Vagal Control Research Articles

Luminal Chemoreceptors and Intrinsic Nerves: Key Modulators of Digestive Motor Function.

This chapter reviews data on the pathways by which luminal, mainly duodenal, chemoreceptors modulate gastro-pyloro-duodenal motor function to control emptying of nutrients into the small intestine. The vagus mediates proximal gastric relaxation caused by nutrient stimulation of duodenal/jejunal mucosal chemoreceptors. Modulation of the spatial patterning and inhibition of antral contractions during duodenal chemoreceptor activation are somewhat conflicting: both vagal control and ascending intramural nerves appear to play a role. Intraduodenal nutrients stimulate the localized pyloric contractions that prevent transpyloric flow via ascending duodenal intramural nerve pathways. Though not yet formally investigated, patterns of activation of the duodenal brake motor mechanism suggest that duodenal loop mucosal chemoreceptors signal to a brake mechanism at the most aborad region of the duodenum via descending intramural duodenal nerves.Intrinsic intramural pathways are important in the control of the first stages of digestion.

Cardiac vagal control among migrants: Associations with mainstream acculturation and perceived ethnic discrimination.

This cross-sectional study examines associations between cardiac vagal control and mainstream acculturation by systematically investigating the independent contributions of resting, reactivity, and recovery Respiratory Sinus Arrhythmia (RSA)-physiological factors contributing to adaptive functioning, including social engagement capacity. This study also examines the moderating role of RSA reactivity in associations between perceived ethnic discrimination and mainstream acculturation. The sample comprised 111 migrants from Maghreb (Morocco, Algeria, and Tunisia) to Montreal, QC, Canada. On average, participants (60 women) were 31 years old and had immigrated 7 years prior to the study. The study design was cross-sectional. We collected both psychophysiological (electrocardiogram) and self-report questionnaire data. All three facets of cardiac vagal control are independently associated with mainstream acculturation: Higher mainstream acculturation was associated with higher resting RSA (β = .24), lower RSA reactivity (β = -.27), and higher recovery RSA (β = .26), controlling for several theoretically relevant covariates. Furthermore, lower RSA reactivity to a discrimination-recall task dampened the relation between perceived discrimination and mainstream acculturation (interaction β = -.20). This study replicates and extends prior work linking RSA and mainstream acculturation using a sample of racialized and marginalized migrants. It provides evidence that RSA is related to migrants' adoption of the mainstream culture and may modulate how they handle perceived ethnic discrimination. Thus, this study also provides evidence that RSA is tied to how individuals successfully navigate novel social environments, including novel cultural contexts. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cervical Spinal Cord Transection (SCT) Increases Gastric Compliance in Anesthetized Rats

Abstract Spinal cord injury (SCI) can markedly alter the autonomic nervous system’s functions. It immediately causes autonomic and somatic hypo- or arreflexia, a state known as spinal shock. SCI determines the enhancement of two gastric reflexes that appear in normal conditions: the receptive and adaptative reflexes. Furthermore, this study also tried to evaluate the causes that led to such modifications: either vagal control, nitric oxide (NO)-pathways or intestine-intestinal reflexes. Male Wistar rats (N=25) were subjected to laminectomy (Sham group) or laminectomy + complete Spinal Cord Transection (SCT), between C7 and T1 vertebrae under anesthesia (SCT group). Before the surgery, the rats had water and food ad libitum; after the surgery, rats were fasted for 24 hours, still having access to water. The next day, all animals were subjected to a catheterism of their right carotid artery, a tracheostomy and a flexible balloon introduction down to the stomach’s fundix region, also under anesthesia. Rats were connected to a Power-Lab® system, via a pressure transducer (in order to measure the arterial pressure – MAP - and the heart rate - HR), and to a modified Plethysmometer (in order to measure the fundical gastric volume - GV variation). Vagal control was studied via cervical vagotomy; NO-mediation - via NO synthesis inhibitors (L-NAME); intestinointestinal reflexes - by using laxatives (Lactulone). Statistical analysis revealed, in some cases, that GV is significantly (p<0.05) augmented in SCT rats (2,4±0,09; 3,1±0,05; 3,7±0,06 ml) than in Sham (2,2±0,12; 2,9±0,12; 3,3±0,15 ml). Nevertheless, MAP and HR, were subsequently lower (p<0.05) in SCT (63,5±21,1mm Hg; 227,1±25,2 BPM) than in the control group (88,2±14,4mm Hg; 427,0±19,2 BPM). In summary, the increase of GV in SCT, seems to involve vagal pathways and/or NO-mediation, but still not neglecting the colic-gastric reflexes.

