Neural Selectivity, Retrieval-Related Reinstatement, and Age-Related MemoryDecline

项目摘要 情节记忆随着年龄的增长而显著下降，而且与其他形式的记忆相比，下降得不成比例。 了解健康受试者与年龄相关的间歇性衰退的认知和神经基础很重要 因为即使是健康的人步入70多岁时的轻微损害(以临床标准衡量)，S也是 足以对生活质量产生不利影响。识别特定的认知过程，及其 神经基质是年龄相关性记忆衰退的最主要原因，是年龄相关性记忆衰退的关键先兆 制定潜在的康复干预措施。同样重要的是，充分了解更多 阿尔茨海默氏症等与年龄相关的神经退行性疾病的严重记忆障碍 如果不知道记忆及其神经底物在不同时期是如何变化的，疾病将很难实现 健康寿命的进程。本研究的目的是调查在年龄相关的疾病中的可能作用。 与编码相关的神经选择性(神经分化)和提取的强度记忆衰退- 相关神经恢复，以及编码和提取相关神经活动之间的关系。 这项拟议研究的起点是最近的发现表明，i)神经选择性和 复职在老年人中比在年轻人中更弱，与年龄密切相关，在 选择性的情况下，预测不同受试者的记忆表现，以及ii)位置的差异 类别选择性编码和提取相关活动的峰值(前移)在老年人中被夸大 成年人和，在副海马皮层，在受试者中，与记忆表现呈负相关。 在这些发现的基础上，拟议的研究将使用功能和结构fMRI来检查 神经选择性、恢复和前移的横断面特征及其与 认知健康成年人(年龄18-90岁)的大样本(N=160)的记忆表现 年)。年龄较大的队列(65-90岁)将在3年后进行随访，以评估选择性， 在基线上获得的恢复或转移指标可以预测认知的纵向变化 表现或大脑结构。对于结构分析，我们将集中在前内侧颞区 与临床前和早期阿尔茨海默病有很大关联的人，目的是检查 功能指标对阿尔茨海默病早期病理的敏感性。第二项研究将使用寿命 样本，以评估上述发现是否适用于听觉通道。第三项研究将 采用极端年龄组设计来检验检索需求的作用(一般回忆与具体回忆 研究事件的详细信息)关于前移的年龄差异。

Project Summary Episodic memory declines substantially and, relative to other forms of memory, disproportionately, with age. Understanding the cognitive and neural bases of age-related episodic decline in healthy subjects is important because even the modest impairment (by clinical standards) typical of healthy individuals entering their 70’s is sufficient to have a detrimental impact on quality of life. Identifying the specific cognitive processes, and their neural substrates, which are most responsible for age-related memory decline is a crucial precursor to the development of potential rehabilitative interventions. Equally important, a full understanding of the much more severe memory impairments characteristic of age-related neurodegenerative diseases such as Alzheimer’s Disease will be difficult to achieve without knowledge of how memory and its neural substrates vary over the course of the healthy lifespan. The aim of the present research is to investigate the possible role in age-related memory decline of the strength of encoding-related neural selectivity (neural differentiation) and retrieval- related neural reinstatement, as well as the relationship between encoding- and retrieval-related neural activity. The starting point for the proposed research is recent findings indicating that, i) neural selectivity and reinstatement are weaker in older than in younger adults, are strongly correlated regardless of age and, in the case of selectivity, predict memory performance across- subjects, and ii) differences in the locations of the peaks of category-selective encoding- and retrieval-related activity (the ‘anterior shift’) are exaggerated in older adults and, in the parahippocampal cortex, correlate negatively across subjects with memory performance. Building on these findings, the proposed research will use functional and structural fMRI to examine the cross-sectional profile of neural selectivity, reinstatement, and the anterior shift, and their relationships with memory performance, in a large (N=160) lifespan sample of cognitively healthy adults (age range 18-90 years). The older cohort (aged 65-90 years) will be followed up after 3 years to assess whether selectivity, reinstatement or shift metrics obtained at baseline are predictive of longitudinal change in cognitive performance or brain structure. For the structural analyses we will focus on anterior medial temporal regions that have been strongly implicated in pre-clinical and early Alzheimer’s Disease, with the aim of examining the sensitivity of the functional metrics to incipient Alzheimer’s pathology. A second study will employ a lifespan sample to assess whether the findings described above generalize to the auditory modality. A third study will employ an extreme age group design to examine the role of retrieval demands (recall of general vs. specific details from the study event) on age differences in the anterior shift.