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: 9386501
• 负责人: Simon W Davis
• 金额: $ 11.45万
• 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 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9386501
• 关键词: Address; Affect; Age-associated memory impairment; Aging; Alzheimer' s Disease; Applications Grants; Attention; Basic Science; Behavior; Behavioral; Bilateral; Brain; Clinical; Clinical Research; Cognition; Cognition Disorders; Cognitive; Cognitive deficits; Communication; Contralateral; Corpus Callosum; Dementia; Development; Disease Progression; Effectiveness; Elderly; Electroencephalography; Electrophysiology (science); Episodic memory; Exhibits; Foundations; Goals; Health; Impaired cognition; Impairment; Institutes; Intervention; Investigation; K-Series Research Career Programs; Left; Link; Longevity; Longitudinal Studies; Measures; Medical; Memory; Memory Disorders; Mentored Research Scientist Development Award; Mentors; Neurodegenerative Disorders; Neurology; Neuronal Plasticity; Neurons; Neurosciences; Neurotransmitters; Older Population; Outcome Study; Participant; Pathway interactions; Patient-Focused Outcomes; Patients; Pattern; Performance; Phase; Physiologic pulse; Population; Prefrontal Cortex; Protocols documentation; Public Health; Research; Research Personnel; Resolution; Resources; Risk; Risk Factors; Role; Science; Semantic memory; Semantics; Side; Site; Specificity; System; Task Performances; Techniques; Testing; Therapeutic; Time; Transcranial magnetic stimulation; Translational Research; Treatment Efficacy; Treatment Protocols; Work; age related; amnestic mild cognitive impairment; attentional control; base; behavioral outcome; clinically significant; cognitive control; cognitive enhancement; cognitive function; cognitive process; cohort; daily functioning; demented; design; effective therapy; experience; experimental study; improved; indexing; memory encoding; mortality; multimodality; neurodegenerative dementia; neuroimaging; neuromechanism; normal aging; novel; pre-clinical; professor; relating to nervous system; spatiotemporal; therapy development; translational study; young adult

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.

项目摘要 这是助理教授和认知神经科学家西蒙·戴维斯（Simon Davis）博士申请K01奖的申请 在杜克大学脑科学学院，一家支持研究人员桥接基础科学的科学研究所 并翻译应用程序。戴维斯博士正在基本和 与年龄有关的认知疾病的翻译研究。该K01奖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，重点是阿尔茨海默氏病（AD），（2）获得实用的专业知识 记忆期间的电生理方法进行半球通信，（3）综合新颖的大脑 基础研究和翻译研究中的刺激和脑电图技术，以及（4）发展新型的大脑刺激 在正常和痴呆的老年人群中增强注意力控制和记忆的方案。到 实现这些目标，戴维斯博士，他在情​​节和语义的神经机制方面具有背景 记忆，已经组建了一个心理团队，完成了他的主要精神，Marty G. Woldorff博士 认知神经科学家在注意力和认知的电生理研究中具有丰富的经验 Control，以及杜克大学神经病学系主任Richard O'Brien博士，他拥有广泛的 对衰老和神经退行性疾病进行多杀症学研究的经验，包括 AD和敏感的轻度认知障碍（MCI-AD），在当前提案中检查的人群。 该提议的重点是理解双边脑相互作用及其在帮助的差距 正常和临床上的人群保持认知健康。戴维斯博士的研究将重点放在 调查这些相互作用的这种神经元机制，并通过精确地应用 TMS，为了检验以下假设：半球之间的兴奋性相互作用可以提供阳性 临床前AD患者的结局（羊膜轻度认知障碍或MCI-AD）。在AIM 1中，博士 戴维斯将建立双边脑机制的空间特异性，并结合行为和高 在记忆编码过程中已知活跃的皮质位点的分辨率结构神经影像学。在AIM 2中，博士 戴维斯将使用新颖 单面TMS，RTM的插入条件和脑电图（EEG）的组合以建立 半球之间的协调活性；最后，在AIM 3中，戴维斯博士将使用纳入RTMS AIM 2中描述的参数用于促进特定的跨膜通信，应用于参与者 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 允许戴维斯博士评估该大脑刺激方案的强度，以减轻与年龄相关的和 与痴呆有关的认知下降。这项研究将使开发新的治疗方案 古老的痴呆症，并构成了神经退行性疾病的纵向研究的基础 在终止K裁决之前，在R01赠款申请中提议。