Structural and functional substrates of associative memory load in aging

项目摘要 健康的老年人和阿尔茨海默病及相关痴呆症患者表现出最严重的 联想记忆（AM）的记忆缺陷，其中多个元素必须作为一个记忆 内聚事件（例如，杂货清单上的物品）。神经影像学研究分别与年龄相关 AM的下降直接导致海马神经活动的增加和白色束完整性的降低 从海马体发出（例如，穹窿）。然而，很少有衰老研究评估了 这些功能和结构的神经基板之间，并没有这样做，与AM。此外，本发明还提供了一种方法， 因为大多数先前的AM研究使用的范例涉及最多只记住成对的刺激， 老龄化对要求更高的协会的影响尚不清楚。神经认知老化理论预测 老年人在更苛刻的认知负荷下无法招募足够的神经资源，导致 与年轻人相比，神经活动更低，认知能力更差。然而，这一理论主要 已经用工作记忆范式进行了测试，并与神经活动有关，可以得出类似的结论。 AM负荷的作用机制可能是AM负荷的行为和神经反应介导的 大脑结构。为了解决这些局限性，我们建议描述AM和 AM的功能和结构神经基质作为关联负荷的函数。年轻40岁，年长40岁 健康的成年人将在功能期间用词对（低负荷）和三联体（高负荷）执行AM任务， 磁共振成像（fMRI）采集，随后进行多室弥散成像（MDI） 顺序我们将评估在低负荷和高负荷条件下海马活动的年龄组差异 使用fMRI（特定目标1）和穹窿完整性使用MDI（特定目标2），以及这些神经基质如何 个别地与AM性能相关。为了验证我们的新假设，即对AM负荷的神经反应是 受白色物质结构完整性的限制，我们进一步提出探索年龄的调节作用 组和AM负荷对海马活动和穹窿完整性的直接关系（具体目标3）。 除了推进我们对健康老龄化中AM缺陷的理解以及穹窿和 海马体的记忆表现，本建议将支持申请人的学习训练目的 另外的理论（例如，老化的认知神经科学），统计学（例如，单变量和多变量 方法）和方法（例如，高级扩散成像）技能。最终，这项工作将确定 在健康老龄化中记忆力下降的行为和神经标志物，从而为未来的工作提供信息。 检测老年人患阿尔茨海默病和相关痴呆症风险的标志物。通过专注于复杂的 结构-功能相互作用，这项工作也将告知该领域，因为它走向大规模，多模式 成像数据集。

PROJECT SUMMARY Healthy older adults and individuals with Alzheimer’s disease and related dementias show the most severe memory deficits for associative memory (AM), in which multiple elements must be remembered as one cohesive event (e.g., items on a grocery list). Neuroimaging research has separately related age-related declines in AM to increased neural activity in the hippocampus and lower integrity of white matter tracts directly emanating from the hippocampus (e.g., fornix). However, very few aging studies have assessed interactions between these functional and structural neural substrates and none have done so in relation to AM. In addition, because most prior AM research has used paradigms that involve remembering at most only pairs of stimuli, the effect of aging on more demanding associations remains unknown. Neurocognitive aging theories predict that older adults cannot recruit sufficient neural resources under more demanding cognitive loads, leading to lower neural activity and poorer cognitive performance than younger adults. Whereas this theory has mainly been tested with working memory paradigms and in relation to neural activity, it follows that a similar mechanism may underlie effects of AM load, and that the behavioral and neural responses may be mediated by brain structure. To address these limitations, we propose to characterize age differences in AM and the functional and structural neural substrates of AM as a function of Associative Load. Forty younger and 40 older healthy adults will perform an AM task with word pairs (low load) and triplets (high load) during functional magnetic resonance imaging (fMRI) acquisition followed by a multicompartment diffusion imaging (MDI) sequence. We will assess age group differences in hippocampal activity during low and high load conditions using fMRI (Specific Aim 1) and in fornix integrity using MDI (Specific Aim 2), and how these neural substrates individually relate to AM performance. To test our novel hypothesis that the neural response to AM load is constrained by white matter structural integrity, we further propose to explore the moderating effects of age group and AM load on the direct relationship between hippocampal activity and fornix integrity (Specific Aim 3). In addition to advancing our understanding of AM deficits in healthy aging and the contribution of the fornix and hippocampus to memory performance, this proposal will support the applicant’s training aims of learning additional theoretical (e.g., cognitive neuroscience of aging), statistical (e.g., univariate and multivariate approaches), and methodological (e.g., advanced diffusion imaging) skills. Ultimately, this work will identify behavioral and neural markers of memory declines in healthy aging, thereby informing future work using these markers to detect older adults at-risk for Alzheimer’s disease and related dementias. By focusing on complex structure-function interactions, this work will also inform the field as it moves toward large-scale, multimodal imaging datasets.