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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.

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The error-related negativity (ERN or Ne) and positivity (Pe) are event-related potential components elicited during simple discrimination tasks after an error response. The ERN and Pe have a fronto-central scalp distribution and may be an indirect measure of anterior cingulate (AC) activity as it relates to performance monitoring. Brain imaging studies suggest that obsessive-compulsive disorder (OCD) is associated with exaggerated activity of the AC while electrophysiological studies have found an association between OCD and pronounced ERNs in adults. The present study explored the relation between obsessive-compulsive behaviors, the ERN, and the Pe in a sample of nonclinical 10-year-old children. It was found that more parent-reported obsessive-compulsive behaviors were associated with larger ERN and Pe components in the children. Results suggest unique contributions of the ERN and Pe in predicting obsessive-compulsive behaviors.

The anterior cingulate cortex (ACC) is central to evaluating performance outcomes and has been linked to individual differences in affective responses to feedback. We used electrophysiological source localization to examine the feedback-related negativity (FRN) and related ACC activity during a gambling task in relation to punishment and reward sensitivity among 16- to 17-year-old adolescents (n=20) and 18- to 29-year-old adults (n=30). The FRN was larger for monetary loss compared to win feedback and larger for high relative to low monetary value feedback, with no age differences in the FRN for win or loss feedback. Self-reported sensitivity to punishment accounted for unique variance (over sex and sensitivity to reward) in FRNs, with higher scores relating to larger FRNs and increased rostral ACC activity. These results support the ACC role in experiencing negative performance feedback, especially for individuals highly sensitive to punishment.

Coupling between EEG delta and beta oscillations is enhanced among anxious and healthy individuals during anticipatory anxiety. EEG coupling patterns associated with psychotherapy have not yet been quantified in socially anxious individuals. In this study, we used a double baseline, repeated measures design, in which 25 adults with a principal diagnosis of social anxiety disorder completed 12 weekly sessions of standardized group cognitive behavioral therapy and four EEG assessments: two at pretreatment, one at midtreatment, and one at posttreatment. Treatment was associated with reductions in symptom severity across multiple measures and informants, as well as reductions in delta-beta coupling at rest and during speech anticipation. Moreover, the clinical group exhibited greater coupling at pretreatment than did post hoc control participants with low social anxiety. The EEG cross-frequency profiles in the clinical group normalized by the posttreatment assessment. These findings provide evidence of concomitant improvement in neural and behavioral functioning among socially anxious adults undergoing psychotherapy.