Brain-Spinal Cord-Muscle Response Training for Spinal Cord Injury

Overseen By Blair Dellenbach, MSOT

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Disqualifiers: Motoneuron injury, Cardiac condition, Cognitive impairment, Epileptic seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Operant Conditioning, specifically Operant Conditioning of Motor-Evoked Potential (MEP Conditioning), can improve movement control for individuals with spinal cord injuries by strengthening the brain's connection to muscles. Participants will engage in activities such as standing, sitting, and walking while researchers monitor muscle activity and brain signals. The goal is to better understand and potentially enhance recovery after such injuries. Ideal candidates have lived with a stable spinal cord injury for over a year and can walk at least 10 meters, even with assistance. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could improve rehabilitation techniques for spinal cord injuries.

Will I have to stop taking my current medications?

The trial expects that you will continue your current medications without change for at least 3 months. Stable use of anti-spasticity medication is also accepted.

What prior data suggests that this brain-spinal cord-muscle response training is safe?

Research has shown that the method used in this study, operant conditioning, is generally safe for people. Studies have found that this training technique improves connections between the brain, spinal cord, and muscles. Participants in past studies have handled the process well, with very few reports of discomfort. The main activity involves placing small sensors on the skin over leg muscles to monitor muscle activity. This is non-invasive and usually causes little or no discomfort.

The stimulation used in operant conditioning, transcranial magnetic stimulation, is applied to the head. It indirectly stimulates brain cells and is reported to be painless for most people. Overall, research suggests that operant conditioning is a well-tolerated treatment option with minimal risk. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about operant conditioning for spinal cord injury because it offers a novel approach to rehabilitation by harnessing the brain's natural ability to adapt. Unlike standard treatments that often focus on physical therapy and medication to manage symptoms, operant conditioning targets the neural pathways directly. This method aims to retrain the brain-spinal cord-muscle connections, potentially leading to improved motor function and greater independence for patients. By focusing on neuroplasticity, this approach could offer a more direct and potentially effective way to restore movement and function.

What evidence suggests that this brain-spinal cord-muscle response training is effective for spinal cord injury?

Research shows that a type of brain training called operant conditioning can help people with spinal cord injuries move better. Studies have found that this training boosts activity in certain leg muscles and improves ankle movement while walking. For instance, people with long-term spinal cord injuries showed better muscle activity and walking ability after this training. In this trial, participants in the Up-conditioning (UC) Group will receive operant conditioning to strengthen the connections between the brain and muscles, leading to better movement control. These improvements suggest that operant conditioning could aid in regaining movement after spinal cord injuries. ^{1 2 4 6 7}

Who Is on the Research Team?

Aiko K Thompson, PhD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for individuals with spinal cord injury who can move at least 10 meters with or without help, have weak ankle movement, and are stable on their current medications. They should be over a year post-injury and neurologically stable. People with severe heart conditions, cognitive impairments, seizures, metal head implants, no muscle response in tests, daily leg stimulation therapy or pregnancy cannot participate.

Inclusion Criteria

I have weakness in lifting my foot or toes upward on at least one side.

My spinal cord injury has been stable for over a year.

I expect my current medication to stay the same for the next 3 months.

Exclusion Criteria

I have a motor neuron injury.

You have a medical device implanted in your chest or above it, such as a pacemaker or cochlear implant.

I have a condition that makes my health unstable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Training

Participants undergo brain-spinal cord-muscle response training to strengthen brain-to-muscle connections

4 months

3 sessions per week

Extended Training

Continued training sessions to further enhance brain-to-muscle connections

3 months

2-3 sessions per week

Follow-up

Participants are monitored for changes in reflexes, muscle activation, and walking ability

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Operant Conditioning

Trial Overview The study examines how brain-spinal cord-muscle response training can improve control of movements after a spinal cord injury. Participants will undergo sessions involving standing, sitting and walking while being monitored through electrodes on the legs and non-painful transcranial magnetic stimulation over the head.

How Is the Trial Designed?

Group I: Up-conditioning (UC) Group Experimental Treatment 1 Intervention

Group II: Control (NC) Group Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Operant-conditioning protocols that reward specific electromyographic responses can effectively modify spinal reflex pathways, leading to changes in reflex activity and associated behaviors in both animals and humans.

In individuals with partial spinal cord injuries, these conditioning techniques can enhance locomotion and promote widespread beneficial plasticity in the nervous system, suggesting a promising therapeutic approach for rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted neuroplasticity for rehabilitation. Thompson, AK., Wolpaw, JR.[2018]

In a study involving 17 chronic spinal cord-injured patients, operant conditioning successfully reduced hyperactive biceps brachii spinal stretch reflexes (SSRs) over 24 training sessions, demonstrating a significant decrease in SSRs (P < 0.001) compared to control subjects.

The reduction in SSRs persisted for up to 4 months after training ended, indicating that operant conditioning can be an effective long-term intervention for managing altered reflexes in spinal cord injury patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operant conditioning of spinal stretch reflexes in patients with spinal cord injuries. Segal, RL., Wolf, SL.[2022]

In individuals with chronic incomplete spinal cord injury (SCI), operant conditioning to increase motor-evoked potentials (MEP) significantly improved ankle dorsiflexion and walking speed during locomotion, indicating enhanced motor function recovery.

