Skin Sympathetic Nerve Activity Research Articles

The Diurnal Profile of Human Basal Pain Sensitivity and Skin Sympathetic Nerve Activity: A Healthy Volunteer Study.

ObjectiveThe diurnal rhythm profile of human basal pain sensitivity and its association with sympathetic nerve activity are not fully understood. This study aimed to examine rhythmic changes in experimental pain sensitivity and skin sympathetic nerve activity in healthy volunteers.MethodsThirty healthy volunteers were included in the study. Experimental pain sensitivity, including pressure pain threshold and tolerance, cold pain threshold (CPT) and tolerance, skin sympathetic nerve activity, and cardiovascular parameters (including heart rate, cardiac output, and peripheral vascular resistance) at six time points throughout the day (08:00, 12:00, 16:00, 20:00, 00:00, and 04:00) were sequentially measured. Circadian rhythm analysis was performed on the mean values of the different measurements and individual subjects.ResultsSignificant differences were found in experimental pain sensitivity, skin sympathetic nerve activity, and non-invasive cardiovascular parameters at different time points (P < 0.05). The minimum measured values of all four types of experimental pain sensitivity were consistently observed at 04:00. Rhythmical analysis showed that the mean values of pressure pain threshold (meta2d P = 0.016) and skin sympathetic nerve activity (meta2d P = 0.039) were significant. Significant diurnal rhythms in pain sensitivity and skin sympathetic nerve activity existed in some individuals but not in others. No significant correlation between experimental pain sensitivity and skin sympathetic nerve activity was found at any time point (P > 0.05).ConclusionSignificant diurnal fluctuations were observed in different pain sensitivities and skin sympathetic nerve activity. No significant correlation between experimental pain sensitivity and sympathetic excitability at different times was found; the reasons for these phenomena remain to be further studied.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ChiCTR2000039709].

Acute Effects of Electronic and Tobacco Cigarette Smoking on Sympathetic Nerve Activity and Blood Pressure in Humans.

: IntroductionAcute tobacco cigarette (TC) smoking increases blood pressure and sympathetic nerve activity, whereas there are scarce data on the impact of electronic cigarette (EC) smoking. We assessed the acute effects of TC, EC and sham smoking on blood pressure, heart rate and sympathetic nervous system. Methods: We studied 12 normotensive male habitual smokers (mean age 33 years) free of cardiovascular disease. The study design was randomized and sham controlled with three experimental sessions (sham smoking, TC smoking and EC smoking). After baseline measurements at rest, the subjects were then asked to smoke (puffing habits left uncontrolled) two TC cigarettes containing 1.1 mg nicotine, EC smoking or simulated smoking with a drinking straw with a filter (sham smoking), in line with previous methodology. Results: EC smoking at 5 and 30 min compared to baseline was accompanied by the augmentation of mean arterial pressure (MAP) and heart rate (p < 0.001 for all). The muscle sympathetic nerve activity (MSNA) decrease was significant during both TC and EC sessions (p < 0.001 for both comparisons) and was similar between them (−25.1% ± 9.8% vs. −34.4% ± 8.3%, respectively, p = 0.018). Both MSNA decreases were significantly higher (p < 0.001 for both comparisons) than that elicited by sham smoking (−4.4% ± 4.8%). Skin sympathetic nerve activity increase was significant in both TC and EC groups (p < 0.001 for both comparisons) and similar between them (73.4% ± 17.9% and 71.9% ± 7%, respectively, p = 0.829). Conclusions: The unfavorable responses of sympathetic and arterial pressure to EC smoking are similar to those elicited by TC in healthy habitual smokers.

Successful continuous positive airway pressure treatment reduces skin sympathetic nerve activity in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with cardiovascular diseases and increased sympathetic tone. We previously demonstrated that patients with OSA have increased skin sympathetic nerve activity (SKNA). The purpose of this study was to test the hypothesis that continuous positive airway pressure (CPAP) treatment reduces SKNA. The electrocardiogram, SKNA, and polysomnographic recording were recorded simultaneously in 9 patients with OSA. After baseline recording, CPAP titration was performed and the pressure was adjusted gradually for the optimal treatment, defined by reducing the apnea-hypopnea index (AHI) to ≤5/h. Otherwise the treatment was considered suboptimal (AHI > 5/h). Fast Fourier transform analyses were performed to investigate the frequency spectrum of SKNA. There were very low frequency (VLF), low frequency (LF), and high frequency (HF) oscillations in SKNA. The HF oscillation matched the frequency of respiration. OSA episodes were more frequently associated with the VLF and LF than with the HF oscillations of SKNA. Compared with baseline, CPAP significantly decreased the arousal index and AHI and increased the minimal and mean oxyhemoglobin levels. Optimal treatment significantly increased the dominant frequency and reduced the heart rate, average SKNA (aSKNA), SKNA burst duration, and total burst area. The dominant frequency negatively correlated with aSKNA. VLF, LF, and HF oscillations are observed in human SKNA recordings. Among them, VLF and LF oscillations are associated with OSA while HF oscillations are associated with normal breathing. CPAP therapy reduces aSKNA and shifts the frequency of SKNA oscillation from VLF or LF to HF.

