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Background: The use of virtual reality (VR) as a rehabilitation tool has been shown to induce motor and cognitive improvements in different populations. Functional magnetic resonance imaging (fMRI) has been used to investigate neuroplasticity resulting from these treatments. We hypothesize that VR rehabilitation induces functional improvement and brain changes that can be detected by fMRI. Objective: To systematically review the effects of VR intervention on the cortical reorganization measured by fMRI and associated with functional improvement. Methods: We performed a systematic review of studies published between 2005 and 2021. Papers were retrieved from six databases using the following keywords: “motor rehabilitation”, “fMRI” and “virtual reality”. Case studies, pre-post studies, cross-sectional studies, and randomized controlled trials published were included. Manuscripts were assessed by The NIH Study Quality Assessment Tools to determine their quality. Results: Twenty-three articles met our eligibility criteria: 18 about VR rehabilitation in stroke and five on other clinical conditions (older adults, cerebral palsy, and Parkinson's disease). Changes in neural patterns of activation and reorganization were revealed in both the ipsilesional and the contralesional hemispheres. Results were located mainly in the primary motor cortex, sensorimotor cortex and supplementary motor area in post-stroke patients in the acute, subacute, and chronic rehabilitation phases, and were associated with functional improvement after VR intervention. Similar effects were observed in older adults and in patients with other neurological diseases with improved performance. Conclusion: Most stroke-related studies showed either restoration to normal or increase of activation patterns or relateralization at/to the ipsilesional hemisphere, with some also reporting a decrease in activity or extent of activation after VR therapy. In general, VR intervention demonstrated evidence of efficacy both in neurological rehabilitation and in performance improvement of older adults, accompanied by fMRI evidence of brain reorganization.

Low-frequency repetitive transcranial magnetic stimulation of the unaffected hemisphere (UH-LF-rTMS) in patients with stroke can decrease interhemispheric inhibition from the unaffected to the affected hemisphere and improve hand dexterity and strength of the paretic hand. The objective of this proof-of-principle study was to explore, for the first time, effects of UH-LF-rTMS as add-on therapy to motor rehabilitation on short-term intracortical inhibition (SICI) and intracortical facilitation (ICF) of the motor cortex of the unaffected hemisphere (M1UH) in patients with ischemic stroke. Eighteen patients were randomized to receive, immediately before rehabilitation treatment, either active or sham UH-LF-rTMS, during two weeks. Resting motor threshold (rMT), SICI, and ICF were measured in M1UH before the first session and after the last session of treatment. There was a significant increase in ICF in the active group compared to the sham group after treatment, and there was no significant differences in changes in rMT or SICI. ICF is a measure of intracortical synaptic excitability, with a relative contribution of spinal mechanisms. ICF is typically upregulated by glutamatergic agonists and downregulated by gabaergic antagonists. The observed increase in ICF in the active group, in this hypothesis-generating study, may be related to M1UH reorganization induced by UH-LF-rTMS.

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