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Electrodermal activity (EDA)—a measure of electrical skin conductance reflecting (exclusive) sympathetic control of the eccrine sweat gland—holds promise as an indicator of central sympathetic activation. The aim of this study was to determine whether combat and blast exposure modulate the EDA response to acute exercise stress in specialised military men. Fifty‐one men (age M = 36.1, SD = 6.5) participated in this study as part of the Explosive Ordnance Disposal Operational Health Surveillance System. The EDA complex (i.e., tonic + phasic conductance) was continuously measured throughout a maximal effort, graded exercise test. As expected, exercise stress resulted in measurable, stepwise increases in EDA before tapering at higher exercise intensities. Individuals with more substantial combat exposure and those with blast exposure demonstrated blunted EDA patterns in comparison to their low/nonexposed counterparts. This blunted pattern might imply sub‐optimal sympathetic nervous system function in the exposed cohorts and enhances our knowledge of factors influencing resilience in these men. [ABSTRACT FROM AUTHOR]

Stressors and mortality salience share considerable conceptual overlap. Thus, we examined the impact of a standard mortality salience and a standard stress manipulation on the activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis via endocrine measures of stress; a neutral control condition completed the design. The results revealed that stress elicits increased salivary α-amylase and salivary cortisol reactions; however, no endocrine reactions were found in the mortality salience and the control conditions. To the contrary, we did not find any differences regarding positive and negative affect between any conditions. Implications for social and health psychology are being discussed. [ABSTRACT FROM AUTHOR]

The increasing prevalence of obesity has resulted in demands for the development of new effective strategies for obesity treatment. Withaferin A (WA) shows a great potential for prevention of obesity by sensitizing leptin signaling in the hypothalamus. However, the mechanism underlying the weight- and adiposity-reducing effects of WA remains to be elucidated. In this study, we report that WA treatment induced white adipose tissue (WAT) browning, elevated energy expenditure, decreased respiratory exchange ratio, and prevented high-fat diet-induced obesity. The sympathetic chemical denervation dampened the WAT browning and also impeded the reduction of adiposity in WA-treated mice. WA markedly upregulated the levels of Prdm16 and FATP1 (Slc27a1) in the inguinal WAT (iWAT), and this was blocked by sympathetic denervation. Prdm16 or FATP1 knockdown in iWAT abrogated the WAT browning-inducing effects of WA and restored the weight gain and adiposity in WA-treated mice. Together, these findings suggest that WA induces WAT browning through the sympathetic nerve-adipose axis, and the adipocytic Prdm16-FATP1 pathway mediates the promotive effects of WA on white adipose browning. [ABSTRACT FROM AUTHOR]

The study investigated the role of α2-adrenergic receptors of the caudal raphe region in the sympathetic and cardiovascular responses to the acute intermittent hypercapnia (AIHc). Urethane-anesthetized, vagotomized, mechanically ventilated Sprague-Dawley rats (n=38) were exposed to the AIHc protocol (5×3 min, 15 % CO2+50 % O2) in hyperoxic background (50 % O2). α2-adrenergic receptor antagonist-yohimbine was applied intravenously (1 mg/kg, n=9) or microinjected into the caudal raphe region (2 mM, n=12) prior to exposure to AIHc. Control groups of animals received saline intravenously (n=7) or into the caudal raphe region (n=10) prior to exposure to AIHc. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were monitored before exposure to the AIHc protocol (T0), during five hypercapnic episodes (THc1-5) and at 15 min following the end of the last hypercapnic episode (T15). Following intravenous administration of yohimbine, RSNA was significantly greater during THc1-5 and at T15 than in the control group (P<0.05). When yohimbine was microinjected into the caudal raphe region, AIHc elicited greater increases in RSNA during THc1-5 when compared to the controls (THc1: 138.0±4.0 % vs. 123.7±4.8 %, P=0.032; THc2: 137.1±5.0 % vs. 124.1±4.5 %, P=0.071; THc3: 143.1±6.4 % vs. 122.0±4.8 %, P=0.020; THc4: 146.1±6.2 % vs. 120.7±5.7 %, P=0.007 and THc5: 143.2±7.7 % vs. 119.2±7.2 %, P=0.038). During THc1-5, significant decreases in HR from T0 were observed in all groups, while changes in MAP were observed in the group that received yohimbine intravenously. These findings suggest that blockade of the α2-adrenegic receptors in the caudal raphe region might have an important role in sympathetic responses to AIHc. [ABSTRACT FROM AUTHOR]

Diverticular disease pathogenesis is still unknown in depth. Adaptation to a severe social stress possibly generates sustained dominance of the sympathetic over the parasympathetic activity, leading through a prolonged spasm of the sigmoid to the creation of diverticula and the related disease. Based on case series, we suggest an imbalance in autonomic nervous activity as a component of the multisystemic complex pathophysiology of diverticular disease. [ABSTRACT FROM AUTHOR]

Cognitive skills are a set of higher-order thinking processes that allow children to learn successfully. By developing cognitive skills, the brain is connected to Rapidly complete the information processes. The aim of this study was to examine the cognitive process development, decision making and eventually cognitive performance in school-age children evaluated by the galvanic skin conductance response (SCR) method. Peripheral SCR signals during cognitive loading were recorded in children in grades 1 to 3 of a representative school in Southern Thailand. Eriksen flanker and dexterity tests were conducted to evaluate the development of its association with cognitive skill. Regression-based analyses showed reduced reaction time on Eriksen flanker (both congruent trials with regression coefficient = -0.02924, p <0.001 and incongruent trials with regression coefficient = -0.04231, p <0.001) and time spent to achieve dexterity tests (regression coefficient = -0.32206379, p <0.05) from students' grades 1 to 3. In SCR modulation, analysis of variance revealed highest peak SCR magnitudes in students grade 3, compared to students in grade 2 (p <0.001) and grade 1 (p =0.046). On the other hands, numbers of peaks were highest in students grade 1 when they were in the calm stage (p <0.001), and highest in student grade 3 (p =0.002) when they were in the focus mind state. These findings support the association of the psychophysiological index of changes in brain and cognitive development among age related experience to focus attention improving under the task. [ABSTRACT FROM AUTHOR]

Purpose: Larger blood pressure (BP) responses to relative-intensity static exercise in men versus women are thought to involve altered muscle metaboreflex activation, but whether this is because of an intrinsic sex difference in metabolite production or differences in muscle strength and absolute load is unknown. Methods : Continuous BP and heart rate were recorded in 200 healthy young men and women (women: n = 109) during 2 min of static handgrip exercise at 30% of maximal voluntary contraction (MVC), followed by 2 min of postexercise circulatory occlusion (PECO). Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (n = 39; women, n = 21), permitting calculation of signal-averaged resting sympathetic transduction (MSNA-diastolic BP). Sex differences were examined with and without statistical adjustment for MVC. Multivariate regression analyses were performed to identify predictors of BP responses. Results : Men had larger systolic BP responses (interactions, P < 0.0001) to static handgrip exercise (24 +/- 10 vs 17 +/- 9 mm Hg [mean +/- SD], P < 0.0001) and PECO (20 +/- 11 vs 16 +/- 9 mm Hg, P < 0.0001). Adjustment for MVC abolished these sex differences in BP (interactions, P > 0.7). In the subset with MSNA, neither burst frequency or incidence responses to static handgrip exercise or PECO differed between men and women (interactions, P > 0.2). Resting sympathetic transduction was also similar (P = 0.8). Multiple linear regression analysis showed that MVC or the change in MSNA, were predictors of BP responses to static handgrip, but only MVC was associated with BP responses during PECO. Conclusions: Sex differences in absolute contraction load contribute to differences in BP responses during muscle metaboreflex isolation using PECO. These data do not support an intrinsic effect of sex as being responsible for exercise BP differences between men and women. [ABSTRACT FROM AUTHOR]

Both anxiety and autism spectrum disorder (ASD) are associated with atypical physiological activity. Few studies have systematically assessed the resting physiological activity in ASD with co-occurring anxiety disorders. We tested 75 participants divided in four groups: youth with ASD, with (ASD + Anxiety = 22, 6F, 12.29 ± 2.83 years old) and without co-occurring anxiety (ASD Alone = 15, 6F, 11.59 ± 2.85 years old) and compared their physiological profile with that of matched typically developing controls (TDC) with (Anxiety Alone = 16, 6F, 11.24 ± 3.36 years old) and without co-occurring anxiety disorders (TDC = 22, 8F, 11.88 ± 2.88 years old). Results indicated reduced sympathetic and parasympathetic activity at rest in ASD as compared to TDC youth. ASD + Anxiety and Anxiety Alone groups showed different sympathetic, but similar parasympathetic activity. These findings suggest that autonomic profile-based approaches may advance research, diagnosis, and treatment of ASD and anxiety. [ABSTRACT FROM AUTHOR]

