Vagal predominance correlates with mood state changes of winter-over expeditioners during prolonged Antarctic residence.

OBJECTIVE: Winter-over expeditioners in Antarctica are challenged by various environmental and psycho-social stress factors, which may induce psychophysiological changes. The autonomic nervous system (ANS) plays a crucial role in the adaptation process under stress. However, the relationship between ANS activity and the mood states of expeditioners remains largely unexplored. This study aims to uncover the pattern of ANS adjustment under extreme Antarctic environments and provide new insights into the correlations between ANS activity and mood state changes, which may provide scientific data for medical interventions. METHODS: Fourteen expeditioners at Zhongshan Station participated in this study. The study was conducted during four representative periods: pre-Antarctica, Antarctica-1 (pre-winter), Antarctica-2 (winter), and Antarctica-3 (summer). The heart rate variability (HRV) of the expeditioners was continuously measured for 24 hours to evaluate ANS activity. Plasma levels of catecholamines were tested by ELISA. Mood states were assessed by the Profile of Mood States (POMS) scale. RESULTS: HRV analysis showed a disturbance of ANS during winter and summer periods. For frequency domain parameters, very low frequency (VLF), low frequency (LF), high frequency (HF), and total power (TP) significantly increased during the second half of the mission. Especially, LF/HF ratio decreased during summer, indicating the predominance of vagal tone. Results of the time domain analysis showed increased heart rate variability during the austral winter and summer. Plasma epinephrine (E) significantly increased during residence in Antarctica. Compared with pre-Antarctica, the vigor, depression, and anger scores of the expeditioners decreased significantly during the austral summer. Notably, the depression score showed a moderate positive correlation with LF/HF, while weak negative correlations with other HRV indicators, including TP, VLF, and LF. Anger score showed a moderate positive correlation with LF/HF and weak negative correlations with the average normal-to-normal (NN) interval, and the root mean square of differences between adjacent RR intervals (RMSSD). Plasma E level weakly correlated with the average NN interval. CONCLUSION: Prolonged residence in Antarctica increased the ANS activities and shifted the cardiac autonomic modulation towards vagal predominance. The alteration of HRV correlated with mood states and plasma epinephrine levels.

What is the Vagal-Adrenal Axis?

Some recent publications have used the term "vagal-adrenal axis" to account for mechanisms involved in the regulation of inflammation by electroacupuncture. This concept proposes that efferent parasympathetic nerve fibers in the vagus directly innervate the adrenal glands to influence catecholamine secretion. Here, we discuss evidence for anatomical and functional links between the vagi and adrenal glands that may be relevant in the context of inflammation and its neural control by factors, including acupuncture. First, we find that evidence for any direct vagal parasympathetic efferent innervation of the adrenal glands is weak and likely artifactual. Second, we find good evidence that vagal afferent fibers directly innervate the adrenal gland, although their function is uncertain. Third, we highlight a wealth of evidence for indirect pathways, whereby vagal afferent signals act via the central nervous system to modify adrenal-dependent anti-inflammatory responses. Vagal afferents, not efferents, are thus the likely key to these phenomena.

A closed-loop negative feedback model for the pancreas: A new paradigm and pathway to a cure.

BACKGROUND AND AIMS: To develop a model that describes how the pancreas functions, how the rate of synthesis of digestive enzymes is regulated, and finally what puts the pancreas to rest between meals. METHODS: We applied the principals of control theory to previously published canine data to develop a model for how the canine pancreas functions. Using this model, we then describe the steps needed to apply this model to the human pancreas. RESULTS: This new closed-loop negative feedback model describes what regulates digestive enzyme synthesis. This model is based on basolateral exocytosis of butyrylcholinesterase (BCHE) into the interstitial space. It is this level of BCHE * BCHE activity that controls the rate of canine pancreas digestive enzyme synthesis, and in the absence of stimulation from the vagus nerve, puts the pancreas to rest between meals. CONCLUSIONS: Finding secretagogue-specific inhibitory enzymes in the human pancreas that are analogous to BCHE in the canine, and blocking its associated receptors, may lead to a cure for human pancreatitis.