Higher Pre-Treatment Skin Sympathetic Nerve Activity and Elevated Resting Heart Rate after Chemoradiotherapy Predict Worse Esophageal Cancer Outcomes

Higher Pre-Treatment Skin Sympathetic Nerve Activity and Elevated Resting Heart Rate after Chemoradiotherapy Predict Worse Esophageal Cancer Outcomes

Skin Sympathetic Nerve Activity and the Short-Term QT Interval Variability in Patients With Electrical Storm.

Background: Skin sympathetic nerve activity (SKNA) and QT interval variability are known to be associated with ventricular arrhythmias. However, the relationship between the two remains unclear.Objective: The aim was to test the hypothesis that SKNA bursts are associated with greater short-term variability of the QT interval (STVQT) in patients with electrical storm (ES) or coronary heart disease without arrhythmias (CHD) than in healthy volunteers (HV).Methods: We simultaneously recorded the ECG and SKNA during sinus rhythm in patients with ES (N = 10) and CHD (N = 8) and during cold-water pressor test in HV (N = 12). The QT and QTc intervals were manually marked and calculated within the ECG. The STVQT was calculated and compared to episodes of SKNA burst and non-bursting activity.Results: The SKNA burst threshold for ES and HV was 1.06 ± 1.07 and 1.88 ± 1.09 μV, respectively (p = 0.011). During SKNA baseline and burst, the QT/QTc intervals and STVQT for ES and CHD were significantly higher than those of the HV. In all subjects, SKNA bursts were associated with an increased STVQT (from 6.43 ± 2.99 to 9.40 ± 5.12 ms, p = 0.002 for ES; from 9.48 ± 4.40 to 12.8 ± 5.26 ms, p = 0.016 for CHD; and from 3.81 ± 0.73 to 4.49 ± 1.24 ms, p = 0.016 for HV). The magnitude of increased STVQT in ES (3.33 ± 3.06 ms) and CHD (3.34 ± 2.34 ms) was both higher than that of the HV (0.68 ± 0.84 ms, p = 0.047 and p = 0.020).Conclusion: Compared to non-bursting activity, SKNA bursts were associated with a larger increase in the QTc interval and STVQT in patients with heart disease than in HV.

Skin sympathetic nerve activity as a biomarker of fitness.

Exercise stress testing is frequently used to expose cardiac arrhythmias. Aerobic exercise conditioning has been used as a nonpharmacologic antiarrhythmic intervention. The purpose of this study was to test the hypothesis that noninvasively recorded skin sympathetic nerve activity (SKNA) is increased during exercise and that SKNA response varies according to fitness levels. Oxygen consumption (VO2) and SKNA were recorded in 39 patients undergoing an incremental exercise test. Patients were grouped by 5 levels of fitness based on age, sex, and VO2max. With exercise, all patients had a significant increase in average SKNA (aSKNA) (1.58 ± 1.12 μV to 4.50 ± 3.06 μV, P=.000) and heart rate (HR) (87.40 ± 20.42 bpm to 154.13± 16.82 bpm, P = .000). A mixed linear model of aSKNA was used with fixed effects of fitness, exercise time, and recovery time, and random effects of subject level intercept and slopes for exercise time and recovery times. The poor fitness group had significantly higher aSKNA than the other groups (P = .0273). For all subjects studied, aSKNA increased by 5% per minute with progression of exercise and decreased by 15% per minute with progression of recovery. The fitness variable encodes information on both comorbidities and body mass index (BMI). Once fitness level is known, comorbidities and BMI are not significantly associated with aSKNA. In all groups, aSKNA positively correlated with HR (R2 = 0.47 ± 0.23) and VO2 (R2 = 0.68 ± 0.25). Fitness level determines the magnitude and time course of SKNA increase during exercise. SKNA may be a useful fitness biomarker in exercise stress testing.