Objective: This study aims to compare the instantaneous effects of chiropractic upper and middle thoracic manipulations on the autonomic nervous system. Material-Method: The study included 30 healthy volunteers aged 18-45 years. Manipulation was applied to the upper thoracic (T1-4) area (n=15, 8 female, 7 male) and to the middle thoracic (T6-9) area (n=15, 7 female, 8 male). Before the application, heart rate, body temperature and skin conductivity (EDA) measurements were performed using the Empatica E4 wristband device. Thoracic HVLA (high velocity low amplitude) manipulation was performed in the supine position. After the application, the measurement made with the Empatica E4 device was repeated. The mean body temperature and skin conductivity values were calculated for the analysis of the data. Heart rate data were evaluated using Kubios heart rate variability (HRV) standard program. Detailed information about the effects of upper and middle thoracic area manipulation on the autonomic nervous system was obtained according to the analysis results of the data obtained before and after manipulation. Correlation analysis of pre- and post-manipulation data and difference analysis between the two groups were performed based on significance level p<0.05. Results: As a result of the research, no significant changes in parasympathetic nervous system values such as RMSSD, pNN50, PNS Index and sympathetic nervous system values such as Stress Index and SNS Index were observed after upper thoracic manipulation. After middle thoracic manipulation, significant decreases occurred in sympathetic nervous system values such as Stress Index, SNS Index, while significant increases occurred in parasympathetic nervous system values such as RMSSD, pNN50, PNS Index. It was observed that there was no significant change in temperature and EDA. Conclusion: As a result of our measurements and analyzes, it was seen that chiropractic upper and middle thoracic manipulations had different instantaneous effects on the autonomic nervous system. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of catheter-based renal denervation for reducing blood pressure in patients with resistant hypertension using a 5 F microtube-irrigated ablation catheter. Methods: Sixty patients with resistant hypertension were divided into two groups: a microtube-irrigated ablation catheter group and a general ablation catheter group. We conducted 12-month follow-up of all patients and recorded clinical blood pressure, ambulatory blood pressure, medication use, and biochemistry test results in both groups at the baseline and at the 12-month follow-up. Results: All patients underwent renal denervation. At the 6-month follow-up, ambulatory blood pressure in the microtube-irrigated ablation catheter group was significantly lower than in the general ablation catheter group (systolic blood pressure 142.0 ± 14.4 mmHg vs. 150.8 ± 17.9 mmHg, P = 0.04; diastolic blood pressure 81.2 ± 7.0 mmHg vs. 87.6 ± 8.0 mmHg, P = 0.002). At the 12-month follow-up, the between-group difference in ambulatory blood pressure was not statistically significant. At the 12-month follow-up, the number of antihypertensive drugs and diuretics used in the microtube-irrigated ablation catheter group was less than in the general ablation catheter group (P = 0.043). There was no statistical difference between the two groups in the results of biochemistry tests and echocardiography. Conclusion: The microtube-irrigated ablation catheter is more effective in treating hypertension than the general ablation catheter at the 6-month follow up and thus fewer antihypertensive drugs were used in the microtube-irrigated ablation catheter group than in the general ablation catheter group. [ABSTRACT FROM AUTHOR]

Long-lasting elevated blood pressure (BP), i.e. hypertension, is a major contributor to morbidity and mortality worldwide. As a multifactorial and systemic disease that involves multiple systems, hypertension remains a challenging disease to study. Models of hypertension are a basic source of knowledge to drive and support the discovery of the specific genetic, cellular, and molecular mechanisms underlying essential hypertension, as well as to discover and introduce new possible treatments to lower BP. Animal models of hypertension deliver a huge amount of information but it is important to choose the proper one for our scientific hypothesis. In this review, we discuss the physiological, and biochemical background of rodent models of hypertension through a systems approach and a myriad of mechanisms and pathways involved in blood pressure control. We also pay attention to how target organs and systems including the kidneys, vasculature, the sympathetic nervous system (SNS), and immunological system, interfere with each other, and their activity is differentially controlled by sodium delivery, which still remains a pivotal troublemaker.

Purpose: The nadir pressure responses to cardiac cycles absent of muscle sympathetic nerve activity (MSNA) bursts (or non-bursts) are typically reported in studies quantifying sympathetic transduction, but the information gained by studying non-bursts is unclear. We tested the hypothesis that longer sequences of non-bursts (≥8 cardiac cycles) would be associated with a greater nadir diastolic blood pressure (DBP) and that better popliteal artery function would be associated with an augmented reduction in DBP., Methods: Resting beat-by-beat DBP (via finger photoplethysmography) and common peroneal nerve MSNA (via microneurography) were recorded in 39 healthy, adults (age 23.4 ± 5.3 years; 19 females). For each cardiac cycle absent of MSNA bursts, the mean nadir DBP (ΔDBP) during the 12 cardiac cycles following were determined, and separate analyses were conducted for ≥8 or < 8 cardiac cycle sequences. Popliteal artery endothelial-dependent (via flow-mediated dilation; FMD) and endothelial-independent vasodilation (via nitroglycerin-mediated dilation; NMD) were determined., Results: The nadir DBP responses to sequences ≥8 cardiac cycles were larger (-1.40 ± 1.27 mmHg) than sequences <8 (-0.38 ± 0.46 mmHg; p < 0.001). In adjusting for sex and burst frequency (14 ± 8 bursts/min), larger absolute or relative FMD (p < 0.01), but not NMD (p > 0.53) was associated with an augmented nadir DBP. This overall DBP-FMD relationship was similar in sequences ≥8 (p = 0.04-0.05), but not <8 (p > 0.72)., Conclusion: The DBP responses to non-bursts, particularly longer sequences, were inversely associated with popliteal endothelial function, but not vascular smooth muscle sensitivity. This study provides insight into the information gained by quantifying the DBP responses to cardiac cycles absent of MSNA., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Type 2 diabetes (T2D) is often accompanied by hypertension, exaggerated blood pressure (BP) responses to sympatho-excitatory stressors, and raised cardiovascular disease risk. Appropriate respiratory-sympathetic coupling and sympathetic transduction to BP are important for short- and longer-term BP control. We tested the hypotheses that respiratory modulation of muscle sympathetic nerve activity (MSNA) and its transduction to BP would be impaired in T2D and associated with higher BP and respiratory-coupled BP variability. Resting MSNA, respiration and beat-to-beat BP were recorded in 20 T2D (49.1 ± 7.4 years; mean ± SD) and 13 healthy control (46.3 ± 9.4 years) participants. MSNA and the transduction of sympathetic bursts (signal-averaging) to mean arterial pressure (MAP) were compared at low and high lung volume phases. The peak MAP response following a sympathetic burst was lower during the high lung volume than low lung volume phase in controls (P = 0.005), whereas it was unchanged with phase in T2D participants (P = 0.522). Respiratory modulation of MSNA was impaired in T2D participants, who had an attenuated reduction in burst incidence from low to the high lung volume phase, versus controls (27.8 ± 38.4% vs. 49.4 ± 24.6%, respectively; P = 0.043). The T2D participants were grouped into unimpaired respiratory modulators (burst incidence modulation median or above) or impaired respiratory modulators (below median). Impaired modulators had higher systolic BP (133 ± 14 vs. 121 ± 11 mmHg, P = 0.046), greater Traube-Hering wave amplitudes (6.3 ± 2.4 vs. 4.6 ± 1.1 mmHg; P = 0.028) and higher BP variability (MAP average real variability, 2.0 ± 0.7 vs. 1.4 ± 0.3, P = 0.033). Respiratory modulation of MSNA and sympathetic transduction to BP are altered in T2D patients and may contribute to their increased hypertension and cardiovascular risk. KEY POINTS: Respiratory-sympathetic coupling and sympathetic transduction to blood pressure (BP) contribute to short- and longer-term BP control. Our understanding of these processes in health and type 2 diabetes (T2D), a condition with high prevalence of hypertension and cardiovascular risk, is incomplete. We found that respiration and sympathetic transduction to BP are coupled in healthy individuals. The mean arterial pressure response to a sympathetic burst was reduced during the high lung volume compared to the low lung volume phase. This coupling was absent in T2D. Respiratory modulation of muscle sympathetic nerve activity (MSNA) is impaired in T2D, with a blunted reduction of MSNA observed during the high lung volume phase. T2D patients with impaired respiratory MSNA modulation had augmented systolic BP, respiratory-related BP excursions (Traube-Hering waves) and BP variability. Abnormal respiratory modulation of MSNA and sympathetic transduction to BP in T2D may contribute to altered blood pressure control and cardiovascular risk in this population., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The purpose of this systematic review and meta-analysis was to examine the effects of exercise training on muscle sympathetic nerve activity (MSNA) in humans. Studies included exercise interventions [randomized controlled trials (RCTs), nonrandomized controlled trials (non-RCTs), or pre-to-post intervention] that reported on adults (≥18 yr) where MSNA was directly assessed using microneurography, and relevant outcomes were assessed [MSNA (total activity, burst frequency, burst incidence, amplitude), heart rate, blood pressure (systolic blood pressure, diastolic blood pressure, or mean blood pressure), and aerobic capacity (maximal or peak oxygen consumption)]. Forty intervention studies ( n = 1,253 individuals) were included. RCTs of exercise compared with no exercise illustrated that those randomized to the exercise intervention had a significant reduction in MSNA burst frequency and incidence compared with controls. This reduction in burst frequency was not different between individuals with cardiovascular disease compared with those without. However, the reduction in burst incidence was greater in those with cardiovascular disease [9 RCTs studies, n = 234, mean difference (MD) -21.08 bursts/100 hbs; 95% confidence interval (CI) -16.51, -25.66; I 2 = 63%] compared with those without (6 RCTs, n = 192, MD -10.92 bursts/100 hbs; 95% CI -4.12, -17.73; I 2 = 76%). Meta-regression analyses demonstrated a dose-response relationship where individuals with higher burst frequency and incidence preintervention had a greater reduction in values post-intervention. These findings suggest that exercise training reduces muscle sympathetic nerve activity, which may be valuable for improving cardiovascular health. NEW & NOTEWORTHY This systematic review and meta-analysis suggests exercise training reduces muscle sympathetic nerve activity (MSNA), which may be valuable for improving cardiovascular health. The reduction in burst incidence was greater among individuals with cardiovascular disease when compared with those without; exercise training may be particularly beneficial for individuals with cardiovascular disease. Meta-regression analyses demonstrated a dose-response relationship, where individuals with higher sympathetic activity preintervention had greater reductions in sympathetic activity post-intervention.

