Altered Autonomic Nervous System Research Articles

A sex-specific pathway linking early life maltreatment, vagal activity, and depressive symptoms

ABSTRACT Background: Experiences of early life maltreatment (ELM) are alarmingly common and represent a risk factor for the development of psychopathology, particularly depression. Research has focused on alterations in autonomic nervous system (ANS) functioning as a mediator of negative mental health outcomes associated with ELM. Early alterations in autonomic vagal activity (vmHRV) may moderate the relationship between ELM and depression, particularly when considering forms of emotional maltreatment. Recent evidence suggests that the relationships of both ELM and vmHRV with depression may be non-linear, particularly considering females. Objective: Building on and extending theoretical considerations and previous work, the present work aims to further the current understanding of the complex relationships between ELM exposure, vmHRV, and depression. Methods: This study uses an adaptive modelling approach, combining exploratory network-based analyses with linear and quadratic moderation analyses, drawing on a large sample of males and females across adolescence (total N = 213; outpatient at-risk sample and healthy controls) and adulthood (total N = 85; community-based convenience sample). Results: Exploratory network-based analyses reveal that exposure to emotional abuse is particularly central within a network of ELM subtypes, depressive symptoms, and concurrent vmHRV in both adolescents and adults. In adults, emotional neglect shows strong associations with both emotional abuse and vmHRV and is highly central as a network node, which is not observed in adolescents. Moderator analyses reveal significant interactions between emotional maltreatment and vmHRV predicting depressive symptoms in adult females. Significant quadratic relationships of emotional maltreatment and vmHRV with depression are observed in both adolescent and adult females. Conclusions: The present findings contribute to the understanding of the psychological and physiological mechanisms by which ELM acts as a risk factor for the development of depression. Ultimately, this will contribute to the development of targeted and effective intervention strategies to mitigate the detrimental effects of early adversity.

Pre-pregnancy BMI Association with Maternal Phenotype and Offspring Neurobehavioral Outcomes

BackgroundAllostatic load due to chronic exposure to physiological or psychological stressors lead to compromised capacity of the body to maintain homeostasis. Obesity as a metabolic stressor is associated with a suboptimal physiological milieu including an inflammatory state and a dysregulated stress axis. Perinatal maternal body mass index (BMI) impacts pregnancy, birth outcomes, and child metabolic and neurodevelopmental health. We examine the impacts of pre-pregnancy BMI on maternal phenotype characteristics throughout pregnancy and fetal heart rate measurements as an early marker of programming effects of altered autonomic nervous system and infant neurobehavioral outcomes with a focus on sex-dimorphic effects. MethodsPregnant women (n=176) attended sessions at gestation weeks 12-22, 23-28, and 34-36, where blood was collected for cytokine analysis and DNA methylation, and Edinburgh post-partum depression scale was administered. On the latter two visits, heart rate assessment was carried out for mothers and fetuses. ResultsMaternal high BMI was associated with higher perinatal depression, increased inflammation, and reduced heart rate variability. DNA methylation of maternal blood indicated enrichment in immune related biological processes. Moreover, we observed a decrease in fetal heart rate variability in female fetuses of women of high BMI, indicating alteration in the neurobehavioral development of the fetus. In infancy, female infants of high BMI mothers had reduced behavioral regulation and orientation to stimulus. ConclusionThis work highlights that the metabolic stress associated with BMI could leave a molecular fingerprint that could explain other maternal physiological and psychological outcomes, which in turn program the fetal neurodevelopmental outcomes.

Autonomic nervous system function before and after trauma-focused psychotherapy in youth with (partial) posttraumatic stress disorder

