Autonomic regulation and vagal tone

Autonomy of autonomic dysfunction in major depression.: Objective: To investigate cardiac autonomic dysfunction in patients with major depressive disorder (MDD). Research in this area has faced several limitations because of the heterogeneity of the disease, the influence of medication, and methodological shortcomings. Methods: Participants were 75 patients suffering from an acute recurrent episode of MDD and 75 matched controls. All participants were assessed at baseline for linear and nonlinear parameters of heart rate variability, QT variability a

Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial.: Background: Despite positive outcomes of transcutaneous vagus nerve stimulation (tVNS) via the auricular branch of the vagus nerve (ABVN), the mechanisms underlying these outcomes remain unclear. Additionally, previous studies have not been controlled the possible placebo effects of tVNS. Objective: To test the hypothesis that tVNS acutely improves spontaneous cardiac baroreflex sensitivity (cBRS) and autonomic modulation, and that these effects are specific to stimulation of ABVN. Methods: Thir

Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity.: Background: Vagus nerve stimulation (VNS) is currently used to treat refractory epilepsy and is being investigated as a potential therapy for a range of conditions, including heart failure, tinnitus, obesity and Alzheimer's disease. However, the invasive nature and expense limits the use of VNS in patient populations and hinders the exploration of the mechanisms involved. Objective: We investigated a non-invasive method of VNS through electrical stimulation of the auricular branch of the vagus n

Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: potential benefits of daily stimulation.: Ageing is associated with attenuated autonomic function. Transcutaneous vagal nerve stimulation (tVNS) improved autonomic function in healthy young participants. We therefore investigated the effects of a single session of tVNS (studies 1 and 2) and tVNS administered daily for two weeks (study 3) in volunteers aged ≥ 55 years. tVNS was performed using modified surface electrodes on the tragus and connected to a transcutaneous electrical nerve stimulation (TENS) machine. Study 1: participants (n=

Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity.: Background: The parasympathetic nervous system, whose main neural substrate is the vagus nerve, exerts a fundamental antinociceptive role and influences gastrointestinal sensori-motor function. Our research question was to whether combined electrical and physiological modulation of vagal tone, using transcutaneous electrical vagal nerve stimulation (t-VNS) and deep slow breathing (DSB) respectively, could increase musculoskeletal pain thresholds and enhance gastroduodenal motility in healthy sub

Sex differences in healthy human heart rate variability: A meta-analysis.: The present meta-analysis aimed to quantify current evidence on sex differences in the autonomic control of the heart, indexed by measures of heart rate variability (HRV) in healthy human subjects. An extensive search of the literature yielded 2020 titles and abstracts, of which 172 provided sufficient reporting of sex difference in HRV. Data from 63,612 participants (31,970 females) were available for analysis. Meta-analysis yielded a total of 1154 effect size estimates (k) across 50 different

RR interval variability is inversely related to inflammatory markers: the CARDIA study.

Recent evidence reveals that the immune system is under the direct control of the vagus nerve via the "cholinergic anti-inflammatory pathway." Stimulation of vagus nerve activity significantly inhibits cytokine levels in animal models, and cholinergic agents inhibit cytokine release by human macrophages. Moreover, when vagus nerve activity is decreased or absent, cytokines are overproduced. Atherosclerosis is an inflammatory disease characterized by elevated levels of CRP and IL-6, but the relationship between cardiac vagal activity and cytokine levels in healthy humans is not well understood. Here we measured RR interval variability, an index of cardiac vagal modulation, and CRP and IL-6 in 757 subjects participating in a subset of the year 15 data collection in the CARDIA study of the evolution of risk factors in young adults. Univariate analysis revealed that all indices of RRV were s…

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Vagus nerve stimulation: a new promising therapeutic tool in inflammatory bowel disease.

Inflammatory bowel disease (IBD), that is Crohn's disease (CD) and ulcerative colitis, affects about 1.5 million persons in the USA and 2.2 million in Europe. The pathophysiology of IBD involves immunological, genetic and environmental factors. The treatment is medico-surgical but suspensive. Anti-TNFα agents have revolutionized the treatment of IBD but have side effects. In addition, a non-negligible percentage of patients with IBD stop or take episodically their treatment. Consequently, a nondrug therapy targeting TNFα through a physiological pathway, devoid of major side effects and with a good cost-effectiveness ratio, would be of interest. The vagus nerve has dual anti-inflammatory properties through its afferent (i.e. hypothalamic-pituitary-adrenal axis) and efferent (i.e. the anti-TNFα effect of the cholinergic anti-inflammatory pathway) fibres. We have shown that there is an inve…

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Reliability of ultra-short-term analysis as a surrogate of standard 5-min analysis of heart rate variability.

