Dopaminergic Neuromodulation of Decision Making in Young and Middle-Aged Adults

描述(由申请人提供)：重要的财务决定是在退休前年龄做出的，这可能会影响个人余生的财务健康。然而，很少有心理学和神经生物学研究考察退休前、中年后期这一阶段的财务决策。这笔赠款的首要目标是开始构建一个更全面的模型，研究支持青年成年和中年后期财务决策的特定心理和神经机制。所有目的都试图了解成年人在成本效益决策上的年龄差异，以及多巴胺能神经调节在支持年轻和晚年中年人的这些偏好方面的具体作用。我们特别关注有努力成本的决策，但我们也将检查多巴胺(DA)对高风险选择的影响。一项单一的多模式神经成像研究将检查年龄和个体差异，包括基本认知和动机变量、决策行为、使用fMRI的神经奖励电路、通过三次放射性配体PET成像会话收集的DA系统的多个方面，以及对药物苯丙胺的行为敏感性。该项目使用D2样受体的放射性配基PET成像，并与[18F]FECNT一起释放[18F]FECNT和DA转运体(DAT)，该项目将首次检验DA功能的多个方面在支持健康年轻人和中年人进行成本效益决策的核心激励过程中的特定作用。我们期望通过fMRI评估的功能神经活动和PET评估的DA功能观察不同的年龄效应。通过各种成像方法，我们期望在中年后期观察腹侧纹状体和中脑功能的一定程度的保存。然而，我们预计在外侧皮质D2受体、纹状体和腹内侧额叶DA释放以及DAT表达方面存在更大的年龄差异。我们期望这些神经生物学年龄差异，特别是在内侧前额叶和纹状体网络中，与决策有关，因此这些系统功能的个体差异与努力成本容忍度的个体差异相关。我们还将包括一个苯丙胺挑战，以考察DA释放对决策偏好的影响。这将是第一个关于人类年龄差异释放DA的研究，也是第一个关于DA药物对成年决策影响的研究。DAT配体[18F]FECNT的并行使用将使我们能够唯一地评估突触前和突触后DA变量的相对和可能的协同影响，并进一步提供DAT表达和苯丙胺诱导的DA释放和苯丙胺的行为效应之间的关系的独特评估。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期成本效益决策的神经基础。这种多模式的成人发展方法有可能更准确地描述参与动机和决策的神经生物学系统，并有可能为未来的干预确定重点目标。

DESCRIPTION (provided by applicant): Vital financial decisions are made during pre-retirement age that can influence financial well-being for the rest of an individual's life. Howeve, very little psychological and neurobiological research has examined financial decision making in this pre-retirement late middle age range. An overarching goal of this grant is to begin to construct a more comprehensive model of the specific psychological and neural mechanisms that support financial decisions in young adulthood and late middle age. All aims seek to understand adult age differences in cost-benefit decisions and the specific role of dopaminergic neuro-modulation in supporting these preferences in young and late middle-age adults. We particularly focus on decisions with effort costs, but we will also examine the influence of dopamine (DA) on risky choice. A single multimodal neuroimaging study will examine age and individual differences in basic cognitive and motivational variables, decision making behavior, neural reward circuits using fMRI, multiple aspects of the DA system collected across three radio- ligand PET imaging sessions, and behavioral sensitivity to the drug amphetamine. Using radioligand PET imaging of D2-like receptors and release with [18F]fallypride and DA transporters (DAT) with [18F]FECNT, the project will provide the first examination of the specific role of multiple aspects of DA function in supporting the core motivational processes underlying cost-benefit decision making in healthy young and middle-aged adults. We expect to observe differential age effects in both functional neural activity assessed with fMRI and DA function assessed with PET. Across imaging methods, we expect to observe some level of preservation of function in the ventral striatum and midbrain in late middle age. However, we expect to observe larger age differences in lateral cortical D2 receptors, striatal and ventromedial prefrontal DA release, and DAT expression. We expect these neurobiological age differences, especially in medial prefrontal and striatal networks, to be associated with decision making, such that individual differences in the function of these systems are associated with individual differences in the tolerance of effort costs. We will also include an amphetamine challenge to examine the influence of DA release on decision preferences. This will be the first study of human age differences in DA release, and the first study of DA drug effects on decision making across adulthood. The parallel use of the DAT ligand [18F]FECNT will allow us to uniquely assess the relative and possibly synergistic impact of presynaptic and postsynaptic DA variables, and to further provide a unique assessment of the relations between DAT expression and amphetamine-induced DA release and the behavioral effect of amphetamine. Beyond contributions to the study of human aging, the work will clarify the neural substrates of cost-benefit decision making across adulthood. This multimodal, adult developmental approach has the potential to more precisely characterize the neurobiological systems involved in motivation and decision making, and has the potential to identify focused targets for future interventions.