The present study investigated the impact of central α 2 -adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α 2 -adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg -1 ; maintenance infusion of 0.1-0.5 µg kg h -1 ) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats -1 , P = 0.003) most strongly for medium-sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats -1 ; P < 0.001). Dexmedetomidine progressively de-recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de-recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats -1 , P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ -0.09 ± 0.07 to Δ -0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium-sized APs (normalized cluster 2: -6.0 ± 5 to -1.6 ± 2 % mmHg -1 ; P = 0.008). These data suggest that α 2 -adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. KEY POINTS: Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear. This microneurographic study investigated the impact of a dexmedetomidine infusion (α 2 -adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns. Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre. Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre. These data suggest that α 2 -adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Short and insufficient sleep are prevalent and associated with cardiovascular disease, with the sympathetic nervous system as a suspected mediator. The purpose of the present study was to investigate the association between objective, actigraphy-based total sleep time (TST), sleep efficiency (SE), and cardiovascular and sympathetic regulation in healthy adults. We hypothesized that short TST and low SE would be associated with elevated resting blood pressure, heart rate (HR), and muscle sympathetic nerve activity (MSNA). Participants included 94 individuals [46 males, 48 females, age: 30 ± 15 yr, body mass index (BMI): 26 ± 4 kg/m 2 ]. All participants underwent at least 7 days of at-home, wristwatch actigraphy monitoring (avg: 10 ± 3 days). Seated blood pressures were assessed using brachial blood pressure measurements, followed by a 10-minute supine autonomic testing session consisting of continuous HR (electrocardiogram), beat-by-beat blood pressure (finger plethysmograph), and MSNA (microneurography) monitoring. Partial correlations were used to determine the relationship between sleep and cardiovascular parameters while accounting for the influence of age, sex, and BMI. TST was not associated with MAP ( R = -0.105, P = 0.321), HR ( R = 0.093, P = 0.383), or MSNA burst frequency (BF; R = -0.168, P = 0.112) and burst incidence (BI; R = -0.162, P = 0.124). Similarly, SE was not associated with MAP ( R = -0.088, P = 0.408), HR ( R = -0.118, P = 0.263), MSNA BF ( R = 0.038, P = 0.723), or MSNA BI ( R = 0.079, P = 0.459). In contrast to recent preliminary findings, our results do not support a significant association between actigraphy-based sleep duration or efficiency and measures of resting blood pressure, heart rate, and MSNA. NEW & NOTEWORTHY The present study investigated the independent association between actigraphy-based sleep duration, efficiency, and measures of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) in adult males and females. Contrary to our hypothesis, the findings do not support an independent association between habitual sleep and cardiovascular or sympathetic neural activity. However, these findings do not preclude a potential association between these parameters in populations with sleep disorders and/or cardiovascular disease.

The sympathetic nervous system is critical for regulating blood pressure (BP) via the arterial baroreflex and sympathetic transduction in the peripheral vasculature. These mechanisms interact, and both may be altered with aging and impacted by menopause. Although age-related decreases in sympathetic transduction have been demonstrated in women, it remains unclear whether sympathetic baroreflex sensitivity (BRS) is impaired in postmenopausal women (POST). We tested the hypothesis that sympathetic BRS would be enhanced in POST compared with premenopausal women (PRE). We examined beat-by-beat BP and muscle sympathetic nerve activity (MSNA) in 19 PRE (22 ± 2 yr, 22 ± 3 kg/m 2 ) and 12 POST (57 ± 5 yr, 24 ± 2 kg/m 2 ) during 10 min of rest. Spontaneous sympathetic BRS was quantified as the slope of a linear regression between MSNA burst incidence and diastolic BP. Sympathetic transduction to mean arterial pressure (MAP) for the 10 cardiac cycles following spontaneous MSNA bursts was assessed via signal averaging method. Resting MAP was similar (PRE: 82 ± 8 vs. POST: 85 ± 8 mmHg, P = 0.43), whereas resting MSNA was elevated in POST (PRE: 10 ± 6 vs. POST: 45 ± 16 bursts/100 heart beats, P < 0.0001). Spontaneous sympathetic BRS was enhanced in POST (PRE: -2.0 ± 1.2 vs. POST: -5.2 ± 1.9 bursts/beat/mmHg, P < 0.0005). Sympathetic transduction to MAP was attenuated in POST (time: P < 0.001, group: P < 0.001, interaction: P < 0.01). These data suggest that sympathetic BRS may be enhanced in POST. Consistent with recent hypotheses, enhanced sensitivity of the arterial baroreflex's neural arc may signify a compensatory response to reduced efficiency of the peripheral arterial baroreflex arc (i.e., sympathetic transduction) to preserve BP buffering capacity. NEW & NOTEWORTHY Studies examining sympathetic baroreflex function with aging remain equivocal, with some studies showing an increase, decrease, or no change in sympathetic baroreflex sensitivity (BRS) in older adults compared with younger adults. With aging, women experience unique physiological changes due to menopause that influence autonomic function. For the first time, we show that postmenopausal women exhibit a greater sympathetic BRS compared with young premenopausal women.

Body posture and biological sex exhibit independent effects on the sympathetic neural responses to dynamic exercise. However, the neural mechanisms (e.g., baroreflex) by which posture impacts sympathetic outflow during rhythmic muscular contractions, and whether biological sex affects posture-mediated changes in efferent sympathetic nerve traffic during exercise, remain unknown. Thus, we tested the hypotheses that increases in muscle sympathetic nerve activity (MSNA) would be greater during upright compared with supine rhythmic handgrip (RHG) exercise, and that females would demonstrate smaller increases in MSNA during upright RHG exercise than males. Twenty young (30 [6] yr; means [SD]) individuals (9 males, 11 females) underwent 6 min of supine and upright (head-up tilt 45°) RHG exercise at 40% maximal voluntary contraction with continuous measurements of MSNA (microneurography), blood pressure (photoplethysmography), and heart rate (electrocardiogram). In the pooled group, absolute MSNA burst frequency ( P < 0.001), amplitude ( P = 0.009), and total MSNA ( P < 0.001) were higher during upright compared with supine RHG exercise. However, body posture did not impact the peak change in MSNA during RHG exercise (range: P = 0.063-0.495). Spontaneous sympathetic baroreflex gain decreased from rest to RHG exercise ( P = 0.006) and was not impacted by posture ( P = 0.347). During upright RHG exercise, males demonstrated larger increases in MSNA burst amplitude ( P = 0.002) and total MSNA ( P = 0.001) compared with females, which coincided with greater reductions in sympathetic baroreflex gain among males ( P = 0.004). Collectively, these data indicate that acute attenuation of baroreflex-mediated sympathoinhibition permits increases in MSNA during RHG exercise and that males exhibit a greater reserve for efferent sympathetic neural recruitment during orthostasis than females. NEW & NOTEWORTHY The impact of posture and sex on cardiovascular control during rhythmic handgrip (RHG) exercise is unknown. We show that increases in muscle sympathetic nerve activity (MSNA) during RHG are partly mediated by a reduction in sympathetic baroreflex gain. In addition, males demonstrate larger increases in total MSNA during upright RHG than females. These data indicate that the baroreflex partly mediates increases in MSNA during RHG and that males have a greater sympathetic vasoconstrictor reserve than females.

