Dopaminergic Modulation of Subjective Valuation across Adulthood

描述（由申请人提供）：在人类追求经济福祉，社会满意度和身体健康的过程中，我们做出的决定需要整合许多特征。几乎所有的决策都需要权衡预期收益和任何相关的“成本”，例如，在实现结果之前的不同时间延迟量，实现不同结果所需的体力消耗，或者选择结果的不确定性。尽管这些特征在日常生活中无处不在，但科学家们直到最近才开始研究这些特征在成年期和老年期的决策过程中是如何被不同地整合在一起的。新出现的理论表明，认知、情感、动机和经验在成年期的变化会影响决策的年龄差异。然而，目前很少有经验证据直接将心理（认知或情感）过程和神经系统功能的具体变化与选择的年龄差异联系起来。这项资助的首要目标是通过扩大最初的机构来显著推进该领域

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.