title: Extent of bilateral neuronal network reorganization and functional recovery in relation to stroke severity.
abstract: Remodeling of neuronal structures and networks is believed to significantly contribute to (partial) restoration of functions after stroke. However, it has been unclear to what extent the brain reorganizes and how this correlates with functional recovery in relation to stroke severity. We applied serial resting-state functional MRI and diffusion tensor imaging together with behavioral testing to relate longitudinal modifications in functional and structural connectivity of the sensorimotor neuronal network to changes in sensorimotor function after unilateral stroke in rats. We found that gradual improvement of functions is associated with wide-ranging changes in functional and structural connectivity within bilateral neuronal networks, particularly after large stroke. Both after medium and large stroke, brain reorganization eventually leads to (partial) normalization of neuronal signal synchronization within the affected sensorimotor cortical network (intraregional signal coherence), as well as between the affected and unaffected sensorimotor cortices (interhemispheric functional connectivity). Furthermore, the bilateral network configuration shifts from subacutely increased "small-worldness," possibly reflective of initial excessive neuronal clustering and wiring, toward a baseline small-world topology, optimal for global information transfer and local processing, at chronic stages. Cortical network remodeling was accompanied by recovery of initially disrupted structural integrity in corticospinal tract regions, which correlated positively with retrieval of sensorimotor functions. Our study demonstrates that the degree of functional recovery after stroke is associated with the extent of preservation or restoration of ipsilesional corticospinal tracts in combination with reinstatement of interhemispheric neuronal signal synchronization and normalization of small-world cortical network organization.
authors.affiliation: Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Maurits P A
authors.initials: MP
authors.lastname: van Meer
authors.forename: Willem M
authors.initials: WM
authors.lastname: Otte
authors.forename: Kajo
authors.initials: K
authors.lastname: van der Marel
authors.forename: Cora H
authors.initials: CH
authors.lastname: Nijboer
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
authors.forename: Jan Willem Berkelbach
authors.initials: JW
authors.lastname: van der Sprenkel
authors.forename: Max A
authors.initials: MA
authors.lastname: Viergever
authors.forename: Rick M
authors.initials: RM
authors.lastname: Dijkhuizen
mesh_terms: D000818:Animals; D016880:Anisotropy; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods / Q000523:psychology; D058256:Brain Waves / Q000502:physiology; D056324:Diffusion Tensor Imaging / Q000379:methods / Q000523:psychology; D020244:Infarction, Middle Cerebral Artery / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000523:psychology; D008297:Male; D015233:Models, Statistical; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*