High reward expectancy during methylphenidate depresses the dopaminergic response to gain and loss

Abstract

Dopamine plays an important role in goal-directed behavior, through its modulatory influence on striatal neurons. It is unclear whether tonic dopamine levels, which regulate the vigor of acting, interact with the phasic dopamine response to reward that drives instrumental behavior. In a randomized placebo-controlled study in healthy volunteers, we show that methylphenidate, a drug that increases tonic dopamine levels, systematically reduced striatal phasic BOLD responses to gain and loss in a gambling task as measured with fMRI. It also increased response vigor and reward expectancy-related BOLD signals in the ventral striatum. These findings suggest that striatal tonic dopamine levels constitute an average reward expectation signal that modulates the phasic dopaminergic response to reward. This offers opportunities for treatment of behavioral disorders associated with abnormal reward sensitivity.

Keywords: Pharmacological fMRI; dopamine; feedback; gambling.

Fig. 1.

During fMRI scanning participants performed a gambling task with the intent to win as many points as possible. A fixation cross was presented for 0.5 s followed by the numbers ‘5’ and ‘25’ (choice cue). The left/right position of these cues was randomized. Participants chose a number by pressing the corresponding button. One second later, the boxes around the numbers turned both green (indicating gain) and both red (indicating loss) and stayed on the screen for 1.5 s. The intertrial interval was 3 s plus RT. When participants chose ‘5’, they could gain or lose 5 (80% of trials, expected small gain or loss), 7 (10%, unexpected small gain or loss) or 125 points (10%, unexpected large gain or loss); when they chose ‘25’, they could win or lose 25 (80%, expected small gain or loss), 27 (10%, unexpected small gain or loss), or 125 points (10%, unexpected large gain or loss). In the present example, the participant chose ‘5’, and gained 125 points. The color bar below indicated the total amount of points collected so far.

Fig. 2.

The average reaction time (in ms) on the next trial for the different gain and loss events, during placebo and MPH (with SDs).

Fig. 3.

A shows the ventral striatal cluster for which the BOLD response is positively correlated with the RPE in the placebo condition (model 1), and B shows the ventral striatal cluster for which the BOLD response correlates positively with the RPE history during placebo (model 3). Both clusters are shown at coronal slices at x = 15.

Fig. 4.

The average percentage signal change (n = 20) with SEM across the two ventral striatal clusters (A) (coronal slices at x = 15) for Choice (B) and for the different types of feedback (C) during the placebo and MPH session (model 4).