Temporal Clustering of Skin Sympathetic Nerve Activity Bursts in Acute Myocardial Infarction Patients.

Backgrounds: Acute myocardial infarction (AMI) affects the autonomic nervous system (ANS) function. The aim of our study is to detect the particular patterns of ANS regulation in AMI. We hypothesize that altered ANS regulation in AMI patients causes synchronized neural discharge (clustering phenomenon) detected by non-invasive skin sympathetic nerve activity (SKNA).Methods: Forty subjects, including 20 AMI patients and 20 non-AMI controls, participated in the study. The wide-band bioelectrical signals (neuECG) were continuously recorded on the body surface for 5 min. SKNA was signal processed to depict the envelope of SKNA (eSKNA). By labeling the clusters, the AMI subjects were separated into non-AMI, non-cluster appearing (AMINCA), and cluster appearing (AMICA) groups.Results: The average eSKNA was significantly correlated with HRV low-frequency (LF) power (rho = −0.336) and high-frequency power (rho = −0.372). The cross-comparison results demonstrated that eSKNA is a valid surrogate marker to assess ANS in AMI patients. The frequency of cluster occurrence was 0.01–0.03 Hz and the amplitude was about 3 μV. The LF/HF ratio of AMICA (median: 1.877; Q1–Q3: 1.483–2.413) revealed significantly lower than AMINCA (median: 3.959; Q1–Q3: 1.840–6.562). The results suggest that the SKNA clustering is a unique temporal pattern of ANS synchronized discharge, which could indicate the lower sympathetic status (by HRV) in AMI patients.Conclusion: This is the first study to identify SKNA clustering phenomenon in AMI patients. Such a synchronized nerve discharge pattern could be detected with non-invasive SKNA signals. SKNA temporal clustering could be a novel biomarker to classify ANS regulation ability in AMI patients.Clinical and Translational Significance: SKNA is higher in AMI patients than in control and negatively correlates with parasympathetic parameters. SKNA clustering is associated with a lower LF/HF ratio that has been shown to correlate with sudden cardiac death in AMI. The lack of SKNA temporal clustering could indicate poor ANS regulation in AMI patients.

Abstract 10432: Simultaneous Recording of Skin Sympathetic Nerve Activity and Blood Pressure in Ambulatory Outpatients with Postural Orthostatic Tachycardia Syndrome

Introduction: neuECG is a method to simultaneously record ECG and skin sympathetic nerve activity (SKNA). Postural orthostatic tachycardia syndrome (POTS) is known to be associated with increased cardiac sympathetic norepinephrine release. Hypothesis: Average SKNA correlates positively with heart rate (HR) and blood pressure (BP) in POTS patients. Methods: We used Bittium Faros 180 Holter Monitor (sampling rate 1,000 Hz) to record neuECG and SpaceLab OnTrak arterial BP monitor (ABPM) to record BP simultaneously over 24-hr in 20 POTS patients (19 women, 38±12 years old). The Faros signals were high pass filtered at 300 Hz to display the SKNA. The same original signals were bandpass filtered 0.05-150 Hz to display ECG. BP was measured every 30-min when awake (7AM to 9 PM) and hourly at night (9 PM to 7 AM). Results: Fig 1 shows an example of typical recording from a 38-year-old woman. Panel A shows average SKNA (aSKNA) 1-min prior to HR and BP measurement. The overall successful ABPM measurement was 90% with average BP of 126/75 mmHg. B shows bursts of SKNA in daytime (red dot in A), but no bursts at night (blue dot in A). C shows a positive correlation between HR, systolic BP (SBP) diastolic BP (DBP) and mean BP (MBP) with aSKNA. For all patients studied, 16 of 20 showed positive correlation between MBP and aSKNA (r=0.559±0.152, p&lt;0.05 for all) and 15 of 20 showed positive correlation between HR and aSKNA (r=0.511±0.175, p&lt;0.05 for all). The nocturnal aSKNA averaged 0.919±0.059 μV (N=17) and 1.060±0.215 (N=3) (p&lt;0.001) in patients with and without nocturnal dip, respectively. However, the overall 24-hr aSKNA (1.036±0.120 vs 1.044±0.095, μV) was not different between these two groups. Conclusions: aSKNA positively correlated with BP and HR in ambulatory outpatients with POTS. High aSKNA at night was associated with nocturnal non-dipping of BP.

