Bilateral Brain Dynamics Supporting Cognition in Normal Aging and Dementia

项目总结 这是对助理教授、认知神经科学家西蒙·戴维斯博士的K01奖的申请 在杜克大学脑科学研究所，一家支持研究人员在基础科学之间架起桥梁的科学机构 和翻译应用程序。戴维斯博士正在确立自己作为一名年轻研究人员的地位，在基础和 老年性认知障碍的翻译研究。这一K01奖项将为戴维斯博士提供 实现以下目标所需的支持：(1)成为认知电生理学专家 EEG和临床研究，重点是阿尔茨海默病(AD)，(2)在 记忆过程中大脑半球通讯的电生理途径，(3)整合新的大脑 基础研究和翻译研究中的刺激和脑电技术，以及(4)开发新的脑刺激 增强正常和痴呆症老年人群注意力控制和记忆的方案。至 实现这些目标，戴维斯博士，他有情节和语义的神经机制背景 Memory组建了一个由他的主要导师、大四学生Marty G.Woldorff博士组成的指导团队 认知神经学家，在注意和认知的电生理学研究方面有丰富经验 和共同导师理查德·奥布莱恩博士，杜克大学神经病学系主任，他有广泛的 对衰老和神经退行性疾病进行多方法研究的经验，包括 AD和遗忘性轻度认知障碍(MCI-AD)，在当前的提案中检查的人群。 这一建议的重点是对双边大脑相互作用及其在帮助中的作用的理解上的差距。 正常和临床老年人群保持认知健康。戴维斯博士的研究将集中在 研究这些相互作用的神经机制，并通过精确地应用 TMS，以检验两个半球之间的兴奋性相互作用可以提供正值的假设 临床前AD患者的预后(遗忘性轻度认知障碍或MCI-AD)。在目标1中，Dr。 戴维斯将结合行为和高密度脑功能建立双侧脑机制的空间特异性。 已知在记忆编码过程中活跃的皮质部位的分辨率结构神经成像。在《目标2》中，Dr。 戴维斯将使用一种新的方法建立大脑半球间额叶交流的潜在动力学 结合单侧TMS、rTMS引流条件和脑电(EEG)建立 两个半球之间的协调活动；最后，在目标3中，戴维斯博士将使用rTMS携带 目标2中描述的促进特定跨半球交流的参数，适用于参与者 执行图片编码任务，这是内存性能的一般任务。这些研究的结果将 允许Davis博士评估这种脑刺激方案在缓解年龄相关性和 痴呆症相关的认知功能减退。这项研究将使开发新的治疗方案成为可能 老年队列中的痴呆症，并形成对神经退行性疾病的纵向研究的基础 在K奖终止之前的R01拨款申请中提出。

PROJECT SUMMARY This is an application for a K01 award to Dr. Simon Davis, an Assistant Professor and cognitive neuroscientist at the Duke Institute of Brain Sciences, a scientific institute that supports researchers bridging basic science and translational applications. Dr. Davis is establishing himself as a young investigator in both basic and translational research of age-related disorders of cognition. This K01 award will provide Dr. Davis with the support necessary to accomplish the following goals: (1) become an expert in Cognitive Electrophysiology (EEG) and Clinical Research, with a focus on Alzheimer’s Disease (AD), (2) gain practical expertise in electrophysiological approaches to hemispheric communication during memory, (3) integrate novel brain stimulation and EEG techniques in both basic and translational studies, and (4) develop novel brain stimulation protocols to enhance attentional control and memory in normative and demented elderly populations. To achieve these goals, Dr. Davis, who has a background on the neural mechanisms of episodic and semantic memory, has assembled a mentoring team comprised of his primary mentor, Dr. Marty G. Woldorff, a senior cognitive neuroscientist with extensive experience in electrophysiological studies of attentional and cognitive control, and co-mentor Dr. Richard O’Brien, Chair of the Neurology Department at Duke, who has extensive experience conducting multimethodological investigations of aging and neurodegenerative disease, including AD and amnestic Mild Cognitive Impairment (MCI-AD), the population examined in the current proposal. This proposal is focused on the gap in understanding of bilateral brain interactions and their role in helping normative and clinical elderly populations maintain cognitive health. Dr. Davis’ research will focus on investigating this neural mechanism of these interactions and promoting them with a precise application of TMS, in order to test the hypothesis that excitatory interactions between the hemispheres can provide positive outcomes for patients with pre-clinical AD (amnestic Mild Cognitive Impairment or MCI-AD). 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 Picture Encoding task, a general task of memory performance. The outcome of these studies will allow Dr. Davis to evaluate the strength of this brain stimulation protocol in alleviating age-related and dementia-related cognitive decline. This research will enable development of novel treatment protocols for dementia in elderly cohorts, and form the basis of a longitudinal study in neurodegenerative disease that will be proposed in an R01 grant application before the termination of the K award.