Brain-Controlled Epidural Stimulation Restores Corticospinal Connectivity to Improve Upper-Limb Function in Chronic Tetraplegia

Spinal cord injury disrupts corticospinal transmission and impairs voluntary motor control. While epidural spinal cord stimulation (ESCS) can augment residual motor output, its capacity to drive long-term neuroplasticity remains unoptimized. Here, we present a first-in-human study showing that an implantable brain-computer interface (BCI) paired with cervical ESCS can potentiate corticospinal connectivity, leading to both immediate and sustained improvements in upper-limb motor function in an individual with chronic, motor-complete cervical SCI. The BCI system decodes motor intent from electrocorticography signals to deliver time-locked stimulation to spinal circuits during volitional movement attempts. This BCI-ESCS paradigm enhanced grip strength and object manipulation immediately and elicited greater increases in corticospinal excitability after a single session compared to tonic ESCS. Notably, a four-week BCI-ESCS therapy led to clinically meaningful improvements in voluntary hand function even without system assistance, with some gains persisting one-month post-therapy. These findings show that intention-driven neuromodulation efficiently induces corticospinal plasticity, offering a mechanistically driven neuromotor recovery approach. Overall, BCI-ESCS can restore volitional control even in an individual with severe paralysis once deemed at the recovery plateau.