Personalized Synchronization of Cortical Rhythms to Improve Memory in Alzheimer's Disease

项目摘要/摘要 阿尔茨海默病是一种严重的衰弱疾病。它影响着全球超过5000万人，其 相关成本估计每年超过3,050亿美元。到本世纪中叶，1.53亿人 预计将患有阿尔茨海默氏症，成本预计将超过1万亿美元，因为全球 人口迅速老龄化。工作记忆受损是认知功能减退的一个主要特征 阿尔茨海默病和残疾的主要驱动因素，严格限制了社会功能，活动 日常生活，和生活质量。工作记忆指的是我们将行为上有用的信息保存在 它是人类认知的基本组成部分，也是 长期记忆。神经科学研究表明，工作记忆功能是 健康大脑中的振荡机制，以及同步振荡的特定模式 动力学对于理解阿尔茨海默病的发病机制可能很重要，这与 长期以来认为阿尔茨海默病是一种脱节综合症的假说。在这里，我们将研究 从生理学角度看阿尔茨海默病工作记忆损害的机制 以大规模大脑网络以及它们如何通过同步电生理相互作用为中心 震荡。我们关注已建立的神经编码方案(即，交叉频率耦合和相位 同步)被假设为索引将信息集成到多个 认知过程中的时间和空间尺度。我们结合了高密度脑电 个性化高清晰度经颅交流电同步振荡的测量 刺激，以确定是否有可能修改额颞部网络的组成部分和原因 工作记忆功能的快速改善。我们的初步数据非常令人鼓舞，表明 我们可以对长程低频振荡的同步性进行因果调制，增加局部相位。 幅度耦合，并将阿尔茨海默病患者的工作记忆能力提高到 相当于人口统计学上匹配的健康对照组。该研究项目的目标是利用 新的神经科学工具和分析方法，以更深入地了解糖尿病的病理生理学 阿尔茨海默病的记忆障碍，并取得具体的翻译进展 用于改善记忆和认知的个性化、非药物干预的发展 阿尔茨海默病和相关痴呆症。

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease is a severely debilitating disorder. It affects over 50 million people worldwide and its associated costs are estimated to exceed $305 billion annually. By mid-century, 153 million people are expected to be living with Alzheimer’s disease and costs are projected to surpass $1 trillion, as the global population rapidly ages. Impaired working memory is a central feature of the cognitive deterioration in Alzheimer’s disease and a primary driver of disability, placing sharp limits on social functioning, activities of daily living, and quality of life. Working memory refers to our ability to hold behaviorally useful information in mind over a period of seconds and is a fundamental building block of human cognition and the gateway to long-term memory. Neuroscience investigations have demonstrated that working memory function is subserved by oscillatory mechanisms in the healthy brain, and that specific patterns of synchronous oscillatory dynamics may be important for understanding the disease mechanisms of Alzheimer’s disease, consistent with the longstanding hypothesis of Alzheimer’s disease as a disconnection syndrome. Here, we examine the mechanisms of working memory impairment in Alzheimer’s disease from a physiologically inspired perspective centered on large-scale brain networks and how they interact through synchronized electrophysiological oscillations. We focus on established neural coding schemes (i.e., cross-frequency coupling and phase synchronization) hypothesized to index flexible large-scale circuits that integrate information across multiple temporal and spatial scales during cognition. We combine high-density electroencephalographic measurements of synchronized oscillations with personalized high-definition transcranial alternating-current stimulation to determine whether it is possible to modify components of frontotemporal networks and cause rapid improvements in working memory function. Our preliminary data are highly encouraging and indicate that we can causally modulate the synchronization of long-range low-frequency oscillations, increase local phase- amplitude coupling, and improve working memory capacity in people with Alzheimer’s disease to levels equivalent to that of demographically matched healthy controls. The goals of the research program are to use novel neuroscience tools and analytic procedures to gain a deeper understanding of the pathophysiology of memory impairment in Alzheimer’s disease, and achieve concrete translational progress toward the development of personalized, non-pharmacological interventions for improving memory and cognition in Alzheimer’s disease and related dementias.