Using lifelike narratives to probe age-related differences in cortico-hippocampal functionality and episodic memory

项目摘要 现实生活中的事件具有复杂的结构，但我们不了解人类大脑如何支持结构化 真实事件的再现。此外，我们不知道衰老如何影响神经表征， 或从记忆中回忆结构化事件。我们对人类记忆的认识 认知老化可能是由于大多数研究都采用了刺激（例如单词列表） 不模拟真实事件的复杂性。最近，逼真的刺激（如故事）提供了一个新的 探索现实生活中事件的记忆的方法，以及作为表征基础的神经基质。 真实事件在功能性磁共振成像（fMRI）中呈现逼真刺激的研究 发现后内侧皮质网络（PM网络）的活动可能代表了 人类记忆中的事件。巧合的是，PM网络特别容易受到阿尔茨海默病的病理影响， 这是一个“临床前”阶段，目前的神经心理学测试不能模拟逼真的事件， 损伤为了为新的、更敏感的认知测试奠定基础， 因此，有必要研究PM网络与现实生活中记忆的功能相关性。 没有痴呆症。该提案将使用功能磁共振成像和最先进的表征相似性分析 技术（RSA）来研究PM网络如何有助于以逼真的方式表示结构化事件 叙述，以及老龄化对这种代表性的影响（目标1）。然后，本建议将研究 年龄对包含结构化叙述的事件回忆的影响（目标2）。实验将在 通过为期两天的功能磁共振成像（目标1）和回忆测试（目标2）在老年人和年轻人中进行。目标将 利用创新的，逼真的叙事范式，已经产生了一个有前途的行为研究， 年轻的成年人，当与fMRI配对时，将能够测试关于神经系统的特定假设。 结构化事件的表示。这些目标测试假设来自一个一般理论： 网络是关于事件类（“事件模式”）的先验知识的基底，其用于解析我们的 日常经验，这种知识反映在人类回忆事件的方式中， 晚些时候。此外，有理论认为，老年人在一段时间内形成了这些事件图式。 辈子目标1将测试老化是否增强结构化事件的神经表征（在PM中 Aim 2将测试结构化事件是否在老年人中表现出保留的回忆。以下 为了实现这些目标，将进行探索性的转化研究， 用可用的神经退化生物标志物来测量逼真的记忆。建议的任何调查结果 这些实验将促进我们对人类记忆和认知老化的理解，并为人类记忆和认知老化奠定基础。 开发更敏感的认知测试，检测明显痴呆症之前的认知障碍。

PROJECT SUMMARY Real-life events have a complex structure, yet we do not understand how the human brain supports structured representations of real-life events. Furthermore, we do not know how aging impacts the neural representation of realistic events, or recall of structured events from memory. This gap in our knowledge of human memory and cognitive aging is likely due to the fact that most investigations have employed stimuli (e.g. lists of words) that do not simulate the complexity of real-life events. Recently, lifelike stimuli (e.g. stories) have offered a new way to probe memory for real-life events, as well as the neural substrates which underlie the representation of real-life events. Studies which present lifelike stimuli during functional magnetic resonance imaging (fMRI) have found that activity in a posterior medial cortical network (PM network) may represent the structure of events in human memory. Coincidentally, the PM network is particularly vulnerable to Alzheimer’s pathology, at a “preclinical” stage when current neuropsychological tests, which do not simulate lifelike events, do not detect impairment. In order to set the stage for new, more sensitive cognitive tests that can detect early cognitive impairment, there is a need to study the functional relevance of the PM network to real-life memory in the absence of dementia. This proposal will use fMRI and state-of-the-art Representational Similarity Analysis techniques (RSA) to study how the PM network contributes to the representation of structured events in lifelike narratives, as well as the impact of aging on this representation (Aim 1). This proposal will then study the impact of aging on recall of events that comprise a structured narrative (Aim 2). Experiments will be conducted in older and younger adults via a two-day protocol with fMRI (Aim 1) and tests of recall (Aim 2). Aims will utilize an innovative, lifelike narrative paradigm which has already yielded a promising behavioral study in younger adults, and which, when paired with fMRI, will enable testing specific hypotheses about the neural representation of structured events. These Aims test hypotheses derived from a general theory: that the PM network is a substrate for prior knowledge about event classes (“event schemas”) that is used to parse our everyday experiences, and that this knowledge is reflected in the manner in which humans recall events at a later time. Moreover, it has been theorized that older adults develop these event schemas over the course of a lifetime. Aim 1 will test whether aging enhances the neural representation of structured events (in the PM network), and Aim 2 will test whether structured events exhibit preserved recall among older adults. Following pursuit of these Aims, exploratory translational studies will be pursued which correlate neural or behavioral measures of lifelike memories with available biomarkers of neurodegeneration. Any findings from proposed experiments will advance our understanding of human memory and cognitive aging, and set the stage for the development of more sensitive cognitive tests that detect cognitive impairment preceding overt dementia.