Striatal dopamine modulates reward-reinforced temporal learning in humans.

The neurobiological mechanisms underlying human time perception remain elusive. Evidence has consistently linked striatal dopamine to timing behaviors, but it is still uncertain how rapid changes in dopamine may modulate human time perception. Many tasks designed to measure time perception utilize instrumental conditioning paradigms that reinforce correctly timed intervals. In these tasks, subjects are shown to improve their performance following repeated presentations of temporal cues - a phenomenon known as temporal learning. We sought to determine the association between rapid changes in human dopamine levels and temporal learning on an interval timing task that tested the reproduction of 1000ms, 3000ms, and 5000ms intervals in the presence and absence of monetary reinforcement. We utilized human voltammetry to measure real-time dopamine concentrations from the striatum of patients with Parkinsons disease while they performed the interval timing task. We first compared task behavior between patients with Parkinsons disease and neurologically healthy controls and found significant differences in the reproduction of 1000ms intervals, but not 3000ms or 5000ms intervals of time. Further, we observed that during 1000ms intervals, increases in striatal dopamine concentrations were associated with increases in temporal errors, but only during the expectation of monetary reinforcement. We also demonstrated that as temporal errors decrease overtime during temporal learning, so do striatal dopamine concentrations. These results suggest that dopamine may be driving temporal learning through the generation of temporal errors in response to positive reinforcement. These findings may have significant implications in our understanding of the role that dopamine plays in time perception. Significance StatementHuman time perception is a fundamental cognitive ability but the interaction between how the human brain perceives time and dopamines role is unclear. This study is the first of its kind to apply human voltammetry to measure rapid changes in dopamine levels associated with temporal learning in the presence and absence of positive reinforcement. We demonstrate that temporal learning may be affected by moment-to-moment changes in dopamine levels, which are also counterintuitively related to the generation of temporal errors in the presence of expectations of rewarding feedback.