Understanding irritability through the lens of self-regulatory control processes in children and adolescents: a systematic review.

Among youths, pathological irritability is highly prevalent and severely disabling. As a frequent symptom, it often leads to referrals to child and adolescent mental health services. Self-regulatory control (SRC) processes are a set of socio-psycho-physiological processes that allow individuals to adapt to their ever-changing environments. This conceptual framework may enhance the current understanding of the cognitive, emotional, behavioural and social dysregulations underlying irritability. The present systematic review (PROSPERO registration: #CRD42022370390) aims to synthesize existing studies that examine irritability through the lens of SRC processes among youths (< 18 years of age). We conducted a comprehensive literature search among six bibliographic databases: Embase.com, Medline ALL Ovid, APA PsycInfo Ovid, Web of Science Core Collection, the Cochrane Database of Systematic Reviews Wiley and ProQuest Dissertations & Theses A&I. Additional searches were performed using citation tracing strategies. The retrieved reports totalled 2612, of which we included 82 (i.e., articles) from 74 studies. More than 85% of reports were published during the last 6 years, highlighting the topicality of this work. The studies sampled n = 26,764 participants (n = 12,384 girls and n = 12,905 boys, n = 1475 no information) with an average age of 8.08 years (SD = 5.26). The included reports suggest that irritability has an association with lower effortful control, lower cognitive control and delay intolerance. Further, evidence indicates both cross-sectional and longitudinal associations between irritability and a lack of regulation skills for positive and negative emotions, particularly anger. Physiological regulation seems to moderate the association between irritability and psychopathology. Finally, the mutual influence between a child's irritability and parenting practice has been established in several studies. This review uses the lens of SRC to illustrate the current understanding of irritability in psychopathology, discusses important gaps in the literature, and highlights new avenues for further research.

Sleep and cardiac autonomic modulation in older adults: Insights from an at-home study with auditory deep sleep stimulation.

The autonomic nervous system regulates cardiovascular activity during sleep, likely impacting cardiovascular health. Aging, a primary cardiovascular risk factor, is associated with cardiac autonomic disbalance and diminished sleep slow waves. Therefore, slow waves may be linked to aging, autonomic activity and cardiovascular health. However, it is unclear how sleep and slow waves are linked to cardiac autonomic profiles across multiple nights in older adults. We conducted a randomized, crossover trial involving healthy adults aged 62-78 years. Across 2 weeks, we applied auditory stimulation to enhance slow waves and compared it with a SHAM period. We measured sleep parameters using polysomnography and derived heart rate, heart rate variability approximating parasympathetic activity, and blood pulse wave approximating sympathetic activity from a wearable. Here, we report the results of 14 out of 33 enrolled participants, and show that heart rate, heart rate variability and blood pulse wave within sleep stages differ between the first and second half of sleep. Furthermore, baseline slow-wave activity was related to cardiac autonomic activity profiles during sleep. Moreover, we found auditory stimulation to reduce heart rate variability, while heart rate and blood pulse wave remained unchanged. Lastly, within subjects, higher heart rate coincided with increased slow-wave activity, indicating enhanced autonomic activation when slow waves are pronounced. Our study shows the potential of cardiac autonomic markers to offer insights into participants' baseline slow-wave activity when recorded over multiple nights. Furthermore, we highlight that averaging cardiac autonomic parameters across a night may potentially mask dynamic effects of auditory stimulation, potentially playing a role in maintaining a healthy cardiovascular system.

Impact trajectories of childhood maltreatment duration on affective and social development.

