Negative Emotions Impact on Decision-Making

Recruiting in Palo Alto (17 mi)

Overseen by Silvia Lopez Guzman, M.D.

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: National Institute of Mental Health (NIMH)

Must not be taking: Psychoactive, Corticosteroids, Pain, Antidepressants

Disqualifiers: Unstable medical, Psychiatric, Substance-related, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Background: Negative emotional states can affect a person s behavior as they make decisions. For example, hunger may make people more impatient; they may then make riskier choices. Other negative emotional states that can change behavior include stress, pain, and sadness. By learning more about how emotions affect thinking and behavior in healthy people, researchers hope to better understand how to identify and treat people with mental disorders. Objective: To learn how negative emotions affect the brain and decision-making behavior. Eligibility: Healthy people aged 18 to 55 years. Design: Participants will have 3 clinic visits in 3 weeks. Participants will fill out questionnaires. They will be asked about their personal history, their personality, and state of mind. For 2 visits, participants will be assigned to different groups. Each group will experience 1 type of emotional stressor: Some participants will watch a video. Some will have to do arithmetic problems. Some will have heat applied to an arm or leg. Some will experience cold by immersing their hand in ice water. For a snack craving test, some will be tempted by food after a 4-hour fast. During these tests, participants will have sensors attached to their bodies. They will be videotaped. Saliva samples will be collected. After the stressors, participants will do tasks on a computer. They will need to make choices. Some participants will perform these decision-making tasks while lying in a brain scanner for functional magnetic resonance imaging. The brain scan involves lying on a table that slides into a cylinder that takes images of the brain. ...

Will I have to stop taking my current medications?

The trial requires that participants do not regularly use psychoactive medications or substances, corticosteroids, or certain pain medications. If you are taking any of these, you may need to stop before participating.

What data supports the effectiveness of the treatment involving the cold pressor test and related stress induction methods on decision-making?

Research shows that the cold pressor test, which involves immersing a hand in ice-cold water, can activate stress responses in the body, similar to other stress-inducing methods. This activation can affect decision-making by altering pain perception and stress levels, which are important factors in how people make decisions under pressure. ^{1 2 3 4 5}

Is the Cold Pressor Test (CPT) safe for humans?

The Cold Pressor Test (CPT) is commonly used in stress research and has been shown to affect physiological responses like heart rate and cortisol levels, but it is generally considered safe for humans when conducted under controlled conditions. ^{4 6 7 8 9}

How does this treatment for negative emotions impact decision-making differ from other treatments?

This treatment is unique because it focuses on how acute stress affects decision-making by amplifying negative emotions and regret, which is not typically addressed by standard treatments. It highlights the role of stress in tilting decision-making towards more emotional and intuitive processing, unlike other treatments that may not consider the emotional impact of stress on decision-making. ^{10 11 12 13 14}

Research Team

Silvia Lopez Guzman, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Eligibility Criteria

Healthy adults aged 18 to 55 who can understand and sign consent, read and write English. Excluded are those using psychoactive drugs or corticosteroids, pregnant women, NIMH staff/family, people with chronic pain or metal in the body that affects MRI scans, left-handed individuals for certain tests, and anyone with medical conditions affecting the study.

Inclusion Criteria

Ability of subject to understand and the willingness to sign a written informed consent document.

I understand my participation will help ensure diversity in the study.

Able to read and write in English to guarantee understanding of all written and spoken instructions, which are in English.

Exclusion Criteria

I have scars, burns, or a recent tattoo that could affect skin sensitivity in the test area.

Has any serious or unstable medical condition or history that in a clinician's assessment implies a cardiovascular, neurological, or physical risk from the study procedures performed to induce negative valence states. This may include chronic systemic disorders that could worsen due to stress (e.g. uncontrolled hypertension, coronary artery disease for example a history of myocardial infarction or stable or unstable angina, or diabetes)

Has any current psychiatric diagnosis (based on SCID) or no diagnosis but scores >=29 on Beck Depression Inventory II or >=26 on Beck Anxiety Inventory

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Experimental Intervention

Participants undergo experimental manipulations of state, including exposure to negative valence states such as stress, pain, and craving, followed by decision-making tasks.

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after intervention, including assessment of decision-making behavior and brain activity.

2-4 weeks

Treatment Details

Interventions

• Cold pressor test (Other)
• Craving (Behavioral Intervention)
• Economic loss (Behavioral Intervention)
• Frustration (Behavioral Intervention)
• Negative valence emotion (Behavioral Intervention)
• Pain (Other)
• Stress (Other)
• Thermal pain (Other)

Trial Overview The trial studies how negative emotions like stress, pain, and craving influence decision-making. Participants undergo emotional stressors (videos, math problems, heat/cold exposure), fill out questionnaires about their state of mind and personality traits while some also perform tasks during an fMRI brain scan.