While trauma-focused psychotherapies have been shown effective in youth with PTSD, the relationship between treatment response and alterations in the autonomic nervous system (ANS) associated with PTSD, remains incompletely understood. During neutral and personalized trauma script imagery heart rate (HR), pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA) were recorded in youth aged 8–18 with PTSD or partial PTSD (n = 76) and trauma-exposed controls (TEC) (n = 27) to determine ANS activity and stress reactivity. Within the patient group, 77.6% met the full DSM-IV diagnostic criteria for PTSD, the remaining 22.4% met the criteria for partial PTSD. Youth with (partial) PTSD were subsequently treated with eight sessions of either trauma-focused cognitive behavioral therapy or eye movement desensitization and reprocessing. PTSD severity was assessed using the Clinician-Administered PTSD scale for Children and Adolescents to divide patients into responders and non-responders. Youth with (partial) PTSD relative to TEC had higher overall HR during both neutral and trauma imagery (p = .05). Youth with (partial) PTSD showed RSA decrease during trauma imagery relative to neutral imagery, the reverse of TEC (p = .01). Relative to non-responders, responders demonstrated a significant baseline to posttreatment increase of RSA response to stress only when employing a ≥ 50% response criterion (p = .05) and not with the primary ≥ 30% criterion (p = .12). Our results suggest overall higher HR and sympathetic nervous system activity as well as vagal withdrawal in response to stress in youth with (partial) PTSD and only provide partial support for normalization of the latter with successful trauma-focused psychotherapy.

3 The Relationship Between Depression, Anxiety, and Autonomic Dysfunction in de novo Parkinson’s Disease Patients Over Time

Objective:Autonomic dysfunction is an important non-motor symptom of Parkinson’s disease (PD), with point prevalence estimates of approximately 50-70%. Common presentations include cardiovascular dysregulation, gastrointestinal dysfunction, impaired thermoregulation, and sexual dysfunction. In the present study, we sought to examine whether autonomic symptoms would predict trajectories of change in depression and anxiety over a 5-year period in newly diagnosed individuals with PD. Given that alterations in autonomic nervous system functioning (e.g., reduced heart rate variability, lower autonomic arousal) are frequently observed in individuals who have anxiety and depression, as well as the negative influence these symptoms can have on quality of life/functioning, we predicted that greater autonomic symptoms would be related to increased mood symptoms over time.Participants and Methods:Participants included 414 individuals from the Parkinson’s Progression Markers Initiative, a prospective study of newly diagnosed and untreated individuals with PD. The PD participants (mean age=61.6+9.7, mean education=15.6+3.0, 92.5% non-Hispanic White) were followed annually for up to five years. Self-reported autonomic symptoms were measured using the Scales for Outcomes in Parkinson’s Disease-Autonomic Dysfunction (SCOPA-AUT), which consists of a total score and 6 subdomain scores (gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, sexual). Mood measures included the Geriatric Depression Scale (GDS) and State-Trait Anxiety Inventory (STAI). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III. Bootstrapped linear regressions were performed to evaluate the relationship between autonomic symptoms (subdomains) and mood using data from the last visit (year 5). For longitudinal analyses, bootstrapped multilevel modeling was used to examine a) changes in SCOPA-AUT total over time (unconditional growth model only) and b) the relationship between mood and SCOPA-AUT total score over time, controlling for age/sex and motor severity.Results:Autonomic symptoms explained 28.2% of the total variance in trait anxiety, with unique predictors of gastrointestinal (/3=.266, p<.001) and thermoregulatory (ß=.202, p=.004) symptoms. For depression, autonomic symptoms explained 27.9% of the total variance, with unique predictors of gastrointestinal (ß=.225, p=.012), thermoregulatory (ß=.178, p=.013), and cardiovascular (ß=.154, p=.012) symptoms. There was a gradual linear increase in total autonomic symptoms over time (b=0.86, p<.001). Greater total autonomic symptoms were associated with higher average trait anxiety (b=0.54, p<.001), slightly greater increase in trait anxiety over time (b=0.04, p<.05), and occasion-to-occasion fluctuations in trait anxiety (b=0.24, p<.001). Similarly, increased total autonomic symptoms were associated with higher average depressive symptoms (b=0.14, p<.001), minimally greater increase in depressive symptoms over time (b=0.01, p<.05), and occasion-to-occasion fluctuations in depressive symptoms (b=0.08, p<.001). Motor severity did not explain individual differences or trajectories of change in depression or trait anxiety.Conclusions:Autonomic symptoms, particularly gastrointestinal, cardiovascular, and thermoregulatory dysfunction, were related to increased mood symptoms in PD patients and predicted increases in depression/anxiety over time. Our findings do not distinguish between two theoretical possibilities - whether autonomic symptoms lead to depression/anxiety versus involvement of co-occurring neural systems underlying both. Regardless, our study highlights the importance of treating autonomic dysfunction in early PD, and future work should incorporate additional measures of autonomic dysfunction (e.g., physiological probes).

Autonomic cardiovascular control during exercise.

