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Approach versus avoidance decisions are at the centre of adaptive behaviour and survival. These decisions are thought to be guided by the value of the choice options, which are a function of the magnitude of predicted rewards and punishments. Moreover, the allocation of attention to choice options is thought to be driven by salience, i.e. the overall importance of the predicted outcomes. While salience increases with the magnitude of both predicted rewards and predicted punishments, value increases with reward but decreases with punishment. In previous research, value and salience have often remained confounded during value-based decision making. Rodent research suggests that value is associated with dopamine and salience with norepinephrine. The present study aims at disentangling value from salience processing during decision-making tasks in healthy subjects by administering dopamine or noradrenaline reuptake inhibitors. This is done by using a single dose challenge in a randomized placebo-controlled between subject's design, administering either methylphenidate (35 mg), reboxetine (8 mg), or placebo to healthy young participants before they perform tasks tapping into various aspects of value and salience.
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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 35 mg methylphenidate 1.5 hours before performing the tasks. |
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| Noradrenaline reuptake inhibitor | Experimental | Participants in the noradrenaline reuptake inhibitor group will be asked to take one pill containing 8 mg reboxetine 1.5 hours before performing the tasks. |
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| Placebo | Placebo Comparator | Participants in the placebo group will be asked to take a placebo pill 1.5 hours before performing the tasks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylphenidate | Drug | 35 mg methylphenidate (Ritalin®) is administered once using a randomized placebo-controlled between subject's design |
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| Measure | Description | Time Frame |
|---|---|---|
| Response time data | The investigators record responses and specifically reaction times during 5 different decision-making tasks. In a value vs salience task, value and salience processing is disentangled during value-based decision-making. Participants either accept or reject compound stimuli that were before associated with monetary outcomes. In a face in the crowd task, participants detect a target face (angry vs happy) in a crowd of opposite face type. During a task on risk and ambiguity decision-making, participants have to decide between safe and lottery options associated with either monetary risk or ambiguity. In an adaptive risk-taking task, participants have to choose between two risky monetary options. In an effort task, participants decide whether they are willing to exert physical effort for monetary reward. Response times are measured in milliseconds from the tasks. The investigators calculate how long participants take to make decisions in each trial. | These tasks take place 1,5 hours after the drug was administered |
| Choice data | As a dependent variable the investigators record responses and specifically choices made during the above-mentioned different decision-making tasks. The investigators evaluate what kind of answers were made during each trial of the decision-making tasks, in respect to correctness or preference (percentage). | These tasks take place 1,5 hours after the drug was administered |
| Measure | Description | Time Frame |
|---|---|---|
| Computational modelling applied to choice data | Computational parameters are mathematically estimated from the data of participants during the above-mentioned decision-making tasks. Specifically, mathematical models will be applied to choice data (percentage). | These tasks take place 1,5 hours after the drug was administered |
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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 |
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| ID | Term |
|---|---|
| D008774 | Methylphenidate |
| D000077593 | Reboxetine |
| ID | Term |
|---|---|
| D010648 | Phenylacetates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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The investigators implement a randomized, double-blind, placebo-controlled between-subjects design, using one factor (pharmacological intervention) with three levels (reboxetine, methylphenidate and placebo).
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All participants will receive the same instructions, and neither the participants 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.
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| Reboxetine | Drug | 8 mg Reboxetine (Edronax®) is administered once using a randomized placebo-controlled between subject's design |
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| Placebos | Drug | A placebo pill is administered once using a randomized placebo-controlled between subject's design |
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| Computational modelling applied to response time data |
Computational parameters are mathematically estimated from the data of participants during the above-mentioned decision-making tasks. Specifically, mathematical models will be applied to response time data (milliseconds). |
| These tasks take place 1,5 hours after the drug was administered |
| D010880 |
| Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009025 | Morpholines |
| D010078 | Oxazines |