Effects of Acute Guarana (Paullinia cupana) Ingestion on Mental Performance and Vagal Modulation Compared to a Low Dose of Caffeine.

Guarana (GUA), a Brazilian seed extract, contains caffeine and other bioactive compounds that may have psychoactive effects. To assess the acute effects of GUA compared to a low dose of caffeine (CAF) on cognitive and mood parameters, twenty participants completed a double-blind, crossover experiment where they ingested capsules containing the following: (1) 100 mg CAF, (2) 500 mg GUA containing 130 mg caffeine, or (3) placebo (PLA). Cognitive tests (Simon and 2N-Back Task) were performed at the baseline (pre-ingestion) and 60 min after ingestion. The response time for the cognitive tests and heart rate variability were unaffected (p > 0.05) by treatment, although 2N-Back was overall faster (p = 0.001) across time. The accuracy in the 2N-Back Task showed a significant interaction effect (p = 0.029) due to higher post-ingestion versus pre-ingestion levels (p = 0.033), but only with the PLA. The supplements also had no effect on cognitive measures following physical fatigue (n = 11). There was an interaction effect on perceived mental energy, where the pre-ingestion of GUA had lower mental pep ratings compared to post-ingestion (p = 0.006) and post-exercise (p = 0.018) levels. Neither the acute ingestion of GUA nor low dose of CAF influenced cognitive performance or provided consistent benefit on mood or mental workload through vagal modulation. Additional investigations are beneficial to determining the lowest effective dose for CAF or GUA to influence mood and/or cognitive performance.

Electrophysiological Properties and Morphology of Cardiac and Pulmonary Motoneurons within the Dorsal Motor Nucleus of the Vagus of Rats.

The dorsal motor nucleus of the vagus (DMV) contains parasympathetic motoneurons that project to the heart and lungs. These motoneurons control ventricular excitability/contractility and airways secretions/blood flow, respectively. However, their electrophysiological properties, morphology and synaptic input activity remain unknown. One important ionic current described in DMV motoneurons controlling their electrophysiological behaviour is the A-type mediated by voltage-dependent K+ (Kv) channels. Thus, we compared the electrophysiological properties, synaptic activity, morphology, A-type current density, and single cell expression of Kv subunits, that contribute to macroscopic A-type currents, between DMV motoneurons projecting to either the heart or lungs of adult male rats. Using retrograde labelling, we visualized distinct DMV motoneurons projecting to the heart or lungs in acutely prepared medullary slices. Subsequently, whole cell recordings, morphological reconstruction and single motoneuron qRT-PCR studies were performed. DMV pulmonary motoneurons were more depolarized, electrically excitable, presented higher membrane resistance, broader action potentials and received greater excitatory synaptic inputs compared to cardiac DMV motoneurons. These differences were in part due to highly branched dendritic complexity and lower magnitude of A-type K+ currents. By evaluating expression of channels that mediate A-type currents from single motoneurons, we demonstrated a lower level of Kv4.2 in pulmonary versus cardiac motoneurons, whereas Kv4.3 and Kv1.4 levels were similar. Thus, with the distinct electrical, morphological, and molecular properties of DMV cardiac and pulmonary motoneurons, we surmise that these cells offer a new vista of opportunities for genetic manipulation providing improvement of parasympathetic function in cardiorespiratory diseases such heart failure and asthma.

The effectiveness of an osteopathic manual technique compared with a breathing exercise on vagal tone as indicated by heart rate variability, a crossover study.

