Transcutaneous vagal nerve stimulation modulates stress-induced plasma ghrelin levels: A double-blind, randomized, sham-controlled trial.

BACKGROUND: Transcutaneous cervical vagus nerve stimulation (tcVNS) has emerged as a potential treatment strategy for patients with stress-related psychiatric disorders. Ghrelin is a hormone that has been postulated to be a biomarker of stress. While the mechanisms of action of tcVNS are unclear, we hypothesized that tcVNS reduces the levels of ghrelin in response to stress. METHODS: Using a randomized double-blind approach, we studied the effects of tcVNS on ghrelin levels in individuals with a history of exposure to traumatic stress. Participants received either sham (n = 29) or active tcVNS (n = 26) after exposure to acute personalized traumatic script stress and mental stress challenges (public speech, mental arithmetic) over a three day period. RESULTS: There were no significant differences in the levels of ghrelin between the tcVNS and sham stimulation groups at either baseline or in the absence of trauma scripts. However, tcVNS in conjunction with personalized traumatic scripts resulted in lower ghrelin levels compared to the sham stimulation group (265.2 ± 143.6 pg/ml vs 478.7 ± 349.2 pg/ml, P = 0.01). Additionally, after completing the public speaking and mental arithmetic tests, ghrelin levels were found to be lower in the group receiving tcVNS compared to the sham group (293.3 ± 102.4 pg/ml vs 540.3 ± 203.9 pg/ml, P = 0.009). LIMITATIONS: Timing of ghrelin measurements, and stimulation of only left vagus nerve. CONCLUSION: tcVNS decreases ghrelin levels in response to various stressful stimuli. These findings are consistent with a growing literature that tcVNS modulates hormonal and autonomic responses to stress.

A Wearable Multimodal Sensing System for Tracking Changes in Pulmonary Fluid Status, Lung Sounds, and Respiratory Markers.

Heart failure (HF) exacerbations, characterized by pulmonary congestion and breathlessness, require frequent hospitalizations, often resulting in poor outcomes. Current methods for tracking lung fluid and respiratory distress are unable to produce continuous, holistic measures of cardiopulmonary health. We present a multimodal sensing system that captures bioimpedance spectroscopy (BIS), multi-channel lung sounds from four contact microphones, multi-frequency impedance pneumography (IP), temperature, and kinematics to track changes in cardiopulmonary status. We first validated the system on healthy subjects (n = 10) and then conducted a feasibility study on patients (n = 14) with HF in clinical settings. Three measurements were taken throughout the course of hospitalization, and parameters relevant to lung fluid status-the ratio of the resistances at 5 kHz to those at 150 kHz (K)-and respiratory timings (e.g., respiratory rate) were extracted. We found a statistically significant increase in K (p < 0.05) from admission to discharge and observed respiratory timings in physiologically plausible ranges. The IP-derived respiratory signals and lung sounds were sensitive enough to detect abnormal respiratory patterns (Cheyne-Stokes) and inspiratory crackles from patient recordings, respectively. We demonstrated that the proposed system is suitable for detecting changes in pulmonary fluid status and capturing high-quality respiratory signals and lung sounds in a clinical setting.

Robust Estimation of Respiratory Variability Uncovers Correlates of Limbic Brain Activity and Transcutaneous Cervical Vagus Nerve Stimulation in the Context of Traumatic Stress.

OBJECTIVE: Variations in respiration patterns are a characteristic response to distress due to underlying neurorespiratory couplings. Yet, no work to date has quantified respiration pattern variability (RPV) in the context of traumatic stress and studied its functional neural correlates - this analysis aims to address this gap. METHODS: Fifty human subjects with prior traumatic experiences (24 with posttraumatic stress disorder (PTSD)) completed a ∼3-hr protocol involving personalized traumatic scripts and active/sham (double-blind) transcutaneous cervical vagus nerve stimulation (tcVNS). High-resolution positron emission tomography functional neuroimages, electrocardiogram (ECG), and respiratory effort (RSP) data were collected during the protocol. Supplementing the RSP signal with ECG-derived respiration for quality assessment and timing extraction, RPV metrics were quantified and analyzed. Specifically, correlation analyses were performed using neuroactivity in selected limbic regions, and responses to active and sham tcVNS were compared. RESULTS: The single-lag unscaled autocorrelation of respiration rate correlated negatively with left amygdala activity and positively with right rostromedial prefrontal cortex (rmPFC) activity for non-PTSD; it also correlated negatively with left and right insulae activity and positively with right rmPFC activity for PTSD. The single-lag unscaled autocorrelation of expiration time was greater following active stimulation for non-PTSD. CONCLUSION: Quantifying RPV is of demonstrable importance to assessing trauma-induced changes in neural function and tcVNS effects on respiratory physiology. SIGNIFICANCE: This is the first demonstration of RPV's pertinence to traumatic stress- and tcVNS-induced neurorespiratory responses. The open-source processing pipeline elucidated herein uniquely includes both RSP and ECG-derived respiration signals for quality assessment, timing estimation, and RPV extraction.

