Neuromodulation through Spinal Cord Stimulation for Functional Restoration and Rehabilitation after Cervical Spinal Cord Injury

Thesis (Ph.D.)--University of Washington, 2020Spinal cord injury (SCI) results in permanent neurological deficits. The limited physical function impacts quality of life and socioeconomic engagement. Up to now, we have no effective interventions to restore impaired function. Activity-dependent plasticity holds great promise to promote recovery of motor and autonomic function. Neuromodulation via electrical stimulation of the spinal cord has shown growing evidence of promoting activity-dependent plasticity and functional gains following SCI. First, we review the background information about the burden and recovery process of SCI. We also summarize current advances of pharmacological, cellular, and neuromodulation approaches. Emerging evidence with stimulation technologies demonstrates potential to facilitate neuroplasticity bridging the lesion. In the second part, we demonstrated a cost- and time-efficient experimental tool to assess forelimb function in a rodent model with severe cervical SCI. This novel strategy for the behavior task may accelerate preclinical trials. By using the behavior tasks, in the third part, we present a clinically viable brain-computer spinal interface to reanimate paralyzed forelimb function in rodents with cervical SCI. We demonstrate a stable and computationally efficient local field potential decoder enabling graded forelimb movements via epidural stimulation. Consequently, the brain-controlled epidural stimulation led to functional improvements in freely moving rats with cervical SCI. The closed-loop algorithm was implemented in an implantable size circuit capable of onboard computing, providing a clinically viable strategy to accelerate the translation of brain-computer interfaces to human use. In the fourth part, we investigate the efficacy of transcutaneous spinal stimulation paired with intensive locomotor training in two individuals with cervical SCI. We present the additive effect of transcutaneous spinal stimulation for locomotor recovery with more coordinated movements. Furthermore, we demonstrate the first evidence of transcutaneous spinal stimulation for restoring bowel function. Lastly, we discuss the potential of these neurotechnology approaches. We address the current limitations of scientific understanding and technology to guide future research to restore sensorimotor and autonomic function following cervical SCI