Breathing Fluctuations Research Articles

Generation and real-time dynamics of vector square waves

The study delves into the characteristics and dynamics of vector square waves in an erbium-doped fiber laser employing a nonlinear optical loop mirror (NOLM). Through experimental investigation, the laser's operational modes, namely stable and periodic pulsating states, are achieved by manipulating polarization controllers (PCs). Within these states, the generation of two square waves with distinct peak power is observed. The vector properties of the pulses are authenticated using a polarized beam splitter (PBS). Furthermore, meticulous adjustment of the PCs reveals phenomena such as multi-pulse periodic breathing and prolonged fluctuations in pulse intensity.

Confounding effects of heart rate, breathing rate, and frontal fNIRS on interoception

Recent studies have established that cardiac and respiratory phases can modulate perception and related neural dynamics. While heart rate and respiratory sinus arrhythmia possibly affect interoception biomarkers, such as heartbeat-evoked potentials, the relative changes in heart rate and cardiorespiratory dynamics in interoceptive processes have not yet been investigated. In this study, we investigated the variation in heart and breathing rates, as well as higher functional dynamics including cardiorespiratory correlation and frontal hemodynamics measured with fNIRS, during a heartbeat counting task. To further investigate the functional physiology linked to changes in vagal activity caused by specific breathing rates, we performed the heartbeat counting task together with a controlled breathing rate task. The results demonstrate that focusing on heartbeats decreases breathing and heart rates in comparison, which may be part of the physiological mechanisms related to “listening” to the heart, the focus of attention, and self-awareness. Focusing on heartbeats was also observed to increase frontal connectivity, supporting the role of frontal structures in the neural monitoring of visceral inputs. However, cardiorespiratory correlation is affected by both heartbeats counting and controlled breathing tasks. Based on these results, we concluded that variations in heart and breathing rates are confounding factors in the assessment of interoceptive abilities and relative fluctuations in breathing and heart rates should be considered to be a mode of covariate measurement of interoceptive processes.

Physiological and motion signatures in static and time-varying functional connectivity and their subject identifiability.

Human brain connectivity yields significant potential as a noninvasive biomarker. Several studies have used fMRI-based connectivity fingerprinting to characterize individual patterns of brain activity. However, it is not clear whether these patterns mainly reflect neural activity or the effect of physiological and motion processes. To answer this question, we capitalize on a large data sample from the Human Connectome Project and rigorously investigate the contribution of the aforementioned processes on functional connectivity (FC) and time-varying FC, as well as their contribution to subject identifiability. We find that head motion, as well as heart rate and breathing fluctuations, induce artifactual connectivity within distinct resting-state networks and that they correlate with recurrent patterns in time-varying FC. Even though the spatiotemporal signatures of these processes yield above-chance levels in subject identifiability, removing their effects at the preprocessing stage improves identifiability, suggesting a neural component underpinning the inter-individual differences in connectivity.

Dinucleotides as simple models of the base stacking-unstacking component of DNA 'breathing' mechanisms.

Regulatory protein access to the DNA duplex ‘interior’ depends on local DNA ‘breathing’ fluctuations, and the most fundamental of these are thermally-driven base stacking-unstacking interactions. The smallest DNA unit that can undergo such transitions is the dinucleotide, whose structural and dynamic properties are dominated by stacking, while the ion condensation, cooperative stacking and inter-base hydrogen-bonding present in duplex DNA are not involved. We use dApdA to study stacking-unstacking at the dinucleotide level because the fluctuations observed are likely to resemble those of larger DNA molecules, but in the absence of constraints introduced by cooperativity are likely to be more pronounced, and thus more accessible to measurement. We study these fluctuations with a combination of Molecular Dynamics simulations on the microsecond timescale and Markov State Model analyses, and validate our results by calculations of circular dichroism (CD) spectra, with results that agree well with the experimental spectra. Our analyses show that the CD spectrum of dApdA is defined by two distinct chiral conformations that correspond, respectively, to a Watson–Crick form and a hybrid form with one base in a Hoogsteen configuration. We find also that ionic structure and water orientation around dApdA play important roles in controlling its breathing fluctuations.

Cerebrovascular Reactivity Mapping Without Gas Challenges: A Methodological Guide.

