Oscillatory markers of cognitive deficits in patients with Alzheimer's disease

摘要/项目总结 老龄化通常与一些有限的认知能力下降有关，尽管老龄化人口的一个亚组 将经历与阿尔茨海默氏病（AD）及其 轻度认知障碍（MCI）的常见前兆。今天大约有510万美国人患有AD， 我们迫切需要了解这些智力下降的神经生理学基础。关注和 工作记忆（WM）过程是MCI中最早和最严重影响的认知功能之一 的AD。注意力被定义为处理资源对特定刺激的优先分配 或刺激，而WM表示用于持续认知的信息的在线临时存储 处理.虽然神经心理学测试显示，在这些领域的患者明显缺陷， MCI和AD，对神经振荡活动和计算动力学的了解要少得多， 这些赤字。目前的研究旨在通过利用空间精度部分弥补这一知识差距 和精确的时间分辨率（即，脑磁图（MEG）成像。使用脑磁图， 我们将确定患有MCI和AD的成年人的注意力和WM功能障碍的神经生理学基础， 与人口统计学上匹配的神经学上健康的老年人样本相比。简而言之，与会者 在MEG记录期间，我将完成两个认知任务，一个是注意力加工，另一个是目标 在WM。这两种认知任务已被证明在健康的人中产生强大的神经振荡活动。 对照所得到的MEG数据将被转换到时间-频率域，并使用 先进的波束形成方法。将使用电神经活动的输出动态功能图 为了检查低频（即，α和θ）振荡活动和动态功能连接， 服务于注意力和WM过程的区域。从本质上讲，我们将确定统计异常的神经 振荡和功能连接的MCI和AD患者，然后将这些神经数据与认知 性能指标。我们的具体目标是：（1）识别异常的θ和α振荡动力学， MCI和轻度AD患者的WM和注意力处理的神经区域，以及（2）量化 MCI和轻度AD患者在这些相同的认知过程中的动态功能连接。到 为此，我们将利用最新的脑磁图和先进的源重建技术，神经振荡 分析方法和神经心理学评估，以描述认知功能障碍的神经生理学基础。 MCI和AD患者的损伤。随着世界人口以极不成比例的方式老化， AD患病率将在未来几十年内上升，与之相关的巨大经济和社会负担 疾病肯定会随之而来。研究旨在更好地了解疾病，并提供潜在的 用于诊断和跟踪疾病进展的标记物可能最终通过指导 并告知新的治疗开发和减少总体财务负担。

ABSTRACT/PROJECT SUMMARY Aging is typically associated with some limited cognitive decline, although a subgroup of the aging population will experience the rapid and progressive declines that are associated with Alzheimer’s disease (AD) and its common precursor, mild cognitive impairment (MCI). With around 5.1 million Americans living with AD today, there is an immediate need to understand the neurophysiological basis of these mental declines. Attention and working memory (WM) processes are among the earliest and most severely affected cognitive functions in MCI and AD. Attention is defined as the preferential allocation of processing resources towards a specific stimulus or stimuli, whereas WM denotes the on-line temporary storage of information to be used in ongoing cognitive processing. Although neuropsychological testing has shown a clear deficit in these domains in patients with MCI and AD, far less is known about the neural oscillatory activity and computational dynamics that underlie these deficits. The current study aims to partially remedy this knowledge gap by utilizing the spatial precision and exquisite temporal resolution (i.e., millisecond) of magnetoencephalographic (MEG) imaging. Using MEG, we will determine the neurophysiological bases of attentional and WM dysfunction in adults with MCI and AD, as compared to a demographically-matched sample of neurologically-healthy older adults. Briefly, participants will complete two cognitive tasks during MEG recording, one tapping attentional processing and another aimed at WM. Both of these cognitive tasks have been shown to produce robust neural oscillatory activity in healthy controls. The resulting MEG data will be transformed into the time-frequency domain and imaged using an advanced beamforming approach. The output dynamic functional maps of electrical neural activity will be used to examine low frequency (i.e., alpha and theta) oscillatory activity and dynamic functional connectivity among regions serving attention and WM processes. Essentially, we will identify the statistically anomalous neural oscillations and functional connectivity in patients with MCI and AD, and then link these neural data to cognitive performance metrics. Our specific aims are: (1) To identify aberrant theta and alpha oscillatory dynamics in neural regions serving WM and attention processing in patients with MCI and mild AD, and (2) to quantify dynamic functional connectivity during these same cognitive processes in patients with MCI and mild AD. To this end, we will utilize the latest MEG and advanced source reconstruction techniques, neural oscillatory analysis methods, and neuropsychological assessment to delineate the neurophysiological bases of cognitive impairments in patients with MCI and AD. With the world population aging in a highly disproportionate manner, AD prevalence is set to rise in future decades, and the hefty economical and societal burdens associated with the disease will certainly follow. Research aimed at better understanding the disease and providing potential markers for diagnosing and tracking disease progression may ultimately reduce the societal impact, by guiding and informing novel treatment development and reducing the overall financial burden.