Background: Despite the increasing demands of ultra-short-term heart rate (HR) variability (HRV) for practical ambulatory applications, there have been few studies that have investigated R-R interval recording for less than 5 min for HRV analysis. It has not been extensively validated, and, currently, no normative data for ultra-short-term HRV exist. The aim of this study was to investigate the relationship between standard 5-min and ultra-short-term HRV by collecting data from a large population consisting of a wide range of age groups. Materials and methods: The 5-min R-R interval series were obtained from 467 healthy volunteers ranging from 8 to 69 years of age. The original R-R interval was segmented into 270, 240, 210, 180, 150, 120, 90, 60, 30, 20, and 10 s, and those HRV features most commonly reported within the literature were calculated and compared with those using the origina…

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Monitoring Athletic Training Status Through Autonomic Heart Rate Regulation: A Systematic Review and Meta-Analysis.

Background: Autonomic regulation of heart rate (HR) as an indicator of the body's ability to adapt to an exercise stimulus has been evaluated in many studies through HR variability (HRV) and post-exercise HR recovery (HRR). Recently, HR acceleration has also been investigated. Objective: The aim of this systematic literature review and meta-analysis was to evaluate the effect of negative adaptations to endurance training (i.e., a period of overreaching leading to attenuated performance) and positive adaptations (i.e., training leading to improved performance) on autonomic HR regulation in endurance-trained athletes. Methods: We searched Ovid MEDLINE, Embase, CINAHL, SPORTDiscus, PubMed, and Academic Search Premier databases from inception until April 2015. Included articles examined the effects of endurance training leading to increased or decreased exercise performance on four measures …

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Heart rate variability and self-control--A meta-analysis.

Heart rate variability (HRV) has been suggested as a biological correlate of self-control. Whereas many studies found a relationship between HRV at rest and self-control, effect sizes vary substantially across studies in magnitude and direction. This meta-analysis evaluated the association between HRV at rest and self-control in laboratory tasks, with a particular focus on the identification of moderating factors (task characteristics, methodological aspects of HRV assessment, demographics). Overall, 24 articles with 26 studies and 132 effects (n=2317, mean age=22.44, range 18.4-57.8) were integrated (random effects model with robust variance estimation). We found a positive average effect of r=0.15, 95% CI [0.088; 0.221], p<0.001 with a moderate heterogeneity (I(2)=56.10%), but observed evidence of publication bias. Meta-regressions did not reveal significant moderators. Due to the pres…

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Meta-analytic evidence for decreased heart rate variability in chronic pain implicating parasympathetic nervous system dysregulation.

Both sympathetic and parasympathetic nervous systems are involved in regulating pain states. The activity of these systems seems to become disturbed in states of chronic pain. This disruption in autonomic balance can be measured through the assessment of heart rate variability (HRV), that is, the variability of the interval between consecutive heart beats. However, there is yet to be a systematic evaluation of the body of literature concerning HRV across several chronic pain conditions. Moreover, modern meta-analytical techniques have never been used to validate and consolidate the extent to which HRV may be decreased in chronic pain. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement guidelines, this study systematically evaluated and critically appraised the literature concerning HRV in people living with chronic pain. After screening 17…

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Heart rate variability and first cardiovascular event in populations without known cardiovascular disease: meta-analysis and dose-response meta-regression.

Aims: Heart rate variability (HRV) is associated with cardiovascular disease (CVD) in individuals with known CVD. It is less clear whether HRV is associated with a first cardiovascular event. Therefore, we performed a meta-analysis to study the association between HRV and incident cardiovascular events in populations without known CVD. Methods and results: We performed a meta-analysis and dose-response meta-regression of studies assessing the association between HRV and CVD. We searched Pubmed, Embase, Web of Science, Cochrane library, ScienceDirect, and CINAHL up to December 2011 for eligible studies. We selected studies that used the standard deviation of the normalized N-N interval (SDNN), low-frequency (LF) or high-frequency (HF) spectral component as a measure of HRV. Primary outcomes were (non)fatal cardiovascular events. Eight studies with a total number of 21 988 participants wer…

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The anatomical basis for transcutaneous auricular vagus nerve stimulation.

