Can MEP conditioning improve corticospinal recruitment of motoneurons in chronic cervical SCI?

The Medical University of South Carolina (MUSC) received a $427,814 Project Grant from the National Institute of Child Health and Human Development (NICHD) under the Child Health and Human Development Extramural Research program (CFDA 93.865) to conduct research examining whether operant conditioning of motor evoked potentials (MEP) to transcranial magnetic stimulation (TMS) can improve corticospinal pathway recruitment in individuals with chronic cervical spinal cord injury (SCI). The two-year project, awarded August 1, 2025, and concluding July 31, 2027, investigates whether MEP operant conditioning—an intervention that targets the corticospinal pathway through up-conditioning to enhance neural plasticity—can increase muscle activation and motor function recovery, particularly for upper limb and wrist function in individuals with tetraplegia who have plateaued under conventional rehabilitation approaches.

The research deliverables include scientific investigation into corticospinal excitability mechanisms and motor recruitment strategies, with specific focus on high-density surface electromyography (HDsEMG) experiments designed to assess motor unit recruitment patterns and decomposition analyses. Northwestern University serves as a sub-awardee site, with Dr. Christopher Heckman and his laboratory providing expertise in motoneuron physiology and motor unit analysis. The sub-award activity includes collaborative protocol development, on-site HDsEMG data collection and analysis, motor unit decomposition studies, and scientific dissemination through presentations and peer-reviewed publications intended to advance rehabilitation interventions targeting motor recovery in spinal cord injury populations.

Abstract

After spinal cord injury (SCI), the excitability and connectivity of cerebral cortex - spinal cord (corticospinal) pathway diminish, often resulting in weak voluntary activation of muscles and impaired motor control. Yet, such corticospinal impairments are reversible at least partially, and an intervention that improves corticospinal excitability for the affected muscles may enhance motor function recovery. At present, no interventions that target corticospinal pathways for treating motor dysfunction are readily available to people with SCI. Operant conditioning of the motor evoked potential (MEP) to transcranial magnetic stimulation (TMS) to induce targeted plasticity in the corticospinal pathway may become one of those interventions. Indeed, in lower limb, people with SCI can increase corticospinal excitability through operant up-conditioning and can improve walking. Supported by those findings, our core hypothesis is that MEP operant conditioning can increase the corticospinal excitability for the targeted muscle and improve its activation and motor functions in which IT participates. Regaining arm/hand function is one of the top priorities of individuals with tetraplegia and often most challenging. Through mass practice and conventional therapy, functions can be restored partially, but IT is likely through compensation rather than induction of relevant corticospinal plasticity. In such cases, corticospinal recruitment of motoneurons and resulting muscle activation could remain impaired and continue to limit function recovery. Abnormal motoneuron recruitment and motor unit firing hinder effective production of motor functions. Thus, to enhance upper limb motor rehabilitation beyond what conventional therapy has achieved, a method to improve corticospinal recruitment of a targeted pool of motoneurons would be needed. Here, we hypothesize that wrist extensor MEP up-conditioning can improve forearm motor functions in people with cervical SCI by increasing the corticospinal excitability and improving corticospinal recruitment of wrist extensor motoneurons. Towards testing this hypothesis, this R21 project aims: (1) to demonstrate that the wrist extensor MEP becomes larger through operant up-conditioning in people with chronic incomplete cervical SCI, extensor carpi radialis (ECR) MEP is up-conditioned in individuals with weak wrist extension due to chronic cervical incomplete SCI; (2) to obtain preliminary data for the functional effects of MEP up-conditioning in people with chronic incomplete cervical SCI, multiple functional tests will be performed before and after conditioning intervention; and (3) to examine whether corticospinal recruitment of wrist extensor motoneurons changes with MEP up-conditioning, motor unit firing is studied using high-density surface EMG (hdsemg) before and after conditioning intervention. This R21 is the first step in understanding how MEP conditioning may improve upper limb functions and corticospinal recruitment of motor units in cervical SCI. Since upper limb functions have tremendous impact on the health, independence, and quality of life in people with tetraplegia, improving them is of critical importance.