Supplemental Material for Cardiac Vagal Control Among Migrants: Associations With Mainstream Acculturation and Perceived Ethnic Discrimination

Supplemental Material for Cardiac Vagal Control Among Migrants: Associations With Mainstream Acculturation and Perceived Ethnic Discrimination

Echo state network models for nonlinear Granger causality.

While Granger causality (GC) has been often employed in network neuroscience, most GC applications are based on linear multivariate autoregressive (MVAR) models. However, real-life systems like biological networks exhibit notable nonlinear behaviour, hence undermining the validity of MVAR-based GC (MVAR-GC). Most nonlinear GC estimators only cater for additive nonlinearities or, alternatively, are based on recurrent neural networks or long short-term memory networks, which present considerable training difficulties and tailoring needs. We reformulate the GC framework in terms of echo-state networks-based models for arbitrarily complex networks, and characterize its ability to capture nonlinear causal relations in a network of noisy Duffing oscillators, showing a net advantage of echo state GC (ES-GC) in detecting nonlinear, causal links. We then explore the structure of ES-GC networks in the human brain employing functional MRI data from 1003 healthy subjects drawn from the human connectome project, demonstrating the existence of previously unknown directed within-brain interactions. In addition, we examine joint brain-heart signals in 15 subjects where we explore directed interaction between brain networks and central vagal cardiac control in order to investigate the so-called central autonomic network in a causal manner. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Optimizing phase variability threshold for automated synchrogram analysis of cardiorespiratory interactions in amateur cyclists.

We propose a procedure suitable for automated synchrogram analysis for setting the threshold below which phase variability between two marker event series is of such a negligible amount that the null hypothesis of phase desynchronization can be rejected. The procedure exploits the principle of maximizing the likelihood of detecting phase synchronization epochs and it is grounded on a surrogate data approach testing the null hypothesis of phase uncoupling. The approach was applied to assess cardiorespiratory phase interactions between heartbeat and inspiratory onset in amateur cyclists before and after 11-week inspiratory muscle training (IMT) at different intensities and compared to a more traditional approach to set phase variability threshold. The proposed procedure was able to detect the decrease in cardiorespiratory phase locking strength during vagal withdrawal induced by the modification of posture from supine to standing. IMT had very limited effects on cardiorespiratory phase synchronization strength and this result held regardless of the training intensity. In amateur athletes training, the inspiratory muscles did not limit the decrease in cardiorespiratory phase synchronization observed in the upright position as a likely consequence of the modest impact of this respiratory exercise, regardless of its intensity, on cardiac vagal control. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Social affiliation moderates the link between depressive symptoms and heart rate variability in healthy middle‐aged and older individuals: An intensive ecologic momentary assessment study

Depressive symptoms have been associated with lower cardiac autonomic control, thus contributing to cardiovascular diseases, especially among older adults. Interpersonal factors have been found to attenuate physiologic stress responses, but little is known about whether these factors (e.g., perceived affiliation) would moderate the relation of depressive symptoms and cardiovascular activation. The present research aimed to investigate the interplay of depressive symptoms and momentary-assessed interpersonal perceptions on cardiac vagal tone as indexed by heart rate variability (HRV). The sample consisted of 78 late middle-aged and older community-dwelling participants (48.7% male, mean age = 59.15years). Participants reported on depressive symptoms and other personal characteristics by questionnaire. Perceptions of interpersonal affiliation, ambulatory HRV, and contextual variables were recorded using ecologic momentary assessment and portable electrocardiogram (ECG) monitoring device throughout 1week (with a maximum of seven times daily). Multilevel analyses found that depressive symptoms were correlated with lower HRV, whereas momentary interpersonal perceptions of higher affiliation were associated with elevated HRV. A significant association was revealed between depressive symptoms and momentary affiliation perceptions on HRV. When individuals were involved in social interactions with higher affiliation, the effect of depressive symptoms on reducing HRV was attenuated. These findings suggested that the effects of subthreshold depressive symptoms on vagal control of the heart could be altered by the quality of interpersonal experiences.