In contrast, the same conditioning had no effect on locomotion in healthy individuals, suggesting that MEP up-conditioning specifically benefits those with impaired motor function due to SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operant conditioning of the motor-evoked potential and locomotion in people with and without chronic incomplete spinal cord injury. Thompson, AK., Fiorenza, G., Smyth, L., et al.[2020]

The spinal cord exhibits activity-dependent plasticity throughout life, which is crucial for motor skill acquisition and recovery after spinal cord injuries, as shown by adaptations from treadmill training in both animals and humans.

Operant conditioning and athletic training can induce significant changes in spinal reflexes and motoneuron activity, highlighting the potential for targeted therapies to enhance recovery and function after spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity-dependent spinal cord plasticity in health and disease. Wolpaw, JR., Tennissen, AM.[2019]

Operant conditioning of tibialis anterior motor-evoked potentials (MEPs) over 10 weeks showed significant improvements in corticospinal excitability, with increases in MEP size by 32-75% and maximum voluntary contraction (MVC) by 28-52% in 3 out of 4 participants with chronic stable multiple sclerosis (MS).

The conditioning also led to improved locomotor function, as evidenced by better EMG modulation in leg muscles and reduced severity of foot drop, suggesting that this approach could be a promising therapy for enhancing mobility in individuals with MS and other central nervous system disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operant Up-Conditioning of the Tibialis Anterior Motor-Evoked Potential in Multiple Sclerosis: Feasibility Case Studies. Thompson, AK., Favale, BM., Velez, J., et al.[2018]

Operant conditioning of the tibialis anterior (TA) motor evoked potential (MEP) significantly enhanced corticospinal excitability in both individuals with chronic incomplete spinal cord injury (SCI) and those without, with MEP size increasing to about 150% of baseline after 24 sessions.

The study demonstrated that this conditioning not only increased MEP size but also reduced the silent period duration by approximately 20%, indicating a facilitation of corticospinal excitation and a suppression of inhibitory mechanisms, which could aid in motor function recovery after CNS injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operant conditioning of the tibialis anterior motor evoked potential in people with and without chronic incomplete spinal cord injury. Thompson, AK., Cote, RH., Sniffen, JM., et al.[2020]

Transcranial magnetic stimulation of the motor cortex can effectively detect preserved innervation in patients with long-standing spinal cord injury (SCI), revealing different H-reflex profiles based on the severity of their impairment.

Higher functioning SCI patients (ASIA levels C and D) showed both early and late excitatory inputs to their motoneuron pools, while those with more severe impairments (ASIA levels A and B) often did not, indicating that this method can identify latent corticospinal connections that other tests may miss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditioning lower limb H-reflexes by transcranial magnetic stimulation of motor cortex reveals preserved innervation in SCI patients. Wolfe, DL., Hayes, KC., Potter, PJ., et al.[2019]

In a study involving 26 patients with severe spinal cord injuries and 12 control subjects, transcranial magnetic stimulation revealed low-amplitude motor evoked potentials (MEPs) in 4 patients with clinically complete paralysis, suggesting the presence of spared motor pathways.

Neurological reinforcement techniques, such as muscle contractions and cutaneous stimulation, were crucial for detecting MEPs in patients, highlighting their importance in accurately assessing motor function in spinal cord injury studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reinforcement of motor evoked potentials in patients with spinal cord injury. Hayes, KC., Allatt, RD., Wolfe, DL., et al.[2007]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6442914/

Operant conditioning of the motor-evoked potential and ... In people with chronic incomplete spinal cord injury (SCI), MEP up-conditioning increased TA activity and improved dorsiflexion during locomotion, while in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07179822

Motoneuron Recruitment and Motor Evoked Potential Up ... The purpose of this research study is to examine the effect of a brain stimulation training to improve the function of brain-spinal cord- ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30625010/

Operant conditioning of the motor-evoked potential and ... In participants with SCI, MEP up-conditioning increased TA activity during the swing-to-swing stance transition phases and ankle joint motion ...

4. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00552/full

Can Operant Conditioning of EMG-Evoked Responses ... Operant conditioning approach as a method to target plasticity in the corticospinal pathway for improving motor function in people with MS.

5. researchgate.net researchgate.net/publication/330266395_Operant_conditioning_of_the_motor_evoked_potential_and_locomotion_in_people_with_and_without_chronic_incomplete_spinal_cord_injury

Operant conditioning of the motor evoked potential and ... In addition, preliminary data suggests that MEP operant conditioning can increase wrist extensor activity in individuals with chronic SCI. ... Functional ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/2018/4725393

Operant Up‐Conditioning of the Tibialis Anterior Motor ... Thus, operant conditioning of an EMG-evoked response that induces spinal and supraspinal plasticity may be used as a gateway to encouraging the ...

7. chp.musc.edu chp.musc.edu/research/centers/nc-nm4r/funding-opportunities

Funding Awards - MUSC College of Health Professions This study expands the application of operant conditioning by examining whether people with stroke are able to increase wrist flexor motor evoked potentials ...