Sleep, the glymphatic system, and social communication development

项目摘要： 睡眠在包括神经、免疫和内分泌系统在内的几个生物过程中起着至关重要的作用。 睡眠的一个关键功能是通过脑脊液（CSF）清除神经元代谢废物 胶质淋巴系统（glymphatic system，GS）GS是一个全脑系统，其功能得到增强， 在睡眠中清除炎症蛋白和代谢物。最近我们在了解 GS强调其在神经发育障碍和发育风险中的作用。具体来说，沈和 同事报告蛛网膜下腔中过量CSF（轴外CSF; EA-CSF）作为早期标志物 孤独症和发展风险与睡眠问题的相关性。MRI提取的EA-CSF体积可用于 作为GS解剖结构的非侵入性标记。虽然导致EA-CSF过量的确切机制是 尽管未知，但已知GS过程在睡眠期间增强。发育期标记为高 睡眠需求（例如，婴儿期），可能反映了对清除神经元代谢废物的需求增加。 在早期发育过程中，睡眠中断可能会影响GS功能，并有可能导致 神经发育风险和恢复力。本研究旨在阐明睡眠与 失调，婴儿期EA-CSF生长模式，以及自闭症儿童的已知关注领域- 社会沟通发展。在本研究中，我们将索引EA-CSF体积数据， 在婴儿连接组项目（U 01 MH 110274）中使用高分辨率 从1到26个月的结构MRI扫描。该数据集的混合加速纵向设计是 非常适合发展模式估计。通过新开发的自动化MRI管道，我们将 EA-CSF模式在生命的前两年。描述EA-CSF发育与EA-CSF的关系 和睡眠失调（目标1），我们将比较两组婴儿的EA-CSF生长模式- 睡眠调节（S-REG）和睡眠失调（S-DYS）。我们通过年龄的相互作用来预测一个群体， S-DYS组显示EA-CSF随时间的生长模式，其相对于S-DYS组显著增加。 REG组。我们认为，S-DYS组EA-CSF的增加可能反映了CSF的失衡 流通/清关。为了评估睡眠失调和EA-CSF生长模式与社会因素的关系， 沟通发展（目标2），我们将完成另一组基于组的分析，以评估是否低于 社会沟通评分存在于（1）S-DYS组和（2）具有非典型EA-CSF生长的婴儿中 模式.这项工作的首要目标是告知睡眠之间的机械通路 失调和神经发育风险。这项研究的重点是EA-CSF，基于其已知的连接， 睡眠、自闭症和其他发育风险指数。使用发展心理病理学方法，这 研究提供了关键的第一步，在翻译如何EA-CSF的增长在一个社区的样本可以告知我们的 了解社交风险和恢复力的潜在神经解剖学标志。

Project Summary: Sleep plays a crucial role in several biological processes including nervous, immune, and endocrine systems. One critical function of sleep is the removal of neuronal metabolic waste via cerebrospinal fluid (CSF) circulation within the glymphatic system (GS). The GS is a brain-wide system with functions that are enhanced during sleep to clear inflammatory proteins and metabolites. Recent advancements in our understanding of the GS highlight its role in neurodevelopmental disorders and developmental risk. Specifically, Shen and colleagues reported excessive CSF in the subarachnoid space (extra-axial CSF; EA-CSF) as an early marker of autism and a correlate of developmental risk and sleep problems. MRI extracted EA-CSF volume can serve as a non-invasive marker of GS anatomy. Although the precise mechanisms leading to excessive EA-CSF are unknown, it is known that GS processes are enhanced during sleep. Developmental periods marked by high sleep need (e.g., infancy), likely reflect an increased need for the clearance of neuronal metabolic waste. Disruptions in sleep, during early development likely influence GS function and have the potential to contribute to neurodevelopmental risk and resilience. This study aims to elucidate the relations between sleep dysregulation, EA-CSF growth patterns in infancy, and a known area of concern for children with autism - social communication development. Within this study, we will index volumetric EA-CSF data from the community sample followed within the Baby Connectome Project (U01MH110274) with high-resolution structural MRI scans from 1 to 26 months of age. The hybrid accelerated longitudinal design of this dataset is well-suited for developmental pattern estimation. With a newly-developed automated MRI pipeline, we will model EA-CSF patterns over the first two years of life. To describe the relations between EA-CSF development and sleep dysregulation (Aim 1), we will compare EA-CSF growth patterns across two groups of infants – those with regulated (S-REG) and dysregulated (S-DYS) sleep. We predict a group by age interaction, with the S-DYS group showing a growth pattern of EA-CSF over time that is significantly increased relative to the S- REG group. We believe the greater increase of EA-CSF in the S-DYS group may reflect an imbalance of CSF circulation/clearance. To assess how sleep dysregulation and EA-CSF growth patterns relate to social communication development (Aim 2), we will complete another set of group-based analyses to assess if lower social communication scores are present in (1) the S-DYS group and (2) infants with atypical EA-CSF growth patterns. The overarching goal of this line of work is to inform mechanistic pathways between sleep dysregulation and neurodevelopmental risk. This study focuses on EA-CSF, based on its known connections to sleep, autism, and other indices of developmental risk. Using a developmental psychopathology approach, this study provides crucial first steps in translating how EA-CSF growth within a community sample can inform our understanding of a potential neuroanatomical marker of social communicative risk and resilience.