Mapping the intrinsic functional organization of auditory cortex in individual subjects using 7T MRI

使用 7T MRI 绘制个体受试者听觉皮层的内在功能组织

• 批准号: 10710929
• 负责人: Jyrki Ahveninen
• 金额: $ 41.75万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10710929
• 关键词: Acceleration; Acoustic Stimulation; Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease patient; Alzheimer' s disease risk; Anatomy; Area; Auditory; Auditory area; Biological Markers; Blood; Brain; Cerebral cortex; Classification; Cognitive; Communication; Complex; Computer Analysis; Coupled; Data; Data Set; Diagnostic; Disease Progression; Functional Magnetic Resonance Imaging; Grain; Hearing problem; Human; Impaired cognition; Individual; Intervention; Language; Link; Machine Learning; Magnetic Resonance Imaging; Maps; Measures; Memory; Memory Loss; Methods; Neural Pathways; Neuropsychology; Participant; Pathologic; Pattern; Peripheral; Pilot Projects; Presbycusis; Public Health; Resolution; Rest; Risk Assessment; Risk Estimate; Risk Factors; Sampling; Specific qualifier value; Speech; Synapses; Syndrome; Testing; Work; age related; auditory processing; behavior test; cognitive process; hearing impairment; high risk; high risk population; inter-individual variation; large datasets; mild cognitive impairment; neuroimaging; novel; pre-clinical; public repository; response; therapy development; ultra high resolution

In response to NOT-AG-22-025, this project combines ultra-high-resolution MRI and advanced computational analyses to identify pathological changes in the functional connectivity of auditory cortices (AC), which are associated with an increased risk for Alzheimer's disease (AD). Accumulating evidence suggest that age-related hearing loss (HL) and central auditory processing difficulties could be significant risk factors for AD. Meanwhile, neuroimaging studies in individuals with age-related peripheral HL (but no AD diagnosis) suggest anatomical and functional changes in the cerebral cortex, which extend from primary ACs to auditory association areas that support complex cognitive processes including speech and language. Here, using methods developed in R01DC017991, we test a hypothesis that functional changes in cortical networks involving AC could be early indicators of AD risk. To date, the pursuit of biomarkers in fine-grained changes in human AC has been complicated by several critical barriers: Human ACs consist of multiple adjacent small regions, which are difficult to distinguish using conventional resolutions available for human functional MRI (fMRI); These small AC areas are activated by broad combinations of features and show considerably large inter-individual variability. Examining functional predictors of auditory processing difficulties in AD thus requires a novel perspective 1) which focuses on how human ACs interact with the rest of the human brain and 2) which allows for individual-level studies of dynamic functional networks instead of conventional fMRI group analyses only. Here, we pursue an entirely novel way to characterize early indicators of pathological changes in the functional organization of human AC in individual participants who are at high risk for AD. Our proposed work is built on recent advances that allow focusing on individual subjects and dynamic functional activity patterns using ultra-high resolution 7T fMRI. The results of computational analyses using new 7T fMRI data, which is collected during the resting state and auditory stimulation of aging participants, will be compared to those obtained with larger-sample (but lower resolution) 3T fMRI data sets obtained from public repositories. (Aim 1) We will first use individualized AC functional connectivity patterns to estimate risk factors for AD, including HL, in large low-resolution fMRI data sets. To validate the results in a different data set, we will use the same AC functional connectivity patterns to classify whether a participant is cognitively normal, has mild cognitive impairment (MCI), or has AD. (Aim 2) We will collect ultra-high resolution 7T fMRI data to examine the interactive impact of age-related auditory processing difficulties and classical risk factors for AD on functional arrangement of fine-grained subregions of AC. Ultimately, the results could help find early indicators of cognitive decline and aid the interventions to target disrupted neural pathways in AD patients with auditory processing difficulties.

为了响应 NOT-AG-22-025，该项目结合了超高分辨率 MRI 和先进的计算 分析以确定听觉皮层（AC）功能连接的病理变化，这些变化是 与阿尔茨海默病（AD）风险增加有关。越来越多的证据表明，与年龄有关 听力损失（HL）和中枢听觉处理困难可能是 AD 的重要危险因素。同时， 对患有年龄相关外周 HL（但未诊断为 AD）的个体进行的神经影像学研究表明，解剖学上 大脑皮层的功能变化，从初级 AC 延伸到听觉关联区， 支持复杂的认知过程，包括语音和语言。在这里，使用开发的方法 R01DC017991，我们测试了一个假设，即涉及 AC 的皮质网络的功能变化可能是 AD 风险的早期指标。 迄今为止，对人类 AC 细粒度变化的生物标志物的追求因以下几个因素而变得复杂 关键障碍：人类AC由多个相邻的小区域组成，使用这些区域很难区分 可用于人体功能 MRI (fMRI) 的常规分辨率；这些小的交流区域被广泛的激活 特征的组合，并显示出相当大的个体间差异。检查功能预测变量 因此，AD 中听觉处理困难的研究需要一个新颖的视角 1)，重点关注人类 ACs 如何 与人脑的其余部分相互作用，2）允许对动态功能进行个体水平的研究 网络而不仅仅是传统的功能磁共振成像组分析。在这里，我们追求一种全新的方式 表征人类 AC 功能组织病理变化的早期指标 AD 高风险个体参与者。我们提出的工作是建立在最新进展的基础上的，这些进展允许 使用超高分辨率 7T fMRI 关注个体受试者和动态功能活动模式。这 使用新的 7T fMRI 数据进行计算分析的结果，这些数据是在静息状态和听觉状态下收集的 老年参与者的刺激，将与使用较大样本（但分辨率较低）3T 获得的刺激进行比较 从公共存储库获得的功能磁共振成像数据集。 （目标1）我们将首先使用个性化的AC功能 在大型低分辨率 fMRI 数据集中估计 AD 风险因素（包括 HL）的连接模式。到 为了在不同的数据集中验证结果，我们将使用相同的 AC 功能连接模式来分类 参与者是否认知正常、患有轻度认知障碍 (MCI) 还是患有 AD。 （目标2）我们将 收集超高分辨率 7T fMRI 数据来检查与年龄相关的听觉处理的交互影响 AD 对 AC 细粒度分区功能安排的困难和经典风险因素。 最终，结果可以帮助找到认知能力下降的早期指标，并帮助干预措施针对 患有听觉处理困难的 AD 患者的神经通路受到破坏。