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 decisions. These theories highlight a central role for reward prediction errors in updating the values associated with available actions. 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 efficacy. 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.

Figure 1

Experimental task and behavioural results. a, Experimental task. Subjects selected either the upper or lower of two abstract visual stimuli presented on a display screen, and subsequently observed the outcome. In this example, the chosen stimulus is associated with a probability of 0.8 of winning £1 and a probability of 0.2 of winning nothing. Durations of the successive screens are given in milliseconds. b, Behavioural results. Left: observed behavioural choices for initial placebo (grey), superimposed over the results from the subsequent drug groups: L-DOPA (green) and haloperidol (red). The learning curves depict, trial by trial, the proportion of subjects that chose the ‘correct’ stimulus (associated with a probability of 0.8 of winning £1) in the gain condition (circles, upper graph), and the ‘incorrect’ stimulus (associated with a probability of 0.8 of losing £1) in the loss condition (squares, lower graph). Right: modelled behavioural choices for L-DOPA (green) and haloperidol (red) groups. The learning curves represent the probabilities predicted by the computational model. Circles and squares representing observed choices have been left for the purpose of comparison. All parameters of the model were the same for the different drug conditions, except the reinforcement magnitude R, which was estimated from striatal BOLD response.

Figure 2

I Statistical parametric maps of prediction error and stimulus-related activity. Coronal slices (bottom) were taken at local maxima of interest indicated by red arrows on the axial projection planes (top). Areas shown in grey on axial planes and in orange or yellow on coronal slices showed significant effect after family-wise error correction for multiple comparisons (P , 0.05). a, Brain activity correlated with prediction errors derived from the computational model. Reward prediction errors (positive correlation) were found by conjunction of gain and loss conditions (left panels), whereas punishment prediction errors (negative correlation) were found in the loss condition alone (right panel). From left to right, MNI (Montreal Neurological Institute) coordinates are given for the maxima found in the left posterior putamen, left ventral striatum and right anterior insula. b, Statistical parametric maps resulting from main contrasts between stimuli conditions. Go and NoGo refer to stimuli position requiring, or not requiring, a button press to get the optimal outcome. Gain, neutral and loss correspond to the different pairs of stimuli. As above, the maxima shown are located in the left posterior putamen, left ventral striatum and right anterior insula, from left to right.

Figure 3

Time course of brain responses reflecting prediction errors. Time courses were averaged across trials throughout the entire learning sessions. Error bars are inter-subject s.e.m. a, Overlaid positive (grey circles) and negative (black squares) reward prediction errors in the striatum for both L-DOPA-treated and haloperidol-treated groups, and in both gain and loss trials. b, Overlaid positive (black squares) and negative (grey circles) punishment prediction errors in the right anterior insula, during the loss trials.