Sequence-Specific Reduction of Interlimb Accuracy Asymmetry Reveals Preserved Motor Learning Dynamics in Chronic Stroke: Insights from Lesion-Aware fMRI

Abstract

Background: People with chronic stroke retain the capacity to learn new motor skills, yet how preserved motor learning is expressed during practice remains incompletely understood. Sequence learning provides a useful model for examining these within-session learning dynamics and their neural basis after stroke. Objective: To characterize a temporally resolved behavioral phenotype of motor sequence learning in chronic stroke and establish its neural context using task-based functional MRI (fMRI). Methods: Twenty-four individuals with chronic stroke and 14 neurologically healthy controls performed a bimanual force-tracking sequence-learning task during functional MRI. Performance convergence was defined as the sequence-specific reduction in the accuracy difference between the paretic and less-affected hands across practice. Neural activity was evaluated using whole-brain, region-of-interest, and functional-connectivity analyses following preprocessing tailored to structurally heterogeneous stroke lesions. Results: Stroke participants demonstrated significant performance convergence despite persistent motor impairment, indicating preserved expression of sequence learning during practice that was not detected by conventional behavioral measures. Lesion-aware fMRI identified robust task-related activation and preserved stage-dependent modulation within cerebellar, premotor, and striatal learning networks, together with reduced bilateral putaminal activity after stroke. However, preregistered analyses found no reproducible associations between individual differences in performance convergence and learning-related activation or functional connectivity. Conclusions: Performance convergence provides a sensitive, temporally resolved behavioral phenotype of preserved motor sequence learning in chronic stroke that complements conventional endpoint measures. Together, performance convergence and task-based functional MRI provide a framework for investigating individual differences in motor learning capacity and their implications for rehabilitation responsiveness.