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The role of the dopamine system in human reinforcement learning

Final Report Summary - DOPAMINE (The role of the dopamine system in human reinforcement learning)

Project objectives:

Reintegration of the researcher. Performance of studies investigating the role of neurotransmitters (messenger molecules in the brain) in cognitive processes. Acquire skills: programming in E-prime and writing ethical proposals.

Description of the work performed:

Programming skills in E-prime were acquired, ethical proposals were written and permission was obtained. MRI safety courses were successfully completed at the Leiden University Medical Center (LUMC, Leiden, The Netherlands). FMRI methods were developed and implemented and two different pharmacology projects were undertaken. In total 86 volunteers participated in the different projects. Most of the data analysis is done and the results are in line with the hypotheses. Three first author papers and two co-author papers were published and one first author paper is in preparation.

Description of the main results achieved so far:

A key aspect of emotional stimuli is their emotional intensity or arousal; the degree to which the stimuli are pleasant or unpleasant. When participants view stimuli that vary in emotional arousal, a late positive-going event-related potential (ERP) component can be recorded at the scalp. Because of its sensitivity to emotional arousal, this late positive potential (LPP) is increasingly used as a tool for studying the role of emotion in social behaviour and for assessing emotional function in clinical populations. Despite the increasing popularity of the LPP, little is known about its neural basis. There is a broad consensus that the LPP reflects the modulation of activity in visual cortical structures, but the source of this modulation is unclear. Although it remains to be substantiated, it has been suggested that the LPP modulation may index re-entrant feedback from the amygdale to the visual cortex.

The LPP holds great promise as a non-invasive neural measure of emotional arousal in healthy and clinical populations. However, the neural basis of the LPP is still poorly understood. We tested the hypothesis that the LPP reflects the indirect effects, in the visual cortex, of ß-receptor activation in the amygdale. The prediction derived from that hypothesis is that LPP amplitude should be dependent on changes in ß-receptor activation. The results presented here provide tentative support for our hypothesis. We found that LPP amplitude depended on individual differences in a ß1-receptor gene polymorphism (G1165C), thus suggesting that the generation of the LPP is mediated, at least in part, by the activation of ß1-receptors. Further, we found that LPP was modulated by the beta-blocker propranolol. More research, including in animal models, is needed to determine the exact pathways and mechanisms by which ß-receptor activation modulates the LPP at the scalp.

In sum, previous work has shown that the LPP reflects the modulation of activity in visual cortical structures. However, not much is known about the source of that modulation. Our results support the hypothesis that one source of the modulation is the activation of ß-receptors in the amygdale.

Reintegration of the researcher was successful. The Leiden Institute for Brain and Cognition (LIBC, Leiden, The Netherlands) awarded the researcher a very competitive starting grant to continue this research at Leiden University