The cardiovascular response to exercise is largely determined by neurocirculatory control mechanisms that help to raise blood pressure and modulate vascular resistance which, in concert with regional vasodilatory mechanisms, promote blood flow to active muscle and organs. These neurocirculatory control mechanisms include a feedforward mechanism, known as central command, and three feedback mechanisms, namely, 1) the baroreflex, 2) the exercise pressor reflex, and 3) the arterial chemoreflex. The hemodynamic consequences of these control mechanisms result from their influence on the autonomic nervous system and subsequent alterations in cardiac output and vascular resistance. Although stimulation of the baroreflex inhibits sympathetic outflow and facilitates parasympathetic activity, central command, the exercise pressor reflex, and the arterial chemoreflex facilitate sympathetic activation and inhibit parasympathetic drive. Despite considerable understanding of the cardiovascular consequences of each of these mechanisms in isolation, the circulatory impact of their interaction, which occurs when various control systems are simultaneously activated (e.g., during exercise at altitude), has only recently been recognized. Although aging and cardiovascular disease (e.g., heart failure, hypertension) have both been recognized to alter the hemodynamic consequences of these regulatory systems, this review is limited to provide a brief overview on the action and interaction of neurocirculatory control mechanisms in health.

The Epigenetic Link of Perinatal BMI to Maternal Phenotype and Fetal Heart Rate

Obesity is a metabolic stressor associated with a suboptimal physiological milieu including an inflammatory state and a dysregulated stress axis. Perinatal maternal BMI impacts pregnancy and birth outcomes along with child metabolic and neurodevelopmental health that are believed to be mediated by epigenetic mechanisms. Our research examines the impacts of pre-pregnancy BMI in a cohort of healthy pregnancies (n=187); first, by characterizing maternal phenotype throughout pregnancy, including her stress physiology (diurnal salivary cortisol), inflammatory status (blood cytokine levels), perinatal depression (EPDS scores), and the underlying epigenetic signature (DNA methylation) in blood that could mediate these effects. Second, we examine the effects of pre-pregnancy BMI on fetal heart rate measurements as an early marker of programming effects of altered autonomic nervous system and the associated placental DNA methylation with a focus on sex-dimorphic effects. Finally, we explore the impact of increasing the allostatic load of high BMI with stress, which was phenotyped in women early in pregnancy driven by data with 27 variables assessing psychological and physical health, on differential placental DNA methylation. To date: regional analysis revealed about 4500 differentially methylated regions (DMR) overall in response to high BMI. Gene ontology enrichment analysis revealed that DM genes annotated to these DMRs were enriched for biological processes involving inflammation in males and RNA silencing in females. This work highlights that the metabolic stress associated with BMI could leave a molecular fingerprint that mediate other maternal physiological and psychological outcomes, which in turn program the fetal neurodevelopmental outcomes.

Oxytocin's Regulation of Thermogenesis May Be the Link to Prader-Willi Syndrome.

Prader-Willi Syndrome (PWS) is a genetic neurodevelopmental disorder that is caused by either the deletion of the paternal allele of 15q11-q13, maternal uniparental disomy of chromosome 15 or defects in the chromosome 15 imprinting centre and is characterized by cognitive impairment, hyperphagia and low metabolic rate with significant risk of obesity, as well as a variety of other maladaptive behaviours and autistic spectrum disorder (ASD). Many of the features seen in PWS are thought to be due to hypothalamic dysfunction resulting in hormonal abnormalities and impaired social functioning. The preponderance of evidence indicates that the Oxytocin system is dysregulated in PWS individuals and that this neuropeptide pathways may provide promising targets for therapeutic intervention although the process by which this dysregulation occurs in PWS awaits mechanistic investigation. PWS individuals present abnormalities in thermoregulation an impaired detection for temperature change and altered perception of pain indicating an altered autonomic nervous system. Recent studies indicate that Oxytocin is involved in thermoregulation and pain perception. This review will describe the update on PWS and the recent discoveries on Oxytocin regulation of thermogenesis together with the potential link between Oxytocin regulation of thermogenesis and PWS to create a new groundwork for the treatment of this condition.

Heart rate variability behavior in athletes after a sports concussion: A systematic review.

