Testing the Contribution of Orbitofrontal Cortex Networks to Decision-making in Healthy Subjects

Overseen By Greg Lane, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Must not be taking: Psychoactive, Seizure-inducing

Disqualifiers: Neurological, Psychiatric, Medical, Cerebrovascular, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 session

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how certain brain networks assist with decision-making using transcranial magnetic stimulation (TMS), which employs magnetic fields to stimulate the brain. Participants are divided into groups receiving either real or sham TMS targeting different brain areas. The trial seeks English-speaking, right-handed adults who are generally healthy and have no history of major brain or mental health issues. As an unphased trial, it offers participants the chance to contribute to groundbreaking research on brain function and decision-making.

Will I have to stop taking my current medications?

Yes, if you are currently using psychoactive medications or medications that increase the likelihood of seizures, you will need to stop taking them to participate in this trial.

What prior data suggests that this method is safe for use in humans?

Research has shown that transcranial magnetic stimulation (TMS) is generally safe. Studies have found that TMS is usually well-tolerated, with only a few experiencing serious side effects. Specifically, research on using TMS over the orbitofrontal cortex (OFC) found it safe for treating conditions like depression and obsessive-compulsive disorder.

When side effects occur, they are usually mild. Individuals might feel a slight tingling or tapping on their scalp during TMS. Headaches can also occur but typically don't last long. Overall, TMS is considered safe and manageable for most individuals. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses transcranial magnetic stimulation (TMS) to explore how specific brain networks in the orbitofrontal cortex (OFC) contribute to decision-making. Unlike other methods that might rely on behavioral studies or neuroimaging alone, TMS allows for direct stimulation of particular brain areas, which can help reveal their precise roles in cognitive processes. This approach is unique because it targets both anterior and posterior OFC networks, potentially providing a more comprehensive understanding of how these regions affect decision-making. By using both real and sham TMS, researchers can better isolate the effects of stimulating these networks, offering insights that could inform future treatments or interventions.

What evidence suggests that this trial's treatments could be effective for decision-making?

This trial will investigate the effects of transcranial magnetic stimulation (TMS) on decision-making by targeting different networks within the orbitofrontal cortex (OFC). Participants will be assigned to one of two treatment arms: one targeting the anterior OFC networks and the other targeting the posterior OFC networks. Studies have shown that TMS can improve symptoms in various mental health conditions. Specifically, research indicates that using TMS on the left side of the brain, particularly the OFC, can reduce symptoms of obsessive-compulsive disorder, depression, and anxiety, especially when other treatments have been ineffective. One study found that TMS might also enhance decision-making, particularly for individuals with substance use issues. Additionally, targeting the right side of the OFC with TMS has shown promise in helping patients with major depression, even when other TMS treatments have not succeeded. This suggests that TMS might affect brain areas involved in decision-making, which is the focus of this study. ^{5 6 7 8 9}

Who Is on the Research Team?

Christina Zelano, PhD

Principal Investigator

Assistant Professor

Are You a Good Fit for This Trial?

This trial is for healthy individuals aged 18-40, right-handed, fluent in English. It's not suitable for those on seizure-risk meds, with a history of fainting or eating disorders, metal implants, significant illnesses like cancer or heart disease, severe allergies or asthma requiring hospitalization, habitual smokers, hearing issues, claustrophobia, high stroke risk factors (like hypertension), psychoactive medication users or major psychiatric conditions.

Inclusion Criteria

Right-handed

Fluent English speakers

Exclusion Criteria

You are taking medications that can increase the risk of seizures.

You have a history of fainting or passing out.

You have a history of eating disorders like anorexia nervosa, bulimia nervosa, or binge-eating disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TMS targeting either anterior or posterior OFC networks, combined with fMRI and olfactory stimuli

1 session

1 visit (in-person)

Follow-up

Participants are monitored for decision-making behavior and resting-state activity after intervention

1 hour

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Real transcranial magnetic stimulation (TMS) before conditioning
• Real transcranial magnetic stimulation (TMS) before devaluation test
• Sham transcranial magnetic stimulation (TMS)

Trial Overview The study tests how the orbitofrontal cortex influences decision-making using transcranial magnetic stimulation (TMS). Participants will receive real TMS before conditioning and devaluation tests to assess their decision-making process compared to sham TMS which serves as a control condition.

