stroke: Relating outcome to motor network connectivity , 2009, Annals of neurology.

[58]  Olaf Sporns,et al.  Network attributes for segregation and integration in the human brain , 2013, Current Opinion in Neurobiology.

[59]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[60]  M M Mesulam,et al.  Large‐scale neurocognitive networks and distributed processing for attention, language, and memory , 1990, Annals of neurology.

[61]  O. Sporns,et al.  Dynamical consequences of lesions in cortical networks , 2008, Human brain mapping.

[62]  Karl J. Friston,et al.  Statistical parametric mapping , 2013 .

[63]  O. Sporns,et al.  Network hubs in the human brain , 2013, Trends in Cognitive Sciences.

[64]  M. Berger,et al.  Mapping functional connectivity in patients with brain lesions , 2008, Annals of neurology.

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

[66]  Danielle S Bassett,et al.  Brain graphs: graphical models of the human brain connectome. , 2011, Annual review of clinical psychology.