Index Of Vagal Tone Research Articles

Maternal Injection with Dexamethasone Results in Female-Biased Autonomic Dysregulation in Rat Offspring

Autonomic dysfunction is an underlying risk factor for cardiovascular disease (CVD). Maternal injection of the synthetic GC dexamethasone (DEX) during the last 4 days of gestation results in female-biased increases in stress-responsive pressor (MAP), heart rate (HR) and altered heart rate variability (HRV) in adult rat offspring, suggesting a role for GC-mediated programming of autonomic function. The present study used pharmacological antagonists for adrenergic (SYM) or cholinergic (PS) receptors to investigate the degree to which changes in SYM or PS activity underlie the autonomic dysfunction in offspring of dams injected with DEX during late gestation. Naïve breeders were injected with DEX (0.4mg/kg/day, s.c.) or vehicle (hydroxypropyl beta cyclodextrin; Veh) on gestation days 18-21. Radiotelemetry was used in adult offspring for recording HR, MAP, and HRV (root mean square of successive differences: RMSSD). At 10-11 weeks rats were randomly assigned to receive SYM antagonists, α-adrenoceptor (prazosin; 0.5mg/kg, i.p.) + β-adrenoceptor (atenolol; 1mg/kg, i.p.), a PS antagonist (homatropine methylbromide; 0.2mg/kg, i.p), or saline (SAL, i.p.). Evaluations were made over 20 min following injection and then during a 20 min restraint. Females were tested on diestrus. In utero DEX exposure resulted in significantly lower RMSSD, an index of vagal tone, in DEX-exposed females and males. PS blockade significantly reduced RMSSD in Veh-, but not DEX-exposed female offspring. SYM blockade did not influence RMSSD in females. In males, PS blockade reduced in RMSSD in both DEX- and Veh-exposed offspring. SYM blockade only reduced RMSSD in males exposed to DEX. Area under the curve (AUC) analysis revealed that in female offspring, SYM blockade resulted in a greater reduction in HR in DEX-exposed offspring, compared to Veh (DEX-SYM: −220 bpm vs. DEX-SAL; Veh-SYM: −197 bpm vs. VEH-SAL) and during restraint (DEX-SYM: −535 bpm vs. DEX-SAL; Veh-SYM: −342 bpm vs. VEH-SAL). PS blockade resulted in a greater increase in HR in Veh-exposed females both following the injection (Veh-PS: −187 bpm vs. VEH-SAL; DEX-PS: −101 bpm vs. DEX-SAL) and during restraint (Veh-PS: −161 bpm vs. VEH-SAL; DEX-PS: −61 bpm vs. DEX-SAL). AUC analysis for MAP showed similar responses to those for HR with SYM blockade having a greater impact in DEX-exposed females and PS blockade having a greater effect in Veh-exposed females. By contrast, in male offspring in utero DEX exposure did not influence HR or MAP responses to SYM or PS blockade. Overall, these findings suggest that maternal DEX injections alter autonomic development primarily in in female offspring and is characterized by a shift from PS to SYM predominance. Better understanding of the mechanisms involved in this programming are important for identifying individuals at risk for CVD and development of interventional strategies for prevention of CVD. Funding: NIH U54 MH118919. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

Concurrent metaboreflex activation increases chronotropic and ventilatory responses to passive leg movement without sex-related differences

