title: Cognitive Flexibility through Metastable Neural Dynamics Is Disrupted by Damage to the Structural Connectome.
abstract: Current theory proposes that healthy neural dynamics operate in a metastable regime, where brain regions interact to simultaneously maximize integration and segregation. Metastability may confer important behavioral properties, such as cognitive flexibility. It is increasingly recognized that neural dynamics are constrained by the underlying structural connections between brain regions. An important challenge is, therefore, to relate structural connectivity, neural dynamics, and behavior. Traumatic brain injury (TBI) is a pre-eminent structural disconnection disorder whereby traumatic axonal injury damages large-scale connectivity, producing characteristic cognitive impairments, including slowed information processing speed and reduced cognitive flexibility, that may be a result of disrupted metastable dynamics. Therefore, TBI provides an experimental and theoretical model to examine how metastable dynamics relate to structural connectivity and cognition. Here, we use complementary empirical and computational approaches to investigate how metastability arises from the healthy structural connectome and relates to cognitive performance. We found reduced metastability in large-scale neural dynamics after TBI, measured with resting-state functional MRI. This reduction in metastability was associated with damage to the connectome, measured using diffusion MRI. Furthermore, decreased metastability was associated with reduced cognitive flexibility and information processing. A computational model, defined by empirically derived connectivity data, demonstrates how behaviorally relevant changes in neural dynamics result from structural disconnection. Our findings suggest how metastable dynamics are important for normal brain function and contingent on the structure of the human connectome.
authors.affiliation: Computational, Cognitive, and Clinical Neuroimaging Laboratory, Division of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, United Kingdom, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, United Kingdom, and.
authors.forename: Peter J
authors.identifier: http://orcid.org/0000-0002-5139-3401
authors.initials: PJ
authors.lastname: Hellyer
authors.affiliation: Computational, Cognitive, and Clinical Neuroimaging Laboratory, Division of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, United Kingdom.
authors.forename: Gregory
authors.initials: G
authors.lastname: Scott
authors.affiliation: Department of Computing, Imperial College London, London SW7 2RH, United Kingdom.
authors.forename: Murray
authors.identifier: http://orcid.org/0000-0001-5984-2964
authors.initials: M
authors.lastname: Shanahan
authors.affiliation: Computational, Cognitive, and Clinical Neuroimaging Laboratory, Division of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Sharp
authors.affiliation: Computational, Cognitive, and Clinical Neuroimaging Laboratory, Division of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, United Kingdom, r.leech@imperial.ac.uk.
authors.forename: Robert
authors.identifier: http://orcid.org/0000-0002-5801-6318
authors.initials: R
authors.lastname: Leech
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000175:diagnosis / Q000378:metabolism*; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis / Q000378:metabolism*; D063132:Connectome / Q000379:methods*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000378:metabolism* / Q000473:pathology; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
keywords: cognitive flexibility; computational modeling; connectome; metastability; traumatic brain injury