Operant Conditioning for ACL Injury

Overseen By Chandramouli Krishnan, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Must not be taking: Seizure threshold reducers

Disqualifiers: Previous ACL injury, Major knee surgery, Diabetes, Hypertension, others

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

Compensation: Varies

Number of Visits: 16

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a form of mental coaching, called operant conditioning, can improve thigh muscle weakness and activation after an ACL injury. Participants will receive either stimulation alone or stimulation with operant conditioning to determine which is more effective. It targets individuals aged 18-45 who have experienced a complete ACL tear and undergone surgery. This approach may benefit those struggling with muscle strength and control after ACL surgery. As an unphased trial, it offers participants the chance to contribute to innovative research that could enhance recovery strategies for ACL injuries.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking drugs that reduce the seizure threshold, you may not be eligible to participate.

What prior data suggests that operant conditioning is safe for improving muscle activation after ACL injury?

Research has shown that operant conditioning can improve muscle control after an ACL injury. This therapy strengthens the brain's signals to the muscles, enhancing muscle strength and activity. In earlier studies, participants experienced increased muscle activity after just one session, suggesting it might safely improve muscle function.

These studies did not report any major safety issues, indicating that operant conditioning is generally well-tolerated. As this method involves mental training and encouragement rather than medication or surgery, it is usually considered safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using operant conditioning for ACL injury recovery because it offers a novel approach to rehabilitation. Unlike traditional treatments that often focus on physical therapy and surgical repair, this method combines operant conditioning training with transcranial magnetic stimulation (TMS) to potentially enhance brain-muscle communication. This unique combination aims to accelerate recovery by directly influencing neural pathways, which could lead to more effective and faster rehabilitation for patients.

What evidence suggests that operant conditioning is effective for improving muscle activation after ACL injury?

Research shows that operant conditioning, which participants in this trial may receive, can improve muscle movement after an ACL injury. Studies have found that it increases the activity of nerve pathways controlling muscles. In previous studies, participants strengthened their muscles using operant conditioning techniques. This method involves mental coaching and encouragement to retrain the brain's connection to the muscles. Overall, early evidence suggests that operant conditioning might be a promising way to enhance recovery and strength after ACL injuries. ^{1 2 4 6 7}

Who Is on the Research Team?

Chandramouli Krishnan, PhD

Principal Investigator

Assistant Professor

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-45 who have had an ACL rupture and subsequent reconstructive surgery. Participants must be willing to follow the study's procedures. Those pregnant, with previous major knee surgeries, on certain drugs, with fainting spells, uncontrolled diabetes or hypertension, ear/heart devices, recurrent headaches, seizures or recent significant knee injuries cannot join.

Inclusion Criteria

Willingness to participate in testing and follow-up as outlined in the protocol

I have a recent, complete tear in my ACL.

I have had ACL reconstructive surgery.

Exclusion Criteria

You have had a previous injury to your ACL (a ligament in your knee).

Be pregnant or plan to become pregnant

You have metal implants in your head.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive operant conditioning training and single pulse transcranial magnetic stimulation 2-3 times a week

8 weeks

16-24 visits (in-person)

Mid-point Evaluation

Assessment of quadriceps strength and voluntary activation using isokinetic dynamometer and electrical superimposition technique

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Operant Conditioning

Trial Overview The study tests if thigh muscle weakness post-ACL injury can be improved using mental coaching (operant conditioning) alongside Single Pulse Transcranial Magnetic Stimulation versus a control group without these interventions.

How Is the Trial Designed?

Group I: Operant Conditioning Experimental Treatment 2 Interventions

Participants will receive operant conditioning training and single pulse transcranial magnetic stimulation 2-3 times a week for about 8 weeks.

Group II: Control Experimental Treatment 2 Interventions

Participants will receive single pulse transcranial magnetic stimulation 2-3 times a week for about 8 weeks without operant conditioning training.

