Quantifying Posttraumatic Stress Disorder Symptoms During Traumatic Memories Using Interpretable Markers of Respiratory Variability.

BACKGROUND: Posttraumatic stress disorder (PTSD) causes heightened fight-or-flight responses to traumatic memories (i.e., hyperarousal). Although hyperarousal is hypothesized to cause irregular breathing (i.e., respiratory variability), no quantitative markers of respiratory variability have been shown to correspond with PTSD symptoms in humans. OBJECTIVE: In this study, we define interpretable markers of respiration pattern variability (RPV) and investigate whether these markers respond during traumatic memories, correlate with PTSD symptoms, and differ in patients with PTSD. METHODS: We recruited 156 veterans from the Vietnam-Era Twin Registry to participate in a trauma recall protocol. From respiratory effort and electrocardiogram measurements, we extracted respiratory timings and rate using a robust quality assessment and fusion approach. We then quantified RPV using the interquartile range and compared RPV between baseline and trauma recall conditions, correlated PTSD symptoms to the difference between trauma recall and baseline RPV (i.e., ∆RPV), and compared ∆RPV between patients with PTSD and trauma-exposed controls. Leveraging a subset of 116 paired twins, we then uniquely controlled for factors shared by co-twins via within-pair analysis for further validation. RESULTS: We found RPV was increased during traumatic memories (p .001), ∆ RPV was positively correlated with PTSD symptoms (p .05), and patients with PTSD exhibited higher ∆ RPV than trauma-exposed controls (p . 05). CONCLUSIONS: This paper is the first to elucidate RPV markers that respond during traumatic memories, especially in patients with PTSD, and correlate with PTSD symptoms. SIGNIFICANCE: These findings encourage future studies outside the clinic, where interpretable markers of respiratory variability are used to track hyperarousal.

A Comparison of Normalization Techniques for Individual Baseline-Free Estimation of Absolute Hypovolemic Status Using a Porcine Model.

Hypovolemic shock is one of the leading causes of death in the military. The current methods of assessing hypovolemia in field settings rely on a clinician assessment of vital signs, which is an unreliable assessment of hypovolemia severity. These methods often detect hypovolemia when interventional methods are ineffective. Therefore, there is a need to develop real-time sensing methods for the early detection of hypovolemia. Previously, our group developed a random-forest model that successfully estimated absolute blood-volume status (ABVS) from noninvasive wearable sensor data for a porcine model (n = 6). However, this model required normalizing ABVS data using individual baseline data, which may not be present in crisis situations where a wearable sensor might be placed on a patient by the attending clinician. We address this barrier by examining seven individual baseline-free normalization techniques. Using a feature-specific global mean from the ABVS and an external dataset for normalization demonstrated similar performance metrics compared to no normalization (normalization: R2 = 0.82 ± 0.025|0.80 ± 0.032, AUC = 0.86 ± 5.5 × 10-3|0.86 ± 0.013, RMSE = 28.30 ± 0.63%|27.68 ± 0.80%; no normalization: R2 = 0.81 ± 0.045, AUC = 0.86 ± 8.9 × 10-3, RMSE = 28.89 ± 0.84%). This demonstrates that normalization may not be required and develops a foundation for individual baseline-free ABVS prediction.

Leveraging Physiological Markers to Quantify the Transient Effects of Traumatic Stress and Non-Invasive Neuromodulation.

Millions around the world suffer from traumatic stress (stress caused by traumatic memories). Transcutaneous cervical vagus nerve stimulation (tcVNS) has been shown to counteract physiological changes associated with traumatic stress. However, little is known regarding the approximate timecourse of tcVNS effects. This knowledge of how quickly tcVNS takes effect is needed to optimize closed-loop tcVNS systems that can mitigate traumatic stress in a timely manner. To address this gap, we studied N=26 participants with history of prior trauma. Participants wore electrocardiogram, photoplethysmogram, seismocardiogram, and respiratory effort sensors throughout a double-blind protocol involving traumatic stress and active tcVNS (n=12) or sham stimulation (n=14). From the physiological signals, we extracted cardiovascular and respiratory markers and studied their dynamics during the traumatic stress and stimulation conditions. We decoupled the short-term transient responses from longer-term cumulative changes by centering each condition's response with respect to data immediately prior to the condition. We thereby elucidate a diverse set of transient physiological responses to tcVNS and traumatic stress. These responses demonstrate that tcVNS-induced changes occur within seconds and have the potential to reduce acute physiological manifestations of traumatic stress.Clinical relevance- Traumatic stress can overpower an individual within seconds and often occurs outside the clinic. This analysis focuses on transient physiological responses to traumatic memories and tcVNS captured using multimodal physiological sensing. We demonstrate that tcVNS-induced changes occur within seconds and have the potential to mitigate some of the short-term effects of traumatic stress.

Towards Quantifying Stress in Patients with a History of Myocardial Infarction: Validating ECG-Derived Patch Features.

