Aberrant cortical entrainment in biomarker-confirmed Alzheimer's disease and mild cognitive impairment

生物标志物证实的阿尔茨海默病和轻度认知障碍中的异常皮质夹带

• 批准号: 10390119
• 负责人: Seth D Springer
• 金额: $ 3.44万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-12 至 2027-01-11
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10390119
• 关键词: Abeta clearance; Activities of Daily Living; Affect; Aging; Agreement; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Amyloid beta-Protein; Animal Model; Attention; Attentional deficit; Biological Markers; Brain; Brain Mapping; Clinical; Clinical Skills; Cognition; Cognitive; Complex; Data; Dementia; Detection; Disease; Early identification; Education; Electroencephalography; Electrophysiology (science); Evaluation; Event-Related Potentials; Exhibits; Financial compensation; Frequencies; Frontotemporal Dementia; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; High Prevalence; Hippocampus (Brain); Human; Image; Impaired cognition; Individual; Interneurons; Intervention; Knowledge; Lead; Learning; Life; Link; Location; Magnetoencephalography; Maps; Measures; Memory; Methods; Neurodegenerative Disorders; Neurology; Neuropsychological Tests; Neuropsychology; Older Population; Output; Participant; Pathologic; Pathology; Patients; Performance; Persons; Phase; Photic Stimulation; Physicians; Physiology; Population; Positron-Emission Tomography; Prefrontal Cortex; Prevalence; Process; Radiology Specialty; Research; Research Project Grants; Rest; Scientist; Secondary to; Severity of illness; Signal Transduction; Source; Statistical Data Interpretation; Stimulus; Task Performances; Techniques; Time; Training; United States; Visual; Visual Cortex; Visual attention; Visuospatial; abeta deposition; age related neurodegeneration; animal data; base; career; cognitive function; cognitive neuroscience; cognitive performance; cognitive task; cognitive testing; density; experience; healthy aging; human old age (65+); hyperphosphorylated tau; improved; indexing; instrumental activity of daily living; mild cognitive impairment; millisecond; mouse model; neuroimaging; neurophysiology; reconstruction; relating to nervous system; response; single photon emission computed tomography; temporal measurement; visual processing; visual stimulus

Abstract/Project Summary The United States population is becoming increasingly older and the prevalence of Alzheimer’s disease (AD) and its common precursor, mild cognitive impairment (MCI), is expected to dramatically rise in the coming years. As such, there is an immediate national need to further understand the neurophysiological basis of these neuro- degenerative diseases. Recent studies have shown disruption of gamma-band neural oscillatory activity in animal models of AD. Further, visual stimulation at gamma frequencies has been shown to increase the clearance of amyloid-β (Aβ) and hyperphosphorylated tau in mouse models, while improving cognitive performance. Despite these groundbreaking findings, research into gamma oscillatory activity in humans with AD remains scarce. Relatedly, visuospatial attention processes are among the earliest and most severely affected cognitive functions in MCI and AD. Dysfunction in this domain has also been shown to be more specific for identifying Alzheimer’s type dementia relative to other forms (e.g., frontotemporal dementia) when compared to dysfunction in other cognitive domains (e.g., memory). Although neuropsychological testing has shown clear deficits in visuospatial attention in patients with MCI and AD, very little is known about the neural oscillatory activity that underlies these deficits. The current study aims to partially remedy these knowledge gaps by utilizing the spatial precision and exquisite temporal resolution (i.e., millisecond) of magnetoencephalographic (MEG) imaging. Briefly, persons with AD, MCI, and demographically-matched controls will complete two cognitive tasks during MEG recording; one examining multispectral visual entrainment activity and another investigating visuospatial attention processing. The resulting MEG data will be transformed into the time-frequency domain and imaged using a beamforming approach. The output dynamic functional maps of electrical neural activity will be used to examine baseline and task-related entrainment and oscillatory activity among regions serving visual and visuospatial processing. In particular, we will identify the statistically anomalous neural oscillations in patients with MCI and AD, and then link these neural data to regional Aβ deposition and overall performance (e.g., general and domain-specific cognition, functional capacity, etc.). Our Aims are: (1) To quantify the cortical dynamics during visual entrainment at specific frequencies (i.e., 20, 35, 40, and 45 Hz) in patients with MCI or mild AD, and decifer the relationship between local gamma activity and quantitative Aβ deposition, and (2) to identify deficits in the tracking of attended visual stimuli in patients with MCI and mild AD, and determine how this relates to cognitive performance. To this end, we will utilize the latest MEG and source reconstruction techniques, neural oscillatory analysis methods, quantitative Aβ PET imaging, and neuropsychological assessments to delineate the neurophysiological bases of cognitive impairments in patients with MCI and AD. This research will aid in illuminating the neural dynamics underlying cognitive dysfunction in those with MCI and AD, with the primary goals of scientific discovery and developing the research and clinical skills of the applicant to produce a successful physician-scientist.

摘要/项目摘要 美国人口越来越大，阿尔茨海默氏病的流行率（AD） 预计未来几年，其常见的前体轻度认知障碍（MCI）预计将显着上升。 因此，民族直接需要进一步了解这些神经生理学的基础 退化性疾病。最近的研究表明，动物γ波段神经振荡活性的破坏 AD模型。此外，已显示在伽马频率上的视觉刺激增加了清除率 小鼠模型中的淀粉样蛋白-β（Aβ）和高磷酸化tau，同时改善认知性能。尽管 这些开创性的发现，对AD的人类γ振荡活动的研究仍然很少。 相关的是，视觉注意过程是最早，最严重影响的认知功能 在MCI和AD中。该域中的功能障碍也已被证明更特定于识别阿尔茨海默氏症 与其他功能障碍相比 认知领域（例如记忆）。 在MCI和AD患者中的注意，对这些基础的神经振荡活性知之甚少 缺陷。当前的研究旨在通过使用空间精度来部分记住这些知识差距 精美的临时分辨率（即毫秒）的磁脑（MEG）成像。简而言之，有人 AD，MCI和人口统计学匹配的控件将在MEG录制过程中完成两个认知任务；一 检查多光谱的视觉娱乐活动和另一种研究视觉注意力处理。 所得的MEG数据将被转换为时频域，并使用波束成像进行成像 方法。电神经活动的输出动态功能图将用于检查基线和 在视觉和视觉处理的区域之间与任务相关的入口和振荡活动。在 特别是，我们将确定MCI和AD患者的统计上异常的神经振荡，然后 将这些神经元数据与区域Aβ沉积和整体性能联系起来（例如，一般和域特异性 认知，功能能力等）。我们的目标是：（1）在视觉夹带期间量化皮质动力学 MCI或轻度AD患者的特定频率（即20、35、40和45 Hz），并确定关系 在局部伽马活性和定量Aβ沉积之间，以及（2）确定在参加的跟踪中的定义 MCI和轻度AD患者的视觉刺激，并确定这与认知性能的关系。对此 最后，我们将利用最新的MEG和源重建技术，神经振荡分析方法， 定量AβPET成像和神经心理学评估，以描绘神经生理基础 MCI和AD患者的认知障碍。这项研究将有助于阐明神经动态 在患有MCI和AD的患者中，认知功能障碍的基本功能障碍是科学发现的主要目标和 发展合适的研究和临床技能，以产生成功的身体科学家。