The Symptom Science of Excessive Daytime Sleepiness: A Multidimensional Approach

项目摘要/摘要 白天过度嗜睡(EDS)是人群中非常常见的症状，并有负面影响 关于一生中的健康和幸福。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 量化EDS有很大的局限性。特别重要的是，目前没有衡量困倦的标准 解释了症状本身的多面性，这是症状中的一个重要障碍 EDS的科学。这一应用基于理解生物学的基本哲学。 过度嗜睡的基础需要更仔细地测量表型本身。更多的用法 准确的客观嗜睡表型将加强对EDS患者的识别，以及 将这些表型映射到特定的大脑回路/通路。初步数据表明， 使用一种结合了多种措施的方法，EDS患者的病情显著增强 嗜睡症。此外，初步研究表明，脑部慢波活动减少 睡眠时边缘上回/体感皮质与丘脑-纹状体功能连接 觉醒，每一个都与白天昏昏欲睡的主观抱怨有关。在这些数据的基础上， 日间嗜睡症状科学的下一个关键步骤是：1)验证多模式的重要性 相对于健康对照组的睡眠亢进评估，以及2)将这些神经生物学发现映射到 白天嗜睡的具体客观衡量标准。因此，这项研究将针对以下三个具体目标 关于EDS症状科学中的这些重要领域的研究。首先，这项调查将核实 一项多模式睡眠过度评估，考虑了白天嗜睡的几个方面，确定了 不明原因EDS患者(n=31)与年龄和性别匹配的健康对照组(n=31)进行比较。第二，它 将确定与慢波局部减少相关的昏昏欲睡的具体客观指标 这些研究参与者睡眠时缘上回/体感皮质的活动。第三，它将 确定与丘脑-纹状体功能降低相关的嗜睡的具体客观指标 在这些相同的研究参与者中，唤醒期间的连接性。这些成就将产生相当大的影响。 论白天嗜睡的症状学，通过提高客观识别人的能力 白天嗜睡，以及可测量的嗜睡表型与相关的生理学联系 大脑中的过程。在这样做的时候，这个项目将开始剖析各种神经生物学途径。 将嗜睡作为一种症状负责，这是开发个性化药物方法的关键一步 通过有针对性的干预措施护理慢性嗜睡患者，以改善预后。

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.