Background: Para-sympathetic vagal activation has profound influence on heart rate and other cardiovascular parameters. We tested the hypothesis that transcutaneous Vagal Nerve Stimulation (tVNS) through the auricular branch of the vagus nerve would attenuate the normal sympathetic response to central blood volume reduction by lower body negative pressure (LBNP)., Method: 10 healthy volunteers (6 female; age 21 ± 2 years; weight 62 ± 13 kg; height 167 ± 12 cm) were included in this cross-over design trial. After 15 min rest in supine position, subjects underwent three 15-min periods of 30 mmHg LBNP intervention with and without cyclic tVNS stimulation. Continuous cardiovascular parameters (Nexfin) were recorded., Results: Overall tVNS did not convincingly attenuate sympathetic response to central hypovolemia. Deactivation of the tVNS during LBNP resulted in increased MAP at 2.3 ± 0.5 mmHg (P < 0.001). Comparing the cyclic actual active stimulation periods to periods with pause during tVNS intervention showed a decrease in HR by 72.9 ± 11.2 to 70.2 ± 11.6 bpm (mean ± SD; P < 0.05), and concomitant increases in SV (86.0 ± 12.1 to 87.2 ± 12.6 mL; P < 0.05), MAP (82.9 ± 6.3 to 84.0 ± 6.2 mmHg; P < 0.05) and TPR (1116.0 ± 111.1 to 1153 ± 104.8 dyn*s/cm5; P < 0.05)., Conclusion: tVNS in 30 s cycles during LBNP can selectively attenuate HR, prompting a compensatory augmented sympathetic response. It would appear the method used in this study at least, has an isolated cardiac inhibitory effect probably mediated by augmented vagal activity on the sinoatrial or atrio-ventricular node, possibly in combination with reduced activity in the sympathetic cardiac nerve., Competing Interests: Declaration of competing interest The authors have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is clear evidence that the sympathetic nervous system (SNS) mediates bone metabolism. Histological studies show abundant SNS innervation of the periosteum and bone marrow-these nerves consist of noradrenergic fibers that immunostain for tyrosine hydroxylase, dopamine beta-hydroxylase, or neuropeptide Y. Nonetheless, the brain sites that send efferent SNS outflow to the bone have not yet been characterized. Using pseudorabies (PRV) viral transneuronal tracing, we report, for the first time, the identification of central SNS outflow sites that innervate bone. We find that the central SNS outflow to bone originates from 87 brain nuclei, sub-nuclei, and regions of six brain divisions, namely the midbrain and pons, hypothalamus, hindbrain medulla, forebrain, cerebral cortex, and thalamus. We also find that certain sites, such as the raphe magnus (RMg) of the medulla and periaqueductal gray (PAG) of the midbrain, display greater degrees of PRV152 infection, suggesting that there is considerable site-specific variation in the levels of central SNS outflow to the bone. This comprehensive compendium illustrating the central coding and control of SNS efferent signals to bone should allow for a greater understanding of the neural regulation of bone metabolism, and importantly and of clinical relevance, mechanisms for central bone pain., Competing Interests: VR, DL, KG, SK Reviewing editor, eLife, AG, RW, FK, LC, HK, OM, OB, SS No competing interests declared, TY Senior editor, eLife, MZ consults for Gershon Lehmann, Guidepoint and Coleman groups, (© 2024, Ryu et al.)

Emotion regulation (ER) is a multifaceted construct, involving behavioral, cognitive, and physiological processes. Although autonomic coordination is theorized to play a crucial role in adaptive functioning, few studies have examined how different individual and contextual factors together may contribute to such coordination. This study examined the joint influences of narrative processing and emotional negativity/lability (N/L) traits on the coordination of the sympathetic and parasympathetic nervous systems in a sample of 112 children, ages 8-12 years (M age  = 10.15 years, SD = 1.33). Children completed a stress-induction task followed by an interview about the task. Children's trait-level N/L was assessed via parent-report on the Emotion Regulation Checklist. Narrative processing was assessed and coded based on children's narrative accounts of the event (i.e., causal coherence, overall emotional tone). Indexes of sympathetic (skin conductance response, SCR) and parasympathetic (respiratory sinus arrhythmia, RSA) functioning were derived from physiological data obtained during the interview. Results revealed that children's trait-level N/L and narrative processing of the stressful event interacted to predict the RSA-SCR correlation. Specifically, children who were high on either N/L or narrative causal coherence, but not both, demonstrated significant RSA-SCR correlation. Similarly, children with high N/L and negative-to-neutral narratives, as well as those with low N/L and neutral-to-positive narratives, exhibited significant RSA-SCR correlation. This work provides empirical evidence that narrative processing and trait N/L, together with RSA-SCR correlation, work in tandem to regulate emotional arousal., (© 2024 Society for Psychophysiological Research.)

Intense inspiratory muscle work can evoke a metabolite-stimulated pressor reflex, commonly referred to as the respiratory muscle metaboreflex. When completing similar relative and absolute levels of inspiratory work, females have an attenuated blood pressure response. We sought to test the hypothesis that the lower blood pressure response to the respiratory muscle metaboreflex in females is associated with a reduced sympathetic response. Healthy young (26 ± 4 yr) males ( n = 9) and females ( n = 7) completed two experimental days. On day 1 , participants completed pulmonary function testing and became familiarized with an inspiratory pressure-threshold loading (PTL) task. On the second day, balloon-tipped catheters were placed in the esophagus and stomach to measure pleural and gastric pressures, and transdiaphragmatic pressure was calculated. A microelectrode was inserted into the fibular nerve to quantify muscle sympathetic nerve activity (MSNA), and participants then completed isocapnic PTL to task failure. There was a significant sex-by-time interaction in the mean arterial pressure (MAP, P = 0.015) and burst frequency ( P = 0.039) response to PTL. Males had a greater rise in MAP (Δ21 ± 9 mmHg) than females (Δ13 ± 5 mmHg, P = 0.026). Males also demonstrated a greater rise in MSNA burst frequency (Δ18 ± 7 bursts/min) than females (Δ10 ± 5 bursts/min, P = 0.015). The effect of sex was observed despite females and males completing the same magnitude of diaphragm work throughout the task ( P = 0.755). Our findings provide novel evidence that the lower blood pressure response to similar relative and absolute inspiratory muscle work in females is associated with lower sympathetic activation. NEW & NOTEWORTHY The blood pressure response to high levels of inspiratory muscle work is lower in females and occurs alongside a reduced sympathetic response. The reduced blood pressure and sympathetic response occur despite males and females performing similar levels of absolute inspiratory work. Our findings provide evidence that sex differences in the respiratory muscle metaboreflex are, in part, sympathetically mediated.

During times of stress, we look to close others for support. Social support conversations are critical for relationship maintenance and well-being. Yet, certain ways of talking about problems-such as co-ruminating-can exacerbate stress. Since social support and co-rumination are both dyadic processes, it is important to examine physiological responses during these conversations in a dyadic manner. Little research has examined physiological synchrony of the sympathetic nervous system (SNS) during social support conversations or co-ruminative conversations. The current research capitalizes on an experimental manipulation of co-rumination using a sample of close friends (147 dyads) and romantic partners (113 dyads) to examine physiological covariation in the context of support. Across both samples, dyads exhibited significant physiological covariation in pre-ejection period reactivity (PEP). Contrary to our hypothesis, dyads in the co-rumination condition did not show more covariation. Close friend dyads did, however, exhibit more covariation as compared to romantic dyads. We also found significant variability in physiological covariation across dyads, with a minority of dyads exhibiting negative covariation of PEP reactivity. The homogeneity of the samples limits the generalizability of the findings and highlights the need for more diverse samples in future work. These findings underline the need for further exploration into the mechanisms that contribute to distinct patterns of physiological synchrony, the conditions in which negative synchrony occurs, and what predicts especially strong positive synchrony. This work extends our understanding of physiological synchrony of the sympathetic nervous system during support conversations and emphasizes the importance of considering heterogeneity in physiological processes., (© 2024 Society for Psychophysiological Research.)

