The Role of Stress Neuromodulators in Decision Making Under Risk and Selective Attention to Threat

Study Overview
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Brief Summary
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Incidental affective states, i.e., affective states can influence decision making and selective attention to threatening information. Acute stress is such an affective state and is a powerful contextual modulator of decision-making processes and selective attention to threat. In terms of physiological and neurohormonal changes, the stress response has been well characterized: Exposure to stress elicits an array of autonomic, endocrine, and behavioral responses. The physiological stress response is mediated by the hypothalamic-pituitary-adrenal (HPA) axis and the locus coeruleus noradrenergic (LC-NA) system with cortisol and norepinephrine (NE) as their end products. There is compelling evidence that the stress hormones cortisol and NE influence cognitive processes. However, only very few studies so far used pharmacological approaches to specify the role of stress neuromodulators on decision making and selective attention to threat and these studies are hardly comparable due to differences in the experimental design, e.g., the decision making task used. Furthermore, the neural underpinnings of stress effects on decision making and selective attention to threat are uninvestigated so far. The aim of the proposed project is to clarify the role of the major stress neuromodulators, NE and cortisol, in their contribution to different processes related to decision making under risk and selective attention to threat. To this end, combined precise pharmacological stimulation, behavioral modeling, and fMRI methods will be applied to systematically disentangle the effects of stress hormones on risk attitudes and loss aversion as well as their relation to neural correlates of processing subjective value and risk. Using pharmacological manipulation, the influence of noradrenergic and glucocorticoid activity on decision making under risk at the behavioral, computational, and neural level will be investigated. In addition, the influence of noradrenergic and glucocorticoid activity on selective attention to threat at the behavioural and neural level using a dot-probe paradigm with fearful and neutral faces will be examined. Participants are randomly assigned to one of four groups: (A) yohimbine, (B) hydrocortisone, (C) yohimbine and hydrocortisone, or (D) placebo.

Official Title
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The Role of Stress Neuromodulators in Decision Making Under Risk

Conditions
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Placebo, Yohimbine, Hydrocortisone, Yohimbine + Hydrocortisone

Intervention / Treatment
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* Drug: Yohimbine
* Drug: Hydrocortisone
* Drug: Yohimbine + Hydrocortisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Right-handed High-school diploma Exclusion Criteria: Former and present DSM-5 axis I disorders according to the Structured Clinical Interview for DSM (SCID) Permanent medication of any kind Medical conditions associated with adrenal dysfunction or well-known impact on HPA activity or cognitive function Steroid use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Yohimbine<br>10 mg | Drug: Yohimbine<br>* Effects on neural correlates of decision-making under risk and selective attention to threat<br>* Other names: Pill (oral administration);|
| Active Comparator: Hydrocortisone<br>10 mg | Drug: Hydrocortisone<br>* Effects on neural correlates of decision-making under risk and selective attention to threat<br>* Other names: Pill (oral administration);|
| Active Comparator: Yohimbine + Hydrocortisone<br>10 mg each | Drug: Yohimbine + Hydrocortisone<br>* Effects on neural correlates of decision-making under risk and selective attention to threat<br>* Other names: Pill (oral administration);|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Effects on neural correlates of decision-making under risk and selective attention to threat<br>* Other names: Pill (oral administration);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk and loss-aversion, choice consistency | Behavioural outcome of the decision-making under risk task modeled using prospect theory (PT) | 45 minutes | 
| Patch-leaving times | Behavioural outcome of the decision-making under risk task including a foraging task part using marginal value theory | 45 minutes | 
| Attentional bias to fearful faces | Behavioural outcome of the dot-probe task | 12 minutes | 
| Blood-oxygen-level-dependent (BOLD) response | In both tasks | 45 + 12 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Salivary cortisol | Treatment check | 3 hours | 
| Salivary alpha amylase | Treatment check | 3 hours | 
| Systolic and diastolic blood pressure | Treatment check | 3 hours | 
| Heart rate | Treatment check | 3 hours |