Kurzfassung

Cognitive flexibility relies on D2-related activity in dopaminergic striato-frontal circuits, whereas stress modulates dopaminergic signaling in subcortical striatal regions and prefrontal cortex (PFC). With regard to resilience, the interaction between these dopaminergic mechanisms may be a critical determinant. We will use PET in order to examine the relationship between dopamine receptor-binding and cognitive flexibility at baseline and under stress challenge conditions. On the one hand,...Cognitive flexibility relies on D2-related activity in dopaminergic striato-frontal circuits, whereas stress modulates dopaminergic signaling in subcortical striatal regions and prefrontal cortex (PFC). With regard to resilience, the interaction between these dopaminergic mechanisms may be a critical determinant. We will use PET in order to examine the relationship between dopamine receptor-binding and cognitive flexibility at baseline and under stress challenge conditions. On the one hand, we will examine the relationship between changes in D2/3 dopamine receptor binding in response to psychosocial stress. On the other hand, we will investigate (i) behavior in the cognitive flexibility task, (ii) neural mechanisms underlying cognitive flexibility (both dopaminergic as measured using PET as well as with respect to blood oxygenation level dependent (BOLD) activation and functional connectivity measured using functional magnetic resonance imaging (fMRI)), and (iii) stress-dependent impairments in cognitive flexibility. Two PET scans will be acquired, one in which an established PET stress induction paradigm is implemented, followed by a behavioral measurement of the cognitive flexibility task, and one in which PET correlates of cognitive flexibility are measured. The planned measurement of participants allows comparisons between fMRI and PET results. This project uses a multimodal approach to clarify the relationship between dopamine system activity, various aspects of psychological flexibility, and resilience to stress. As various aspects of psychological flexibility rely upon striato-frontal dopaminergic signaling this approach provides a mechanistic link to neurobiological stress responses.
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