title: Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward.
abstract: 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.
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA 24016; read@vt.edu kenk@vtc.vt.edu.
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Kishida
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA 24016;
authors.forename: Ignacio
authors.initials: I
authors.lastname: Saez
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA 24016;
authors.forename: Terry
authors.initials: T
authors.lastname: Lohrenz
authors.affiliation: Department of Neurosurgery, Wake Forest Health Sciences, Winston-Salem, NC 27157;
authors.forename: Mark R
authors.initials: MR
authors.lastname: Witcher
authors.affiliation: Department of Neurosurgery, Wake Forest Health Sciences, Winston-Salem, NC 27157;
authors.forename: Adrian W
authors.initials: AW
authors.lastname: Laxton
authors.affiliation: Department of Neurosurgery, Wake Forest Health Sciences, Winston-Salem, NC 27157;
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Tatter
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA 24016;
authors.forename: Jason P
authors.initials: JP
authors.lastname: White
authors.affiliation: Department of Neurosurgery, Wake Forest Health Sciences, Winston-Salem, NC 27157;
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ellis
authors.affiliation: Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA 98195; Department of Pharmacology, University of Washington, Seattle, WA 98195;
authors.forename: Paul E M
authors.initials: PE
authors.lastname: Phillips
authors.affiliation: 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 read@vt.edu kenk@vtc.vt.edu.
authors.forename: P Read
authors.initials: PR
authors.lastname: Montague
mesh_terms: D002755:Choice Behavior / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism; D005717:Games, Experimental; D006801:Humans; D008279:Magnetic Resonance Imaging; D010300:Parkinson Disease / Q000378:metabolism; D012201:Reward
chemical_list: D004298:Dopamine
keywords: counterfactual prediction error; decision-making; dopamine; human fast-scan cyclic voltammetry; reward prediction error