Sleep, the glymphatic system, and social communication development

睡眠、类淋巴系统和社交沟通发展

• 批准号: 10308110
• 负责人: AMY J SCHWICHTENBERG
• 金额: $ 7.53万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10308110
• 关键词: Address; Age-Months; Anatomy; Area; Biological Process; Blood Circulation; Brain; Cerebrospinal Fluid; Child; Communities; Data; Data Set; Development; Endocrine system; Excision; General Population; Glucose; Goals; Growth; Homeostasis; Hybrids; Image; Immune system; Impairment; Infant; Infant Development; Inflammatory; Intercellular Fluid; Language Development; Learning; Life; Link; Literature; MRI Scans; Magnetic Resonance Imaging; Measures; Metabolic; Modeling; Nervous system structure; Neurodevelopmental Disorder; Neurons; Parents; Pathway interactions; Pattern; Physiology; Play; Process; Production; Psychopathology; Reporting; Resolution; Risk; Role; Sampling; Sampling Studies; Scanning; Series; Sleep; Sleep Disorders; Sleep disturbances; Subarachnoid Space; System; Time; Toddler; Translating; Work; age group; arachnoid villi; autism spectrum disorder; autistic children; base; connectome; early childhood; emotion regulation; glymphatic system; indexing; infancy; longitudinal design; protein metabolite; relating to nervous system; resilience; skills; sleep regulation; social; social communication; wasting

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.

项目概要： 睡眠在神经、免疫和内分泌系统等多个生物过程中发挥着至关重要的作用。 睡眠的一项关键功能是通过脑脊液 (CSF) 清除神经元代谢废物 类淋巴系统 (GS) 内的循环。 GS 是一个功能增强的全脑系统 在睡眠期间清除炎症蛋白和代谢物。我们对这个问题的理解最近取得了进展 GS 强调其在神经发育障碍和发育风险中的作用。具体来说，沉和 同事报告称，蛛网膜下腔内过多的脑脊液（轴外脑脊液；EA-CSF）是早期标志物 自闭症以及发育风险和睡眠问题的相关性。 MRI 提取的 EA-CSF 体积可用于 作为 GS 解剖学的非侵入性标记。尽管导致 EA-CSF 过多的确切机制尚不明确。 未知，已知 GS 过程在睡眠期间增强。发育时期的特点是高 睡眠需求（例如婴儿期）可能反映了清除神经元代谢废物的需求增加。 早期发育过程中的睡眠中断可能会影响 GS 功能，并有可能促成 神经发育风险和恢复力。本研究旨在阐明睡眠与睡眠之间的关系 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 - 社会交往的发展。在本研究中，我们将从以下位置索引体积 EA-CSF 数据： Baby Connectome 项目 (U01MH110274) 中跟踪的社区样本具有高分辨率 1 至 26 个月龄的结构 MRI 扫描。该数据集的混合加速纵向设计为 非常适合发育模式估计。凭借新开发的自动化 MRI 管道，我们将 模拟生命头两年的 EA-CSF 模式。描述 EA-CSF 发育之间的关系 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）的人。我们通过年龄互动来预测一个群体， S-DYS 组显示 EA-CSF 随着时间的推移的生长模式，相对于 S-DYS 组显着增加 REG 组。我们认为 S-DYS 组中 EA-CSF 的较大增加可能反映了 CSF 的不平衡 流通/间隙。评估睡眠失调和 EA-CSF 生长模式与社交的关系 沟通发展（目标 2），我们将完成另一组基于小组的分析，以评估是否较低 (1) S-DYS 组和 (2) EA-CSF 生长不典型的婴儿存在社交沟通评分 模式。这一系列工作的首要目标是了解睡眠之间的机制途径 失调和神经发育风险。本研究重点关注 EA-CSF，基于其已知的与 睡眠、自闭症和其他发育风险指标。使用发展精神病理学方法，这 研究提供了关键的第一步，以转化社区样本中的 EA-CSF 生长如何为我们提供信息 了解社会沟通风险和复原力的潜在神经解剖学标记。