INTRODUCTION: Parasympathetic nervous system (PSNS) function can be inferred by heart rate variability (HRV) providing indications about an individual's health. Manual therapy may influence PSNS function, however the research outcomes in this regard are equivocal. This study explored the PSNS effect of a measured breathing technique with suboccipital balanced ligamentous tension, an osteopathic manipulative therapy technique. METHODS: Healthy adult participants in this crossover study (n = 18) were randomly allocated into two groups with differing order of interventions. A 1:1 breathing rate of 6 breaths per minute maintained for 5 min was compared to the osteopathic intervention. HRV was measured for 5 min before and after each intervention and analysed using the root mean square of successive differences (RMSSD) between normal heartbeats and high frequency normalised units (HFnu). RESULTS: The RMSSD data demonstrated no significant difference between groups or within groups (p > 0.05) over time. HFnu results showed a significant between-group difference over the four time points (p = 0.004) with a medium effect size (ηp2 = 0.240), and no significant within-group difference (p > 0.05). DISCUSSION: The osteopathic intervention raised HRV to a small extent, however measured breathing lowered HRV. In the group that received the osteopathic technique first, HFnu values continued to rise post-osteopathic treatment possibly indicating an increasing parasympathetic effect over time. Recommendations for future studies include changing the breathing ratio to ensure parasympathetic response, take into account potential delayed effects of interventions, consider outcome measures less variable than HRV, and longer follow up times. CONCLUSION: This study suggests parasympathetic stimulation may occur with the application of suboccipital balanced ligamentous tension and sympathetic stimulation from measured breathing.

A body-brain circuit that regulates body inflammatory responses.

The body-brain axis is emerging as a principal conductor of organismal physiology. It senses and controls organ function1,2, metabolism3 and nutritional state4-6. Here we show that a peripheral immune insult strongly activates the body-brain axis to regulate immune responses. We demonstrate that pro-inflammatory and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of an emerging inflammatory response. In turn, the brain tightly modulates the course of the peripheral immune response. Genetic silencing of this body-brain circuit produced unregulated and out-of-control inflammatory responses. By contrast, activating, rather than silencing, this circuit affords neural control of immune responses. We used single-cell RNA sequencing, combined with functional imaging, to identify the circuit components of this neuroimmune axis, and showed that its selective manipulation can effectively suppress the pro-inflammatory response while enhancing an anti-inflammatory state. The brain-evoked transformation of the course of an immune response offers new possibilities in the modulation of a wide range of immune disorders, from autoimmune diseases to cytokine storm and shock.

Moderate cardiac vagal tone is associated with more cooperation in children.

Childhood is a crucial period for prosocial development, including cooperative behaviors. Recent studies have shown a quadratic relation (inverted U-shape curve) between cardiac vagal tone (CVT) and various prosocial emotions and behaviors in children, but data are lacking on cooperative behaviors. In a sample of 111 school-aged children (M = 7.77; SD = 1.24, range: 6-11), we tested the association between the root mean square of successive differences in interbeat intervals (RMSSD) at rest, and cooperative behavior in a task designed to be comparable to a stag hunt game. We found evidence for an association between RMSSD and cooperation that follows an inverted U-shape. In addition, older children were more likely to cooperate than younger children. Lastly, we found an interaction between RMSSD and age such that the association between RMSSD and cooperation behavior was present for younger but not older children. In addition, we proposed an extension of the Johnson-Neyman test to assess the significant region of interaction between age and the linear and quadratic RMSSD. These results add to a growing literature suggesting that moderate RMSSD is associated with greater prosocial behavior and provide novel evidence that this association extends to children's cooperation.

Identifying vagal bronchopulmonary afferents mediating cough response to inhaled sulfur dioxide in mice.

