Correlation Analysis of Synchronization Type and Degree in Respiratory Neural Network

Pre-Bötzinger complex (PBC) is a necessary condition for the generation of respiratory rhythm. Due to the existence of synaptic gaps, delay plays a key role in the synchronous operation of coupled neurons. In this study, the relationship between synchronization and correlation degree is established for the first time by using ISI bifurcation and correlation coefficient, and the relationship between synchronization and correlation degree is discussed under the conditions of no delay, symmetric delay, and asymmetric delay. The results show that the phase synchronization of two coupling PBCs is closely related to the weak correlation, that is, the weak phase synchronization may occur under the condition of incomplete synchronization. Moreover, the time delay and coupling strength are controlled in the modified PBC network model, which not only reveals the law of PBC firing transition but also reveals the complex synchronization behavior in the coupled chaotic neurons. Especially, when the two coupled neurons are nonidentical, the complete synchronization will disappear. These results fully reveal the dynamic behavior of the PBC neural system, which is helpful to explore the signal transmission and coding of PBC neurons and provide theoretical value for further understanding respiratory rhythm.

Pertussis and pertussis-like syndrome in young children

The most common infectious diseases with a risk of severe, non-smooth course and unfavorable outcome in young children, including the first year of life, are pertussis and respiratory syncytial viral infection (RSV infection), often occurring with pertussis-like syndrome.Objective: to establish clinical and laboratory differential diagnostic criteria for pertussis and RSV infection in children of the first year of life.Materials and methods: A retrospective comparative study was conducted, which included patients of the first year of life (from 1 month to 11 months and 29 days), regardless of the duration of hospitalization and duration of the disease: 48 patients with pertussis and 26 with acute RSV infection.Results: The compared groups of patients were comparable in age, the number of severe forms (4.6 ± 0.5 months, 17% for pertussis and 4.0 ± 0.2 months, 16% for RS infection). The disease in both cases began subacute, however, with RSV infection 92% of children were hospitalized in the first 5 days from the onset of the disease, with pertussis — in the first week of the period of convulsive cough — 47.9%, in the second week — 41.7%, in the third week — 10.4%. 52% of patients with RSV infection had no fever or (in 32%) did not exceed 1—3 days. In 41.3% of patients it was subfebrile (37—38 °C), in 21.1% it was febrile (38—39 °C). In patients with pertussis the onset of the disease took place against the background of normal body temperature. In patients with RSV infection, bronchiolitis was recorded in 24% of cases, obstructive bronchitis — in 60%. Patients with pertussis, 89.6% of whom were not vaccinated and 10.4% did not complete the initial course of vaccination, had a typical paroxysmal cough with reprises. Complications in the form of respiratory rhythm disturbances were recorded in 14.6% of cases, pneumonia — in 6.3%. Comparison of hematological parameters revealed highly significant differences in the levels of leukocytosis and relative lymphocytosis (p < 0.001), as well as thrombocytosis (p < 0.01), with the predominance of all indicators in patients with pertussis.Conclusion. Differential diagnostic criteria for the similarity of the clinical picture may be established hematological differences: pronounced leukocytosis due to lymphocytosis, increasing in dynamics, and thrombocytosis in pertussis and normocytosis with moderate lymphocytosis, a possible tendency to thrombocytosis in severe RSV infection.

Putting the theory into 'burstlet theory': A biophysical model of bursts and burstlets in the respiratory preBötzinger complex

