Characterizing vigilance in fMRI data and its relation to age-related cognitive impairment.

项目摘要/摘要 磁共振成像(MRI)是一种强大的非侵入性脑活动成像工具，允许 研究人类大脑功能和结构的动态变化的活动模式和结构 功能障碍。功能磁共振成像(FMRI)信号变化与警觉状态和皮质下-皮质 作为警觉波动的基础的网络，正越来越多地被认为是脑梗塞的fMRI信号 对神经科学和疾病研究都感兴趣。然而，在日常生活中，警惕在很大程度上被忽视了 FMRI研究，尽管受试者倾向于在扫描仪中入睡，并且某些患者群体可能 容易疲劳或白天困倦。更准确地描述了警惕在疾病中的作用， 以及它在功能磁共振数据中的作用，可能是开发成像生物标记物以及改进治疗的关键。我的 到目前为止，博士工作(Aim 1.1)开发了一种仅基于fMRI数据提取警戒指标的方法， 利用健康年轻人同时fMRI-EEG之间的相关性建立与警觉相关的活动模式 成年人。在我的F99阶段，我将(目标1.2)调查最先进的图像采集/处理 多回波独立分量分析(ME-ICA)方法提高了fMRI的对应性 信号和脑电信号，以及使用ME-ICA方法是否提高了检测皮质下的灵敏度 唤醒网络。最后，我将(在目标1.3中)尝试区分轻度认知受损(MCI)患者 通过利用基于功能磁共振成像的警觉作为生物标记物来控制健康的衰老。通过比较警戒性 波动和功能连通性差异的警觉网络感兴趣的区域，我们寻求 了解警惕在早期阿尔茨海默病中的作用。 提议的项目将帮助候选人Sarah Goodale；实现她成为一名 在一家专注于研究的机构中，处于老化神经成像最前沿的独立研究员。这个项目 提供脑电和功能磁共振成像分析和高级统计方法方面的前沿研究培训。此外， 拟议的研究将提供专业和技术培训，使候选人做好成功的准备 进入博士后(K00)阶段。博士后实验室将扩大萨拉的培训范围，将 结构成像以表征结构退变对功能网络的影响 与年龄相关的认知衰退。范德堡大学是实现这些目标的理想环境，因为它(1) 鼓励协作，(2)拥有最先进的技术资源来执行尖端研究，以及(3) 包含著名的教师，鼓励培训、指导和有抱负的研究人员的发展。 为F99和K00阶段提出的完整计划旨在开发一个独立的 神经成像科学家为成功的博士后职位做准备，并过渡到专注于老龄化的职业生涯。 最终目标是成为一名独立的终身调查员。

PROJECT SUMMARY/ABSTRACT Magnetic resonance imaging (MRI) is a powerful non-invasive tool for imaging brain activity that allows for investigating the dynamically changing activity patterns and structure that give rise to human brain function and dysfunction. Functional MRI (fMRI) signal variations linked with vigilance states, and the subcortical-cortical networks that underlie these fluctuations in vigilance, are being increasingly recognized as fMRI signals of interest both for neuroscience and in studying disease. However, vigilance has been largely ignored in routine fMRI studies, despite the fact that subjects tend to fall asleep in the scanner and certain patient populations may be susceptible to fatigue or daytime sleepiness. More precisely characterizing the role of vigilance in disease, and its effects in fMRI data, could be key for developing imaging biomarkers as well as improving treatment. My doctoral work thus far, (Aim 1.1) developed a method for extracting a vigilance metric, based on fMRI data alone, using a vigilance-related activity pattern built from correlations between simultaneous fMRI-EEG in healthy young adults. For my F99 phase, I will (Aim 1.2) investigate whether a state-of-the-art image acquisition/processing method, multi-echo independent component analysis (ME-ICA), improves the correspondence between fMRI signal and EEG signal, and whether using the ME-ICA approach improves sensitivity in detecting subcortical arousal networks. Finally, I will (in Aim 1.3) attempt to distinguish between mild cognitive impaired (MCI) patients and healthy aging controls by leveraging fMRI-based vigilance as a biomarker. By comparing vigilance fluctuations and functional connectivity differences in vigilance network regions of interest, we seek to understand the role of vigilance in early-stage Alzheimer’s disease. The proposed project will help the candidate, Sarah Goodale; achieve her career goal of becoming an independent investigator at the forefront of aging neuroimaging at a research-focused institution. This project provides cutting-edge research training in EEG and fMRI analysis and advanced statistical methods. Further, the proposed studies will provide professional and technical training to prepare the candidate to successfully transition the postdoctoral (K00) phase. The postdoctoral laboratory will extend Sarah’s training to incorporate structural imaging to characterize the impact of structural degeneration on functional networks with respect to age-related cognitive decline. Vanderbilt University is an ideal environment to achieve these goals as it (1) encourages collaboration, (2) has state-of-the-art technical resources to perform cutting-edge research, and (3) contains renowned faculty that encourage training, mentorship, and the development of aspiring researchers. The complete plan proposed for both the F99 and K00 phases is designed to develop an independent neuroimaging scientist prepared for a successful postdoctoral position and transition to an aging focused career, with an ultimate goal of becoming an independent tenured investigator.