Bilateral Brain Dynamics Supporting Cognition in Normal Aging and Dementia

双侧大脑动力学支持正常衰老和痴呆症的认知

• 批准号: 10395738
• 负责人: Simon W Davis
• 金额: $ 4.88万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10395738
• 关键词: Achievement; Address; Administrative Supplement; Adult; Affect; Alzheimer' s Disease; Attention; Award; Behavior; Behavioral; Bilateral; Brain; Brain region; Budgets; COVID-19 pandemic; Clinical; Cognition; Cognitive deficits; Communication; Contralateral; Corpus Callosum; Dementia; Development; Effectiveness; Elderly; Electroencephalography; Electrophysiology (science); Episodic memory; Foundations; Functional Magnetic Resonance Imaging; Funding; Genetic; Global Change; Goals; Impaired cognition; Impairment; Intervention; Knowledge; Left; Link; Manuscripts; Measures; Mediating; Memory; Memory impairment; Neuronal Plasticity; Neurons; Neurophysiology - biologic function; Neuropsychology; Neurosciences; Parents; Participant; Pathway interactions; Patients; Pattern; Performance; Phase; Physiologic pulse; Population; Prefrontal Cortex; Protocols documentation; Public Health; Publications; Research; Resolution; Resources; Risk; Risk Factors; Role; Semantics; Side; Site; Specificity; Structure; Task Performances; Technology; Testing; Therapeutic; Time; Transcranial magnetic stimulation; Work; age related; aging brain; amnestic mild cognitive impairment; base; behavioral outcome; brain health; clinically significant; cognitive benefits; cognitive enhancement; cognitive function; cognitive process; cohort; cost; design; effective therapy; executive function; experimental study; improved; indexing; insight; memory encoding; mild cognitive impairment; multimodality; network models; neurodegenerative dementia; neuroimaging; neuromechanism; normal aging; novel; novel strategies; relating to nervous system; spatiotemporal; symposium; tool; young adult

Project Summary This is an application for an Funded Extension (Administrative Supplement award) to an existing project, Using fMRI-guided TMS to increase central executive function in older adults. This award will provide our team with the support necessary to extend our existing EEG-TMS paradigm to patients with a prodromal form of Alzheimer’s Disease (AD) known as amnestic Mild Cognitive Impairment (MCI), and investigate the role of brain health factors in mediating the TMS-related memory performance benefits associated with communication between a network of frontoparietal brain regions in these populations. The main goal of the project is to address develop a novel approach to memory-based neurostimulation therapies. Neurostimulation affects multiple sites within a cortical network, but these global effects have not been used as targets for stimulation because of limited knowledge about what influence these localized sites have on global changes in brain state. To address this problem, we will use multimodal neuroimaging tools and network modeling approaches developed though the parent U01 project, to demonstrate how focal neurostimulation improves the efficacy of TMS for enhancing memory function. These goals will be addressed in the Administrative Supplement under our three specific aims. In Aim 1, Dr. Davis will establish the spatial specificity of bilateral brain mechanisms with combination of behavior and high-resolution structural neuroimaging in cortical sites known to be active during memory encoding. In Aim 2, Dr. Davis will establish the underlying dynamics of interhemispheric frontal communication using a novel combination of single-sided TMS, rTMS entraining conditions, and electroencephalography (EEG) to establish the coordinated activity between the hemispheres; Lastly, in Aim 3, Dr. Davis will use the rTMS entraining parameters delineated in Aim 2 to promote specific cross- hemispheric communication, applied to participants performing a Word Encoding task, a general task of memory performance. The ongoing work will provide an important tool for studying the dynamics of network connectivity of memory states in the aging brain, as well as new information on the effectiveness of brain stimulation technologies as a therapeutic approach for cognitive decline. The parent K01 project has made foundational advances towards these goals, as we have demonstrated the ability of to selectively modulate memory-related neural functions in healthy older adults and MCI. The project has proceeded successfully through Years 1-3, with multiple conference publications and prepared manuscripts, and the achievement of developmental goals in Clinical and Electrophysiology didactics. However, as outlined in the Budget Justification, the project has incurred a significant delay due to the COVID- 19 global pandemic, and in order to complete the project we request additional funds through this Supplement. The scientific goals and approach remain unchanged from the original proposal.

项目概要 这是对现有项目的资助扩展（行政补充奖）的申请，使用 功能磁共振成像引导的 TMS 可增强老年人的中枢执行功能。这个奖项将为我们的团队提供 将我们现有的 EEG-TMS 范式扩展到患有前驱症状的患者所需的支持 阿尔茨海默氏病 (AD) 被称为遗忘性轻度认知障碍 (MCI)，并研究 大脑健康因素介导与 TMS 相关的记忆表现益处 这些人群的额顶脑区域网络之间的通信。 该项目的主要目标是开发一种基于记忆的神经刺激的新方法 疗法。神经刺激会影响皮质网络内的多个部位，但这些全局效应尚未得到证实。 由于对这些局部站点的影响了解有限，因此将其用作刺激目标 大脑状态的整体变化。为了解决这个问题，我们将使用多模态神经影像工具和网络 通过母体 U01 项目开发的建模方法，以展示局灶性神经刺激如何 提高TMS增强记忆功能的功效。这些目标将在行政管理中得到解决 根据我们的三个具体目标进行补充。在目标 1 中，戴维斯博士将建立双边的空间特异性 结合行为和皮质部位高分辨率结构神经成像的大脑机制 已知在内存编码期间处于活动状态。在目标 2 中，戴维斯博士将建立以下基本动态： 使用单侧 TMS、rTMS 夹带的新颖组合进行半球间额叶通信 条件和脑电图 (EEG) 以确定半球之间的协调活动； 最后，在目标 3 中，戴维斯博士将使用目标 2 中描述的 rTMS 夹带参数来促进特定的交叉 半球通信，应用于执行单词编码任务的参与者，这是一项一般的记忆任务 表现。正在进行的工作将为研究网络连接动态提供重要工具 衰老大脑中的记忆状态，以及有关大脑刺激有效性的新信息 技术作为认知衰退的治疗方法。 正如我们所证明的那样，母体​​ K01 项目在实现这些目标方面取得了基础性进展 选择性调节健康老年人和 MCI 中与记忆相关的神经功能的能力。这 项目已成功进行了第一年至第三年，并出版了多份会议出版物并准备了 手稿，以及临床和电生理学教学发展目标的实现。 然而，正如预算理由中所述，由于新冠疫情，该项目出现了严重延误。 19 全球大流行，为了完成该项目，我们通过本补充文件请求额外资金。 科学目标和方法与最初的提案保持不变。