Reconceptualizing autonomic function testing in migraine: a systematic review and meta-analysis.

BACKGROUND: Autonomic nervous system (ANS) testing has aided in our ability to evaluate autonomic dysfunction in migraine patients. We reviewed the literature in multiple databases which investigate ANS function in migraine patients and healthy subjects. METHODS: This systematic review and meta-analysis examined the respective deep breathing, Valsalva manoeuvre, orthostatic and isometric challenge results, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses of Observational Studies in Epidemiology (MOOSE) statements. RESULTS: Seven articles met all inclusion criteria. Fixed-effects meta-analysis showed migraine patients (n = 424), collectively, had lower interictal autonomic test results compared with healthy controls (n = 268). In detail, this was true for the standardized mean difference (g) of deep breathing (g= -0.32; 95% confidence interval (CI) -0.48, -0.16), orthostatic challenge (g= -0.28; 95% CI -0.44, -0.13) and isometric challenge (g= -0.55; 95% CI -0.71, -0.39) and for the difference of means (MD) of the Valsalva ratio (MD = -0.17; 95% CI -0.23, -0.10). CONCLUSIONS: Interictal ANS dysfunction can be identified in migraine patients when compared to healthy controls. These findings indicate the importance to evaluate ANS function in migraine patients - especially, as migraine-specific prophylactic therapies (such as anti-calcitonin gene-related peptide (CGRP) antibodies) may affect the function of the ANS.

Bidirectional brain-body interactions during natural story listening.

Narratives can synchronize neural and physiological signals between individuals, but the relationship between these signals, and the underlying mechanism, is unclear. We hypothesized a top-down effect of cognition on arousal and predicted that auditory narratives will drive not only brain signals but also peripheral physiological signals. We find that auditory narratives entrained gaze variation, saccade initiation, pupil size, and heart rate. This is consistent with a top-down effect of cognition on autonomic function. We also hypothesized a bottom-up effect, whereby autonomic physiology affects arousal. Controlled breathing affected pupil size, and heart rate was entrained by controlled saccades. Additionally, fluctuations in heart rate preceded fluctuations of pupil size and brain signals. Gaze variation, pupil size, and heart rate were all associated with anterior-central brain signals. Together, these results suggest bidirectional causal effects between peripheral autonomic function and central brain circuits involved in the control of arousal.

Smelling TNT: Trends of the Terminal Nerve.

There is very little knowledge regarding the terminal nerve, from its implications in the involvement and pathogenesis of certain conditions, to its embryological origin. With this review, we try to summarize the most important evidence on the terminal nerve, aiming to clarify its anatomy and the various functions attributed to it, to better interpret its potential involvement in pathological processes. Recent studies have also suggested its potential role in the control of human reproductive functions and behaviors. It has been hypothesized that it plays a role in the unconscious perception of specific odors that influence autonomic and reproductive hormonal systems through the hypothalamic-pituitary-gonadal axis. We used the PubMed database and found different articles which were then selected independently by three authors. We found 166 articles, of which, after careful selection, only 21 were analyzed. The terminal nerve was always thought to be unimportant in our body. It was well studied in different types of animals, but few studies have been completed in humans. For this reason, its function remains unknown. Studies suggest a possible implication in olfaction due to the anatomical proximity with the olfactive nerve. Others suggest a more important role in reproduction and sexual behaviors. New emerging information suggests a possible role in Kallmann syndrome and COVID-19.

Heart Rate Variability and Pulse Rate Variability: Do Anatomical Location and Sampling Rate Matter?

Wearable technology and neuroimaging equipment using photoplethysmography (PPG) have become increasingly popularized in recent years. Several investigations deriving pulse rate variability (PRV) from PPG have demonstrated that a slight bias exists compared to concurrent heart rate variability (HRV) estimates. PPG devices commonly sample at ~20-100 Hz, where the minimum sampling frequency to derive valid PRV metrics is unknown. Further, due to different autonomic innervation, it is unknown if PRV metrics are harmonious between the cerebral and peripheral vasculature. Cardiac activity via electrocardiography (ECG) and PPG were obtained concurrently in 54 participants (29 females) in an upright orthostatic position. PPG data were collected at three anatomical locations: left third phalanx, middle cerebral artery, and posterior cerebral artery using a Finapres NOVA device and transcranial Doppler ultrasound. Data were sampled for five minutes at 1000 Hz and downsampled to frequencies ranging from 20 to 500 Hz. HRV (via ECG) and PRV (via PPG) were quantified and compared at 1000 Hz using Bland-Altman plots and coefficient of variation (CoV). A sampling frequency of ~100-200 Hz was required to produce PRV metrics with a bias of less than 2%, while a sampling rate of ~40-50 Hz elicited a bias smaller than 20%. At 1000 Hz, time- and frequency-domain PRV measures were slightly elevated compared to those derived from HRV (mean bias: ~1-8%). In conjunction with previous reports, PRV and HRV were not surrogate biomarkers due to the different nature of the collected waveforms. Nevertheless, PRV estimates displayed greater validity at a lower sampling rate compared to HRV estimates.