Cerebrovascular reactivity (CVR) is defined as the ability of vessels to alter their caliber in response to vasoactive factors, by means of dilating or constricting, in order to increase or decrease regional cerebral blood flow (CBF). Importantly, CVR may provide a sensitive biomarker for pathologies where vasculature is compromised. Furthermore, the spatiotemporal dynamics of CVR observed in healthy subjects, reflecting regional differences in cerebral vascular tone and response, may also be important in functional MRI studies based on neurovascular coupling mechanisms. Assessment of CVR is usually based on the use of a vasoactive stimulus combined with a CBF measurement technique. Although transcranial Doppler ultrasound has been frequently used to obtain global flow velocity measurements, MRI techniques are being increasingly employed for obtaining CBF maps. For the vasoactive stimulus, vasodilatory hypercapnia is usually induced through the manipulation of respiratory gases, including the inhalation of increased concentrations of carbon dioxide. However, most of these methods require an additional apparatus and complex setups, which not only may not be well-tolerated by some populations but are also not widely available. For these reasons, strategies based on voluntary breathing fluctuations without the need for external gas challenges have been proposed. These include the task-based methodologies of breath holding and paced deep breathing, as well as a new generation of methods based on spontaneous breathing fluctuations during resting-state. Despite the multitude of alternatives to gas challenges, existing literature lacks definitive conclusions regarding the best practices for the vasoactive modulation and associated analysis protocols. In this work, we perform an extensive review of CVR mapping techniques based on MRI and CO2 variations without gas challenges, focusing on the methodological aspects of the breathing protocols and corresponding data analysis. Finally, we outline a set of practical guidelines based on generally accepted practices and available data, extending previous reports and encouraging the wider application of CVR mapping methodologies in both clinical and academic MRI settings.

A crosscorrelation analysis of fluctuations in heart rate and breathing when diagnosing the autonomic disorders in patients with hypotonic type of functional dysphonia

To conduct a cross-correlation analysis of the frequency of breathing and heart rhythm variability (HRV) in the diagnosis of autonomic disorders in patients with hypotonic type of functional dysphonia. Twenty-eight women, aged between 21 and 63 years, with hypotonic type of functional dysphonia were examined. The examination of patients included an analysis of anamnesis, an objective ENT study by common methods, videostroboscopy of the larynx, and determination of the functional state of the autonomic nervous system (ANS). It was shown that in such patients, HRV contains alternating RR-intervals, which reduce the correlation coefficient between breathing fluctuations and sinus respiratory arrhythmia. In the majority of patients, ANS dysfunction is detected in the form of insufficient autonomic activity support, while the correlation coefficients (Rc) provide additional information about the autonomic tone. At high values of the correlation coefficient, the autonomic tone is optimal or reduced, at low values (below 0,5) it is optimal or elevated. At the same time, the correlation coefficient, which tends to zero at normal indicators of the total HRV power, indicates the state of ANS tension, which is associated with increased autonomic tone and can be one of the causes of sinus respiratory arrhythmia. The crosscorrelation analysis of HRV and breathing in patients with hypotonic type of functional dysphonia is one of the quantitative methods of the diagnosis of vegetative dystonia.

Entropy Analysis for the Evaluation of Respiratory Changes Due to Asbestos Exposure and Associated Smoking.

Breathing is a complex rhythmic motor act, which is created by integrating different inputs to the respiratory centres. Analysing nonlinear fluctuations in breathing may provide clinically relevant information in patients with complex illnesses, such as asbestosis. We evaluated the effect of exposition to asbestos on the complexity of the respiratory system by investigating the respiratory impedance sample entropy (SampEnZrs) and recurrence period density entropy (RPDEnZrs). Similar analyses were performed by evaluating the airflow pattern sample entropy (SampEnV’) and recurrence period density entropy (RPDEnV’). Groups of 34 controls and 34 asbestos-exposed patients were evaluated in the respiratory impedance entropy analysis, while groups of 34 controls and 30 asbestos-exposed patients were investigated in the analysis of airflow entropy. Asbestos exposition introduced a significant reduction of RPDEnV’ in non-smoker patients (p < 0.0004), which suggests that the airflow pattern becomes less complex in these patients. Smoker patients also presented a reduction in RPDEnV’ (p < 0.05). These finding are consistent with the reduction in respiratory system adaptability to daily life activities observed in these patients. It was observed a significant reduction in SampEnV’ in smoker patients in comparison with non-smokers (p < 0.02). Diagnostic accuracy evaluations in the whole group of patients (including non-smokers and smokers) indicated that RPDEnV’ might be useful in the diagnosis of respiratory abnormalities in asbestos-exposed patients, showing an accuracy of 72.0%. In specific groups of non-smokers, RPDEnV’ also presented adequate accuracy (79.0%), while in smoker patients, SampEnV’ and RPDEnV’ presented adequate accuracy (70.7% and 70.2%, respectively). Taken together, these results suggest that entropy analysis may provide an early and sensitive functional indicator of interstitial asbestosis.

