Dopaminergic Modulation of Subjective Valuation across Adulthood

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DESCRIPTION (provided by applicant): In the human pursuit of financial well-being, social satisfaction, and physical health the decisions we make require the integration of a number of features. Nearly all decisions require the weighing of expected benefits with any associated "costs", such as varying amounts of temporal delay until outcomes are realized, the exertion of physical effort required to achieve various outcomes, or uncertainty about the outcome of a choice. Despite their ubiquity in everyday life, scientists have only recently started to examine how these features may be differentially integrated for decision making across adulthood and into old age. Emerging theories suggest that changes in cognition, emotion, motivation, and experience across adulthood influence age differences in decision making. However, there is currently very little empirical evidence directly linking specific changes in psychological (cognitive or affective) processes and neural system function with age differences in choice. The overarching goal of this grant is to significantly advance the field by broadening the initial body of work on decision making over the adult life span in order to create a foundation for future research. Our integrative approach, which includes measurement of cognitive and affective individual differences, decision making behavior and functional and structural brain imaging (MRI, fMRI, PET), will be applied to the study of individual and age differences in preferences for time, effort, and uncertainty across a range of decision making domains (financial, social, health). Using radioligand PET imaging of dopamine D2-like receptors with [18F]fallypride in a large life-span sample of healthy adults between the ages of 20 and 85, the project will provide the first whole-brain (midbrain, subcortical, and cortical) examination of the specific role of dopamine receptors in supporting the core motivational valuation processes underlying decision making. All participants will complete decision making tasks while undergoing fMRI to test whether differences in choice behavior and functional neural activity are influenced by age differences in D2-like receptor levels. We expect individual differences in the functional activation and dopaminergic function of these structures to be related to the decision preferences of individuals. We further theorize that mesolimbic aspects of the dopamine system will show smaller age differences when compared to anterior lateral cortical regions. We expect these mesolimbic regions (a ventromedial corticostriatal-midbrain network) to play a primary role in the integration of decision "costs" across domains. Beyond contributions to the study of human aging, the work will clarify the neural substrates of subjective valuation processes across adulthood. This multimodal, adult developmental approach has the potential to more precisely characterize the neurobiological systems involved in integrating motivational and cognitive processes in decision making. This work will provide a necessary foundation from which to understand and treat potential decision-making impairments across adulthood by identifying focused targets for future interventions.