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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 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.
Glossary
- CC=
- corpus callosum;
- contra-CB=
- contralesional cerebellum 8;
- CST=
- corticospinal tract;
- DTI=
- diffusion tensor imaging;
- FA=
- fractional anisotropy;
- FC=
- functional connectivity;
- FM-UE=
- Fugl-Meyer Assessment–Upper Extremity;
- FWE=
- familywise error;
- IPL=
- inferior parietal lobe;
- ipsi-PMd=
- ipsilesional dorsal premotor cortex;
- M1=
- primary motor cortex;
- MFG=
- middle frontal gyrus;
- MNI=
- Montreal Neurological Institute;
- PMd=
- dorsal premotor cortex;
- PMv=
- ventral premotor cortex;
- PoG=
- postcentral gyrus;
- preSMA=
- presupplementary motor area;
- S1=
- primary somatosensory cortex;
- SMA=
- supplementary motor area;
- SMATT=
- sensorimotor area tract template;
- SMC=
- sensorimotor cortex;
- TFCE=
- threshold-free cluster enhancement;
- TMS=
- transcranial magnetic stimulation;
- tDCS=
- transcranial current stimulation
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally as first authors.
↵† These authors contributed equally as senior authors.
Submitted and externally peer reviewed. The handling editor was José Merino, MD, MPhil, FAAN.
Editorial, page 271
- Received April 18, 2022.
- Accepted in final form September 15, 2022.
- © 2022 American Academy of Neurology
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