OBJECTIVE: To systematically review and examine the current literature regarding the effects of Virtual Reality (VR)-based rehabilitation on neural plasticity changes in stroke survivors. DATA SOURCES: Six bioscience and engineering databases were searched, including Medline via EBSCO, Embase, PsycINFO, IEEE Explore, Cumulative Index of Nursing and Allied Health, and Scopus. STUDY SELECTION: Studies reporting on the pre-post assessment of a VR intervention with neural plasticity measures published between 2000 to 2021 were included. DATA EXTRACTION: Two independent reviewers conducted study selection, data extraction and quality assessment. Methodological quality of controlled trials was assessed using the Physiotherapy Evidence Database scale. Risk of bias of pre-post intervention and case studies was evaluated using the National Institutes of Health Quality Assessment Tool. DATA SYNTHESIS: Twenty-seven studies (total n = 232) were included. Seven randomized controlled trials were rated as good quality while the two clinical controlled trials were moderate. Based on the risk of bias assessment, one pre-post study and one case study were graded as good quality, one pre-post study and one case study were poor, the other 14 studies were all at fair. After the VR intervention, main neurophysiological findings across studies include: (1) improved interhemispheric balance, (2) enhanced cortical connectivity, (3) increased cortical mapping of the affected limb muscles, (4) the improved neural plasticity measures were correlated to the enhanced behavior outcomes, (5) increased activation of regions in frontal cortex and (6) the mirror neuron system may be involved. CONCLUSIONS: Virtual reality induced changes in neural plasticity for stroke survivors. Positive correlations between the neural plasticity changes and functional recovery elucidates the mechanisms of VR's therapeutic effects in stroke rehabilitation. This review prompts systematic understanding of the neurophysiological mechanisms of VR-based stroke rehabilitation and summarizes the emerging evidence for ongoing innovation of VR systems and application in stroke rehabilitation.

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