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.

项目摘要 这是对现有项目的资助扩展（行政补充奖）的申请，使用 fMRI引导的TMS可提高老年人的中央执行功能。该奖项将为我们的团队提供 必要的支持，以扩大我们现有的EEG-TMS范式，以患者的前驱形式， 阿尔茨海默病（AD）被称为遗忘型轻度认知障碍（MCI），并研究 大脑健康因素介导与TMS相关的记忆性能益处， 在这些人群中，额顶叶脑区网络之间的通信。 该项目的主要目标是开发一种新的基于记忆的神经刺激方法 治疗神经刺激会影响皮层网络内的多个部位，但这些全局效应尚未得到证实。 由于对这些局部部位对神经元的影响了解有限， 大脑状态的整体变化。为了解决这个问题，我们将使用多模式神经成像工具和网络 通过母项目U 01开发的建模方法，以证明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 补充我们的三个具体目标。在目标1中，Davis博士将建立双侧的空间特异性 结合行为和皮质部位高分辨率结构神经成像的脑机制 已知在记忆编码期间是活动的。在目标2中，戴维斯博士将建立 使用单侧经颅磁刺激、rTMS夹带 条件和脑电图（EEG），以建立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，适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 性能正在进行的工作将为研究网络连接的动态提供重要工具 以及大脑刺激有效性的新信息 技术作为认知能力下降的治疗方法。 正如我们已经证明的那样，母项目K 01已经朝着这些目标取得了基础性的进展 在健康老年人和MCI中选择性调节记忆相关神经功能的能力。的 该项目在第1-3年取得了成功，出版了多份会议出版物，并编写了 手稿，并在临床和电生理学教学的发展目标的实现。 然而，正如预算理由中所述，由于新冠病毒，该项目已出现重大延误- 19全球大流行病，为了完成该项目，我们要求通过本补充额外的资金。 科学目标和方法与最初的建议保持不变。