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决定，我们需要一些功能的集成。几乎所有的决策都需要权衡预期收益与任何相关的“成本”，如实现结果之前的不同时间延迟，实现各种结果所需的体力劳动，或选择结果的不确定性。尽管它们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如何在成年和老年的决策中差异化地整合。新兴的理论表明，成年后认知、情感、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。这项赠款的总体目标是通过扩大最初的机构， 在成年人的生命周期中进行决策的工作，以便为未来的研究奠定基础。我们的综合方法，其中包括认知和情感的个体差异，决策行为和功能和结构脑成像（MRI，fMRI，PET）的测量，将被应用到个人和年龄差异的偏好的时间，努力和不确定性的研究在一系列决策领域（金融，社会，健康）。使用放射性配体PET成像多巴胺D2样受体与[18F]fallypride在20至85岁之间的健康成年人的大样本寿命，该项目将提供第一个全脑（中脑，皮质下和皮质）检查多巴胺受体在支持决策的核心动机评估过程中的特定作用。所有参与者将完成决策任务，同时接受fMRI，以测试选择行为和功能性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。我们预计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。我们进一步推测，中脑边缘的多巴胺系统方面将显示较小的年龄差异相比，前外侧皮质区域。我们希望这些中脑边缘区域（腹内侧皮质纹状体-中脑网络）在跨域决策“成本”的整合中发挥主要作用。除了对人类衰老研究的贡献外，这项工作还将澄清整个成年期主观评价过程的神经基础。这种多模式的成人发展方法有可能更精确地描述参与决策中整合动机和认知过程的神经生物学系统。这项工作将提供一个必要的基础，从中了解和治疗潜在的决策障碍，通过确定未来干预的重点目标。 公共卫生相关性：该提案旨在利用多模态神经成像技术来表征成年人一生中动机、认知和决策的个体和年龄差异。这项工作将形成一个关于成人发育和衰老决策的转化研究计划的基础，并有可能最终促进识别成年人或所有年龄段的次优决策的特定标志物，以指导适当干预措施的设计。这项研究的长期目标是通过改善个人层面的决策来改善所有成年人的身体，情感和财务健康。

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. PUBLIC HEALTH RELEVANCE: The proposal aims to characterize individual and age differences in motivation, cognition, and decision making over the adult life span using multimodal neuroimaging techniques. This work will form the basis of a translational research program on decision making over adult development and aging, and has the potential to eventually facilitate identification of specific markers for suboptimal decision making in adults o all ages to inform the design of appropriate interventions. The long-term goal of this line of research is to improve the physical, emotional, and financial health of all adults by improving decision making at the individual level.