Pathway-Specific Mediation Effect Between Structure, Function, and Motor Impairment After Subcortical Stroke
Qiurong Yu1, Dazhi Yin1, Marcus Kaiser1
1From the Shanghai Key Laboratory of Magnetic Resonance (Q.Y., G.X., M.G., F.L., J.L., M.F.), School of Physics and Electronic Science, East China Normal University; Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education) (D.Y.), School of Psychology and Cognitive Science, East China Normal University; Shanghai Changning Mental Health Center (D.Y.); Precision Imaging Beacon (M.K.), School of Medicine, University of Nottingham, United Kingdom; and School of Medicine (M.K.), Shanghai Jiao Tong University, China.
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:
Thirty-five patients (mean age 52.7 ± 10.2 years, 27 men) and 43 healthy controls (mean age 56.2 ± 9.3 years, 21 men) were enrolled. Among the 6 CSTs, we identified 9 structurally and functionally covaried pathways, originating from the ipsilesional primary motor area (M1), dorsal premotor area (PMd), and primary somatosensory cortex (p < 0.05, corrected). FC for the bilateral M1, PMd, and ventral premotor cortex covaried with secondary degeneration of the corresponding CC sections (p < 0.05, corrected). Moreover, these covarying structures and functions were significantly correlated with the Fugl-Meyer Assessment (upper extremity) scores (p < 0.05, uncorrected). In particular, FC between the ipsilesional PMd and contralesional cerebellum (β = -0.141, p < 0.05, CI = [-0.319 to -0.015]) and interhemispheric FC of the PMd (β = 0.169, p < 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.