This systematic review aims to investigate the adaptations of the autonomic nervous system (ANS) after a concussion by measuring HRV in athletes over the age of 16 after injury. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Web of Science, Pubmed, SCOPUS, and Sport Discus were searched using predefined search terms to identify relevant original cross-sectional, longitudinal, and cohort epidemiological studies published before December 2021. After screening 1737 potential articles, four studies met the inclusion criteria. Studies included participants with concussion (n = 63) and healthy control athletes (n = 140) who practised different sports. Two studies describe a decrease in HRV following a sports concussion, and one proposed that the resolution of symptoms does not necessarily reflect ANS recovery. Lastly, one study concluded that submaximal exercise induces alteration in ANS, not seen in rest after an injury. In the frequency domain, a decrease in high frequency power and an increase of low frequency/high frequency ratio is expected, as the activity of the sympathetic nervous system increases, and the parasympathetic nervous system decreases after injury. In the frequency domain, heart rate variability (HRV) may help monitor the activity of ANS evaluating signals of somatic tissue distress and early identification of other types of musculoskeletal injuries. Further research should investigate the relationship between HRV and other musculoskeletal injuries.

Cardiac Vagal Regulation Is Impeded in Children With Cyclic Vomiting Syndrome.

The pathophysiology underlying cyclic vomiting syndrome (CVS) remains undefined. Scant data and distinct clinical features point to altered autonomic nervous system function. Autonomic signaling can be noninvasively assessed through cardiac indices of parasympathetic vagal regulation, which is reduced in children with disorders of gut-brain interaction. We aimed to examine dynamic cardiac vagal regulation in children with CVS compared with that in healthy controls (HC). A total of 31 children with CVS evaluated in a tertiary care CVS center and 66 HC (ages 8-18 years) underwent cardiac autonomic function assessment. Electrocardiogram recordings were conducted during 3-minute sit/stand/sit posture challenges. The electrocardiogram-derived variables heart period, respiratory sinus arrhythmia (RSA), and vagal efficiency (VE) were analyzed using linear regression and mixed-effects modeling. After exclusion of medication confounders, 23 patients with CVS were included in analyses. Both groups were comparable in age, gender, and body mass index. Compared with HC, children with CVS had shorter heart period (standardized mean difference range: 1.15-1.22, all P values < 0.05) and lower RSA (SMD range: 0.66-0.88, all P values < 0.05). Patients with CVS had significantly lower VE during the entire course of posture shifts, compared with HC ( B = -19.87, SE = 6.95, t = -2.86, P = 0.005, SMD = 0.76). Children with CVS have suboptimal parasympathetic autonomic regulation compared with HC, indexed by reduced RSA and VE, even during their interepisodic well phase. Abnormal vagal modulation may underlie CVS pathophysiology, comorbidities, and triggers. Assessing VE during posture stressors could inform therapeutic interventions.

The effects of a 3-day mountain bike cycling race on the autonomic nervous system (ANS) and heart rate variability in amateur cyclists: a prospective quantitative research design

BackgroundThe acute and chronic adaptation of endurance athletes’ hearts shows that increased volume of endurance exercise might cause an acute reduction in cardiac function, causing a physiological cascade that leads to the release of cardiac biomarkers specific to cardiomyocyte stress. Heart rate variability (HRV) is a valuable tool used as a physiological measurement to evaluate the autonomic nervous system (ANS). It is frequently used to assess cardiac autonomic regulation, determining a patient’s risk for unfavorable events. This study set out to determine the changes in the ANS by participating in a 3-day mountain bike cycling race in amateur cyclists using HRV as an outcome measure.MethodsSixteen healthy participants (male and female) participating in a 3-day mountain bike cycling race underwent five-minute resting electrocardiography recordings in a supine position 2 days before the race (baseline testing). In addition, HRV measurements were recorded after each race day and 24 h post-race (recovery).ResultsTime-domain and frequency-domain measures showed significant changes from baseline HRV parameters after each race day (p ≤ 0.05). In addition, our data revealed that the mean heart rate and R–R variability intervals did not return to baseline values after 24 h of recovery. Thus, autonomic nervous system (ANS) alterations may be due to changes in cardiac sympatho-vagal balance.ConclusionsThe main strength of this study is using HRV as a measuring and screening tool to assess cardiac autonomic activity, whereby the state of the ANS before and after endurance races can be measured. Thus, physicians, athletes, and coaches can determine the stress of endurance races on the ANS and plan recovery strategies. The reasoning is that if the ANS is in a state of sub-optimal function, susceptible amateur athletes might be at risk for a cardiovascular event or maladaptation due to the endurance race.