Previous studies in animal models showed that exercise-induced metabolites accumulation may sensitize the mechanoreflex-induced response. The aim of this study was to assess whether the magnitude of the central hemodynamic and ventilatory adjustments evoked by isolated stimulation of the mechanoreceptors in humans are influenced by the prior accumulation of metabolic byproducts in the muscle. 10 males and 10 females performed two exercise bouts consisting of 5-min of intermittent isometric knee-extensions performed 10% above the previously determined critical force. Post-exercise, the subjects recovered for 5 min either with a suprasystolic circulatory occlusion applied to the exercised quadriceps (PECO) or under freely-perfused conditions (CON). Afterwards, 1-min of continuous passive leg movement was performed. Central hemodynamics, pulmonary data, and electromyography from exercising/passively-moved leg were recorded throughout the trial. Root mean square of successive differences (RMSSD, index of vagal tone) was also calculated. Δpeak responses of heart rate (ΔHR) and ventilation (Delta dot{V}_{{text{E}}}) to passive leg movement were higher in PECO compared to CON (ΔHR: 6 ± 5 vs 2 ± 4 bpm, p = 0.01; 3.9 ± 3.4 vs 1.9 ± 1.7 L min−1, p = 0.02). Δpeak of mean arterial pressure (ΔMAP) was significantly different between conditions (5 ± 3 vs − 3 ± 3 mmHg, p < 0.01). Changes in RMSSD with passive leg movement were different between PECO and CON (p < 0.01), with a decrease only in the former (39 ± 18 to 32 ± 15 ms, p = 0.04). No difference was found in all the other measured variables between conditions (p > 0.05). These findings suggest that mechanoreflex-mediated increases in HR and dot{V}_{{text{E}}} are sensitized by metabolites accumulation. These responses were not influenced by biological sex.

Common eating habit patterns are associated with a high maximum occlusal force and pre-eating cardiac vagal tone.

Masticatory function is associated with nervous function, including autonomic nervous function, and both functions are influenced by human habits. In a previous preliminary study of 53 young women, we found that eating habit patterns were associated with occlusal force as an indicator of masticatory function. Therefore, we hypothesized that relationships exist between occlusal force, the autonomic nervous system, and eating habit patterns. To test our hypothesis, we analyzed the relationship between heart rate variability measured before and after lunch in 53 young women, and measured and surveyed maximum occlusal force and eating habit patterns, respectively, in these participants. High occlusal force was associated with an increased high-frequency (HF) component (vagal tone index) of the heart rate variability index immediately before lunch (standardized regression coefficient (β)=0.417, P=0.002). Each of the eating habit items surveyed in a questionnaire showed a similar tendency for the HF component immediately before lunch and maximum occlusal force; in particular, "Habit of eating breakfast" and "Number of meals per day" were significantly associated with both variables. Additionally, total eating habit scores related to higher maximum occlusal force were associated with an increase in the HF component immediately before lunch (β=0.514, P<0.001). The maximum occlusal force and the pre-eating HF component values were stratified by total eating habit scores (into low, medium, high categories), and the high scores were significantly higher than the medium or low scores. Occlusal force and the pre-eating cardiac vagal response of individuals were characterized by their common eating habit patterns, indicating that eating habits may be simultaneously associated with the development of masticatory function, nervous system development, and cardiovascular rhythm. Although further research is needed to investigate these relationships in detail, our findings provide insights that will inform the study of physical functions, neurodevelopment, habitual behaviors, and health in humans.

Different Relationship Between Glycemic Status and Autonomic Function in Patients with Type 2 Diabetes Mellitus and in Healthy Controls

