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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Transcranial Magnetic Stimulation (TMS) can alter how the brain processes rewards during decision-making tasks. Researchers aim to determine if TMS can influence brain signals involved in understanding rewards and making choices. Two different TMS approaches are being tested to assess their impact on this process. Individuals with stable mental and physical health who are not on certain medications may be suitable candidates for this study. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research in brain science.

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 prior data suggests that Transcranial Magnetic Stimulation is safe for reward learning studies?

Research has shown that transcranial magnetic stimulation (TMS) is generally safe and well-tolerated. Studies have found that common side effects of TMS are minor and manageable, such as headaches or slight discomfort at the stimulation site. Serious side effects are rare and can often be avoided with proper safety measures.

Additionally, safety data suggests that many TMS procedures are low risk. Methods used in studies, like single-pulse TMS, pose minimal risk to participants. Overall, TMS is widely regarded as having an excellent safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial Magnetic Stimulation (TMS) for reward learning because it offers a unique approach compared to traditional methods for enhancing cognitive function. Unlike standard treatments that may rely on medications to alter brain chemistry, TMS uses magnetic fields to directly stimulate specific brain areas involved in learning and motivation. This method could potentially enhance the brain's natural reward processing capabilities more precisely and with fewer side effects. The study explores two distinct phases of TMS application—peak and trough—which might pinpoint optimal timing for stimulation, potentially improving the effectiveness of TMS in enhancing cognitive tasks related to reward learning.

What evidence suggests that Transcranial Magnetic Stimulation is effective for reward processing?

This trial will study the effects of transcranial magnetic stimulation (TMS) on reward learning. Studies have shown that TMS can influence how the brain processes rewards. Research suggests that TMS might enhance reward learning by targeting brain areas involved in decision-making. For instance, some studies indicate that TMS can alter brain circuits related to reward learning, potentially reducing issues like suicidal thoughts by improving reward processing. While TMS has shown promise in treating conditions such as Alzheimer's and Parkinson's disease, its role in reward learning remains under investigation. Early findings suggest it might aid decision-making by altering reward perception. Participants in this trial will receive either Single-pulse Peak Phase TMS or Single-pulse Trough Phase TMS to explore these effects further. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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) 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9853407/

Evaluating the treatment outcomes of repetitive transcranial ... The repetitive transcranial magnetic stimulation (rTMS) shows great potential in the treatment of Alzheimer's disease (AD).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01260740

The Effect of Transcranial Magnetic Stimulation on ... By studying the effect of TMS on reaction time, learning, and memory, researchers hope to better understand how to treat conditions such as Parkinson's disease ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/da/1767477

Therapeutic Efficacy of Reward Circuit‐Targeted ... The DLPFC–NAcc circuit may serve as an effective treatment target for reducing suicide ideation due to its crucial functions in reward learning, ...

4. nature.com nature.com/articles/s41386-025-02225-w

Neurodevelopmental considerations for transcranial ... Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for neuropsychiatric disorders that shows initial efficacy, ...

5. mdpi.com mdpi.com/2076-3417/14/14/6178

An Insight from a Naturalistic Observational Study The results indicated that TMS significantly improved symptom scores, but no significant cognitive enhancement was observed. Statistical ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3656498/

Safety and tolerability of repetitive transcranial magnetic ... Safety of TMSCG. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research.

7. nimh.nih.gov nimh.nih.gov/news/media/2020/sarah-h-lisanby-transcranial-magnetic-stimulation-safety-and-risk

Sarah H. Lisanby: Transcranial Magnetic Stimulation Safety ... The safety profile of TMS is excellent. The common side effects tend to be minor and are easily managed. The serious side effects are rare and can be prevented ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1388245720305149

Safety and recommendations for TMS use in healthy ... Given the accumulated safety data from rTMS experience to date, some research protocols may qualify for minimal risk/minimal burden status based on local ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT07197346

Repetitive Transcranial Magnetic Stimulation Primed Self ... This study aims to investigate the additive effects of combining self-controlled practice with repetitive transcranial magnetic stimulation ...