Altered Low Frequency Heart Rate Variability Associated with Agoraphobia in Panic Disorder: A Retrospective Study.

This study aimed to compare the clinical features of panic disorder (PD) with comorbid agoraphobia to those of PD alone. We focused on autonomic nervous system (ANS) alterations reflected in heart rate variability (HRV) and executive function deficits reflected in the Stroop test. We retrospectively compared psychometric features, Stroop test results, and resting-state HRV across three groups: a subclinical group with anxiety attack history, a PD group without agoraphobia, and a PD group with agoraphobia. The subclinical group included 10 male and 34 female, the PD without agoraphobia group included 17 male and 19 female, and the PD with agoraphobia group included 11 male and 18 female. The PD with agoraphobia group had higher Symptom Checklist-95 scores than the other groups. Both PD groups had longer reaction times in the Stroop test than the subclinical group. There were no significant differences in HRV parameters between the PD groups with and without agoraphobia. Compared with the subclinical group, the PD with agoraphobia group showed significantly lower values of the natural logarithm of low-frequency HRV. Our results do not support that executive function deficits and ANS alterations are more pronounced with comorbid agoraphobia among PD groups. However, PD with agoraphobia patients showed more complex and severe clinical symptoms in their self-reports. Compared with the subclinical group, PD patients with agoraphobia showed specific features in the natural logarithm of low-frequency HRV. Our findings suggest that agoraphobia comorbidity should be considered when evaluating or treating patients with PD.

Heart rate fragmentation as a marker of altered autonomic nervous system activity: A novel predictor of atrial fibrillation occurrence in the general population

Heart rate fragmentation as a marker of altered autonomic nervous system activity: A novel predictor of atrial fibrillation occurrence in the general population

Heart rate fragmentation as a marker of altered global autonomic nervous system activity: a novel predictor of atrial fibrillation occurrence in the general population

Abstract Background The dysfunction of the autonomic nervous system (ANS) plays an important role in the initiation and maintenance of atrial fibrillation (AF). However, the meaning of high heart rate variability (HRV) in predicting AF is still under debate due to conflicting results in population-based studies. Short-term HRV is conceptually attributed to vagal tone modulation. But recent data suggest that a component of short-term HRV, called heart rate fragmentation, is related to ANS breakdown. On the other hand, parasympathetic activity could be assess by a novel metric, the deceleration capacity (DC). Objective To assess predictive capacity of novel HRV-derived metrics, whether fragmentation indices or parameters of vagal tone, regarding the occurrence of AF in general population during long-term follow-up. Methods A cohort study was designed to prospectively assess the predictive value of ANS activity level among a healthy retired French population, regarding cardiovascular events and mortality. 1011 subjects aged 65 were enrolled in the study from 2000 to 2002. The enrolled population had no history of AF and a low cardiovascular risk. A median follow-up of 17.8 years (16.0–18.5) was managed. HRV data were acquired by 24-h Holter electrocardiogram (ECG) monitoring at baseline and assessed by frequency domain and time domain methods. Heart rate fragmentation using the percentage of inflection points (PIP), and assessment of specific parasympathetic activity using DC were then calculated. The study outcome was the onset of AF during follow-up, defined as a standard 12-lead ECG or Holter recording with ≥30 s of AF. Results AF was diagnosed in 123 patients along the 18-year follow-up, representing a cumulative incidence of 13.4%. Using univariate analysis (Figure 1A), a higher percentage of NN intervals that differ by more than 50 ms from the previous interval (pnn50) and root mean square differences of successive NN intervals (RMSSD) were associated with AF onset (p&amp;lt;0.01). A lower ratio of low-frequency and high-frequency component (LF/HF) was the only frequency-domain parameter found to predict the AF occurrence (p&amp;lt;0.01). The occurrence of AF was predicted by a higher PIP (p&amp;lt;0.01) and lower DC (p&amp;lt;0.01). Through multivariate analysis using clinical parameters that reached statistical significance in univariate analysis (Figure 1B), higher PIP was found as an independent predictor of AF occurrence (HR=2.1, 95% CI: 1.1–3.9, p=0.02), as well as male gender (HR=2.1, 95% CI: 1.1–3.9, p=0.02), and non-sustained supraventricular tachycardia (HR=2.1, 95% CI: 1.1–3.9, p=0.02). Conclusion (see Figure 2) Elevated PIP, a marker of heart rate fragmentation secondary to impaired ANS activity, is an independent predictor of the onset of AF in the healthy general population. Therefore, high HRV associated to AF occurrence could be the consequence of general ANS impairment rather than increased parasympathetic activity. Funding Acknowledgement Type of funding sources: None.

