Serotonergic Modulation of Prefrontal Cortex during Negative Feedback in Probabilistic Reversal Learning
Open accessAbstract
This study used functional magnetic resonance imaging to examine the effects of acute tryptophan (TRP) depletion (ATD), a well-recognized method for inducing transient cerebral serotonin depletion, on brain activity during probabilistic reversal learning. Twelve healthy male volunteers received a TRP-depleting drink or a balanced amino-acid drink (placebo) in a double-blind crossover design. At 5 h after drink ingestion, subjects were scanned while performing a probabilistic reversal learning task and while viewing a flashing checkerboard. The probabilistic reversal learning task enabled the separate examination of the effects of ATD on behavioral reversal following negative feedback and negative feedback per se that was not followed by behavioral adaptation. Consistent with previous findings, behavioral reversal was accompanied by significant signal change in the right ventrolateral prefrontal cortex (PFC) and the dorsomedial prefrontal cortex. ATD enhanced reversal-related signal change in the dorsomedial PFC, but did not modulate the ventrolateral PFC response. The ATD-induced signal change in the dorsomedial PFC during behavioral reversal learning extended to trials where subjects received negative feedback but did not change their behavior. These data suggest that ATD affects reversal learning and the processing of aversive signals by modulation of the dorsomedial PFC.
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In humans, transient cerebral serotonin depletion affects processing of negative feedback during reversal learning.
“In humans, transient cerebral serotonin depletion affects processing of negative feedback during reversal learning107.”
From Cognitive and behavioural flexibility: Neural mechanisms and clinical considerations (2021) · cites this paper as [107]
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- Authors
- Evers, E. A. T., Cools, R., Clark, L., van der Veen, F. M., Jolles, J., Sahakian, B. J., & Robbins, T. W.
- Affiliations
- University of Cambridge (GB)
- Maastricht University (NL)
- Addenbrooke's Hospital (GB)
- Corresponding author
- Cools, Roshan
- Venue
- Neuropsychopharmacology
- Published
- 2005-02-02
- Volume
- 30
- Issue
- 6
- Pages
- 1138-1147
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2116892542
- Cited by
- 208
- References
- 9
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 10 · 2020: 6 · 2019: 10 · 2018: 5 · 2017: 12 · 2016: 3 · 2015: 6 · 2014: 12 · 2013: 9 · 2012: 14
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Wellcome Trust
- ZonMw
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- serotonin, tryptophan depletion, probabilistic reversal learning, negative feedback, dorsomedial prefrontal cortex, ventrolateral prefrontal cortex, prefrontal cortex activation
- MeSH terms
- Adolescent, Adult, Affect, Amino Acids, Biofeedback, Psychology, Brain Mapping, Double-Blind Method, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Oxygen, Psychomotor Performance, Reinforcement, Psychology, Reversal Learning, Serotonin, Tryptophan, Prefrontal Cortex, Cross-Over Studies
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