Childhood maltreatment (CM) deeply impacts victims' social competences. The aim of the present study was to investigate the effect that CM duration exerts on victims' affective and social development testing three different impact trajectories (i.e., linear, logarithmic and quadratic) and its physiological (facial mimicry and autonomic regulation of the heart) and behavioral (percentage of anger recognition false alarm) markers. In a cross-sectional design, 73 Sierra Leonean youths (all males, 5-17 years old) were enrolled in the study. Of those, 36 were homeless all abandoned at the age of 4 and exposed to CM, whereas 37 were controls. Only physiological markers of affective development were influenced by CM duration. A quadratic relation between the autonomic regulation recorded at rest and CM duration was found, indicating initial physiological compensation followed by progressive autonomic withdrawal. Furthermore, CM duration was associated to a specific linear decrease of facial mimicry and vagal regulation in response to angry and sad facial expressions whereas no influences were detected for happy and fearful faces. The results of the present study provide insightful clues on victims' natural patterns of resilience, deterioration, and chronicity, allowing a deeper comprehension of the developmental pathways through which early life adversities place youths on a track of lifelong health disparities.

Hormonal Imbalance as a Prognostic Factor of Physical Development of Children with Intellectual Disability.

INTRODUCTION: The purpose was to study the indicators of physical development of primary-school-aged children with intellectual disability by observing the type of autonomic nervous regulation and their levels of catecholamines and serotonin. METHODS: A total of 168 primary school age children were examined, of which 54 had intellectual disability. The autonomic nervous system was assessed using cardiointervalography; anthropometric parameters were applied in accordance with recommendations. The contents of serotonin and catecholamines in blood plasma and lymphocytes were assessed using enzyme immunoassay and luminescent histochemical methods. RESULTS AND CONCLUSIONS: Delayed physical and mental development in children with intellectual disability were associated with low serotonin levels in this group of children. The optimal option for the physical development of children with intellectual disability is a sympathetic type of autonomic nervous regulation, while negative-type vagotonic nervous regulation was associated with the maximum delay in physical development. The hypersympathetic type of nervous regulation was accompanied by minimal changes in physical development, despite the hormonal imbalance in the ratio of catecholamines and serotonin. The level of the neurotransmitter serotonin is a prognostic marker of the physical development of children of primary school age. The total amount of catecholamines and serotonin in blood plasma has a direct relationship with the amount of these neurotransmitters in blood lymphocytes; the more hormones in plasma, the more of them in lymphocytes. Therefore, the determination of the contents of catecholamines and serotonin in lymphocytes can be used as a model for studying neurotransmitters in humans.

Heartbeat-evoked potentials following voluntary hyperventilation in epilepsy patients: respiratory influences on cardiac interoception.

Introduction: Current evidence indicates a modulating role of respiratory processes in cardiac interoception, yet whether altered breathing patterns influence heartbeat-evoked potentials (HEP) remains inconclusive. Methods: Here, we examined the effects of voluntary hyperventilation (VH) as part of a clinical routine examination on scalp-recorded HEPs in epilepsy patients (N = 80). Results: Using cluster-based permutation analyses, HEP amplitudes were compared across pre-VH and post-VH conditions within young and elderly subgroups, as well as for the total sample. No differences in the HEP were detected for younger participants or across the full sample, while an increased late HEP during pre-VH compared to post-VH was fond in the senior group, denoting decreased cardiac interoceptive processing after hyperventilation. Discussion: The present study, thus, provides initial evidence of breathing-related HEP modulations in elderly epilepsy patients, emphasizing the potential of HEP as an interoceptive neural marker that could partially extend to the representation of pulmonary signaling. We speculate that aberrant CO2-chemosensing, coupled with disturbances in autonomic regulation, might constitute the underlying pathophysiological mechanism behind the obtained effect. Available databases involving patient records of routine VH assessment may constitute a valuable asset in disentangling the interplay of cardiac and ventilatory interoceptive information in various patient groups, providing thorough clinical data to parse, as well as increased statistical power and estimates of effects with higher precision through large-scale studies.

Full-Term and Preterm Newborns Differ More Significantly in Photoplethysmographic Waveform Variability than Heart Rate Variability.

