Bilateral Brain Dynamics Supporting Cognition in Normal Aging and Dementia

项目摘要 这是一个K 01奖的应用程序西蒙·戴维斯博士，助理教授和认知神经科学家 在杜克脑科学研究所，一个支持研究人员连接基础科学的科学机构 和翻译应用。戴维斯博士正在将自己打造成一名基础和基础领域的年轻研究员 年龄相关认知障碍的转化研究。这个K 01奖项将为戴维斯博士提供 必要的支持，以实现以下目标：（1）成为认知电生理学的专家 (EEG)和临床研究，重点是阿尔茨海默病（AD），（2）获得实用的专业知识， 记忆过程中大脑半球通讯的电生理学途径，（3）整合新的大脑 刺激和脑电图技术在基础和转化研究，（4）开发新的脑刺激 协议，以提高注意力控制和记忆在正常和痴呆老年人群。到 戴维斯博士，他有一个关于情景和语义的神经机制的背景， 他组建了一个由他的主要导师Marty G.大四学生沃尔多夫 认知神经科学家，在注意力和认知的电生理学研究方面拥有丰富经验 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和遗忘型轻度认知障碍（MCI-AD），在目前的建议中检查的人群。 这项建议的重点是在理解双边大脑相互作用的差距和他们的作用，帮助 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，并通过精确应用 TMS，为了检验这一假设，即大脑半球之间的兴奋性相互作用可以提供积极的 临床前AD（遗忘型轻度认知障碍或MCI-AD）患者的结局。在目标1中，博士。 戴维斯将建立双边大脑机制的空间特异性与行为和高- 分辨率结构神经成像在已知的大脑皮层网站是活跃的记忆编码。在目标2中，博士 戴维斯将使用一本小说建立大脑半球间额叶交流的潜在动力学 结合单侧TMS、rTMS夹带条件和脑电图（EEG）， 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夹带 目标2中描述的参数，用于促进特定的跨半球沟通，适用于参与者 执行图片编码任务，这是记忆性能的一般任务。这些研究的结果将 允许戴维斯博士评估这种脑刺激方案在减轻年龄相关和 痴呆相关的认知能力下降这项研究将有助于开发新的治疗方案， 老年痴呆症，并形成神经退行性疾病纵向研究的基础， 在K裁决终止之前，R 01赠款申请中提出的。

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.