Transcutaneous auricular Vagus Nerve Stimulation and Median Nerve Stimulation reduce acute stress in young healthy adults: a single-blind sham-controlled crossover study.

Stress is a major determinant of health and wellbeing. Conventional stress management approaches do not account for the daily-living acute changes in stress that affect quality of life. The combination of physiological monitoring and non-invasive Peripheral Nerve Stimulation (PNS) represents a promising technological approach to quantify stress-induced physiological manifestations and reduce stress during everyday life. This study aimed to evaluate the effectiveness of three well-established transcutaneous PNS modalities in reducing physiological manifestations of stress compared to a sham: auricular and cervical Vagus Nerve Stimulation (taVNS and tcVNS), and Median Nerve Stimulation (tMNS). Using a single-blind sham-controlled crossover study with four visits, we compared the stress mitigation effectiveness of taVNS, tcVNS, and tMNS, quantified through physiological markers derived from five physiological signals peripherally measured on 19 young healthy volunteers. Participants underwent three acute mental and physiological stressors while receiving stimulation. Blinding effectiveness was assessed via subjective survey. taVNS and tMNS relative to sham resulted in significant changes that suggest a reduction in sympathetic outflow following the acute stressors: Left Ventricular Ejection Time Index (LVETI) shortening (tMNS: p = 0.007, taVNS: p = 0.015) and Pre-Ejection Period (PEP)-to-LVET ratio (PEP/LVET) increase (tMNS: p = 0.044, taVNS: p = 0.029). tMNS relative to sham also reduced Pulse Pressure (PP; p = 0.032) and tonic EDA activity (tonicMean; p = 0.025). The nonsignificant blinding survey results suggest these effects were not influenced by placebo. taVNS and tMNS effectively reduced stress-induced sympathetic arousal in wearable-compatible physiological signals, motivating their future use in novel personalized stress therapies to improve quality of life.

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.

Transcutaneous Cervical Vagus Nerve Stimulation Lengthens Exhalation in the Context of Traumatic Stress.

Transcutaneous electrical stimulation of the vagus nerve is believed to deliver afferent signaling to the brain that, in turn, yields downstream changes in peripheral physiology, including cardiovascular and respiratory parameters. While the effects of transcutaneous cervical vagus nerve stimulation (tcVNS) on these parameters have been studied broadly, little is known regarding the specific effects of tcVNS on exhalation time and the spontaneous respiration cycle. By understanding such effects, tcVNS could be used to counterbalance sympathetic hyperactivity following distress by enhancing vagal tone through parasympathetically favored modulation of inspiration and expiration - specifically, lengthened expiration relative to inspiration. We thus investigated the effects of tcVNS on respiration timings by decomposing the respiration cycle into inspiration and expiration times and incorporating state-of-the-art respiration quality assessment algorithms for respiratory effort belt and electrocardiogram derived respiration signals. This enabled robust estimation of respiration timings from quality measurements alone. We thereby found that tcVNS increases expiration time minutes after stimulation, compared to a sham control (N = 26). This suggests that tcVNS could counteract sympathovagal imbalance, given the relationship between expiration and heightened vagal tone.

Transcutaneous Cervical Vagus Nerve Stimulation Inhibits the Reciprocal of the Pulse Transit Time's Responses to Traumatic Stress in Posttraumatic Stress Disorder.

Research has shown that transcutaneous cervical vagus nerve stimulation (tcVNS) yields downstream changes in peripheral physiology in individuals afflicted with posttraumatic stress disorder (PTSD). While the cardiovascular effects of tcVNS have been studied broadly in prior work, the specific effects of tcVNS on the reciprocal of the pulse transit time (1/PTT) remain unknown. By quantifying detectable effects, tcVNS can be further evaluated as a counterbalance to sympathetic hyperactivity during distress - specifically, we hypothesized that tcVNS would inhibit 1/PTT responses to traumatic stress. To investigate this, the electrocardiogram (ECG), photoplethysmogram (PPG), and seismocardiogram (SCG), were simultaneously measured from 24 human subjects suffering from PTSD. Implementing state-of-the-art signal quality assessment algorithms, relative changes in the pulse arrival time (PAT) and the pre-ejection period (PEP) were estimated solely from signal segments of sufficient quality. Thereby computing relative changes in 1/PTT, we find that tcVNS results in reduced 1/PTT responses to traumatic stress and the first minute of stimulation, compared to a sham control (corrected p < 0.05). This suggests that tcVNS induces inhibitory effects on blood pressure (BP) and/or vasoconstriction, given the established relationship between 1/PTT and these parameters.Clinical Relevance- Relative changes in 1/PTT are induced by varying vasomotor tone and/or BP - it has therefore piqued considerable interest as a potential surrogate of continuous BP. Studying its responses to tcVNS thus furthers understanding of tcVNS-induced cardiovascular modulation. The positive effects detailed herein suggest a potential role for tcVNS in the long-term management of PTSD.