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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.

We thank Sim4Life by ZMT, www.zurichmedtech.com for their support. We thank Brian K. Kwon for critically reading the manuscript and his insightful suggestions.

A spinal cord injury interrupts pathways from the brain and brainstem that project to the lumbar spinal cord, leading to paralysis. Here we show that spatiotemporal epidural electrical stimulation (EES) of the lumbar spinal cord1–3 applied during neurorehabilitation4,5 (EESREHAB) restored walking in nine individuals with chronic spinal cord injury. This recovery involved a reduction in neuronal activity in the lumbar spinal cord of humans during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential for a patient to walk after spinal cord injury. To identify these putative neurons, we modelled the technological and therapeutic features underlying EESREHAB in mice. We applied single-nucleus RNA sequencing6–9 and spatial transcriptomics10,11 to the spinal cords of these mice to chart a spatially resolved molecular atlas of recovery from paralysis. We then employed cell type12,13 and spatial prioritization to identify the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons are not required for walking before spinal cord injury, we demonstrate that they are essential for the recovery of walking with EES following spinal cord injury. Augmenting the activity of these neurons phenocopied the recovery of walking enabled by EESREHAB, whereas ablating them prevented the recovery of walking that occurs spontaneously after moderate spinal cord injury. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after paralysis. Moreover, our methodology establishes a framework for using molecular cartography to identify the neurons that produce complex behaviours.

B ODY weight support (BWS) systems are widely used in gait research and rehabilitation. This paper introduces a new 3D overground BWS system, called the RYSEN 7. The RYSEN is designed to be intrinsically safe and low power consuming, while still performing at least as well as existing BWS systems regarding human-robot interaction. These features are mainly achieved by decoupling degrees of freedom between motors: slow/high-torque motors for vertical motion and fast/low-torque motors for horizontal motion. This paper explains the design and evaluates its performance on power consumption and safety. Power consumption is expressed in terms of the sum of the positive mechanical output power of all motor axes. Safety is defined as the difference between the mechanical power available for horizontal and vertical movements and the mechanical power that is needed to perform its task. The results of the RYSEN are compared to the performance of three similar systems: a gantry, the FLOAT and a classic cable robot. The results show that the RYSEN and a gantry consume approximately the same amount of power. The amount is approximately half the power consumed by the next best system. For the safety, the gantry is taken as the benchmark, because of its perfect decoupling of directions. The RYSEN has a surplus of 268 W and 126 W for horizontal and vertical movements respectively. This is significantly lower than the next best system, which has a surplus of 1088 W and 1967 W respectively.

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