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

皮质节律的个性化同步可改善阿尔茨海默氏病的记忆力

基本信息

批准号：
10709218
负责人：
Robert Reinhart
金额：
$ 41.25万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10709218
关键词：
Activities of Daily Living Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease patient Alzheimer&apos s disease related dementia Area Behavioral Brain Brain Diseases Cephalic Code Cognition Cognitive Cognitive deficits Cortical Synchronization Coupled Coupling Data Data Collection Dementia Deterioration Development Disease Double-Blind Method Economics Electroencephalography Electrophysiology (science)Ensure Frequencies Functional disorder Future Goals Health Care Costs Human Impairment Individual Individual Differences Intervention Investigation Knowledge Maintenance Measurement Measures Mediating Memory Memory impairment Methods Nature Network-based Neurosciences Pattern Performance Periodicity Persons Phase Physiological Population Prefrontal Cortex Procedures Protocols documentation Public Health Quality of life Randomized Reproducibility of Results Research Research Personnel Sample Size Scheme Short-Term Memory Social Functioning Source Specificity Syndrome System Techniques Temporal Lobe Testing Therapeutic Therapeutic Intervention Validity of Results cognitive function cost cost estimate density disability drug development executive function experimental study flexibility functional disability improved indexing interest long term memory mild cognitive impairment neural neuromechanism neurophysiology neuroregulation novel novel therapeutics pathological aging power analysis programs reconstruction segregation social statistics support network theories tool translational neuroscience translational progress

项目摘要

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.

项目概要/摘要阿尔茨海默病是一种严重的使人衰弱的疾病，影响着全世界超过 5000 万人。据估计，到本世纪中叶，每年的相关费用将超过 3050 亿美元。预计患有阿尔茨海默病的患者的费用预计将超过 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能力下降的一个主要特征。阿尔茨海默病是导致残疾的主要原因，严重限制了社会功能、活动日常生活和生活质量是指我们保存对行为有用的信息的能力。大脑在几秒钟内的变化，是人类认知的基本组成部分，也是通往神经科学研究表明，工作记忆功能是受到健康大脑中振荡机制的促进，并且同步振荡的特定模式动力学对于理解阿尔茨海默病的疾病机制可能很重要，与长期以来，人们一直认为阿尔茨海默氏症是一种失联综合症，在此，我们来研究一下。从生理学角度探讨阿尔茨海默病工作记忆损伤的机制以大规模大脑网络及其如何通过同步电生理学相互作用为中心我们专注于已建立的神经编码方案（即跨频耦合和相位）同步）试图索引跨多个集成信息的灵活的大规模电路我们结合了高密度脑电图在认知过程中的时间和空间尺度。使用个性化高清经颅交流电测量同步振荡刺激以确定是否有可能改变额颞叶网络的组成部分并引起我们的初步数据非常令人鼓舞，表明工作记忆功能的快速改善。我们可以因果地调制远程低频振荡的同步，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一定水平相当于人口统计匹配的健康对照。该研究计划的目标是使用。新颖的神经科学工具和分析程序，以更深入地了解病理生理学阿尔茨海默病的记忆障碍，并在这方面取得具体的转化进展开发个性化的非药物干预措施以改善记忆和认知阿尔茨海默病和相关痴呆症。