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

Most spinal cord injuries (SCI) spare descending motor pathways and sublesional networks, which can be activated through motor cortex and spinal cord stimulation to mitigate locomotor deficits. However, the potential synergy between cortical and spinal stimulation as a neuroprosthetic intervention remains unknown. Here, we first investigated 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 recovery of skilled locomotion. As a further refinement, 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 rostral 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. HighlightsO_LICortical and spinal stimulations summate motor outputs via distinct pathways. C_LIO_LIEach improves gait post-SCI, but combined stimulation maximizes gait improvement. C_LIO_LIIntegrating cortico-spinal stimulation into rehabilitation promotes lasting recovery. C_LIO_LIEES capabilities extended using high-frequency lumbosacral protocols. C_LI