TMS for Reward Learning

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Central nervous system

Disqualifiers: Neurological, Seizure, Bipolar, Schizophrenia, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

28 Participants Needed

Trial Summary

What is the purpose of this trial?

Our specific aim is to examine the effects of TMS on reward processing during goal-directed behavior. In these experiments the investigators will utilize a scalp-recorded brain oscillation called frontal midline theta that is believed to index the sensitivity of the cingulate cortex to reward feedback. Here the investigators will asked whether this electrophysiological signal can be modulated up or down using TMS while participants engage in decision making tasks, and if so, whether it would affect the encoding of rewards and subsequent choices during task performance.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on uninterruptable central nervous system medication. It's best to discuss your specific medications with the trial coordinators.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation (TMS) for Reward Learning?

Research shows that high-frequency repetitive transcranial magnetic stimulation (rTMS) over the prefrontal region can increase dopamine release, which is linked to reward learning. Additionally, rTMS has been found to reduce cravings and improve cognitive function in individuals with addictive disorders, suggesting its potential effectiveness in enhancing reward learning. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) generally safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe when used within recommended guidelines. Common side effects are usually minor, such as headaches, and there is a low risk of more serious events like seizures, which can be minimized by screening for risk factors. ^{6 7 8 9 10}

How is TMS treatment different from other treatments for reward learning?

TMS (Transcranial Magnetic Stimulation) is unique because it noninvasively stimulates specific brain regions, like the prefrontal cortex, to enhance dopamine release, which is important for reward learning. Unlike medications, it uses magnetic fields to influence brain activity directly, offering a novel approach to modifying brain function related to reward processing. ^{2 4 5 11 12}

Eligibility Criteria

This trial is for individuals struggling with addiction. Participants should be able to perform decision-making tasks and have no conditions that would interfere with TMS treatment or the measurement of brain activity.

Inclusion Criteria

Be willing to provide informed consent

Be able to comply with protocol requirements and likely to complete all study procedures

My mental and physical health is stable.

Exclusion Criteria

I have a history of an immune, hormone, viral, or blood vessel disorder that affects my brain.

I don't have a history of major neurological issues, head injuries, or any metal implants in my head.

I have never been diagnosed with bipolar disorder, schizophrenia, PTSD, dementia, or major depression.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single-pulse TMS during goal-directed behavior tasks over two sessions within two weeks

2 weeks

2 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Transcranial Magnetic Stimulation

Trial Overview The study tests if Active single pulse Transcranial Magnetic Stimulation (TMS) to the frontal cortex can influence reward processing in the brain during goal-directed behavior, potentially affecting choices and task performance.

Participant Groups

Group I: Single-pulse Trough Phase TMS Experimental Treatment 1 Intervention

Participants will receive a single active TMS pulse during the trough phase target of each task trial and delivered at 110% of participants' resting motor threshold over the predefined frontal target . For the second TMS session, participants will receive single pulse Sham TMS during the peak phase target of each task trial and delivered at 110% of participants' resting motor threshold over the predefined frontal target. Total number of TMS pulse for each session is 520 pulses

Group II: Single-pulse Peak Phase TMS Experimental Treatment 1 Intervention

Participants will receive a single active TMS pulse during the peak phase target of each task trial and delivered at 110% of participants' resting motor threshold over the predefined frontal target . For the second TMS session, participants will receive single pulse Sham TMS during the peak phase target of each task trial and delivered at 110% of participants' resting motor threshold over the predefined frontal target. Total number of TMS pulse for each session is 520 pulses

Transcranial Magnetic Stimulation is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Findings from Research

In a study involving 9 healthy men with pathological gambling, repeated transcranial magnetic stimulation (rTMS) and continuous theta burst stimulation (cTBS) were found to reduce the desire to gamble and the physiological effects associated with gambling, such as diastolic blood pressure.

While neither treatment significantly affected impulsive betting behavior, both increased Stroop interference, suggesting that these interventions may alter cognitive processes related to gambling reinforcement rather than directly changing gambling behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of High Frequency Repeated Transcranial Magnetic Stimulation and Continuous Theta Burst Stimulation on Gambling Reinforcement, Delay Discounting, and Stroop Interference in Men with Pathological Gambling. Zack, M., Cho, SS., Parlee, J., et al.[2019]

The study found that the expectation of rewards during a slot machine simulation increased intracortical inhibition in the primary motor cortex (M1), suggesting that reward anticipation can influence motor cortex activity.

Receiving a large reward prior to a trial further enhanced this effect, indicating a potential link between reward processing and motor learning, possibly mediated by dopaminergic neurons projecting to M1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reward-related activity in the human motor cortex. Kapogiannis, D., Campion, P., Grafman, J., et al.[2021]

In a study involving 22 patients with gambling disorder, real rTMS applied to the left DLPFC significantly reduced cue-induced gambling cravings compared to sham treatment, indicating its potential efficacy in managing cravings.