Feedback field control improves the precision of T2 * quantification at 7T.

T2 * mapping offers access to a number of important structural and physiological tissue parameters. It is robust against RF field variations and overall signal scaling. However, T2 * measurement is highly sensitive to magnetic field errors, including perturbations caused by breathing motion at high baseline field. The goal of this work is to assess this issue in T2 * mapping of the brain and to study the benefit of field stabilization by feedback field control. T2 * quantification in the brain was investigated by phantom and in vivo measurements at 7T. Repeated measurements were made with and without feedback field control using NMR field sensing and dynamic third-order shim actuation. The precision and reliability of T2 * quantification was assessed by studying variation across repeated measurements as well as fitting errors. Breathing effects were found to introduce significant error in T2 * mapping results. Field control mitigates this problem substantially. In a phantom it virtually eliminates the effects of emulated breathing fluctuations in the head. In vivo it enhances the structural fidelity of T2 * maps and reduces fitting residuals along with standard deviation. In conclusion, feedback field control improves the fidelity of T2 * mapping in the presence of field perturbations. It is an effective means of countering bulk susceptibility effects of breathing and hence holds particular promise for efforts to leverage high field for T2 * studies in vivo.

Exercise training improves characteristics of exercise oscillatory ventilation in chronic heart failure.

Background Exercise oscillatory ventilation in chronic heart failure has been suggested as a factor related to adverse cardiac events, aggravated prognosis and higher mortality. Exercise training is well known to affect exercise capacity and mechanisms of pathophysiology beneficially in chronic heart failure. Little is known, however, about the exercise training effects on characteristics of exercise oscillatory ventilation in chronic heart failure patients. Design and methods Twenty (out of 38) stable chronic heart failure patients exhibited exercise oscillatory ventilation (age 54 ± 11 years, peak oxygen uptake 15.0 ± 5.0 ml/kg per minute). Patients attended 36 sessions of high intensity interval exercise. All patients underwent cardiopulmonary exercise testing before and after the programme. Assessment of exercise oscillatory ventilation was based on the amplitude of cyclic fluctuations in breathing during rest and exercise. All values are mean ± SD. Results Exercise training reduced ( P < 0.05) the percentage of exercise oscillatory ventilation duration (79.0 ± 13.0 to 50.0 ± 25.0%), while average amplitude (5.2 ± 2.0 to 4.9 ± 1.6 L/minute) and length (44.0 ± 10.9 to 41.0 ± 6.7 seconds) did not change ( P > 0.05). Exercise oscillatory ventilation patients also increased exercise capacity ( P < 0.05). Conclusions A rehabilitation programme based on high intensity interval training improved exercise oscillatory ventilation observed in chronic heart failure patients, as well as cardiopulmonary efficiency and functional capacity.

Analysing Small DNA Constructs via a Chromophore Model within the Point Dipole Approximation

As all the genetic information contained within DNA is buried within the duplex helix, there must be a series of breathing fluctuations that expose the nucleic bases to aid roles like replication, transcription, and repair. The work presented here uses a classical chromophore model under the point dipole approximation to calculate the circular dichroism as well as the absorption spectra of oligonucleotides at individual conformational states. This analysis will aid in the evaluation of these breathing fluctuations by treating systems of dimers and small length oligonucleotides as local models of these fluctuations.

