Abstract

BackgroundThe autonomic nervous system (ANS) maintains physiological homeostasis in various organ systems via parasympathetic and sympathetic branches. ANS function is altered in common diffuse and focal conditions and heralds the beginning of environmental and disease stresses. Reliable, sensitive, and quantitative biomarkers, first defined in healthy participants, could discriminate among clinically useful changes in ANS function. This framework combines controlled autonomic testing with feature extraction during physiological responses.MethodsTwenty-one individuals were assessed in two morning and two afternoon sessions over two weeks. Each session included five standard clinical tests probing autonomic function: squat test, cold pressor test, diving reflex test, deep breathing, and Valsalva maneuver. Noninvasive sensors captured continuous electrocardiography, blood pressure, breathing, electrodermal activity, and pupil diameter. Heart rate, heart rate variability, mean arterial pressure, electrodermal activity, and pupil diameter responses to the perturbations were extracted, and averages across participants were computed. A template matching algorithm calculated scaling and stretching features that optimally fit the average to an individual response. These features were grouped based on test and modality to derive sympathetic and parasympathetic indices for this healthy population.ResultsA significant positive correlation (p = 0.000377) was found between sympathetic amplitude response and body mass index. Additionally, longer duration and larger amplitude sympathetic and longer duration parasympathetic responses occurred in afternoon testing sessions; larger amplitude parasympathetic responses occurred in morning sessions.ConclusionsThese results demonstrate the robustness and sensitivity of an algorithmic approach to extract multimodal responses from standard tests. This novel method of quantifying ANS function can be used for early diagnosis, measurement of disease progression, or treatment evaluation.Trial registrationThis study registered with Clinicaltrials.gov, identifier NCT04100486. Registered September 24, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04100486.

Highlights

  • The autonomic nervous system (ANS) regulates and integrates the physiology of the heart, lung, spleen, intestines, and other organ systems

  • The findings demonstrated significant deviations of ANS responses correlated with body mass index (BMI), and showed trends related to circadian rhythm

  • Monitoring physiological signals to compute average responses Cardiovascular, pupil dilation, and electrodermal activity (EDA) signals were synchronously recorded for each participant, with raw recordings for ECG and blood pressure (BP) used to calculate heart rate (HR), heart rate variability (HRV) (RMSSD), and mean arterial pressure (MAP) (Fig. 3)

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Summary

Introduction

The autonomic nervous system (ANS) regulates and integrates the physiology of the heart, lung, spleen, intestines, and other organ systems. Regulation depends on a balance between the sympathetic and parasympathetic systems, in which it is possible to monitor real-time ANS activity by recording neural activity from candidate cranial and peripheral nerves (Barman & Yates, 2017; Cracchiolo et al, 2019; Devor et al, 1994; Masi et al, 2019; Yoshimura et al, 1994; Zanos, 2019; Zanos et al, 2018). This daunting recording task would require implanted electrodes, a challenging prospect for animal experiments, no less clinical diagnosis and treatment. This framework combines controlled autonomic testing with feature extraction during physiological responses

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