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

神经选择性、检索相关恢复和年龄相关记忆衰退

• 批准号: 10711196
• 负责人: Michael D Rugg
• 金额: $ 67.36万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711196
• 关键词: Adult; Affect; Age; Alzheimer like pathology; Alzheimer' s Disease; Alzheimer' s disease pathology; Anterior; Auditory; Behavioral; Brain; Categories; Characteristics; Clinical; Cognitive; Development; Elderly; Episodic memory; Event; Experimental Designs; Face; Functional Magnetic Resonance Imaging; Goals; Impairment; Individual; Intervention; Judgment; Knowledge; Location; Longevity; MRI Scans; Measures; Medial; Memory; Memory Loss; Memory impairment; Methods; Modality; Music; Neuropsychological Tests; Pattern; Performance; Photophobia; Publishing; Quality of life; Rehabilitation therapy; Reporting; Research; Retrieval; Role; Sample Size; Sampling; Source; Speech; Stimulus; Stream; Structure; Support System; Testing; Time; Water; age difference; age effect; age group; age related; age related neurodegeneration; aged; base; cognitive ability; cognitive performance; cognitive process; cohort; design; experience; experimental study; follow-up; healthy aging; memory encoding; memory process; memory retrieval; middle age; neural; neural patterning; novel; pathological aging; pre-clinical; therapy development; visual processing; young adult

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.

项目摘要 随着年龄的增长，情节记忆会大幅下降，而且与其他形式的记忆相比，不成比例。 了解健康受试者中年龄相关性发作性衰退的认知和神经基础是重要的 因为即使是进入70多岁的健康人典型的适度损伤（按临床标准）， 足以对生活质量产生不利影响。识别特定的认知过程， 神经基质，这是最负责与年龄相关的记忆衰退是一个重要的前体， 开发潜在的康复干预措施。同样重要的是，充分理解 老年性神经退行性疾病（如阿尔茨海默氏症）的严重记忆障碍 如果不了解记忆及其神经基质在不同的时间段内是如何变化的， 健康的生命周期。本研究的目的是探讨年龄相关的可能作用， 编码相关神经选择性（神经分化）和提取强度的记忆下降- 相关的神经恢复，以及编码和检索相关的神经活动之间的关系。 这项研究的出发点是最近的发现，表明：i）神经选择性， 恢复在老年人中比年轻人弱，无论年龄如何都有很强的相关性， 选择性的情况下，预测跨学科的记忆表现，和ii）在位置的差异， 类别选择性编码和提取相关活动的峰值（“前移”）在老年人中被夸大了。 在成年人中，海马旁皮质与记忆表现呈负相关。 基于这些发现，拟议的研究将使用功能和结构fMRI来检查 神经选择性、恢复和前移的横截面轮廓，以及它们与 在认知健康成人（年龄范围18-90岁）的大样本（N=160）中， 年）。年龄较大的队列（年龄65-90岁）将在3年后随访，以评估选择性， 基线时获得的恢复或变化指标可预测认知功能的纵向变化， 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密切相关，目的是检查 功能指标对早期阿尔茨海默病的敏感性。第二项研究将使用寿命 样本，以评估上述研究结果是否推广到听觉模态。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（一般与具体的回忆 来自研究事件的细节）关于前移位的年龄差异。