No abstract

Epidural electrical stimulation (EES) of the spinal cord restores locomotion in animal models of spinal cord injury (SCI) but is less effective in humans. Here, we hypothesized that this inter-species discrepancy is due to interference between EES and proprioceptive information in humans. Computational simulations, preclinical and clinical experiments reveal that EES blocks a significant amount of proprioceptive input in humans, but not in rats. This transient deafferentation prevents the modulation of reciprocal inhibitory networks involved in locomotion and reduces or abolishes the conscious perception of leg position. Consequently, continuous EES can only facilitate locomotion within a narrow range of stimulation parameters and is unable to provide meaningful locomotor improvements in humans without rehabilitation. Simulations showed that burst stimulation and spatiotemporal stimulation profiles mitigate the cancellation of proprioceptive information, enabling robust control over motoneuron activity. This demonstrates the importance of stimulation protocols that preserve proprioceptive information to facilitate walking with EES.

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restored walking in people with spinal cord injury (SCI). However, EES was delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed a software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis, as part of an ongoing clinical trial (clinicaltrials.gov, NCT02936453). Within a single day, activity-specific stimulation programs enabled the three individuals to stand, walk, cycle, swim, and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.