Academic journal article Cognitive, Affective and Behavioral Neuroscience

Computational Heterogeneity in the Human Mesencephalic Dopamine System

Academic journal article Cognitive, Affective and Behavioral Neuroscience

Computational Heterogeneity in the Human Mesencephalic Dopamine System

Article excerpt

Published online: 13 August 2013

© The Author)s) 2013. This article is published with open access at

Abstract Recent evidence in animals has indicated that the mesencephalic dopamine system is heterogeneous anatomi- cally, molecularly, and functionally, and it has been suggested that the dopamine system comprises distinct functional sys- tems. Identifying and characterizing these systems in humans will have widespread ramifications for understanding drag addiction and mental health disorders. Model-based studies in humans have suggested an analogous computational het- erogeneity, in which dopaminergic targets in striatum encode both experience-based learning signals and counterfactual learning signals that are based on hypothetical information. We used brainstem-tailored fMRI to identify mesencephalic sources of experiential and counterfactual learning signals. Participants completed a decision-making task based on investing in markets. This sequential investment task generat- ed experience-based learning signals, in the form of temporal difference (TD) reward prediction errors, and counterfactual learning signals, in the form of "fictive errors." Fictive errors are reinforcement learning signals based on hypothetical in- formation about "what could have been." An additional learn- ing signal was constructed to be relatable to a motivational salience signal. Blood oxygenation level dependent responses in regions of substantia nigra (SN) and ventral tegmental area (VTA), where dopamine neurons are located, coded for TD and fictive errors, and additionally were related to the moti- vational salience signal. These results are highly consistent with animal electrophysiology and provide direct evidence that human SN and VTA heterogeneously handle important reward-harvesting computations.

Keywords Decisionmaking * Dopamine * Reward * Reinforcement learning * Brainstem fMRI * SN * VTA

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Current theories of dopamine function posit a single compu- tational role for dopamine neurons in communicating errors in reward prediction to target brain regions (Bayer & Glimcher, 2005; Montague, Dayan, & Sejnowski, 1996; Schultz, Dayan, & Montague, 1997). Recent empirical work in animals has shown that dopamine neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) are hetero- geneous, with anatomical, molecular, and-importantly- functional differences (Brischoux, Chakraborty, Brierley, & Ungless, 2009; Joshua, Adler, Rosin, Vaadia, & Bergman, 2008; Lammel et al., 2008; Matsumoto & Hikosaka, 2009; for a review, see Roeper, 2013).

Functional differences have been examined in both rodents and nonhuman primates. In rodents, some dopamine neurons were shown to phasically respond to aversive events (Brischoux et al., 2009), which dopamine neurons were ex- plicitly thought not to do (Ungless, Magill, & Bolam, 2004). In nonhuman primates, as well, dopamine neurons have been identified that respond phasically to aversive events but also to cues predicting those aversive events. These dopamine neurons were mainly located dorsolaterally within the SNc, relative to dopamine neurons that fired according to reward prediction error theory (Matsumoto & Hikosaka, 2009). This distinction has been interpreted as a functional gradient span- ning the VTA and SNc, as opposed to anatomically discrete groups of dopamine neurons with different functional proper- ties. The dopamine neurons responding to aversive events have been posited to encode a motivational salience signal, which can be used for more efficient reward harvesting (Kakade & Dayan, 2002), instead of just coding for reward prediction errors (Bromberg-Martin, Matsumoto, & Hikosaka, 2010; Matsumoto & Hikosaka, 2009).

On the basis of this emerging animal literature illuminating heterogeneity in the dopamine system, it has been hypothe- sized that multiple dopamine systems, with different firing properties and different efferent projections (Lammel et al. …

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