The Potential of Rehabilitation to Amplify Experience-Induced Myelin Plasticity and Remyelination in Multiple...

This narrative review synthesizes emerging evidence on experience-dependent myelin plasticity and its relevance for neurorehabilitation in persons with multiple sclerosis (MS). Building on foundational work demonstrating motor learning-induced neuroplasticity, we highlight growing recognition that myelination remains adaptable across the lifespan and may be harnessed to support motor relearning, neuroprotection, and remyelination in MS.

Preclinical and human studies demonstrate that neuronal activity, especially that induced by motor learning, regulates oligodendrocyte behavior and myelin remodeling. Rodent models show that skilled training enhances oligodendrocyte precursor cell proliferation and myelin thickness, while human neuroimaging confirms training-related increases in myelin-sensitive metrics within task-relevant systems. In MS, early evidence from exercise and motor training studies suggests task-specific white matter plasticity, though sample sizes remain small and imaging outcomes heterogeneous. Additional work points to synergistic potential between behavioral training, neuromodulation, and pharmacologic remyelinating agents. Notably, the combination of exercise and clemastine produces robust remyelination in preclinical models. With MS patients now living longer, aging introduces additional vulnerabilities-including inflammation, microglial dysfunction, and reduced regenerative capacity-but myelin retains responsiveness to behavioral and environmental enrichment. Experience-dependent myelin plasticity represents a promising but underexplored mechanism for enhancing neurorehabilitation outcomes. Motor learning, physical exercise, and multimodal interventions may support adaptive myelination, though optimized dosing, timing, and biomarkers remain undefined. Future research should employ targeted, multimodal imaging approaches and integrate behavioral, neuromodulatory, and pharmacologic strategies, in addition to following patients longitudinally post-intervention, to clarify the therapeutic potential of activity-driven remyelination.