Neurophysiological and Autonomic Correlates of Metacognitive Control of and Resistance to Distractors in Ecological Setting: A Pilot Study.

In organisational contexts, professionals are required to decide dynamically and prioritise unexpected external inputs deriving from multiple sources. In the present study, we applied a multimethodological neuroscientific approach to investigate the ability to resist and control ecological distractors during decision-making and to explore whether a specific behavioural, neurophysiological (i.e., delta, theta, alpha and beta EEG band), or autonomic (i.e., heart rate-HR, and skin conductance response-SCR) pattern is correlated with specific personality profiles, collected with the 10-item Big Five Inventory. Twenty-four participants performed a novel Resistance to Ecological Distractors (RED) task aimed at exploring the ability to resist and control distractors and the level of coherence and awareness of behaviour (metacognition ability), while neurophysiological and autonomic measures were collected. The behavioural results highlighted that effectiveness in performance did not require self-control and metacognition behaviour and that being proficient in metacognition can have an impact on performance. Moreover, it was shown that the ability to resist ecological distractors is related to a specific autonomic profile (HR and SCR decrease) and that the neurophysiological and autonomic activations during task execution correlate with specific personality profiles. The agreeableness profile was negatively correlated with the EEG theta band and positively with the EEG beta band, the conscientiousness profile was negatively correlated with the EEG alpha band, and the extroversion profile was positively correlated with the EEG beta band. Taken together, these findings describe and disentangle the hidden relationship that lies beneath individuals' decision to inhibit or activate intentionally a specific behaviour, such as responding, or not, to an external stimulus, in ecological conditions.

Comparing multimodal physiological responses to social and physical pain in healthy participants.

Background: Previous physiology-driven pain studies focused on examining the presence or intensity of physical pain. However, people experience various types of pain, including social pain, which induces negative mood; emotional distress; and neural activities associated with physical pain. In particular, comparison of autonomic nervous system (ANS) responses between social and physical pain in healthy adults has not been well demonstrated. Methods: We explored the ANS responses induced by two types of pain-social pain, associated with a loss of social ties; and physical pain, caused by a pressure cuff-based on multimodal physiological signals. Seventy-three healthy individuals (46 women; mean age = 20.67 ± 3.27 years) participated. Behavioral responses were assessed to determine their sensitivity to pain stimuli. Electrocardiogram, electrodermal activity, photoplethysmogram, respiration, and finger temperature (FT) were measured, and 12 features were extracted from these signals. Results: Social pain induced increased heart rate (HR) and skin conductance (SC) and decreased blood volume pulse (BVP), pulse transit time (PTT), respiration rate (RR), and FT, suggesting a heterogeneous pattern of sympathetic-parasympathetic coactivation. Moreover, physical pain induced increased heart rate variability (HRV) and SC, decreased BVP and PTT, and resulted in no change in FT, indicating sympathetic-adrenal-medullary activation and peripheral vasoconstriction. Conclusion: These results suggest that changes in HR, HRV indices, RR, and FT can serve as markers for differentiating physiological responses to social and physical pain stimuli.

The relationship between the tumor and its innervation: historical, methodical, morphological, and functional assessments - A minireview.