Sulfur dioxide (SO2), a common environmental and industrial air pollutant, possesses a potent effect in eliciting cough reflex, but the primary type of airway sensory receptors involved in its tussive action has not been clearly identified. This study was carried out to determine the relative roles of three major types of vagal bronchopulmonary afferents [slowly adapting receptors (SARs), rapidly adapting receptors (RARs), and C-fibers] in regulating the cough response to inhaled SO2. Our results showed that inhalation of SO2 (300 or 600 ppm for 8 min) evoked an abrupt and intense stimulatory effect on bronchopulmonary C-fibers, which continued for the entire duration of inhalation challenge and returned toward the baseline in 1-2 min after resuming room air-breathing in anesthetized and mechanically ventilated mice. In stark contrast, the same SO2 inhalation challenge generated a distinct and consistent inhibitory effect on both SARs and phasic RARs; their phasic discharges synchronized with respiratory cycles during the baseline (breathing room air) began to decline progressively within 1-3 min after the onset of SO2 inhalation, ceased completely before termination of the 8-min inhalation challenge, and then slowly returned toward the baseline after >40 min. In a parallel study in awake mice, inhalation of SO2 at the same concentration and duration as that in the nerve recording experiments evoked cough responses in a pattern and time course similar to that observed in the C-fiber responses. Based on these results, we concluded that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough response to inhaled SO2.NEW & NOTEWORTHY This study demonstrated that inhalation of a high concentration of sulfur dioxide, an irritant gas and common air pollutant, completely and reversibly inhibited the neural activities of both slowly adapting receptor and rapidly adapting receptor, two major types of mechanoreceptors in the lungs with their activities conducted by myelinated fibers. Furthermore, the results of this study suggested that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough reflex responses to inhaled sulfur dioxide.

Humanity's evolved nest and its relation to cardiac vagal regulation in the first years of life.

BACKGROUND: The Evolved Developmental Niche (EDN) is a millions-year-old developmental system that matches the maturational schedule of the offspring, optimizing health. Every animal has a developmental niche. AIMS: Humanity has fallen away from providing its EDN. Does it matter? STUDY DESIGN: Several components of humanity's EDN were reviewed (breastfeeding, positive touch, allomothers, responsive care, free play) in relation to cardiac vagal nerve regulation, a signal of healthy development. Focal subjects were young children. OUTCOME MEASURES: A review of research on the selected EDN components in relation to vagal nerve function was performed. Data were available for all but the allomother component, which is typically not measured by western researchers, although allomothers provide EDN components alongside parents. RESULTS: Apart from the lack of research on allomother effects, all these EDN components have been shown to influence cardiac vagal regulation in young children. CONCLUSIONS: Converging evidence suggests that providing the EDN in early life may not only support aspects of a child's primal health system, but bolster capacities for social health and wellness, the cornerstone of a positive life trajectory.

Vagus nerve stimulation in bursts can efficiently modulate gastric contractions and contraction frequency at varying gastric pressures.

OBJECTIVE: There has been recent clinical interest in the use of vagus nerve stimulation (VNS) for treating gastrointestinal disorders as an alternative to drugs or gastric electrical stimulation. However, effectiveness of burst stimulation has not been demonstrated. We investigated the ability of bursting and continuous VNS to influence gastric and pyloric activity under a range of stimulation parameters and gastric pressures. The goals of this study were to determine which parameters could optimally excite or inhibit gastric activity. MATERIALS AND METHODS: Data were collected from 21 Sprague-Dawley rats. Under urethane anesthesia, a rubber balloon was implanted into the stomach, connected to a pressure transducer and a saline infusion pump. A pressure catheter was inserted at the pyloric sphincter and a bipolar nerve cuff was implanted onto the left cervical vagus nerve. The balloon was filled to 15 cmH2O. Stimulation trials were conducted in a consistent order; the protocol was then repeated at 25 and 35 cmH2O. The nerve was then transected and stimulation repeated to investigate directionality of effects. RESULTS: Bursting stimulation at the bradycardia threshold caused significant increases in gastric contraction amplitude with entrainment to the bursting frequency. Some continuous stimulation trials could also cause increased contractions but without frequency changes. Few significant changes were observed at the pylorus, except for frequency entrainment. These effects could not be uniquely attributed to afferent or efferent activity. SIGNIFICANCE: Our findings further elucidate the effects of different VNS parameters on the stomach and pylorus and provide a basis for future studies of bursting stimulation for gastric neuromodulation.

