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至关重要。 虽然促进这种沟通的解剖学途径已经得到了很好的表征， 两个系统之间的电动耦合仍然是难以捉摸的，特别是在开发过程中。一 调节心脏功能的大脑结构的分布式网络发生了深刻的变化， 在人生的前二十年里，这些解剖学变化和出生后心脏的影响 对血管-心血管偶联的成熟了解甚少。然而，这是一个基本的机制， 这一点如果受到损害，可能会导致这两个系统的严重缺陷。在完整人脑的宏观尺度上 和心脏，同时采集的电生理数据可能会为两者提供变革性的新见解。 电动力系统耦合及其由失调和应激源的调节。迄今为止， 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， 在美国，影响了多达10%的儿童，在清醒和睡眠期间的这种电动耦合仍然存在， 不太了解。该项目旨在通过两个潜在的方法来显著提高该领域的知识 转型贡献。目标1将制定一个蓝图正常电动相互作用之间的 开发大脑和心脏，在清醒和睡眠期间，通过利用大量现有数据， 临床生理学研究（包括EEG和ECG），来自无基础疾病证据的患者 疾病共1400例患者同时进行EEG和ECG检查，年龄从婴儿到青年 成年期将使用尖端的信号和机器学习工具和模型进行分析，以建立一个 大脑和心脏之间电动相互作用的典型发展轨迹。目标2将使用 这份蓝图系统地研究了睡眠障碍对心血管疾病的不利影响， 453名OSA儿童（5-10岁）和约400名打鼾儿童（不符合标准 用于OSA），使用来自儿童腺样体扁桃体切除术试验（CHAT）的公开可用的多导睡眠图数据。 基线和随访时的动态EEG-ECG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。偏离规范耦合将作为一个函数进行调查， 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， 仍然严重未得到充分利用。该项目将利用这些大数据， 然而，目前难以捉摸的机制，可能会影响整个生命周期的认知和心血管健康。 此外，建立一个规范的发展轨迹，心血管耦合， 成为未来研究的重要资源。调查结果可能会提供变革性的见解， 这两个器官之间的沟通，必要的，以保持各自的长期健康。

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.