Heart rate variability and delirium in acute non-cardioembolic stroke: a prospective, cross-sectional, cohort study

ObjectivesDelirium is an acute fluctuating disorder of attention and awareness. It is associated with autonomic dysfunction and increased mortality. The primary endpoint of our study was to measure autonomic activity in acute stroke patients, by means of heart rate variability analysis, in order to identify autonomic modifications that can predispose to delirium.MethodsPatients were consecutively enrolled from the stroke unit. Inclusion criteria were age ≥ 18 years and diagnosis of stroke with onset within the previous 72 h confirmed by neuroimaging. Exclusion criteria were atrial fibrillation, congestive heart failure, and conditions requiring intensive care unit. Patients were evaluated by means of Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-Intensive Care Unit (CAM-ICU) at baseline, after 72 h, or when symptoms suggesting delirium occurred. For each patient, ECG was recorded at baseline assessment and HRV analysis was conducted on five consecutive minutes of artifact-free ECG traces.ResultsFifty-six ECGs were available for analysis. During the study period, 11 patients developed delirium. Patients with and without delirium did not differ for sex, age, severity of stroke, and comorbidities. The delirium group had greater standard deviation of the heart rate (DLR − :9.16 ± 8.28; DLR + : 14.36 ± 5.55; p = 0.026) and lower power spectral density of the HF component (DLR − : 38.23 ± 19.23 n.u.; DLR + : 25.75 ± 8.77 n.u.; p = 0.031).ConclusionsAcute non-cardioembolic stroke patients with increased variability of heart rate and decreased vagal control are at risk for delirium.

Heart rate variability improves in 3-5-year-old children following a 6-month physical activity-based intervention: the Active Early Learning (AEL) cluster randomised controlled trial.

Heart rate variability (HRV) measurement provides non-invasive assessment of autonomic stability and cardiometabolic disease risk. Insufficient physical activity in early childhood may contribute to negative cardiometabolic health. The Active Early Learning (AEL) study was a 6-month randomised controlled trial investigating the effects of a physical activity-based program incorporating movement within the daily curriculum of preschool children. The current study assessed the effects of the AEL intervention on HRV as a measure of cardiac vagal control. Children aged between 3-5years and enrolled in a preschool with an attendance of ≥15 children were eligible. Physical activity was recorded using an Actigraph wGT3x accelerometer worn at the waist of participants over 3 consecutive days. A Polar H10 chest strap measured HRV with the HF-band and RMSSD representing cardiac vagal control. After 6months of the AEL trial, linear mixed model analyses revealed a significant intervention effect for increased HF (p = 0.044). The control group did not demonstrate changes in cardiac vagal control after the intervention ceased. Independent of age, sex, physical activity and BMI, the AEL study elicited significant improvements in the cardiac vagal control of participants who received the intervention. Findings highlight the importance of investigating HRV for assessing the cardiometabolic health in young children. ANZCTR trial registration number: ACTRN12619000638134. Novelty: The AEL curriculum improved child HRV independent of age, sex, physical activity and BMI. Heart rate and RR intervals did not demonstrate changes for the intervention and control groups. Multivariate programs for developing physical competence, confidence, knowledge and motivation may improve child health.

