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The aim of the present project is to elucidate the neuropharmacological mechanisms underlying value (choice preference) and attention (choice randomness) processing in humans. More specifically, the investigators test whether dopaminergic, noradrenergic and cholinergic interventions affect neural and behavioral processing of valuation and attention during decision-making. The investigators do this by up-regulating dopaminergic, noradrenergic or cholinergic neurotransmission pharmacologically through administration of methylphenidate, reboxetine, or nicotine. We test the hypothesis that methylphenidate, reboxetine, or nicotine reduce choice randomness and that this effect is underpinned by an effect on attention and/or value processing.
To simultaneously assess and dissociate choice preference and randomness in stable environments, the investigators plan to use two tasks: (1) a variant of the RISKGARP task, a well-established risky decision-making task and (2) a modified Becker-DeGroot-Marshak task that measures choice preference and the width of preference representations with the range of willingness to pay procedure (range-WTP). Note that wider representations should result in more choice randomness. The investigators will assess choice randomness also by repeating the same decision questions several times within each task and by relating the preferences measured by the RISKGARP task to those measured by the range-BDM task by using the same options in both tasks. To assess the impact of changing environments and learning on choice preference and randomness, participants will perform two established exploration/exploitation tasks. One (3) is a foraging task that has been combined with different pharmacological manipulations and the other (4) is a variant of the four-armed bandit task, which allows distinguishing value- or information-based exploration from random choice. Blood and saliva samples may be taken. Blood samples may be used to determine levels of the administrated substances and to assess genetic variation. Saliva samples may be used to determine cortisol and testosterone levels.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dopamine reuptake inhibitor | Experimental | Participants in the dopamine reuptake inhibitor group will be asked to take one pill containing 20 mg methylphenidate 1.5 hours before the experimental session. One hour later (30 minutes before testing begins), participants will be asked to chew a placebo gum. |
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| Noradrenaline reuptake inhibitor | Experimental | Participants in the noradrenaline reuptake inhibitor group will be asked to take one pill containing 4 mg reboxetine 1.5 hours before the experimental session. One hour later (30 minutes before testing begins), participants will be asked to chew a placebo gum. |
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| Cholinergic receptor agonist | Experimental | Participants in the cholinergic receptor agonist group will be asked to take a placebo pill 1.5 hours before the experimental session. One hour later (30 minutes before testing begins), participants will be asked to chew a gum with 2 mg of nicotine. |
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| Placebo | Placebo Comparator | Participants in the placebo group will be asked to take a placebo pill 1.5 hours before the experimental session. One hour later (30 minutes before testing begins), participants will be asked to chew a placebo gum. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylphenidate | Drug | A 20 mg methylphenidate (Ritalin®) is administered only once for the dopamine reuptake inhibitor group. |
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| Measure | Description | Time Frame |
|---|---|---|
| Choice data | Choice data made by participants are measured from the experimental tasks. More specifically, the investigators calculate choice preferences, such as the percentage of trials in which participants chose options with probabilistic outcomes in the RISKGARP task and the bids they made in the Range-WTP task, the percentage of exploitative/explorative choices in the four-armed bandit task, and the leaving time in the foraging task. Moreover, the investigators determine choice sub-optimality, such as the number of choices violating transitivity in the RISKGARP task, the inconsistency of bids in repeated trials in the Range-WTP task, the percentage of selecting the worst option in the four-armed bandit task, and the difference between optimal leaving time and actual leaving time in the foraging task. | All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour. |
| Response time data | Response times are measured from experimental tasks. The investigators calculate how long participants take to make decisions in each trial. | All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour. |
| Measure | Description | Time Frame |
|---|---|---|
| The size of pupil dilation | Pupil size is measured using eye-tracker while participants perform the experimental tasks. Baseline pupil size is also measured before the drug/placebo administration. | Pupil size is measured in the main experimental session before drug/placebo administration and through study completion lasting about 1 hour. |
| Measure | Description | Time Frame |
|---|---|---|
| Computational parameters estimated from experimental data | Computational parameters are estimated from the data of participants during the decision-making tasks. Specifically, mathematical models will be applied to above-mentioned choice data and/or response time data. The estimated parameters reflect choice preference and stochasticity and are complementary to the descriptive measurements mentioned above. For example, utility functions will be estimated and the choice preferences are described by the concavititvity of utility functions. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Philippe Tobler, PhD | University of Zurich | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Zurich | Zurich | 8006 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37639601 | Derived | Doren N, Chung HK, Grueschow M, Quednow BB, Hayward-Konnecke H, Jetter A, Tobler PN. Acetylcholine and noradrenaline enhance foraging optimality in humans. Proc Natl Acad Sci U S A. 2023 Sep 5;120(36):e2305596120. doi: 10.1073/pnas.2305596120. Epub 2023 Aug 28. |
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| ID | Term |
|---|---|
| D008774 | Methylphenidate |
| D000077593 | Reboxetine |
| D000074164 | Nicotine Chewing Gum |
| ID | Term |
|---|---|
| D010648 | Phenylacetates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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This is a double-blind, randomized, placebo-controlled, between-participant study. In this experiment. Participants will receive a preferential dopamine reuptake inhibitor, a selective noradrenaline reuptake inhibitor, a natural nicotinic acetylcholine receptor agonist, or placebo under double-blind conditions.
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All participants will receive the same instructions, and neither they nor the experimenters are informed which drug is used. Participants must take the drug in front of the investigator, to ensure correct intake and compliance.
| Reboxetine | Drug | A 4 mg reboxetine (Edronax®) is administered only once for the noradrenaline reuptake inhibitor group. |
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| Nicotine gum | Drug | A 2 mg nicotine (Nicorette®) gum is administered only once for the cholinergic receptor agonist group. |
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| Placebo pill | Drug | A placebo pill is administered only once. |
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| Placebo gum | Drug | A placebo gum is administered only once. |
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| All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour. |
| D010880 |
| Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009025 | Morpholines |
| D010078 | Oxazines |
| D002638 | Chewing Gum |
| D053149 | Plant Gums |
| D001704 | Biopolymers |
| D011108 | Polymers |
| D046911 | Macromolecular Substances |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D061485 | Tobacco Use Cessation Devices |
| D013812 | Therapeutics |
| D002182 | Candy |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |