Improving Working Memory in Older Adults by Restoring Large-Scale Cortical Interactions

项目摘要/摘要 在过去的一个世纪里，我们目睹了认知能力下降和 1-3岁老年人中的痴呆症，预计未来几年随着全球人口的增加，痴呆症的增长会更快 年龄在3-5岁之间。几十年来，工作记忆的缺陷--持有行为有用信息的能力--在 思维“在一段时间内--这是观察到的正常认知衰退的一个主要特征 成年人的寿命和与痴呆相关的异常快速的认知退化，例如 阿尔茨海默病6-10岁。这些事实促使人们需要更多地了解大脑 与年龄相关的工作记忆缺陷的潜在机制，并开发有效的方法来维持或 甚至可以提高11-13岁老年人的认知能力。在这里，我们建议研究一下 从生理学角度看健康人与年龄相关的工作记忆损害 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 节拍14-18。我们的重点是神经编码方案(即，交叉频率耦合和相位同步) 假设索引灵活的大规模电路，这些电路集成了跨多个时间和 认知过程中的空间尺度。我们结合了高密度脑电(EEG)测量 个性化定制高清晰度交流电刺激同步节律 (HD-TAC)19-21，以确定是否可以修改额颞部网络的组件和 提高老年人的工作记忆能力。我们的初步数据显示 令人鼓舞，并表明我们可以因果性地操纵远程低频的同步 节律，增加局部相位-幅度耦合，并迅速改善老年人的工作记忆行为 60-76岁的成年人的准确度水平相当于20岁的人。这项研究的目标 计划是使用新的神经科学工具和分析程序来更深入地了解 与年龄相关的工作记忆损害的大脑机制，并为 开发有效的非药物干预措施改善健康老龄化和老年人的认知能力 临床人群。

PROJECT SUMMARY/ABSTRACT Over the last century, we have witnessed an astonishing rise in the prevalence of cognitive decline and dementia in older adults 1-3, which is expected to grow even faster in coming years as the global population rapidly ages 3-5. For decades, deficits in working memory - the ability to hold behaviorally useful information “in mind” over a period of seconds - have characterized a central feature of the normal cognitive decline observed across the adult lifespan and the abnormal rapid cognitive deterioration associated with dementias, such as Alzheimer's disease 6-10. These facts motivate the need to advance greater understanding of the brain mechanisms underlying age-related working memory deficits, and develop effective methods to maintain or even improve cognitive performance in older adults 11-13. Here, we propose to examine the mechanisms of age-related working memory impairment in healthy humans from a physiologically inspired perspective centered on large-scale brain networks and how they interact through synchronized electrophysiological rhythms 14-18. We focus on 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 (EEG) measurements of synchronized rhythms with individually customized high-definition transcranial alternating-current stimulation (HD-tACS) 19-21 to determine whether it is possible to modify components of frontotemporal networks and cause improvements in working memory performance for older adults. Our preliminary data are highly encouraging and indicate that we can causally manipulate the synchronization of long-range low-frequency rhythms, increase local phase-amplitude coupling, and rapidly improve working memory behavior in older adults aged 60-76 years to accuracy levels equivalent to those of 20-year-olds. The goals of the research program are to use novel neuroscience tools and analysis procedures to gain a deeper understanding of the brain mechanisms underlying age-related working memory impairment, and contribute new knowledge to the development of effective, non-pharmacological interventions for improving cognition in healthy aging and clinical populations.