BACKGROUND: Features of cardiovascular autonomic regulation in infants are poorly studied compared with adults. However, the clinical significance of autonomic dysfunction in infants is very high. The goal of our research was to study the temporal and frequency-dependent features, as well as low-frequency synchronization in cardiovascular autonomic regulation in full-term vs. preterm newborns, based on the analysis of their heart rate variability (HRV) and photoplethysmographic waveform variability (PPGV). METHODS: The study included three groups of newborns: 64 full-term newborns (with a gestational age at birth of 37-40 weeks) with a physiological course of the neonatal adaptation; 23 full-term newborns (with a gestational age at birth of 37-40 weeks) with a pathological course of the neonatal adaptation; and 17 preterm newborns (with a postconceptional age of 34 weeks or more). We conducted spectral analysis of HRV and PPGV, along with an assessment of the synchronization strength between low-frequency oscillations in HRV and in PPGV (synchronization index). We employed several options for the boundaries of the high-frequency (HF) band: 0.15-0.40 Hz, 0.2-2 Hz, 0.15-0.8 Hz, and 0.24-1.04 Hz. RESULTS: Preterm newborns had higher heart rate, RMSSD, and PNN50 values relative to both groups of full-term newborns. Values of SDNN index and synchronization index (S index) were similar in all groups of newborns. Differences in frequency domain indices of HRV between groups of newborns depended on the considered options of HF band boundaries. Values of frequency domain indices of PPGV demonstrated similar differences between groups, regardless of the boundaries of considered options of HF bands and the location of PPG signal recording (forehead or leg). An increase in sympathetic influences on peripheral blood flow and a decrease in respiratory influences were observed along the following gradient: healthy full-term newborns → preterm newborns → full-term newborns with pathology. CONCLUSIONS: Differences in frequency domain indices of autonomic regulation between the studied groups of newborns depended on the boundaries of the considered options of the HF band. Frequency domain indices of PPGV revealed significantly more pronounced differences between groups of newborns than analogous HRV indicators. An increase in sympathetic influences on peripheral blood flow and a decrease in respiratory influences were observed along the following gradient: healthy full-term newborns → preterm newborns → full-term newborns with pathology.

Lactate and hydrogen ions play a predominant role in evoking the exercise pressor reflex during ischaemic contractions but not during freely perfused contractions.

We investigated the role played by lactate and hydrogen in evoking the exercise pressor reflex (EPR) in decerebrated rats whose hindlimb muscles were either freely perfused or ischaemic. Production of lactate and hydrogen by the contracting hindlimb muscles was manipulated by knocking out the myophosphorylase gene (pygm). In knockout rats (pygm-/-; n = 13) or wild-type rats (pygm+/+; n = 13), the EPR was evoked by isometrically contracting the triceps surae muscles. Blood pressure, tension, blood flow, renal sympathetic nerve activity and blood lactate concentrations were measured. Intramuscular metabolites and pH changes induced by the contractions were quantified by 31P-magnetic resonance spectroscopy (n = 5). In a subset of pygm-/- rats (n = 5), contractions were evoked with prior infusion of lactate (pH 6.0) in an attempt to restore the effect of lactate and hydrogen ions. Contraction of freely perfused muscles increased blood lactate and decreased muscle pH in pygm+/+ rats only. Despite these differences, the reflex pressor and sympathetic responses to freely perfused contraction did not differ between groups (P = 0.992). During ischaemia, contraction increased muscle lactate and hydrogen ion production in pygm+/+ rats (P < 0.0134), whereas it had no effect in pygm-/- rats (P > 0.783). Likewise, ischaemia exaggerated the reflex pressor, and sympathetic responses to contraction in pygm+/+ but not in pygm-/- rats. This exaggeration was restored when a solution of lactate (pH 6.0) was infused prior to the contraction in pygm-/- rats. We conclude that lactate and hydrogen accumulation in contracting myocytes play a key role in evoking the metabolic component of the EPR during ischaemic but not during freely perfused contractions. KEY POINTS: Conflicting results exist about the role played by lactate and hydrogen ions in evoking the exercise pressor reflex. Using CRISP-Cas9, we rendered the myophosphorylase gene non-functional to block the production of lactate and hydrogen ions. The exercise pressor reflex was evoked in decerebrated rats by statically contracting the triceps surae muscles with or without muscle ischaemia. Static contraction elevated the concentration of lactate and hydrogen ions in pygm+/+ but not in pygm-/- rats. Despite these differences, the exercise pressor reflex was not different between groups. Acute muscle ischaemia exaggerated the concentration of lactate and hydrogen ions in pygm+/+ but not in pygm-/- rats. Likewise, acute muscle ischaemia exaggerated the exercise pressor reflex in pygm+/+ but not in pygm-/- rats. We conclude that lactate and hydrogen play a key role in evoking the exercise pressor reflex during ischaemic but not during freely perfused contractions.

