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

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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.