ABSTRACTNeuroimaging and neurological studies suggest that stroke is a brain network syndrome. While causing local ischemia and cell damage at the site of injury, stroke strongly perturbs the functional organization of brain networks at large. Critically, functional connectivity abnormalities parallel both behavioral deficits and functional recovery across different cognitive domains. However, the reasons for such relations remain poorly understood. Here, we tested the hypothesis that alterations in inter-areal communication underlie stroke-related modulations in functional connectivity (FC). To this aim, we used resting-state fMRI and Granger causality analysis to quantify information transfer between brain areas and its alteration in stroke. Two main large-scale anomalies were observed in stroke patients. First, inter-hemispheric information transfer was strongly decreased with respect to healthy controls. Second, information transfer within the affected hemisphere, and from the affected to the intact hemisphere was reduced. Both anomalies were more prominent in resting-state networks related to attention and language, and they were correlated with impaired performance in several behavioral domains. Overall, our results support the hypothesis that stroke perturbs inter-areal communication within and across hemispheres, and suggest novel therapeutic approaches aimed at restoring normal information flow.SIGNIFICANCE STATEMENTA thorough understanding of how stroke perturbs brain function is needed to improve recovery from the severe neurological syndromes affecting stroke patients. Previous resting-state neuroimaging studies suggested that interaction between hemispheres decreases after stroke, while interaction between areas of the same hemisphere increases. Here, we used Granger causality to reconstruct information flows in the brain at rest, and analyze how stroke perturbs them. We showed that stroke causes a global reduction of inter-hemispheric communication, and an imbalance between the intact and the affected hemisphere: information flows within and from the latter are impaired. Our results may inform the design of stimulation therapies to restore the functional balance lost after stroke.
Large-scale Granger causality analysis on resting-state functional MRI