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Center of Neuromodulation for Rehabilitation

Collaborator

Trials

4

Recruited

120+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

National Center of Neuromodulation for Rehabilitation

Collaborator

Trials

12

Recruited

240+

Published Research Related to This Trial

Operant conditioning protocols can effectively modify spinal reflexes, which are fundamental behaviors, providing valuable insights into the mechanisms of learning.

These protocols can also promote neural plasticity, potentially aiding in the recovery of motor skills like walking in individuals with spinal cord injuries or related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The simplest motor skill: mechanisms and applications of reflex operant conditioning. Thompson, AK., Wolpaw, JR.[2021]

After anterior cruciate ligament reconstruction (ACLR), patients showed increased feelings of learned helplessness (LH) as they progressed from 3 months post-surgery to their return to play, indicating a psychological impact during recovery.

The study found that neural excitability and quadriceps strength were inconsistent and linked to feelings of helplessness, suggesting that addressing both physical and psychological factors could improve recovery outcomes for ACLR patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in physical and neurocognitive wellness across recovery after ACLR: A preliminary look into learned helplessness. Burland, JP., Lepley, AS., DiStefano, LJ., et al.[2020]

Traumatic knee injuries, like ACL sprains, can lead to long-term health issues, including chronic pain and disability, highlighting the importance of effective rehabilitation strategies.

The study suggests that psychological factors, particularly learned helplessness, may negatively impact recovery after ACL reconstruction by affecting both neural activity and rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Learned Helplessness After Anterior Cruciate Ligament Reconstruction: An Altered Neurocognitive State? Burland, JP., Lepley, AS., Cormier, M., et al.[2020]

The study involved 20 participants (9 with ACL injuries and 11 controls) and found that traumatic musculoskeletal injuries lead to significant changes in brain structure and function, particularly in the corticomotor system, which is linked to muscle control and movement.

Using intermittent theta burst stimulation (iTBS), researchers were able to normalize muscle function and corticospinal excitability in individuals with ACL injuries, suggesting that targeted brain therapies could enhance recovery from such injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in brain structure and theta burst stimulation-induced plasticity implicate the corticomotor system in loss of function after musculoskeletal injury. Flanagan, SD., Proessl, F., Dunn-Lewis, C., et al.[2021]

Mechanical perturbation training using an automated device showed similar effectiveness to manual perturbation training in improving knee function and biomechanics in patients with acute ACL ruptures, based on a study of 18 patients.

Both training methods led to significant improvements in patient-reported knee function and biomechanical measures, with the mechanical group outperforming the manual group in specific performance tests like triple hops and timed hops.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Biomechanical Efficacies of Mechanical Perturbation Training After Anterior Cruciate Ligament Rupture. Nawasreh, Z., Logerstedt, D., Marmon, A., et al.[2021]

In a study with 13 subjects, operant conditioning significantly influenced pain reports, showing that verbal reinforcement could alter pain ratings even when the pain stimulus remained constant.

When subjects were reinforced for increasing pain reports while the actual pain stimulus was reduced, they still reported higher pain levels, indicating that pain perception can be manipulated through reinforcement, supporting the operant conditioning theory of pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlling pain reports through operant conditioning: a laboratory demonstration. Linton, SJ., Götestam, KG.[2022]

Operant conditioning can induce both hyperalgesic (increased pain sensitivity) and allodynic (pain from normally non-painful stimuli) effects in healthy individuals, as shown in a systematic review of 8 studies involving 401 participants.

The results indicate that pain perception can be influenced by reinforcement strategies, but the findings are limited by a small number of studies and potential biases, particularly in the context of allodynic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reward for Pain: Hyperalgesia and Allodynia Induced by Operant Conditioning: Systematic Review and Meta-Analysis. Adamczyk, WM., Buglewicz, E., Szikszay, TM., et al.[2020]

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]

Chronic back pain patients (CBP) are more susceptible to operant conditioning influences, which may contribute to the persistence of their pain, as shown in a study involving 30 CBP patients and 30 healthy controls.

