Improving multi-step planning in aging by overcoming deficits in memory encoding

项目概要/摘要 这项R21提案的目的是调查与年龄相关的衰退的行为和神经特征 在记忆功能服务的多步规划。我们预计，这里获得的结果将作为 支持一项研究计划的初步发现，该计划使用神经成像来评估这些回路是如何 在老年性疾病中，如阿尔茨海默病和轻度认知障碍（MCI）中，这些蛋白质会发生改变。 以前对老龄化决策的研究主要集中在涉及重复的任务上。 特定动作或刺激的强化（例如顺序强化学习任务），或比较 在直接指示其值的项目之间（例如赌博）。一种独立的决策形式， 与日常经验更密切相关的是那些选择取决于计划的选择： 从我们过去的经验不同的事件，并重新组装它们，以实现新的目标， 例如，寻找一家你可能经过但从未进入的冰淇淋店。 这些类型的决定，除了在老年人中相对研究不足之外，在老年人中也是不同的。 他们依赖于长期的情景记忆众所周知，情节记忆会随着年龄的增长而下降。特定 已知情景记忆的一个方面是随着年龄的增长而下降的称为模式分离的计算： 创造不同神经模式的能力，这些模式反映具有相似或重叠感觉特征的输入（例如， 两种口味的冰淇淋）。模式分离使我们能够快速检索和重用信息， 面对干扰。我们可以用记忆相似性任务来衡量行为中的模式分离 (MST)这是一种短而广泛使用的检测方法，可以预测整个生命周期中的认知和神经缺陷。 虽然我们知道模式分离和计划都随着年龄的增长而下降，我们知道这两者都是 功能是由相同的神经结构在健康成人的支持，我们不知道他们是否共存于 同样的神经回路，我们也不知道模式分离的下降是否会导致规划能力的下降。 在这里，我们的目标是填补这一知识空白，检查（目标1）老年人的能力， 多步骤计划，以及它如何对应于模式分离;（目的2）进一步询问是否考虑到 一个人在模式分离方面的下降可以让我们以一种改进的方式来构建他们的经历， 他们在这些经验的基础上构建计划的能力;（目标3）是否神经回路 模式分离和规划重叠，以及它们在正常认知老化中如何相互作用。总而言之，拟议的 研究将确定我们是否可以通过考虑个人因素来改善个人决策 记忆功能的差异;研究结果将为早期发现和治疗广泛的 一系列的衰老疾病。

Project Summary/Abstract The objective of this R21 proposal is to investigate the behavioral and neural signatures of age-related decline in memory function in service of multi-step planning. We anticipate that the results obtained here will serve as preliminary findings in support of a research program using neuroimaging to evaluate how these circuits are altered in diseases of aging, such as Alzheimer's Disease and Mild Cognitive Impairment (MCI). Previous research into decision-making in aging has focused primarily on tasks that involve repeated reinforcement of specific actions or stimuli (e.g. sequential reinforcement learning tasks), or on comparisons between items whose values are directly instructed (e.g. gambles). A separate form of decisions, arguably more germane to everyday experience, are those in which choices depend on planning: searching through disparate events from our past experience, and reassembling them to achieve new goals introduced in the moment (e.g. seeking an ice cream store you may have passed by but never entered). These types of decisions, in addition to being relatively under-studied in older adults, are also distinct in that they depend on long-term, episodic memory. Episodic memory is known to decline in age. A specific aspect of episodic memory that is known to decline with age is the computation called pattern separation: the ability to create divergent neural patterns that reflect inputs with similar or overlapping sensory features (e.g. two flavors of ice cream). Pattern separation allows us to rapidly retrieve and re-use information even in the face of interference. We can measure pattern separation in behavior using the Mnemonic Similarity Task (MST), a short, widely used assay that predicts cognitive and neural deficits across the lifespan. While we know that pattern separation and planning both decline with age, and we know that both functions are supported by the same neural structures in healthy adults, we do not know if they co-exist in the same neural circuits, nor do we know if a decline in pattern separation yields a decline in planning ability. Here, we aim to fill this gap in knowledge, examining (Aim 1) the ability of older adults to construct multi-step plans, and how it corresponds to pattern separation; (Aim 2) to further ask whether taking account of an individual’s decline in pattern separation can allow us to structure their experiences in a way that improves their ability to later construct plans on the basis of those experiences; (Aim 3) whether neural circuits for pattern separation and planning overlap, and how they interact in normal cognitive aging. In sum, the proposed research will determine whether we can improve individual decision-making by taking account of individual differences in memory function; the findings will inform research into early detection and treatment of a wide range of diseases of aging.