Cortical thinning and functional reorganization as well as related transcriptomic signatures during early motor recovery following acute basal ganglia ischemic stroke

Abstract Background Acute basal ganglia ischemic stroke (ABGIS) commonly causes severe motor impairment, yet early spatiotemporal patterns of cortical morphological alterations and functional reorganization alongside the spatially coupled transcriptomic signatures remain unclear. Methods Twenty-six ABGIS patients and thirty-three normal controls (NCs) received multimodal MRI and neurological examinations, and patients were reassessed at 1-month follow-up. Cortical morphological changes and brain functional reorganization were analyzed based on cortical thickness (CT) and functional connectivity (FC). We identified the most discriminative FC features based on machine learning (ML) classification and interpretability analyses, and investigated transcriptomic signatures associated with FC alterations via the Allen Human Brain Atlas. Results No differences in CT were found between baseline ABGIS patients (ABGIS_1) and NCs. Compared with ABGIS_1, follow-up patients (ABGIS_2) exhibited reduced CT in the left postcentral gyrus (PoCG.L), left superior parietal lobule (SPL.L), and left supramarginal gyrus (SMG.L). Compared with NCs, ABGIS_1 showed decreased FC from PoCG.L/SPL.L to sensorimotor cortex and occipital cortex. ABGIS_2 presented elevated FC relative to ABGIS_1 between PoCG.L and the right precentral gyrus (PreCG.R), and between SPL.L and the bilateral precentral gyrus as well as right superior occipital gyrus. Longitudinal increases in FC between PoCG.L/SPL.L and PreCG.R were positively correlated with improvements in Fugl-Meyer Assessment scores. ML models coupled with interpretability analyses preliminarily demonstrated that FC between PoCG.L/SPL.L and PreCG.R made prominent contributions to classification. Transcriptomic analysis revealed that gene sets correlated with FC alterations were mainly enriched in neuronal synaptic structure and synaptic signaling, chromatin regulation, as well as DNA and RNA metabolism. Conclusions This study verifies progressive cortical thinning and adaptive functional reorganization during early motor recovery following ABGIS, with such brain functional alterations paralleling distinct transcriptomic signatures, providing neuropathological and spatial transcriptomic clues for interpreting early motor recovery.