The acceptance of the tumor as a non-isolated structure within the organism has opened a space for the study of a wide spectrum of potential direct and indirect interactions, not only between the tumor tissue and its vicinity, but also between the tumor and its macroenvironment, including the nervous system. Although several lines of evidence have implicated the nervous system in tumor growth and progression, for many years, researchers believed that tumors lacked innervation and the notion of indirect neuro-neoplastic interactions via other systems (e.g., immune, or endocrine) predominated. The original idea that tumors are supplied not only by blood and lymphatic vessels, but also autonomic and sensory nerves that may influence cancer progression, is not a recent phenomenon. Although in the past, mainly due to the insufficiently sensitive methodological approaches, opinions regarding the presence of nerves in tumors were inconsistent. However, data from the last decade have shown that tumors are able to stimulate the formation of their own innervation by processes called neo-neurogenesis and neo-axonogenesis. It has also been shown that tumor infiltrating nerves are not a passive, but active components of the tumor microenvironment and their presence in the tumor tissue is associated with an aggressive tumor phenotype and correlates with poor prognosis. The aim of the present review was to 1) summarize the available knowledge regarding the course of tumor innervation, 2) present the potential mechanisms and pathways for the possible induction of new nerve fibers into the tumor microenvironment, and 3) highlight the functional significance/consequences of the nerves infiltrating the tumors.

Electrocardiographic and Autonomic Nervous System Changes after Changes in the Posture of Children and Adolescents with Duchenne Muscular Dystrophy. / Alterações Eletrocardiográficas e do Sistema Nervoso Autônomo com a Mudança de Postura em Crianças e Adolescentes com Distrofia Muscular de Duchenne.

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is a rare inherited neuromuscular disease. At first, cardiac involvement may be asymptomatic. Therefore, assessing patients using non-invasive methods can help detect any changes. OBJECTIVES: Analyze the electrocardiogram (ECG) test and heart rate variability (HRV) of the DMD group and compare the information with that of the age-matched control group. METHODS: A prospective study with 27 male patients with DMD (11.9 years old), who underwent clinical evaluation, ECG, echocardiogram, and Holter monitoring. ECG (200% increase) was assessed by two independent observers. HRV was measured over time (24 h) and in the frequency domain, in the supine and sitting positions. The healthy group consisted of nine patients (11.0 years old). A value of p < 0.05 was considered statistically significant. RESULTS: The mean ejection fraction (EF) was 60% (34 to 71%). The Kappa coefficient for ECG measurements ranged from 0.64 to 1.00. An increase in the R/S ratio in V1 was observed in 25.9% of the subjects, pathological Q wave in 29.6%, and fragmented QRS in 22.2% in inferior/high lateral regions, with a negative correlation with EF (p = 0.006). There was low HRV, without the influence of any variable, including treatment. With the change in position, there was an increase in HR (p = 0.004), but there was no change in HRV. The LF/HF ratio was 2.7 in the DMD group and 0.7 in the control group (p = 0.002). CONCLUSIONS: In DMD subjects, prominent R waves in V1 and changes in the inferior/high lateral regions occurred in almost 30% of the cases. Lower vagal tone was observed without the influence of the variables age, ejection fraction, QT dispersion, and treatment. Despite the increase in HR, there was no adequate HRV response to the change in position.

FUNDAMENTO: Distrofia Muscular de Duchenne (DMD) é uma doença neuromuscular hereditária rara. O acometimento cardíaco inicial pode ser assintomático. Portanto, a avaliação por métodos não invasivos pode auxiliar sua abordagem. OBJETIVOS: Analisar o eletrocardiograma (ECG) e a variabilidade da frequência cardíaca (VFC) do grupo com DMD, e comparar com a do grupo controle pareado por idade. MÉTODOS: Estudo prospectivo com 27 pacientes masculinos com DMD (idade de 11,9 anos) que foram submetidos à avaliação clínica, ECG, ecocardiograma e Holter. ECG (aumento de 200%) foi avaliado por dois observadores independentes. VFC foi feita no domínio do tempo (24 h) e da frequência na posição supina e sentada. O grupo saudável foi de nove pacientes (11,0 anos). Um valor de p < 0,05 foi considerado estatisticamente significante. RESULTADOS: A média da fração de ejeção (FE) foi de 60% (34 a 71%). O coeficiente de Kappa para as medidas do ECG variou de 0,64 a 1,00. Foram verificados aumento da relação R/S em V1 em 25,9%, onda Q patológica em 29,6% e QRS fragmentado em 22,2% em regiões inferior/lateral alta, este com correlação negativa com FE (p = 0,006). Houve baixa VFC, sem influência de nenhuma variável, inclusive tratamento. Com a mudança da posição, houve aumento da FC (p = 0,004), porém não houve alteração da VFC. A relação LF/HF foi de 2,7 na DMD e de 0,7 no controle (p = 0,002). CONCLUSÕES: Nos participantes com DMD, as ondas R proeminentes em V1 e alterações nas regiões inferior/lateral alta ocorreram em quase 30% dos casos. Houve menor tônus vagal sem influência das variáveis idade, fração de ejeção, dispersão do QT e tratamento. Apesar do aumento da FC, não houve resposta adequada da VFC com a mudança de posição.