How Is the Trial Designed?

Group I: TMS targeting OFC anterior networks Experimental Treatment 3 Interventions

Participants will receive TMS and sham targeting the OFC network.

Group II: Experimental: TMS targeting posterior OFC networks Experimental Treatment 3 Interventions

Participants will receive TMS and sham targeting the posterior OFC network.

Real transcranial magnetic stimulation (TMS) before conditioning is already approved in United States, European Union, Canada for the following indications:

Approved in United States as TMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Migraines
• Smoking cessation

Approved in European Union as TMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Approved in Canada as TMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Published Research Related to This Trial

Repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex (DLPFC) significantly increased risk-taking behavior in a motor response task, as evidenced by more frequent ceiling hits compared to sham stimulation.

The study indicates that the right DLPFC plays a crucial role in impulse control during goal-directed tasks, suggesting that modulation of this brain region can shift decision-making towards immediate rewards while reducing sensitivity to negative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diminished Risk-Aversion After Right DLPFC Stimulation: Effects of rTMS on a Risky Ball Throwing Task. Tulviste, J., Bachmann, T.[2020]

Different sham transcranial magnetic stimulation (TMS) techniques can produce varying levels of cortical stimulation, with some sham conditions inducing significant brain activity, which could affect trial outcomes.

The study found that a two-wing 45-degree tilt sham condition resulted in only 24% lower voltage than active TMS, indicating that not all sham methods are equally effective in mimicking a true placebo, highlighting the importance of selecting appropriate sham techniques in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials. Lisanby, SH., Gutman, D., Luber, B., et al.[2022]

A series of 9 sessions of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on the left dorsolateral prefrontal cortex significantly reduced depression scores in healthy young men, as measured by the Beck Depression Inventory (BDI).

Despite the positive effect on BDI scores, the study found no significant long-term changes in mood-related visual analogue scales (VAS), with one scale indicating participants felt more 'gloomy' immediately after stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation influences mood in healthy male volunteers. Schaller, G., Lenz, B., Friedrich, K., et al.[2022]

Transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) altered decision-making processes in healthy female subjects, leading to a bias towards non-veridical choices, indicating that the mechanisms for non-veridical and veridical decision-making are distinct.

Specifically, 1 Hz TMS of the right DLPFC not only shifted decision-making bias but also improved performance in a visuospatial working memory task, suggesting that stimulation can enhance cognitive functions by influencing interconnected brain regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation on non-veridical decision making. Tulviste, J., Goldberg, E., Podell, K., et al.[2019]

Disrupting the left lateral prefrontal cortex (LPFC) using low-frequency repetitive transcranial magnetic stimulation (rTMS) led to an increased preference for immediate rewards over larger delayed rewards, indicating a role of this brain region in self-control during decision-making.

The study suggests that the left LPFC is specifically involved in intertemporal choices, as rTMS did not affect decisions involving only delayed rewards or the valuation of rewards, highlighting its targeted influence on self-control mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lateral prefrontal cortex and self-control in intertemporal choice. Figner, B., Knoch, D., Johnson, EJ., et al.[2022]

High-frequency repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex improved response inhibition in healthy young men, as evidenced by fewer commission errors during attention tasks compared to sham stimulation.

The study involved 17 participants and suggests that rTMS may enhance attentional control, indicating potential therapeutic applications for conditions related to attentional deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute high-frequency rTMS of the left dorsolateral prefrontal cortex and attentional control in healthy young men. Hwang, JH., Kim, SH., Park, CS., et al.[2019]

In patients with Parkinson's disease, the expectation of benefit from sham rTMS (placebo-rTMS) led to significant changes in dopamine neurotransmission, as indicated by a reduction in [11C] raclopride binding potentials in the striatum, suggesting a strong placebo effect.

This study highlights the need for placebo-controlled trials in rTMS research, as it demonstrates that even sham treatments can induce measurable changes in brain function, which could impact the interpretation of clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic application of transcranial magnetic stimulation in Parkinson's disease: the contribution of expectation. Strafella, AP., Ko, JH., Monchi, O.[2023]

In a meta-analysis of 93 randomized controlled trials involving repetitive transcranial magnetic stimulation (TMS), the overall incidence of adverse events (AEs) was found to be higher in the active TMS group (29.3%) compared to the placebo group (13.6%), indicating a 2.60 times greater risk of experiencing AEs with active treatment.