The Lack of Systemic and Subclinical Side Effects of Botulinum Neurotoxin Type-A in Patients Affected by Post-Stroke Spasticity: A Longitudinal Cohort Study.

Botulinum Neurotoxin type-A (BoNT-A) is the treatment of choice for focal post-stroke spasticity (PSS). Due to its mechanism of action and the administration method, some authors raised concern about its possible systemic diffusion leading to contralateral muscle weakness and autonomic nervous system (ANS) alterations. Stroke itself is a cause of motor disability and ANS impairment; therefore, it is mandatory to prevent any source of additional loss of strength and adjunctive ANS disturbance. We enrolled 15 hemiparetic stroke survivors affected by PSS already addressed to BoNT-A treatment. Contralateral handgrip strength and ANS parameters, such as heart rate variability, impedance cardiography values, and respiratory sinus arrythmia, were measured 24 h before (T0) and 10 days after (T1) the ultrasound (US)-guided BoNT-A injection. At T1, neither strength loss nor modification of the basal ANS patterns were found. These findings support recent literature about the safety profile of BoNT-A, endorsing the importance of the US guide for a precise targeting and the sparing of “critical” structures as vessels and nerves.

Autonomic Changes Are More Durable After Radiofrequency Than Pulsed Electric Field Pulmonary Vein Ablation.

Pulmonary vein isolation (PVI) by radiofrequency (RF) energy is associated with a collateral ganglionated plexi ablation. Pulsed electric field (PEF) is a nonthermal energy source that preferentially affects the myocardial cells and spares neural tissue. This study investigated whether PVI by a PEF compared with RF energy will result in less prominent alteration of the cardiac autonomic nervous system. A total of 31 patients with atrial fibrillation underwent PVI using a novel lattice-tip catheter and PEF energy (n=18) or a conventional irrigated-tip catheter and RF energy (n=13). The response of the sinoatrial node and atrioventricular node to extracardiac high-frequency, high-output, right vagal nerve stimulation was evaluated at baseline and during and at the end of the ablation procedure. Substantial reduction in responsiveness was arbitrarily defined as stimulation-inducible pause<1.5 seconds. Reduced response of the sinoatrial node was documented in 13 of 13 (100%) and 6 of 18 (33%) patients (P=0.0001) in RF and PEF groups, respectively. Reduced response of the atrioventricular node was found in 10 of 11 (93%) and 6 of 18 (33%) patients (P = 0.002) in RF and PEF groups, respectively. The major effects were observed predominantly during ablation around the right pulmonary veins. Early recovery of ganglionated plexi function was noticed only in the PEF ablation group. RF ablation resulted in higher acceleration of the sinus rhythm compared with PEF ablation (20 ± 13 beats/min vs 12 ± 10 beats/min; P = 0.04). PEF compared with RF energy used for PVI induces significantly weaker and less durable suppression of cardiac autonomic regulations.

Prenatal smoking and drinking are associated with altered newborn autonomic functions.

