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

项目总结/摘要 在上个世纪，我们目睹了认知能力下降的流行率惊人地上升， 1-3岁老年人痴呆症，随着全球人口的增长， 快速3-5岁。几十年来，工作记忆的缺陷-保持行为有用信息的能力“， 在几秒钟的时间内，“大脑”的功能已经成为观察到的正常认知能力下降的中心特征。 以及与痴呆症相关的异常快速认知衰退，如 老年痴呆症6-10.这些事实激发了对大脑更深入理解的需求 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 甚至可以改善11-13岁老年人的认知能力。在这里，我们建议检查的机制， 从生理学角度看健康人与年龄相关的工作记忆损伤 集中在大规模的大脑网络以及它们如何通过同步电生理学相互作用， 节奏14-18.我们专注于神经编码方案（即，交叉频率耦合和相位同步） 假设索引灵活的大规模电路，集成跨多个时间和 认知过程中的空间尺度。我们结合联合收割机高密度脑电图（EEG）测量， 通过个性化定制的高清晰度经颅交流电刺激实现同步节律 （HD-tACS）19-21，以确定是否有可能修改额颞叶网络的组件， 导致老年人工作记忆能力的提高。我们的初步数据显示 令人鼓舞的，并表明我们可以因果操纵的同步远程低频 节奏，增加局部相位振幅耦合，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。研究的目标 计划是使用新的神经科学工具和分析程序，以获得更深入的了解， 大脑机制潜在的年龄相关的工作记忆障碍，并贡献新的知识， 开发有效的非药物干预措施，以改善健康老龄化的认知能力， 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.