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: 10553117
• 负责人: Seth D Springer
• 金额: $ 3.54万
• 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/10553117
• 关键词: Abeta clearance; Activities of Daily Living; Affect; Aging; Agreement; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Alzheimer' s disease patient; Amyloid beta-Protein; Animal Model; Attention; Attentional deficit; Biological Markers; Brain; Brain Mapping; Clinical; Clinical Skills; Cognition; Cognitive; Compensation; Complex; Data; Dementia; Detection; Disease; Early identification; Education; Electroencephalography; Electrophysiology (science); Evaluation; Event-Related Potentials; Exhibits; Frequencies; Frontotemporal Dementia; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; High Prevalence; Hippocampus; Human; Image; Impaired cognition; Individual; Interneurons; Intervention; Knowledge; 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; neural; neuroimaging; neurophysiology; reconstruction; 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 美国人口老龄化加剧，阿尔茨海默病（AD）患病率增加 其常见前兆——轻度认知障碍（MCI）预计在未来几年将急剧上升。 因此，国家迫切需要进一步了解这些神经生理学基础 最近的研究表明，动物的伽玛带神经振荡活动受到破坏。 此外，伽马频率的视觉刺激已被证明可以增加 AD 的清除率。 淀粉样蛋白-β (Aβ) 和过度磷酸化的 tau 蛋白在小鼠模型中的作用，同时提高认知能力。 这些突破性的发现，即对 AD 患者伽马振荡活动的研究仍然很少。 相关地，视觉空间注意力过程是最早且受影响最严重的认知功能之一 在 MCI 和 AD 中，该领域的功能障碍也被证明对于识别阿尔茨海默病更具特异性。 与其他类型的痴呆（例如额颞叶痴呆）相比，与其他类型的功能障碍相比 尽管神经心理学测试显示视觉空间存在明显缺陷。 尽管人们对 MCI 和 AD 患者的关注度很高，但人们对这些疾病背后的神经振荡活动知之甚少。 当前的研究旨在通过利用空间精度和空间精度来部分弥补这些知识差距。 简而言之，脑磁图 (MEG) 成像的精确时间分辨率（即毫秒）。 AD、MCI 和人口统计匹配对照将在 MEG 记录期间完成两项认知任务； 检查多光谱视觉夹带活动，另一个研究视觉空间注意力处理。 生成的 MEG 数据将被转换到时频域并使用波束形成进行成像 电神经活动的输出动态功能图将用于检查基线和 服务于视觉和视觉空间处理的区域之间与任务相关的夹带和振荡活动。 特别是，我们将识别 MCI 和 AD 患者的统计异常神经振荡，然后 将这些神经数据与区域 Aβ 沉积和整体表现（例如，一般和特定领域 认知、功能能力等）。我们的目标是：（1）量化视觉夹带过程中的皮质动态。 在 MCI 或轻度 AD 患者中以特定频率（即 20、35、40 和 45 Hz）进行研究，并确定关系 局部伽马活动和定量 Aβ 沉积之间的关系，以及 (2) 识别跟踪参与的缺陷 MCI 和轻度 AD 患者的视觉刺激，并确定其与认知表现的关系。 最后，我们将利用最新的脑磁图和源重建技术、神经振荡分析方法、 定量 Aβ PET 成像和神经心理学评估，以描绘神经生理学基础 这项研究将有助于阐明 MCI 和 AD 患者的认知障碍的神经动力学。 MCI 和 AD 患者潜在的认知功能障碍，其主要目标是科学发现和 发展申请人的研究和临床技能，以培养一名成功的医师科学家。