Reduced Cell Excitability of Cardiac Postganglionic Parasympathetic Neurons Correlates With Myocardial Infarction-Induced Fatal Ventricular Arrhythmias in Type 2 Diabetes Mellitus

ObjectiveWithdrawal of cardiac vagal activity is considered as one of the important triggers for acute myocardial infarction (MI)-induced ventricular arrhythmias in type 2 diabetes mellitus (T2DM). Our previous study demonstrated that cell excitability of cardiac parasympathetic postganglionic (CPP) neurons was reduced in T2DM rats. This study investigated whether cell excitability of CPP neurons is associated with cardiac vagal activity and MI-induced ventricular arrhythmias in T2DM rats.MethodsRat T2DM was induced by a high-fat diet plus streptozotocin injection. MI-evoked ventricular arrhythmia was achieved by surgical ligation of the left anterior descending coronary artery. Twenty-four-hour, continuous ECG recording was used to quantify ventricular arrhythmic events and heart rate variability (HRV) in conscious rats. The power spectral analysis of HRV was used to evaluate autonomic function. Cell excitability of CPP neurons was measured by the whole-cell patch-clamp technique.ResultsTwenty-four-hour ECG data demonstrated that MI-evoked fatal ventricular arrhythmias are more severe in T2DM rats than that in sham rats. In addition, the Kaplan-Meier analysis demonstrated that the survival rate over 2 weeks after MI is significantly lower in T2DM rats (15% in T2DM+MI) compared to sham rats (75% in sham+MI). The susceptibility to ventricular tachyarrhythmia elicited by programmed electrical stimulation was higher in anesthetized T2DM+MI rats than that in rats with MI or T2DM alone (7.0 ± 0.58 in T2DM+MI group vs. 3.5 ± 0.76 in sham+MI). Moreover, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP) and the maximum rate of increase of left ventricular pressure (LV dP/dtmax) in response to vagal efferent nerve stimulation were blunted in T2DM rats. Furthermore, T2DM increased heterogeneity of ventricular electrical activities and reduced cardiac parasympathetic activity and cell excitability of CPP neurons (current threshold-inducing action potentials being 62 ± 3.3 pA in T2DM rats without MI vs. 27 ± 1.9 pA in sham rats without MI). However, MI did not alter vagal control of the ventricular function and CPP neuronal excitability, although it also induced cardiac autonomic dysfunction and enhanced heterogeneity of ventricular electrical activities.ConclusionThe reduction of CPP neuron excitability is involved in decreased cardiac vagal function, including cardiac parasympathetic activity and vagal control of ventricular function, which is associated with MI-induced high mortality and malignant ventricular arrhythmias in T2DM.

A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system

SummaryWe developed a spatially-tracked single neuron transcriptomics map of an intrinsic cardiac ganglion, the right atrial ganglionic plexus (RAGP) that is a critical mediator of sinoatrial node (SAN) activity. This 3D representation of RAGP used neuronal tracing to extensively map the spatial distribution of the subset of neurons that project to the SAN. RNA-seq of laser capture microdissected neurons revealed a distinct composition of RAGP neurons compared to the central nervous system and a surprising finding that cholinergic and catecholaminergic markers are coexpressed, suggesting multipotential phenotypes that can drive neuroplasticity within RAGP. High-throughput qPCR of hundreds of laser capture microdissected single neurons confirmed these findings and revealed a high dimensionality of neuromodulatory factors that contribute to dynamic control of the heart. Neuropeptide-receptor coexpression analysis revealed a combinatorial paracrine neuromodulatory network within RAGP informing follow-on studies on the vagal control of RAGP to regulate cardiac function in health and disease.

Exploring autonomic regulation in children with ADHD with and without comorbid anxiety disorder through three systematic levels of cardiac vagal control analysis: Rest, reactivity, and recovery.

