Spinal cord injury (SCI) often disrupts corticospinal drive, resulting in weak voluntary activation of muscles and impaired motor control. Thus, an intervention that further improves corticospinal function could enhance motor recovery. However, such neuromodulatory interventions are not currently available to people with incomplete SCI. For example, other than conventional physical therapy, the most common treatment for foot drop (weak ankle dorsiflexion), which often impairs gait in this population, is an ankle foot orthosis. These standard treatments do not aim to restore corticospinal drive and may even depress it further. Operant conditioning of a stimulus-triggered EMG response, which can target beneficial plasticity to the pathway that produces the response may be able to fill this gap. The overarching hypothesis of this project is that increasing the size of the motor evoked potential (MEP) elicited by transcranial magnetic stimulation through operant conditioning can improve corticospinal activation of the targeted muscle and thereby improve motor function in which that muscle participates. In people with incomplete SCI, the tibialis anterior (TA) MEP is often small, reflecting reduced corticospinal excitability. This weakened corticospinal activation of TA contributes to foot drop, which further impairs their gait through a chain of compensation and maladaptation at knee and hip. Thus, a therapy that increases corticospinal excitability for TA may reduce foot drop and other associated problems, and thereby improve walking. Recent small studies of TA MEP conditioning suggest that MEP up-conditioning can increase the corticospinal excitability for TA and can improve gait in people with chronic SCI. Building upon those initial findings, this project seeks to characterize the physiological mechanisms and effects of TA MEP conditioning. Individuals with weak dorsiflexion due to chronic incomplete SCI are exposed to 42 1-hr MEP sessions (6 baseline followed by 36 up-conditioning or 36 control sessions). Before baseline and after 12, 24, 36 conditioning (or control) sessions, (1) to characterize the cortical and corticospinal mechanisms of the TA MEP changes produced by MEP up-conditioning, cortical MEP map, MEP recruitment curve, short-interval cortical inhibition, cervicomedullary MEP, H-reflex, and F-wave are measured; and (2) to characterize the impact of TA MEP up- conditioning on locomotor function, bilateral locomotor EMG and kinematics measurements, 10-m and 6-min walking tests, and locomotor reflex testing are performed. Determining how MEP conditioning induces cortical and corticospinal plasticity and how such plasticity changes locomotion in people with incomplete SCI will illuminate the dynamic process of inducing and shaping functionally-relevant CNS multi-site plasticity through guiding targeted plasticity. The results will help to navigate development and clinical translation of MEP operant conditioning, as a novel non-invasive therapy that may complement other therapies and further enhance recovery in people with SCI or other disorders.
Developing new neurorehabilitation approaches is critically important for maximizing function recovery and re- establishing an active, productive, fulfilling life in people after SCI. Through this project, we seek to characterize the physiological mechanisms and effects of MEP operant conditioning, and thereby its value as a neuromodulation tool for rehabilitation. Successful completion of this project will accelerate development and clinical translation of MEP operant conditioning, as a novel non-invasive therapy that may complement other therapies and further enhance recovery in people with SCI or other disorders.