Project Summary / Abstract
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.