Prenatal smoking and drinking are associated with sudden infant death syndrome and neurodevelopmental disorders. Infants with these outcomes also have altered autonomic nervous system (ANS) regulation. We examined the effects of prenatal smoking and drinking on newborn ANS function. Pregnant women were enrolled in Northern Plains, USA (NP) and Cape Town (CT), South Africa. Daily drinking and weekly smoking data were collected prenatally. Physiological measures were obtained during sleep 12-96 h post-delivery. In all, 2913 infants from NP and 4072 from CT were included. In active sleep, newborns of mothers who smoked throughout pregnancy, compared to non-smokers, had higher breathing rates (2.2 breaths/min; 95% CI: 0.95, 3.49). Quit-early smoking was associated with reductions in beat-to-beat heart rate variability (HRV) in active (-0.08 s) and quiet sleep (-0.11 s) in CT. In girls, moderate-high continuous smoking was associated with increased systolic (3.0 mmHg, CI: 0.70, 5.24) and diastolic blood pressure (2.9 mmHg, CI: 0.72, 5.02). In quiet sleep, low-continuous drinking was associated with slower heart rate (-4.5 beat/min). In boys, low-continuous drinking was associated with a reduced ratio of low-to-high frequency HRV (-0.11, CI: -0.21, -0.02). These findings highlight potential ANS pathways through which prenatal drinking and smoking may contribute to neurodevelopment outcomes. In this prospective cohort study of 6985 mother-infant dyads prenatal drinking and smoking were associated with multiple ANS parameters. Smoking was associated with increased neonatal breathing rates among all infants, and heart rate variability (HRV) and blood pressure (BP) among girls. Drinking was associated with reductions in HR and BP among all newborns, and reductions in the ratio of low to-high frequency HRV among boys. These findings suggest that prenatal smoking and drinking alter newborn ANS which may presage future neurodevelopmental disorders.

Temporal Clustering of Skin Sympathetic Nerve Activity Bursts in Acute Myocardial Infarction Patients.

Backgrounds: Acute myocardial infarction (AMI) affects the autonomic nervous system (ANS) function. The aim of our study is to detect the particular patterns of ANS regulation in AMI. We hypothesize that altered ANS regulation in AMI patients causes synchronized neural discharge (clustering phenomenon) detected by non-invasive skin sympathetic nerve activity (SKNA).Methods: Forty subjects, including 20 AMI patients and 20 non-AMI controls, participated in the study. The wide-band bioelectrical signals (neuECG) were continuously recorded on the body surface for 5 min. SKNA was signal processed to depict the envelope of SKNA (eSKNA). By labeling the clusters, the AMI subjects were separated into non-AMI, non-cluster appearing (AMINCA), and cluster appearing (AMICA) groups.Results: The average eSKNA was significantly correlated with HRV low-frequency (LF) power (rho = −0.336) and high-frequency power (rho = −0.372). The cross-comparison results demonstrated that eSKNA is a valid surrogate marker to assess ANS in AMI patients. The frequency of cluster occurrence was 0.01–0.03 Hz and the amplitude was about 3 μV. The LF/HF ratio of AMICA (median: 1.877; Q1–Q3: 1.483–2.413) revealed significantly lower than AMINCA (median: 3.959; Q1–Q3: 1.840–6.562). The results suggest that the SKNA clustering is a unique temporal pattern of ANS synchronized discharge, which could indicate the lower sympathetic status (by HRV) in AMI patients.Conclusion: This is the first study to identify SKNA clustering phenomenon in AMI patients. Such a synchronized nerve discharge pattern could be detected with non-invasive SKNA signals. SKNA temporal clustering could be a novel biomarker to classify ANS regulation ability in AMI patients.Clinical and Translational Significance: SKNA is higher in AMI patients than in control and negatively correlates with parasympathetic parameters. SKNA clustering is associated with a lower LF/HF ratio that has been shown to correlate with sudden cardiac death in AMI. The lack of SKNA temporal clustering could indicate poor ANS regulation in AMI patients.

Heart Rate Variability and Inflammatory Stress Response in Young African American Men: Implications for Cardiovascular Risk.

Background: African American men have a disproportionately higher incidence of and suffer greater severity and earlier death from cardiovascular disease (CVD). A common feature of many diseases, which disproportionately afflict disadvantaged African Americans, is inflammation. In particular, inflammation plays a decisive role in the pathogenesis of CVD in that persistent inflammation contributes to plaque evolution and destabilization. Adverse childhood experiences increase the risk for adult inflammatory based disease, particularly cardiovascular disease. This inflammatory burden becomes evident during stressful events and may be related to alterations in autonomic nervous system (ANS) activity. We previously reported that African American men who experienced childhood adversity exhibited a greater inflammatory (IL-6) response to acute stress challenge (Trier Social Stress Test – TSST). The purpose of this study was to determine whether altered ANS activity, as measured by heart rate variability (HRV), contributes to a greater proinflammatory response to stress in those exposed to childhood adversity.Methods: Thirty-four African American adult males underwent the TSST while instrumented with Holter monitors to record continuous heart rate for HRV determination. HRV was calculated as the low frequency (LF) to high frequency (HF) heart rate ratio (LF/HF), with higher LF/HF ratios corresponding to higher sympathetic vs. parasympathetic activity. Salivary samples were collected pre- and post-TSST to measure the proinflammatory cytokine IL-6. Childhood adversity was assessed by the Childhood Trauma Questionnaire.Results: Hierarchical linear modeling demonstrated that higher levels of physical abuse were related to a steeper rise in LF/HF ratio during the TSST. Further, a higher LF/HF ratio, in combination with greater exposure to emotional and physical abuse was associated with a greater IL-6 response to the TSST.Conclusions: These findings suggest that adverse childhood experiences associate with an adult phenotype characterized by an altered ANS response to stress as well as a greater proinflammatory (IL-6) response to an acute stressor. Elevations in salivary inflammatory markers have been associated with increased CVD risk. In conclusion, these findings suggest a role for the ANS in the underlying neuro-biological processes whereby childhood adversity predisposes to a more intense inflammatory response to stressful challenge during adulthood.

