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.

项目摘要/摘要 白天过度嗜睡（EDS）是人口中非常普遍的症状，并且具有负面影响 关于整个寿命的健康和福祉。尽管ED很重要，但对 与白天迟感有关的大脑的生物学变化，以及目前用于的客观措施 量化EDS具有重大局限性。特别重要的是，当前没有嗜睡的度量 说明症状本身的多维性质，这是症状的重大障碍 Eds科学。该应用基于理解生物学的基本哲学基础 过度嗜睡的基础要求更仔细地测量表型本身。使用更多 精确的客观嗜睡表型将增强对ED的人的识别以及 将这些表型映射到特定的脑电路/途径。初步数据表明识别 EDS患者使用多种度量的方法大大增强 高血压。此外，初步研究表明，慢波活性降低 睡眠期间和丘脑纹状体功能连通性期间的超边分级/体感皮层 唤醒，每个都与白天嗜睡的主观抱怨有关。在这些数据的基础上， 白天嗜睡的症状科学的下一个关键步骤是1）验证多模式的重要性 相对于健康对照的高血压评估，以及2）将这些神经生物学发现映射到 白天迟感的特定客观度量。因此，这项研究将针对针对的三个特定目标 在EDS症状科学中朝着这些重要的调查领域。首先，此调查将验证是否 一项多模式的高血压评估，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相比，具有无法解释的ED的人（n = 31）（n = 31）。第二，它 将确定与慢波局部减少有关的嗜睡的特定客观度量 在这些研究参与者中，在上半钟度/体感皮层中睡眠期间的活性。第三，它将 确定与丘脑纹状体功能降低相关的嗜睡的特定客观度量 在这些相同的研究参与者中唤醒期间的连通性。这些成就将产生很大的影响 关于白天嗜睡的症状科学，通过增强客观地识别患者的能力 白天迟感，以及将可测量的嗜睡表型与相关生理学联系起来 大脑中的过程。这样，这个项目将开始剖析各种神经生物学途径 负责嗜睡为症状，这是开发个性化医学方法的关键步骤 通过针对性干预措施改善预后的慢性嗜睡患者的护理。