About this trial
This research study aims to determine whether and how caffeine intake affects learning process through reward feedback compared to placebo. The data acquired from this study would improve our understanding on the consequence and mechanism of caffeine intake in the aspect of learning process.
Participants will perform a reinforcement learning task (i.e. Probabilistic Selection Task) and a motor inhibition task (i.e. Go/NoGo task) in a brain scan. The scan will be done with the Siemens Biograph mMR positron emission tomography (PET)/ magnetic resonance imaging (MRI) 3 Tesla scanner. The PET allows us to see the changes in the "reward signals" - dopamine - in the brain using a radioactive dye called \[11C\]Raclopride. The MRI, on the other hand, enables us to take detailed pictures of the brain activities during cognitive tasks using a high-powered magnet. Reviewing these pictures will help us understand the influence of caffeine on reward signals and brain activities during the learning process.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age ≥ 18 and ≤ 45.
Habitual caffeine intake ≥ 100 mg and ≤ 450 mg daily.
Non-smokers.
Clinically healthy.
Disqualifiers
Pregnant or lactating women.
Women using hormonal contraceptives.
BMI < 18.5 or > 29.9
Sleep disturbance or extreme chronotype.
Trial design
Crossover
Treatments tested in this trial
Caffeine (200 mg)
DrugCaffeine (200mg) will be administered per os 20 minutes prior to the PET/fMRI data acquisition.
Placebo
DrugLactose tablet will be administered per os 20 minutes prior to the PET/fMRI data acquisition.
Treatment groups
Trial outcomes
Primary outcomes
Dopamine D2/D3 receptor availability
Dopamine D2/D3 receptor availability will be measured and indexed by the \[11C\]Raclopride nondisplaceable binding potential (BPND).
Effects of caffeine on reinforcement learning assessed by Probabilistic Selection Task (PST) in fMRI
Reinforcement learning and the associated brain activity will be measured using PST in a fMRI scan. The reinforcement learning is indexed by the accuracy of the task performance on the behavioral level and the hemodynamic response to reward feedback on the neural level.
Secondary outcomes
Effects of caffeine on motor inhibition assessed by a Go/NoGo task in fMRI
Motor inhibition and the associated brain activity will be examined using Go/NoGo in a fMRI scan. The reinforcement learning is indexed by the accuracy of the task performance on the behavioral level and the hemodynamic response during the inhibition of motor reactions on the neural level.
Effects of caffeine on salience measured by Salience Attribution Test (SAT)
Participants' salience to reward stimuli linked to the Probabilistic Selection Task will be assessed using Salience Attribution Test. In the task, participants will use a visual analogue scale to indicate their estimation of the reward probability (0 to 100%) of each stimulus they have learned in the task during the scan. The salience will be indicated by the difference between their estimation and the real probability, as well as the contrast between high and low probability in estimation and in reality.
Other outcomes
Effects of caffeine on cerebral blood flow
Cerebral blood flow will be measured using an MR sequence, Arterial Spin Labeling, during the fMRI acquisition and used as a covariate in fMRI analysis. This outcome measurement will be used as a potential covariate in the fMRI analyses to account for the impact of caffeine's vasoconstrictive effects.
Effects of caffeine on subjective sleepiness as measured by Karolinska Sleepiness Scale (KSS)
KSS is a 10-point cale, in which 1 is equivalent to extremely alert, while 10 is equivalent to extremely sleepy. The scale is to measure the participant's sleepiness state, which will be used as a potential covariate in the behavioral analyses.
Effects of caffeine on anxiety levels measured by State-Trait Anxiety Inventory- adult version (STAI-A)
The part of STAI-A that assesses the anxiety level for the moment of answering includes 20 statements, such as "I feel calm", "I feel tense" etc. Participants will use a 4-point scale to answer whether they feel "not at all", "somewhat", "moderately so", or "very much so" to each statement. This outcome measurement will be used as a potential covariate in the behavioral analyses.
Effects of caffeine on fMRI brain connectivity during resting state
As an exploratory outcome, resting-state fMRI sequence will be sued to examine whether caffeine intake will affect brain connectivity.
Sponsors and contacts
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Hsiao-Ying Wey
Lead sponsor
Martinos Center for Biomedical Imaging
Sponsor institution