High Skin Sympathetic Nerve Activity in Patients with Recurrent Syncope.

(1) Background: The autonomic imbalance plays a role in vasovagal syncope (VVS) diagnosed by head-up tilting test (HUT). neuECG is a new method of recording skin electrical signals to simultaneously analyze skin sympathetic nerve activity (SKNA) and electrocardiogram. We hypothesize that SKNA is higher in subjects with tilt-positive than tilt-negative and the SKNA surges before syncope. (2) Methods: We recorded neuECG in 41 subjects who received HUT (according to the “Italian protocol”), including rest, tilt-up, provocation and recovery phases. Data were analyzed to determine the average SKNA (aSKNA, μV) per digitized sample. Electrocardiogram was used to calculate standard deviation of normal-to-normal beat intervals (SDNN). The “SKNA-SDNN index” was calculated by rest aSKNA multiplied by the ratio of tilt-up to rest SDNN. (3) Results: 16 of 41 (39%) subjects developed syncope. The aSKNA at rest phase is significantly higher in the tilt-positive (1.21 ± 0.27 µV) than tilt-negative subjects (1.02 ± 0.29 µV) (p = 0.034). There are significant surges and withdraw of aSKNA 30 s before and after syncope (both p ≤ 0.006). SKNA-SDNN index is able to predict syncope (p < 0.001). (4) Conclusion: Higher SKNA at rest phase is associated with positive HUT. The SKNA-SDNN index is a novel marker to predict syncope during HUT.

Sympathetic nerve activity changes following acute exposures to electronic and tobacco cigarette smoking in humans

Abstract Background/Introduction Tobacco cigarette (TC) smoking acutely increases blood pressure and sympathetic nerve activity, whereas there are scarce data on the impact of electronic cigarette (EC). Purpose The aim of the study was to assess the acute effects of TC, EC and sham smoking on blood pressure, heart rate and sympathetic nervous system in healthy subjects. Methods We studied 12 normotensive male habitual smokers (mean age 33 years) free of cardiovascular disease. The study design was randomized and placebo controlled with 3 experimental sessions (sham smoking, tobacco cigarette smoking, and e-cigarette smoking) in random order, each session on a separate day. Subjects smoked 2 tobacco cigarettes containing 1.1 mg nicotine or simulate smoking (sham smoking) with the 2 cigarettes separated by 5 minutes. Additionally, participants smoked e-cigarettes for a period of 5 and 30 minutes. In all occasions, sympathetic drive was assessed by muscle sympathetic nerve activity (MSNA) (baroreflex-dependent) and skin sympathetic nerve activity (SSNA) (baroreflex-independent) based on established methodology (microneurography). Results After the first and second TC smoking, there was significant increase in mean arterial pressure (MAP) (by 6 and 8 mmHg, respectively, overall p&amp;lt;0.001) and heart rate (by 8 and 12 beats/minute, respectively, overall p&amp;lt;0.001) compared to baseline. Similarly, EC smoking at 5 and 30 minutes compared to baseline was accompanied by augmentation of MAP (by 6 and 10 mmHg, respectively, overall p&amp;lt;0.001) and heart rate (by 5 and 9 beats/minute, respectively, overall p&amp;lt;0.001). Sham smoking was accompanied by a reduction in MAP after the first and second cigarette compared to baseline (by 2 and 4 mmHg, respectively, p=0.001), whereas there was no significant difference in heart rate (p=NS). The first and second TC smoking was characterized by lower muscle MSNA (by 6 and 6 bursts/minute, respectively, overall p&amp;lt;0.001) compared to baseline, whereas SSNA was increased (by 9 and 10 bursts/minute respectively, overall p&amp;lt;0.001). Additionally, EC smoking at 5 and 30 minutes caused a decrease in MSNA (by 8 and 8 bursts/minute, respectively, overall p&amp;lt;0.00) and an augmentation in SSNA (by 7 and 9 bursts per minute, respectively, overall p&amp;lt;0.001) compared to baseline. Sham smoking had no significant effect on MSNA and SSNA (p=NS for both). Conclusions Sympathetic, pressor and heart rate unfavorable responses to EC smoking are similar to those elicited by TC in healthy subjects. Our findings provide novel insights into the negative impact of EC on cardiovascular system and support opinions recommending great caution concerning EC use. Funding Acknowledgement Type of funding sources: None.

