Neuromodulation of Motivated Cognition and Decision Making Across Adulthood

描述(由申请人提供)：这个独立之路奖的目标是在候选人从博士后实习生过渡到专注于决策神经科学的独立科学家的过程中，扩大他的知识基础、方法专长和理论发展技能。大量关于衰老心理的行为研究表明，随着寿命的延长，认知和动机都会发生变化。许多著名的认知老化理论都集中在神经调节的变化上，特别是神经递质多巴胺(DA)。然而，DA不仅与认知功能的变异性有关，而且在动机中也起着重要的作用。然而，年龄相关的DA功能变化与动机因素之间的关系几乎没有得到研究。最初的K99指导阶段的目标是开始检查成年后动机和认知之间的相互作用，增加候选人对多巴胺系统的知识基础，获得计算建模的经验，并通过多种成像测量扩大候选人的专业知识。为了实现这些目标，候选人将开展一个协作性多模式成像项目，重点是澄清DA功能和自我调节之间的联系(R21-DA033611)。该项目将包括抑制控制的行为和功能磁共振测量，以及一组健康成年人大脑受体可用性的PET测量。所有参与者将完成两个行为任务，这两个任务捕捉到动机认知控制的不同方面，并参与不同的、尽管重叠的神经网络。候选人将开始扩展这一工作，以及他以前在年龄段差异方面的工作 在这个K99阶段，将年龄差异的动机认知和决策纳入横断面研究。建议的R00项目将研究成年期(20-80岁)动机认知控制和决策之间的关系。除了PET扫描，受试者还将在接受fMRI检查的同时完成行为任务，fMRI评估奖励处理和抑制控制。参与者还将完成一整套认知和动机个体差异测量、与激励兼容的行为经济学任务，以及健康和退休研究(HRS)调查的子集。该项目还将作为开发纵向多模式成像协议的基础研究。总而言之，该项目的指导阶段和独立阶段将提供一个框架，以开发更综合和全面的人类衰老理论，将DA功能对认知和动机的作用的神经科学理论与衰老的心理学理论相结合。候选人职业生涯的一个长期目标是开发一种基于计算知识和神经生物学的关于成人发育和衰老过程中的动机认知的理论。通过这一机制的支持将大大增加候选人获得R01的可能性，以支持在职业生涯的早期阶段进行纵向多模式成像研究。 公共卫生相关性：相关性该提案旨在利用行为和多模式神经成像技术来表征成年人一生中动机和认知的变化。这项工作将形成一个关于年龄相关的奖赏处理和认知控制变化的转换研究计划的基础，并有可能最终促进识别老年人次优决策的特定标记，并为适当干预的设计提供信息。这一研究的长期目标是通过改善个人层面的决策来改善老年人的经济和情绪健康。

DESCRIPTION (provided by applicant): The goal of this Pathway to Independence Award is to expand the base of knowledge, methodological expertise, and theoretical development skills of the candidate as he transitions from a post-doctoral trainee to an independent scientist focused on the decision neuroscience of aging. A wealth of behavioral research on the psychology of aging reveals change over the life span in both cognition and motivation. Many prominent theories of cognitive aging are centered on changes in neuromodulation, focusing specifically on the neurotransmitter dopamine (DA). However, DA is not only implicated in variability in cognitive function, but also plays an important role in motivation. Yet, the relatio between age-related changes in DA functioning and motivational factors has received little study. The goal of the initial K99 mentored phase is to begin to examine interactions between motivation and cognition across adulthood, increase the candidate's base of knowledge of the dopamine system, gain experience with computational modeling, and expand the candidate's expertise with multiple imaging measures. To achieve these goals, the candidate will conduct a collaborative multimodal imaging project focused on clarifying the link between DA functioning and self-regulation (R21-DA033611). The project will include behavioral and fMRI measures of inhibitory control as well as PET measures of receptor availability across the brain in a group of healthy adults. All participants will complete two behavioral tasks that capture distinct aspects o motivated cognitive control and engage distinct, albeit overlapping neural networks. The candidate will begin to extend this line of work as well as his previous work on age differences in decision making into a cross-sectional study of age differences in motivated cognition and decision making in this K99 phase. The proposed R00 project will examine relationships between motivated cognitive control and decision making across adulthood (ages 20-80). In addition to a PET scan, subjects will complete behavioral tasks while undergoing fMRI that assess reward processing and inhibitory control. Participants will also complete a full battery of cognitive and motivational individual difference measures, incentive-compatible behavioral economics tasks, as well as a subset of the Health and Retirement Study (HRS) survey. This project will also serve as a foundational study for the development of a longitudinal multi-modal imaging protocol. Together, the mentored and independent phases of this project will provide a framework toward developing a more integrative and comprehensive theory of human aging that incorporates neuroscientific theories of the role of DA function for cognition and motivation with psychological theories of aging. A long-term goal of the candidate's career is to develop a computationally-informed and neurobiologically-specific theory of motivated cognition across adult development and aging. Support through this mechanism will greatly increase the likelihood of the candidate's obtaining an R01 to support a longitudinal multimodal imaging study at an earlier career stage than otherwise possible. PUBLIC HEALTH RELEVANCE: Relevance The proposal aims to characterize changes in motivation and cognition over the adult life span using behavioral and multimodal neuroimaging techniques. This work will form the basis of a translational research program on age-related change in reward processing and cognitive control, and has the potential to eventually facilitate identification of specific markers for suboptimal decision making in older adults and inform the design of appropriate interventions. The long-term goal of this line of research is to improve the financial and emotional health of older adults by improving decision making at the individual level.