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

Trial Summary

What is the purpose of this trial?

This research study examines the contribution of orbitofrontal cortex (OFC) networks to 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 data supports the effectiveness of this treatment?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can influence decision-making and mood by affecting brain areas like the prefrontal cortex. For example, rTMS has been found to improve attentional control and response inhibition, which are important for decision-making. Additionally, the placebo effect in brain stimulation studies highlights the importance of expectation in perceived treatment benefits. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Research shows that transcranial magnetic stimulation (TMS), including its variations like repetitive TMS (rTMS) and sham TMS, is generally safe and well-tolerated in humans. Some studies have noted side effects, but these are typically mild and include things like headaches or scalp discomfort. ^{4 6 7 8 9}

How does transcranial magnetic stimulation (TMS) differ from other treatments for decision-making processes?

Transcranial magnetic stimulation (TMS) is unique because it uses magnetic fields to stimulate specific areas of the brain, like the orbitofrontal cortex, to influence decision-making processes. Unlike traditional treatments that might involve medication, TMS is non-invasive and directly targets brain activity, potentially altering how decisions are made by affecting neural networks involved in risk-taking and valuation. ^{4 5 10 11 12}

Research Team

Christina Zelano, PhD

Principal Investigator

Assistant Professor

Eligibility Criteria

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

Age between 18 and 40 years old

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

References

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

Lateralized effect of rapid-rate transcranial magnetic stimulation of the prefrontal cortex on mood. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Acute high-frequency rTMS of the left dorsolateral prefrontal cortex and attentional control in healthy young men. [2019]

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

Therapeutic application of transcranial magnetic stimulation in Parkinson's disease: the contribution of expectation. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. Poland pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation on non-veridical decision making. [2019]

6. United States 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. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Sham or real--post hoc estimation of stimulation condition in a randomized transcranial magnetic stimulation trial. [2015]

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

Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials. [2022]

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

Repetitive transcranial magnetic stimulation influences mood in healthy male volunteers. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation (tDCS) over the orbitofrontal cortex reduces delay discounting. [2023]

11. France pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex decreases valuations during food choices. [2010]

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

Lateral prefrontal cortex and self-control in intertemporal choice. [2022]