ASSESSMENT OF REACTIVITY TO THE BODY UNDER CONDITIONS OF PHYSICAL ACTIVITY IN STUDENTS AGED 17-20 YEARS.

Physical activity is such an essential socio-biological element, which provides a balance between the body and the external environment and contributes to the improvement of metabolic process regulation mechanisms. However, the abuse of physical activity often leads to unwanted changes in the basic physiological processes in the athletes' organism, due to the impact of a variety of reasons. The state of the organism's regulatory systems and the provision of the necessary adaptation of the organism to physical activity are crucial in assessing the athlete's physical fitness. It is known that during physical exertion, the functional state of the organism is determined by a reaction limiting the efficiency of the cardiovascular and respiratory systems. It was revealed that with long-term physical activity restriction, blood circulation regulatory mechanisms, as well as synocardial reflexes, are disrupted. This research is devoted to the study of students' organism adaptive capabilities depending on the central or autonomous type of vegetative regulation. Registration and analysis of ECG of students by the method of variational heart rate monitoring were carried out. With the help of a special program, the students' heart rate integral indicators were analyzed. All studies were carried out twice: before physical exertion and immediately after physical exertion. In this study, we aimed to explore the adaptive capabilities of students bodies depending on the central or autonomous type of autonomic regulation. Three types of response to physical activity have been identified: optimal, paradoxical, and atypical. In all types of reactions, a certain level and direction of intensity of the processes of regulation of the athletes' organism is expressed. The study of the distinctive features of vegetative regulation makes it possible to assess athletes' organism functional state better and determine violations of their adaptive capabilities. According to the research results, based on the primary signs of the athletes' organism adaptive capabilities and the corresponding reaction, it is possible to determine the optimal dose of physical exertion for athletes.

Indomethacin-Responsive Headache Disorders.

OBJECTIVE: This article describes the clinical features and treatment of the indomethacin-responsive headache disorders paroxysmal hemicrania and hemicrania continua. LATEST DEVELOPMENTS: Both paroxysmal hemicrania and hemicrania continua are treated with indomethacin at the lowest clinically useful dose. It has recently become clear that some patients with either condition may respond to treatment with noninvasive vagus nerve stimulation, which can be both indomethacin sparing and, in some cases, headache controlling. Given the lifelong nature of both paroxysmal hemicrania and hemicrania continua, brain imaging with MRI is recommended when the conditions are identified, specifically including pituitary views. ESSENTIAL POINTS: Paroxysmal hemicrania and hemicrania continua are indomethacin-responsive headache disorders that offer a rewarding and unique opportunity to provide marked clinical improvement when recognized and treated appropriately. These disorders share the final common pathway of the trigeminal-autonomic reflex, with head pain and cranial autonomic features, and are differentiated pathophysiologically by the pattern of brain involvement, which can be seen using functional imaging. They have distinct differential diagnoses to which the clinician needs to remain alert.

Analysis of Heart Rate Variability in Individuals Affected by Amyotrophic Lateral Sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) produces alterations in the autonomic nervous system (ANS), which explains the cardiac manifestations observed in patients. The assessment of heart rate variability (HRV) is what best reflects the activity of the ANS on heart rate. The Polar H7 Bluetooth® device proves to be a non-invasive and much faster technology than existing alternatives for this purpose. OBJECTIVE: The goal of this study is to determine HRV using Polar H7 Bluetooth technology in ALS patients, comparing the obtained measurements with values from healthy individuals. METHOD: The sample consisted of 124 participants: 68 diagnosed with ALS and 56 healthy individuals. Using Polar H7 Bluetooth technology and the ELITE HRV application, various HRV measurements were determined for all participants, specifically the HRV index, RMSSD, RMSSD LN, SDNN index, PNN50, LF, HF, LF/HF ratio, HR average, and HF peak frequency. RESULTS: Statistically significant differences were observed between ALS patients and healthy individuals in the HRV index, RMSSD, RMSSD LN, SDNN index, PNN50, HF, and LF, where healthy individuals exhibited higher scores. For the HR average, the ALS group showed a higher value. Values were similar when comparing men and women with ALS, with only a higher HF peak frequency observed in women. CONCLUSION: The Polar H7 Bluetooth® device is effective in determining heart rate variability alterations in ALS, being a promising prognostic tool for the disease.