Participant Groups

Group I: 5 Experimental Treatment 1 Intervention

within-subjects experimental study, where each subject will receive a neutral state and a negative state induction intervention in a cross-over design (counterbalanced order across participants).

Group II: 4 Experimental Treatment 1 Intervention

within-subjects experimental study, where each subject will receive a neutral state and a negative state induction intervention in a cross-over design (counterbalanced order across participants).

Group III: 3 Experimental Treatment 1 Intervention

within-subjects experimental study, where each subject will receive a neutral state and a negative state induction intervention in a cross-over design (counterbalanced order across participants).

Group IV: 2 Experimental Treatment 1 Intervention

within-subjects experimental study, where each subject will receive a neutral state and a negative state induction intervention in a cross-over design (counterbalanced order across participants).

Group V: 1 Experimental Treatment 1 Intervention

within-subjects experimental study, where each subject will receive a neutral state and a negative state induction intervention in a cross-over design (counterbalanced order across participants).

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Dr. Joshua A. Gordon

National Institute of Mental Health (NIMH)

Chief Executive Officer since 2016

MD, PhD

Dr. Shelli Avenevoli

National Institute of Mental Health (NIMH)

Chief Medical Officer

PhD

Findings from Research

Both the cold pressor test (CPT) and mental arithmetic stress (PASAT) significantly reduced pain induced by hypertonic saline in the masseter muscle, with reductions of 35.8% and 30.8% respectively, compared to a control session.

CPT decreased vagal activity, indicating a shift in autonomic function, while PASAT increased heart rate without affecting heart rate variability, suggesting different underlying mechanisms for pain modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental stressors alter hypertonic saline-evoked masseter muscle pain and autonomic response. Bendixen, KH., Terkelsen, AJ., Baad-Hansen, L., et al.[2012]

The cold pressor arm wrap (CPAW) is a practical and effective alternative to the traditional cold pressor test (CPT) for inducing stress, using MRI-safe gel packs instead of water, making it suitable for various research environments.

CPAW successfully activates the sympatho-adrenomedullary (SAM) and hypothalamic-pituitary-adrenal (HPA) axes at levels comparable to CPT, ensuring similar physiological responses while being safer and more convenient for studies involving sensitive equipment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An alternative to the traditional cold pressor test: the cold pressor arm wrap. Porcelli, AJ.[2021]

In a study with 56 participants, exposure to cold (via the cold pressor test) primarily drove cortisol responses and pain perception, while the cognitive task (Paced Auditory Serial Addition Task) enhanced cardiovascular reactions without affecting pain ratings.

The simultaneous administration of cognitive and physical stressors showed additive effects on cardiovascular reactivity, indicating that performing cognitive tasks during physical stress does not significantly interfere with stress responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining mental and physical stress: Synergy or interference? Finke, JB., Zhang, X., Plein, D., et al.[2021]

Colder water temperatures in the cold pressor test significantly reduced behavioral pain tolerance (BPT) and increased sensory (SR) and affective ratings (AR) of pain in college women, indicating that physical factors strongly influence pain perception.

Labeling the pain experience with more severe terms decreased pain tolerance and increased affective ratings, suggesting that psychological factors also play a crucial role in how pain is experienced, although sensory ratings remained unchanged.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The physical and psychological experience of pain: the effects of labeling and cold pressor temperature on three pain measures in college women. Hirsch, MS., Liebert, RM.[2021]

The Trier Social Stress Test (TSST) produced significantly higher levels of ACTH and cortisol compared to the Cold Pressor Test (CPT) in a study of 31 subjects, indicating a stronger activation of the HPA axis during social stress.

While the TSST led to lower mood ratings than the CPT, the CPT may still be useful for assessing stress responses in patients with diverse diagnoses, such as PTSD and alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stress reactivity: biological and subjective responses to the cold pressor and Trier Social stressors. McRae, AL., Saladin, ME., Brady, KT., et al.[2022]

The review outlines various methods to induce stress in humans, such as the Trier Social Stress Test and cold pressor test, which are crucial for studying how the body reacts to stress and for developing new treatments.

