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

44 Participants Needed

Trial Summary

What is the purpose of this trial?

The study team is currently recruiting volunteers who are interested in participating in a brain-spinal cord-muscle response training study that aims to better understand the changes that take place in the nervous system as a result of this type of training. After spinal cord injury, brain-to-muscle connections are often interrupted. Because these connections are important in movement control, when they are not working well, movements may be disturbed. Researchers have found that people can learn to strengthen these connections through training. Strengthening these connections may be able to improve movement control and recovery after injuries. Research participants will be asked to stand, sit, and walk during the study sessions. Electrodes are placed on the skin over leg muscles for monitoring muscle activity. For examining brain-to-muscle connections, the study team will use transcranial magnetic stimulation. The stimulation is applied over the head and will indirectly stimulate brain cells with little or no discomfort. Participation in this study requires approximately three sessions per week for four months, followed by two to three sessions over another three months. Each session lasts approximately 1 hour.

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 data supports the effectiveness of the treatment Brain-Spinal Cord-Muscle Response Training for Spinal Cord Injury?

Research shows that operant conditioning, a key part of this treatment, can increase muscle activity and improve movement in people with spinal cord injuries by enhancing the pathways in the brain and spinal cord that control movement. This suggests that the treatment could help improve motor function recovery in these patients. ^{1 2 3 4 5}

Is the Brain-Spinal Cord-Muscle Response Training for Spinal Cord Injury safe for humans?

Research on similar treatments, like operant conditioning and targeted plasticity interventions, shows they are generally safe for humans. Studies involving people with spinal cord injuries and other conditions have not reported significant safety concerns, suggesting these methods are safe when conducted under proper protocols. ^{1 2 5 6 7}

How is the treatment Operant Conditioning different from other treatments for spinal cord injury?

Operant Conditioning is unique because it uses a training method to enhance the brain-spinal cord-muscle connection by encouraging specific muscle responses, which can lead to improved motor function recovery. Unlike other treatments, it focuses on targeted plasticity (the brain's ability to change and adapt) in specific pathways, potentially offering a novel way to improve movement control after spinal cord injury. ^{2 3 4 5 8}

Research Team

Aiko K Thompson, PhD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Operant conditioning of the motor-evoked potential and locomotion in people with and without chronic incomplete spinal cord injury. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Operant conditioning of the tibialis anterior motor evoked potential in people with and without chronic incomplete spinal cord injury. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Conditioning lower limb H-reflexes by transcranial magnetic stimulation of motor cortex reveals preserved innervation in SCI patients. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Reinforcement of motor evoked potentials in patients with spinal cord injury. [2007]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Targeted neuroplasticity for rehabilitation. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Operant conditioning of spinal stretch reflexes in patients with spinal cord injuries. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Operant Up-Conditioning of the Tibialis Anterior Motor-Evoked Potential in Multiple Sclerosis: Feasibility Case Studies. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Activity-dependent spinal cord plasticity in health and disease. [2019]