Bilateral Brain Dynamics Supporting Cognition in Normal Aging and Dementia

项目摘要 这是对现有项目的资助延期(行政补充奖励)的申请，使用 FMRI引导TMS增加老年人的中央执行功能。这个奖项将为我们的团队提供 将我们现有的EEG-TMS范例扩展到前驱形式的脑震荡患者所需的支持 阿尔茨海默病(AD)称为遗忘性轻度认知障碍(MCI)，并探讨其作用机制 大脑健康因素在调节与TMS相关的记忆表现方面的益处 在这些人群中，额顶脑区网络之间的交流。 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 治疗。神经刺激影响大脑皮层网络中的多个部位，但这些全局影响尚未出现 用作刺激的目标，因为对这些局部化站点对 大脑状态的全球变化。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 通过母公司U01项目开发的建模方法，以演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 在我们的三个具体目标下补充。在目标1中，戴维斯博士将建立双边的空间特异性 大脑皮质部位行为和高分辨率结构神经成像相结合的脑机制 已知在存储器编码期间是活动的。在《目标2》中，戴维斯博士将建立 利用单侧TMS、rTMS携带的新组合进行大脑半球间额叶通信 条件，脑电(EEG)，以确定大脑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携带参数来促进特定的交叉 大脑半球交流，适用于完成单词编码任务的参与者，这是一种一般的记忆任务 性能。正在进行的工作将为研究网络连通性的动力学提供重要工具 关于老化大脑的记忆状态，以及关于大脑刺激有效性的新信息 技术作为一种治疗认知衰退的方法。 正如我们所展示的那样，母公司K01项目已经朝着这些目标取得了基础性的进展 有选择地调节健康老年人和MCI记忆相关神经功能的能力。这个 项目成功地进行了1-3年，出版了多份会议出版物，并编写了 手稿，以及临床和电生理学教学发展目标的实现。 然而，正如预算理由中所概述的那样，由于COVID的原因，该项目已出现重大延误- 19全球大流行病，为了完成这一项目，我们通过本补编请拨额外资金。 科学目标和方法与最初的提议保持不变。

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.