Rapid functional remodeling of the targeted contralesional hemisphere induced by one week of noninvasive closed-loop neurofeedback guides motor recovery in post-stroke patients with chronic motor impairment: a phase I trial

Post-stroke hemiplegia of the upper extremities continues to pose a significant therapeutic hurdle. Contralesional uncrossed corticospinal pathways (CST) are involved in the recovery processes. Here, we test the feasibility, safety, and preliminary efficacy of targeted upregulation of uncrossed CST excitability using self-modulation training of cortical activities. In this phase I trial, eight individuals with persistent (1-8 years) severe post-stroke motor disability, who did not respond to conventional rehabilitation, voluntarily actuated their affected shoulder using a closed-loop, noninvasive digital connection, bridging the contralesional motor cortex (M1) and an exoskeleton robot. While patients attempted to elevate the affected arm, scalp electroencephalogram signals over the contralesional M1 were processed online to provide them with feedback on induced excitability change. Extensive neurophysiological examinations were conducted to evaluate the intervention effect using whole-head EEG and magnetic stimulations. The digital connection reconstructed neural pathways, allowing arm elevation contingent on voluntary upregulation of contralesional M1 excitability without any adverse effects. As evidenced by clinical score increases and neurophysiological examinations, seven days of consecutive system use resulted in rapid, sustained, and clinically significant improvement in motor function when removed from the system and promoted contralesional M1 functional remodeling. This closed-loop system is safe, feasible, and a promising intervention that recruits intact neural resources to allow patients to recover upper-extremity motor abilities. Larger clinical trials are needed to confirm these results.