Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans
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Theories of instrumental learning are centred on understanding how success and failure are used to improve future decisions. These theories highlight a central role for reward prediction errors in updating the values associated with available actions. In animals, substantial evidence indicates that the neurotransmitter dopamine might have a key function in this type of learning, through its ability to modulate cortico-striatal synaptic efficacy. However, no direct evidence links dopamine, striatal activity and behavioural choice in humans. Here we show that, during instrumental learning, the magnitude of reward prediction error expressed in the striatum is modulated by the administration of drugs enhancing (3,4-dihydroxy-L-phenylalanine; L-DOPA) or reducing (haloperidol) dopaminergic function. Accordingly, subjects treated with L-DOPA have a greater propensity to choose the most rewarding action relative to subjects treated with haloperidol. Furthermore, incorporating the magnitude of the prediction errors into a standard action-value learning algorithm accurately reproduced subjects' behavioural choices under the different drug conditions. We conclude that dopamine-dependent modulation of striatal activity can account for how the human brain uses reward prediction errors to improve future decisions.
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Prediction error signalling is dopamine-dependent in humans.
“This quantity is operationalised within computational models of learning as 'prediction error' (PE) (see Supplemental Information box 1) (2, 4-6) and is dopamine-dependent in humans (7).”
From Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis (2020) · cites this paper as [7]
The signed prediction error indicates whether an outcome is better or worse than expected and plays a crucial role in changing the value allocated to cues, thereby guiding future decisions.
“First, the signed prediction error indicates whether an outcome is better or worse than expected, and thereby plays a crucial role in changing the value allocated to cues, thereby guiding future decisions [14–21].”
From Precision weighting of cortical unsigned prediction error signals benefits learning, is mediated by dopamine, and is impaired in psychosis (2021) · cites this paper as [19]
Functional imaging studies on humans support the model that ventral striatum signals reward prediction errors via dopamine.
“Functional imaging studies on humans support this model (O’Doherty et al., 2003, 2006; Pessiglione et al., 2006).”
From Top-Down Dysregulation—From ADHD to Emotional Instability (2016) · cites this paper as Pessiglione et al., 2006
Studies in healthy human volunteers have shown dopaminergic modulation of the brain response to a reward prediction error response using fMRI.
“Studies in healthy human volunteers have shown dopaminergic modulation of the brain response to a reward prediction error response using fMRI (Bernacer et al. 2013; Eisenegger et al. 2014; Pessiglione et al. 2006).”
From Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder (2019) · cites this paper as Pessiglione et al. 2006
Previous studies have shown that both drugs can exert bidirectional effects on reward prediction error-associated responses.
“Nevertheless, previous studies have shown that both drugs can exert bidirectional effects on reward prediction error–associated responses.”
From Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder (2019) · cites this paper as Pessiglione et al. 2006
Dopamine agonist-like medications have been shown to be capable of enhancing or attenuating reward prediction error-associated responses, with directionality dependent on the particular task, agonist, and dose employed.
“Furthermore, dopamine agonist–like medications have also been shown to be capable of enhancing (Pessiglione et al. 2006) or attenuating (Bernacer et al. 2013) reward prediction error–associated responses, with the directionality of the effect being dependent on the particular task, agonist, and dose employed.”
From Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder (2019) · cites this paper as Pessiglione et al. 2006
The anterior insula is crucially involved in RPE processing.
“Additionally, we hypothesized the anterior insular activity to be altered, because this region is crucially involved in RPE processing (Pessiglione et al., 2006; Seymour et al., 2004; Voon et al., 2010; Wittmann et al., 2008)”
From Cognitive flexibility in adolescence: Neural and behavioral mechanisms of reward prediction error processing in adaptive decision making during development (2015) · cites this paper as Pessiglione et al., 2006
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“Functional imaging studies on humans support this model (O’Doherty et al., 2003, 2006; Pessiglione et al., 2006).”
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- Authors
- Pessiglione, M., Seymour, B., Flandin, G., Dolan, R. J., & Frith, C. D.
- Affiliations
- University College London (GB)
- Wellcome Centre for Human Neuroimaging (GB)
- Corresponding author
- Pessiglione, Mathias
- Venue
- Nature
- Published
- 2006-08
- Volume
- 442
- Issue
- 7106
- Pages
- 1042-1045
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2636869
- OpenAlex
- W2046713808
- Cited by
- 1,584
- References
- 39
- Citations by year
- 2026: 42 · 2025: 50 · 2024: 77 · 2023: 86 · 2022: 57 · 2021: 107 · 2020: 149 · 2019: 64 · 2018: 98 · 2017: 100 · 2016: 91 · 2015: 104 · 2014: 80 · 2013: 86 · 2012: 103
- FWCI
- 18.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- Cambridge University Engineering Department Publications Database (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (078865)
- Fondation Fyssen
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
- Keywords
- dopamine, reward prediction error, reward-seeking behavior, operant conditioning, striatum, L-DOPA, haloperidol, decision-making, gambling
- MeSH terms
- Adult, Algorithms, Behavior, Computer Simulation, Computers, Dopamine, Female, Forecasting, Haloperidol, Humans, Learning, Levodopa, Male, Models, Neurological, Punishment, Reward, Dopamine Agents, Neostriatum, Dopamine Antagonists
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