Autonomic neuropathy is a common complication in diabetes mellitus (DM). Decreased vagal nerve activity and augmented sympathetic nerve activity have been reported in patients with DM. However, the relationship between autonomic function and glycemic status in DM and in individuals without DM remains unclear. We hypothesized that indices of sympathetic and vagal nerve activity are related to glycemic status. Eleven patients who were clinically diagnosed with type‐2 DM (HbA1c, 6.8 ± 0.3%; age, 54 ± 3 yrs), and 20 healthy non‐DM individuals (including 10 pre‐DM; HbA1c &lt; 6.5%; range 5.1‐6.1%; age, 59 ± 2 yrs) were studied (19 male, 12 female). Five DM patients had hypertension. Patients with DM and hypertensives were treated with standard medications. Beat‐by‐beat blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) were recorded under resting conditions. HR variability (HRV) was calculated and spontaneous cardiovagal baroreflex sensitivity (CBRS) was evaluated with the sequence method. CBRS in DM was lower than in non‐DM subjects (P &lt; 0.05). MSNA in DM was also lower than in non‐DM subjects (P &lt; 0.05). In linear regression analyses with data from all subjects, CBRS was negatively correlated with fasting blood glucose (FBG) (R = ‐0.47), insulin (R = ‐0.42), and homeostasis model assessment of insulin resistance (HOMA‐IR) (R = ‐0.43) (P &lt; 0.05 for all). MSNA was negatively correlated with HbA1c and HOMA‐IR (R = ‐0.41, ‐0.42, respectively; both, P &lt; 0.05). The high frequency (HF) component of HRV (i.e., an index of vagal tone) was negatively correlated with insulin (R = ‐0.46) and HOMA‐IR (R = ‐0.42) in all subjects (P &lt; 0.05 for both). In non‐DM subjects, CBRS was negatively correlated with FBG (R = ‐0.53, P &lt;0.05). HF was negatively correlated with FBG (R = ‐0.51), insulin (R = ‐0.66), and HOMA‐IR (R = ‐0.66) (P &lt; 0.05 for all), but MSNA was not correlated with glycemic/insulin status in non‐DM subjects. Whereas in DM patients, MSNA tended to be negatively correlated with HOMA‐IR (R = ‐0.77, P = 0.07). In the present study, both MSNA and vagal activity (CBRS and HF) were decreased in relation to the glycemic/insulin status. Vagal nerve activity was associated with the glycemic/insulin status even in non‐DM subjects (i.e., healthy and pre‐DM). Based on these results, we speculate that both vagal and sympathetic nerves were injured by DM progression, and that vagal neuropathy preceded the sympathetic neuropathy. Our results differ from prior reports that showed that MSNA in DM was higher than in non‐DM. However, in our study subjects, the severity of DM was mild, and except for hypertension in 5 subjects, none had manifestations of diabetic end‐organ damage. Differences in the duration and severity of DM as well as the effects of the treatments could contribute to the differences in the results. Further studies on the autonomic function during the DM progression are warranted.

Autonomic Testing in Collegiate Athletes Following SARS‐Cov‐2 Infection

To date, more than 46 million people in the United States have contracted the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which causes COVID‐19. Over 700 thousand total cases have been linked to American colleges and universities. Post‐acute sequelae of SARS‐CoV‐2 infection may affect varied systems. It was reported that sympathetic nerve activity following SARS‐CoV‐2 infection was elevated in young individuals. Cardiovascular autonomic function post‐acute SARS‐CoV‐2 infection in other populations such as athletes, however, has not been thoroughly investigated. Collegiate athletes are a unique population given that they might have a high level of physical fitness before the infection. The present study examined 16 collegiate athletes (12 men and 4 women, age: 20±1 yrs, height: 181±10 cm, weight: 81±18 kg) who were evaluated ~2 weeks after testing positive for SARS‐CoV‐2 by polymerase chain reaction assay. These subjects were asymptomatic or with mild/moderate symptoms during infection. None of the subjects had been hospitalized for COVID‐19 and all subjects were asymptomatic at the time of the study. Beat‐by‐beat blood pressure (BP) with Finometer, and heart rate (HR) from ECG were recorded during 10 minutes of supine rest, Valsalva maneuver, slow breathing (6 breaths/min), handgrip exercise, and 10 minutes of standing. BP, HR, heart rate variability (HRV), and cardiac baroreflex sensitivity (CBRS), and venous blood aldosterone and renin levels were analyzed. The vagal tone index from HRV in 3 of 16 athletes was lower than normative values. The responses in BP to Valsalva maneuver during phases IIa (i.e., “early”) and IIb (i.e., “late”) were mildly abnormal in 4 athletes and moderately abnormal in one athlete. The Valsalva ratio was below the normal range in 6 athletes. In response to slow breathing, the respiratory sinus arrhythmia amplitude was below the normal range in 3 athletes. In response to handgrip exercise, one athlete had an atypical response where BP decreased while HR was increased from baseline. Three of the subjects were unable to tolerate an orthostatic challenge for 10 minutes. Four out of 16 athletes had abnormally elevated renin activity and 1 out 16 elevated aldosterone levels. It is important to note that while several athletes had abnormal responses to the various autonomic tests, these abnormalities did not correlate with symptoms seen during the infection. Our data suggest that SARS‐CoV‐2 infection may reduce parasympathetic and increase sympathetic tone and may contribute to the autonomic disfunction associated in a subset of collegiate athletes even after recovering from COVID‐19. This study provides further evidence for potential long‐term cardiovascular autonomic effects of Covid‐19 infection even in healthy young trained athletes. Further studies with a larger patient population as well as suitable healthy control subjects are warranted.

