Non-lesioned subcortical brain volumes are associated with post-stroke sensorimotor behavior across 28 cohorts worldwide: An ENIGMA Stroke Recovery study

ABSTRACT Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Subcortical regions play critical roles in the control and regulation of sensorimotor circuits. Identifying relationships between sensorimotor behavior and non-lesioned subcortical volumes will reveal new neural targets for improving outcomes. We pooled high-resolution T1-weighted MRI brain scans and behavioral data in 828 individuals with unilateral stroke from 28 cohorts worldwide (age: median 63, interquartile range 19 years; 516 males, 312 females). Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behavior to non-lesioned subcortical volumes. We analyzed subacute (≤90 days) and chronic (≥180 days) stroke; sub-analyses in chronic stroke were performed on class of sensorimotor deficit (impairment, activity limitations) and side of lesioned hemisphere, with exploratory analyses in early stroke (≤21 days) and across time (Bonferroni-corrected, p Worse sensorimotor behavior was associated with a smaller ipsilesional thalamic volume in both subacute (n=274, d=0.46) and early stroke (n=179; d=0.68). In chronic stroke (n=404), worse sensorimotor behavior was associated with smaller ipsilesional putamen (d=0.52) and nucleus accumbens (d=0.39) volumes, and a larger ipsilesional lateral ventricle volume (d=-0.42), representing atrophy. In chronic stroke, worse sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n=256) was associated with a smaller ipsilesional putamen (d=0.72), and larger lateral ventricle (d=-0.41), while several measures of activity limitations (n=116) showed no significant relationships. Side of lesion (left=214, right=190) had no impact. The full cohort (n=828) revealed associations of sensorimotor behavior with the ipsilesional nucleus accumbens (d=0.23), putamen (d=0.33), thalamus (d=0.33), and lateral ventricle (d=-0.23). This analysis identified significant relationships between sensorimotor behavior and key subcortical regions at different times post-stroke. While further longitudinal studies are needed, these findings may represent brain imaging markers of resilience and reserve and provide putative neuroanatomical targets for improving sensorimotor outcomes post-stroke.