Dopaminergic Modulation of Subjective Valuation across Adulthood

描述(由申请人提供)：在人类对经济福祉、社会满意度和身体健康的追求中，我们所做的决定需要整合许多特征。几乎所有的决定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、实现各种结果所需的体力消耗，或对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，但科学家直到最近才开始研究这些特征如何在成年和老年的决策过程中进行不同的整合。新出现的理论表明，成年后认知、情绪、动机和经验的变化会影响决策的年龄差异。然而，目前很少有经验证据将心理(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直接联系起来。这笔赠款的首要目标是通过扩大初始机构来显著促进该领域的发展 关于成年人一生决策的工作，以便为未来的研究创造基础。我们的综合方法，包括测量认知和情感个体差异、决策行为和功能和结构脑成像(MRI、fMRI、PET)，将被应用于研究一系列决策领域(金融、社会、健康)在时间、努力和不确定性偏好上的个人和年龄差异。该项目在20岁至85岁的健康成年人的大样本中使用放射性配基PET对多巴胺D2样受体和[18F]FolyPride进行成像，该项目将首次对多巴胺受体在支持核心激励评估过程中的特定作用进行全脑(中脑、皮质下和皮质)检查。所有参与者将在接受功能磁共振检查的同时完成决策任务，以测试选择行为和功能神经活动的差异是否受到D2样受体水平的年龄差异的影响。我们期望这些结构的功能激活和多巴胺能功能的个体差异与个体的决策偏好有关。我们进一步推论，与前外侧皮质区相比，多巴胺系统的中脑边缘部分的年龄差异较小。我们期望这些中边缘区域(腹内侧皮层-纹状体-中脑网络)在跨域决策“成本”的整合中发挥主要作用。除了对人类衰老的研究做出贡献外，这项工作还将阐明成年后主观评估过程的神经基础。这种多模式的成人发展方法有可能更准确地描述参与决策过程中整合动机和认知过程的神经生物学系统。这项工作将通过确定未来干预的重点目标，为理解和治疗成年后潜在的决策障碍提供必要的基础。

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.