Uncovering sympathetic nervous system dysfunction in disorders of consciousness via heart rate variability during head-up tilt test.

Few standardized tools are available for evaluation of disorders of consciousness (DOC). The potential of heart rate variability (HRV) during head-up tilt (HUT) test was investigated as a complementary evaluation tool. Twenty-one DOC patients and 21 healthy participants were enrolled in this study comparing clinical characteristics and HRV time- and frequency-domain outcomes and temporal changes during HUT test. During the 1st-5th min of the HUT, DOC group showed a significant increase and decrease in log low frequency (LF) (p = 0.045) and log normalized high frequency (nHF) (p = 0.02), respectively, compared to the supine position and had lower log normalized LF (nLF) (p = 0.004) and log ratio of low-to-high frequency (LF/HF) (p = 0.001) compared to healthy controls. As the HUT continued from the 6th to the 20th min, DOC group exhibited a significant increase in log LF/HF (16th-20th min) (p < 0.05), along with a decrease in log nHF (6th-10th and 16th-20th min) (p < 0.05) and maintained lower log LF, log nLF, and log LF/HF than controls (p < 0.05). 1st-10th min after returning to the supine position, DOC group demonstrated a significant decrease in log nHF (p < 0.01) and increases in log LF/HF (p < 0.01) and had lower log LF (p < 0.01) and log nLF (p < 0.05) compared to controls. In contrast, the control group exhibited a significant decrease in log nHF (p < 0.05) and increase in log LF/HF (p < 0.05) throughout the entire HUT test. Notably, no significant differences were observed when comparing time-domain outcomes reflecting parasympathetic nervous system between the two groups. HRV during HUT test indicated a delayed and attenuated autonomic response, particularly in the sympathetic nervous system, in DOC patients compared with healthy individuals.

Respiratory modulation of the heart rate: A potential biomarker of cardiorespiratory function in human.

In recent decade, wearable digital devices have shown potentials for the discovery of novel biomarkers of humans' physiology and behavior. Heart rate (HR) and respiration rate (RR) are most crucial bio-signals in humans' digital phenotyping research. HR is a continuous and non-invasive proxy to autonomic nervous system and ample evidence pinpoints the critical role of respiratory modulation of cardiac function. In the present study, we recorded longitudinal (7 days, 4.63 ± 1.52) HR and RR of 89 freely behaving human subjects (Female: 39, age 57.28 ± 5.67, Male: 50, age 58.48 ± 6.32) and analyzed their dynamics using linear models and information theoretic measures. While HR's linear and nonlinear characteristics were expressed within the plane of the HR-RR directed flow of information (HR→RR - RR→HR), their dynamics were determined by its RR→HR axis. More importantly, RR→HR quantified the effect of alcohol consumption on individuals' cardiorespiratory function independent of their consumed amount of alcohol, thereby signifying the presence of this habit in their daily life activities. The present findings provided evidence for the critical role of the respiratory modulation of HR, which was previously only studied in non-human animals. These results can contribute to humans' phenotyping research by presenting RR→HR as a digital diagnosis/prognosis marker of humans' cardiorespiratory pathology.

Effects of slow breathing training on hemodynamic changes, cardiac autonomic function and neuroendocrine response in people with high blood pressure: A randomized control trial.

