Neuroanatomical and functional outcomes of pediatric obstructive sleep apnea

描述（由申请人提供）：小儿阻塞性睡眠呼吸暂停（OSA）与执行功能受损相关，临床表现为学习、注意力、记忆力和学校表现受损，沿着神经心理发育异常。成年人的OSA与功能性脑激活的区域改变（增加和减少）、基于体素的形态测量的皮质灰质体积减少以及扩散张量成像的皮质下白色物质完整性改变相关。目前尚不清楚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导致直接脑损伤，导致皮质灰质丢失，改变白色物质的完整性，受损的静息状态的相互作用，和任务相关的功能性脑激活。此外，这些异常可能不容易逆转。实验性睡眠片段化导致海马体记忆和神经发生的长时程增强受损，而睡眠剥夺进一步导致细胞应激。缺氧可导致细胞丢失、凋亡增加，并激活多种神经元损伤机制。正常< 1 Hz的皮层神经元缓慢振荡的中断可以改变突触中的钙动力学，并且可能阻止睡眠的假定突触降尺度功能。OSA可导致显著的神经元、髓鞘和突触损伤。 我们研究的长期目标是确定OSA对大脑发育和儿童认知发病率的影响，以及作为成年期执行和情感功能障碍的危险因素。我们的研究将使用最先进的基于解剖和功能神经成像技术的磁共振成像（MRI），测量标准的多导睡眠图和神经心理学变量，并计算标准和新的睡眠质量和睡眠呼吸指数。本申请的具体目的是证明小儿OSA对1）皮质灰质和皮质下白色物质的影响，使用3特斯拉的高分辨率解剖磁共振成像; 2）功能性MRI上的工作记忆（包括外侧前额叶皮质的执行网络）和编码（包括海马的编码网络）任务相关激活。静息状态脑激活评估将补充上述方法。我们将评估治疗前和治疗后6个月（扁桃体切除术或气道正压通气）与健康年龄、体重指数、性别和坦纳分期匹配对照的差异。 神经解剖学指标（皮质厚度、各向异性分数、纤维长度、表观扩散系数）与执行网络区域（例如，背外侧前额叶、后顶叶、前扣带回）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进行探讨。

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.