Efficacy of Brain-Computer Interface Therapy for Upper Limb Rehabilitation in Chronic Stroke: Systematic Review and Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Over 50% of people with chronic stroke experience persistent upper limb dysfunction. Brain-computer interface (BCI) therapy, creating a sensorimotor loop via neural feedback, is a promising alternative; yet, its optimal application remains unclear. OBJECTIVE: This meta-analysis evaluates BCI's efficacy on motor function, tone, and activities of daily living (ADL) in chronic stroke and identifies optimal feedback modalities and intervention parameters. METHODS: We systematically searched Cochrane Library, Embase, PubMed, Scopus, Web of Science, and Wanfang Data from inception to October 2025 for randomized controlled trials (RCTs) comparing BCI-based training to control interventions in adults with chronic stroke. Primary outcomes were upper limb motor function (Fugl-Meyer Assessment for upper extremity [FMA-UE], Action Research Arm Test [ARAT]), muscle tone (Modified Ashworth Scale [MAS]), and ADL (Modified Barthel Index [MBI], Motor Activity Log [MAL]). Screening, data extraction, and risk-of-bias assessment were performed independently. Meta-analysis used a random-effects model with Hartung-Knapp-Sidik-Jonkman adjustment. Pooled mean differences (MDs) with 95% CIs and 95% prediction intervals (PIs) were calculated. Subgroup analyses examined feedback modalities, intervention intensity, and follow-up effects. Sensitivity analysis was also conducted. RESULTS: From 3529 records, 21 RCTs (650 participants) were included. BCI training significantly improved motor function (FMA-UE: MD 2.50, 95% CI 0.60-4.40; P=.01; 95% PI -2.52 to 7.22) and ADL performance (MBI: MD 8.38, 95% CI 2.23-14.53; P=.02; 95% PI -3.92 to 20.53; MAL: MD 2.09, 95% CI 0.42-3.76; P=.03; 95% PI -0.69 to 4.54). No significant effects were observed for fine motor skills (ARAT: MD 0.18, 95% CI -0.27 to 0.62; P=.30; 95% PI -3.64 to 3.99) or muscle tone (MAS: MD -0.48, 95% CI -1 to 0.03; P=.06; 95% PI -1.27 to 0.35). Subgroup analyses revealed that BCI-functional electrical stimulation (FES) yielded the greatest improvement in motor recovery (FMA-UE: MD 5, 95% CI 1.86-8.13; P=.01). The optimal intervention protocol was identified as 30-minute sessions, administered 4-5 times per week over 2 weeks (total of 10-12 sessions). However, benefits were not sustained at follow-up. CONCLUSIONS: Low- to moderate-certainty evidence suggests that BCI training, particularly the BCI-FES paradigm, can improve upper limb motor function and ADL in people with chronic stroke on average. However, wide prediction intervals indicate the effect may vary substantially across settings, ranging from negligible to beneficial. Subgroup analyses suggested a potential optimal protocol of 30-minute sessions, 4-5 times per week for 2 weeks, but these findings are limited by the small number of studies in each subgroup and the high risk of bias in several included trials. Therefore, this proposed protocol should be viewed as preliminary and requires validation in future, high-quality RCTs. Future research should also focus on identifying patient subgroups most likely to benefit and on strategies to sustain long-term gains. TRIAL REGISTRATION: PROSPERO CRD420251063808; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251063808.