Uncovering and exploiting the return of voluntary motor programs after paralysis using a bi-cortical neuroprosthesis

Abstract

Rehabilitative and neuroprosthetic approaches after spinal cord injury (SCI) aim to reestablish voluntary control of movement. Promoting recovery requires a mechanistic understanding of the return of volition over action, but the relationship between re-emerging cortical commands and the return of locomotion is not well established. We introduced a neuroprosthesis delivering targeted bi-cortical stimulation in a clinically relevant contusive SCI model. In healthy and SCI cats, we controlled hindlimb locomotor output by tuning stimulation timing, duration, amplitude, and site. In intact cats, we unveiled a large repertoire of motor programs. After SCI, the evoked hindlimb lifts were highly stereotyped, yet effective in modulating gait and alleviating bilateral foot drag. Results suggest that the neural substrate underpinning motor recovery had traded-off selectivity for efficacy. Longitudinal tests revealed that the return of locomotion after SCI was time-locked with recovery of the descending drive, which advocates for rehabilitation interventions directed at the cortical target. HighlightsO_LIA bilateral cortical implant allowed for the delivery of alternate bilateral stimulation coherently with locomotion, which modulated gait trajectories. C_LIO_LIWe analyzed the effects of stimulation parameters - timing, duration, amplitude, and site of stimulation - to maximize the improvement of locomotor output after paralysis. C_LIO_LIA varied repertoire of motor programs evoked in intact cats was reduced to one stereotyped response after spinal cord injury (SCI) consisting in flexion modulation that efficiently alleviated hindlimb dragging. C_LIO_LIAfter SCI, the return of cortical gait control emerged in synchrony with locomotor recovery. C_LI