The array of end organ innervations of the vagus nerve, coupled with increased basic science evidence, has led to vagus nerve stimulation (VNS) being explored as a management option in a number of clinical disorders, such as heart failure, migraine and inflammatory bowel disease. Both invasive (surgically implanted) and non-invasive (transcutaneous) techniques of VNS exist. Transcutaneous VNS (tVNS) delivery systems rely on the cutaneous distribution of vagal afferents, either at the external ear (auricular branch of the vagus nerve) or at the neck (cervical branch of the vagus nerve), thus obviating the need for surgical implantation of a VNS delivery device and facilitating further investigations across a wide range of uses. The concept of electrically stimulating the auricular branch of the vagus nerve (ABVN), which provides somatosensory innervation to several aspects of the external…

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Causal effects of the early caregiving environment on development of stress response systems in children.

Disruptions in stress response system functioning are thought to be a central mechanism by which exposure to adverse early-life environments influences human development. Although early-life adversity results in hyperreactivity of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis in rodents, evidence from human studies is inconsistent. We present results from the Bucharest Early Intervention Project examining whether randomized placement into a family caregiving environment alters development of the autonomic nervous system and HPA axis in children exposed to early-life deprivation associated with institutional rearing. Electrocardiogram, impedance cardiograph, and neuroendocrine data were collected during laboratory-based challenge tasks from children (mean age = 12.9 y) raised in deprived institutional settings in Romania randomized to a high-quality fo…

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The A52 Breath Method: A Narrative Review of Breathwork for Mental Health and Stress Resilience.

Breathwork - deliberately altering the way one breathes - has gained growing attention as an emerging non-pharmacological intervention for mental health and stress regulation. A novel yet ancient method that remains largely underexplored in the literature, breathwork requires structured, evidence-based investigation to optimize its application. This review analyses the existing literature on slow, diaphragmatic, nasal breathing and breath-holding techniques, to propose the A52 Breath Method-a theoretically grounded approach for enhancing stress resilience. A narrative review of breathwork literature was conducted that focused on the physiological and psychological mechanisms underpinning stress reduction. Medical databases were searched: 465 articles were screened and 30 studies underwent full-text review. Studies examining slow breathing (≤ 6 breaths per minute), diaphragmatic activatio…

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Acceptance versus reappraisal: Behavioral, autonomic, and neural effects.

Emotion regulation (ER) is an important skill for well-being. Cognitive reappraisal is a goal-oriented cognitive change strategy. Acceptance involves decentering from immediate habits of reactivity, observing moment-to-moment shifts in thoughts, emotions, and sensations. These two regulation strategies are thought to have different effects on emotion; however, no study has examined the differential effects of reappraisal and acceptance on behavioral, autonomic, and brain responses in the context of ideographic personally salient negative self-beliefs. Thirty-five right-handed, healthy adults were presented idiographic negative self-beliefs embedded in autobiographical scripts. We measured negative emotion ratings, autonomic psychophysiology, and functional magnetic resonance imaging blood oxygen-level dependent responses while participants read neutral statements, reacted to their own ne…

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Effect of Heart Rate Variability Biofeedback on Sport Performance, a Systematic Review.

Aim is to determine if the training with heart rate variability biofeedback allows to improve performance in athletes of different disciplines. Methods such as database search on Web of Science, SpringerLink, EBSCO Academic Search Complete, SPORTDiscus, Pubmed/Medline, and PROQUEST Academic Research Library, as well as manual reference registration. The eligibility criteria were: (a) published scientific articles; (b) experimental studies, quasi-experimental, or case reports; (c) use of HRV BFB as main treatment; (d) sport performance as dependent variable; (e) studies published until October 2016; (f) studies published in English, Spanish, French or Portuguese. The guidelines of the PRISMA statement were followed. Out of the 451 records found, seven items were included. All studies had a small sample size (range from 1 to 30 participants). In 85.71% of the studies (n = 6) the athletes e…

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Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans.

Background: Tract-tracing studies in cats and rats demonstrated that the auricular branch of the vagus nerve (ABVN) projects to the nucleus tractus solitarii (NTS); it has remained unclear as to whether or not the ABVN projects to the NTS in humans. Objective: To ascertain whether non-invasive electrical stimulation of the cymba conchae, a region of the external ear exclusively innervated by the ABVN, activates the NTS and the "classical" central vagal projections in humans. Methods: Twelve healthy adults underwent two fMRI scans in the same session. Electrical stimulation (continuous 0.25ms pulses, 25Hz) was applied to the earlobe (control, scan #1) and left cymba conchae (scan #2). Statistical analyses were performed with FSL. Two region-of-interest analyses were performed to test the effects of cymba conchae stimulation (compared to baseline and control, earlobe, stimulation) on the c…

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Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with …

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Photoplethysmography pulse rate variability as a surrogate measurement of heart rate variability during non-stationary conditions.

In this paper we assessed the possibility of using the pulse rate variability (PRV) extracted from the photoplethysmography signal as an alternative measurement of the HRV signal in non-stationary conditions. The study is based on analysis of the changes observed during a tilt table test in the heart rate modulation of 17 young subjects. First, the classical indices of HRV analysis were compared to the indices from PRV in intervals where stationarity was assumed. Second, the time-varying spectral properties of both signals were compared by time-frequency (TF) and TF coherence analysis. Third, the effect of replacing PRV with HRV in the assessment of the changes of the autonomic modulation of the heart rate was considered. Time-invariant HRV and PRV indices showed no statistically significant differences (p > 0.05) and high correlation (>0.97). Time-frequency analysis revealed that the TF…

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Preliminary results of an open label study of heart rate variability biofeedback for the treatment of major depression.

Unlabelled: Major depressive disorder (MDD) is a common mood disorder that can result in significant discomfort as well as interpersonal and functional disability. A growing body of research indicates that autonomic function is altered in depression, as evidenced by impaired baroreflex sensitivity, changes in heart rate, and reduced heart rate variability (HRV). Decreased vagal activity and increased sympathetic arousal have been proposed as major contributors to the increased risk of cardiovascular mortality in participants with MDD, and baroreflex gain is decreased. Study objectives: To assess the feasibility of using HRV biofeedback to treat major depression. Design: This was an open-label study in which all eleven participants received the treatment condition. Participants attended 10 weekly sessions. Questionnaires and physiological data were collected in an orientation (baseline) s…

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Effect of aging on baroreflex function in humans.

Arterial blood pressure (BP) is regulated via the interaction of various local, humoral, and neural factors. In humans, the major neural pathway for acute BP regulation involves the baroreflexes. In response to baroreceptor activation/deactivation, as occurs during transient changes in BP, key determinants of BP, such as cardiac period/heart rate (via the sympathetic and parasympathetic nervous system) and vascular resistance (via the sympathetic nervous system), are modified to maintain BP homeostasis. In this review, the effects of aging on both the parasympathetic and sympathetic arms of the baroreflex are discussed. Aging is associated with decreased cardiovagal baroreflex sensitivity (i.e., blunted reflex changes in R-R interval in response to a change in BP). Mechanisms underlying this decrease may involve factors such as increased levels of oxidative stress, vascular stiffening, a…

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Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review.

Objective: The goal of this systematic literature review is to determine whether there are differences and similarities in heart rate variability (HRV) between adult patients with fibromyalgia (FM), chronic fatigue syndrome (CFS), and healthy pain-free control subjects. Methods: To obtain relevant articles, PubMed and Web of Knowledge were searched for case-control studies. Selection of the literature was based on selection criteria ascertaining studies with adult human patient groups comparing HRV. Risk of bias and levels of evidence were determined. Results: Sixteen case-control studies were included, 10 comparing FM patients to controls and 6 comparing CFS patients to controls. Methodological quality was moderate to good. Both time domain and frequency domain measurements were used. The majority of the researchers observed lower HRV in FM patients compared to healthy control persons, …

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The effect of heart rate variability biofeedback on performance psychology of basketball players.

Coping with pressure and anxiety is an ineluctable demand of sports performance. Heart rate variability (HRV) Biofeedback (BFB) shall be used as a tool for self regulating physiological responses resulting in improved psycho physiological interactions. For further analysis, the present study has been designed to examine the relationship between anxiety and performance and also effectiveness of biofeedback protocol to create stress-eliciting situation in basketball players. Thirty basketball players of university level and above (both male and female) aged 18-28 years, who scored a minimum of 20 in state trait anxiety inventory, were randomly divided into three equal groups- Experimental (Biofeedback) group, Placebo group and Control (No Treatment) group. The BFB group received HRV BFB training for 10 consecutive days for 20 min that included breathing at individual's resonant frequency t…

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Behavioral neurocardiac training in hypertension: a randomized, controlled trial.

