Disrupted interhemispheric functional connectivity between the bilateral precentral gyri and associated transcriptomic signatures in acute basal ganglia ischemic stroke.

Abstract

Acute basal ganglia ischemic stroke (BGIS) often leads to motor dysfunction, but the mechanisms of functional reorganization, particularly the underlying molecular basis, remain unclear. This study aimed to investigate the local and global functional reorganization patterns and their associated molecular basis in acute BGIS. Regional homogeneity (ReHo) and seed-based functional connectivity (FC) analyses were used to assess local and global brain connectivity, respectively. We identified a key classification feature using support vector machine (SVM) and logistic regression (LR) models combined with SHapley Additive exPlanations (SHAP) analysis, which was then spatially correlated with Allen Human Brain Atlas (AHBA) transcriptomic data via partial least squares (PLS) regression, followed by functional enrichment analysis. Compared with healthy controls (HCs), BGIS patients demonstrated decreased ReHo in the bilateral precentral gyri, along with reduced interhemispheric FC between these regions. The SVM and LR models effectively distinguished patients from HCs (AUCs = 0.877 and 0.868, respectively), identifying this reduced interhemispheric FC (seeded in the right precentral gyrus) as the top discriminative feature based on SHAP. Genes spatially correlated with this feature were enriched in synaptic function, ion homeostasis, and energy metabolism in the contralesional hemisphere. In summary, disrupted interhemispheric FC between the bilateral precentral gyri represents a key neuroimaging marker in acute BGIS. This disconnection was associated with transcriptomic signatures of synaptic inhibition and metabolic reorganization. Our multimodal findings advance the understanding of post-stroke motor dysfunction.