No abstract

Rationale-The dopaminergic system, particularly D2-like dopamine receptors, has been strongly implicated in reward processing. Animal studies have emphasized the role of phasic dopamine (DA) signaling in reward-related learning, but these processes remain largely unexplored in humans.Objectives-To evaluate the effect of a single, low dose of a D2/D3 agonist-pramipexole-on reinforcement learning in healthy adults. Based on prior evidence indicating that low doses of DA agonists decrease phasic DA release through autoreceptor stimulation, we hypothesized that 0.5 mg of pramipexole would impair reward learning due to presynaptic mechanisms.Methods-Using a double-blind design, a single 0.5 mg dose of pramipexole or placebo was administered to 32 healthy volunteers, who performed a probabilistic reward task involving a differential reinforcement schedule as well as various control tasks.Results-As hypothesized, response bias toward the more frequently rewarded stimulus was impaired in the pramipexole group, even after adjusting for transient adverse effects. In addition, the pramipexole group showed reaction time and motor speed slowing and increased negative affect; however, when adverse physical side effects were considered, group differences in motor speed and negative affect disappeared.Conclusions-These findings show that a single low dose of pramipexole impaired the acquisition of reward-related behavior in healthy participants, and they are consistent with prior evidence suggesting that phasic DA signaling is required to reinforce actions leading to reward. The potential implications of the present findings to psychiatric conditions, including depression and impulse control disorders related to addiction, are discussed.

Background Previous studies investigating attentional biases in social anxiety disorder (SAD) have yielded mixed results. Recent event-related potential (ERP) studies employing the dot-probe paradigm in non-anxious participants have shown that the P1 component is sensitive to visuospatial attention toward emotional faces. We used a dot-probe task in conjunction with high-density ERPs and source localization to investigate attentional biases in SAD. Method Twelve SAD and 15 control participants performed a modified dot-probe task using angry-neutral and happy-neutral face-pairs. The P1 component elicited by face-pairs was analyzed to test the hypothesis that SAD participants would display early hypervigilance to threat-related cues. The P1 component to probes replacing angry, happy or neutral faces was used to evaluate whether SAD participants show sustained hypervigilance or rather decreased visual processing of threat-related cues at later processing stages. Results Compared to controls, SAD participants showed relatively (a) potentiated P1 amplitudes and fusiform gyrus activation to angry-neutral vs. happy-neutral face-pairs; (b) decreased P1 amplitudes to probes replacing emotional (angry and happy) vs. neutral faces; and (c) higher sensitivity (d′) to probes following angry-neutral vs. happy-neutral face-pairs. SAD participants also showed significantly shorter reaction times to probes replacing angry vs. happy faces, but no group differences emerged for reaction time. Conclusions The results provide electrophysiological support for early hypervigilance to angry faces in SAD with involvement of the fusiform gyrus, and reduced visual processing of emotionally salient locations at later stages of information processing, which might be a manifestation of attentional avoidance.

During reinforcement learning, phasic modulations of activity in midbrain dopamine neurons are conveyed to the dorsal anterior cingulate cortex (dACC) and basal ganglia and serve to guide adaptive responding. While the animal literature supports a role for the dACC in integrating reward history over time, most human electrophysiological studies of dACC function have focused on responses to single positive and negative outcomes. The present electrophysiological study investigated the role of the dACC in probabilistic reward learning in healthy subjects using a task that required integration of reinforcement history over time. We recorded the feedback-related negativity (FRN) to reward feedback in subjects who developed a response bias toward a more frequently rewarded (“rich”) stimulus (“learners”) versus subjects who did not (“non-learners”). Compared to non-learners, learners showed more positive (i.e., smaller) FRNs and greater dACC activation upon receiving reward for correct identification of the rich stimulus. In addition, dACC activation and a bias to select the rich stimulus were positively correlated. The same participants also completed a monetary incentive delay (MID) task administered during functional magnetic resonance imaging. Compared to non-learners, learners displayed stronger basal ganglia responses to reward in the MID task. These findings raise the possibility that learners in the probabilistic reinforcement task were characterized by stronger dACC and basal ganglia responses to rewarding outcomes. Furthermore, these results highlight the importance of the dACC to probabilistic reward learning in humans.