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 the close-loop feedback that can be provided with these systems, but more evidence is needed regarding their clinical and neuroplasticity effects. Methods: A randomized controlled trial was performed using the ReHand-BCI system that provides feedback with a robotic hand orthosis. The experimental group (EG) used the ReHand-BCI, while sham-BCI was given to the control group (CG). Both groups performed 30 therapy sessions, with primary outcomes being the Fugl-Meyer Assessment for the Upper Extremity (FMA-UE) and the Action Research Arm Test (ARAT). Secondary outcomes were hemispheric dominance, measured with electroencephalography and functional magnetic resonance imaging, white matter integrity via diffusion tensor imaging, and corticospinal tract integrity and excitability, measured with transcranial magnetic stimulation. Results: At post-treatment, patients in both groups had significantly different FMA-UE scores (EG: baseline = 24.5[20, 36], post-treatment 28[23, 43], CG: baseline = 26[16, 37.5], post-treatment = 34[17.3, 46.5]), while only the EG had significantly different ARAT scores at post-treatment (EG: baseline = 8.5[5, 26], post-treatment = 20[7, 36], CG: baseline = 3[1.8, 30.5], post-treatment = 15[2.5, 40.8]). In addition, across the intervention, the EG showed trends of more pronounced ipsilesional cortical activity and higher ipsilesional corticospinal tract integrity, although these differences were not statistically different compared to the control group, likely due to the study's sample size. Conclusion: To the authors' knowledge, this is the first clinical trial that has assessed such a wide range of physiological effects across a long BCI intervention, implying that a more pronounced ipsilesional hemispheric dominance is associated with upper extremity motor recovery. Therefore, the study brings light into the neuroplasticity effects of a closed-loop BCI-based neurorehabilitation intervention in stroke. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04724824.