Early Multimodal Motor Training After Stroke Promotes Motor Recovery and Whole‐Brain Structural Remodeling

Background Early task‐specific rehabilitation is critical for recovery after stroke, yet it remains unclear whether combining established rehabilitative training principles into an early multimodal motor training (EMT) paradigm improves recovery by engaging only local peri‐infarct adaptation or a broader, longitudinally detectable pattern of structural brain remodeling. Methods Male rats were assigned to stroke+EMT, stroke, EMT, or control groups. Focal photothrombotic stroke was induced in the right sensorimotor cortex. EMT began 2 days after stroke and consisted of an obstacle‐based training paradigm with variable and progressively increasing difficulty delivered over 8 weeks. Skilled locomotion was assessed using the ladder‐rung test. Longitudinal T2‐weighted magnetic resonance imaging and deformation‐based morphometry were used to quantify structural brain alterations. Significant loci from voxel‐wise group×time interaction F‐contrast maps (family‐wise error‐corrected, P <0.05) were summarized as structural events and analyzed according to their spatial and temporal organization. Results EMT improved poststroke motor recovery and was associated with broader structural remodeling than stroke or EMT alone (82 versus 15 and 10 structural events, respectively). These alterations extended beyond peri‐infarct tissue, were bilaterally distributed, and mapped to both sensorimotor and higher‐order brain systems, with frequent homotopic occurrence (74.4%) and multinetwork assignment (50.0%). Structural events were distributed across 6 temporal profiles, indicating distinct early‐to‐late remodeling courses rather than a single monotonic process. Conclusions These findings support a shift in how early poststroke rehabilitation is conceptualized: not as a local process confined to isolated brain regions, but as a driver of distributed, bilateral, and temporally organized structural remodeling across multiple brain systems.