Despite the higher incidence of AEs, TMS is considered a safe and well-tolerated intervention, with common side effects including headache and dizziness, highlighting the importance of recognizing nocebo effects in both clinical trials and practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. Zis, P., Shafique, F., Hadjivassiliou, M., et al.[2022]

Transcranial direct current stimulation (tDCS) of the orbitofrontal cortex (OFC) effectively reduces delay discounting (DD) in healthy subjects, indicating a potential method to influence decision-making processes.

The study found no correlation between delay discounting and working memory performance or baseline impulsivity, suggesting that the OFC's role in DD is distinct from these cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation (tDCS) over the orbitofrontal cortex reduces delay discounting. Moro, AS., Saccenti, D., Vergallito, A., et al.[2023]

In a study involving 33 patients undergoing rTMS treatment, the sham condition used was effective as most participants could not distinguish between real and sham stimulation, indicating its suitability for clinical trials.

Both groups, those receiving real stimulation and those receiving sham, showed a high willingness to recommend rTMS to others, suggesting that the treatment is perceived positively regardless of the actual stimulation received.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sham or real--post hoc estimation of stimulation condition in a randomized transcranial magnetic stimulation trial. Herwig, U., Cardenas-Morales, L., Connemann, BJ., et al.[2015]

Using repetitive transcranial magnetic stimulation (rTMS) on the right dorsolateral prefrontal cortex (DLPFC) during a food valuation task led to a decrease in the values participants assigned to food stimuli, suggesting a causal role of the DLPFC in decision-making processes.

The study indicates that the DLPFC is not just correlated with valuation signals but actively participates in computing values at the time of making choices, highlighting its importance in economic decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex decreases valuations during food choices. Camus, M., Halelamien, N., Plassmann, H., et al.[2010]

In a study with 10 normal volunteers, rapid-rate transcranial magnetic stimulation (rTMS) did not produce overall mood changes, but it did show that stimulation of the left prefrontal cortex increased feelings of sadness and decreased feelings of happiness compared to stimulation of the right prefrontal and midfrontal areas.

These findings suggest that different areas of the prefrontal cortex have distinct effects on mood, highlighting the importance of lateralized brain function in emotional regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lateralized effect of rapid-rate transcranial magnetic stimulation of the prefrontal cortex on mood. Pascual-Leone, A., Catalá, MD., Pascual-Leone Pascual, A.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12293014/

Transcranial Direct Current Stimulation over the ... Results: Linear mixed-effects models showed that anodal tDCS over the left OFC reduced participants' metacognitive sensitivity compared to sham ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772408525001036

Augmentative transcranial magnetic stimulation over the ... Our data support the efficacy and tolerability of rTMS over the left OFC on obsessive-compulsive, depressive, and anxious symptoms in treatment-resistant OCD.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10051603/

Functional Activity in the Effect of Transcranial Magnetic ... Transcranial magnetic stimulation (TMS) can be a safe and effective choice for the treatment of depression. Functional neuroimaging provides ...

4. nature.com nature.com/articles/s41398-024-03000-z

Modulation of dlPFC function and decision-making ... This study explores the impact of repetitive transcranial magnetic stimulation (rTMS) on decision-making capabilities in individuals with methamphetamine use ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0924977X17320023

1 Hz rTMS of the right orbitofrontal cortex for major ... 1 Hz right OFC-rTMS appears safe and tolerable, and may achieve remission in MDD patients even when conventional rTMS has failed.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4203001/

Repetitive transcranial magnetic stimulation over the ... This pilot study was designed to assess the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the right orbitofrontal cortex ( ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178122004486

Use of right orbitofrontal repetitive transcranial magnetic ... Right orbitofrontal rTMS augmentation is safe and may be effective for treatment of OCD-MDD. Abstract. We examined the safety and efficacy of repetitive ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5925584/

Meta-analysis of the Efficacy and Safety of Repetitive ... After Meta-analysis, we found that treatment combined rTMS with antidepressants improves depressive symptoms in patients with depression.

9. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?lcdid=34869&ver=42&=

Repetitive Transcranial Magnetic Stimulation (rTMS) in Adults Use this page to view details for the Local Coverage Determination for Repetitive Transcranial Magnetic Stimulation (rTMS) in Adults.