Paroxysmal atrial fibrillation prediction based on morphological variant P-wave analysis with wideband ECG and deep learning

Background and objectiveAtrial fibrillation (AF) is one of the most frequent asymptomatic arrhythmias associated with significant morbidity and mortality. Identifying the susceptibility to AF based on routine or continuous ECG recording is of considerable interest. Despite several P-wave characteristics and skin sympathetic nerve activity (SKNA) linked to AF onset, neither factor has offered accurate predictability. We propose a deep learning enabled method for AF risk prediction. MethodsWe develop a novel MVPNet to predict the upcoming onset of paroxysmal AF. MVPNet combines wavelet-based feature extraction and a deep learning classifier. MVPNet detect the approaching of AF onset by analyzing the template and frequency in P-wave segments. The morphological variant P-wave (MVP) analysis includes P-wave and SKNA features cross temporal-spectral domain. Subsequently, we designed an optimized lightweight convolutional neural network model to detect the MVP features of pre-AF episodes during sinus rhythm segments. Wideband ECG data obtained through the neuECG protocol from eight PAF patients with 177 times AF occurrence in this study. We compared the accuracy of AF prediction between ordinary ECG and neuECG. ResultsThe MVPNet effectively predicted the onset of AF episodes. 89% of ECG recorded at 5 min before the AF onset can be identified using neuECG. The proposed deep learning model, MVPNet, obtained a better precision and inference speed with less computing resources than existing models. The gradient activation map showed that neuECG recording may be a superior AF risk predictor. ConclusionsMVP analysis combined SKNA and P-wave parameters to improve predictive accuracy. The proposed MVPNet based on neuECG is superior to existing AF risk assessment with improved reliability and effectiveness. The method can be potentially applied in clinical scenarios for real-time, continuous AF prediction.

B-IN02-10 USING HOLTER MONITOR TO RECORD SKIN SYMPATHETIC NERVE ACTIVITY

neuECG is a new method to simultaneously record ECG and skin sympathetic nerve activity (SKNA). The available equipment for neuECG recording is expensive and not fully portable. To test the hypothesis that Bittium Faros 180, a small (4.8 x 2.9 x 1.2 cm) Holter monitor, can be used to record neuECG in ambulatory outpatients. We placed conventional ECG patch electrodes on the chest of 5 female outpatients (39±17 years old). The electrodes were connected to Biomation ME6000 (sampling rate 10,000 Hz) and Faros (sampling rate 1,000 Hz) during orthostatic testing (from supine to 3-min standing, then sitting). The ME6000 signals were bandpass filtered 500-1000 Hz while the Faros signals were high pass filtered at 300 Hz to display the SKNA. The same original signals were bandpass filtered 0.05-150 Hz to display ECG. The total recording time was 18.8±19.7 minutes/patient. As shown in Panel A, these two devices recorded similar patterns of nerve activities. While the amplitude of the SKNA was lower in Faros than in ME6000, they track each other over time (Panel B) with good correlations (Panel C, each dot is 1-min). For all 5 patients studied, the average SKNA (aSKNA) at supine, 1, 2 and 3 min after standing up and after sitting down were 1.02±0.34, 1.43±0.37, 1.18±0.12, 1.19±0.28 and 1.20±0.18 μV for ME6000 and were 0.94±0.05,1.05±0.10, 1.01±0.09, 0.99±0.08, 0.98±0.09 μV for Faros 180, respectively. The r values averaged 0.774 (N=5, P<0.001 for all). Holter monitors with sampling rate of 1000 Hz can be used to record neuECG. It will enable the direct measurements of SKNA in ambulatory outpatients to study the neural mechanisms of cardiac arrhythmias.

Loss of nocturnal dipping pattern of skin sympathetic nerve activity during and following an extended-duration work shift in residents in training