Contemporary discussion of the baroreflex includes the efferent vascular-sympathetic and cardiovagal arms. Since sympathetic postganglionic neurons also innervate the left ventricle (LV), it is often assumed that the LV produces a sympathetically mediated increase in contractility during baroreceptor unloading, but this has not been characterized using a load-independent index of contractility. We aimed to determine 1 ) whether LV contractility increases in response to baroreceptor unloading and 2 ) whether such increases are mediated via the sympathetic or parasympathetic arm of the autonomic nervous system. Ten male Wistar rats were anesthetized (urethane) and instrumented with arterial and LV pressure-volume catheters to measure mean arterial pressure (MAP) and load-independent LV contractility [maximal rate of increase in pressure adjusted to end-diastolic volume (PAdP/d t max )], respectively. Rats were placed in a servo-controlled lower-body negative pressure (LBNP) chamber to reduce MAP by 10% for 60 s to mechanically unload baroreceptors under control conditions. LBNP was repeated in each animal following infusions of cardiac autonomic blockers using esmolol (sympathetic), atropine (parasympathetic), and esmolol + atropine. Under control conditions, PAdP/d t max increased during baroreceptor unloading (26 ± 6 vs. 31 ± 9 mmHg·s -1 ·μL -1 , P = 0.031). During esmolol, there was no increase in LV contractility during baroreceptor unloading (11 ± 2 vs. 12 ± 2, P = 0.125); however, during atropine, there was an increase in LV contractility during baroreceptor unloading (26 ± 6 vs. 31 ± 9, P = 0.019). During combined esmolol and atropine, there was a small increase in contractility versus control (13 ± 3 vs. 15 ± 4, P = 0.046). Our results demonstrate that, in anesthetized rats, LV contractility increases in response to baroreceptor unloading, which is largely sympathetically mediated. NEW & NOTEWORTHY This study empirically demonstrates a sympathetically mediated increase in LV contractility in response to baroreceptor unloading using a load-independent index of cardiac contractility in the anesthetized rat.

The purpose of the present study was to clarify the impact of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. Nine older females (mean ± SD, 70 ± 6 yr) and 11 younger females (20 ± 1 yr) completed the study. A passive leg raising (PLR) test was performed wherein the participants were positioned supine (baseline, 0°), and their lower limbs were passively lifted at 10°, 20°, 30°, and 40° (3 min at each angle). Muscle sympathetic nerve activity (MSNA) was recorded via microneurography of the left radial nerve. The central venous pressure was estimated based on peripheral venous pressure (eCVP), which was monitored using a cannula in the right large antecubital vein. Baseline MSNA was higher in older females than in younger females. MSNA burst frequency (BF) decreased during the PLR test in both older and younger females, but the magnitude of the decrease in MSNA BF was smaller in older females than in younger females (older, -3.5 ± 1.5 vs. younger, -6.3 ± 1.5 bursts/min at 40° from baseline, P = 0.014). The eCVP increased during the PLR in both groups, and there was no difference in the changes in eCVP between the two groups (older, +1.07 ± 0.37 vs. younger, +1.12 ± 0.33 mmHg at 40° from baseline, P = 0.941). These results suggest that inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age in females. NEW & NOTEWORTHY There were no available data concerning the effect of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. The magnitude of the decrease in muscle sympathetic nerve activity during passive leg raising (10°-40°) was smaller in older females than in young females. In females, inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age.

Na V 1.7 plays a crucial role in inducing and conducting action potentials in pain-transducing sensory nociceptor fibres, suggesting that Na V 1.7 blockers could be effective non-opioid analgesics. While SCN9A is expressed in both sensory and autonomic neurons, its functional role in the autonomic system remains less established. Our single neuron rt-PCR analysis revealed that 82% of sympathetic neurons isolated from guinea-pig stellate ganglia expressed Na V 1.7 mRNA, with Na V 1.3 being the only other tetrodotoxin-sensitive channel expressed in approximately 50% of neurons. We investigated the role of Na V 1.7 in conducting action potentials in postganglionic sympathetic nerves and in the sympathetic adrenergic contractions of blood vessels using selective Na V 1.7 inhibitors. Two highly selective Na V 1.7 blockers, GNE8493 and PF 05089771, significantly inhibited postganglionic compound action potentials by approximately 70% (P < 0.01), with residual activity being blocked by the Na V 1.3 inhibitor, ICA 121431. Electrical field stimulation (EFS) induced rapid contractions in guinea-pig isolated aorta, pulmonary arteries, and human isolated pulmonary arteries via stimulation of intrinsic nerves, which were inhibited by prazosin or the Na V 1 blocker tetrodotoxin. Our results demonstrated that blocking Na V 1.7 with GNE8493, PF 05089771, or ST2262 abolished or strongly inhibited sympathetic adrenergic responses in guinea-pigs and human vascular smooth muscle. These findings support the hypothesis that pharmacologically inhibiting Na V 1.7 could potentially reduce sympathetic and parasympathetic function in specific vascular beds and airways. KEY POINTS: 82% of sympathetic neurons isolated from the stellate ganglion predominantly express Na V 1.7 mRNA. Na V 1.7 blockers inhibit action potential conduction in postganglionic sympathetic nerves. Na V 1.7 blockade substantially inhibits sympathetic nerve-mediated adrenergic contractions in human and guinea-pig blood vessels. Pharmacologically blocking Na V 1.7 profoundly affects sympathetic and parasympathetic responses in addition to sensory fibres, prompting exploration into the broader physiological consequences of Na V 1.7 mutations on autonomic nerve activity., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Sinusoidal galvanic vestibular stimulation (sGVS) induces robust modulation of muscle sympathetic nerve activity (MSNA) alongside perceptions of side-to-side movement, sometimes with an accompanying feeling of nausea. We recently showed that transcranial alternating current stimulation (tACS) of the dorsolateral prefrontal cortex (dlPFC) also modulates MSNA, but does not generate any perceptions. Here, we tested the hypothesis that when the two stimuli are given concurrently, the modulation of MSNA would be additive. MSNA was recorded from 11 awake participants via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve at the fibular head. Sinusoidal stimuli (± 2 mA, 0.08 Hz, 100 cycles) were applied in randomised order as follows: (i) tACS of the dlPFC at electroencephalogram (EEG) site F4 and referenced to the nasion; (ii) bilateral sGVS applied to the vestibular apparatuses via the mastoid processes; and (iii) tACS and sGVS together. Previously obtained data from 12 participants supplemented the data for stimulation protocols (i) and (ii). Cross-correlation analysis revealed that each stimulation protocol caused significant modulation of MSNA (modulation index (paired data): 35.2 ± 19.4% for sGVS; 27.8 ± 15.2% for tACS), but there were no additive effects when tACS and sGVS were delivered concurrently (32.1 ± 18.5%). This implies that the vestibulosympathetic reflexes are attenuated with concurrent dlPFC stimulation. These results suggest that the dlPFC is capable of blocking the processing of vestibular inputs through the brainstem and, hence, the generation of vestibulosympathetic reflexes., (© 2024. The Author(s).)