However, the study found no significant impact of rTMS on actual gambling behavior, suggesting that while it may help with cravings, further research is needed to understand its overall effectiveness in treating gambling disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single session of repetitive transcranial magnetic stimulation of the prefrontal cortex reduces cue-induced craving in patients with gambling disorder. Gay, A., Boutet, C., Sigaud, T., et al.[2020]

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex (DLPFC) enhances responsiveness to rewarding stimuli, as shown in a study with 18 healthy volunteers using a probabilistic reward task.

Participants exhibited a greater response bias toward more frequently rewarded stimuli after HF-rTMS compared to sham stimulation, suggesting that HF-rTMS may influence dopaminergic activity related to reward learning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of high-frequency rTMS over the left dorsolateral prefrontal cortex on reward responsiveness. Ahn, HM., Kim, SE., Kim, SH.[2016]

Repetitive transcranial magnetic stimulation (rTMS) shows promise in treating addiction by potentially correcting dysfunctions in the brain's reward system, which are often overlooked in traditional treatments.

The therapy may help reduce cravings by addressing the underlying hedonic dysregulation associated with addiction, suggesting a new avenue for effective interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Light in the Darkness: Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat the Hedonic Dysregulation of Addiction. Pettorruso, M., di Giannantonio, M., De Risio, L., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

In a study involving 20 patients with unipolar depression, the pain associated with left prefrontal repetitive transcranial magnetic stimulation (rTMS) decreased by 48% over 15 treatment sessions, indicating that discomfort may lessen with continued use.

The reduction in pain was most significant in the first few days but continued steadily throughout the treatment, suggesting that patients may tolerate rTMS better over time, which could encourage ongoing treatment despite initial discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreasing procedural pain over time of left prefrontal rTMS for depression: initial results from the open-label phase of a multi-site trial (OPT-TMS). Anderson, BS., Kavanagh, K., Borckardt, JJ., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is generally a well-tolerated treatment for depression, with mild side effects like headaches being the most common, while severe adverse effects are rare.

Special precautions are necessary for certain groups, such as adolescents, pregnant women, and individuals with metal implants, but with proper assessment and monitoring, rTMS can be safely administered to many patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. Taylor, R., Galvez, V., Loo, C.[2019]

Repetitive transcranial magnetic stimulation (rTMS) is generally safe for older adults with late-life depression, with only 12.4% reporting any adverse events and serious adverse events occurring in just 1.5% of cases, based on a review of 11 studies involving 353 patients.

The most common adverse events were mild, such as headaches (6.9%) and discomfort at the stimulation site (2.7%), although some serious adverse events, including psychiatric hospitalization and increased suicidal ideation, were noted in case reports, highlighting the need for further research to ensure safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. Overvliet, GM., Jansen, RAC., van Balkom, AJLM., et al.[2021]

Repetitive Transcranial Magnetic Stimulation (rTMS) has a good overall safety profile for treating depression, with common side effects like headaches being minor and manageable.

While there is a low incidence of serious side effects such as seizures and hypomania, these are linked to specific risk factors, suggesting that proper screening can enhance patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Loo, CK., McFarquhar, TF., Mitchell, PB.[2021]

A single session of high-frequency rTMS (10 Hz) over the left dorsolateral prefrontal cortex significantly reduced cigarette craving in 16 nicotine-dependent participants, demonstrating its potential efficacy as a noninvasive treatment.

The reduction in craving was notably greater with real rTMS compared to sham treatment, suggesting that rTMS may be a promising tool for aiding smoking cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving. Li, X., Hartwell, KJ., Owens, M., et al.[2022]

In a study involving 22 problematic substance users, 10-Hz TMS applied to the prefrontal cortex successfully enhanced the reward positivity signal in the anterior midcingulate cortex, indicating improved reward processing.

Participants receiving active TMS showed better performance in reward-based learning tasks compared to those in the SHAM group, suggesting that TMS may be a promising intervention for addressing reward-related dysfunction in substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recovery of reward function in problematic substance users using a combination of robotics, electrophysiology, and TMS. Biernacki, K., Lin, MH., Baker, TE.[2023]

References

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

Effects of High Frequency Repeated Transcranial Magnetic Stimulation and Continuous Theta Burst Stimulation on Gambling Reinforcement, Delay Discounting, and Stroop Interference in Men with Pathological Gambling. [2019]

2. France pubmed.ncbi.nlm.nih.gov

Reward-related activity in the human motor cortex. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A single session of repetitive transcranial magnetic stimulation of the prefrontal cortex reduces cue-induced craving in patients with gambling disorder. [2020]

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

The effects of high-frequency rTMS over the left dorsolateral prefrontal cortex on reward responsiveness. [2016]

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

A Light in the Darkness: Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat the Hedonic Dysregulation of Addiction. [2021]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

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

Decreasing procedural pain over time of left prefrontal rTMS for depression: initial results from the open-label phase of a multi-site trial (OPT-TMS). [2021]

8. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. [2021]

10. England pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. [2021]

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

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Recovery of reward function in problematic substance users using a combination of robotics, electrophysiology, and TMS. [2023]