The ReHand-BCI trial: a randomized controlled trial of a brain-computer interface for upper extremity stroke neurorehabilitation

Background: Brain-computer interfaces (BCI) are a promising complementary therapy for stroke rehabilitation due to closed-loop feedback, but more evidence is needed on clinical and neuroplasticity effects. Methods: A randomized controlled trial compared ReHand-BCI (experimental group, EG) providing robotic hand orthosis feedback driven by motor intention with sham-BCI (control group, CG) where orthosis activation was random. Both groups received 30 sessions. Primary outcomes were Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Action Research Arm Test (ARAT). Secondary outcomes included hemispheric dominance (EEG laterality coefficient, fMRI laterality index), white matter integrity (DTI ratio of fractional anisotropy), and corticospinal tract integrity/excitability (TMS). Results: Both groups showed significant within-group improvements in FMA-UE at post-treatment (EG baseline 24.5 [20, 36] to 28 [23, 43]; CG baseline 26 [16, 37.5] to 34 [17.3, 46.5]). Only EG showed significant ARAT improvement at post-treatment (EG baseline 8.5 [5, 26] to 20 [7, 36]; CG baseline 3 [1.8, 30.5] to 15 [2.5, 40.8]). EG exhibited trends toward more ipsilesional cortical activity and higher ipsilesional CST integrity, but these did not reach statistical significance versus CG, likely due to sample size. Conclusion: This trial assessed a broad set of physiological effects over a long BCI intervention, suggesting that more pronounced ipsilesional hemispheric dominance is associated with upper extremity motor recovery. Findings illuminate neuroplasticity effects of closed-loop BCI-based neurorehabilitation after stroke. Clinical trial registration: NCT04724824.

Jessica Cantillo-Negrete, Martín Emiliano Rodríguez-García, Paul Carrillo-Mora, Oscar Arias-Carrión, Emmanuel Ortega-Robles, Marlene A. Galicia-Alvarado, Raquel Valdés-Cristerna, Ana G. Ramirez-Nava, Claudia Hernandez-Arenas, Jimena Quinzaños-Fresnedo, Ma. del Refugio Pacheco-Gallegos, Norma Marín-Arriaga, Ruben I. Carino-Escobar