The Symptom Science of Excessive Daytime Sleepiness: A Multidimensional Approach

白天过度嗜睡的症状科学：多维方法

• 批准号: 10022519
• 负责人: David T Plante
• 金额: $ 23.26万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-23 至 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10022519
• 关键词: Achievement; Address; Affect; Age; Area; Arousal; Automobiles; Biological; Biology; Brain; Cataplexy; Cell Nucleus; Chronic; Clinical; Complex; Data; Development; Disease; Drowsiness; Excessive Daytime Sleepiness; Exhibits; Goals; Health; Hypersomnolence; Individual; Injury; Intervention; Investigation; Lead; Link; Longevity; Maintenance; Maps; Measurable; Measurement; Measures; Mediating; Medical; Mental disorders; Narcolepsy; Nature; Nerve Degeneration; Nervous System Physiology; Neuraxis; Neurobiology; Neurotransmitters; Obstructive Sleep Apnea; Occupational; Participant; Pathway interactions; Patient Care; Patients; Personal Satisfaction; Persons; Phenotype; Philosophy; Physiological Processes; Population; Productivity; Public Health; Regulation; Research; Rest; Risk; Risk Factors; Scientific Inquiry; Sleep; Sleep Apnea Syndromes; Sleep Deprivation; Somatosensory Cortex; Structure of supramarginal gyrus; Symptoms; Test Result; Testing; Wakefulness; Workplace; alertness; awake; base; cerebrovascular; common symptom; disability; experience; falls; functional disability; improved outcome; large datasets; multimodality; neurobehavioral; neurophysiology; personalized medicine; response; sex; symptom science; vigilance

PROJECT SUMMARY/ABSTRACT Excessive daytime sleepiness (EDS) is a very common symptom in the population, and has negative effects on health and well-being across the life span. Despite the importance of EDS, little is known about the biological changes in the brain associated with daytime somnolence, and objective measures currently used to quantify EDS have significant limitations. Of particular importance is that no current measure of sleepiness accounts for the multidimensional nature of the symptom itself, which is a significant barrier in the symptom science of EDS. This application is grounded in the fundamental philosophy that to understand the biological bases of excessive sleepiness requires that the phenotype itself be more carefully measured. The use of more precise objective sleepiness phenotypes will enhance the identification of persons with EDS, as well as the mapping of these phenotypes to specific brain circuits/pathways. Preliminary data suggest that identification of patients with EDS is dramatically enhanced using an approach that incorporates multiple measures of hypersomnolence. In addition, preliminary studies demonstrate that reduced slow wave activity in the supramarginal gyrus/somatosensory cortex during sleep and thalamostriatal functional connectivity during wake, are each associated with the subjective complaint of daytime sleepiness. Building on these data, the next crucial steps in the symptom science of daytime sleepiness are to 1) verify the importance of multimodal hypersomnolence assessments relative to healthy controls, and 2) to map these neurobiological findings to specific objective measures of daytime somnolence. Thus, this study will address three Specific Aims targeted towards these vital areas of inquiry in the symptom science of EDS. First, this investigation will verify whether a multimodal hypersomnolence assessment, that considers several facets of daytime sleepiness, identifies persons with unexplained EDS (n=31) compared to age- and sex-matched healthy controls (n=31). Second, it will identify specific objective measures of sleepiness that are associated with local reductions in slow wave activity during sleep in the supramarginal gyrus/somatosensory cortex in these study participants. Third, it will identify specific objective measures of sleepiness that are associated with reduced thalamostriatal functional connectivity during wake in these same research participants. These achievements will have a sizeable impact on the symptom science of daytime sleepiness, by enhancing the ability to objectively identify persons with daytime somnolence, as well as linking measurable sleepiness phenotypes to associated physiological processes in the brain. In so doing, this project will begin to dissect the various neurobiological pathways responsible for sleepiness as a symptom, a crucial step in developing personalized medicine approaches to the care of patients with chronic sleepiness through targeted interventions to improve outcomes.

项目总结/摘要 白天过度嗜睡（EDS）是人群中非常常见的症状，并具有负面影响 健康和幸福的影响。尽管EDS很重要，但人们对它知之甚少。 与白天嗜睡相关的大脑生物学变化，以及目前用于 EDS的量化有很大的局限性。特别重要的是，目前没有任何衡量睡眠的标准， 解释了症状本身的多维度性质，这是症状中的一个重要障碍 EDS科学这个应用程序是基于基本的哲学，即要了解生物 过度嗜睡的基础需要更仔细地测量表型本身。使用更 精确的客观嗜睡表型将增强对EDS患者的识别， 将这些表型映射到特定的脑回路/通路。初步数据显示， EDS患者使用一种结合多种措施的方法， 嗜睡此外，初步研究表明，减少慢波活动，在 边缘上回/躯体感觉皮层在睡眠和丘脑纹状体功能连接 醒，都与白天嗜睡的主观抱怨有关。基于这些数据， 日间嗜睡症状科学的下一个关键步骤是：1）验证多模态的重要性， 相对于健康对照的嗜睡评估，以及2）将这些神经生物学发现映射到 日间嗜睡的具体客观指标。因此，本研究将解决三个具体目标， 对EDS症状科学中这些重要领域的研究。首先，这项调查将核实 多模态嗜睡评估，考虑了白天嗜睡的几个方面， 与年龄和性别匹配的健康对照组（n = 31）相比，不明原因EDS患者（n = 31）。二是 将确定与慢波局部减少相关的嗜睡的具体客观测量 这些研究参与者的边缘上回/躯体感觉皮层在睡眠期间的活动。三是将 确定与丘脑纹状体功能降低相关的嗜睡的具体客观测量 在这些研究参与者清醒时的连接性。这些成就将产生相当大的影响 在白天嗜睡的症状科学，通过提高客观识别的人的能力， 白天嗜睡，以及将可测量的嗜睡表型与相关的生理 大脑中的过程。这样做，这个项目将开始剖析各种神经生物学途径 负责嗜睡作为一种症状，在发展个性化的医疗方法， 通过有针对性的干预措施来改善慢性嗜睡患者的护理结果。