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

基本信息

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
项目类别：
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

项目摘要

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）：小儿阻塞性睡眠呼吸暂停（OSA）与执行功能受损有关，并在临床上表现为学习，注意力，记忆和学校表现的障碍，以及神经心理学的异常。成人中的OSA与功能性脑激活的区域变化（增加和减少）有关，基于体素的形态计量学上的皮质灰质体积减少以及对扩散张量成像的皮层白质完整性改变。 OSA对发育中的大脑的影响是否相似，以及这些后果是否可逆。中心假设是，小儿OSA会导致直接的脑损伤，导致皮质灰质损失，白质完整性改变，静止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可逆。实验睡眠碎片化导致海马长期增强记忆和神经发生的损害，而睡眠剥夺进一步导致细胞应激。缺氧会导致细胞丧失，增强凋亡并激活多种神经元损伤的机制。正常<1 Hz慢的皮质神经元振荡的破坏会改变突触中的钙动力学，也许可以防止睡眠的突触降低降低功能。 OSA可能会导致明显的神经元，髓磷脂和突触损伤。我们研究的长期目标是确定OSA对大脑发育和小儿认知发病率的影响，并确定成年后执行和情感功能障碍的危险因素。我们的研究将使用最前沿的磁共振成像（MRI）基于解剖和功能性神经影像学技术，测量标准的多摄影学和神经心理学变量，以及计算标准和新颖的睡眠质量和睡眠呼吸指数。我们针对此应用的具体目的是使用高分辨率的解剖学磁共振成像在3特斯拉时证明小儿OSA对1）皮质灰质和皮质下白质的影响； 2）工作记忆（包括前额叶皮层的执行网络）和编码（包括海马的编码网络）功能MRI的任务激活相关。静止状态大脑激活评估将补充上述方法。我们将评估与健康年龄，体重指数，性别和坦纳阶段相匹配的控制，治疗前和6个月（扁桃体切除术或气道正压）的差异。神经解剖指标（皮质厚度，各向异性，纤维长度，明显的扩散系数）和功能激活量和％血氧水平依赖性信号变化的相关性与神经心理学表现，神经解剖异常，功能成像异常和多个学术疾病疾病严重程度有关。公共卫生相关性：睡眠呼吸暂停与睡眠期间的气流反复障碍有关，导致睡眠中断和睡眠期间氧气下降。人们担心这种变化会损害发展中的大脑。该研究项目将使用磁共振成像，该技术使用强大但安全的磁场来研究大脑结构和功能，以研究睡眠呼吸暂停对儿童（8-13岁）大脑的影响。