Impact of post-stroke cognitive impairment and brain connectivity on early versus late motor skill learning

Cognition is more engaged during early than later motor skill learning (MSkL), yet the impact of post-stroke cognitive impairment (PSCI) and brain connectivity on early MSkL remains unclear. We hypothesized that early MSkL would be impaired in people with chronic stroke compared to healthy individuals (HI), and that this impairment would be associated with PSCI, lesion burden, and structural and functional connectivity. Fifty-three people with chronic stroke and twenty-one mean age-matched HI completed a comprehensive neuropsychological assessment and trained with their contralesional/non-dominant upper limb on a speed/accuracy trade-off task across two sessions, one-week apart. Early and late MSkL were modelled and related to PSCI. To identify neural substrates and predictors of post-stroke early MSkL, multimodal brain imaging included voxel-based lesion symptom mapping, whole-brain microstructural integrity and structural-functional connectivity analyses. Both HI and people with stroke demonstrated typical MSkL patterns (retention and generalization), but HI showed steeper early MSkL. PSCI correlated with poorer early MSkL. Lesions overlapping the corticospinal tract, insula and frontal white matter tracts were associated with early MSkL deficits, while higher microstructural integrity in the posterior corpus callosum correlated with better early MSkL. Structural and functional connectome-based predictive modeling identified subcortical, temporal, visual-associative, and insular hubs with interhemispheric connections as key predictors of early MSkL after stroke. These findings indicate that early MSkL is selectively impaired in chronic stroke and related to PSCI and lesion burden. Multimodal neuroimaging highlighted the role of an interhemispheric network involving sensorimotor, salience, and associative regions in supporting early MSkL in chronic stroke.