Analysis of Fractal Correlation Properties of Heart Rate Variability during an Initial Session of Eccentric Cycling.

Eccentric cycling (ECC) has attracted attention as a method to improve muscle strength and aerobic fitness in populations unable to tolerate conventional methods. However, agreement on exercise prescription targets have been problematic. The current report is an initial exploration of a potentially useful tool, a nonlinear heart rate (HR) variability (HRV) index based on the short-term scaling exponent alpha1 of detrended fluctuation analysis (DFA a1), which has been previously shown to correspond to exercise intensity. Eleven male volunteers performed 45 min of concentric (CON) cycling and ECC separated by 1 month. Work rates were matched for HR (~50% of the maximal HR) during the first 5 min and remained stable thereafter. HRV, HR, oxygen consumption (VO2), and cycling power were monitored and evaluated at elapsed times of 10 (T10) and 45 (T45) minutes duration. HR significantly increased between ECC T10 and ECC T45 (p = 0.003, d = 1.485), while DFA a1 significantly decreased (p = 0.004, d = 1.087). During CON, HR significantly increased (p < 0.001 d = 1.570) without significant DFA a1 change (p = 0.48, d = 0.22). Significantly higher HR was observed at T45 in ECC than in CON (p = 0.047, d = 1.059). A session of unaccustomed ECC lead to decreased values of DFA a1 at T45 in comparison to that seen with CON at similar VO2. ECC lead to altered autonomic nervous system balance as reflected by the loss of correlation properties compared to CON.

Decreased Autonomic Reactivity and Psychiatric Comorbidities in Neurological Patients With Medically Unexplained Sensory Symptoms: A Case-Control Study

Up to 48% of patients with medically unexplained symptoms seen in neurological practice suffer from sensory symptoms, which could be of functional nature or secondary to psychiatric disorders. These patients show high medical care utilization causing elevated healthcare costs. Despite the high prevalence, little is known about clinical characteristics and pathophysiological mechanisms. For functional disorders such as irritable bowel syndrome, a reduction of heart rate variability (HRV) has been shown, suggesting a dysfunction of the autonomic nervous system (ANS). The aim of this study was to investigate psychological data and functional changes of the ANS in patients with medically unexplained sensory symptoms (MUSS). In this exploratory pilot study, 16 patients (11 females, 31.6 ± 11.9 years) with MUSS, who were recruited at a single tertiary neurological center, underwent a structured clinical interview (SCID) to evaluate psychiatric comorbidities. Patients and age- and sex-matched healthy volunteers filled in questionnaires, and individual sensory thresholds (perception, pain) were detected by quantitative sensory testing (QST). HRV was assessed at baseline and under three different experimental conditions (tonic pain stimulus, placebo application, cold-face test). All tests were repeated after 6–8 weeks. SCID interviews revealed clinical or subclinical diagnoses of psychiatric comorbidities for 12 patients. Questionnaires assessing somatization, depression, anxiety, and perceived stress significantly discriminated between patients with MUSS and healthy controls. While there was no difference in QST, reduced ANS reactivity was found in patients during experimental conditions, particularly with regard to vagally mediated HRV. Our pilot study of neurological patients with MUSS reveals a high prevalence of psychiatric comorbidities and provides evidence for altered ANS function. Our data thus give insight in possible underlying mechanisms for these symptoms and may open the door for a better diagnostic and therapeutic approach for these patients in the future.