MEP Up-conditioning to Target Corticospinal Plasticity

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.

• Maximum Voluntary Contraction - ECR [Time frame: Reported as an average of the 6 baseline sessions (over weeks 1-2) and average of the last 6 conditioning sessions (over weeks 8-10)]
• Capabilities Upper Extremity Test (CUE-T) [Time frame: Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post]
• Graded and Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) [Time frame: Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post]
• Spinal Cord Independence Measure (SCIM III) [Time frame: Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post]
• Life Situation Questionnaire Revised (LSQ-R) [Time frame: Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post]