Non-invasive closed-loop spinal stimulation restores leg stepping control in humans with paraplegia

Gait disturbance in individuals with spinal cord injury (SCI) at levels rostral to the lumbar locomotor centre results from disconnection between the supraspinal system and the spinal locomotor centre. Here, we present a non-invasive volition-controlled spinal stimulation paradigm that empowers paraplegic individuals to regain stepping control in their impaired legs. Using hand muscle-controlled magnetic stimulation targeting the lumbar spinal motor circuits in the preserved lumber cord, individuals with chronic SCI achieved control of start-stop motion, step length and cadence of bilateral cyclic stepping in paralysed legs. Stimulus-induced cyclic stepping with leg muscle EMG activity was evoked in all participants with complete or incomplete SCI, regardless of the lesion site between the thoracic and lumbar spinal cord. Combining voluntary gait effort with closed-loop stimulation further enhanced leg movements. Repeated application of this closed-loop stimulation led to progressive improvement in stimulus-induced stepping and muscle responses, particularly in participants with thoracic SCI, and in stimulus-free stepping, particularly in participants with incomplete SCI. Our findings indicate that the preserved lumbar spinal motor circuit plays a crucial role in improving stimulus-induced stepping, whereas the preserved descending pathway is required for improving stimulus-free stepping. This non-invasive closed-loop spinal stimulation paradigm bypasses the lesion site on the spinal cord and strengthens both the preserved spinal circuits and the descending pathways to allow bilateral stepping control to be regained after SCI. This approach holds great promise for SCI-related gait rehabilitation because it has the potential to lead to functional recovery. Furthermore, this approach offers a viable alternative for individuals with contraindications to invasive procedures or those who do not consent to surgical treatments.