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Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans

Abstract

Theories of instrumental learning are centred on understanding how success and failure are used to improve future decisions1. These theories highlight a central role for reward prediction errors in updating the values associated with available actions2. 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 efficacy3. 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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Figure 1: Experimental task and behavioural results.
Figure 2: Statistical parametric maps of prediction error and stimulus-related activity.
Figure 3: Time course of brain responses reflecting prediction errors.

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Acknowledgements

We thank K. Friston for discussions, B. Draganski for assistance in the double-blind procedure, and J. Daunizeau for assistance in the statistical analysis. This work was funded by the Wellcome Trust research programme grants. M.P. received a grant from the Fyssen Foundation.

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Correspondence to Mathias Pessiglione.

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Pessiglione, M., Seymour, B., Flandin, G. et al. Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans. Nature 442, 1042–1045 (2006). https://doi.org/10.1038/nature05051

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