It also highlights the importance of assessing stress through biochemical markers like cortisol and physiological changes like heart rate and galvanic skin response, providing a comprehensive approach to understanding stress responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experimental stress studies: methods and assessment. Bali, A., Jaggi, AS.[2015]

In a study involving 219 police officers, virtual reality (VR) training was found to induce higher levels of perceived stress compared to a 2D simulator (VirTra V-300) when no pain stimulus was applied.

Adding a pain stimulus during training increased perceived stress in the VirTra simulator but did not enhance the sense of presence or training responses in the VR system, suggesting that VR training is realistic enough on its own.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No pain, no gain? The effects of adding a pain stimulus in virtual training for police officers. Kleygrewe, L., Hutter, RIV., Oudejans, RRD.[2023]

The newly developed automated bilateral feet Cold Pressor Test (CPT) effectively eliminates biases associated with traditional hand immersion methods, such as laterality bias and motor response effects, making it a more reliable tool for stress research.

In a study with 28 healthy male students, the bilateral feet CPT produced significant physiological and subjective stress responses, indicating its validity and feasibility as a stress test that can be used in psychobiological research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of an automated bilateral feet cold pressor test. Bachmann, P., Zhang, X., Larra, MF., et al.[2019]

Acute stress significantly increases cortisol levels and amplifies negative emotions related to decision-making, particularly when comparing actual outcomes to potential alternatives (counterfactuals).

Under stress, individuals are more likely to make decisions that avoid regret, indicating that stress shifts decision-making towards more emotional and intuitive processes rather than rational analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute stress amplifies experienced and anticipated regret in counterfactual decision-making. Wu, Y., van Dijk, E., Li, H.[2021]

Positive emotions can increase pain tolerance and threshold in individuals, including those with substance dependence, indicating that emotional state plays a significant role in pain perception.

The study found that changes in arm temperature did not mediate the relationship between affect and pain modulation, suggesting that non-drug approaches to managing pain could be effective even in people with alcohol or cocaine dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Affective modulation of pain in substance-dependent veterans. Rhudy, JL., Dubbert, PM., Parker, JD., et al.[2014]

In two studies with 24 participants each, it was found that both positive and negative emotions reduce the brain's processing resources for tasks, as indicated by a smaller P3 component in emotional conditions compared to neutral ones.

The results suggest that negative emotions take priority in processing, potentially draining resources needed for task performance, while positive emotions also have a similar but less pronounced effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attentional resource allocation to emotional events: An ERP study. Meinhardt, J., Pekrun, R.[2022]

In a study with 50 college students, positive affect combined with external mental imagery significantly increased pain tolerance during a cold-pressor test, suggesting that mental imagery can effectively reduce pain perception.

The results indicated that the combination of positive affect and external imagery led to the lowest reported pain levels, highlighting the cognitive influence on pain management rather than physiological responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactive effects of the affect quality and directional focus of mental imagery on pain analgesia. Alden, AL., Dale, JA., DeGood, DE.[2022]

In a study involving 90 students (45 women and 45 men), physiological stress (from the Cold Pressor Test) and combined physiological and psychosocial stress did not significantly change risk-taking behavior compared to a no-stress condition, suggesting that the type of stressor may not always influence decision-making under risk.

However, the study found that men generally made riskier decisions than women, and the type of stressor affected this behavior differently for each sex, indicating that both sex and stress type play important roles in decision-making under risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decision making in response to physiological and combined physiological and psychosocial stress. Nowacki, J., Heekeren, HR., Deuter, CE., et al.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

The effects of experimental pain and induced optimism on working memory task performance. [2018]

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

Experimental stressors alter hypertonic saline-evoked masseter muscle pain and autonomic response. [2012]

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

An alternative to the traditional cold pressor test: the cold pressor arm wrap. [2021]

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

Combining mental and physical stress: Synergy or interference? [2021]

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

The physical and psychological experience of pain: the effects of labeling and cold pressor temperature on three pain measures in college women. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Stress reactivity: biological and subjective responses to the cold pressor and Trier Social stressors. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Clinical experimental stress studies: methods and assessment. [2015]

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

No pain, no gain? The effects of adding a pain stimulus in virtual training for police officers. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Validation of an automated bilateral feet cold pressor test. [2019]

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

Acute stress amplifies experienced and anticipated regret in counterfactual decision-making. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Affective modulation of pain in substance-dependent veterans. [2014]

12. England pubmed.ncbi.nlm.nih.gov

Attentional resource allocation to emotional events: An ERP study. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

Interactive effects of the affect quality and directional focus of mental imagery on pain analgesia. [2022]

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

Decision making in response to physiological and combined physiological and psychosocial stress. [2019]