mep up-conditioning to target corticospinal plasticity

Conditions: Spinal Cord Injury; Tetraplegia/Tetraparesis

Summary: individuals with chronic cervical spinal cord injury will complete a 10-week training protocol where participants receive non-invasive brain stimulation and feedback on the size of the corresponding muscle response (wrist extensor). investigators will assess the impact of the brain stimulation training on 1) the brain-to-spinal cord-to-muscle connection and 2) motor functions of the arm and hand. also, brain and spine magnetic resonance imaging will be collected before and after the training. the imaging measurements will tell investigators about how spinal damage, brain function, and brain structure relate to motor presentation and the response to the training.

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.

Eligibility criteria:
inclusion criteria: * adult (≥18 yrs old) * a history of injury to spinal cord at or above c6 * \>6 months post sci * weak wrist extension at least unilaterally * expectation that current medication will be maintained without change for at least 3 months. stable use of anti-spasticity medication (e.g., baclofen, diazepam, tizanidine) is accepted. exclusion criteria: * motoneuron injury * medically unstable condition * cognitive impairment * a history of epileptic seizures * metal implants in the cranium * implanted biomedical device in or above the chest (e.g., a cardiac pacemaker, cochlear implant) * extensive use of functional electrical stimulation to the arm on a daily basis * pregnancy (due to changes in posture and potential medical instability) * contraindications to mri * no measurable mep elicited in the ecr * unable to produce any voluntary ecr emg activity

Keywords: central nervous system nervous system rehabilitation studies spinal cord spinal cord injury upper extremity upper limb motor impairment tetraplegia quadriplegia