Inspiratory breathing rhythms arise from synchronized neuronal activity in a bilaterally distributed brainstem structure known as the preBötzinger complex (preBötC). In in vitro slice preparations containing the preBötC, extracellular potassium must be elevated above physiological levels (to 7-9mM) to observe regular rhythmic respiratory motor output in the hypoglossal nerve to which the preBötC projects. Reexamination of how extracellular K+ affects preBötC neuronal activity has revealed that low amplitude oscillations persist at physiological levels. These oscillatory events are sub-threshold from the standpoint of transmission to motor output and are dubbed burstlets. Burstlets arise from synchronized neural activity in a rhythmogenic neuronal subpopulation within the preBötC that in some instances may fail to recruit the larger network events, or bursts, required to generate motor output. The fraction of subthreshold preBötC oscillatory events (burstlet fraction) decreases sigmoidally with increasing extracellular potassium. These observations underlie the burstlet theory of respiratory rhythm generation. Experimental and computational studies have suggested that recruitment of the non-rhythmogenic component of the preBötC population requires intracellular Ca2+ dynamics and activation of a calcium-activated non-selective cationic current. In this computational study, we show how intracellular calcium dynamics driven by synaptically triggered Ca2+ influx as well as Ca2+ release/uptake by the endoplasmic reticulum in conjunction with a calcium-activated non-selective cationic current can explain all of the key observations underlying the burstlet theory of respiratory rhythm generation. Thus, we provide a mechanistic basis to unify the experimental findings on rhythm generation and motor output recruitment in the preBötC.

Substance P/ Neurokinin-1 Receptor, Trigeminal Ganglion, Latency, and Coronavirus Infection-Is There Any Link?

Novel Severe Acute Respiratory Syndrome-Corona Virus-2 infection (SARS-CoV-2) is an acute respiratory and infectious disease. This perspective aims to provide a basic understanding of the inflammation caused by SARS-CoV-2 and its relation to the trigeminal ganglion (TG). The virus enters through the mucous membranes of the orofacial region and reaches the TG, where it resides and takes control of its peptides including Substance P (SP). SP is the main neuropeptide, neuromodulator, and neuro-hormone of TG, associated with nociception and inflammation under noxious stimulus. SP release is triggered and, consequently, affects the immune cells and blood vessels to release the mediators for inflammation. Hence, cytokine storm is initiated and causes respiratory distress, bronchoconstriction, and death in complicated cases. Neurokinin-1 Receptor (NK-1R) is the receptor for SP and its antagonists, along with glucocorticoids, may be used to alleviate the symptoms and treat this infection by blocking this nociceptive pathway. SP seems to be the main culprit involved in the triggering of inflammatory pathways in SARS-CoV-2 infection. It may have a direct association with cardio-respiratory rhythm, sleep-wake cycle, nociception, and ventilatory responses and regulates many important physiological and pathological functions. Its over-secretion should be blocked by NK-1R antagonist. However, experimental work leading to clinical trials are mandatory for further confirmation. Here, it is further proposed that there is a possibility of latency in SARS-CoV-2 virus infection if it is acting through TG, which is the main site for other viruses that become latent.

Extending the spectral decomposition of Granger causality to include instantaneous influences: application to the control mechanisms of heart rate variability

Assessing Granger causality (GC) intended as the influence, in terms of reduction of variance of surprise, that a driver variable exerts on a given target, requires a suitable treatment of ‘instantaneous’ effects, i.e. influences due to interactions whose time scale is much faster than the time resolution of the measurements, due to unobserved confounders or insufficient sampling rate that cannot be increased because the mechanism of generation of the variable is inherently slow (e.g. the heartbeat). We exploit a recently proposed framework for the estimation of causal influences in the spectral domain and include instantaneous interactions in the modelling, thus obtaining (i) a novel index of undirected instantaneous causality and (ii) a novel measure of GC including instantaneous effects. An effective procedure to speed up the optimization of parameters in this frame is also presented. After illustrating the proposed formalism in a theoretical example, we apply it to two datasets of cardiovascular and respiratory time series and compare the values obtained within the frequency bands of physiological interest by the proposed total measure of causality with those derived from the standard GC analysis. We find that the inclusion of instantaneous causality allows us to correctly disentangle the baroreflex mechanism from the effects related to cardiorespiratory interactions. Moreover, studying how controlling the respiratory rhythm acts on cardiovascular interactions, we document an increase of the direct (non-baroreflex mediated) influence of respiration on the heart rate in the respiratory frequency band when switching from spontaneous to paced breathing. This article is part of the theme issue ‘Advanced computation in cardiovascular physiology: new challenges and opportunities’.

