Dose-response effects of d-amphetamine on effort-based decision-making and reinforcement learning

Abstract

Effort-related decision-making and reward learning are both dopamine-dependent, but preclinical research suggests they depend on different dopamine signaling dynamics. Therefore, the same dose of a dopaminergic medication could have differential effects on effort for reward vs. reward learning. However, no study has tested how effort and reward learning respond to the same dopaminergic medication within subjects. The current study aimed to test the effect of therapeutic doses of d-amphetamine on effort for reward and reward learning in the same healthy volunteers. Participants (n = 30) completed the Effort Expenditure for Reward Task (EEfRT) measure of effort-related decision-making, and the Probabilistic Reward Task (PRT) measure of reward learning, under placebo and two doses of d-amphetamine (10 mg, and 20 mg). Secondarily, we examined whether the individual characteristics of baseline working memory and willingness to exert effort for reward moderated the effects of d-amphetamine. d-Amphetamine increased willingness to exert effort, particularly at low to intermediate expected values of reward. Computational modeling analyses suggested this was due to decreased effort discounting rather than probability discounting or decision consistency. Both baseline effort and working memory emerged as moderators of this effect, such that d-amphetamine increased effort more in individuals with lower working memory and lower baseline effort, also primarily at low to intermediate expected values of reward. In contrast, d-amphetamine had no significant effect on reward learning. These results have implications for treatment of neuropsychiatric disorders, which may be characterized by multiple underlying reward dysfunctions.

Fig. 1. Overall drug effects on the EEfRT.

a Main effect of d-amphetamine on % hard task choices. Error bars represent standard error of the mean. b Probability × amount interaction.

Fig. 2. Computational modeling results on the EEfRT.

a Changes in mean values for parameter k (effort sensitivity) across doses of d-amphetamine. b Changes in mean values for parameter h (probability sensitivity) across doses of d-amphetamine.

Fig. 3. Baseline effort moderator analyses on the EEfRT.

Graphs display one standard deviation below and above the mean baseline effort for visual purposes only. In the analysis, baseline effort was used as a continuous moderator. a % hard task choices by probability in low baseline effort. b % hard task choices by probability in high baseline effort. c % hard task choices by probability and amount in low baseline effort. d % hard choices by probability and amount in high baseline effort.

Fig. 4. Working memory moderator analyses on the EEfRT.

Graphs display low and high working memory for visual purposes only. In the analysis, working memory was used as a continuous moderator. a % hard task choices by probability and amount in low working memory. b % hard task choices by probability and amount in high working memory.