Abstract
Understanding the relationships between brain organization and behavior is a central goal of neuroscience. Traditional teaching emphasizes that the human cerebrum includes many distinct areas for which damage or dysfunction would lead to a unique and specific behavioral syndrome. This teaching implies that brain areas correspond to encapsulated modules that are specialized for specific cognitive operations. However, empirically, local damage from stroke more often produces one of a small number of clusters of deficits and disrupts brain-wide connectivity in a small number of predictable ways (relative to the vast complexity of behavior and brain connectivity). Behaviors that involve shared operations show correlated deficits following a stroke, consistent with a low-dimensional behavioral space. Because of the networked organization of the brain, local damage from a stroke can result in widespread functional abnormalities, matching the low dimensionality of behavioral deficit. In alignment with this, neurological disease, psychiatric disease, and altered brain states produce behavioral changes that are highly correlated across a range of behaviors. We discuss how known structural and functional network priors in addition to graph theoretical concepts such as modularity and entropy have provided inroads to understanding this more complex relationship between brain and behavior. This model for brain disease has important implications for normal brain-behavior relationships and the treatment of neurological and psychiatric diseases.
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Funding
JS was supported by NIMH funded Research Education Grant R25 MH112473, McDonnell Center for Systems Neuroscience NRP 3921-26239 N, and National Institute of Health grant 5T32GM007200-39. MC was supported by FLAG-ERA JTC 2017 (grant ANR-17-HBPR-0001); MIUR—Departments of Excellence Italian Ministry of Research (MART_ECCELLENZA18_01); Fondazione Cassa di Risparmio di Padova e Rovigo (CARIPARO)—Ricerca Scientifica di Eccellenza 2018 – (Grant Agreement 55403); Ministry of Health Italy NEUROCONN (RF-2008 -12366899); Celeghin Foundation Padova (CUP C94I20000420007); BIAL foundation grant (No. 361/18); H2020 European School of Network Neuroscience- euSNN, H2020-SC5-2019–2, (Grant Agreement number 869505); H2020 Visionary Nature Based Actions For Health, Wellbeing & Resilience in Cities (VARCITIES), H2020-SC5-2019–2 (Grant Agreement 869505); Ministry of Health Italy EYEMOVINSTROKE (RF-2019–12369300); National Institute of Neurological Disorders and Stroke grant 5R01-NS095741-05, National Institute of Child Health and Human Development award 5R01HD061117. The authors declare no conflicts of interest.
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Siegel, J.S., Shulman, G.L. & Corbetta, M. Mapping correlated neurological deficits after stroke to distributed brain networks. Brain Struct Funct 227, 3173–3187 (2022). https://doi.org/10.1007/s00429-022-02525-7
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DOI: https://doi.org/10.1007/s00429-022-02525-7