It is not established whether behavioral interventions add benefit to pharmacological therapy for hypertension. We hypothesized that behavioral neurocardiac training (BNT) with heart rate variability biofeedback would reduce blood pressure further by modifying vagal heart rate modulation during reactivity and recovery from standardized cognitive tasks ("mental stress"). This randomized, controlled trial enrolled 65 patients with uncomplicated hypertension to BNT or active control (autogenic relaxation), with six 1-hour sessions over 2 months with home practice. Outcomes were analyzed with linear mixed models that adjusted for antihypertensive drugs. BNT reduced daytime and 24-hour systolic blood pressures (-2.4+/-0.9 mm Hg, P=0.009, and -2.1+/-0.9 mm Hg, P=0.03, respectively) and pulse pressures (-1.7+/-0.6 mm Hg, P=0.004, and -1.4+/-0.6 mm Hg, P=0.02, respectively). No effect was observ…

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Heart rate variability biofeedback: effects of age on heart rate variability, baroreflex gain, and asthma.

Objectives: To present additional analysis of data from a previously published study showing that biofeedback training to increase heart rate variability (HRV) can be an effective component in asthma treatment. HRV and intervention-related changes in HRV are negatively correlated with age. Here we assess the effects of age on biofeedback effects for asthma. Design: Ten sessions of HRV biofeedback were administered to 45 adults with asthma. Medication was prescribed by blinded physicians according to National Heart, Lung, and Blood Institute criteria. Medication needs were reassessed biweekly. Results: Decreases in need for controller medication were independent of age. There were larger acute decreases in forced oscillation frequency dependence in the older group but larger increases in HRV variables in the younger group. Differences between age groups were smaller among subjects trained…

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Analysis of Heart Rate Variability and Implication of Different Factors on Heart Rate Variability.

Background: The heart is the central organ of the circulatory system, which maintains the flow of blood along with the transport of nutrients to different cells and tissues. A well-functioning cardiac state is a complicated mode of changeability. A healthy heart is not only about oscillation, as the rhythmometer is not the same in every circumstance. Heart rate shows variations so that it can be regulated according to psychophysiological conditions to maintain the effect of the internal-external stimulus. Objective: The main objective of this review is to provide a piece of all-inclusive information about heart rate variability (HRV) and different variables affecting HRV. The direct interconnection so that HRV can be used in clinical practices. Methods: This review article contains a detailed survey of literature about HRV available in different online sources such as; Google Scholar, Sc…

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Heart rate variability: are you using it properly? Standardisation checklist of procedures.

Background: Heart rate variability is used as an assessment method for cardiac autonomic modulation. Since the Task Force's publication on heart rate variability in 1996, the European Heart Rhythm Association Position Paper in 2015 and a recent publication in 2017, attention has been paid to recommendations on using heart rate variability analysis methods, as well as their applications in different physiological conditions and clinical studies. This analysis has proved to be useful as a complementary tool for clinical evaluation and to assess the effect of non-pharmacological therapeutic interventions, such as physical exercise programmes, on cardiac autonomic modulation. Objective: The aim of this article is to make recommendations and to develop a checklist of normalisation procedures regarding the use of heart rate variability data collection and analysis methodology, focusing on the …

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Pitfalls of assessment of autonomic function by heart rate variability.

Although analysis of heart rate variability is widely used for the assessment of autonomic function, its fundamental framework linking low-frequency and high-frequency components of heart rate variability with sympathetic and parasympathetic autonomic divisions has developed in the 1980s. This simplified framework is no longer able to deal with much evidence about heart rate variability accumulated over the past half-century. This review addresses the pitfalls caused by the old framework and discusses the points that need attention in autonomic assessment by heart rate variability.

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Advances in heart rate variability signal analysis: joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society.

Following the publication of the Task Force document on heart rate variability (HRV) in 1996, a number of articles have been published to describe new HRV methodologies and their application in different physiological and clinical studies. This document presents a critical review of the new methods. A particular attention has been paid to methodologies that have not been reported in the 1996 standardization document but have been more recently tested in sufficiently sized populations. The following methods were considered: Long-range correlation and fractal analysis; Short-term complexity; Entropy and regularity; and Nonlinear dynamical systems and chaotic behaviour. For each of these methods, technical aspects, clinical achievements, and suggestions for clinical application were reviewed. While the novel approaches have contributed in the technical understanding of the signal character …

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