<h3>Research Objectives</h3> The corticospinal pathway and its plasticity are essential in sensorimotor function recovery after neuromuscular injuries. To determine if operant up-conditioning of the motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) can increase corticospinal excitability and enhance sensorimotor rehabilitation, we are testing this neuromodulation approach in three different ongoing subprojects. We hypothesized that MEP up-conditioning can improve corticospinal activation of the targeted muscle and thereby improve functions in which that muscle participates. <h3>Design</h3> Each subproject utilizes operant MEP up-conditioning methodology. Standard MEP conditioning protocol consists of 6 baseline and 24 conditioning sessions (3/week, 30-45 min each). In each session, 250 single-pulse MEPs are elicited using TMS with or without operant conditioning (i.e., feedback on performance). Before and after conditioning, electrophysiological, kinematic, and functional assessments are performed. <h3>Setting</h3> Controlled laboratory. <h3>Participants</h3> Volunteers with chronic incomplete spinal cord injury (SCI), or with early-stage knee osteoarthritis (OA). <h3>Interventions</h3> See Design. <h3>Main Outcome Measures</h3> Target muscle MEP size, EMG, kinematics. <h3>Results</h3> Dorsiflexor MEP conditioning in people with chronic incomplete SCI: We hypothesize up-conditioning of the tibialis anterior (TA) MEP induces CNS plasticity that affects TA activation and improves locomotion. Initial studies found up-conditioning can increase TA MEP size and improve locomotion. Our current work aims to characterize cortical and corticospinal mechanisms of changes in MEP, locomotor EMG, and kinematics. Forearm extensor MEP conditioning in people with SCI: We hypothesize that corticospinal excitability for the wrist extensors can be increased through MEP conditioning and that it will help improve forearm motor function. Initial results support such possibilities in individuals with chronic incomplete cervical SCI. Quadriceps MEP conditioning in people with knee OA: We hypothesize that up-conditioning can increase quadriceps MEP size and improve quadriceps activation in individuals with early-stage knee OA. We are developing a protocol to examine the effects of MEP up-conditioning on quadriceps activation and function. <h3>Conclusions</h3> These projects will facilitate the dissemination of MEP conditioning as a neurorehabilitation tool to enhance functional recovery after neuromuscular injuries. <h3>Author(s) Disclosures</h3> Authors listed have no conflicts of interest to declare.