Unveiling gender differences in psychophysiological dynamics: support for a two-dimensional autonomic space approach.

Introduction: To date, studies focusing on the connection between psychological functioning and autonomic nervous system (ANS) activity usually adopted the one-dimensional model of autonomic balance, according to which activation of one branch of the ANS is accompanied by an inhibition of the other. However, the sympathetic and parasympathetic branches also activate independently; thus, co-activation and co-inhibition may occur, which is demonstrated by a two-dimensional model of ANS activity. Here, we apply such models to assess how markers of the autonomic space relate to several critical psychological constructs: emotional contagion (EC), general anxiety, and positive and negative affect (PA and NA). We also examined gender differences in those psychophysiological relations. Methods: In the present study, we analyzed data from 408 healthy students, who underwent a 5-min group baseline period as part of their participation in several experiments and completed self-reported questionnaires. Electrocardiogram (ECG), electrodermal activity (EDA), and respiration were recorded. Respiratory sinus arrhythmia (RSA), pre-ejection period (PEP), as well as cardiac autonomic balance (CAB) and regulation (CAR) and cross-system autonomic balance (CSAB) and regulation (CSAR), were calculated. Results: Notably, two-dimensional models were more suitable for predicting and describing most psychological constructs. Gender differences were found in psychological and physiological aspects as well as in psychophysiological relations. Women's EC scores were negatively correlated with sympathetic activity and positively linked to parasympathetic dominance. Men's PA and NA scores were positively associated with sympathetic activity. PA in men also had a positive link to an overall activation of the ANS, and a negative link to parasympathetic dominance. Discussion: The current results expand our understanding of the psychological aspects of the autonomic space model and psychophysiological associations. Gender differences and strengths and weaknesses of alternative physiological models are discussed.

Infant sustained attention differs by context and social content in the first 2 years of life.

Sustained attention (SA) is an endogenous form of attention that emerges in infancy and reflects cognitive engagement and processing. SA is critical for learning and has been measured using different methods during screen-based and interactive contexts involving social and nonsocial stimuli. How SA differs by measurement method, context, and stimuli across development in infancy is not fully understood. This 2-year longitudinal study examines attention using one measure of overall looking behavior and three measures of SA-mean look duration, percent time in heart rate-defined SA, and heart rate change during SA-in N = 53 infants from 1 to 24 months across four unique task conditions: social videos, nonsocial videos, social interactions (face-to-face play), and nonsocial interactions (toy engagement). Results suggest that developmental changes in attention differ by measurement method, task context (screen or interaction), and task stimulus (social or nonsocial). During social interactions, overall looking and look durations declined after age 3-4 months, whereas heart rate-defined attention measures remained stable. All SA measures were greater for videos than for live interaction conditions throughout the first 6 months, but SA to social and nonsocial stimuli within each task context were equivalent. In the second year of life, SA measured with look durations was greater for social videos compared to other conditions, heart rate-defined SA was greater for social videos compared to nonsocial interactions, and heart rate change during SA was similar across conditions. Together, these results suggest that different measures of attention to social and nonsocial stimuli may reflect unique developmental processes and are important to compare and consider together, particularly when using infant attention as a marker of typical or atypical development. RESEARCH HIGHLIGHTS: Attention measure, context, and social content uniquely differentiate developmental trajectories of attention in the first 2 years of life. Overall looking to caregivers during dyadic social interactions declines significantly from 4 to 6 months of age while sustained attention (SA) to caregivers remains stable. Heart rate-defined SA generally differentiates stimulus context where infants show greater SA while watching videos than while engaging with toys.

