Effects of PPP1R1B (DARPP-32) Polymorphism on Feedback-Related Brain Potentials Across the Life Span

Maximizing gains during probabilistic reinforcement learning requires the updating of choice – outcome expectations at the time when the feedback about a specific choice or action is given. Extant theories and evidence suggest that dopaminergic modulation plays a crucial role in reinforcement learning and the updating of choice – outcome expectations. Furthermore, recently a positive component of the event-related potential about 200 ms (P2) after feedback has been suggested to reflect such updating. The efficacy of dopaminergic modulation changes across the life span. However, to date investigations of age-related differences in feedback-related P2 during reinforcement learning are still scarce. The present study thus aims to investigate whether individual differences in the feedback-related P2 would be associated with polymorphic variations in a dopamine relevant gene PPP1R1B (also known as DARPP-32) and whether the genetic effect may differ between age groups. We observed larger P2 amplitudes in individuals carrying the genotype associated with higher dopamine receptor efficacy, i.e., a allele homozygotes of a single nucleotide polymorphism (rs907094) of the PPP1R1B gene. Moreover, this effect was more pronounced in children and older adults in comparison to adolescents and younger adults. Together, our findings indicate that polymorphic variations in a dopamine relevant gene are associated with individual differences in brain-evoked potentials of outcome updating and hint at the possibility that genotype effects on neurocognitive phenotypes may vary as a function of brain maturation and aging

Sexual Differentiation of the Prefrontal Cortex in Humans: Examining Behavioural Sex Differences and the Modulatory Role of Androgens

Sex hormones are important factors in the establishment of sex differences in the brain and behaviour during the prenatal developmental period and during adulthood. One brain area that has received little attention with respect to the study of sex differences is the prefrontal cortex (PFC). The PFC is involved in cognitive functions not limited to working memory, reinforcement learning, and inhibitory control. Currently, our understanding of the hormonal modulation of the PFC by sex steroids is also limited. The overall objectives of the present thesis were: to test the hypothesis that select cognitive functions known to depend on the PFC exhibit sex differences, to investigate whether some of these functions are influenced by developmental and/or adult androgens, and to begin to determine the functional components of PFC-dependent cognitive tasks that are responsible for eliciting sex differences. In Study 1, there was no evidence for a sex difference on two working memory tasks (Self-Ordered Pointing and the n-back), but males selected more advantageous cards than females on the Iowa Gambling Task (IGT) and were more accurate during the reversal phase of a probabilistic reversal learning task. In Study 2, the relationship between current and developmental androgens and performance on the IGT was investigated. Financial risk-taking was assessed as a potential mediator of the relationships. Circulating testosterone was found to be negatively correlated with the number of good card selections on the IGT, but there was no evidence to suggest that risk-taking was a mediator. On the other hand, there was evidence that developmental levels of androgens (using digit ratio as a proxy measure) may influence IGT performance in adulthood indirectly through an effect on risk-taking. In Study 3, females were more accurate than males on a reinforcement learning task under conditions where learning was based on positive feedback, whereas males were faster on an interference inhibition task than females. Taken together, the set of studies described in the present dissertation advance our knowledge regarding the sexual differentiation of the PFC and add to our current understanding of the modulatory role played by sex steroids on certain cognitive functions dependent on the PFC

Developmental changes in the reward positivity : an electrophysiological trajectory of reward processing

Children and adolescents learn to regulate their behavior by utilizing feedback from the environment but exactly how this ability develops remains unclear. To investigate this question, we recorded the event-related brain potential (ERP) from children (8-13 years), adolescents (14-17 years) and young adults (18-23 years) while they navigated a "virtual maze" in pursuit of monetary rewards. The amplitude of the reward positivity, an ERP component elicited by feedback stimuli, was evaluated for each age group. A current theory suggests the reward positivity is produced by the impact of reinforcement learning signals carried by the midbrain dopamine system on anterior cingulate cortex, which utilizes the signals to learn and execute extended behaviors. We found that the three groups produced a reward positivity of comparable size despite relatively longer ERP component latencies for the children, suggesting that the reward processing system reaches maturity early in development. We propose that early development of the midbrain dopamine system facilitates the development of extended goal-directed behaviors in anterior cingulate cortex. 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license

Unraveling the influence of trial-based motivational changes on performance monitoring stages in a flanker task

Performance monitoring (PM) is a vital component of adaptive behavior and known to be influenced by motivation. We examined effects of potential gain (PG) and loss avoidance (LA) on neural correlates of PM at different processing stages, using a task with trial-based changes in these motivational contexts. Findings suggest more attention is allocated to the PG context, with higher amplitudes for respective correlates of stimulus and feedback processing. The PG context favored rapid responses, while the LA context emphasized accurate responses. Lower response thresholds in the PG context after correct responses derived from a drift–diffusion model also indicate a more approach-oriented response style in the PG context. This cognitive shift is mirrored in neural correlates: negative feedback in the PG context elicited a higher feedback-related negativity (FRN) and higher theta power, whereas positive feedback in the LA context elicited higher P3a and P3b amplitudes, as well as higher theta power. There was no effect of motivational context on response-locked brain activity. Given the similar frequency of negative feedback in both contexts, the elevated FRN and theta power in PG trials cannot be attributed to variations in reward prediction error. The observed variations in the FRN indicate that the effect of outcome valence is modulated by motivational salience