Altered Functional Connectivity Between Cortical Premotor Areas and the Spinal Cord in Chronic Stroke

Neuroscience research has contributed significantly to understanding alterations in brain structure and function after ischemic stroke. Technical limitations have excluded the spinal cord from imaging-based research. Available data are restricted to a few microstructural analyses, and functional connectivity data are absent. The present study attempted to close this knowledge gap and assess alterations in corticospinal coupling in chronic stroke and their relation to motor deficits.

In this cross-sectional study, patients with chronic stroke and healthy controls underwent corticospinal functional magnetic resonance imaging while performing a simple force generation task at the University Medical Center Hamburg-Eppendorf between September 2021 and June 2023. Task-related activation was localized in the ipsilesional ventral premotor cortex, the supplementary motor area, and the cervical spinal cord. Psycho-physiological interactions and linear modeling were used to infer functional connectivity between cortical motor regions and the cervical spinal cord and their associations with clinical scores.

Thirteen well-recovered patients with stroke (1 woman, 12 men; mean age, 62.6 years; mean time after stroke: 47.6 months) and 13 healthy controls (5 women, 8 men; mean age, 64.5 years) were included. The main finding was that ventral premotor cortex and supplementary motor area showed topographically distinct alterations in their connectivity with the spinal cord. Specifically, we found a reduced coupling between the supplementary motor area and the ipsilateral ventral spinal cord and an enhanced coupling between the ventral premotor cortex and ventral and intermediate central spinal zones. Lower supplementary motor area and higher ventral premotor cortex-related spinal cord couplings were correlated with residual deficits.

This work provides first-in-human functional insights into stroke-related alterations in the functional connectivity between cortical premotor areas and the spinal cord, suggesting that different premotor areas and spinal neuronal assemblies might be involved in coupling changes. It adds a novel, promising approach to better understanding stroke recovery and developing innovative models to comprehend treatment strategies with spinal cord stimulation.