In resistant hypertensive patients acute carotid baroreflex stimulation is associated with a blood pressure (BP) reduction, believed to be mediated by a central sympathoinhbition.The evidence for this sympathomodulatory effect is limited, however. This meta-analysis is the first to examine the sympathomodulatory effects of acute carotid baroreflex stimulation in drug-resistant and uncontrolled hypertension, based on the results of microneurographic studies. The analysis included 3 studies assessing muscle sympathetic nerve activity (MSNA) and examining 41 resistant uncontrolled hypertensives. The evaluation included assessment of the relationships between MSNA and clinic heart rate and BP changes associated with the procedure. Carotid baroreflex stimulation induced an acute reduction in clinic systolic and diastolic BP which achieved statistical significance for the former variable only [systolic BP: -19.98 mmHg (90% CI, -30.52, -9.43), P < 0.002], [diastolic BP: -5.49 mmHg (90% CI, -11.38, 0.39), P = NS]. These BP changes were accompanied by a significant MSNA reduction [-4.28 bursts/min (90% CI, -8.62, 0.06), P < 0.07], and by a significant heart rate decrease [-3.65 beats/min (90% CI, -5.49, -1.81), P < 0.001]. No significant relationship was detected beween the MSNA, systolic and diastolic BP changes induced by the procedure, this being the case also for heart rate. Our data show that the acute BP lowering responses to carotid baroreflex stimulation, although associated with a significant MSNA reduction, are not quantitatively related to the sympathomoderating effects of the procedure. This may suggest that these BP effects depend only in part on central sympathoinhibition, at least in the acute phase following the intervention., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Assessing the development and function of the sympathetic nervous system in diseases on a large scale is challenging. Here, we present a protocol to generate human pluripotent stem cell (hPSC)-derived postganglionic sympathetic neurons (symNs) differentiated via neural crest cells (NCCs), which can be cryopreserved. We describe steps for hPSC replating, NCC replating and cryobanking, and symN differentiation. We then demonstrate the functionality of the hPSC-derived symNs, focusing on electrophysiological activity, calcium flux, and norepinephrine dynamics. For complete details on the use and execution of this protocol, please refer to Wu et al. 1 , 2 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Somatic and sympathetic tones fluctuate together seamlessly across daily behaviors. In this issue of Cell, Zhang et al. describe populations of spinal projecting neurons in the rostral ventromedial medulla (rVMM) that harmonize somatic motor function and sympathetic activation. The coordinated regulation plays a vital role in supporting behaviors associated with various arousal states., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems., Competing Interests: Declaration of interests Z.H. is a co-founder of Rugen and Myrobalan and an advisor of Axonis., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The brain-bone axis has emerged as a captivating field of research, unveiling the intricate bidirectional communication between the central nervous system (CNS) and skeletal metabolism. This comprehensive review delves into the current state of knowledge surrounding the brain-bone axis, exploring the complex mechanisms, key players, and potential clinical implications of this fascinating area of study. The review discusses the neural regulation of bone metabolism, highlighting the roles of the sympathetic nervous system, hypothalamic neuropeptides, and neurotransmitters in modulating bone remodeling. In addition, it examines the influence of bone-derived factors, such as osteocalcin and fibroblast growth factor 23, on brain function and behavior. The therapeutic potential of targeting the brain-bone axis in the context of skeletal and neurological disorders is also explored. By unraveling the complex interplay between the CNS and skeletal metabolism, this review aims to provide a comprehensive resource for researchers, clinicians, and students interested in the brain-bone axis and its implications for human health and disease., (© 2024. The Author(s).)

Skin sympathetic nerve activity (SSNA) is primarily involved in thermoregulation and emotional expression; however, the brain regions involved in the generation of SSNA are not completely understood. In recent years, our laboratory has shown that blood-oxygen-level-dependent signal intensity in the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are positively correlated with bursts of SSNA during emotional arousal and increases in signal intensity in the vmPFC occurring with increases in spontaneous bursts of SSNA even in the resting state. We have recently shown that unilateral transcranial alternating current stimulation (tACS) of the dlPFC causes modulation of SSNA but given that the current was delivered between electrodes over the dlPFC and the nasion, it is possible that the effects were due to current acting on the vmPFC. To test this, we delivered tACS to target the right vmPFC or dlPFC and nasion and recorded SSNA in 11 healthy participants by inserting a tungsten microelectrode into the right common peroneal nerve. The similarity in SSNA modulation between ipsilateral vmPFC and dlPFC suggests that the ipsilateral vmPFC, rather than the dlPFC, may be causing the modulation of SSNA during ipsilateral dlPFC stimulation., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

When we become engrossed in novels, films, games, or even our own wandering thoughts, we can feel present in a reality distinct from the real world. Although this subjective sense of presence is, presumably, a ubiquitous aspect of conscious experience, the mechanisms that produce it are unknown. Correlational studies conducted in virtual reality have shown that we feel more present when we are afraid, motivating claims that physiological changes contribute to presence; however, such causal claims remain to be evaluated. Here, we report two experiments that test the causal role of subjective and physiological components of fear (i.e., activation of the sympathetic nervous system) in generating presence. In Study 1, we validated a virtual reality simulation capable of inducing fear. Participants rated their emotions while they crossed a wooden plank that appeared to be suspended above a city street; at the same time, we recorded heart rate and skin conductance levels. Height exposure increased ratings of fear, presence, and both measures of sympathetic activation. Although presence and fear ratings were correlated during height exposure, presence and sympathetic activation were unrelated. In Study 2, we manipulated whether the plank appeared at height or at ground level. We also captured participants' movements, which revealed that alongside increases in subjective fear, presence, and sympathetic activation, participants also moved more slowly at height relative to controls. Using a mediational approach, we found that the relationship between height exposure and presence on the plank was fully mediated by self-reported fear, and not by sympathetic activation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Heart rate and vascular tension baroreflex exhibit resonance characteristics at approximately 0.1 and 0.03 Hz. In this study, we aimed to induce postural resonance (PR) through rhythmic postural adjustments. To assess the viability of this technique, we investigated the acute impacts of postural resonance on blood pressure, sympathetic nerve activity, and mood. Fifteen healthy study participants, consisting of 8 males and 7 females, were selected for this self-controlled study. Skin sympathetic nerve activity was continuously monitored during both the intervention and stress test on the experimental day. After PR intervention, the diastolic blood pressure and mean arterial pressure in the PR group exhibited significant reductions compared to the CON group (P = 0.032, CON = 71.67 ± 2.348, PR = 64.08 ± 2.35; P = 0.041, CON = 75.00 ± 2.17, PR = 81.67 ± 2.17). After PR intervention both left brachial ankle pulse wave velocity and right brachial ankle pulse wave velocity exhibited a significant reduction compared to pre-intervention levels (from 1115.86 ± 150.08 to 1048.43 ± 127.40 cm/s, p < 0.001; 1103.86 ± 144.35 to 1060.43 ± 121.35 cm/s, p = 0.018). PR intervention also led to a significant decrease in burst frequency and duration (P = 0.049; CON = 8.96 ± 1.17, PR = 5.51 ± 1.17) and a noteworthy decrease in burst amplitude and burst threshold during the cold-pressor test (P = 0.002; P = 0.002). Additionally, VAS scores exhibited a substantial increase following PR (P = 0.035, CON = 28.4 ± 4.49, PR = 42.17 ± 4.10). PR can induce resonance effects within the cardiovascular system, resulting in the effective reduction of blood pressure, skin sympathetic nerve activity and pulse wave velocity, and decreased burst amplitude and burst threshold of the sympathetic nerve during the cold-pressor test., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Reno-renal reflexes are disturbed in cardiovascular and hypertensive conditions when elevated levels of pro-inflammatory mediators/cytokines are present within the kidney. We hypothesised that exogenously administered inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin (IL)-1β modulate the renal sympatho-excitatory response to chemical stimulation of renal pelvic sensory nerves., Methods: In anaesthetised rats, intrarenal pelvic infusions of vehicle [0.9% sodium chloride (NaCl)], TNF-α (500 and 1000 ng/kg) and IL-1β (1000 ng/kg) were maintained for 30 min before chemical activation of renal pelvic sensory receptors was performed using randomized intrarenal pelvic infusions of hypertonic NaCl, potassium chloride (KCl), bradykinin, adenosine and capsaicin., Results: The increase in renal sympathetic nerve activity (RSNA) in response to intrarenal pelvic hypertonic NaCl was enhanced during intrapelvic TNF-α (1000 ng/kg) and IL-1β infusions by almost 800% above vehicle with minimal changes in mean arterial pressure (MAP) and heart rate (HR). Similarly, the RSNA response to intrarenal pelvic adenosine in the presence of TNF-α (500 ng/kg), but not IL-1β, was almost 200% above vehicle but neither MAP nor HR were changed. There was a blunted sympatho-excitatory response to intrapelvic bradykinin in the presence of TNF-α (1000 ng/kg), but not IL-1β, by almost 80% below vehicle, again without effect on either MAP or HR., Conclusion: The renal sympatho-excitatory response to renal pelvic chemoreceptor stimulation is modulated by exogenous TNF-α and IL-1β. This suggests that inflammatory mediators within the kidney can play a significant role in modulating the renal afferent nerve-mediated sympatho-excitatory response., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Trauma-induced hemorrhage is a leading cause of death in prehospital settings. Experimental data demonstrate that females have a lower tolerance to simulated hemorrhage (i.e., central hypovolemia). However, the mechanism(s) underpinning these responses are unknown. Therefore, this study aimed to compare autonomic cardiovascular responses during central hypovolemia between the sexes. We hypothesized that females would have a lower tolerance and smaller increase in muscle sympathetic nerve activity (MSNA) to simulated hemorrhage., Methods: Data from 17 females and 19 males, aged 19-45 yr, were retrospectively analyzed. Participants completed a progressive lower-body negative pressure (LBNP) protocol to presyncope to simulate hemorrhagic tolerance with continuous measures of MSNA and beat-to-beat hemodynamic variables. We compared responses at baseline, at two LBNP stages (-40 and -50 mmHg), and at immediately before presyncope. In addition, we compared responses at relative percentages (33%, 66%, and 100%) of hemorrhagic tolerance, calculated via the cumulative stress index (i.e., the sum of the product of time and pressure at each LBNP stage)., Results: Females had lower tolerance to central hypovolemia (female: 561 ± 309 vs male: 894 ± 304 min·mmHg [time·LBNP]; P = 0.003). At LBNP -40 and -50 mmHg, females had lower diastolic blood pressures (main effect of sex: P = 0.010). For the relative LBNP analysis, females exhibited lower MSNA burst frequency (main effect of sex: P = 0.016) accompanied by a lower total vascular conductance (sex: P = 0.028; main effect of sex)., Conclusions: Females have a lower tolerance to central hypovolemia, which was accompanied by lower diastolic blood pressure at -40 and -50 mmHg LBNP. Notably, females had attenuated MSNA responses when assessed as relative LBNP tolerance time., (Copyright © 2024 by the American College of Sports Medicine.)

