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.

注意力和目标导向认知的神经网络的结构和功能变化可能有助于 与年龄相关的记忆力下降，妨碍日常生活。虽然在具体说明 内侧颞叶的变化如何影响记忆， 注意力和目标状态表征也被假设影响情景编码和提取， 年轻人和老年人，并有助于与年龄相关的记忆变化。同样重要的是，在 无症状（“健康”）老年人，临床前阿尔茨海默病（AD）病理可能会扰乱注意力， 目标编码，对记忆产生有害影响。在这里，我们的目标是使用创新的功能， 分子和结构的措施来表征注意力，目标状态和记忆之间的相互作用， 并检查（a）他们对试验水平、受试者水平和组水平记忆差异的贡献，以及（B） 与AD病理学的关系我们将利用目标导向的情景编码和检索范式， 尖端的认知神经科学工具，包括基于任务的脑电图功能磁共振成像与瞳孔测量， （“健康”）老年人（65-79岁）和年轻人（18-30岁）。试验水平的注意力缺失将通过 α和θ振荡功率和瞳孔直径的波动;试验级目标状态的强度将是 通过额顶叶BOLD模式的多变量分析进行定量。目标1-2将涉及：如何 注意力和目标状态表征的相互作用影响皮层和海马的情节机制 编码（目标1）和检索（目标2），以及这些相互作用中与年龄相关的变化如何与 不同年龄段的记忆力差异此外，我们将研究如何分子和结构的生物标志物， “健康”老年人的病理性衰老（AD）与神经、瞳孔测量和行为测定有关， 注意力、目标状态、记忆以及它们之间的相互作用。通过PET-MR，我们将测量（a）整体β-淀粉样蛋白（Aβ） 额顶叶皮质中的负荷和局部Aβ，以及（B）蓝斑完整性，注意力的核心结构， 唤醒和目标导向的认知，以及AD病理学的早期部位。使用分类（Aβ+ vs. Aβ-）和 目标3将解决：临床前病理学的分子和结构生物标志物 年龄预测的差异，注意失误和目标编码，占显着的共享或独特的 无症状个体记忆的行为和神经测量的差异？承诺，可行性， 所提出的研究的新奇是建立在强有力的初步数据基础上的， 多模式测量，以发现功能，结构和早期病理如何相互作用， 注意力、目标编码和衰老中的记忆。该项目将促进理解（a）如何时刻- 注意力和目标编码的时刻和个体差异影响年轻人的学习和记忆， 老年人，以及（B）这些差异如何与有和无AD病理的衰老中的记忆衰退相关。 后者有望揭示AD风险的新神经认知生物标志物。