Abstract
Almost all sympathetic outflow control pathways travel through the spinal cord for affecting the peripheral tissues.
Cervical spinal cord injury impacts sympathetic outflow control, leading to several debilitating deficits (in addition
to paralysis), including an inability to redistribute blood to active tissues and muscle fatigue. There are currently
no consistently effective treatments for sympathetic outflow control dysfunction following cervical spinal cord
injury. The long-term goal of this research is to address this significant gap using vagus nerve stimulation paired
with rehabilitation to enhance sympathetic outflow control following cervical spinal cord injury. Pairing vagus
nerve stimulation with movements during rehabilitation leads to the rapid release of plasticity enhancing
neuromodulators, leading to the reorganization of motor control systems. The objective of this proposal is to
determine the specific effects of vagus nerve stimulation paired with rehabilitation on sympathetic outflow control
following cSCI, and determine the neural pathways contributing to these effects. We will also assess the optimal
delivery regime for vagus nerve stimulation (with or without rehabilitation). Our central hypothesis is that vagus
nerve stimulation precisely paired with movements during rehabilitation enhances the plasticity of spared
sympathetic outflow control circuits, leading to improved motor endurance and muscle fatigue resistance
following cSCI. We will assess this hypothesis via three specific aims: 1) determine the effects of vagus nerve
stimulation paired with rehabilitation on forelimb muscle and cardiovascular function; and measure changes in
2) cortical and 3) subcortical plasticity related to sympathetic outflow control. We will pursue these aims using
multidisciplinary assessments, leveraging electrophysiological and neuroanatomical techniques. The proposed
research is significant, as it will determine if vagus nerve stimulation paired with rehabilitation is a viable therapy
for treating sympathetic control dysfunction following cervical spinal cord injury. Furthermore, these results will
elucidate the critical relationships between forelimb function, sympathetic outflow control, vagus nerve
stimulation therapy, and neuroplasticity.