BackgroundExtended-duration work shifts (EDWSs) might affect the health of physician residents, causing autonomic alteration. Skin sympathetic nerve activity (SKNA) recorded by noninvasive neuro-electrocardiography (neuECG) is used to estimate cardiac sympathetic tone. In this study, we aim to evaluate the impact of EDWSs on nocturnal SKNA assessed in resident doctors. MethodsTwenty-four residents working EDWSs and 12 PhD students not working nightshift schedules were prospectively recruited. The neuECG was performed between 12 am and 6 am for 5 consecutive nights. SKNA was filtered from neuECG recorded signals. The questionnaires regarding work stress and sleep quality, blood pressure, and salivary alpha-amylase and cortisol levels were administered. ResultsThe hours of weekly working and sleep opportunities were similar between residents and students, while residents reported more work stress and worse sleep quality. In residents, SKNA at 6 am (SKNA6am) was significantly higher than SKNA2am during the precall night, revealing a dipping pattern. However, the SKNA dipping disappeared during the on-call night and prominently flattened during the first postcall night, the full recovery of which was delayed until the second postcall nights. The morning blood pressure and salivary alpha-amylase and cortisol levels were similar between the precall and postcall days. In contrast, SKNA in students exhibited a constant dipping profile for all recorded nights. ConclusionsIn healthy young adults, SKNA presents a dip night. The SKNA dip is impaired by working a nightshift, with a delayed recovery. The neuECG might serve as a useful tool to detect subclinical autonomic disturbances in shiftworkers.

Sympathoexcitation causes differing responses in supraorbital vs. peripheral skin nerves: implications for rosacea

Previous studies indicate that common fibular, tibial, and radial skin sympathetic nerve activity (SSNA) increases with physical stress in an exercise intensity-dependent manner but abates during ischemia when class III & IV muscle afferents are stimulated without the engagement of the motor cortex. It is currently unknown if these peripheral nerve responses are similar to those of facial nerves. Rosacea, a facial flushing disorder, results in substantially higher physical and mental stress-induced increases in SSNA, but whether this level of SSNA is modifiable is unknown. We tested the hypotheses that physical stress increases supraorbital SSNA in an intensity-dependent manner and that post-exercise muscle ischemia (PEMI) does not modulate supraorbital SSNA. Nine healthy subjects (5M/4F) participated in a series of physical stressors known to be symptom-triggering in individuals with rosacea. Forehead SSNA (supraorbital microneurography) was measured during handgrip exercise for 1 minute at 15%, 30%, and 45% of maximum hand grip strength. Additionally, 2 minutes of handgrip at 30% of maximum, followed by 2 minutes of PEMI (upper-arm arterial occlusion) were completed to assess the role of muscle afferents in the SSNA response. Skin blood flow (laser-Doppler flowmetry) and transepithelial water loss/sweat rate (TEWL/SR; capacitance hygrometry) were measured on both the forehead and the ventral forearm during procedures. Heart rate (HR; ECG) and mean arterial pressure (MAP; finger photoplethysmography) were also recorded. All intensities of handgrip increased HR and MAP, and these responses were positivity correlated with intensity. Handgrip also increased SSNA, but there was no association with intensity. No changes in skin blood flow or TEWL/SR were observed across trials. PEMI maintained handgrip-induced elevations of MAP and SSNA, albeit at a reduced magnitude compared to baseline. Contrary to our hypothesis, physical stress did not increase supraorbital SSNA in an intensity-dependent manner (15%, 30%, and 45% of maximum handgrip strength). Furthermore, unlike peripheral SSNA which increases during physical stress but abates during PEMI, these data indicate that ischemia or ischemic pain increases supraorbital SSNA. These data imply that supraorbital SSNA differs in control and regulation from peripheral nerves, and these differences could potentially account for altered supraorbital SSNA results observed in individuals with rosacea.

Development of GUI and Computational Algorithms for Real‐Time Physiological Autonomic Activity Tracking

Many modern diseases involve some form of autonomic disturbance/dysfunction, including diabetes, gastroparesis, and autoimmune inflammatory diseases. For some of these autonomic disruptive diseases, few studies have been able to quantify the autonomic dysfunction. Previous attempts usually resort to invasive means that carry additional risk to the patient. In addition, to properly stimulate the autonomic nervous system (ANS) artificially for treatment, quantification of dysfunction is needed for personalized medical treatment. This research has led to the development of a non-invasive, data-driven diagnostic tool that may be able to identify the type and degree of autonomic dysfunction by simply recording signals from the heart, stomach, and other vitals data, and feeding them into data-driven software. Here, BioCom Lab under Dr. Ward has developed a MATLAB-based research software that can filter and analyze several forms of biological signals for tailored viewing in a graphical user interface (GUI). The software includes several custom heart rate variability (HRV) analysis methods, several custom electrogastrogram analysis methods, and additional skin sympathetic nerve activity (SKNA) analysis implemented all into the GUI (see Fig. 1) for non-invasive physiological monitoring of potential autonomic activity. The software has been developed for real time and post hoc analysis of large data sets, enabling new insights into precise physiological monitoring by incorporating averaged data points with reference to an event or timepoint. For example, the GUI has been used on several large sets of patient data to discover the temporal interplay between autonomic activity and the cardiovascular and gastrointestinal systems where patients were monitored before and after water and Ensure drink consumption (Fig. 2). In this study's data, the GUI provided new visuals and insight from the capability to average 31 patients’ data with the same time base relative to the stimulus while also providing comparison capabilities between organ systems analysis. This research tool provides a new way to understand parasympathetic and sympathetic influence on organs, also enabling the ability to help identify timepoints of parasympathetic activity, as opposed to sympathetic activity, by monitoring organ activity. The research tool at hand has the potential to create better, less-invasive diagnostics that can help physicians to select the best course of treatment for their patients, as well as provide new analytical and visual tools for researchers to track effects on the ANS from both non-electrical and electrical stimuli.