Infant physiological activity and the early emergence of social communication.

Early in life, social engagement is facilitated by effective regulation during times of rest and stress. Physiological regulation during social play and in response to sudden environmental changes or social stressors may play an important role in sustaining social engagement in infancy and facilitate the acquisition of early social-communication skills. The aim of this study was to investigate the role of physiological activity during social play, including respiratory sinus arrhythsmia (RSA) and heart rate-defined attention, in the early emergence of social-communication skills. Using RSA as an index of vagal tone, we measured vagal tone, vagal suppression, and heart rate-defined sustained attention during a social interaction with a caregiver (i.e., the Still-Face procedure) in 21 infants aged 3-4 months. At 9 months, caregivers reported on their infant's early social-communication skills. Results suggest that RSA, RSA suppression, and heart rate-defined sustained attention to a caregiver are significantly associated with early-emerging social-communication skills at 9 months. In addition, RSA and heart rate-defined sustained attention during social play were highly related. Suppression of RSA during the Still-Face phase of the infant-caregiver interaction emerged as a particularly strong predictor of later-developing social-communication skills, including 9-month-olds' ability to use eye gaze, facial expression, and gestures to communicate.

The Vagal Autonomic Pathway of COVID-19 at the Crossroad of Alzheimer's Disease and Aging: A Review of Knowledge.

Coronavirus Disease 2019 (COVID-19) pandemic-triggered mortality is significantly higher in older than in younger populations worldwide. Alzheimer’s disease (AD) is related to aging and was recently reported to be among the major risk factors for COVID-19 mortality in older people. The symptomatology of COVID-19 indicates that lethal outcomes of infection rely on neurogenic mechanisms. The present review compiles the available knowledge pointing to the convergence of COVID-19 complications with the mechanisms of autonomic dysfunctions in AD and aging. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is prone to neuroinvasion from the lung along the vagus nerve up to the brainstem autonomic nervous centers involved in the coupling of cardiovascular and respiratory rhythms. The brainstem autonomic network allows SARS-CoV-2 to trigger a neurogenic switch to hypertension and hypoventilation, which may act in synergy with aging- and AD-induced dysautonomias, along with an inflammatory “storm”. The lethal outcomes of COVID-19, like in AD and unhealthy aging, likely rely on a critical hypoactivity of the efferent vagus nerve cholinergic pathway, which is involved in lowering cardiovascular pressure and systemic inflammation tone. We further discuss the emerging evidence supporting the use of 1) the non-invasive stimulation of vagus nerve as an additional therapeutic approach for severe COVID-19, and 2) the demonstrated vagal tone index, i.e., heart rate variability, via smartphone-based applications as a non-serological low-cost diagnostic of COVID-19. These two well-known medical approaches are already available and now deserve large-scale testing on human cohorts in the context of both AD and COVID-19.

Quantifying the dynamic nature of vagal responsivity in infancy: Methodological innovations and theoretical implications.

According to polyvagal theory, rapid modulation of the vagal brake develops early in infancy and supports social interactions. Despite being viewed as a dynamic system, researchers typically assess vagal regulation using global measures of respiratory sinus arrhythmia (RSA; an index of vagal tone). This study sought to capture the dynamic property of RSA and evaluate individual differences in within-infant RSA responsivity during mother-infant interaction. RSA was evaluated in a sample of 135 6-month-old Mexican-American infants during a 5-min free play task. Mothers reported on their children's behavioral problems and competence at 18months using the Brief Infant-Toddler Social and Emotional Assessment. Time-varying estimates of infant RSA during the interaction were obtained using a multiple window technique and spectrogram analysis. Using structural equation modeling, we evaluated whether within-infant SD of RSA predicted infants' behavioral problems and competence at 18months, after adjusting for infants' mean RSA and covariates. Greater within-infant SD of RSA predicted more behavior problems at 18months. This study demonstrates that assessing intra-individual variability in RSA, or the extent to which infants fluctuate around their average level of RSA during a task, enhances our ability to test polyvagal theory's central tenet: vagal regulation supports well-regulated social interaction.

