Most rehabilitation interventions after spinal cord injury (SCI) only target the sublesional spinal networks, peripheral nerves, and muscles. However, mammalian locomotion is not a mere act of rhythmic pattern generation. Recovery of cortical control is essential for voluntary movement and modulation of gait. We developed an intracortical neuroprosthetic intervention to SCI, with the goal to condition cortical locomotor control. Neurostimulation delivered in phase coherence with ongoing locomotion immediately alleviated primary SCI deficits, such as leg dragging, in rats with incomplete SCI. Cortical neurostimulation achieved high fidelity and markedly proportional online control of leg trajectories in both healthy and SCI rats. Long-term neuroprosthetic training lastingly improved cortical control of locomotion, whereas short training held transient improvements. We performed longitudinal awake cortical motor mapping, unveiling that recovery of cortico-spinal transmission tightly parallels return of locomotor function in rats. These results advocate directly targeting the motor cortex in clinical neuroprosthetic approaches.
