Cerebro-cerebellar structure-function coupling’s role in motor recovery after infarction

OBJECTIVE: To investigate the pathway-specific structure-function coupling induced by focal subcortical infarction and its influence on clinical symptoms. METHODS: In this prospective study, 50 patients with unilateral subcortical infarction and motor impairment and 50 matched controls underwent resting state fMRI, DTI, and Fugl-Meyer-Assessment lower-extremity (FMA-LE) at 7-14- and 30-days post-infarction. To analyze the pathway-specific structure-function coupling, we evaluated the association between structural integrity of the corticospinal tract (CST), dentate thalamocortical tract (DTCT), cortico-pontocerebellar tract (CPCT), and dorsal spinocerebellar tract (DSCT) and functional connectivity (FC) of corresponding subregions. Moderation analysis assesses whether the structure-function coupling pathway moderates FMA-LE. RESULTS: At baseline, patients exhibited significantly lower structural integrity of DTCT, DSCT, and CST than controls. We found structure-function couplings in the three motor pathways of the cerebro-cerebellar circuit: (1) contralesional thalamus to ipsilesional cerebellum-crus_2 with dentate thalamocortical tract (DTCT), (2) contralesional thalamus to cerebellum vermis_10 with dorsal spinocerebellar tract (DSCT), (3) ipsilesional precentral gyrus to frontal medial gyrus with CST. The baseline DSCT structural integrity specificity modulates the relationship between FC and FMA-LE over 30 days. CONCLUSIONS: We observed that cerebro-cerebellar circuit structure-function coupling after infarction, based on its anatomy and mapped to motor function (with DSCT as the key pathway mediating/moderating prognosis), serves as a potent biomarker for lower limb prognosis and a basis for precise rehabilitation.