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Background: Motor rehabilitation is routinely used in clinical practice as an effective method to reduce progressive disability gain in multiple sclerosis (MS), but rehabilitation approaches are typically unstandardized, and only few studies have investigated the impact of rehabilitation on brain neuroplasticity.

Objective: To summarize and critically analyze studies applying MRI markers of functional connectivity and structural changes to assess the effect of motor rehabilitation on brain neuroplasticity in MS.

Methods: Literature search was performed using PubMed and EMBASE, selecting studies having as a subject motor rehabilitation and advanced MRI techniques investigating neuroplasticity in adult patients affected by MS.

Results: Seventeen out of 798 papers were selected, of which 5 applied structural MRI (4 diffusion tensor imaging, 1 volumetric measurements), 7 applied functional fMRI (5 task-related fMRI, 2 resting-state fMRI) whereas the remaining 5 applied both structural and functional imaging.

Discussion: The considerable data heterogeneity and the small sample sizes characterizing the studies limit interpretation and generalization of the results. Overall, motor rehabilitation promotes clinical improvement, paralleled by positive adaptive brain changes, whose features and extent depend upon different variables, including the type of rehabilitation approach. MRI markers of functional and structural connectivity should be implemented in studies testing the efficacy of motor rehabilitation. They allow for a better understanding of neuroplastic mechanisms underlying rehabilitation-mediated clinical achievements, facilitating the identification of …