UCLA

Upper motor neuron injury damages the descending circuits connecting the brain to sensory and motor neurons responsible for sensing and interacting with the world. While spinal cord stimulation is showing extraordinary promise as a novel therapeutic to restore lost motor function following spinal cord injury, we have yet to fully characterize the mechanisms of its action or identify the limits of its therapeutic potential. Towards these ends I conducted a series of three studies which utilized spinal stimulation in novel subject populations to map the cervical spinal cord, identify and modulate aberrant spinal physiology, and enhance upper limb function. In the first study a group of SCI subjects with motor complete lesions, half of which had no measurable hand strength, received transcutaneous stimulation to the cervical spinal cord alone and in combination with the partial serotonergic agonist buspirone. Stimulation but not buspirone significantly improved hand function in subjects with measurable strength prior to the study and maintained hand strength for up to five months following treatment in more functional subjects. In the second study, two subjects who demonstrated improvement with transcutaneous stimulation but failed to maintain it 5 months after treatment, received epidural stimulators. The different properties and performance outcomes of the two forms of stimulation were compared in these severely impaired subjects. Finally in a cohort of rats, epidural stimulation was used to map the cervical spinal cord, track physiological changes in the spinal cord following a severe stroke injury to the motor cortex, and treat observed deficits in reaching success and muscle activity. While 20 Hz stimulation enhanced afferent derived spinal activity, only 1 Hz stimulation resulted in improved reaching success and muscle activity. Together these studies further our understanding, by identifying patient pools most receptive to spinal cord stimulation, characterizing the different properties and functional outcomes of transcutaneous versus epidural stimulation, and illustrating the potential to utilize spinal cord stimulation for other forms of upper motor neuron injury.