Neuroanatomical and functional outcomes of pediatric obstructive sleep apnea

小儿阻塞性睡眠呼吸暂停的神经解剖学和功能结局

• 批准号: 8190113
• 负责人: Robert Joseph Thomas
• 金额: $ 25万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-14 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8190113
• 关键词: Adult; Affective; Aftercare; Age; Anatomy; Animal Model; Anisotropy; Anterior; Apolipoproteins; Apoptosis; Area; Attention; Biological; Body mass index; Brain; Brain Injuries; Breathing; Calcium; Cells; Cellular Stress; Child; Childhood; Choline; Cognitive; Complement; Continuous Positive Airway Pressure; Creatine; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Diffusion weighted imaging; Drops; Fiber; Free Radicals; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Gender; Gliosis; Goals; Hippocampus (Brain); Hypoxia; Imaging Techniques; Impairment; Injury; Kinetics; Lateral; Learning; Length; Lipid Peroxidation; Long-Term Potentiation; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mediating; Mediator of activation protein; Membrane; Memory; Morbidity - disease rate; Myelin; N-acetylaspartate; Neuronal Injury; Neurons; Nitric Oxide Synthase; Obstruction; Obstructive Sleep Apnea; Outcome; Oxygen; Parietal; Patients; Pattern; Performance; Platelet Activation; Polysomnography; Prefrontal Cortex; Recovery; Recovery of Function; Relative (related person); Reporting; Research; Research Project Grants; Resolution; Rest; Risk; Risk Factors; Rodent Model; Schools; Severity of illness; Short-Term Memory; Signal Transduction; Sleep; Sleep Apnea Syndromes; Sleep Deprivation; Sleep Fragmentations; Staging; Structure; Synapses; System; Task Performances; Techniques; Technology; Thick; Time; Tonsillectomy; basal forebrain; base; blood oxygen level dependent; cytokine; executive function; functional outcomes; gray matter; indexing; magnetic field; morphometry; myoinositol; neurogenesis; neuroimaging; neuron loss; neuropsychological; novel; pressure; prevent; standard measure; white matter

DESCRIPTION (provided by applicant): Pediatric obstructive sleep apnea (OSA) is associated with impaired executive function, and manifests clinically as impairments in learning, attention, memory, and school performance, along with abnormal neuropsychological development. OSA in adults has been associated with regional alterations (both increases and decreases) in functional brain activation, cortical grey matter volume reductions on voxel-based morphometry, and altered subcortical white matter integrity on diffusion tensor imaging. It is unknown if the effects of OSA on a developing brain are similar, and if these consequences are reversible. The central hypothesis is that pediatric OSA causes direct brain injury that result in cortical grey matter loss, altered white matter integrity, impaired resting state interactions, and task-related functional brain activation. Moreover, these abnormalities may not be readily reversible. Experimental sleep fragmentation causes impaired hippocampal long-term potentiation of memory and neurogenesis, while sleep deprivation further leads to cellular stress. Hypoxia can cause cell loss, enhance apoptosis and activate multiple mechanisms of neuronal injury. Disruption of the normal < 1 Hz slow cortical neuronal oscillation can alter calcium kinetics in the synapses and perhaps prevent a putative synaptic downscaling function of sleep. OSA can plausibly result in significant neuronal, myelin, and synaptic injury. The long-term goals of our research are to determine the impact of OSA on brain development and pediatric cognitive morbidity, and as a risk factor for executive and affective dysfunction in adulthood. Our research will use cutting edge magnetic resonance imaging (MRI) based anatomical and functional neuroimaging techniques, measure standard polysomnographic and neuropsychological variables, and compute standard and novel sleep quality and sleep-breathing indices. Our specific aims for this application are to demonstrate the impact of pediatric OSA on 1) cortical grey matter and subcortical white matter, using high resolution anatomical magnetic resonance imaging at 3 Tesla; 2) working memory (executive network including the lateral prefrontal cortex) and encoding (encoding network including the hippocampus) task- related activation on functional MRI. Resting state brain activation assessments will complement the above approaches. We will assess differences from healthy age, body mass index, gender, and Tanner stage matched controls, pre and 6-months post treatment (tonsillectomy or positive airway pressure). Correlations of neuroanatomical indices (cortical thickness, fractional anisotropy, fiber length, apparent diffusion coefficient) and functional activation volumes and % blood oxygen level dependent signal change, in areas of the executive network (e.g., dorsolateral prefrontal, posterior parietal, anterior cingulate) will be explored in relation to neuropsychological performance, neuroanatomical abnormalities, functional imaging abnormalities, and polysomnographic disease severity. PUBLIC HEALTH RELEVANCE: Sleep apnea is associated with repeated obstructions of airflow during sleep, resulting in sleep disruption and drops in oxygen during sleep. There is concern that such changes can harm the developing brain. This research project will use magnetic resonance imaging, a technique that uses powerful but safe magnetic fields to look at brain structure and function, to study the impact of sleep apnea on the child's (age 8-13 years) brain.

描述（由申请人提供）：儿童阻塞性睡眠呼吸暂停（OSA）与执行功能受损有关，临床表现为学习、注意力、记忆和学业表现受损，同时伴有神经心理发育异常。成人OSA与功能性脑激活的区域改变（增加或减少）、基于体素形态学的皮质灰质体积减少以及弥散张量成像的皮质下白质完整性改变有关。目前尚不清楚阻塞性睡眠呼吸暂停对发育中的大脑的影响是否相似，以及这些后果是否可逆。核心假设是，儿童阻塞性睡眠呼吸暂停导致直接脑损伤，导致皮质灰质丢失，白质完整性改变，静息状态相互作用受损，以及与任务相关的功能性脑激活。此外，这些异常可能不容易逆转。实验性睡眠碎片化导致海马记忆和神经发生的长期增强功能受损，而睡眠剥夺进一步导致细胞应激。缺氧可引起细胞损失，促进细胞凋亡，激活多种机制的神经元损伤。破坏正常的< 1hz的皮层神经元缓慢振荡可以改变突触中的钙动力学，并可能阻止假定的睡眠突触降尺度功能。OSA可能导致显著的神经元、髓鞘和突触损伤。我们研究的长期目标是确定阻塞性睡眠呼吸暂停对大脑发育和儿童认知疾病的影响，以及作为成年期执行和情感功能障碍的危险因素。我们的研究将使用尖端的磁共振成像（MRI）为基础的解剖和功能神经成像技术，测量标准的多导睡眠图和神经心理学变量，并计算标准和新颖的睡眠质量和睡眠呼吸指数。我们的具体目的是证明儿童OSA对1)皮质灰质和皮质下白质的影响，使用高分辨率解剖磁共振成像在3特斯拉；2)功能性MRI上工作记忆（包括外侧前额皮质在内的执行网络）和编码（包括海马在内的编码网络）任务相关激活。静息状态脑活动评估将补充上述方法。我们将评估健康年龄、体重指数、性别和Tanner分期匹配对照、治疗前和治疗后6个月（扁桃体切除术或气道正压通气）的差异。在执行网络区域（如背外侧前额叶、后顶叶、前扣带），神经解剖学指标（皮质厚度、分数各向异性、纤维长度、表观扩散系数）、功能激活体积和血氧水平依赖的信号变化与神经心理学表现、神经解剖学异常、功能成像异常和多导睡眠图疾病严重程度的关系将被探讨。