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.

项目总结/摘要 重要的财务决策是在退休前做出的，这可能会影响其他人的财务状况 一个人的生活。然而，很少有心理学和神经生物学研究考察了财务状况， 在这个退休前的中年范围内做出决定。该补助金的首要目标是开始 构建一个更全面的特定心理和神经机制模型， 年轻人和中年后期的财务决策。所有的目的都是为了了解成年人的年龄差异 在成本效益决策和多巴胺能神经调节在支持这些具体作用 年轻人和中年人的偏好。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）对风险选择的影响。单一多模式神经影像学研究 将研究年龄和基本认知和动机变量，决策的个体差异 行为，使用功能磁共振成像的神经奖励电路，从三个无线电收集的DA系统的多个方面- 配体PET成像，以及对安非他明的行为敏感性。使用放射性配体PET D2样受体和[18 F]Fallypride释放成像和DA转运蛋白（DAT）与[18 F]FECNT， 该项目将提供第一次审查的具体作用，多方面的DA功能，支持 健康青年和中年人成本效益决策的核心动机过程 成年人了我们希望在功能性神经活动的fMRI评估中观察到不同的年龄效应， 用PET评估DA功能。在各种成像方法中，我们希望观察到一定程度的保留， 在中年晚期腹侧纹状体和中脑的功能。然而，我们希望观察到更大的年龄 外侧皮质D2受体、纹状体和腹内侧前额叶DA释放和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，这样，在这些功能的个体差异 系统与努力成本容忍度的个体差异有关。我们还将包括一个 安非他明的挑战，以检查DA释放对决策偏好的影响。这将是第一 研究人类年龄差异的DA释放，并首次研究DA药物对决策的影响， 成年DAT配体[18 F]FECNT的平行使用将使我们能够独特地评估相对和 可能是突触前和突触后DA变量的协同影响，并进一步提供一个独特的 DAT表达与苯丙胺诱导的DA释放和行为学改变的关系 安非他明的作用。除了对人类衰老研究的贡献外，这项工作还将阐明神经系统的作用。 成本效益决策的基础。这种多模式的成人发展方法 有可能更精确地描述参与动机的神经生物学系统， 这是一个重要的决策过程，并有可能为未来的干预确定重点目标。