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Bogdan, Ryan

During reinforcement learning, phasic modulations of activity in midbrain dopamine neurons are conveyed to the dorsal anterior cingulate Cortex (dACC) and basal ganglia (BG) 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 BG 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 BG responses to rewarding outcomes. Furthermore, these results highlight the importance of the dACC to probabilistic reward learning in humans.

Background. Anhedonia and stress sensitivity have been identified as promising depressive phenotypes. Research suggests that stress-induced anhedonia is a possible mechanism underlying the association between stress and depression. The present proof-of-concept study assessed whether hedonic capacity and stress perception are heritable and whether their genetic and environmental contributions are shared. Method. Twenty monozygotic (MZ) and 15 dizygotic (DZ) twin pairs completed a probabilistic reward task that provides an objective behavioral measure of hedonic capacity (reward responsiveness) and completed several questionnaires including the Perceived Stress Scale (PSS). Bivariate Cholesky models were used to investigate whether covariation between (1) depressive symptoms and hedonic capacity, (2) depressive symptoms and perceived stress, and (3) perceived stress and hedonic capacity resulted from shared or residual genetic and environmental factors. Results. Additive genetic (A) and individual-specific environment (E) factors contributed to 46% and 54% of the variance in hedonic capacity, respectively. For perceived stress, 44% and 56%, of the variance was accounted for by A and E factors, respectively. The genetic correlation between depression and hedonic capacity was moderate (r(a)=0.29), whereas the correlation between depression and stress perception was large (r(a)=0.67). Genetic and environmental correlations between hedonic capacity and stress perception were large (r(a)=0.72 and r(e)= -0.43). Conclusions. The present study provides initial feasibility for using a twin approach to investigate genetic contributions of a laboratory-based anhedonic phenotype. Although these preliminary findings indicate that hedonic capacity and perceived stress are heritable, with substantial shared additive genetic contributions, replications in larger samples will be needed.

Incentive delay tasks implicate the striatum and medial frontal cortex in reward processing. However, prior studies delivered more rewards than penalties, possibly leading to unwanted differences in signal-to-noise ratio. Also, whether particular brain regions are specifically involved in anticipation or consumption is unclear. We used a task featuring balanced incentive delivery and an analytic strategy designed to identify activity specific to anticipation or consumption. Reaction time data in two independent samples (n = 13 and n = 8) confirmed motivated responding. Functional magnetic resonance imaging revealed regions activated by anticipation (anterior cingulate) versus consumption (orbital and medial frontal cortex). Ventral striatum was active during reward anticipation but not significantly more so than during consumption. Although the study features several methodological improvements and helps clarify the neural basis of incentive processing, replications in larger samples are needed.

Preclinical studies suggest that stress exerts depressogenic effects by impairing hedonic capacity, in humans, however, the precise mechanisms linking stress and depression are largely unknown. As an initial step towards better understanding the association between stress and anhedonia, the present study tested, in two independent samples, whether individuals reporting elevated stress exhibit decreased hedonic capacity. The Perceived Stress Scale (PSS) measured the decree to which participants appraised their daily life as unpredictable, uncontrollable, and overwhelming. Hedonic capacity was objectively assessed using a signal-detection task based on a differential reinforcement schedule. Decreased reward responsiveness (i.e., the participants propensity to modulate behavior as a function of reward) was used as an operational measure of hedonic capacity. In both Study 1 (n = 88) and Study 2 (n = 80), participants with high PSS scores displayed blunted reward responsiveness and reported elevated anhedonic symptoms. Additionally, PSS scores predicted reduced reward responsiveness even after controlling for general distress and anxiety symptoms. These findings are consistent with preclinical data highlighting links between stress and anhedonia, and offer promising insights into potential mechanisms linking stress to depression.