BACKGROUND: High blood pressure (BP) is a non-communicable disease that is a risk factor for cardiovascular disease and is the leading cause of mortality and morbidity worldwide. High BP can be managed by both pharmacological and non-pharmacological interventions. Non-pharmacological treatment, such as slow-breathing training (SBT), has been shown to reduce BP. However, there are few studies on the effect of SBT on both cardiac activation and oxidative stress in people with high BP. OBJECTIVES: To explore the effect of SBT on cardiac autonomic function (i.e., heart rate variability: HRV) and neuroendocrine response (i.e., salivary cortisol). METHODS: One hundred people (including 89 women) with high BP were randomly assigned to either a control (n = 50) or intervention group (n = 50). The intervention program was conducted for 30 min per day, for 5 days per week, for 4 weeks, with a total of 20 sessions of the SBT at the rate of 10 times per minute, whereas the control group was required to continue with their daily routine. HRV, BP, and salivary cortisol were measured before and after the intervention program. A two-way mixed ANOVA was performed for within-group and between-group comparisons over time. RESULTS: Of the 100 participants, 71 individuals completed the study. The participants in the intervention group had a lower BP and salivary cortisol levels compared to those in the control group (p < .05). Further, those participants showed an increase in the standard deviation of normal R-R intervals after the 4-week intervention program (p < .05). CONCLUSION: This study provided evidence demonstrating the effect of SBT on cardiac autonomic and stress reactivity, which has important implications for health promotion in people with high BP. CLINICAL TRIAL REGISTRATION NUMBER: TCTR20180302008.

Effect of psychosocial factors on autonomic nervous system activity in patients with heart failure.

Autonomic imbalance predicts worse clinical outcomes in patients with heart failure (HF). Managing the variables affecting heart rate variability (HRV) might improve the clinical outcomes of patients with HF. This study aimed to investigate variables affecting HRV. We assessed autonomic nervous system activity (low-frequency [Lf], high-frequency [Hf], and Lf/Hf ratio) in 60 patients with HF, employing standard measures to capture short-term HRV. To estimate the independent effects of variables such as well-known cardiac risk factors and psychosocial conditions on HRV, multivariate analyses were conducted. For psychosocial variables, we assessed depression and quality of life in patients and their family caregivers. We also assessed the self-care behavior of patients and their caregivers' burden. Depression in family caregivers and self-care behavior of patients were independently associated with a decreased Hf (ß-coefficient = 0.309, P = .039 and ß-coefficient = -0.029, P = .047, respectively). Depression of family caregivers and self-care behavior of patients may affect HRV in patients with HF.

Clinical Characteristics and Outcomes in Young-Onset Multiple System Atrophy.

BACKGROUND: Young-onset multiple system atrophy (YOMSA) is defined as the onset of multiple system atrophy (MSA) before the age of 40 years old. YOMSA is rare and there is much uncertainty of the phenotype and natural history in patients with YOMSA. OBJECTIVE: The objective is to evaluate the characteristics and disease course of patients with YOMSA. METHODS: We retrospectively reviewed medical records of patients with MSA who were evaluated at all Mayo Clinic sites from 1998 to 2021. We identified patients with YOMSA and evaluated clinical characteristics, autonomic function testing results, and disease course. RESULTS: Of 1496 patients with a diagnosis of clinically probable or clinically established MSA, 20 patients had YOMSA. The median age of onset was 39.1 (interquartile range [IQR] = 37.1, 40.1) years; 13 patients (65%) were male. MSA-parkinsonism was the most common subtype (65%). The median duration of symptom onset to YOMSA diagnosis was 4.9 (IQR = 3.7, 9) years. At the time of medical record review, 17 patients were deceased with a median survival of 8.3 (IQR = 7, 10.9) years. Univariate analysis showed that initial onset of autonomic failure predicted unfavorable survival (hazard ratio = 2.89, P = 0.04) compared to those who presented with motor impairment only at onset. At the time of YOMSA diagnosis, composite autonomic severity score was available in 19 patients with a median of 5 (IQR = 4, 6.5). CONCLUSIONS: YOMSA resembles MSA in most aspects including phenotype and prognosis, although the diagnosis is usually delayed. The presence of autonomic failure at symptom onset may be a poor predictor for survival.

Autonomic cardiac function in children and adolescents with long COVID: a case-controlled study.

