Introduction: Supraspinal influence on spinal networks remains incompletely understood yet is crucial for restoring motor function after neurological insults, including spinal cord injury or stroke. Neuromodulation interventions have been employed with varying success to aid recovery and can be utilized to investigate the relationship between supraspinal and spinal networks. Material and methods: We elicited hindlimb muscle responses by motor cortex stimulation paired with either epidural or transcutaneous spinal stimulation in neurologically intact Long-Evans rats and Yucatan miniature pigs. Results: Our findings indicate that modulation of sensorimotor networks using the two stimulation modalities varies with the intensity of spinal stimulation. Specifically, spinal stimulation at near-motor-threshold levels modulates the magnitude of the weak descending volleys, with pronounced increases in compound motor evoked potential magnitude of up to 400–500 %. As spinal stimulation intensity increased, we observed a transition from modulated cortically evoked motor responses toward modulated spinally evoked motor responses. However, when the intensity of spinal stimulation exceeded the supra-motor-threshold, the conditioned responses were abolished. We also examined the effects of timing between paired cortical and spinal stimulation and found that the highest modulation occurred when delivering spinal stimulation using a latency approximately equal to the central conduction time of cortical stimulation. Conclusion: The capacity of cortical stimulation to modulate the effects of spinal modulation can be described as a convergence of supraspinal and spinal networks on the motor pathway. Overall, our results suggest potential stimulation strategies that capitalize on supraspinal-spinal interactions without the need for targeting individual motor pools with focal spinal stimulation.
