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

多巴胺能神经调节对青壮年决策的影响

• 批准号: 8632817
• 负责人: DAVID HAROLD ZALD
• 金额: $ 53.29万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8632817
• 关键词: Adherence; Adult; Age; Aging; Amphetamines; Autoreceptors; Behavior; Behavioral; Biological Preservation; Cognitive; Corpus striatum structure; Costs and Benefits; Data; Decision Making; Development; Dextroamphetamine; Dopamine; Dopamine D2 Receptor; Dopaminergic Agents; Elderly; Emotional; Exercise; Expenditure; Financial Support; Functional Magnetic Resonance Imaging; Future; Globus Pallidus; Goals; Grant; Health; Human; Image; Incentives; Individual; Individual Differences; Intervention; Lateral; Life; Ligands; Measurable; Measures; Medial; Midbrain structure; Modeling; Motivation; Neurobiology; Participant; Perception; Performance at work; Personal Satisfaction; Pharmaceutical Preparations; Physical Efforts; Placebos; Play; Positron-Emission Tomography; Prefrontal Cortex; Probability; Radio; Regimen; Relative (related person); Research; Rest; Retirement; Rewards; Role; Sampling; Scanning; Site; Staging; System; Techniques; Testing; Thalamic structure; Translational Research; Ventral Striatum; Work; age difference; age effect; age group; age related; base; career; cost; demographics; design; discounting; dopamine D3 receptor; dopamine system; dopamine transporter; financial decision making; frontal lobe; imaging modality; improved; indexing; middle age; motivational processes; neurobehavioral; neuroimaging; neuromechanism; neuroregulation; postsynaptic; preference; presynaptic; programs; psychologic; public health relevance; radioligand; receptor; relating to nervous system; response; reward processing; young adult

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.

项目摘要 /摘要 重大财务决策是在退休期期间做出的，可能会影响其余的财务状况 一个人的生活。但是，很少的心理和神经生物学研究检查了财务 在这个退休前的中期晚期范围内决策。这笔赠款的总体目标是开始 构建支持特定心理和神经机制的更全面的模型 成年和中年晚期的财务决策。所有目标都试图了解成人年龄差异 在成本效益的决策中以及多巴胺能神经调节在支持这些方面的具体作用 年轻和晚期成年人的偏好。我们特别关注努力成本的决策，但我们 还将检查多巴胺（DA）对风险选择的影响。一项多模式神经影像学研究 将检查基本认知和动机变量的年龄和个体差异，决策 行为，使用fMRI的神经奖励电路，在三个无线电上收集的DA系统的多个方面 配体PET成像课程和对药物苯丙胺的行为敏感性。使用放射性宠物 D2样受体的成像，并用[18F] Fallypride和DA转运蛋白（DAT）释放[18F] Fecnt， 项目将对DA功能多个方面的特定作用进行首次检查 健康的年轻和中年人 成年人。我们期望在通过fMRI和 通过PET评估的DA功能。在成像方法中，我们希望观察到一定程度的保存 中期晚期的腹侧纹状体和中脑的功能。但是，我们希望观察到更长的年龄 侧面皮质D2受体，纹状体和腹侧前额叶DA释放以及DAT的差异 表达。我们期望这些神经生物学年龄差异，尤其是内侧前额叶和纹状体 网络与决策相关联，使得这些功能的个体差异 系统与努力成本的容忍度上的个体差异有关。我们还将包括一个 苯丙胺挑战以检查DA释放对决策偏好的影响。这将是第一个 研究DA发行中的人年龄差异以及对DA药物对跨决策的影响的首次研究 成年。 DAT配体[18F] FECNT的并行使用将使我们能够唯一评估亲戚和 可能对突触前和突触后DA变量的协同影响，并进一步提供独特的 评估DAT表达与苯丙胺诱导的DA释放与行为的关系 苯丙胺的作用。除了对人类衰老研究的贡献之外，工作还将阐明神经 成年期成本效益决策的基板。这种多模式的成人发展方法 有可能更精确地表征与动机和动机有关的神经生物学系统 决策，并有可能确定未来干预措施的重点目标。