Trait impulsiveness and response inhibition in young adults: Moderating role of resting respiratory sinus arrhythmia

Trait impulsiveness is a multifaceted construct that includes motor-, attention/cognitive- and non-planning facets, but how specific impulsiveness facets are associated with the deficit of response inhibition is not well understood. Resting respiratory sinus arrhythmia (RSA), which is considered as an index of cardiac vagal tone has been demonstrated to play a moderating role in the associations between many individual's variables. Whether resting RSA moderates the relationships between the facets of trait impulsiveness and response inhibition remains unknown. To examine these issues, data of self-reported trait impulsiveness, as assessed using the Barratt Impulsiveness Scale (BIS-II), 5-min resting RSA, and response accuracy (ACC) on a modified Go/NoGo task were collected from 132 college students. Results indicated that ACC of NoGo condition on the Go/NoGo task was negatively correlated with BIS motor and BIS total. Trait motor impulsiveness negatively predicted ACC of NoGo condition on the Go/NoGo task in the low resting RSA group but not in the high resting RSA group. This finding suggests that cardiac vagal tone could moderate the association between trait impulsiveness, especially motor impulsiveness, and deficits of response inhibition.

Children with orthostatic intolerance exhibit elevated markers of inflammation in the dorsal medulla.

Children with orthostatic intolerance (OI) have exaggerated decreases in heart rate variability (HRV) and suppression of baroreflex sensitivity (BRS) with standing. Accompanying brain transmitter and metabolite profiles are unknown. In this study, we used proton (1H) magnetic resonance spectroscopy (1H-MRS) to quantify markers of neuronal and glial integrity in a pilot study of children with OI compared with asymptomatic controls. Eighteen participants ages 10-18 yr were evaluated for blood pressure, heart rate (HR), and calculated indexes of autonomic function in supine and upright positions and, within an average of 2 wk, underwent 1H-MRS scans of dorsal medulla on a clinical 3T magnet while supine. As a result, of the 18 participants, 11 tested positive for OI and 7 did not. OI subjects exhibited higher HR and lower HRV and high-frequency α-index (HFα), an index of parasympathetic vagal tone, during standing compared with non-OI. HRV, sequence all (Seq All), high- and low-frequency (HFα and LFα) estimates of the spontaneous BRS decreased significantly, while BP variabilty increased significantly during standing only in subjects with OI. OI subjects had higher myoinositol (mIns) and total choline (tCho), markers of glial inflammation. Upright HFα and Seq All inversely correlated to supine tCho and mIns, respectively, independent of age and sex. In conclusions, in this pilot study, children with OI exhibit higher mIns and tCho in the dorsal medulla while supine that may reflect the well-established impairment in regulation of the autonomic nervous system upon standing. Neuroinflammation as an underlying cause or consequence of autonomic dysfunction is an intriguing possibility requiring further study.NEW & NOTEWORTHY (1H) magnetic resonance spectroscopy detected elevated markers of neuroinflammation in the dorsal medulla in children with impaired autonomic responses to head upright tilt. This first report of altered brain metabolites in this population provides a basis for future clinical studies using this methodology to aide in understanding complex autonomic disease states.

The higher the basal vagal tone the better the motor imagery ability.

