Hypoglossal motor output is altered by C4 epidural electrical stimulation via ascending spinal and peripheral feedback pathways

After cervical spinal cord injury (cSCI), swallowing dysfunction is common and increases mortality via aspiration pneumonia. While these deficits have often been attributed to secondary damage from complications of injury management, there has recently been a greater appreciation for the modulatory role of spinal populations in swallow generation that are disrupted by injury. Here, we illustrate in a rodent model of cSCI that epidural spinal stimulation (ESS) of the phrenic motor nucleus at spinal segment C4 alters motor output at the hypoglossal motor nucleus through activation of excitatory ascending spinal pathways and inhibitory peripheral sensory feedback mechanisms. These findings highlight the importance of spinal-brainstem communication in shaping the motor program of swallow-related musculature and offer the potential for stimulation of the cervical spinal cord to be a therapeutic target for restoring swallowing function after injury. NEW & NOTEWORTHYIn two varying severity models of spinal cord injury, we demonstrate the effects of spinal cord stimulation at C4 on the distal hypoglossal motor nucleus. We show that despite being anatomically distant, electrical stimulation of the phrenic motor nucleus increases hypoglossal motor output through ascending spinal pathways and dampens it through peripheral pathways. These findings highlight the importance of spinal-brainstem communication and illustrate the ability of spinal stimulation to restore this communication after injury.