Although the mechanisms underlying the pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in the long-term complications or persisting symptoms observed in a significant proportion of patients after SARS-CoV-2 infection. However, studies focused on autonomic dysfunction have primarily been conducted in adults, while autonomic function has not yet been investigated in pediatric subjects. In this study, for the first time, we assessed whether pediatric patients with long COVID present abnormalities in autonomic cardiac function. Fifty-six long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed by time-domain and frequency-domain heart rate variability parameters. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with long COVID had significant changes in HRV variables compared to healthy controls: significantly lower r-MSSD (root mean square of successive RR interval differences, 47.4 ± 16.9 versus 60.4 ± 29.1, p = 0.02), significant higher values VLF (very low frequency, 2077.8 ± 1023.3 versus 494.3 ± 1015.5 ms, p = 0.000), LF (low frequency, 1340.3 ± 635.6 versus 354.6 ± 816.8 ms, p = 0.000), and HF (high frequency, 895.7 ± 575.8 versus 278.9 ± 616.7 ms, p = 0.000). No significant differences were observed between the two groups both in systolic and diastolic parameters by echocardiography.  Conclusion: These findings suggest that pediatric patients with long COVID have an imbalance of cardiac autonomic function toward a relative predominance of parasympathetic tone, as already reported in adult patients with long COVID. Further studies are needed to clarify the clinical significance of this autonomic dysfunction and demonstrate its role as a pathophysiological mechanism of long COVID, paving the way for effective therapeutic and preventive strategies. What is Known: • Long Covid in children has been described globally, but studies have mostly focused on collecting the temporal evolution of persisting symptoms. What is New: • Cardiac autonomic imbalance toward a relative predominance of parasympathetic tone is a mechanism underlying Long Covid in children, as also described in adults.

Autonomic neuronal modulations in cardiac arrhythmias: Current concepts and emerging therapies.

The pathophysiology of atrial fibrillation and ventricular tachycardia that result in cardiac arrhythmias is related to the sustained complicated mechanisms of the autonomic nervous system. Atrial fibrillation is when the heart beats irregularly, and ventricular arrhythmias are rapid and inconsistent heart rhythms, which involves many factors including the autonomic nervous system. It's a complex topic that requires careful exploration. Cultivation of speculative knowledge on atrial fibrillation; the irregular rhythm of the heart and ventricular arrhythmias; rapid oscillating waves resulting from mistakenly inconsistent P waves, and the inclusion of an autonomic nervous system is an inconceivable approach toward clinical intricacies. Autonomic modulation, therefore, acquires new expansions and conceptions of appealing therapeutic intelligence to prevent cardiac arrhythmia. Notably, autonomic modulation uses the neural tissue's flexibility to cause remodeling and, hence, provide therapeutic effects. In addition, autonomic modulation techniques included stimulation of the vagus nerve and tragus, renal denervation, cardiac sympathetic denervation, and baroreceptor activation treatment. Strong preclinical evidence and early human studies support the annihilation of cardiac arrhythmias by sympathetic and parasympathetic systems to transmigrate the cardiac myocytes and myocardium as efficient determinants at the cellular and physiological levels. However, the goal of this study is to draw attention to these promising early pre-clinical and clinical arrhythmia treatment options that use autonomic modulation as a therapeutic modality to conquer the troublesome process of irregular heart movements. Additionally, we provide a summary of the numerous techniques for measuring autonomic tone such as heart rate oscillations and its association with cutaneous sympathetic nerve activity appear to be substitute indicators and predictors of the outcome of treatment.

Impact of different cooling solutions on autonomic modulation in horses in a novice endurance ride.

Cooling down is essential for horse recovery before veterinary inspection during an endurance ride. As salt potentially decreases water temperature, we tested whether adding salt to the water used to cool horses could aid their recovery. Twelve healthy Arabian horses participating in a novice endurance ride were divided evenly into two groups. Heart rate variability (HRV) variables, including time and frequency domains, non-linear results, and autonomic nervous system indices, were determined before recovery and at 1-min intervals for 9 min during recovery using either cold or cold-saline water. An interaction between water type and time was observed in the modulation of the SD of beat-to-beat (RR) intervals, square root of the mean squared differences between successive RR intervals (RMSSD), HRV triangular index, very low-frequency band (VLF), low-frequency band/high-frequency band ratio, and SD of the Poincaré plot perpendicular to the line of identity (SD1) non-linear results. A decrease in heart rate and the sympathetic nervous system index corresponding to an increase in RR intervals and the parasympathetic nervous system (PNS) index was observed over time. A rise in the triangular interpolation of the normal-to-normal intervals, number of successive RR interval pairs that differ more than 50 ms, low-frequency band, and total power, coinciding with decreased stress index, was detected at 9 min of recovery. A difference between RMSSD and SD1 was observed between groups, in which they were higher in horses cooling with cold-saline water when compared to cold water at 5 min after cooling began. An increase in VLF was seen at 9 min only in horses cooled with cold-saline water. In conclusion, different water types distinctly impacted HRV in horses. The predominant PNS activity in horses recovering with cold-saline water reflects its positive impact on cooling during an endurance ride.