A positive association between resting state vagal tone and performance of a few cognitive functions has been proposed. Aim of this study was to investigate the possible association between vagal tone and motor imagery (MI), as MI is based on high-level cognitive processes such as attention, working memory and inhibitory control. The experiment consisted of the execution of a motor sequence and of the MI of the same action in the kinesthetic and internal visual modality. Participants with high (High, N=15) and low (Low, N=16) vagal tone at rest, were characterized for imagery and executive functions abilities through the Motor imagery questionnaire and standard cognitive tests (Trail Making test A and B, Digit span and Corsi test). We studied as indices of vagal tone a few variables estimated from heart rate variability: the sroot mean square of successive heart-beat-intervals differences (RMSSD), the high frequency band (HF), the standard deviation 1 of Poincaré plot (SD1). As indices of MI ability we measured the isochrony between real and imagined movements and the reported vividness of imagery. A significantly greater isochrony was observed in Highs than in Lows only for the kinesthetic modality of imagery. Isochrony was not predicted by trait imagery abilities and did not correlate with vividness reports. Also, a reduction of the vagal control, which is the typical autonomic correlate of MI, was observed during both imagery tasks only in Highs. These findings indicate a cross-talk between the cardiovascular control and the proprioceptive representation of movement and reinforce the theory of bi-directional communication between heart and brain.

Presence of age- and sex-related differences in heart rate variability despite the maintenance of a suitable level of accelerometer-based physical activity

There is currently a lack of information adjacent on the influence of sex and age in heart rate variability (HRV), adjusted according to accelerometer-based physical activity (PADL). We hypothesized that the effect of sex and age on the HRV should be reduced or absent in individuals with a suitable PADL level. We aim to evaluate the influence of sex and age on HRV, adjusted for the confounding effects of the PADL level. A total of 485 age-stratified subjects (18–39, 40–59, and ≥60 years) underwent HRV analyses at rest and 7-day assessments of accelerometer-based PADL. Multivariate analyses of covariance were done using log-transformed HRV indices as outcomes, age and sex as fixed factors, and PADL, cardiovascular risk, fat body mass, and heart rate (HR) at rest as covariates. Despite the adjustment for directly measured PADL, women had better indices of vagal tone, whereas men had higher sympathetic influence. Also, compared to middle-aged and older adults, younger individuals (ages 18–39 years) presented better HRV. Multiple regression analyses confirmed that age and sex were the main predictors of HRV indices, even after adjusting for PADL directly assessed by triaxial accelerometer and HR. We also observed that the correlation between some HRV indexes and the different indexes of physical activity directly evaluated was significant, but not very consistent. Thus, HRV indices are influenced by age and sex, regardless of accelerometer-based physical activity. Interventions with physical activity and exercise aimed at improving the autonomic modulation of asymptomatic adults should take such differences into account.

Association between changes in heart rate variability during the anticipation of a stressful situation and the stress-induced cortisol response

Vagal activity – reflecting the activation of stress regulatory mechanisms and prefrontal cortex activation – is thought to play an inhibitory role in the regulation of the hypothalamus–pituitary–adrenal axis. However, most studies investigating the association between stress-induced changes in heart rate variability (HRV, an index of cardiac vagal tone) and cortisol have shown a non-significant relationship. It has been proposed that physiological changes observed during anticipation of a stressor allow individuals to make behavioral, cognitive, and physiological adjustments that are necessary to deal with the upcoming actual stressor. In this study, in a large sample of 171 healthy adults (96 men and 75 women; mean age = 29.98, SD = 11.07), we investigated whether the cortisol response to a laboratory-based stress task was related to anticipation-induced or stress task-induced changes in HRV. As expected, regression analyses showed that a larger decrease in HRV during the anticipation of a stress task was related to higher stress task-induced cortisol increase, but not cortisol recovery. In line with prior research, the stress task-induced change in HRV was not significantly related to cortisol increase or recovery. Our results show for the first time that anticipatory HRV (reflecting differences in stress regulation and prefrontal activity before the encounter with the stressor) is important to understand the stress-induced cortisol increase.