Autonomic nervous system (ANS) dysregulation, characterized by reduced vagally mediated Heart Rate Variability (HRV), has been associated with Attention-Deficit/ Hyperactivity Disorder (ADHD). This study investigated the dynamic vagal modulation of cardiac output in response to shifts in environmental demands in children and adolescents with ADHD, with and without a comorbid anxiety disorder. High-frequency HRV (HF-HRV) measures were obtained from 46 children and adolescents ranging from 6 to 17 (M=9.38; SD = 2.31) years old, during three successive experimental conditions: a baseline recording followed by a sustained attention task, and a post-task recovery period. Findings support the reliability of the d2 Test, a cancelation test of attention and concentration, to induce parasympathetic withdrawal and extend prior work on "vagal flexibility". Further, these findings suggest a pattern of group differences in ANS functioning in children with ADHD, with and without a comorbid anxiety disorder. Only the ADHD without comorbid anxiety group showed a normative autonomic response to the cognitive challenge (reduced HF-HRV). The participants did not display an adaptive process of restoration following the cognitive challenge; the HRV suppression was prolonged during post-task recovery period, suggesting that ANS responded as if the cognitive stressor was still present. The current paper covers and discusses theoretical implications for the abnormalities in neurophysiological functioning and the different physiological responses in the two ADHD subtypes.

Cardiac vagal tone: a neurophysiological mechanism that evolved in mammals to dampen threat reactions and promote sociality.

Cardiac vagal tone: a neurophysiological mechanism that evolved in mammals to dampen threat reactions and promote sociality.

Peripheral Vascular Abnormalities in Anorexia Nervosa: A Psycho-Neuro-Immune-Metabolic Connection.

Immune, neuroendocrine, and autonomic nervous system dysregulation in anorexia nervosa lead to cardiovascular complications that can potentially result in increased morbidity and mortality. It is suggested that a complex non-invasive assessment of cardiovascular autonomic regulation—cardiac vagal control, sympathetic vascular activity, and cardiovascular reflex control—could represent a promising tool for early diagnosis, personalized therapy, and monitoring of therapeutic interventions in anorexia nervosa particularly at a vulnerable adolescent age. In this view, we recommend to consider in the diagnostic route, at least in the subset of patients with peripheral microvascular symptoms, a nailfold video-capillaroscopy as an easy not invasive tool for the early assessing of possible cardiovascular involvement.

DMV extrasynaptic NMDA receptors regulate caloric intake in rats.

Acute high-fat diet (aHFD) exposure induces a brief period of hyperphagia before caloric balance is restored. Previous studies have demonstrated that this period of regulation is associated with activation of synaptic N-methyl-D-aspartate (NMDA) receptors on dorsal motor nucleus of the vagus (DMV) neurons, which increases vagal control of gastric functions. Our aim was to test the hypothesis that activation of DMV synaptic NMDA receptors occurs subsequent to activation of extrasynaptic NMDA receptors. Sprague-Dawley rats were fed a control or high-fat diet for 3–5 days prior to experimentation. Whole-cell patch-clamp recordings from gastric-projecting DMV neurons; in vivo recordings of gastric motility, tone, compliance, and emptying; and food intake studies were used to assess the effects of NMDA receptor antagonism on caloric regulation. After aHFD exposure, inhibition of extrasynaptic NMDA receptors prevented the synaptic NMDA receptor–mediated increase in glutamatergic transmission to DMV neurons, as well as the increase in gastric tone and motility, while chronic extrasynaptic NMDA receptor inhibition attenuated the regulation of caloric intake. After aHFD exposure, the regulation of food intake involved synaptic NMDA receptor–mediated currents, which occurred in response to extrasynaptic NMDA receptor activation. Understanding these events may provide a mechanistic basis for hyperphagia and may identify novel therapeutic targets for the treatment of obesity.

