Altered directional functional connectivity underlies post-stroke cognitive recovery

Abstract

Cortical ischemic strokes result in cognitive deficits depending on the area of affected brain. However, we have demonstrated that difficulties with attention and processing speed can occur even with small subcortical infarcts. Symptoms appear independent of lesion location, suggesting they arise from generalized disruption of cognitive networks. Longitudinal studies evaluating directional measures of functional connectivity in this population are lacking. We evaluated six patients with minor stroke exhibiting cognitive impairment 6-8 weeks post-infarct and four age-similar controls. Resting state magnetoencephalography data were collected. Clinical and imaging evaluations of both groups were repeated six and twelve months later. Network Localized Granger Causality was used to determine differences in directional connectivity between groups and across visits, which were correlated with clinical performance. Directional connectivity patterns remained stable across visits for controls. After stroke, inter-hemispheric connectivity between frontoparietal cortex and non-frontoparietal cortex significantly increased between visits 1 and 2, corresponding to uniform improvement in reaction times and cognitive scores. Initially, the majority of functional links originated from non-frontal areas contralateral to the lesion, connecting to ipsilesional brain regions. By visit 2, inter-hemispheric connections, directed from ipsilesional to contralesional cortex significantly increased. At visit 3, patients demonstrating continued favorable cognitive recovery showed less reliance on these interhemispheric connections. These changes were not observed in those without continued improvement. Our findings provide supporting evidence that the neural basis of early post-stroke cognitive dysfunction occurs at the network-level, and continued recovery correlates with evolution of inter-hemispheric connectivity.

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