Combining cortical and spinal stimulation maximizes the improvement of gait after spinal cord injury

Most spinal cord injuries (SCI) spare descending and sublesional circuits that can be targeted through motor cortex and spinal cord stimulation to mitigate locomotor deficits. However, the potential synergy between cortical and spinal stimulation remains unknown. Here, we first investigated the phase-locked electrical stimulation of the motor cortex and lumbar spinal cord at 40 Hz in a rat model of unilateral SCI. Combining cortical and lumbar stimulation around the anticipated lift synergistically enhanced leg movements. When integrated into rehabilitation training, cortical stimulation proved essential for the recovery of skilled locomotion. We next investigated the effects of high-frequency (330 Hz) lumbar and sacral stimulation combined with cortical stimulation. Timely integration during the swing phase showed that cortical and lumbar stimulations enhance the initial and mid-swing phases, while sacral stimulation improves extension velocity in the late swing. These findings indicate that supraspinal and sublesional neuromodulation offer complementary neuroprosthetic effects in targeted SCI gait rehabilitation.