Send to

Choose Destination
Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):200-5. doi: 10.1073/pnas.1513619112. Epub 2015 Nov 23.

Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward.

Author information

Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA 24016;
Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA 24016;
Department of Neurosurgery, Wake Forest Health Sciences, Winston-Salem, NC 27157;
Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA 98195; Department of Pharmacology, University of Washington, Seattle, WA 98195;
Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA 24016; Department of Physics, Virginia Tech, Blacksburg, VA 24060; Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, United Kingdom


In the mammalian brain, dopamine is a critical neuromodulator whose actions underlie learning, decision-making, and behavioral control. Degeneration of dopamine neurons causes Parkinson's disease, whereas dysregulation of dopamine signaling is believed to contribute to psychiatric conditions such as schizophrenia, addiction, and depression. Experiments in animal models suggest the hypothesis that dopamine release in human striatum encodes reward prediction errors (RPEs) (the difference between actual and expected outcomes) during ongoing decision-making. Blood oxygen level-dependent (BOLD) imaging experiments in humans support the idea that RPEs are tracked in the striatum; however, BOLD measurements cannot be used to infer the action of any one specific neurotransmitter. We monitored dopamine levels with subsecond temporal resolution in humans (n = 17) with Parkinson's disease while they executed a sequential decision-making task. Participants placed bets and experienced monetary gains or losses. Dopamine fluctuations in the striatum fail to encode RPEs, as anticipated by a large body of work in model organisms. Instead, subsecond dopamine fluctuations encode an integration of RPEs with counterfactual prediction errors, the latter defined by how much better or worse the experienced outcome could have been. How dopamine fluctuations combine the actual and counterfactual is unknown. One possibility is that this process is the normal behavior of reward processing dopamine neurons, which previously had not been tested by experiments in animal models. Alternatively, this superposition of error terms may result from an additional yet-to-be-identified subclass of dopamine neurons.


counterfactual prediction error; decision-making; dopamine; human fast-scan cyclic voltammetry; reward prediction error

Comment in

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center