Disrupted Nighttime Sleep (DNS) in Pediatric Narcolepsy

摘要 该提案将支持这项研究，并进一步支持基兰·马斯基博士作为内科科学家在 睡眠神经学。Maski博士的长期目标是研究人类夜间睡眠的神经生理学。 儿童发作性睡病及其与认知和心理共病的关系 识别潜在的睡眠神经生理学诊断和预测生物标记物，并开发和测试睡眠- 减轻儿童发作性睡病患者疾病负担的具体治疗。为了实现这些目标，一个 培训计划侧重于(1)学习睡眠动力学的分析技能，(2)认知和 行为神经科学和睡眠-觉醒生理学，(3)纵向和临床试验研究设计 促进罕见疾病研究的建议是为了补充Maski博士在儿童神经学和 安眠药。这项培训将通过正式的课程作业、动手培训和多种方式完成。 与世界知名的睡眠唤醒神经生理学专家进行学科指导(托马斯·斯卡梅尔博士)和 认知神经科学(罗伯特·斯蒂克戈尔德博士)。其他具有以下专业知识的顾问和合作者 利用远程视听的数学建模、统计学、行为科学和研究方法 技术将丰富马斯基博士的培训和拟议中的研究。培训将在以下背景下进行 哈佛医学院、哈佛大学陈天海公共卫生学院和波士顿丰富的学术环境 儿童医院。这项研究计划旨在测试扰乱夜间睡眠的中心假说 儿童发作性睡病1型(NT1)是一种特殊而动态的睡眠病理形式，它损害了 睡眠时发生的正常情绪和记忆过程。为了检验这一假设，我们提出了三个假设 目标是相互赞许但又独立的。在目标1中，我们进行了一项横断面研究，以定义 与其他睡眠障碍和对照相比，儿童NT1独有的测量方法。在目标2中，我们研究了变化 在儿科NT1队列中使用翻译分析方法的糖尿病肾病。最后，在目标3中，我们调查了 非药物治疗的儿童NT1患者和非药物治疗的儿童NT1患者之间睡眠结构的预测变化 已确定的羟丁酸钠治疗(一种治疗糖尿病肾病的镇静药物)和健康的、年龄匹配的对照组 确定睡眠碎片对记忆巩固和睡眠后情绪过程的直接影响。 公共健康：大量证据表明睡眠与认知和情绪过程有关。然而，人们对此知之甚少。 儿科神经系统疾病中发生的特殊病理性睡眠变化及其作用 在繁重的认知和心理并存的发展中发挥作用。这项建议的目的是 提供新的分析方法来表征发作性睡病等神经系统疾病的睡眠病理 显示睡眠中断的直接认知和心理影响的新方法，并形成 为针对睡眠的治疗策略奠定基础，以减轻神经系统疾病的疾病负担。

ABSTRACT The proposal will support the research and further Dr. Kiran Maski's training as a physician-scientist in sleep neurology. Dr. Maski's long-term objectives are to examine the neurophysiology of nocturnal sleep in pediatric narcolepsy and its relationship to cognitive and psychological co-morbidities common to this disease, to identify potential sleep neurophysiological diagnostic and predictive biomarkers, and develop and test sleep- specific treatments to reduce disease burden of pediatric narcolepsy patients. To achieve these goals, a training plan focused on (1) analytic skills to study sleep dynamics, (2) fundamental knowledge in cognitive and behavioral neuroscience and sleep-wake physiology, (3) longitudinal and clinical trial research design to facilitate rare disease research is proposed to complement Dr. Maski's background in child neurology and sleep medicine. This training will be accomplished through formal coursework, hands on training, and multi- disciplinary mentorship with world-renown experts in sleep-wake neurophysiology (Dr. Thomas Scammell) and cognitive neuroscience (Dr. Robert Stickgold). Additional consultants and collaborators with expertise in mathematical modeling, statistics, behavioral science, and research methodology utilizing remote audiovisual technology will enrich Dr. Maski's training and proposed research. This training will occur in the context of the rich scholarly environment of Harvard Medical School, Harvard T.H. Chan School of Public Health and Boston Children's Hospital. The research plan is devised to test the central hypothesis that disrupted nighttime sleep (DNS) in pediatric narcolepsy type 1 (NT1) is a specific and dynamic form of sleep pathology that impairs normal emotional and memory processes that occur during sleep. To test this hypothesis, we propose three complimentary but independent aims. In Aim 1, we conduct a cross-sectional study to define DNS with measures unique to pediatric NT1 compared to other sleep disorders and controls. In Aim 2, we study changes in DNS using translational analytic methods within a pediatric NT1 cohort. Lastly, in Aim 3, we investigate predicted changes to sleep architecture between drug-free pediatric NT1 patients, pediatric NT1 patients on established sodium oxybate therapy (a sedating drug that treats DNS) and healthy, aged-matched controls to determine direct effects of sleep fragmentation on memory consolidation and post-sleep emotional processes. Public Health: Substantial evidence links sleep with cognitive and emotional processes. Yet , little is known of the specific pathologic sleep changes that occur in pediatric neurologic diseases and the role this pathology plays in the development of burdensome cognitive and psychological co-morbidities. This proposal serves to provide new analytic methods to characterize sleep pathology in neurological diseases like narcolepsy, test novel methods that show direct cognitive and psychological effects of sleep disruption, and forms the foundation for sleep-specific treatment strategies to reduce disease burden in neurological diseases.