Does Caffeine Facilitate Human Reward Learning Behaviors?

Study Overview
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Brief Summary
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Learning from the rewards is underlying the formulation of knowledge and habits in daily life. Caffeine is the most commonly used psychoactive substance that could change one's mind state by affecting the brain and nervous system. By such effects, caffeine enhances reward signals - dopamine - in human brains. In this research study, we will find out whether taking caffeine acutely or daily can enhance reward learning processes.

Detailed Description
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Reward learning is associated with the formulation of habits, memories, and beliefs. Positive (receiving an unexpected reward) and negative reinforcement (eliminating an unwanted state) learning are primarily modulated by striatal dopamine D1 and D2 receptors. While caffeine, a psychostimulant regularly consumed by 80% worldwide population, is known to facilitate striatal dopamine signaling, the potential of caffeine on enhancing reward learning in humans remains unknown. In this double-blind, randomized, crossover study, 36 young healthy non-smoking habitual caffeine consumers (daily dose 100 - 450 mg) who are aged between 18 and 40 will be examined. Each of the 36 participants (18 F, 18 M) will undergo an acute caffeine condition, a daily caffeine condition, and a daily placebo condition. Each condition consists of 7 days - 6 ambulatory days followed by 1 laboratory visit. In the ambulatory part, participants will abstain from caffeine, nicotine, medications, and recreational drugs. Compliance to the interventions and abstinence of caffeine will be monitored by salivary caffeine concentration every day. Bedtime and sleep quality will be recorded in sleep diary. On the laboratory visit, participants will perform cognitive tasks on a 2.5h task battery, which includes a probabilistic selection task, a motor inhibition task, and a salience attribution test. We also measure their arousal and anxiety levels 1h after the second intake on the laboratory visit. We will use Bayes factor analyses to test our confirmatory hypotheses (on the primary outcomes): 1) Caffeine enhances the accuracy of reward learning; 2) Daily intake of caffeine facilitates the negative reinforcement compared to acute its intake. On the secondary outcomes, we examine the exploratory hypotheses that caffeine enhances motor inhibition and motivational salience. Arousal and anxiety levels will be examined as a covariate which potentially contribute to the caffeine-induced changes in reward learning performance.

Official Title
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Caffeine and Reward Learning: Characterizing Behavioral Expression of Adenosine-Dopamine Interaction

Conditions
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Caffeine

Intervention / Treatment
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* Dietary Supplement: caffeine
* Dietary Supplement: mannitol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and ≤ 40 Clinically healthy Non-smokers Exclusion Criteria: Habitual caffeine intake < 100 mg or > 450 mg Pregnant or lactating women Women using hormonal contraceptives BMI < 18.5 or > 29.9 Sleep disturbance or extreme chronotypes Nicotine or recreational drug users Depression, anxiety, psychosis, or neurologic disorders Severe heart or cardiovascular diseases Diabetes or metabolic diseases Under chronic medications Incapable to operate the tasks or comprehend the study information in German or English Users of the Bopomo alphates utilized as stimuli in the reward learning tasks Current enrolment in other clinical trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>7 days placebo intake. | Dietary Supplement: mannitol<br>* two doses per day: 200 mg in the morning & 100 mg in the afternoon<br>|
| Active Comparator: Acute caffeine<br>6 days placebo followed by 1 day caffeine intake. | Dietary Supplement: caffeine<br>* two doses per day: 200 mg caffeine in the morning; 100 mg caffeine in the afternoon<br>Dietary Supplement: mannitol<br>* two doses per day: 200 mg in the morning & 100 mg in the afternoon<br>|
| Experimental: Daily caffeine<br>7 days caffeine intake | Dietary Supplement: caffeine<br>* two doses per day: 200 mg caffeine in the morning; 100 mg caffeine in the afternoon<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The accuracy (% of correct answers) in implicit learning through different probabilities of monetary reward feedback | Through a probabilistic selection task, participant will go through a training phase to learn the rules which options may be more likely to return monetary feedback, and the knowledge learned will be tested in a second phase where the task difficulty is increased, and no feedback is provided. The overall accuracy in the testing phases will be examined, as well as the accuracies in choosing or avoiding the highest and lowest reward-probability stimuli. | 1-hour after the second intake on the 7th day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The errors in motor inhibition (rates of false alarm) in a motor inhibition task | Through a reaction-inhibition task (Go/NoGo), participants will go through two phases of the task: 1) Only respond to a specific stimulus when it shows; 2) Respond to all stimuli except for the specific stimulus. The accuracy in motor inhibition will be indicated by the errors made in the no-go signals (i.e. false alarm). | 1.5-hour after the second intake on the 7th day | 
| Salience attribution behaviors | subjective perception towards the probabilities (0 -100%) of reward feedback from each choice in the probabilistic selection task. | 1.5-hour after the second intake on the 7th day |