Operant conditioning of the wrist extensor motor evoked potential to target corticospinal plasticity and upper limb motor recovery after cervical spinal cord injury

/ABSTRACT Corticospinal function is essential in generating and controlling voluntary movements. Cervical spinal cord injury (SCI) disrupts corticospinal connections, therefore, often results in weak voluntary activation of muscles and impaired motor control in the upper limb (UL). An intervention that improves corticospinal function could enhance motor function recovery; however, such interventions are not currently readily available to people with incomplete SCI. Operant up-conditioning of a motor evoked potential [MEP] to transcranial magnetic stimulation (non- invasive brain stimulation) that can increase corticospinal excitability for the targeted muscle may be able to fill this gap. The overarching hypothesis is that targeting beneficial plasticity to the corticospinal pathway can change the brain and spinal cord and improve upper limb motor function in people with chronic cervical SCI. As initial steps towards testing this, the proposed project aims to apply MEP operant up-conditioning in the wrist extensor of the affected UL, improve corticospinal activation of the wrist extensor, and thereby improve motor functions in which the wrist is involved in individuals with cervical SCI. Recent studies suggest that MEP up- conditioning is feasible and can increase MEP size that reflects corticospinal excitability. Building on those studies, this project will examine the effects of wrist extensor MEP operant up-conditioning in people with chronic cervical SCI. Individuals with weak wrist extension due to incomplete cervical SCI will undergo a standard MEP up-conditioning protocol (6 baseline and 24 up-conditioning sessions over 10 weeks). Before and after the intervention period, neurophysiological measurements, clinical and functional assessments, neuroimaging of the spinal cord and brain will be performed. The results will facilitate development and clinical translation of MEP operant conditioning as a novel non-invasive therapy that may complement other therapies and further enhance motor function recovery in people with SCI or other disorders, which aligns with the mission of NICHD to optimize the abilities of individuals with neurological disorders. The proposed project serves as a career development and research training opportunity for the applicant. Over the course of proposed two years, the applicant will acquire unique research skills that are essential in the applicant’s future SCI research as an independent principal investigator; those include, but not limited to, MEP operant conditioning (which is available only at the Medical University of South Carolina [MUSC] EPOC lab), neurophysiological assessment, spinal imaging, and advanced brain imaging. The applicant will also receive career development education/training, such as clinical trial design/implementation, grant writing, and DEI and leadership skills. In combination with frequent virtual meetings with non-MUSC mentorship team members, most of in-person training will occur at MUSC. Neuroimaging, neuromodulation, and rehabilitation research programs have been rapidly growing at MUSC, providing an ideal training environment for the applicant to start developing own independent career as a successful academic researcher in neurorehabilitation. Project Number: 1K99HD117041-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Allison Lewis | Institution: MEDICAL UNIVERSITY OF SOUTH CAROLINA, CHARLESTON, SC | Award Amount: $115,881 | Activity Code: K99 | Study Section: Special Emphasis Panel[ZHD1 DSR-C (02)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1K99HD11704101