THE PROGRESSIVE ELEVATION OF SPONTANEOUS CORTICAL ACTIVITY IN HAND (PESCAH) PROJECT

手部自发皮质活动逐步提升 (PESCAH) 项目

• 批准号: 10321801
• 负责人: Tony W Wilson
• 金额: $ 51.86万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10321801
• 关键词: AIDS dementia; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Adult; Affect; Age; Aging; Area; Behavioral; Brain; Brain Mapping; Brain region; Cerebral cortex; Chronic; Classification; Cognition; Cognition Disorders; Complication; Data; Development; Disease; Economics; Elderly; Exhibits; Felis catus; Functional disorder; General Population; Gold; HIV; HIV Infections; HIV-associated neurocognitive disorder; Hour; Human; Impairment; Individual; Knowledge; Laboratories; Life Expectancy; Link; Machine Learning; Magnetoencephalography; Maps; Motor; Motor Cortex; Movement; Nature; Neurobiology; Neurologic; Neurons; Neuropsychological Tests; Neuropsychology; Occipital lobe; Participant; Patients; Performance; Periodicity; Persons; Physiological; Physiology; Population; Prevalence; Quality of life; Reaction Time; Reporting; Research; Risk; Role; Sampling; Somatosensory Cortex; Synaptic Potentials; System; Targeted Research; Task Performances; Terminal Disease; Testing; Time; Unemployment; Visual Cortex; Western World; age related; antiretroviral therapy; base; behavioral impairment; cognitive function; cognitive performance; comorbidity; deep learning; electric field; healthy aging; indexing; learning strategy; medication compliance; neuroimaging; neurophysiology; nonhuman primate; novel; relating to nervous system; somatosensory

Project Summary/Abstract Although HIV-infected patients in the western world have a life expectancy near that of the general population, they are at a significantly elevated risk of developing HIV-associated neurocognitive disorders (HAND). Such disorders are the most common neurological complication of HIV disease, with prevalence estimates ranging from 35-70% of all HIV-infected patients, and research targeting such comorbidities has been identified as a top priority by the Office of AIDS Research (NOT-OD-15-137). While the mechanisms that underlie HAND are not well understood, numerous human neuroimaging studies have examined the brain regions that may be involved, and overall these studies have been largely successful in identifying the critical hubs and large-scale networks. However, many questions remain regarding basic circuit dysfunction within these brain regions, and consequently there is a clear and common need to further investigate the key physiological parameters that may underlie the development and progression of HAND, especially in the context of aging. It is well known that human cortical neurons exhibit spontaneous firing in the absence of incoming exogenous and endogenous input. Across a neuronal population, these discharges summate with local dendritic currents and synaptic potentials to produce cortical rhythmic activity, which is often referred to as “spontaneous activity.” Such spontaneous rhythms are ubiquitous throughout the human brain, but their role in modulating cognition is only beginning to be understood. Recently, we used magnetoencephalography (MEG) to show that the strength of spontaneous activity directly affects neural oscillatory activity in the same cortical area, and in-turn modulates real time task performance in controls and HIV-infected adults. Additionally, we have shown that spontaneous activity in multiple brain regions increases with advancing age, that this increase is deleterious to performance, and that these effects are accentuated in patients with HAND. In fact, our preliminary data suggests that the level of spontaneous activity in specific brain regions may distinguish age-matched HIV-infected patients with and without HAND. In this project, we will quantify the trajectory of age-related elevations in spontaneous cortical activity in a large group of HIV-infected adults and demographically-matched controls. We will then evaluate how the strength of such spontaneous activity affects local neural oscillations and real time cognitive performance. Based on extensive preliminary data, we hypothesize that spontaneous activity will increase with age in both groups, and that the slope of this increase will be steeper in HIV-infected adults relative to controls, and further accentuated in those with HAND. Importantly, we also hypothesize that these increases will be associated with proportional changes in the strength of the neural oscillations underlying cognition, and behavioral performance indices such as accuracy and reaction time. Finally, in Aim 3, we will utilize deep learning methods to classify our sample into groups based on the neurophysiological metrics derived from MEG, with the gold standard being their overall neuropsychological profile.

项目概要/摘要 尽管西方世界艾滋病毒感染者的预期寿命接近普通人群， 他们患艾滋病毒相关神经认知障碍（HAND）的风险显着升高。 疾病是艾滋病毒疾病最常见的神经系统并发症，患病率估计范围 占所有 HIV 感染者的 35-70%，针对此类合并症的研究已被确定为 艾滋病研究办公室 (NOT-OD-15-137) 的首要任务是，而 HAND 的机制是 尚不清楚，许多人类神经影像学研究已经检查了可能存在的大脑区域 总体而言，这些研究在确定关键枢纽和大规模 然而，关于这些大脑区域内的基本回路功能障碍仍然存在许多问题。 因此，明确且普遍需要进一步研究关键生理参数， 可能是 HAND 发生和进展的基础，尤其是在衰老的背景下。 众所周知，人类皮质神经元在没有外源传入的情况下表现出自发放电 在神经元群体中，这些放电与局部树突电流相结合。 和突触电位产生皮质节律活动，通常称为“自发活动”。 这种自发节律在人脑中普遍存在，但它们在调节认知方面的作用是 最近，我们使用脑磁图（MEG）来显示这种强度。 自发活动的直接影响同一皮质区域的神经振荡活动，并反过来调节 此外，我们还证明了对照组和感染艾滋病毒的成年人的实时任务表现。 多个大脑区域的活动随着年龄的增长而增加，这种增加对表现有害， 事实上，我们的初步数据表明，这些影响在 HAND 患者中更为明显。 特定大脑区域的自发活动水平可以区分年龄匹配的 HIV 感染者 在这个项目中，我们将量化自发升高的与年龄相关的轨迹。 然后我们将研究一大群感染艾滋病毒的成年人和人口统计学匹配的对照组的皮质活动。 评估这种自发活动的强度如何影响局部神经振荡和实时认知 基于大量的初步数据，我们敢于说自发活动会随着时间的推移而增加。 两组的年龄，并且相对于对照组，感染艾滋病毒的成年人的这种增加的斜率会更大， 重要的是，我们还认为这些增加将在手部患者中进一步加剧。 与认知神经振荡强度的成比例变化相关，并且 最后，在目标 3 中，我们将利用深度。 学习方法根据来自的神经生理学指标将我们的样本分组 MEG，黄金标准是他们的整体神经心理学特征。