Reconfiguration of brain networks and its association with cognition across the lifespan

大脑网络的重构及其与整个生命周期认知的关联

• 批准号: 10161648
• 负责人: Gaelle Eve Doucet
• 金额: $ 32.92万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10161648
• 关键词: Adult; Age; Aging; Behavioral; Brain; Brain Mapping; Characteristics; Cognition; Cognitive; Cognitive aging; Data; Development; Elderly; Functional Magnetic Resonance Imaging; Heterogeneity; Image; Impaired cognition; Individual; Lead; Link; Literature; Longevity; Nerve Degeneration; Participant; Persons; Physiology; Population; Rest; Role; United States; Work; age related; aging brain; base; brain dysfunction; cognitive ability; cognitive neuroscience; cognitive task; connectome; healthy aging; improved; indexing; inter-individual variation; network dysfunction; neuroimaging; novel

Older individuals represent 15% of the United States population, and this is expected to exceed 20% by 2050. It is therefore critical that we improve our understanding of the physiology of healthy brain aging and the mechanisms that may lead to cognitive decline in older people. It is well accepted that the brain is functionally organized into multiple interacting networks. Extensive literature has demonstrated that the spatial and functional organization of the brain connectome shows age-related alterations in later life. Yet, most neuroimaging studies have focused on one single cognitive state such as task or resting-state and ignored the role of brain connectome reconfiguration across states in cognitive aging. However, growing evidence suggests that the dynamic reconfiguration of the brain functional connectome across cognitive states can predict cognitive ability. Therefore, this lack of a more integrative view may limit our capacity to identify the mechanisms leading to cognitive decline in late adulthood. Based on our prior studies and pilot analyses, we show that collecting functional magnetic resonance imaging (fMRI) data from both resting-state and several cognitive tasks will improve the characterization of the brain functional connectome and its links to cognition in late adulthood. In this context, the aim of this application is to combine these imaging data with cognitive and behavioral information to identify the role of spatial and functional reconfigurations of the brain networks to predict cognitive decline and heterogeneity associated with aging. To achieve this, we will use both resting-state and task-based functional magnetic resonance imaging (fMRI) from 130 healthy participants between 19 and 88 years-old. Our first aim (Aim 1) is to quantify inter-individual variability in global and domain-specific cognition and its association with age. We will use a novel metric, called person-based similarity index, that allows us to identify participants whose cognitive profile significantly differs from that of other participants thus enabling a detailed examination of the characteristics that may drive cognitive heterogeneity in older age. We will then identify age-based changes in the spatial (Aim 2) and functional (Aim 3) reconfigurations of brain networks by cognitive states. We will demonstrate that a reduced degree of network reconfiguration across conditions is associated with higher cognitive decline in older individuals, relative to the younger individuals. The successful completion of this project will provide an integrative view of the brain reconfiguration across cognitive states in healthy aging and will quantify its association with cognitive decline in older healthy individuals. By mapping the brain functional connectome underlying late adulthood, this work has the potential to elucidate how dysfunction of the brain networks contributes to cognitive aging in healthy and neurodegenerative conditions.

老年人占美国人口的 15%，预计到 2050 年这一比例将超过 20%。因此，我们必须提高对健康大脑老化的生理学以及可能导致老年人认知能力下降的机制的了解。 。人们普遍认为，大脑在功能上被组织成多个相互作用的网络。大量文献表明，大脑连接组的空间和功能组织在晚年表现出与年龄相关的变化。然而，大多数神经影像学研究都集中在一种单一的认知状态，例如任务或静息状态，而忽略了认知衰老中跨状态的大脑连接组重新配置的作用。然而，越来越多的证据表明，大脑功能连接组在认知状态下的动态重新配置可以预测认知能力。因此，缺乏更综合的观点可能会限制我们识别导致成年晚期认知能力下降的机制的能力。根据我们之前的研究和初步分析，我们表明，从静息状态和多项认知任务中收集功能磁共振成像（fMRI）数据将改善大脑功能连接组的表征及其与成年晚期认知的联系。在这种情况下，该应用的目的是将这些成像数据与认知和行为信息相结合，以确定大脑网络的空间和功能重新配置的作用，以预测与衰老相关的认知衰退和异质性。为了实现这一目标，我们将使用 130 名 19 至 88 岁健康参与者的静息态和基于任务的功能磁共振成像 (fMRI)。我们的第一个目标（目标 1）是量化全局和特定领域认知的个体间差异及其与年龄的关联。我们将使用一种称为基于人的相似性指数的新颖指标，它使我们能够识别认知特征与其他参与者显着不同的参与者，从而能够详细检查可能导致老年认知异质性的特征。然后，我们将通过认知状态识别大脑网络空间（目标 2）和功能（目标 3）重新配置中基于年龄的变化。我们将证明，相对于年轻人，不同条件下网络重构程度的降低与老年人认知能力下降程度更高有关。该项目的成功完成将为健康老龄化过程中认知状态下的大脑重新配置提供一个综合视角，并将量化其与老年健康个体认知能力下降的关系。通过绘制成年晚期的大脑功能连接组图，这项工作有可能阐明大脑网络功能障碍如何导致健康和神经退行性疾病中的认知衰老。