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 their closed-loop feedback, but more evidence is needed on clinical efficacy and neuroplasticity effects. Methods: A randomized controlled trial evaluated the ReHand-BCI system providing feedback via a robotic hand orthosis. The experimental group (EG) received BCI-controlled orthosis; the control group (CG) received sham-BCI (random orthosis activation). Both groups completed 30 therapy sessions. Primary outcomes were Fugl-Meyer Assessment for the Upper Extremity (FMA-UE) and Action Research Arm Test (ARAT). Secondary outcomes included hemispheric dominance (EEG laterality coefficient and fMRI laterality index), white matter integrity (DTI ratio of fractional anisotropy, rFA), and corticospinal tract integrity/excitability (TMS). Results: Both groups improved FMA-UE at post-treatment (EG median: baseline 24.5 [20, 36] to 28 [23, 43]; CG: 26 [16, 37.5] to 34 [17.3, 46.5]). Only the EG showed significant ARAT improvement at post-treatment (EG: 8.5 [5, 26] to 20 [7, 36]; CG: 3 [1.8, 30.5] to 15 [2.5, 40.8]). The EG exhibited trends toward more pronounced ipsilesional cortical activity and higher ipsilesional corticospinal tract integrity, though between-group differences were not statistically significant, likely due to sample size. Conclusion: This trial is the first to assess a wide set of physiological effects across a long BCI intervention, suggesting that more pronounced ipsilesional hemispheric dominance is associated with recovery of upper extremity motor function. The study sheds light on neuroplasticity effects of closed-loop BCI-based neurorehabilitation in stroke. Clinical trial registration: NCT04724824.