Effects of the cold face test on heart rate variability in students

The purpose of this study was to determine the effects of the cold pressor test on heart rate variability in students. Sixty five students with a mean age of 20.61±0.13 years take part in the study (86% women, 14% men). They were studied in the morning hours in a quiet room at a comfortable temperature. Time domain (SDNN, RMSSD, pNN50), frequency domain (TP, HF, VLF, LF and LF/HF ratio) and nonlinear (SD1, SD2, ApEn, SampEn, D2, DFA1, DFA2) parameters of HRV were obtained from all participants for 5 minutes before and 5 minutes during cold face test (0–1 °C cold compresses) in a supine position. Statistical analysis was performed using Mann-Whitney test. Heart rate during cold face test was significantly lower than that during rest period (74.03±1.26 vs 76.74±1.21 beat/min, p=0.006). Time domain parameters were found to be higher during cold face test than that during rest (SDNN: 52.6±2.85 vs 43,61±2,23 ms, p=0.006; RMSSD: 59.87±4.08 vs 44.99±2.93 ms, p=0.001 and pNN50: 30.49±2.38 vs 22.07±2.13 %, p=0.003). There was no differences during cold face test period and rest period in TP (2517.24±301.8 vs 2097.89±249.98 ms2, p=0.456; VLF: 92.44±12.21 vs 83.59±9.99 ms2, p=0.452; LF: 1024.98±132.06 vs 932.86±107.70 ms2, p=0.896. High frequency parameter was significantly higher during cold face test than that during rest (1395.36±184.39 vs 1078.11±143.13 ms2, p=0.013). Nonlinear measures were significantly higher during cold face test than that during rest (SD1: 42.39±2.89 vs 31.83±2.07 ms, p=0.001; SD2: 60.52±3.04 vs 52.45±2.50 ms, p=0.025). ApEn and D1 were significantly lower during cold face test than that during rest (respectively, 1.15±0.01 vs 1.40±0.01 and 0.87±0.03 vs 1.01±0.02, p<0.001). The other HRV parameters including D2, LF/HF ratio, pLF, pHF, SampEn, DFA2 were not significantly different. These results suggest that cold face test has been associated with increased vagal cardiac control and decrease entropy and D1.

Ivabradine augments high-frequency dynamic gain of the heart rate response to low- and moderate-intensity vagal nerve stimulation under β-blockade.

Our previous study indicated that intravenously administered ivabradine (IVA) augmented the dynamic heart rate (HR) response to moderate-intensity vagal nerve stimulation (VNS). Considering an accentuated antagonism, the results were somewhat paradoxical; i.e., the accentuated antagonism indicates that an activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels via the accumulation of intracellular cyclic adenosine monophosphate (cAMP) augments the HR response to VNS, whereas the inhibition of HCN channels by IVA also augmented the HR response to VNS. To remove the possible influence from the accentuated antagonism, we examined the effects of IVA on the dynamic vagal control of HR under β-blockade. In anesthetized rats (n = 7), the right vagal nerve was stimulated for 10 min according to binary white noise signals between 0 and 10 Hz (V0-10), between 0 and 20 Hz (V0-20), and between 0 and 40 Hz (V0-40). The transfer function from VNS to HR was estimated. Under β-blockade (propranolol, 2 mg/kg iv), IVA (2 mg/kg iv) did not augment the asymptotic low-frequency gain but increased the asymptotic high-frequency gain in V0-10 (0.53 ± 0.10 vs. 1.74 ± 0.40 beats/min/Hz, P < 0.01) and V0-20 (0.79 ± 0.14 vs. 2.06 ± 0.47 beats/min/Hz, P < 0.001). These changes, which were observed under a minimal influence from sympathetic background tone, may reflect an increased contribution of the acetylcholine-sensitive potassium channel (IK,ACh) pathway after IVA, because the HR control via the IK,ACh pathway is faster and acts in the frequency range higher than the cAMP-mediated pathway.NEW & NOTEWORTHY Since ivabradine (IVA) inhibits hyperpolarization-activated cyclic nucleotide-gated channels, interactions among the sympathetic effect, vagal effect, and IVA can occur in the control of heart rate (HR). To remove the sympathetic effect, we estimated the transfer function from vagal nerve stimulation to HR under β-blockade in anesthetized rats. IVA augmented the high-frequency dynamic gain during low- and moderate-intensity vagal nerve stimulation. Untethering the hyperpolarizing effect of acetylcholine-sensitive potassium channels after IVA may be a possible underlying mechanism.

