AUTHOR=Cui Yao , Cong Fang , Zeng Ming , Wang Jun TITLE=Effects and mechanisms of synchronous virtual reality action observation and electrical stimulation on upper extremity motor function and activities of daily living in patients with stroke: a protocol for a randomized controlled trial JOURNAL=Frontiers in Neurology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1499178 DOI=10.3389/fneur.2025.1499178 ISSN=1664-2295 ABSTRACT=BackgroundExisting rehabilitation techniques are not satisfactory in improving motor function after stroke, resulting in heavy social burdens. With discovery of mirror neuron system (MNS), action observation (AO) has become a promising strategy to promote motor learning in rehabilitation. Based on MNS theory and virtual reality (VR) technology, we designed an innovative rehabilitative approach: synchronous 360° VR video AO (VRAO) and neuromuscular electrical stimulation (NMES). We hypothesized that VRAO+NMES could enhance MNS activation, thus to improve upper limb motor function and activities of daily living in stroke survivors.MethodsTo explore the efficacy and mechanism of VRAO+NMES, we designed this single center, evaluator blinded, prospective, two arm parallel group randomized controlled trial with 1:1 allocation ratio. The experiment group will receive VRAO+NMES, while the control group will receive VR landscape observation combined with NMES. The Fugl-Meyer Assessment for Upper Extremity is the primary outcome of this study, Brunstrom Recovery Stages for Upper Extremity, Manual Muscle Test, Range of Motion, Modified Barthel Index, and Functional Independence Measure are the secondary outcomes. In addition, functional near-infrared spectroscopy (fNIRS) and surface electromyography (sEMG) will be used to evaluate the activation of MNS brain regions and related muscles, respectively.DiscussionApplying VR in AO therapy (AOT) has become popular, another study direction to improve AOT is to combine it with peripheral stimulations simultaneously. Due to its full immersive characteristic and multi-sensory input, 360° videos based VRAO+NMES could improve the motivation and engagement level of participants. In addition, fNIRS and sEMG test results may act as good biomarkers to predict rehabilitation outcomes, helping select suitable candidates for this new intervention.ConclusionThe results of this study will provide evidence for the feasibility and potential clinical efficacy of VRAO+NMES in stroke rehabilitation, thus to promote the clinical applicability and generalize its use in hospital, community, and home rehabilitation settings.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=178276, Identifier [ChiCTR2200063552].