Skin blood flow is commonly determined by laser Doppler flowmetry (LDF). It has been suggested that pathophysiological conditions can be assessed by analysis of specific frequency domains of the LDF signals. We tested whether physiological stimuli that activate myogenic and neurogenic mechanisms would affect relevant portions of the laser Doppler spectrum. LDF sensors were placed on the right forearm of 14 healthy volunteers for myogenic (six females) and 13 for neurogenic challenge (five females). Myogenic responses were tested by positioning the arm ∼50° above/below heart level. Neurogenic responses were tested by immersing the left hand into an ice slurry with and without topical application of local anaesthetic. Short-time Fourier analyses were computed over the range of 0.06 to 0.15 Hz for myogenic and 0.02 to 0.06 Hz for neurogenic. No significant differences in spectral density were observed (P = 0.40) in the myogenic range with arm above (7 ± 54 × 10 -4  dB) and below heart (7 ± 14 × 10 -4  dB). Neurogenic spectral density showed no significant increase from baseline to cold pressor test (0.0017 ± 0.0013 and 0.0038 ± 0.0039 dB; P = 0.087, effect size 0.47). After application of anaesthetic, neurogenic spectral density was unchanged between the baseline and cold pressor test (0.0014 ± 0.0025 and 0.0006 ± 0.0005 dB; P = 0.173). These results suggest that changes in the myogenic and neurogenic spectral density of LDF signals did not fully reflect the skin vascular function activated by pressure manipulation and sympathetic stimulation. Therefore, LDF myogenic and neurogenic spectral density data should be interpreted with caution., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Although cardiac autonomic markers (CAMs) are commonly used to assess cardiac reinnervation in heart-transplant patients, their relationship to the degree of sympathetic and vagal cardiac reinnervation is not well understood yet. To study this relationship, we applied a mathematical model of the cardiovascular system and its autonomic control., Methods: By simulating varying levels of sympathetic and vagal efferent sinoatrial reinnervation, we analyzed the induced changes in CAMs including resting heart rate (HR), bradycardic and tachycardic HR response to Valsalva maneuver, root mean square of successive differences between normal heartbeats (RMSSD), low-frequency (LF), high-frequency (HF), and total spectral power (TSP)., Results: For assessment of vagal cardiac reinnervation levels >20%, resting HR (ρ = 0.99, p < 0.05), RMSSD (ρ = 0.97, p < 0.05), and TSP (ρ = 0.96, p < 0.05) may be equally suitable as HF-power (ρ = 0.97, p < 0.05). To assess sympathetic reinnervation, LF/HF ratio (ρ = 0.87, p < 0.05) and tachycardic response to Valsalva maneuver (ρ = 0.9, p < 0.05) may be more suitable than LF-power (ρ = 0.77, p < 0.05)., Conclusions: Our model reports mechanistic relationships between CAMs and levels of efferent autonomic sinoatrial reinnervation. The results indicate differences in the suitability of these markers to assess vagal and sympathetic reinnervation. Although our analysis is purely conceptual, the developed model can help to gain important insights into the genesis of CAMs and their relationship to efferent sinoatrial reinnervation and, thus, provide indications for clinical study evaluation., Competing Interests: Disclosure statement The authors declare that they do not have any financial relationships that may cause a conflict of interest., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Microneurographic recordings of muscle sympathetic nerve activity (MSNA) reflect postganglionic sympathetic axonal activity directed toward the skeletal muscle vasculature. Recordings are typically evaluated for spontaneous bursts of MSNA; however, the filtering and integration of raw neurograms to obtain multiunit bursts conceals the underlying c-fiber discharge behavior. The continuous wavelet transform with matched mother wavelet has permitted the assessment of action potential discharge patterns, but this approach uses a mother wavelet optimized for an amplifier that is no longer commercially available (University of Iowa Bioengineering Nerve Traffic Analysis System; Iowa NTA). The aim of this project was to determine the morphology and action potential detection performance of mother wavelets created from the commercially available NeuroAmp (ADinstruments), from distinct laboratories, compared with a mother wavelet generated from the Iowa NTA. Four optimized mother wavelets were generated in a two-phase iterative process from independent datasets, collected by separate laboratories (one Iowa NTA, three NeuroAmp). Action potential extraction performance of each mother wavelet was compared for each of the NeuroAmp-based datasets. The total number of detected action potentials was not significantly different across wavelets. However, the predictive value of action potential detection was reduced when the Iowa NTA wavelet was used to detect action potentials in NeuroAmp data, but not different across NeuroAmp wavelets. To standardize approaches, we recommend a NeuroAmp-optimized mother wavelet be used for the evaluation of sympathetic action potential discharge behavior when microneurographic data are collected with this system. NEW & NOTEWORTHY The morphology of custom mother wavelets produced across laboratories using the NeuroAmp was highly similar, but distinct from the University of Iowa Bioengineering Nerve Traffic Analysis System. Although the number of action potentials detected was similar between collection systems and mother wavelets, the predictive value differed. Our data suggest action potential analysis using the continuous wavelet transform requires a mother wavelet optimized for the collection system.

The aim of our study is to investigate the sympathetic output and baroreflex via renal sympathetic nerve activity (RSNA) recording in a model of severe hypertension which exhibits arterial, cardiac, and renal damages, the spontaneously hypertensive rat (SHR) under lowered NO bioavailability. SHR are treated from 18 to 20 weeks of age with a low dose of L-NAME, a NO synthase inhibitor, in drinking water (SHRLN) and compared to SHR and normotensive Wistar Kyoto (WKY) rats. After the two-week treatment, rats are anesthetized for RSNA, mean blood pressure (MBP), and heart rate (HR) recording. MBP is higher in SHR than in WKY and higher in SHRLN than in SHR. Compared to WKY, SHR displays an alteration in the baroreflex with a displacement of the sympathoinhibition curve to highest pressures; this displacement is greater in SHRLN rats. The bradycardic response is reduced in SHRLN compared to both SHR and WKY. In hypertensive rats, SHR and SHRLN, basal RSNA is modified, the maximal amplitude of burst is reduced, but minimal values are increased, indicating an increased basal RSNA with reduced bursting activity. The temporal correlation between RSNA and HR is preserved in SHR but altered in 10 SHRLN out of 10. The RSNA inhibition triggered by the Bezold–Jarisch reflex activation is not modified in hypertensive rats, SHR or SHRLN, in contrast to that triggered by the baroreflex. Histological analysis of the carotid bifurcation does not reveal any abnormality in SHRLN at the level of the carotid sinus. In conclusion, data indicate that the sympathetic outflow is altered in SHRLN with a strong reduction of the baroreflex sympathoinhibition and suggest that its central pathway is not involved. These additional results on SHRLN also confirm the usefulness of this model of severe hypertension with multiple target organ damages. [ABSTRACT FROM AUTHOR]