Hydrogel-based electrodes for selective cervical vagus nerve stimulation

Objective. Electrical vagus nerve stimulation (VNS) has the potential to treat a wide variety of diseases by modulating afferent and efferent communication to the heart, lungs, esophagus, stomach, and intestines. Although distal vagal nerve branches, close to end organs, could provide a selective therapeutic approach, these locations are often surgically inaccessible. In contrast, the cervical vagus nerve has been targeted for decades using surgically implantable helix electrodes to treat epileptic seizures and depression; however, to date, clinical implementation of VNS has relied on an electrode with contacts that fully wrap around the nerve, producing non-selective activation of the entire nerve. Here we demonstrate selective cervical VNS using cuff electrodes with multiple contacts around the nerve circumference to target different functional pathways. Approach. These flexible probes were adjusted to the diameter of the nerve using an adhesive hydrogel wrap to create a robust electrode interface. Our approach was verified in a rat model by demonstrating that cervical VNS produces neural activity in the abdominal vagus nerve while limiting effects on the cardiovascular system (i.e. changes in heart rate or blood pressure). Main results. This study demonstrates the potential for selective cervical VNS as a therapeutic approach for modulating distal nerve branches while reducing off target effects. Significance. This methodology could potentially be refined to treat gastrointestinal, metabolic, inflammatory, cardiovascular, and respiratory diseases amenable to vagal neuromodulatory control.

Vagal control of the heart decreases during increasing imminence of interoceptive threat in patients with panic disorder and agoraphobia

Theoretically, panic disorder and agoraphobia pathology can be conceptualized as a cascade of dynamically changing defensive responses to threat cues from inside the body. Guided by this trans-diagnostic model we tested the interaction between defensive activation and vagal control as a marker of prefrontal inhibition of subcortical defensive activation. We investigated ultra-short-term changes of vagally controlled high frequency heart rate variability (HRV) during a standardized threat challenge (entrapment) in n = 232 patients with panic disorder and agoraphobia, and its interaction with various indices of defensive activation. We found a strong inverse relationship between HRV and heart rate during threat, which was stronger at the beginning of exposure. Patients with a strong increase in heart rate showed a deactivation of prefrontal vagal control while patients showing less heart rate acceleration showed an increase in vagal control. Moreover, vagal control collapsed in case of imminent threat, i.e., when body symptoms increase and seem to get out of control. In these cases of defensive action patients either fled from the situation or experienced a panic attack. Active avoidance, panic attacks, and increased sympathetic arousal are associated with an inability to maintain vagal control over the heart suggesting that teaching such regulation strategies during exposure treatment might be helpful to keep prefrontal control, particularly during the transition zone from post-encounter to circa strike defense.Trial Registration Number: ISRCTN80046034.

Cardiac vagal control in response to acute stress during pregnancy: Associations with life stress and emotional support.

Life stressors during pregnancy can disrupt maternal stress regulation and negatively impact offspring health. Despite the important role of cardiac vagal control (e.g., heart rate variability; HRV) in stress regulation, few studies have investigated how life stressors and emotional support influence vagal control during pregnancy. This study aimed to (a) characterize patterns of cardiac vagal control in response to a stressor administered in pregnancy, and (b) examine the effects of life stress and emotional support on vagal control during rest, reactivity, and recovery. Participants included 191 pregnant women (79% Black; 21% White) living in an urban U.S. city (73% receiving public assistance). Heart rate (HR) and HRV (indexed by RMSSD) were recorded continually during the preparation, task, and recovery periods of the Trier Social Stress Test (TSST). Participants reported recent life stressors (e.g., relationship problems, financial hardship) and emotional support. Piecewise growth curve modeling was used to model rates of reactivity and recovery, adjusting for gestational age at time of assessment and recent health problems. Life stress predicted greater HR and HRV reactivity to the TSST as well as greater HRV recovery (vagal rebound). However, associations were only evident for women reporting high emotional support. Results suggest that pregnant women living with frequent life stressors may exhibit more rapid autonomic responses to acute stress, including more rapid vagal rebound after stressors, potentially reflecting physiological adaptation to anticipated high-stress environments; emotional support may enhance these responses. Studies are needed to investigate long-term health outcomes related to this stress response pattern.