Kompleks Bölgesel Ağrı Sendromu Olan ve Olmayan Hastalarda Cilt İletkenlik Monitörü Kullanılarak Sempatik Aktivitenin Karşılaştırılması

Aim: Sympathetic system dysfunction has been described among the theories involved in the pathophysiology of complex regional pain syndrome. Objective measurement of the sympathetic activity of the affected extremity in patients with complex regional pain syndrome has not been compared to normal subjects in the literature. The skin conductance monitor is a non-invasive monitor that can objectively measure sympathetic skin activity of the extremity. In this study, we aimed to compare the differences in sympathetic activity of extremities in subjects with and without complex regional pain syndrome by using a skin conductance monitor. Material and Methods: Sympathetic skin responses were evaluated in 63 subjects, including 25 measurements on the affected extremities in 13 patients with lower extremity complex regional pain syndrome type 1 and 50 measurements in 50 normal subjects in the control group. Among the skin conductance indices, the "peaks per second (0.02)" index was used as the main sympathetic skin response index. Descriptive criteria and the mean values of sympathetic skin response measurements were compared. Results: When sympathetic skin responses were compared with a skin conductance monitor using the "peaks per second (0.02)" index, no statistically significant difference was found between the complex regional pain syndrome and control groups in terms of sympathetic activity in the extremities (p=0.837). Conclusion: In this study, skin sympathetic nerve activity in the affected limb of patients with complex regional pain syndrome was similar to normal subjects. Further studies are required to assess the changes in sympathetic activity in complex regional pain syndrome.

Absence of reliable physiological signature of illusory body ownership revealed by fine-grained autonomic measurement during the rubber hand illusion.

The neural representation of a 'biological self' is linked theoretically to the control of bodily physiology. In an influential model, selfhood relates to internal agency and higher-order interoceptive representation, inferred from the predicted impact of efferent autonomic nervous activity on afferent viscerosensory feedback. Here we tested if an altered representation of physical self (illusory embodiment of an artificial hand) is accompanied by sustained shifts in autonomic activity. Participants (N = 37) underwent procedures for induction of the rubber hand illusion (synchronous stroking of own unseen hand and observed stroking of artificial hand) and a control condition (asychronous stroking). We recorded electrocardiography, electrodermal activity, and a non-invasive measure of multiunit skin sympathetic nerve activity (SKNA) from the chest. We compared these autonomic indices between task conditions, and between individuals who did and did not experience the illusion. Bayes factors quantified the strength of evidence for and against null hypotheses. Observed proprioceptive drift and subjective reports confirmed the efficacy of the synchronous (vs asynchronous) condition in inducing illusory hand ownership. Stringent discriminant analysis classified 24/37 individuals as experiencing the rubber hand illusion. Surprisingly, heart rate, heart rate variability, electrodermal activity, and SKNA measures revealed no autonomic differences between synchronous vs asynchronous conditions, nor between individuals who did or did not experience the rubber hand illusion. Bayes factors indicated substantial evidence for no physiological differences. In contrast to earlier reports, our autonomic data show the absence of a reliable change in physiological state during the rubber hand illusion. More encompassing perturbations of self-experience, for example in full body illusions, may nevertheless be coupled to, or facilitated by, changes in efferent autonomic activity and afferent viscerosensory feedback. Our findings suggest that such changes in bodily physiology are not sustained as an obligatory component of the rubber hand illusion.

