Personalized assistive EMG-controlled virtual reality interface combined with cerebellar-iTBS for post-stroke arm recovery (ERICA): study protocol for a three-arm randomized controlled trial

Stroke survivors frequently experience long-lasting motor impairments of the upper limb that limit their independence and quality of life. While recovery is most pronounced in the early phases, targeted rehabilitation can still promote meaningful improvements in the chronic stage by stimulating neuroplasticity. Immersive virtual reality and myoelectric control interfaces can deliver intensive, engaging, task-specific training, while cerebellar non-invasive stimulation has shown potential to enhance motor recovery. This trial investigates whether combining cerebellar intermittent theta burst stimulation with personalized virtual reality training, with assistance provided through myoelectric control, can improve upper limb function in patients with chronic stroke. This study is a randomized, controlled, parallel-group trial with three arms. Forty-five participants with chronic stroke will be randomly assigned to (1) active cerebellar intermittent theta burst stimulation followed by assisted myoelectric control virtual reality training, (2) sham stimulation with the same virtual reality training, or (3) conventional physical therapy. Each participant will receive twelve 30-min sessions over 4 weeks. Assisted myoelectric control uses surface electromyographic signals from residual muscle activity to drive movements in the virtual environment. An adaptive algorithm provides corrective assistance by moving a virtual end-effector according to the projection of the patient’s electromyographic activity onto more physiological activation patterns and gradually reducing support as performance improves. The primary outcome is upper limb motor function, assessed with the Fugl-Meyer Assessment for Upper Extremity. Secondary outcomes include tests of manual dexterity, functional independence, electromyographic activity, and corticospinal excitability. Assessments will be conducted at baseline, immediately after the last session of intervention, and at 6-week follow-up by blinded evaluators. This trial is the first to systematically test the combined effect of cerebellar stimulation and physiologically grounded myoelectric assistance within an immersive virtual reality setting. By integrating top-down neuromodulation of cerebello-cortical circuits with bottom-up task-specific feedback, the approach aims to optimize neural plasticity and promote motor recovery beyond standard therapy. If effective, the intervention could provide a novel and personalized rehabilitation strategy for chronic stroke survivors. ClinicalTrials.gov NCT06911671. Registered on 3 February 2023.