Patients with prior myocardial infarction (MI) have an increased risk of experiencing a secondary event which is exacerbated by mental stress. Our team has developed a miniaturized patch with the capability to capture electrocardiogram (ECG), seismocardiogram (SCG) and photoplethysmogram (PPG) signals which may provide multimodal information to characterize stress responses within the post-MI population in ambulatory settings. As ECG-derived features have been shown to be informative in assessing the risk of MI, a critical first step is to ensure that the patch ECG features agree with gold-standard devices, such as the Biopac. However, this is yet to be done in this population. We, thus, performed a comparative analysis between ECG-derived features (heart rate (HR) and heart rate variability (HRV)) of the patch and Biopac in the context of stress. Our dataset contained post-MI and healthy control subjects who participated in a public speaking challenge. Regression analyses for patch and Biopac HR and HRV features (RMSSD, pNN50, SD1/SD2, and LF/HF) were all significant (p<0.001) and had strong positive correlations (r>0.9). Additionally, Bland-Altman analyses for most features showed tight limits of agreement: 0.999 bpm (HR), 11.341 ms (RMSSD), 0.07% (pNN50), 0.146 ratio difference (SD1/SD2), 0.750 ratio difference (LF/HF).Clinical relevance- This work demonstrates that ECG-derived features obtained from the patch and Biopac are in agreement, suggesting the clinical utility of the patch in deriving quantitative metrics of physiology during stress in post-MI patients. This has the potential to improve post-MI patients' outcomes, but needs to be further evaluated.

Enabling Continuous Breathing-Phase Contextualization via Wearable-Based Impedance Pneumography and Lung Sounds: A Feasibility Study.

Chronic respiratory diseases affect millions and are leading causes of death in the US and worldwide. Pulmonary auscultation provides clinicians with critical respiratory health information through the study of Lung Sounds (LS) and the context of the breathing-phase and chest location in which they are measured. Existing auscultation technologies, however, do not enable the simultaneous measurement of this context, thereby potentially limiting computerized LS analysis. In this work, LS and Impedance Pneumography (IP) measurements were obtained from 10 healthy volunteers while performing normal and forced-expiratory (FE) breathing maneuvers using our wearable IP and respiratory sounds (WIRS) system. Simultaneous auscultation was performed with the Eko CORE stethoscope (EKO). The breathing-phase context was extracted from the IP signals and used to compute phase-by-phase (Inspiratory (I), expiratory (E), and their ratio (I:E)) and breath-by-breath acoustic features. Their individual and added value was then elucidated through machine learning analysis. We found that the phase-contextualized features effectively captured the underlying acoustic differences between deep and FE breaths, yielding a maximum F1 Score of 84.1 ±11.4% with the phase-by-phase features as the strongest contributors to this performance. Further, the individual phase-contextualized models outperformed the traditional breath-by-breath models in all cases. The validity of the results was demonstrated for the LS obtained with WIRS, EKO, and their combination. These results suggest that incorporating breathing-phase context may enhance computerized LS analysis. Hence, multimodal sensing systems that enable this, such as WIRS, have the potential to advance LS clinical utility beyond traditional manual auscultation and improve patient care.

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.

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.

Towards Estimation of Tidal Volume and Respiratory Timings via Wearable-Patch-Based Impedance Pneumography in Ambulatory Settings.

OBJECTIVE: Evaluating convenient, wearable multi-frequency impedance pneumography (IP)-based respiratory monitoring in ambulatory persons with novel electrode positioning. METHODS: A wearable multi-frequency IP system was utilized to estimate tidal volume (TV) and respiratory timings in 14 healthy subjects. A 5.1 cm × 5.1 cm tetrapolar electrode array, affixed to the sternum, and a conventional thoracic electrode configuration were employed to measure the respective IP signals, patch and thoracic IP. Data collected during static postures-sitting and supine-and activities-walking and stair-stepping-were evaluated against a simultaneously-obtained spirometer (SP) volume signal. RESULTS: Across all measurements, estimated TV obtained from the patch and thoracic IP maintained a Pearson correlation coefficient (r) of 0.93 ± 0.05 and 0.95 ± 0.05 to the ground truth TV, respectively, with an associated root-mean-square error (RMSE) of 0.177 L and 0.129 L, respectively. Average respiration rates (RRs) were extracted from 30-second segments with mean-absolute-percentage errors (MAPEs) of 0.93% and 0.74% for patch and thoracic IP, respectively. Likewise, average inspiratory and expiratory timings were identified with MAPEs less than 6% and 4.5% for patch and thoracic IP, respectively. CONCLUSION: We demonstrated that patch IP performs comparably to traditional, cumbersome IP configurations. We also present for the first time, to the best of our knowledge, that IP can robustly estimate breath-by-breath TV and respiratory timings during ambulation. SIGNIFICANCE: This work represents a notable step towards pervasive wearable ambulatory respiratory monitoring via the fusion of a compact chest-worn form factor and multi-frequency IP that can be readily adapted for holistic cardiopulmonary monitoring.