Purpose: In normotensive patients with obstructive sleep apnea (OSA), the muscle sympathetic nerve activity (MSNA) response to exercise is increased while metaboreflex control of MSNA is decreased. We tested the hypotheses that acute intermittent hypercapnic hypoxia (IHH) in males free from OSA and associated comorbidities would augment the MSNA response to exercise but attenuate the change in MSNA during metaboreflex activation. Methods: Thirteen healthy males (age = 24 ± 4 yr) were exposed to 40 min of IHH. Before and after IHH, the pressor response to exercise was studied during 2 min of isometric handgrip exercise (at 30%maximal voluntary contraction), whereas themetaboreflex was studied during 4min of postexercise circulatory occlusion (PECO).Mean arterial pressure (MAP), heart rate (HR), and fibularMSNA were recorded continuously. MSNA was quantified as burst frequency (BF) and total activity (TA).Mixed effects linear models were used to compare the exercise pressor andmetaboreflex before and after IHH. Results: As expected, IHH led to significant increases in MSNA BF, TA, and MAP at baseline and throughout exercise and PECO. However, during handgrip exercise, the change from baseline inMAP,HR,MSNABF, and TA was similar before and after IHH(All P > 0.31).During PECO, the change from baseline inMSNA BF and TA was similar after IHH, whereas the change from baseline inMAP (Δ14mmHg, 95% CI = 7-19, vs Δ16mmHg, 95% CI = 10-21; P < 0.01) wasmodestly increased. Conclusion: After acute IHH,MSNAresponse to handgrip exercise and metaboreflex activationwere preserved in healthy young males despite overall increases in resting MSNA and MAP. Chronic IHH and comorbidities often associated with OSA may be required to modulate the exercise pressor reflex and metaboreflex. [ABSTRACT FROM AUTHOR]

Background. Changes in the composition and diversity of gut microbiota, which can be altered by autonomic nerve activity, contribute to the development of heart failure (HF). Renal denervation (RDN) can improve cardiac function by reducing sympathetic nerve activity. However, whether the beneficial role of RDN on HF is related to gut microbiota is unknown. Methods. Thirty rats were assigned to a control, HF (with induced transverse aortic constriction (TAC)), RDN (with RDN induced 10 weeks after TAC), Nog (HF rats with Nogo-P4-administered 8 weeks after RDN), and NEP (HF rats with NEP1-40-administered 8 weeks after RDN) group. Then, 16SrRNA amplicon sequencing and analyses of fecal samples were performed. Results. Beta diversity analyses revealed that compared to the HF group, the RDN, Nog, and NEP groups clustered closer to the control group. The Firmicutes/Bacteroidetes ratio was reduced in the HF group (1.59) compared with the control group (3.21) and was significantly decreased compared to the Nog (7.19), RDN (6.20), and NEP (4.42) groups. At the genus level, the HF group showed decreased abundances of Lactobacillus and Alistipes and increased abundances of Bacteroides and Clostridium compared with the control group. The abundances of Lactobacillus and Alistipes were increased, and those of Bacteroides and Clostridium were decreased in the RDN, Nog, and NEP groups compared to the HF group. However, no differences were observed between the three groups that underwent RDN. The microbial function showed the same tendency. Conclusions. RDN reversed the abnormal changes in the gut microbiome in HF rats. Inhibition of reinnervation after RDN did not affect intestinal bacteria. [ABSTRACT FROM AUTHOR]

Background: Neurolytic splanchnic nerve block is used to manage pancreatic cancer pain. However, its impact on survival and quality of life remains controversial. The authors' primary hypothesis was that pain relief would be better with a nerve block. Secondarily, they hypothesized that analgesic use, survival, and quality of life might be affected.Methods: This randomized, double-blind, parallel-armed trial was conducted in five Chinese centers. Eligible patients suffering from moderate to severe pain conditions were randomly assigned to receive splanchnic nerve block with either absolute alcohol (neurolysis) or normal saline (control). The primary outcome was pain relief measured on a visual analogue scale. Opioid consumption, survival, quality of life, and adverse effects were also documented. Analgesics were managed using a protocol common to all centers. Patients were followed up for 8 months or until death.Results: Ninety-six patients (48 for each group) were included in the analysis. Pain relief with neurolysis was greater for the first 3 months (largest at the first month; mean difference, 0.7 [95% CI, 0.3 to 1.0]; adjusted P < 0.001) compared with placebo injection. Opioid consumption with neurolysis was lower for the first 5 months (largest at the first month; mean difference, 95.8 [95% CI, 67.4 to 124.1]; adjusted P < 0.001) compared with placebo injection. There was a significant difference in survival (hazard ratio, 1.56 [95% CI, 1.03 to 2.35]; P = 0.036) between groups. A significant reduction in survival in neurolysis was found for stage IV patients (hazard ratio, 1.94 [95% CI, 1.29 to 2.93]; P = 0.001), but not for stage III patients (hazard ratio, 1.08 [95% CI, 0.59 to 1.97]; P = 0.809). No differences in quality of life were observed.Conclusions: Neurolytic splanchnic nerve block appears to be an effective option for controlling pain and reducing opioid requirements in patients with unresectable pancreatic cancer.Editor’s Perspective: [ABSTRACT FROM AUTHOR]

Background: Transcutaneous electrical acupoint stimulation (TEAS) improves autonomic balance and reduces oxidative stress in subjects with chronic diseases, that decreases the risk of low-grade chronic inflammatory diseases, including cardiovascular diseases. However, these beneficial effects have never been demonstrated in healthy subjects. Objectives: To evaluate the acute effects of TEAS on autonomic balance and oxidative stress of healthy subjects. Methods: A randomized clinical trial was conducted with male healthy subjects (18-30 years old), randomly allocated to control (no intervention; n = 14), placebo (placebo intervention; n = 14) and TEAS group (at PC5 and PC6 acupoints; n = 13). The protocol consisted of accommodation (20 min), intervention (40 min), and recovery (30 min) periods. The acute effects of TEAS on hemodynamics were studied through measurements of heart rate, blood pressure and double product; on the autonomic nervous system by assessing heart rate variability; and on oxidative stress by quantifying reactive oxygen species in saliva samples, collected at the end of each period. Results: TEAS increased heart rate and double-product compared to control and placebo groups (p < 0.01). Moreover, TEAS increased sympathetic and reduced parasympathetic tonus, increasing the sympathovagal balance compared to the control and placebo groups. However, TEAS exerted no effect on oxidative stress in saliva samples. Conclusion: In healthy subjects, TEAS at PC5 and PC6 acupoints acutely improved autonomic balance, increasing sympathetic and reducing parasympathetic tonus, reflecting little improvement on hemodynamic responses. Whether it could be used as a cardioprotective strategy remains uncertain since it exerted no effect on oxidative stress. [ABSTRACT FROM AUTHOR]

The article presents the Heart failure-specific inverse relationship between the muscle sympathetic response to dynamic leg exercise and VO2peak. Topics discussed include Exercise intolerance, a symptom afflicting the majority of patients with heart failure with reduced ejection fraction (HFrEF), has been attributed classically to a range of disturbances; and the purpose of the present work was to test the hypothesis that the percent predicted VO2peak of patients with HFrEF relates.

The article presents the Heart failure-specific inverse relationship between the muscle sympathetic response to dynamic leg exercise and VO2peak. Topics discussed include Exercise intolerance, a symptom afflicting the majority of patients with heart failure with reduced ejection fraction (HFrEF), has been attributed classically to a range of disturbances; and the purpose of the present work was to test the hypothesis that the percent predicted VO2peak of patients with HFrEF relates.

The counterregulatory response to hypoglycemia is an essential survival function. It is controlled by an integrated network of glucose-responsive neurons, which trigger endogenous glucose production to restore normoglycemia. The complexity of this glucoregulatory network is, however, only partly characterized. In a genetic screen of a panel of recombinant inbred mice we previously identified Fgf15, expressed in neurons of the dorsomedial hypothalamus (DMH), as a negative regulator of glucagon secretion. Here, we report on the generation of Fgf15CretdTomato mice and their use to further characterize these neurons. We show that they were glutamatergic and comprised glucose-inhibited and glucose-excited neurons. When activated by chemogenetics, Fgf15 neurons prevented the increase in vagal nerve firing and the secretion of glucagon normally triggered by insulin-induced hypoglycemia. On the other hand, they increased the activity of the sympathetic nerve in the basal state and prevented its silencing by glucose overload. Higher sympathetic tone increased hepatic Creb1 phosphorylation, Pck1 mRNA expression, and hepatic glucose production leading to glucose intolerance. Thus, Fgf15 neurons of the DMH participate in the counterregulatory response to hypoglycemia by a direct adrenergic stimulation of hepatic glucose production while suppressing vagally induced glucagon secretion. This study provides new insights into the complex neuronal network that prevents the development of hypoglycemia. [ABSTRACT FROM AUTHOR]