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.

Stroke is one of the main causes of disabilities caused by injuries to the human central nervous system, yielding a wide range of mild to severe impairments that can compromise sensorimotor and cognitive functions. Although rehabilitation protocols may improve function of stroke survivors, patients often reach plateaus while undergoing therapy. Recently, virtual reality (VR) technologies have been paired with traditional rehabilitation aiming to improve function recovery after stroke. Aiming to better understand structural brain changes due to VR rehabilitation protocols, we modeled the brain as a graph and extracted three measures representing the network's topology: degree, clustering coefficient and betweenness centrality (BC). In this single case study, our results indicate that all metrics increased on the ipsilesional hemisphere, while remaining about the same at the contralesional site. Particularly, the number of functional connections increased in the lesion area overtime. In addition, the BC displayed the highest variations, and in brain regions related to the patient's cognitive and motor impairments; hence, we argue that this measure could be regarded as an indicative for brain plasticity mechanisms.

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