Effects of Caffeine on Reinforcement Learning in Healthy Adults Using PET/MRI
NCT ID: NCT06763172
Last Updated: 2025-01-09
Study Results
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Basic Information
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RECRUITING
PHASE4
12 participants
INTERVENTIONAL
2023-05-17
2026-12-31
Brief Summary
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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.
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Detailed Description
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Reinforcement learning, a dopamine-mediated cognitive process crucially involved in various human behaviors including habit, preference, belief, and resistance to change, is often found altered in dopamine-associated disorders. For instance, hyper-dopaminergic function in the striatum, as observed in psychosis, leads to a reduction in reward learning and a blunted task-related neural activity. Through the antagonistic effect of A2AR on D2R signaling, blocking A2AR can potentially enhance D2R-mediated negative reinforcement, a.k.a. a "no-go" response. In rodents, A2AR agonists diminish reinforcement of psychostimulants, while an A2AR antagonist can facilitate reward-seeking effects of reinforcers. Hence, in this double-blind randomized crossover study, the investigators aim to use caffeine, an adenosine antagonist as well as a commonly used psychostimulant by nearly 80% of the worldwide population, to examine whether blocking A2AR will enhance D2R-modulated reinforcement learning/no-go responses through modulating D2R signaling pharmacologically.
The long-term goal of this study is to further the understanding of molecular mechanisms related to A2AR-D2R heterodimers and the clinical potential of modulating A2AR-D2R interactions. Twelve young healthy non-smokers will enroll in this study. Each participant will undergo a caffeine and a placebo condition. In each condition, participants will first go through a 6-day ambulatory washout period where participants will be asked to abstain from caffeinated dietary, alcohol, and drugs, and stay in regular bed- and wakeup time. On day 7, a PET/fMRI scan will take place at noon, and a caffeine or placebo tablet will be administered orally 20 mins prior to the scan.
Simultaneous PET/fMRI will be used to examine the association between the neurochemical changes (i.e., D2/D3R availability as quantified by \[11C\]Raclopride) and the hemodynamic responses (i.e., task-related blood oxygen level-dependent fMRI activity) during reinforcement learning in the caffeine condition compared to placebo. It is hypothesized that enhanced D2/D3R availability mediates the facilitating effect of caffeine on reinforcement learning. Specifically, the investigators expect that caffeine will enhance fMRI responses in reward-related brain regions, and that the increased fMRI response will positively correlate with a change in D2/D3R availability.
Conditions
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Study Design
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RANDOMIZED
CROSSOVER
BASIC_SCIENCE
TRIPLE
Study Groups
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Caffeine
Caffeine tablet, 200mg
Caffeine (200 mg)
Caffeine (200mg) will be administered per os 20 minutes prior to the PET/fMRI data acquisition.
Placebo
Lactose tablet
Placebo
Lactose tablet will be administered per os 20 minutes prior to the PET/fMRI data acquisition.
Interventions
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Caffeine (200 mg)
Caffeine (200mg) will be administered per os 20 minutes prior to the PET/fMRI data acquisition.
Placebo
Lactose tablet will be administered per os 20 minutes prior to the PET/fMRI data acquisition.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Habitual caffeine intake ≥ 100 mg and ≤ 450 mg daily.
* Non-smokers.
* Clinically healthy.
* Have normal vision or corrected to normal vision.
Exclusion Criteria
* Women using hormonal contraceptives.
* BMI \< 18.5 or \> 29.9
* Sleep disturbance or extreme chronotype.
* Urine test positive on one of the following substances: benzoylecgonine, morphine, d-Methamphetamine, d-Amphetamine, Benzodiazepines, Secobarbital, Methadone, Buprenorphine Glucuronide, Nortriptyline, MDMA, Oxycodone, PCP, Propoxyphene, and Cannabis/THC
* Diagnosis of depression, anxiety, psychosis, or neurologic disorders in the last 5 years.
* Heart or cardiovascular diseases.
* Diabetes or other metabolic diseases.
* Under chronic medications, for instance, painkiller and steroid.
* Allergy to lactose (main ingredient of blank control dose)
* Incapable to operate the tasks or comprehend the study information in English.
* Metallic foreign bodies such as cardiac pacemakers, perfusion pumps, aneurysm clips, metallic tattoos anywhere on the body, tattoos near the eye.
* Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions
* Inability to lie flat on scanner bed for about 90 min as assessed by physical examination and medical history (e.g. arthritis)
* Recent exposure to radiation (i.e., PET from other research studies) that, when combined with this study, would be above the allowable limits
* Pregnancy or breastfeeding: A negative serum or urine pregnancy test is required on the day of the PET procedure
* Body weight of \> 300 lbs (weight limit of the MRI scanner table)
18 Years
45 Years
ALL
Yes
Sponsors
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Hsiao-Ying Wey
OTHER
Responsible Party
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Hsiao-Ying Wey
Prof.
Locations
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Athinoula A. Martinos Center for Biomedical Imaging
Charlestown, Massachusetts, United States
Countries
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Central Contacts
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Facility Contacts
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Role: backup
Hsiao-Ying Wey, PhD
Role: backup
Yu-Shiuan Lin, PhD
Role: backup
References
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Bedingfield JB, King DA, Holloway FA. Cocaine and caffeine: conditioned place preference, locomotor activity, and additivity. Pharmacol Biochem Behav. 1998 Nov;61(3):291-6. doi: 10.1016/s0091-3057(98)00092-6.
Moran EK, Culbreth AJ, Kandala S, Barch DM. From neuroimaging to daily functioning: A multimethod analysis of reward anticipation in people with schizophrenia. J Abnorm Psychol. 2019 Oct;128(7):723-734. doi: 10.1037/abn0000461. Epub 2019 Aug 29.
Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Wong C, Ma J, Pradhan K, Tomasi D, Thanos PK, Ferre S, Jayne M. Sleep deprivation decreases binding of [11C]raclopride to dopamine D2/D3 receptors in the human brain. J Neurosci. 2008 Aug 20;28(34):8454-61. doi: 10.1523/JNEUROSCI.1443-08.2008.
Kaasinen V, Aalto S, Nagren K, Rinne JO. Dopaminergic effects of caffeine in the human striatum and thalamus. Neuroreport. 2004 Feb 9;15(2):281-5. doi: 10.1097/00001756-200402090-00014.
Volkow ND, Wang GJ, Logan J, Alexoff D, Fowler JS, Thanos PK, Wong C, Casado V, Ferre S, Tomasi D. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain. Transl Psychiatry. 2015 Apr 14;5(4):e549. doi: 10.1038/tp.2015.46.
Ferre S, Bonaventura J, Tomasi D, Navarro G, Moreno E, Cortes A, Lluis C, Casado V, Volkow ND. Allosteric mechanisms within the adenosine A2A-dopamine D2 receptor heterotetramer. Neuropharmacology. 2016 May;104:154-60. doi: 10.1016/j.neuropharm.2015.05.028. Epub 2015 Jun 4.
Other Identifiers
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IRB2022P001681
Identifier Type: -
Identifier Source: org_study_id
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