While both groups learned at similar rates, CBP patients exhibited slower extinction of pain responses and prolonged muscle tension, indicating that their pain responses are more deeply ingrained and harder to modify.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of operant conditioning in chronic pain: an experimental investigation. Flor, H., Knost, B., Birbaumer, N.[2022]

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]

Only about 50% of athletes who undergo anterior cruciate ligament reconstruction (ACLR) can return to competitive sports, and there is a significant risk of re-injury, with up to 20% experiencing a second ACL rupture within the first year after surgery.

Current rehabilitation programs may not effectively address the deficits caused by the initial injury and surgery, highlighting the need for new approaches that incorporate motor learning principles to enhance recovery and reduce the risk of re-injury and early osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Principles of Motor Learning to Support Neuroplasticity After ACL Injury: Implications for Optimizing Performance and Reducing Risk of Second ACL Injury. Gokeler, A., Neuhaus, D., Benjaminse, A., et al.[2020]

In a study with 21 participants using fMRI, operant conditioning was found to significantly reduce pain ratings more than classical conditioning when exposed to high pain stimuli, indicating its potential efficacy in pain modulation.

Neural activity in the brain showed that operant conditioning activated the temporoparietal junction more than classical conditioning, while also reducing activity in the primary somatosensory cortex during pain, suggesting different underlying mechanisms for these two types of learning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operant and classical learning principles underlying mind-body interaction in pain modulation: a pilot fMRI study. Lee, IS., Jung, WM., Lee, YS., et al.[2021]

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]

A retrospective review of 16 treatment-resistant children with motor performance issues showed that a multi-site, performance-contingent reward program led to improvements in motor skills, with 14 out of 16 patients demonstrating progress.

The program involved using surface electromyography to reward correct muscle recruitment patterns, suggesting that this method can effectively enhance motor function in children with specific therapy needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of multiple-site performance-contingent SEMG reward programming in pediatric rehabilitation: a retrospective review. Bolek, JE.[2009]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11569524/

Conditioning of Motor Evoked Responses After Anterior ... Operant conditioning of motor evoked torque (MEP TORQUE) can directly target the corticospinal pathway in patients with anterior cruciate ligament (ACL) ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38864306/

Conditioning of Motor Evoked Responses After Anterior ... Operant conditioning may be a feasible approach to improve corticospinal excitability after ACL reconstruction.

3. researchgate.net researchgate.net/publication/381340664_Conditioning_of_Motor_Evoked_Responses_After_Anterior_Cruciate_Ligament_Reconstruction_Effects_of_Stimulus_Intensity

Conditioning of Motor Evoked Responses After Anterior ... Results TKA participants were able to successfully increase their MEP TORQUE in a single session ( F 3,81 = 10.719, p < 0.001) and induce acute corticospinal ...

4. withpower.com withpower.com/trial/phase-anterior-cruciate-ligament-injuries-8-2017-a9465

Operant Conditioning for ACL Injury The purpose of this study is to examine if thigh muscle weakness and the lack of muscle activation that accompanies ACL injury can be improved through a ...

5. esskajournals.onlinelibrary.wiley.com esskajournals.onlinelibrary.wiley.com/doi/pdf/10.1002/ksa.12480

Number of conditioning trials, but not stimulus intensity ... Operant conditioning of motor evoked potentials. (MEPs) is an emerging technique that has shown the potential to enhance muscle strength, ...

6. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/19417381241257258

Conditioning of Motor Evoked Responses After Anterior ... Operant conditioning of motor evoked torque (MEP TORQUE) can directly target the corticospinal pathway in patients with anterior cruciate ligament (ACL) ...

7. ovid.com ovid.com/journals/sphe/pdf/10.1177/1941738119835163~conditioning-brain-responses-to-improve-quadriceps-function

Conditioning Brain Responses to Improve Quadriceps Function ... Background: Persistent quadriceps weakness and activation failure are common in individuals with anterior cruciate ligament (ACL) reconstruction.