Functional and 123I-MIBG scintigraphy assessment of cardiac adrenergic dysfunction in diabetes.

OBJECTIVES: To assess the agreement between clinical cardiovascular adrenergic function and cardiac adrenergic innervation in type 2 diabetes patients (T2D). METHODS: Thirty-three patients with T2D were investigated bimodally through (1) a standardized clinical cardiovascular adrenergic assessment, evaluating adequacy of blood pressure responses to the Valsalva maneuver and (2) 123I-meta-iodobenzylguanidine (MIBG) scintigraphy assessing myocardial adrenergic innervation measured as early and delayed heart heart/mediastinum (H/M) ratio, and washout rate (WR). RESULTS: T2D patients had significantly lower early and delayed H/M-ratios, and lower WR, compared to laboratory specific reference values. Thirteen patients had an abnormal adrenergic composite autonomic severity score (CASS > 0). Patients with abnormal CASS scores had significantly higher early H/M ratios (1.76 [1.66-1.88] vs. 1.57 [1.49-1.63], p < 0.001), higher delayed H/M ratios (1.64 [1.51:1.73] vs. 1.51 [1.40:1.61] (p = 0.02)), and lower WR (-0.13(0.10) vs -0.05(0.07), p = 0.01). Lower Total Recovery and shorter Pressure Recovery Time responses from the Valsalva maneuver was significantly correlated to lower H/M early (r = 0.55, p = 0.001 and r = 0.5, p = 0.003, respectively) and lower WR for Total Recovery (r = -0.44, p = 0.01). CONCLUSION: The present study found impairment of sympathetic innervation in T2D patients based on parameters derived from MIBG cardiac scintigraphy (low early H/M, delayed H/M, and WR). These results confirm prior studies. We found a mechanistically inverted relationship with favourable adrenergic cardiovascular responses being significantly associated unfavourable MIBG indices for H/M early and delayed. This paradoxical relationship needs to be further explored but could indicate adrenergic hypersensitivity in cardiac sympathetic denervated T2D patients.

Periodic repolarization dynamics: Different methods for quantifying low-frequency oscillations of repolarization.

BACKGROUND: Periodic repolarization dynamics (PRD) is an electrocardiographic biomarker that quantifies low-frequency (LF) instabilities of repolarization. PRD is a strong predictor of mortality in patients with ischaemic and non-ischaemic cardiomyopathy. Until recently, two methods for calculating PRD have been proposed. The wavelet analysis has been widely tested and quantifies PRD in deg2 units by application of continuous wavelet transformation (PRDwavelet). The phase rectified signal averaging method (PRDPRSA) is an algebraic method, which quantifies PRD in deg. units. The correlation, as well as a conversion formula between the two methods remain unknown. METHOD: The first step for quantifying PRD is to calculate the beat-to-beat change in the direction of repolarization, called dT°. PRD is subsequently quantified by means of either wavelet or PRSA-analysis. We simulated 1.000.000 dT°-signals. For each simulated signal we calculated PRD using the wavelet and PRSA-method. We calculated the ratio between PRDwavelet and PRDPRSA for different values of dT° and RR-intervals and applied this ratio in a real-ECG validation cohort of 455 patients after myocardial infarction (MI). We finally calculated the correlation coefficient between real and calculated PRDwavelet. PRDwavelet was dichotomized at the established cut-off value of ≥5.75 deg2. RESULTS: The ratio between PRDwavelet and PRDPRSA increased with increasing heart-rate and mean dT°-values (p < 0.001 for both). The correlation coefficient between PRDwavelet and PRDPRSA in the validation cohort was 0.908 (95% CI 0.891-0.923), which significantly (p < 0.001) improved to 0.945 (95% CI 0.935-0.955) after applying the formula considering the ratio between PRDwavelet and PRDPRSA obtained from the simulation cohort. The calculated PRDwavelet correctly classified 98% of the patients as low-risk and 87% of the patients as high-risk and correctly identified 97% of high-risk patients, who died within the follow-up period. CONCLUSION: This is the first analytical investigation of the different methods used to calculate PRD using simulated and clinical data. In this article we propose a novel algorithm for converting PRDPRSA to the widely validated PRDwavelet, which could unify the calculation methods and cut-offs for PRD.

