MEP Up-conditioning to Target Corticospinal Plasticity (uMEP2)

Operant Conditioning of the Wrist Extensor Motor Evoked Potential to Target Corticospinal Plasticity and Upper Limb Motor Recovery After Cervical Spinal Cord Injury

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.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injury; Tetraplegia/Tetraparesis
• Intervention / Treatment: Behavioral: Up-conditioning of the wrist extensor motor evoked potential

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 11
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Recruitment Contact; Phone Number: 843-792-6313; Email: stecb@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Allison Lewis, DPT, PhD; Phone Number: 843-792-6313; Email: lewisaf@musc.edu
      • Principal Investigator: Allison Lewis, DPT, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Operant Up-Conditioning of the Motor Evoked Potential; The intervention consists of approximately 6 baseline sessions and 24 conditioning sessions at a pace of 3 sessions/week, 1-2 hour duration, over 10 weeks. At the beginning of each session, electromyographic (EMG) recording and nerve stimulating electrodes are placed over the arm. In all sessions, motor evoked potentials (MEPs) will be measured while the sitting subject provides a pre-set level of background muscle EMG with joint angles fixed. In 225 control trials of each baseline sessions and the first 20 trials of conditioning sessions the subject will receive no feedback as to MEP size (i.e., control MEPs). In 225 conditioning trials of each conditioning session, the subject will be encouraged to increase the target muscle MEP, and will receive immediate feedback as to whether MEP size was above a criterion (i.e., whether the trial was a success).

Behavioral: Up-conditioning of the wrist extensor motor evoked potential; At the beginning of each session, EMG recording and nerve stimulating electrodes are placed over the arm. In all sessions, MEPs will be measured while the sitting subject provides a pre-set level of background muscle EMG with joint angles fixed. In 225 control trials of each baseline sessions and the first 20 trials of conditioning sessions the subject will receive no feedback as to MEP size (i.e., control MEPs). In 225 conditioning trials of each conditioning session, the subject will be encouraged to increase the target muscle MEP, and will receive immediate feedback as to whether MEP size was above a criterion (i.e., whether the trial was a success).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extensor Carpi Radialis (ECR) Motor Evoked Potential (MEP) amplitude	Size of MEP elicited at the fixed stimulus intensity (e.g., ~ 10-15% maximum stimulator output) of transcranial magnetic stimulation (TMS) above motor threshold) (in %M wave maximum amplitude)	Reported as an average of the 6 baseline sessions (over weeks 1-2) and average of the last 6 conditioning sessions (over weeks 8-10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Voluntary Contraction - ECR	Maximum voluntary contraction measured by electromyography (EMG) (in mV); average of two trials	Reported as an average of the 6 baseline sessions (over weeks 1-2) and average of the last 6 conditioning sessions (over weeks 8-10)
Capabilities Upper Extremity Test (CUE-T)	The CUE-T is an objective clinical measure of a person with tetraplegia's ability to complete actions with the arm and hand. This scale measures motor function. It consists of 19 tasks (17 unilateral, 2 bilateral). Scoring is based completion of the action, number of repetitions, or time to complete depending on the item and converted from raw score to 5-point scale (0-4, 4 is best).	Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post
Graded and Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP)	The GRASSP is a clinical impairment measure to assess sensorimotor hand function in people with cervical SCI. The GRASSP tests 3 domains of hand function including strength, sensibility, and prehension. The GRASSP contains 6 tasks for each side scored from 0-5 for a possible score of 0-30 per side or 0-60 total, where higher scores are better.	Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post
Spinal Cord Independence Measure (SCIM III)	The SCIM is a self-report survey of daily activity independence in self-care, respiration and sphincter management, and mobility. The scores range from 0-100, where higher scores represent greater independence.	Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post
Life Situation Questionnaire Revised (LSQ-R)	The LSQ-R is a self-report survey of quality of life that contains 20 life satisfaction items and 30 life problems items. All items are evaluated using a 5-point scale. For the satisfaction items, a score of 1 indicates "very dissatisfied," while a score of 5 denotes "very satisfied." For the problems items, a score of 1 represents "no problem," and a score of 5 signifies a "major problem."	Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ECR MEP recruitment curve	Maximum MEP size (in mV and %maximum M-wave (Mmax)) and active MEP threshold (in %maximum stimulator output (MSO)	Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post
Silent Period Duration	Silent period duration measured as the time from the start of the MEP to the recovery of EMG activity to the prestimulus level (ms)	Reported as an average of the 6 baseline sessions (over weeks 1-2) and average of the last 6 conditioning sessions (over weeks 8-10)
Spine imaging - lesion overlap with lateral corticospinal tract (LCST) or motor tract damage	Percent by volume of overlap between lesion and the LCST	Baseline
Spine imaging - Lesion volume	Volume of the lesion from the lesion segmentation in cubic millimeters	Baseline
Brain imaging - Diffusion Kurtosis Imaging (DKI) - Kurtosis Fractional Anisotropy	Kurtosis fractional anisotropy (KFA) is a ratio value that reflects the directional variation of non-Gaussian water diffusion, reflecting tissue complexity.	Baseline
Brain Imaging - Diffusion Kurtosis Imaging - Axial Kurtosis	Axial kurtosis (AK) is the kurtosis along the axial direction of the diffusion ellipsoid; closer to 0 in white matter, because it represents less diffusion restriction.	Baseline
Brain imaging - Resting state connectivity of sensorimotor network	Connectivity between pairs of brain regions as Fisher's z transformed correlation coefficients. Brain regions in the sensorimotor network include primary motor cortex (M1), somatosensory cortex (S1), ventral premotor (PMv), dorsal premotor (PMd), supplementary motor area (SMA), and pre-supplementary motor area (preSMA).	Baseline
Brain Imaging - Diffusion Tensor - Fractional Anisotropy	Corticospinal tract fractional anisotropy (FA) measures general microstructural integrity. FA is a ratio value where values closer to 1 suggest greater anisotropy of water diffusion, suggesting a tendency for water to diffuse in a single direction and greater structural integrity.	Baseline

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Doscher Neurorehabilitation Research Program
• Investigators: Principal Investigator: Allison Lewis, DPT, PhD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: May 8, 2025
• First Submitted That Met QC Criteria: May 19, 2025
• First Posted (Actual): May 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: upper limb; Central Nervous System; spinal cord injury; quadriplegia; Nervous System; upper extremity; tetraplegia; Spinal Cord; motor impairment; Rehabilitation Studies
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Paralysis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurologic Manifestations; Spinal Cord Injuries; Quadriplegia
• Other Study ID Numbers: Pro00138869; 1K99HD117041 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be shared with the OpenNEURO repository (MRI data) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Data and Specimen Hub (DASH) (clinical assessments and EMG data).

IPD Sharing Access Criteria

Data on NICHD DASH is available via controlled access. The requester must provide details about the study, funding source, principal investigator, and the names and email addresses of the authorized representative or Institutional Business Official, as well as any affiliated personnel. Additionally, the submission must include the NICHD DASH Data Use Agreement and, if required by the requested study, IRB Approval for Data Request. The requesting institution must also maintain active Federalwide Assurance (FWA) status

MRI data in OpenNEURO is open to the public. Participants can opt in or out of sharing MRI data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No