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


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 con-tribute to psychiatric conditions such as schizophrenia, addiction, and depression. Experiments in animal models suggest the hypothesis that dopamine release in human striatum encodes re-ward 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 measure-ments cannot be used to infer the action of any one specific neuro-transmitter. We monitored dopamine levels with subsecond temporal resolution in humans (n = 17) with Parkinson’sdiseasewhilethey 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 pro-cess is the normal behavior of reward processing dopamine neurons, which previously had not been tested by experiments in animal mod-els. Alternatively, this superposition of error terms may result from an additional yet-to-be-identified subclass of dopamine neurons.

Proceedings of the National Academy of Sciences