Transcutaneous spinal cord stimulation and its impact on cardiovascular autonomic regulation after spinal cord injury.

Individuals with spinal cord injury (SCI) have significant dysfunction in cardiovascular autonomic regulation. Although recent findings postulate that spinal cord stimulation improves autonomic regulation, limited scope of past methods have tested only above level sympathetic activation, leaving significant uncertainty. To identify whether transcutaneous spinal cord stimulation improves cardiovascular autonomic regulation, two pairs of well-matched individuals with and without high thoracic, complete SCI were recruited. Baseline autonomic regulation was characterized with multiple tests of sympathoinhibition and above/below injury level sympathoexcitation. At three subsequent visits, testing was repeated with the addition submotor threshold transcutaneous spinal cord stimulation at three previously advocated frequencies. Uninjured controls demonstrated no autonomic deficits at baseline and had no changes with any frequency of stimulation. As expected, individuals with SCI had baseline autonomic dysfunction. In a frequency-dependent manner, spinal cord stimulation enhanced sympathoexcitatory responses, normalizing previously impaired Valsalva's maneuvers. However, stimulation exacerbated already impaired sympathoinhibitory responses, resulting in significantly greater mean arterial pressure increases with the same phenylephrine doses compared with baseline. Impaired sympathoexcitatory response below the level of injury were also further exacerbated with spinal cord stimulation. At baseline, neither individual with SCI demonstrated autonomic dysreflexia with the noxious foot cold pressor test; the addition of stimulation led to a dysreflexic response in every trial, with greater relative hypertension and bradycardia indicating no improvement in cardiovascular autonomic regulation. Collectively, transcutaneous spinal cord stimulation demonstrates no improvements in autonomic regulation after SCI, and instead likely generates tonic sympathoexcitation which may lower the threshold for dangerous autonomic dysreflexia.NEW & NOTEWORTHY Spinal cord stimulation increases blood pressure after spinal cord injury, though it is unclear if this restores natural autonomic regulation or induces a potentially dangerous pathological reflex. We performed comprehensive autonomic testing batteries, with and without transcutaneous spinal cord stimulation at multiple frequencies. Across 96 independent tests, stimulation did not change uninjured control responses, though all frequencies facilitated pathological reflexes without improved autonomic regulation for those with spinal cord injuries.

Dorsal Motor Vagal Neurons Can Elicit Bradycardia and Reduce Anxiety-Like Behavior.

Cardiovagal neurons (CVNs) innervate cardiac ganglia through the vagus nerve to control cardiac function. Although the cardioinhibitory role of CVNs in nucleus ambiguus (CVNNA) is well established, the nature and functionality of CVNs in dorsal motor nucleus of the vagus (CVNDMV) is less clear. We therefore aimed to characterize CVNDMV anatomically, physiologically, and functionally. Optogenetically activating cholinergic DMV neurons resulted in robust bradycardia through peripheral muscarinic (parasympathetic) and nicotinic (ganglionic) acetylcholine receptors, but not beta-1-adrenergic (sympathetic) receptors. Retrograde tracing from the cardiac fat pad labeled CVNNA and CVNDMV through the vagus nerve. Using whole cell patch clamp, CVNDMV demonstrated greater hyperexcitability and spontaneous action potential firing ex vivo despite similar resting membrane potentials, compared to CVNNA. Chemogenetically activating DMV also caused significant bradycardia with a correlated reduction in anxiety-like behavior. Thus, DMV contains uniquely hyperexcitable CVNs capable of cardioinhibition and robust anxiolysis.

Maternal cardiorespiratory coupling: differences between pregnant and nonpregnant women are further amplified by sleep-stage stratification.

