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

注意和目标定向认知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，并阻碍日常生活。虽然在具体规定方面取得了相当大的进展 内侧颞叶的变化如何影响记忆、瞬间和个体差异 注意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， 无症状的(健康的)老年人，临床前阿尔茨海默病(AD)的病理可能会扰乱注意力和 目标编码，对记忆有害的后果。在这里，我们的目标是使用创新的功能， 描述注意力、目标状态和记忆之间相互作用的分子和结构方法， 并考察(A)他们对试验水平、受试者水平和小组水平记忆差异的贡献，以及(B) 它们与AD病理的关系。我们将利用目标导向的情节编码和检索范例，以及 尖端认知神经科学工具，包括无症状患者基于任务的EEG-fMRI和斜视测量 (‘健康’)老年人(65-79岁)和年轻人(18-30岁)。试验水平的注意力疏忽将通过以下方式进行测试 α和θ振荡功率和瞳孔直径的波动；试探级目标状态的强度将是 通过对额顶粗体图案的多变量分析进行量化。目标1-2将涉及：如何 注意和目标状态表征的交互作用影响发作的皮层和海马区机制 编码(目标1)和提取(目标2)，以及这些交互作用中与年龄相关的变化与 不同年龄的记忆差异？此外，我们将研究分子和结构生物标记物如何 “健康”老年人的病理性衰老(AD)与神经、瞳孔测量和行为分析有关。 注意力、目标状态、记忆以及它们之间的相互作用。通过正电子发射计算机断层扫描-磁共振，我们将测量(A)全球β-淀粉样蛋白(Aβ) 额顶皮质的负荷和区域Aβ，以及(B)蓝斑的完整性，这是一个需要注意的核心结构， 觉醒和目标导向的认知，以及AD病理的早期位置。使用定语(Aβ与Aβ-)和 持续分析，目标3将解决：临床前病理的分子和结构生物标记物 年龄预测注意力疏忽和目标编码的差异，说明显著的共同或独特 无症状个体的行为和神经记忆测量的差异？承诺，可行性， 拟议研究的新颖性建立在强大的初步数据基础上，并源于 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、目标编码和衰老过程中的记忆。该项目将促进对(A)时刻如何- 注意和目标编码的瞬间和个体差异影响青少年和青少年的学习和记忆 老年人，以及(B)这些差异如何与有和没有AD病理的衰老中的记忆力下降有关。 后者有望揭示AD风险的新的神经认知生物标志物。

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.