Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide

Background and Purpose 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. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behavior at different timepoints after stroke. Methods We pooled high-resolution T1-weighted MRI brain scans and behavioral data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behavior to non-lesioned subcortical volumes (Bonferroni-corrected, p<0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Results Worse sensorimotor behavior was associated with a smaller ipsilesional thalamic volume in both early (n=179; d =0.68) and subacute (n=274, d =0.46) stroke. 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 ( d =-0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n=256) was associated with smaller ipsilesional putamen ( d =0.72) and larger lateral ventricle ( d =-0.41) volumes, while several measures of activity limitations (n=116) showed no significant relationships. In the full cohort across all time (n=828), sensorimotor behavior was associated with the volumes of the ipsilesional nucleus accumbens ( d =0.23), putamen ( d =0.33), thalamus ( d =0.33), and lateral ventricle ( d =-0.23). Conclusions We demonstrate significant relationships between post-stroke sensorimotor behavior and reduced volumes of subcortical gray matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings may provide additional targets for improving post-stroke sensorimotor outcomes. ### Competing Interest Statement N.J. and P.M.T. are MPI of a research grant from Biogen, Inc for work unrelated to the contents of this manuscript. S.C.C. has served as a consultant for Constant Therapeutics, MicroTransponder, Neurolutions, SanBio, Stemedica, Fujifilm Toyama Chemical Co., NeuExcell, Medtronic, and TRCare. M.A.P. has received Research Funding & Travel Grant (Bionic Vision Technologies Pty Ltd) unrelated to the contents of this manuscript.