Pregnancy complications are associated with abnormal maternal autonomic regulation. Subsequently, thoroughly understanding maternal autonomic regulation during healthy pregnancy may enable the earlier detection of complications, in turn allowing for the improved management thereof. Under healthy autonomic regulation, reciprocal interactions occur between the cardiac and respiratory systems, i.e., cardiorespiratory coupling (CRC). Here, we investigate, for the first time, the differences in CRC between healthy pregnant and nonpregnant women. We apply two algorithms, namely, synchrograms and bivariate phase-rectified signal averaging, to nighttime recordings of ECG and respiratory signals. We find that CRC is present in both groups. Significantly less (P < 0.01) cardiorespiratory synchronization occurs in pregnant women (11% vs. 15% in nonpregnant women). Moreover, there is a smaller response in the heart rate of pregnant women corresponding to respiratory inhalations and exhalations. In addition, we stratified these analyses by sleep stages. As each sleep stage is governed by different autonomic states, this stratification not only amplified some of the differences between groups but also brought out differences that remained hidden when analyzing the full-night recordings. Most notably, the known positive relationship between CRC and deep sleep is less prominent in pregnant women than in their nonpregnant counterparts. The decrease in CRC during healthy pregnancy may be attributable to decreased maternal parasympathetic activity, anatomical changes to the maternal respiratory system, and the increased physiological stress accompanying pregnancy. This work offers novel insight into the physiology of healthy pregnancy and forms part of the base knowledge needed to detect abnormalities in pregnancy.NEW & NOTEWORTHY We compare CRC, i.e., the reciprocal interaction between the cardiac and respiratory systems, between healthy pregnant and nonpregnant women for the first time. Although CRC is present in both groups, CRC is reduced during healthy pregnancy; there is less synchronization between maternal cardiac and respiratory activity and a smaller response in maternal heart rate to respiratory inhalations and exhalations. Stratifying this analysis by sleep stages reveals that differences are most prominent during deep sleep.

Effects of Early Adverse Life Events on Depression and Cognitive Performance from the Perspective of the Heart-Brain Axis.

Early adverse life events (EALs) increase susceptibility to depression and impair cognitive performance, but the physiological mechanisms are still unclear. The target of this article is to clarify the impact of adverse childhood experiences on emotional and cognitive performance from the perspective of the heart-brain axis. We used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to test cognitive function and the Childhood Trauma Questionnaire (CTQ) to assess adverse childhood experiences. Heart rate variability (HRV) and electroencephalograms (EEG) were acquired at rest. We observed that subjects with depression had experienced more traumatic events during their childhood. Furthermore, they exhibited lower heart rate variability and higher power in the delta, theta, and alpha frequency bands. Moreover, heart rate variability partially mediated the association between childhood trauma exposure and depressive symptoms. Our findings suggested that adverse life events in childhood could influence the development of depression in adulthood, which might be linked to cardiac autonomic dysfunction and altered brain function.

A Comparative Review of Vagal Nerve Stimulation Versus Baroreceptor Activation Therapy in Cardiac Diseases.

Sympathetic imbalance coupled with impairment of baroreceptor control is a key factor responsible for hemodynamic abnormalities in congestive heart failure. Vagal nerve stimulation (VNS) and baroreceptor activation therapy (BAT) are two novel interventions for the same. In this paper, we review the role of sympathovagal alterations in cardiac diseases like heart failure, arrhythmia, hypertension (HTN), etc. Studies like neural cardiac therapy for heart failure (NECTAR-HF), autonomic regulation therapy to enhance myocardial function and reduce progression of heart failure (ANTHEM-HF), and baroreflex activation therapy for heart failure (BEAT-HF), which comprise the history, efficacy, limitations, and current protocols, were extensively analyzed in contrast to one another. Vagal nerve stimulation reverses the reflex inhibition of cardiac vagal efferent activity, which is caused as a result of sympathetic overdrive during the course for heart failure. It has shown encouraging results in certain pre-clinical studies; however, there is also a possibility of serious cardiovascular adverse events if given in higher than the recommended dosage. Attenuated baroreflex sensitivity is attributed to cardiac arrhythmogenesis during heart failure. Baroreceptor activation therapy reverses this phenomenon. However, the surgical procedure for baroreceptor stimulation can have unwarranted complications, including worsening heart failure and hypertension. Considering the effectiveness of the given modalities and taking into account the inconclusive evidence of their adverse events, more clinical trials are needed for establishing the future prospects of these interventional approaches.

