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

项目摘要/摘要 重要的财务决定是在退休前做出的，这可能会影响其他人的财务健康 一个人的生活。然而，很少有心理学和神经生物学的研究考察金融 在退休前、中年后期这一范围内的决策。这笔赠款的首要目标是开始 构建更全面的特定心理和神经机制模型，以支持 青壮年和中年后期的财务决策。所有目标都试图了解成年人的年龄差异 在成本效益决策中以及多巴胺能神经调节在支持这些决策中的特定作用 年轻人和中年后期的喜好。我们特别关注有努力成本的决策，但我们 还将研究多巴胺(DA)对高风险选择的影响。一项单一的多模式神经成像研究 将考察年龄和个体在基本认知和动机变量、决策方面的差异 行为，使用功能磁共振的神经奖励电路，通过三个无线电收集的DA系统的多个方面- 配基PET成像会议，以及对药物苯丙胺的行为敏感性。使用放射性配基PET [18F]FECNT对D2样受体的成像和[18F]FECNT对[18F]FECNT的释放 该项目将首次审查发展议程职能的多个方面在支持方面的具体作用 中青年健康人群成本效益决策的核心动机过程 成年人。我们期望观察不同年龄对功能性核磁共振和功能性神经活动的影响。 用正电子发射计算机断层扫描(PET)评估DA功能。通过成像方法，我们希望观察到一定程度的保存 中年后期腹侧纹状体和中脑的功能。然而，我们预计会观察到更大的年龄 大脑皮质外侧D2受体、纹状体和腹内侧额前区DA释放及DAT的差异 表情。我们预计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，与决策相关联，从而使这些网络的功能存在个体差异 系统与个体在对努力成本的容忍度上的差异有关。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。这将是第一次 人类多巴胺释放的年龄差异研究，以及多巴胺药物对决策影响的首次研究 成人期。DAT配体[18F]FECNT的并行使用将使我们能够唯一地评估相对和 可能是突触前和突触后DA变量的协同影响，并进一步提供了独特的 苯丙胺诱导的多巴胺释放与DAT表达及行为学的关系 安非他明的作用。除了对人类衰老的研究做出贡献外，这项工作还将澄清神经 成年期成本效益决策的基础。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 并有可能为今后的干预行动确定重点目标。

PROJECT SUMMARY / ABSTRACT Vital financial decisions are made during pre-retirement age that can influence financial well-being for the rest of an individual's life. However, 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 neuromodulation 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.