Pathway-Specific Mediation Effect Between Structure, Function, and Motor Impairment After Subcortical Stroke

Abstract

BACKGROUND AND OBJECTIVE: To investigate the pathway-specific correspondence between structural and functional changes resulting from focal subcortical stroke and their causal influence on clinical symptom. METHODS: In this retrospective, cross-sectional study, we mainly focused on patients with unilateral subcortical chronic stroke with moderate-severe motor impairment assessed by Fugl-Meyer Assessment (upper extremity) and healthy controls. All participants underwent both resting-state fMRI and diffusion tensor imaging. To parse the pathway-specific structure-function covariation, we performed association analyses between the fine-grained corticospinal tracts (CSTs) originating from 6 subareas of the sensorimotor cortex and functional connectivity (FC) of the corresponding subarea, along with the refined corpus callosum (CC) sections and interhemispheric FC. A mediation analysis with FC as the mediator was used to further assess the pathway-specific effects of structural damage on motor impairment. RESULTS: < 0.05, CI = [0.015-0.391]) showed significant mediation effects in the prediction of motor impairment with structural damage of the CST and CC. DISCUSSIONS: This study reveals causal influence of structural and functional pathways on motor impairment after subcortical stroke and provides a promising way to investigate pathway-specific structure-function coupling. Clinically, our findings may offer a circuit-based evidence for the PMd as a critical neuromodulation target in more impaired patients with stroke and also suggest the cerebellum as a potential target.