Computational modelling and neural correlates of reinforcement learning following three-week escitalopram: a double-blind, placebo-controlled semi-randomised study
Abstract Reinforcement learning is a fundamental aspect of adaptive behaviour, since it involves the acquisition and updating of associations between actions and their outcomes based on the rewarding or punishing consequences. Acute experimental manipulations of serotonin have provided compelling ev...
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Nature Publishing Group
2025-05-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03392-6 |
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| author | Christelle Langley Graham K. Murray Sophia Armand Franziska Knolle Rudolf N. Cardinal Annette Johansen Peter S. Jensen Jianfeng Feng Dea S. Stenbæk Gitte M. Knudsen Patrick M. Fisher Barbara J. Sahakian |
| author_facet | Christelle Langley Graham K. Murray Sophia Armand Franziska Knolle Rudolf N. Cardinal Annette Johansen Peter S. Jensen Jianfeng Feng Dea S. Stenbæk Gitte M. Knudsen Patrick M. Fisher Barbara J. Sahakian |
| author_sort | Christelle Langley |
| collection | DOAJ |
| description | Abstract Reinforcement learning is a fundamental aspect of adaptive behaviour, since it involves the acquisition and updating of associations between actions and their outcomes based on the rewarding or punishing consequences. Acute experimental manipulations of serotonin have provided compelling evidence for its role in reinforcement learning. However, it remains unknown how more chronic manipulation of serotonin, which holds greater clinical relevance, affects reinforcement learning and the underlying neural mechanisms. Consequently, we aimed to investigate the effect of a three-week administration of the SSRI, escitalopram, on a reinforcement learning paradigm during functional magnetic resonance imaging. The study used a double-blind, placebo-controlled design with 64 healthy volunteers. Participants were semi-randomised, ensuring matched groups for age, sex and intelligence quotient (IQ), to receive either 20 mg of escitalopram (n = 32) or placebo (n = 32) for at least 21 days. We analysed group differences in reinforcement learning using both analysis of covariance as well as innovative hierarchical Bayesian modelling of the reinforcement learning task. Escitalopram reduced learning from punishment during punishment trials. A key novel finding was that there was decreased activation of the intraparietal sulcus in the escitalopram group when compared to the placebo group during reward trials. The involvement of the intraparietal sulcus suggests that escitalopram affects the encoding of value outcome, which may lead to reduced reinforcement sensitivity, and thereby impacting adaptive learning from feedback. Understanding these mechanisms may help to optimize SSRI treatment to mitigate clinical symptoms and improve quality of life for neuropsychiatric patients, by elucidating serotonin’s effects on affect, cognition, and behaviour. |
| format | Article |
| id | doaj-art-0c4764f7e8a84a7eade8e5d061073455 |
| institution | OA Journals |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-0c4764f7e8a84a7eade8e5d0610734552025-08-20T02:29:46ZengNature Publishing GroupTranslational Psychiatry2158-31882025-05-011511810.1038/s41398-025-03392-6Computational modelling and neural correlates of reinforcement learning following three-week escitalopram: a double-blind, placebo-controlled semi-randomised studyChristelle Langley0Graham K. Murray1Sophia Armand2Franziska Knolle3Rudolf N. Cardinal4Annette Johansen5Peter S. Jensen6Jianfeng Feng7Dea S. Stenbæk8Gitte M. Knudsen9Patrick M. Fisher10Barbara J. Sahakian11Department of Psychiatry, University of CambridgeDepartment of Psychiatry, University of CambridgeNeurobiology Research Unit, Copenhagen University Hospital RigshospitaletDepartment of Psychiatry, University of CambridgeDepartment of Psychiatry, University of CambridgeNeurobiology Research Unit, Copenhagen University Hospital RigshospitaletNeurobiology Research Unit, Copenhagen University Hospital RigshospitaletInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan UniversityNeurobiology Research Unit, Copenhagen University Hospital RigshospitaletNeurobiology Research Unit, Copenhagen University Hospital RigshospitaletNeurobiology Research Unit, Copenhagen University Hospital RigshospitaletDepartment of Psychiatry, University of CambridgeAbstract Reinforcement learning is a fundamental aspect of adaptive behaviour, since it involves the acquisition and updating of associations between actions and their outcomes based on the rewarding or punishing consequences. Acute experimental manipulations of serotonin have provided compelling evidence for its role in reinforcement learning. However, it remains unknown how more chronic manipulation of serotonin, which holds greater clinical relevance, affects reinforcement learning and the underlying neural mechanisms. Consequently, we aimed to investigate the effect of a three-week administration of the SSRI, escitalopram, on a reinforcement learning paradigm during functional magnetic resonance imaging. The study used a double-blind, placebo-controlled design with 64 healthy volunteers. Participants were semi-randomised, ensuring matched groups for age, sex and intelligence quotient (IQ), to receive either 20 mg of escitalopram (n = 32) or placebo (n = 32) for at least 21 days. We analysed group differences in reinforcement learning using both analysis of covariance as well as innovative hierarchical Bayesian modelling of the reinforcement learning task. Escitalopram reduced learning from punishment during punishment trials. A key novel finding was that there was decreased activation of the intraparietal sulcus in the escitalopram group when compared to the placebo group during reward trials. The involvement of the intraparietal sulcus suggests that escitalopram affects the encoding of value outcome, which may lead to reduced reinforcement sensitivity, and thereby impacting adaptive learning from feedback. Understanding these mechanisms may help to optimize SSRI treatment to mitigate clinical symptoms and improve quality of life for neuropsychiatric patients, by elucidating serotonin’s effects on affect, cognition, and behaviour.https://doi.org/10.1038/s41398-025-03392-6 |
| spellingShingle | Christelle Langley Graham K. Murray Sophia Armand Franziska Knolle Rudolf N. Cardinal Annette Johansen Peter S. Jensen Jianfeng Feng Dea S. Stenbæk Gitte M. Knudsen Patrick M. Fisher Barbara J. Sahakian Computational modelling and neural correlates of reinforcement learning following three-week escitalopram: a double-blind, placebo-controlled semi-randomised study Translational Psychiatry |
| title | Computational modelling and neural correlates of reinforcement learning following three-week escitalopram: a double-blind, placebo-controlled semi-randomised study |
| title_full | Computational modelling and neural correlates of reinforcement learning following three-week escitalopram: a double-blind, placebo-controlled semi-randomised study |
| title_fullStr | Computational modelling and neural correlates of reinforcement learning following three-week escitalopram: a double-blind, placebo-controlled semi-randomised study |
| title_full_unstemmed | Computational modelling and neural correlates of reinforcement learning following three-week escitalopram: a double-blind, placebo-controlled semi-randomised study |
| title_short | Computational modelling and neural correlates of reinforcement learning following three-week escitalopram: a double-blind, placebo-controlled semi-randomised study |
| title_sort | computational modelling and neural correlates of reinforcement learning following three week escitalopram a double blind placebo controlled semi randomised study |
| url | https://doi.org/10.1038/s41398-025-03392-6 |
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