Exploring Autonomic Alterations during Seizures in Temporal Lobe Epilepsy: Insights from a Heart-Rate Variability Analysis.

Epilepsy's impact on cardiovascular function and autonomic regulation, including heart-rate variability, is complex and may contribute to sudden unexpected death in epilepsy (SUDEP). Lateralization of autonomic control in the brain remains the subject of debate; nevertheless, ultra-short-term heart-rate variability (HRV) analysis is a useful tool for understanding the pathophysiology of autonomic dysfunction in epilepsy patients. A retrospective study reviewed medical records of patients with temporal lobe epilepsy who underwent presurgical evaluations. Data from 75 patients were analyzed and HRV indices were extracted from electrocardiogram recordings of preictal, ictal, and postictal intervals. Various HRV indices were calculated, including time domain, frequency domain, and nonlinear indices, to assess autonomic function during different seizure intervals. The study found significant differences in HRV indices based on hemispheric laterality, language dominancy, hippocampal atrophy, amygdala enlargement, sustained theta activity, and seizure frequency. HRV indices such as the root mean square of successive differences between heartbeats, pNN50, normalized low-frequency, normalized high-frequency, and the low-frequency/high-frequency ratio exhibited significant differences during the ictal period. Language dominancy, hippocampal atrophy, amygdala enlargement, and sustained theta activity were also found to affect HRV. Seizure frequency was correlated with HRV indices, suggesting a potential relationship with the risk of SUDEP.

Clinical surrogates of dysautonomia predict lethal outcome in COVID-19 on intensive care unit.

BACKGROUND: Unpredictable vegetative deteriorations made the treatment of patients with acute COVID-19 on intensive care unit particularly challenging during the first waves of the pandemic. Clinical correlates of dysautonomia and their impact on the disease course in critically ill COVID-19 patients are unknown. METHODS: We retrospectively analyzed data collected during a single-center observational study (March 2020-November 2021) which was performed at the University Medical Center Hamburg-Eppendorf, a large tertiary medical center in Germany. All patients admitted to ICU due to acute COVID-19 disease during the study period were included (n = 361). Heart rate variability (HRV) and blood pressure variability (BPV) per day were used as clinical surrogates of dysautonomia and compared between survivors and non-survivors at different time points after admission. Intraindividual correlation of vital signs with laboratory parameters were calculated and corrected for age, sex and disease severity. RESULTS: Patients who deceased in ICU had a longer stay (median days ± IQR, survivors 11.0 ± 27.3, non-survivors 14.1 ± 18.7, P = 0.85), in contrast time spent under invasive ventilation was not significantly different (median hours ± IQR, survivors 322 ± 782, non-survivors 286 ± 434, P = 0.29). Reduced HRV and BPV predicted lethal outcome in patients staying on ICU longer than 10 days after adjustment for age, sex, and disease severity. Accordingly, HRV was significantly less correlated with inflammatory markers (e.g. CRP and Procalcitonin) and blood carbon dioxide in non-survivors in comparison to survivors indicating uncoupling between autonomic function and inflammation in non-survivors. CONCLUSIONS: Our study suggests autonomic dysfunction as a contributor to mortality in critically ill COVID-19 patients during the first waves of the pandemic. Serving as a surrogate for disease progression, these findings could contribute to the clinical management of COVID-19 patients admitted to the ICU. Furthermore, the suggested measure of dysautonomia and correlation with other laboratory parameters is non-invasive, simple, and cost-effective and should be evaluated as an additional outcome parameter in septic patients treated in the ICU in the future.