Motoneuron Recruitment and Motor Evoked Potential Up-Conditioning (MEP) in Spinal Cord Injury (SCI)

Official title

Can MEP Conditioning Improve Corticospinal Recruitment of Motoneurons in Chronic Cervical SCI?

Overview

The purpose of this research study is to examine the effect of a brain stimulation training to improve the function of brain-spinal cord- muscle connections. Because brain-to-muscle pathways are very important in our movement control, restoring function of these pathways may improve movement problems after injuries. Spinal cord injury causes damage to the brain-to-muscle connection. However, when the injury is "incomplete", there is a possibility that some of the brain-to-muscle pathways are still connected and may be trained to improve movement function. For examining brain-to-muscle pathways, investigators use a transcranial magnetic stimulator. Investigators hope that the results of this research study will help us develop new treatments for people who have movement disabilities. This study will require about 42 visits over the first 14 weeks, and another 6 visits over an additional 3 months. Each visit will take about 1 ½ hours.

Detailed description

Regaining arm/hand function is one of the top priorities of individuals with tetraplegia and is a challenging problem, partly due to the complex nature of upper limb motor function. Through mass practice and conventional therapy, functions can be restored partially, 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. In people with incomplete SCI, voluntary activation of the muscles below the injury level is often diminished, due at least partly to impaired motor unit behaviors. Abnormal motoneuron recruitment and motor unit firing, also found in other CNS disorders, would certainly hinder effective production of motor functions. Thus, to enhance upper limb motor rehabilitation beyond what conventional therapy has been able to achieve, a method to improve corticospinal recruitment of a targeted pool of motoneurons would be needed. Here, investigators 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.

Interventions

• Behavioral Motor Evoked Potential (MEP) Operant Conditioning
  Operant conditioning is a method to induce behavioral learning based on the consequence (reward) of the behavior. With operant conditioning of the motor evoked potential (MEP), the neuronal excitability and behavior of the corticospinal pathway that involves production of MEP is targeted and trained (i.e., up-trained with up-conditioning). The individual is rewarded only for changing the target muscle's MEP size without changing background muscle activity. Since MEP size reflects the corticospin

Primary outcome measures

• Percent change in the size of the Motor Evoked Potential (MEP) from baseline to final conditioning sessions. [Time frame: Baseline (average of 6 sessions over 2 weeks) and final phase (average of sessions 19-24 over weeks 7-8 of intervention)]
• Change in Spinal Cord Independence Measure--version III (SCIM III) score [Time frame: Baseline (Week 0), mid-intervention (Week 5, after session 12), post-intervention (Week 9, after session 24), and follow-up at 1 month (Week 13) and 3 months (Week 21) post-intervention.]

Eligibility criteria

Inclusion criteria

• Adult (≥18 yrs old)
• a history of injury to spinal cord at or above C6
• neurologically stable (>1 year post SCI)
• medical clearance to participate
• 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. (Because only neurologically stable subjects will enter this study, medication changes will be unlikely.)
• In participants with bilateral wrist extension weakness in whom Extensor Carpi Radialis (ECR) MEP can be elicited in both arms, the more severely impaired arm is studied. In participants with unilateral wrist weakness or in participants with bilateral wrist weakness in whom an ECR MEP can be elicited in only one arm, that arm is studied.

Exclusion criteria

• motoneuron injury
• unstable medical condition
• cognitive impairment (because the studied intervention is a learning-based intervention)
• a history of epileptic seizures
• a pre-existing or confounding neurological condition (e.g., history of MS, Stroke, Parkinson's disease)
• metal implants in the cranium
• implanted biomedical device in or above the chest (e.g., a cardiac pacemaker, cochlear implant)
• no measurable MEP elicited in the ECR
• inability to produce any voluntary ECR EMG activity
• extensive use of functional electrical stimulation to the arm on a daily basis (as it may interfere with or augment the effects of MEP conditioning itself)
• pregnancy (due to changes in posture and potential medical instability)
• inability or unwillingness of subject or legal guardian/representative to give informed consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• Medical University of South Carolina — Charleston

Identifiers

NCT: NCT07179822 · Pro00145581 · 1R21HD118383

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