Robust Characterization of Brain-Heart Coupling Across Development and Modulations by Disordered Sleep

摘要 大脑和心脏之间的平衡沟通对心血管和认知健康都至关重要。 尽管促进这种交流的解剖学途径已经有了很好的特征，但 这两个系统之间的电动力耦合仍然难以捉摸，特别是在开发过程中。一个 调节心脏功能的大脑结构的分布式网络经历了深刻的变化和 在生命的头二十年里进行了重组。这些解剖变化对出生后心脏的影响 关于脑-心血管耦合的成熟还知之甚少。然而，这是一种基本的机制 如果这一点受到损害，可能会导致这两个系统都出现重大赤字。在完整的人脑的宏观尺度上 和心脏，同时获得的电生理数据可能为两者提供变革性的新见解 电动力系统耦合及其无序和应激源的调节。到目前为止， 这种压力源，特别是与阻塞性睡眠呼吸暂停(OSA)相关的不健康睡眠，是一种 在美国，高达10%的儿童在清醒和睡眠期间会受到这种电动力学耦合的影响 人们对此知之甚少。该项目旨在通过两个潜在的途径显著提高该领域的知识 变革性的贡献。目标1将开发一张正常的电动力相互作用的蓝图 通过利用现有的大量数据，在清醒和睡眠期间开发大脑和心脏 临床生理学检查(包括脑电和心电图)来自没有潜在证据的患者 疾病。总共1400名患者，从婴儿期到青壮年，同时进行脑电和心电图检查 成人将使用尖端的信号和机器学习工具和模型进行分析，以建立 大脑和心脏之间电动力学相互作用的典型发展轨迹。AIM 2将使用 这份蓝图旨在系统地研究睡眠障碍对脑血管的不良影响 453名阻塞性睡眠呼吸暂停综合征(5-10岁)儿童和约400名打鼾症儿童(不符合标准)的配对 对于OSA)，使用来自儿童腺扁桃体切除术试验(CHAT)的公开可用多导睡眠图数据。 基线和随访时的动态脑电-心电相互作用将与正常系统耦合进行比较 目标1中估计的相同年龄范围。将作为以下函数调查与标准耦合的偏差 认知结果。临床生理学/多导睡眠图研究包含大量有价值的信息，但 仍然严重未得到充分利用。该项目将利用这些大数据有力地描述 然而，目前还不清楚可能会影响认知和心血管健康的机制。 此外，脑-心血管耦合的标准发展轨迹的建立可能 成为未来研究的重要研究资源。这些发现可能会为我们提供对 这两个器官之间的沟通，是维持各自长期健康所必需的。

ABSTRACT Balanced communication between the brain and heart is critical to both cardiovascular and cognitive health. Although the anatomical pathways facilitating this communication have been well characterized, the electrodynamic coupling between the two systems remains elusive, particularly during development. A distributed network of brain structures that regulates cardiac function undergoes profound changes and reorganization during the first two decades of life. The impact of these anatomical changes and postnatal heart maturation on cerebro-cardiovascular coupling is poorly understood. Yet, this is a fundamental mechanism that, if impaired, may lead to significant deficits in both systems. At the macroscale of the intact human brain and heart, simultaneously acquired electrophysiological data may provide transformative new insights into both electrodynamic system coupling and its modulation by disorders and stressors. To date, the adverse effects of such stressors, particularly unhealthy sleep associated with Obstructive Sleep Apnea (OSA), a disorder that affects up to 10% of children in the US, on this electrodynamic coupling during wakefulness and sleep remain poorly understood. This project aims to significantly improve the field’s knowledge through two potentially transformative contributions. Aim 1 will develop a blueprint of normal electrodynamic interaction between the developing brain and heart, during wakefulness and sleep, by leveraging the large volume of existing data from clinical physiological studies (which include both EEG and ECG) from patients with no evidence of underlying disease. A total of n ~= 1400 patients, with simultaneous EEG and ECG, spanning in age infancy to young adulthood will be analyzed using cutting-edge signal and machine learning tools and models, to establish a typical developmental trajectory of the electrodynamic interaction between the brain and heart. Aim 2 will use this blueprint to systematically investigate the adverse impact of disordered sleep on cerebro-cardiovascular coupling in 453 children with OSA (ages 5-10 years) and ~400 children with snoring (who did not meet criteria for OSA), using publicly available polysomnography data from the Childhood Adenotonsillectomy Trial (CHAT). Dynamic EEG-ECG interactions at baseline and follow up will be compared to normal system coupling in the same age range, estimated in Aim 1. Deviations from normative coupling will be investigated as a function of cognitive outcomes. Clinical physiology/polysomnography studies contain a wealth of valuable information but remain severely underutilized. This project will leverage these Big Data to robustly characterize a fundamental yet currently elusive mechanism that may affect both cognitive and cardiovascular health across the lifespan. In addition, the establishment of a normative developmental trajectory of cerebro-cardiovascular coupling may become a significant research resource for future studies. Findings may provide transformative insights into the communication between the two organs, necessary to maintain their respective long-term health.