Sympathetic nerve outflow to skin in a case with dentatorubral-pallidoluysian atrophy

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by slowly progressive cerebellar ataxia. Previously, autonomic symptoms or dysfunction have not been reported. To evaluate subclinical autonomic dysfunction regarding thermoregulatory function in SCA, we recorded sympathetic outflow to skin in a DRPLA patient confirmed by genetic analysis. We recorded skin sympathetic nerve activity (SSNA), which was elicited and recorded by using the microneurographical technique. In results, the resting frequency of SSNA bursts was very low (8.2 ± 0.4 bursts/min [institutional normal range: 20.8 ± 2.4 bursts/min]). However, acceleration of SSNA bursts induced by mental arithmetic stress was confirmed. The amplitude of reflex bursts induced by electrical stimuli was slightly low (9.6 ± 1.6 μV [institutional normal range: 10.9 ± 2.2 μV]), and the reflex latency was mildly prolonged (872 ± 23.7 msec [institutional normal range: 761.9 ± 51.7 msec]). These results suggest potentially central autonomic dysfunction in this patient with DRPLA. To our knowledge, this is the first report to record SSNA and confirm subclinical autonomic dysfunction in a case with DRPLA.

Skin sympathetic nerve activity as a biomarker for neurologic recovery during therapeutic hypothermia for cardiac arrest

Targeted temperature management (TTM) improves neurologic outcome after cardiac arrest. However, better neurologic prognostication is needed. The purpose of this study was to test the hypothesis that noninvasive recording of skin sympathetic nerve activity (SKNA) and its association with heart rate (HR) during TTM may serve as a biomarker of neurologic status. SKNA recordings were analyzed from 29 patients undergoing TTM. Patients were grouped based on Clinical Performance Category (CPC) score into group 1 (CPC 1-2) representing a good neurologic outcome and group 2 (CPC 3-5) representing a poor neurologic outcome. Of the 29 study participants, 18 (62%) were deemed to have poor neurologic outcome. At all timepoints, low average skin sympathetic nerve activity (aSKNA) was associated with poor neurologic outcome (odds ratio 22.69; P = .002) and remained significant (P = .03) even when adjusting for presenting clinical factors. The changes in aSKNA and HR during warming in group 1 were significantly correlated (ρ = 0.49; P <.001), even when adjusting for corresponding temperature and mean arterial pressure measurements (P = .017), whereas this correlation was not observed in group 2. Corresponding to high aSKNA, there was increased nerve burst activity during warming in group 1 compared to group 2 (0.739 ± 0.451 vs 0.176 ± 0.231; P = .013). Neurologic recovery was retrospectively associated with SKNA. Patients undergoing TTM who did not achieve neurologic recovery were associated with low SKNA and lacked a significant correlation between SKNA and HR. These preliminary results indicate that SKNA may potentially be a useful biomarker to predict neurologic status in patients undergoing TTM.

Vestibular modulation of skin sympathetic nerve activity in sopite syndrome induced by low-frequency sinusoidal motion.

Sopite syndrome, centered around the drowsiness, lethargy, and irritability associated with motion sickness, can be induced by exposure to low-frequency motion. It is known that the vestibular apparatus plays an important role in the pathogenesis of motion sickness, which features several autonomic responses, and we have previously documented increased vestibular modulation of skin sympathetic nerve activity (SSNA) and an increase in skin blood flow associated with nausea. Here, we assessed whether imperceptibly slow sinusoidal motion, sufficient to induce sopite syndrome but not nausea, also modulates SSNA and skin blood flow. Participants were seated upright and exposed to a randomized set of sinusoidal linear accelerations, ranging from 0.03 Hz at 0.5 mG to 0.2 Hz at 5 mG, via a motorized platform. At all frequencies vestibular modulation was greater than the cardiac modulation of SSNA, but cardiac modulation and skin blood flow were both significantly lower during the motion than at baseline. We conclude that sopite syndrome is associated with a marked modulation of sympathetic outflow to the skin and cutaneous vasoconstriction.NEW & NOTEWORTHY Little is known about the autonomic consequences of sopite syndrome-the drowsiness that can be induced by low-amplitude cyclic motion. We recorded skin sympathetic nerve activity (SSNA) in seated participants exposed to slow sinusoidal linear acceleration (0.03-0.2 Hz), which preferentially activates hair cells in the utricular part of the otolithic organs, at amplitudes that generated no sensations of motion. At all frequencies, there was a clear vestibular modulation of SSNA and cutaneous vasoconstriction.