RETRACTED ARTICLE: Variable heart rate and a flexible mind: Higher resting-state heart rate variability predicts better task-switching

The neurovisceral integration model proposes that heart rate variability (HRV) is linked to prefrontal cortex activity via the vagus nerve, which connects the heart and the brain. HRV, an index of cardiac vagal tone, has been found to predict performance on several cognitive control tasks that rely on the prefrontal cortex. However, the link between HRV and the core cognitive control function “shifting” between tasks and mental sets is under-investigated. Therefore, the present study tested the neurovisceral integration model by examining, in 90 participants, the relationship between vagally mediated resting-state HRV and performance in a task-switching paradigm that provides a relatively process-pure measure of cognitive flexibility. As predicted, participants with higher resting-state HRV (indexed both by time domain and frequency domain measures) showed smaller switch costs (i.e., greater flexibility) than individuals with lower resting-state HRV. Our findings support the neurovisceral integration model and indicate that higher levels of vagally mediated resting-state HRV promote cognitive flexibility.

Morphology of subcortical brain nuclei is associated with autonomic function in healthy humans.

The autonomic nervous system (ANS) is a brain body interface which serves to maintain homeostasis by influencing a plethora of physiological processes, including metabolism, cardiorespiratory regulation and nociception. Accumulating evidence suggests that ANS function is disturbed in numerous prevalent clinical disorders, including irritable bowel syndrome and fibromyalgia. While the brain is a central hub for regulating autonomic function, the association between resting autonomic activity and subcortical morphology has not been comprehensively studied and thus was our aim. In 27 healthy subjects [14 male and 13 female; mean age 30 years (range 22-53 years)], we quantified resting ANS function using validated indices of cardiac sympathetic index (CSI) and parasympathetic cardiac vagal tone (CVT). High resolution structural magnetic resonance imaging scans were acquired, and differences in subcortical nuclei shape, that is, 'deformation', contingent on resting ANS activity were investigated. CSI positively correlated with outward deformation of the brainstem, right nucleus accumbens, right amygdala and bilateral pallidum (all thresholded to corrected P < 0.05). In contrast, parasympathetic CVT negatively correlated with inward deformation of the right amygdala and pallidum (all thresholded to corrected P < 0.05). Left and right putamen volume positively correlated with CVT (r = 0.62, P = 0.0047 and r = 0.59, P = 0.008, respectively), as did the brainstem (r = 0.46, P = 0.049). These data provide novel evidence that resting autonomic state is associated with differences in the shape and volume of subcortical nuclei. Thus, subcortical morphological brain differences in various disorders may partly be attributable to perturbation in autonomic function. Further work is warranted to investigate these findings in clinical populations. Hum Brain Mapp 39:381-392, 2018. © 2017 Wiley Periodicals, Inc.

Low cardiac vagal tone index by heart rate variability differentiates bipolar from major depression

Objectives: Major depressive disorder (MDD) and depression in bipolar disorder (BD) are often difficult to distinguish from each other. Autonomic nervous system (ANS) dysregulation is associated with various depressive symptoms and inflammatory response disinhibition. The beat-to-beat pattern of heart rate (heart rate variability, HRV) offers a non-invasive portal to ANS function and provides a reliable index of resting cardiac vagal tone. We quantified HRV and measured inflammatory biomarkers in MDD and BD patients in an effort to derive potential diagnostic criteria for MDD and BD.Methods: Sixty-four MDD and 37 BD patients were enrolled. HRV was assessed and blood was drawn at baseline after antidepressant washout and prior to study initiation. HRV was quantified and corrected for artefacts.Results: MDD subjects had significantly higher baseline respiratory sinus arrhythmia (P = 0.05) and LF-HRV (P < 0.01) in comparison to BD subjects. Compared to MDD subjects, BD subjects had significantly higher baseline levels of IL-10 (P < 0.01) and MCP-1 (P < 0.01). In the MDD group only, baseline LF-HRV was significantly positively correlated to baseline levels of IL-10 (r = 0.47, P < 0.01).Conclusions: Reduced vagal tone and higher levels of inflammatory biomarkers may distinguish BD from MDD and reveal an underlying pathophysiology of depression involving ANS dysfunction and chronic immune system dysregulation.

