MedPath

MEP Up-conditioning to Target Corticospinal Plasticity

Early Phase 1
Not yet recruiting
Conditions
Spinal Cord Injury
Tetraplegia/Tetraparesis
Registration Number
NCT06989905
Lead Sponsor
Medical University of South Carolina
Brief Summary

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.

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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
11
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Extensor Carpi Radialis (ECR) Motor Evoked Potential (MEP) amplitudeReported as an average of the 6 baseline sessions (over weeks 1-2) and average of the last 6 conditioning sessions (over weeks 8-10)

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)

Secondary Outcome Measures
NameTimeMethod
Maximum Voluntary Contraction - ECRReported as an average of the 6 baseline sessions (over weeks 1-2) and average of the last 6 conditioning sessions (over weeks 8-10)

Maximum voluntary contraction measured by electromyography (EMG) (in mV); average of two trials

Capabilities Upper Extremity Test (CUE-T)Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post

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).

Graded and Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP)Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post

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.

Spinal Cord Independence Measure (SCIM III)Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post

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.

Life Situation Questionnaire Revised (LSQ-R)Baseline, after the 24th conditioning session (typically within 1 week), 1 month and 3 months post

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."

Trial Locations

Locations (1)

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

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