The Development of a New Vagus Nerve Simulation Electroceutical to Improve the Signal Attenuation in a Living Implant Environment.

An electroceutical is a medical device that uses electrical signals to control biological functions. It can be inserted into the human body as an implant and has several crucial advantages over conventional medicines for certain diseases. This research develops a new vagus nerve simulation (VNS) electroceutical through an innovative approach to overcome the communication limitations of existing devices. A phased array antenna with a better communication performance was developed and applied to the electroceutical prototype. In order to effectively respond to changes in communication signals, we developed the steering algorithm and firmware, and designed the smart communication protocol that operates at a low power that is safe for the patients. This protocol is intended to improve a communication sensitivity related to the transmission and reception distance. Based on this technical approach, the heightened effectiveness and safety of the prototype have been ascertained, with the actual clinical tests using live animals. We confirmed the signal attenuation performance to be excellent, and a smooth communication was achieved even at a distance of 7 m. The prototype showed a much wider communication range than any other existing products. Through this, it is conceivable that various problems due to space constraints can be resolved, hence presenting many benefits to the patients whose last resort to the disease is the VNS electroceutical.

Heart rate variability and vasovagal tone index in brachycephalic dogs.

Brachycephalic breeds of dogs, most of which show signs of the brachycephalic syndrome may have greater parasympathetic stimulation than other breeds, leading to higher values of heart rate variability and vagal tone index. The aim of this study was to establish a computerized electrocardiographic study and an assessment of the vagus sympathetic balance through heart rate variability and vagal tone index of five brachycephalic breeds compared to mesocephalic dogs. Sixty dogs were used, divided into groups made up of Boxers, English Bulldogs, French Bulldogs, Pugs, Shih-Tzu and no defined breed mesocephalic dogs. Statistical analysis was carried out using the Shapiro-Wilk test, Kruskal-Wallis and Dunn's test or ANOVA and Bonferroni (p<0.05). In the evaluation of vagal sympathetic balance among all the dogs, there was a negative correlation between heart rate and HRV 10RR (r = - 0.7678; p < 0.0001), HRV 20RR (r = - 0.8548, p < 0.0001) and VVTI (r = - 0.2770; p = 0.0321). It can therefore be concluded that the dog's breed and morphology did not alter its electrocardiographic parameters or heart rate variability. The vagal tone index, which in other studies differed in brachycephalic dogs, showed no difference when compared separately in brachycephalic breeds.

Speed of heart rate changes during postural provocations in children and adolescents.

Heart rate is under constant autonomic influence but the development of the influence in children is not fully understood. Continuous electrocardiograms were obtained in 1045 healthy school-age children (550 females) during postural provocations with body position changes between supine, sitting, standing, supine, standing, sitting and supine (in this order), 10 min in each position with position changes within 20 s. Heart rate was measured in each position and speed of heart rate changes between positions were assessed by regressions of rates versus timing of individual cardiac cycles. Supine heart rate was gradually decreasing with age: 82.32 ± 9.92, 74.33 ± 9.79, 67.43 ± 9.45 beats per minute (bpm) in tertile age groups < 11, 11-15, > 15 years, respectively (p < 0.0001), with no significant sex difference. Averaged speed of heart rate changes differed little between sexes and age groups but was significantly faster during rate deceleration than acceleration (e.g., supine ↔ standing: 2.99 ± 1.02 vs. 2.57 ± 0.68 bpm/s, p < 0.0001). The study suggests that in children, vagal heart rate control does not noticeably change between ages of approximately 6-19 years. The gradual resting heart rate decrease during childhood and adolescence is likely caused by lowering of cardiac sympathetic influence from sympathetic overdrive in small children to adult-like sympatho-vagal balance in older adolescents.

Transcutaneous auricular vagus nerve stimulation enhances short-latency afferent inhibition via central cholinergic system activation.