High vagally mediated resting-state heart rate variability is associated with superior action cascading

The neurovisceral integration model suggests that individual differences in heart rate variability (HRV), an index of vagal tone, may relate to prefrontal cortical activity and predict performance on cognitive control tasks. The aim of this study was to further verify this model by investigating the relationship between vagally-mediated resting-state HRV and action cascading, a crucial cognitive control function which refers to the ability to cope with multiple response options when confronted with various task goals. Resting-state HRV and performance on the stop-change paradigm, which provides a relatively well-established diagnostic measure of action cascading and response inhibition, was assessed in 88 healthy volunteers (age range 18–33). Compared to individuals with low resting-state HRV, participants with high resting-state HRV showed enhanced action cascading performance, both when a disruption (stopping) and change towards an alternative response were required simultaneously, and when requirements were cascaded (i.e. when the stopping process had already finished at the time the change was required). Our findings represent an important step towards extending our understanding of the neurovisceral integration model in cognitive control.

Abstract P204: Gender-specific Relationships Between Plasma Levels of Endocannabinoids and Vagal and Sympathetic Control of Heart Rate in Normotensive Obese Older Adults

Previous studies in obese individuals indicate higher circulating endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) than in lean counterparts. However, the association between plasma endocannabinoids and autonomic control of blood pressure and heart rate has not been assessed in obesity. In a sample of normotensive, obese older adults we analyzed plasma content of the endocannabinoids AEA and total AG using mass spectrometry and examined correlations with various indices of spontaneous sympathovagal activity. Spontaneous baroreflex sensitivity (BRS) for heart rate control was calculated by spectral analysis of arterial pressure (AP) time (Sequence [Seq] Up, Seq Down and Seq All) and frequency (low-frequency [LF] and high-frequency [HF] α) domains from continuous resting AP recordings. In addition, time domain analysis was used to calculate heart rate variability (HRV) and blood pressure variability, indices of cardiac vagal tone and vascular sympathetic tone, respectively. The sample included 8 males and 17 females with a mean age of 68.4 ± 0.6 years, a mean body mass index of 35.0 ± 0.8 kg/m 2 , and mean AP of 101.0 ± 2.2 mmHg. Across the complete sample, we report a significant inverse correlation between plasma AG content and HFα, an index of the vagally-mediated parasympathetic spontaneous BRS ( r = -0.50, P &lt; 0.05). We further report a significant inverse correlation between plasma AG and the vagal spontaneous BRS (Seq Up) in males ( r = -0.87, P &lt; 0.01) but not in females. However, in females but not males we found significant positive relationships between AEA and LFα, an index of sympathetic spontaneous BRS ( r = 0.49, P &lt; 0.05), and AEA and HRV ( r = 0.50, P &lt; 0.05). These results are consistent with a role for the endocannabinoid system to modulate autonomic control of the circulation in populations at risk for hypertension and cardiovascular disease, and suggest gender differences that have yet to be elucidated.

Respiratory sinus arrhythmia moderates the impact of maternal prenatal anxiety on infant negative affectivity

Maternal prenatal anxiety is associated with infants' temperamental negative affectivity (NA), but it is unclear to what extent children vary in their susceptibility to prenatal influences. We tested a hypothesis that infants' respiratory sinus arrhythmia (RSA), an index of parasympathetic vagal tone and a potential marker of differential susceptibility to environmental influences, moderates the effects of maternal prenatal anxiety on the development of infant NA. Prenatal anxiety was assessed during the last trimester of pregnancy in a low-risk community sample. Infant NA, baseline RSA, and maternal postnatal anxiety were assessed at 8-10 months of infant age. Regression analyses were performed to predict infant NA on the basis of prenatal anxiety, infant baseline RSA, and their interaction (N = 173). Maternal prenatal anxiety and infant RSA interactively predicted infant NA at 8-10 months. Among infants with high RSA, a significant positive association between prenatal anxiety and infant NA was observed, whereas prenatal anxiety did not predict infant NA among infants with low RSA. Vagal tone, as indexed by baseline RSA, may provide a promising marker of differential susceptibility to the long-term effects of varying intrauterine conditions.