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The connectomics of brain disorders
Alex Fornito1, Andrew Zalesky2 and Michael Breakspear3,4
Abstract | Pathological perturbations of the brain are rarely confined to a single locus; instead, they often spread via axonal pathways to influence other regions. Patterns of such disease propagation are constrained by the extraordinarily complex, yet highly organized, topology of the underlying neural architecture; the socalled connectome. Thus, network organization fundamentally influences brain disease, and a connectomic approach grounded in network science is integral to understanding neuropathology. Here, we consider how brainnetwork topology shapes neural responses to damage, highlighting key maladaptive processes (such as diaschisis, transneuronal degeneration and dedifferentiation), and the resources (including degeneracy and reserve) and processes (such as compensation) that enable adaptation. We then show how knowledge of network topology allows us not only to describe pathological processes but also to generate predictive models of the spread and functional consequences of brain disease.
Monash Clinical and Imaging Neuroscience, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia 3168.
Melbourne Neuropsychiatry Centre and Melbourne School of Engineering, The University of Melbourne, Parkville, Victoria, Australia 3053.
Systems Neuroscience Group, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia 4029.
Metro North Mental Health Service, The Royal Brisbane and Womens Hospital, Herston, Queensland, Australia 4029. Correspondence to A.F. email: mailto:alex.fornito%40monash.edu?subject=Nature%20Reviews
Web End [email protected] doi:10.1038/nrn3901
The ancient Roman physician Galen was one of the first to propose that pathology in one part of the nervous system could affect other regions when he posited that animal spirits could flow through interconnecting neural pathways1,2. This hypothesis was revisited nearly two millennia later by Brown-Squard, who suggested that the effects of focal brain damage on remote regions resulted from actions at a distance3. von Monakow extended the concept, and coined the term diaschisis (derived from Greek and meaning shocked throughout) to describe the depression of function that can arise in undamaged brain regions that are connected to a lesioned site2,4 (reviewed in REF.5). At a similar time, Wernicke proposed an associative theory of brain function, in which higher-order cognitive processes arose from the integration of multiple, spatially distributed neural systems and in which disorders as diverse as aphasia and schizophrenia resulted from the disruption of specific associative pathways6 (see also REF.7). Wernickes contemporaries,...