Effects of attention and goal-state lapses on memory in healthy and pathological aging

注意力和目标状态失误对健康和病理衰老记忆的影响

• 批准号: 10611846
• 负责人: Anthony D Wagner
• 金额: $ 74.61万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611846
• 关键词: Accounting; Address; Adopted; Adult; Affect; Age; Aging; Alzheimer disease detection; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Arousal; Attention; Behavioral; Behavioral Assay; Behavioral Sciences; Biological Assay; Biological Markers; Categories; Code; Cognition; Cognitive; Color; Data; Diameter; Disease; Elderly; Episodic memory; Functional Magnetic Resonance Imaging; Goals; Grain; Hippocampus; Individual; Individual Differences; Learning; Link; Location; Magnetic Resonance Imaging; Measures; Medial; Mediating; Memory; Memory Loss; Memory impairment; Molecular; Multivariate Analysis; Neurocognitive; Neurosciences; Pathology; Pattern; Performance; Positron-Emission Tomography; Probability; Process; Public Health; Pupil; Research; Resolution; Retrieval; Science; Short-Term Memory; Site; Sorting; Source; Specific qualifier value; Stimulus; Structure; Temporal Lobe; age related; cognitive neuroscience; distraction; functional magnetic resonance imaging/electroencephalography; healthy aging; indexing; innovation; innovative technologies; locus ceruleus structure; memory encoding; memory recognition; memory retrieval; multimodality; neural; neural network; novel; novel marker; pathological aging; pre-clinical; psychologic; theories; tool; young adult; β-amyloid burden

Structural and functional changes in neural networks of attention and goal-directed cognition likely contribute to age-related memory decline and impede daily living. While considerable progress has been made in specifying how changes in the medial temporal lobe affect memory, moment-to-moment and individual differences in attention and goal-state representation are also hypothesized to impact episodic encoding and retrieval in young and older adults, and to contribute to age-related memory change. Of equal importance, in asymptomatic (`healthy') older adults, preclinical Alzheimer's disease (AD) pathology may disrupt attention and goal coding, with deleterious consequences for memory. Here, we aim to use innovative functional, molecular, and structural measures to characterize interactions between attention, goal states, and memory, and to examine (a) their contributions to trial-level, subject-level, and group-level memory differences, and (b) their relation to AD pathology. We will leverage goal-directed episodic encoding and retrieval paradigms and cutting-edge cognitive neuroscience tools, including task-based EEG-fMRI with pupillometry in asymptomatic (`healthy') older (65-79 yrs) and young adults (18-30 yrs). Trial-level attentional lapses will be assayed via fluctuations of alpha and theta oscillatory power and pupil diameter; the strength of trial-level goal states will be quantified via multivariate analyses of frontoparietal BOLD patterns. Aims 1-2 will address: How do interactions in attention and goal-state representation affect cortical and hippocampal mechanisms of episodic encoding (Aim 1) and retrieval (Aim 2), and how do age-related changes in these interactions relate to memory differences across age? Moreover, we will examine how molecular and structural biomarkers of pathological aging (AD) in `healthy' older adults relate to neural, pupillometry, and behavioral assays of attention, goal states, memory, and their interactions. Via PET-MR, we will measure (a) global β-amyloid (Aβ) burden and regional Aβ in frontoparietal cortex, and (b) locus coeruleus integrity, a core structure for attention, arousal, and goal-directed cognition, and an early site of AD pathology. Using categorical (Aβ+ vs. Aβ-) and continuous analyses, Aim 3 will address: Do molecular and structural biomarkers of pathology in preclinical aging predict differences in attentional lapses and goal coding, accounting for significant shared or unique variance in behavioral and neural measures of memory in asymptomatic individuals? The promise, feasibility, and novelty of the proposed research are grounded in strong preliminary data and derive from the use of multi-modal measures to discover how function, structure, and early pathology interact to affect attention, goal coding, and memory in aging. The project will advance understanding of (a) how moment-to- moment and individual differences in attention and goal coding affect learning and remembering in young and older adults, and (b) how these differences relate to memory decline in aging with and without AD pathology. The latter holds promise for revealing novel neurocognitive biomarkers of AD risk.

注意力和目标认知的神经网络的结构和功能变化可能有助于 与年龄有关的记忆力下降并阻碍日常生活。虽然在指定方面取得了很大进展 内侧临时叶的变化如何影响记忆，时刻的力矩和个体差异 注意力和目标状态表示形式也被认为会影响情节编码和检索 年轻人和老年人，并为与年龄相关的记忆变化做出贡献。同等重要的 无症状（“健康”）老年人，临床前阿尔茨海默氏病（AD）病理可能会破坏注意力和 目标编码，对内存产生有害后果。在这里，我们旨在使用创新的功能， 分子和结构措施，以表征注意力，目标状态和记忆之间的相互作用， 并检查（a）它们对试验级，主题级和群体级记忆差的贡献，以及（b） 他们与广告病理学的关系。我们将利用目标指导的情节编码和检索范例， 尖端的认知神经科学工具，包括基于任务的EEG-FMRI，具有无症状的化学测定法 （“健康”）年龄较大（65 - 79年）和年轻人（18-30岁）。试验级的注意失误将通过 Alpha和Theta振荡能力和学生直径的波动；试用级目标状态的实力将是 通过对额叶大胆模式的多元分析进行量化。目标1-2将解决：如何 注意力和目标状态表示中的相互作用会影响发作的皮质和海马机制 编码（AIM 1）和检索（AIM 2），以及与年龄相关的这些相互作用的变化如何 年龄之间的记忆差异？此外，我们将研究分子和结构生物标志物 “健康”老年人中的病理衰老（AD）与神经元，化学测定法和行为测定有关 注意，目标状态，记忆及其互动。通过PET-MR，我们将测量（a）全局β-淀粉样蛋白（Aβ） 额叶皮质中的负担和区域Aβ，以及（b）基因座共鲁斯完整性，核心的核心结构，引起注意的核心结构 唤醒和目标定向的认知以及AD病理学的早期部位。使用分类（Aβ+与Aβ-）和 连续分析，AIM 3将解决：在临床前进行病理的分子和结构生物标志物 衰老预测注意力失误和目标编码的差异，占重大共享或独特的差异 无症状个体中记忆行为和神经测量的差异？承诺，可行性， 拟议研究的新颖性基于强大的初步数据，并从使用中得出 多模式的措施，以发现功能，结构和早期病理如何相互作用 注意，目标编码和衰老中的记忆。该项目将促进对（a）的理解 注意力和目标编码方面的时刻和个体差异会影响年轻人的学习和记忆 老年人，以及（b）这些差异与有或没有AD病理学的衰老的记忆下降如何相关。 后者有望揭示AD风险的新型神经认知生物标志物。