The present study examined the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on short-latency afferent inhibition (SAI), as indirect biomarker of cholinergic system activation. 24 healthy adults underwent intermittent taVNS (30 s on/30 s off, 30 min) or continuous taVNS at a frequency of 25 Hz (15 min) along with earlobe temporary stimulation (15 min or 30 min) were performed in random order. The efficiency with which the motor evoked potential from the abductor pollicis brevis muscle by transcranial magnetic stimulation was attenuated by the preceding median nerve conditioning stimulus was compared before taVNS, immediately after taVNS, and 15 min after taVNS. Continuous taVNS significantly increased SAI at 15 min post-stimulation compared to baseline. A positive correlation (Pearson coefficient = 0.563, p = 0.004) was observed between baseline SAI and changes after continuous taVNS. These results suggest that 15 min of continuous taVNS increases the activity of the cholinergic nervous system, as evidenced by the increase in SAI. In particular, the increase after taVNS was more pronounced in those with lower initial SAI. This study provides fundamental insight into the clinical potential of taVNS for cholinergic dysfunction.

High-Frequency Heart Rate Variability Is Prospectively Associated With Sleep Complaints in a Healthy Working Cohort.

OBJECTIVE: Vagus nerve functioning, as indexed by high-frequency heart rate variability (HF-HRV), has been implicated in a wide range of mental and physical health conditions, including sleep complaints. This study aimed to test associations between HF-HRV measured during sleep (sleep HF-HRV) and subjective sleep complaints 4 years later. METHODS: One hundred forty-three healthy employees (91% male; MAge = 47.8 years [time 2], SD = 8.3 years) of an industrial company in Southern Germany completed the Jenkins Sleep Problems Scale, participated in a voluntary health assessment, and were given a 24-hour ambulatory heart rate recording device in 2007. Employees returned for a health assessment and completed the Jenkins Sleep Problems Scale 4 years later. RESULTS: Hierarchical regression analyses showed that lower sleep HF-HRV measured in 2007 was associated with higher self-reported sleep complaints 4 years later after controlling for covariates (rab,c = -0.096, b = -0.108, 95% CI, -0.298 to 0.081, ΔR2 = 0.009, p = .050). CONCLUSIONS: These data are the first to show that lower sleep HF-HRV predicted worse sleep 4 years later, highlighting the importance of vagus nerve functioning in adaptability and health.

Voluntary wheel running as a promising strategy to promote autonomic resilience to social stress in females: Vagal tone lies at the heart of the matter.

Social stress is a major risk factor for comorbid conditions including cardiovascular disease and depression. While women exhibit 2-3× the risk for these stress-related disorders compared to men, the mechanisms underlying heightened stress susceptibility among females remain largely unknown. Due to a lack in understanding of the pathophysiology underlying stress-induced comorbidities among women, there has been a significant challenge in developing effective therapeutics. Recently, a causal role for inflammation has been established in the onset and progression of comorbid cardiovascular disease/depression, with women exhibiting increased sensitivity to stress-induced immune signaling. Importantly, reduced vagal tone is also implicated in stress susceptibility, through a reduction in the vagus nerve's well-recognized anti-inflammatory properties. Thus, examining therapeutic strategies that stabilize vagal tone during stress may shed light on novel targets for promoting stress resilience among women. Recently, accumulating evidence has demonstrated that physical activity exerts cardio- and neuro-protective effects by enhancing vagal tone. Based on this evidence, this mini review provides an overview of comorbid cardiovascular and behavioral dysfunction in females, the role of inflammation in these disorders, how stress may impart its negative effects on the vagus nerve, and how exercise may act as a preventative. Further, we highlight a critical gap in the literature with regard to the study of females in this field. This review also presents novel data that are the first to demonstrate a protective role for voluntary wheel running over vagal tone and biomarkers of cardiac dysfunction in the face of social stress exposure in female rats.