Response-contingent learning to modulate synaptic plasticity for spinal cord injury

Project Summary/Abstract Over 17,000 new cases of spinal cord injuries (SCIs) are experienced annually in the U.S. due to motor vehicle collisions, sports injuries, and other traumatic events. In addition to the loss of mobility, numerous complications including urinary tract infections, pressure sores, and chronic central neuropathic pain (CNP) significantly impact the quality of life and contribute to morbidity and mortality. However, no effective treatments exist for individuals with SCIs. A mechanism- based approach that based on individual spinal learning to promote motor recovery and re- balance the pain circuitry would be the key to developing personalized SCI treatment. In the New Innovator Award program, our team will develop novel response-contingent neuromodulation devices to electrically modulate neural circuit plasticity. This individualized treatment strategy will be based on establishing a close-loop electrical stimulation paradigm via novel design of neuromodulation to self-train spinal circuitry. Our team will assess if the motor- contingent electrical stimulation can promote motor recovery and pain sensitization and investigate the underlying molecular mechanisms associated with spinal plasticity using the rat SCI model. The proposed work will determine the biology behind adaptive plasticity associated with NP and lay down the foundation to develop a close-loop electrical modulation technology for individualized neurotrauma treatment in the future.