Heart rate variability changes in mild-symptomatic, physically fit male in 4-6 weeks from the end of SARS-Cov-2 infection

SARS-Cov-2 infection, due to inflammation processes, can affect autonomic nervous system and heart rate variability (HRV) even after disease. Previous studies showed significant changes in HRV parameters in severe (including fatal) infection of SARS-Cov-2. However, HRV analysis for the asymptomatic or mild-symptomatic Covid-19 patients have not been reported. In this study, we suggested that there is an influence of a SARS-Cov-2 infection on the HRV in such patients after weeks form disease.Sixty-five ECG Holter recordings from young (mean age 22.6 ± 3.4 years), physically fit male subjects after 4-6 weeks from the second negative test (considered to be the beginning of recovery) and twenty-six control male subjects (mean age 23.2 ± 2.9 years) were considered in the study. Night-time RR time series were extracted from ECG signals. Selected linear, frequency as well as nonlinear HRV parameters were calculated. We found significant differences in Porta’s symbolic analysis parameters V0 and V2 (p<0.001), α2 (p<0.001), very low frequency component (VLF; p=0.022), and respiratory peak (from PRSA method; p=0.012). These differences may be caused by the changes of the parasympathetic autonomic nervous system as well as by the coupling of respiratory rhythm with heart rate due to an increase in pulmonary arterial vascular resistance.The results suggest that the changes in the HRV, thus autonomic nervous system, are measurable after a few weeks from the beginning of the recovery even in the post-Covid group of young and physically active population. We indicated HRV sensitive markers which could be used in the long-term monitoring of recovered patients.

Effects of Cardiac Resynchronization Therapy on Cardio-Respiratory Coupling

In this study, the effect of cardiac resynchronization therapy (CRT) on the relationship between the cardiovascular and respiratory systems in heart failure subjects was examined for the first time. We hypothesized that alterations in cardio-respiratory interactions, after CRT implantation, quantified by signal complexity, could be a marker of a favorable CRT response. Sample entropy and scaling exponents were calculated from synchronously recorded cardiac and respiratory signals 20 min in duration, collected in 47 heart failure patients at rest, before and 9 months after CRT implantation. Further, cross-sample entropy between these signals was calculated. After CRT, all patients had lower heart rate and CRT responders had reduced breathing frequency. Results revealed that higher cardiac rhythm complexity in CRT non-responders was associated with weak correlations of cardiac rhythm at baseline measurement over long scales and over short scales at follow-up recording. Unlike CRT responders, in non-responders, a significant difference in respiratory rhythm complexity between measurements could be consequence of divergent changes in correlation properties of the respiratory signal over short and long scales. Asynchrony between cardiac and respiratory rhythm increased significantly in CRT non-responders during follow-up. Quantification of complexity and synchrony between cardiac and respiratory signals shows significant associations between CRT success and stability of cardio-respiratory coupling.

Phox2b mutation mediated by Atoh1 expression impaired respiratory rhythm and ventilatory responses to hypoxia and hypercapnia

Retrotrapezoid nucleus (RTN) neurons are involved in central chemoreception and respiratory control. Lineage tracing studies demonstrate RTN neurons to be derived from Phox2b and Atoh1 expressing progenitor cells in rhombere 4. Phox2b exon 3 mutations cause congenital central hypoventilation syndrome (CCHS), producing an impaired respiratory response to hypercapnia and hypoxia. Our goal was to investigate the extent to which a conditional mutation of Phox2b within Atoh1-derived cells might affect a) respiratory rhythm; b) ventilatory responses to hypercapnia and hypoxia and c) number of RTN-chemosensitive neurons. Here, we used a transgenic mouse line carrying a conditional Phox2bΔ8 mutation activated by cre-recombinase. We crossed them with Atoh1Cre mice. Ventilation was measured by whole body plethysmograph during neonate and adult life. In room air, experimental and control groups showed similar basal ventilation; however, Atoh1Cre/Phox2bΔ8 increased breath irregularity. The hypercapnia and hypoxia ventilatory responses were impaired in neonates. In contrast, adult mice recovered ventilatory response to hypercapnia, but not to hypoxia. Anatomically, we observed a reduction of the Phox2b+/TH- expressing neurons within the RTN region. Our data indicates that conditionally expression of Phox2b mutation by Atoh1 affect development of the RTN neurons and are essential for the activation of breathing under hypoxic and hypercapnia condition, providing new evidence for mechanisms related to CCHS neuropathology