Dual motor cortex and spinal cord neuromodulation improves rehabilitation efficacy and restores skilled locomotor function in a rat cervical contusion injury model.

Motor recovery after spinal cord injury is limited due to sparse descending pathway axons caudal to the injury. Rehabilitation is the primary treatment for paralysis in humans with SCI, but only produces modest functional recovery. Here, we determined if dual epidural motor cortex (M1) intermittent theta burst stimulation (iTBS) and cathodal transcutaneous spinal direct stimulation (tsDCS) enhances the efficacy of rehabilitation in improving motor function after cervical SCI. iTBS produces CST axon sprouting and tsDCS enhances M1-evoked spinal activity and muscle contractions after SCI. Rats were trained to perform the horizontal ladder task. Animals received a moderate midline C4 contusion, producing bilateral forelimb impairments. After 2 weeks, animals either received 10 days of iTBS+tsDCS or no stimulation; subsequently, all animals received 6 weeks of daily rehabilitation on the horizontal ladder task. Lesion size was not different in the two animal groups. Rehabilitation alone improved performance by a 22% reduction in skilled locomotion error rate, whereas stimulation+rehabilitation was markedly more effective (52%), and restored error rate to pre-injury levels. Stimulation+rehabilitation significantly increased CST axon length caudal to the injury and the amount of ventral horn label was positively correlated with functional improvement. The stimulation+rehabilitation group had significantly less proprioceptive afferent terminal labelling in the intermediate zone and fewer synapses on motoneurons . Afferent fiber terminal labeling was negatively correlated with motor recovery. Thus, the dual neuromodulation protocol promotes adaptive plasticity in corticospinal and proprioceptive afferents networks after contusion SCI, leading to enhanced rehabilitation efficacy and recovery of skilled locomotion.