Functional reorganization of the contralesional precentral gyrus following acute subcortical ischemic stroke and its association with gene expression profile.

BACKGROUND: Motor recovery after ischemic stroke involves complex functional reorganization, yet the underlying molecular and cellular mechanisms remain poorly understood. This study integrated longitudinal neuroimaging and brain-wide transcriptomic data to characterize the functional dynamics and their gene-expression correlates during motor recovery following subcortical ischemic stroke.

METHODS: We recruited 34 patients with acute right subcortical ischemic stroke and 32 age- and sex-matched healthy controls. All participants underwent baseline resting-state functional magnetic resonance imaging, with 22 patients completing a 3-month follow-up scan. Spontaneous neural activity was assessed using the amplitude of low-frequency fluctuations (ALFF), followed by seed-based whole-brain functional connectivity (FC) analysis from regions with longitudinal ALFF differences. We then applied partial least squares (PLS) regression to spatially correlate longitudinal ALFF changes with transcriptomic data from the Allen Human Brain Atlas, identifying a gene expression profile spatially associated with these ALFF changes. These genes were subsequently subjected to functional enrichment and cell-type specificity analyses.

RESULTS: Compared with healthy controls, acute-stage stroke patients showed significantly decreased ALFF in the contralesional precentral gyrus. At 3-month follow-up, ALFF in this region significantly increased, accompanied by strengthened interhemispheric FC with its ipsilesional homologue. Critically, these longitudinal changes in ALFF and interhemispheric FC were significantly correlated with motor recovery. Based on PLS regression, we further identified a specific gene expression profile spatially correlated with the observed ALFF changes. This gene set was specifically enriched in excitatory and inhibitory neurons and was primarily involved in synaptic structure and signaling.

CONCLUSIONS: By linking macroscale imaging dynamics with microscale molecular features, this study demonstrates that the contralesional precentral gyrus plays a supportive role in motor recovery during the subacute phase of subcortical ischemic stroke, with neuronal synaptic plasticity as a potential mechanism. Collectively, these findings inform stage-specific strategies to target interhemispheric inhibition.