Confederates in the Attic: Posttraumatic Stress Disorder, Cardiovascular Disease, and the Return of Soldier's Heart.

Da Costa originally described Soldier's Heart in the 19th Century as a syndrome that occurred on the battlefield in soldiers of the American Civil War. Soldier's Heart involved symptoms similar to modern day posttraumatic stress disorder (PTSD) as well as exaggerated cardiovascular reactivity felt to be related to an abnormality of the heart. Interventions were appropriately focused on the cardiovascular system. With the advent of modern psychoanalysis, psychiatric symptoms became divorced from the body and were relegated to the unconscious. Later, the physiology of PTSD and other psychiatric disorders was conceived as solely residing in the brain. More recently, advances in psychosomatic medicine led to the recognition of mind-body relationships and the involvement of multiple physiological systems in the etiology of disorders, including stress, depression PTSD, and cardiovascular disease, has moved to the fore, and has renewed interest in the validity of the original model of the Soldier's Heart syndrome.

Quantifying acute physiological biomarkers of transcutaneous cervical vagal nerve stimulation in the context of psychological stress.

BACKGROUND: Stress is associated with activation of the sympathetic nervous system, and can lead to lasting alterations in autonomic function and in extreme cases symptoms of posttraumatic stress disorder (PTSD). Vagal nerve stimulation (VNS) is a potentially useful tool as a modulator of autonomic nervous system function, however currently available implantable devices are limited by cost and inconvenience. OBJECTIVE: The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on autonomic responses to stress. METHODS: Using a double-blind approach, we investigated the effects of active or sham tcVNS on peripheral cardiovascular and autonomic responses to stress using wearable sensing devices in 24 healthy human participants with a history of exposure to psychological trauma. Participants were exposed to acute stressors over a three-day period, including personalized scripts of traumatic events, public speech, and mental arithmetic tasks. RESULTS: tcVNS relative to sham applied immediately after traumatic stress resulted in a decrease in sympathetic function and modulated parasympathetic/sympathetic autonomic tone as measured by increased pre-ejection period (PEP) of the heart (a marker of cardiac sympathetic function) of 4.2 ms (95% CI 1.6-6.8 ms, p < 0.01), decreased peripheral sympathetic function as measured by increased photoplethysmogram (PPG) amplitude (decreased vasoconstriction) by 47.9% (1.4-94.5%, p < 0.05), a 9% decrease in respiratory rate (-14.3 to -3.7%, p < 0.01). Similar effects were seen when tcVNS was applied after other stressors and in the absence of a stressor. CONCLUSION: Wearable sensing modalities are feasible to use in experiments in human participants, and tcVNS modulates cardiovascular and peripheral autonomic responses to stress.

Quantifying and Reducing Motion Artifacts in Wearable Seismocardiogram Measurements During Walking to Assess Left Ventricular Health.

GOAL: Our objective is to provide a framework for extracting signals of interest from the wearable seismocardiogram (SCG) measured during walking at normal (subject's preferred pace) and moderately fast (1.34-1.45 m/s) speeds. METHODS: We demonstrate, using empirical mode decomposition (EMD) and feature tracking algorithms, that the pre-ejection period (PEP) can be accurately estimated from a wearable patch that simultaneously measures electrocardiogram and sternal acceleration signals. We also provide a method to determine the minimum number of heartbeats required for an accurate estimate to be obtained for the PEP from the accelerometer signals during walking. RESULTS: The EMD-based denoising approach provides a statistically significant increase in the signal-to-noise ratio of wearable SCG signals and also improves estimation of PEP during walking. CONCLUSION: The algorithms described in this paper can be used to provide hemodynamic assessment from wearable SCG during walking. SIGNIFICANCE: A major limitation in the use of the SCG, a measure of local chest vibrations caused by cardiac ejection of blood in the vasculature, is that a user must remain completely still for high-quality measurements. The motion can create artifacts and practically render the signal unreadable. Addressing this limitation could allow, for the first time, SCG measurements to be obtained reliably during movement-aside from increasing the coverage throughout the day of cardiovascular monitoring, analyzing SCG signals during movement would quantify the cardiovascular system's response to stress (exercise), and thus provide a more holistic assessment of overall health.