Age effects on memory and reward systems in decision making

项目摘要 衰老伴随着神经化学系统的深刻变化以及聚集性的积累 蛋白质。到目前为止，这些过程对认知的影响一直是孤立地研究的。建议数 研究采取了新的步骤来连接这些领域，以开发一个关于变化如何跨越的综合模型 在衰老过程中，多个神经系统相互作用，影响高层决策。 候选人和职业目标：该项目将支持候选人在以下方面的基本培训和发展 认知老化领域，特别关注奖赏和记忆系统的下降如何相互作用 有助于提高决策能力。候选人有很强的研究记录，定义了 神经调节剂塑造认知的功能机制。支持候选人发起一项 可持续的、跨学科的独立研究计划，两位专家导师将提供个性化 训练。首先，应聘者将接受神经经济学和金融决策领域的培训， 她将申请进入认知衰老领域。其次，应聘者将接受PET评估方法的培训 老年阿尔茨海默病的病理与伴发内侧颞叶记忆功能 成年人。这一新颖的研究计划将利用候选人已有的专业知识，同时开发 将认知老化研究的两条重要路线连接起来的关键技能。 环境：劳伦斯伯克利国家实验室的非凡资源和科学界 和加州大学伯克利分校哈斯商学院提供了理想的环境来培养候选人的 发展成为一名创新和成功的独立调查员。候选人将有权访问 最先进的人类神经成像技术，并将得到丰富的机构文化的支持，促进 创造性、跨学科的协作。 研究活动：衰老伴随着1)多巴胺系统功能障碍，这会影响 腹侧纹状体对奖赏的反应，以及2)过度磷酸化的tau聚集，与MTL相关 退化和记忆中断。拟议的K99研究将勾勒出独立和互动的 这些过程在调节财务决策的核心组成部分中的作用：奖励学习和 记忆。这些研究将结合健康老年人的PET成像，这是一项新的实验室任务 特别是探索纹状体与MTL的相互作用，以及真实世界金融能力的有效衡量标准。这个 拟议的R00研究将把实验室任务与功能磁共振配对，以定义激活和 纹状体和MTL之间的网络活动是与年龄相关的表现障碍的基础和最佳预测 真实世界金融能力的个体差异。总而言之，这些研究将有助于建立新的 跨系统交互作用如何影响衰老中的高级认知，同时确定潜在的靶点 弥补衰退。

Project Summary Aging is accompanied by profound changes in neurochemical systems as well as accumulation of aggregated proteins. To date, the influence of these processes on cognition has been studied in isolation. The proposed research takes novel steps to bridge these fields to develop an integrative model of how changes across multiple neural systems interact to affect high-level decision making in aging. Candidate and career goals: This project will support the candidate’s essential training and development in the field of cognitive aging, with a particular focus on how decline in reward and memory systems interact to contribute to decision making ability. The candidate has a strong track record of research defining the functional mechanisms by which neuromodulators shape cognition. To support the candidate in launching a sustainable, cross-disciplinary independent research program, two expert mentors will provide individualized training. First, the candidate will train in the field of the neuroeconomics and financial decision making, which she will apply to the field of cognitive aging. Second, the candidate will train in PET methods for assessing Alzheimer’s disease pathology and accompanying medial temporal lobe (MTL) memory function in older adults. This novel research program will capitalize on the candidate’s established expertise while developing critical skills to connect two important lines of cognitive aging research. Environment: The exceptional resources and scientific community at Lawrence Berkeley National Laboratory and UC Berkeley Haas School of Business provide and ideal environment to foster the candidate’s development into an innovative and successful independent investigator. The candidate will have access to state-of-the-art human neuroimaging technology and will be supported by a rich institutional culture promoting creative, cross-disciplinary collaborations. Research activity: Aging is accompanied by 1) dysfunction of the dopamine system, which affects the response to rewards in ventral striatum, and 2) aggregation of hyperphosphorylated tau, associated with MTL degeneration and memory disruption. The proposed K99 studies will delineate the independent and interactive roles of these processes in modulating central components of financial decision making: reward learning and memory. These studies will combine PET imaging in healthy older adults, a novel laboratory task designed specifically to probe striatal-MTL interactions, and a validated measure of real-world financial capacity. The proposed R00 studies will pair the laboratory task with functional MRI to define the patterns of activation and network activity between striatum and MTL that underlie age-related disruption in performance and best predict individual differences in real-world financial capacity. Together, these studies will contribute to new models of how cross-system interactions influence high-level cognition in aging while identifying potential targets for remediating decline.