Studies of T4 Primosome DNA Unwinding by Single-Molecule Fluorescence-Detected Linear Dichroism

The replication machine (replisome) of the T4 bacteriophage is an important model system for studies of DNA synthesis in all higher organisms. The helicase-primase (primosome) complex is one of three major sub-assemblies of the replisome, whose function is to processively unwind double-stranded DNA to expose single-stranded daughter strands for template-directed DNA synthesis. The detailed mechanism by which the primosome complex assembles and performs duplex DNA unwinding is not understood. Recently, we developed and applied single-molecule fluorescence-detected linear dichroism (smFLD), which can detect fluctuations of the transition dipole orientation on microsecond-to-millisecond time scales. We have studied model DNA replication fork constructs with cyanine fluorophores rigidly incorporated at the fork junction to monitor 'breathing' of the backbone as it interacts with the weakly binding T4 hexameric helicase. Our recent results [1] indicate that the time scale and distribution of microsecond breathing fluctuations at the replication fork junction are heavily influenced by the presence of the weakly binding T4 helicase, and suggest that these motions are on the pathway to the formation of the fully assembled DNA-primosome complex. The possible significance of these findings for helicase mechanisms will be discussed.[1] Phelps, C.; Lee, W.; Jose, D.; von Hippel, P. H.; Marcus, A. H. “Single-Molecule FRET and Linear Dichroism Studies of DNA ‘Breathing’ and Helicase Binding at Replication Fork Junctions,” Proc. Nat. Acad. Sci. (in press, accepted July 26, 2013, doi/10.1073/ pnas.1314862110).

Fifty years of DNA “Breathing”: Reflections on old and new approaches

The coding sequences for genes, and much other regulatory information involved in genome expression, are located 'inside' the DNA duplex. Thus the "macromolecular machines" that read-out this information from the base sequence of the DNA must somehow access the DNA "interior." Double-stranded (ds) DNA is a highly structured and cooperatively stabilized system at physiological temperatures, but is also only marginally stable and undergoes a cooperative "melting phase transition" at temperatures not far above physiological. Furthermore, due to its length and heterogeneous sequence, with AT-rich segments being less stable than GC-rich segments, the DNA genome 'melts' in a multistate fashion. Therefore the DNA genome must also manifest thermally driven structural ("breathing") fluctuations at physiological temperatures that should reflect the heterogeneity of the dsDNA stability near the melting temperature. Thus many of the breathing fluctuations of dsDNA are likely also to be sequence dependent, and could well contain information that should be "readable" and useable by regulatory proteins and protein complexes in site-specific binding reactions involving dsDNA "opening." Our laboratory has been involved in studying the breathing fluctuations of duplex DNA for about 50 years. In this "Reflections" article we present a relatively chronological overview of these studies, starting with the use of simple chemical probes (such as hydrogen exchange, formaldehyde, and simple DNA "melting" proteins) to examine the local stability of the dsDNA structure, and culminating in sophisticated spectroscopic approaches that can be used to monitor the breathing-dependent interactions of regulatory complexes with their duplex DNA targets in "real time."

A New Approach to Separate Haemodynamic Signals for Brain-Computer Interface Using Independent Component Analysis and Least Squares

Brain-computer interface (BCI) is one technology that allows a user to communicate with external devices through detecting brain activity. As a promising noninvasive technique, functional near-infrared spectroscopy (fNIRS) has recently earned increasing attention in BCI studies. However, in practice fNIRS measurements can suffer from significant physiological interference, for example, arising from cardiac contraction, breathing, and blood pressure fluctuations, thereby severely limiting the utility of the method. Here, we apply the multidistance fNIRS method, with short-distance and long-distance optode pairs, and we propose the combination of independent component analysis (ICA) and least squares (LS) with the fNIRS recordings to reduce the interference. The short-distance fNIRS measurement is treated as the virtual channel and the long-distance fNIRS measurement is treated as the measurement channel. Least squares is used to optimize the reconstruction value for brain activity signal. Monte Carlo simulations of photon propagation through a five-layered slab model of a human adult head were implemented to evaluate our methodology. The results demonstrate that the ICA method can separate the brain signal and interference; the further application of least squares can significantly recover haemodynamic signals contaminated by physiological interference from the fNIRS-evoked brain activity data.

Breathing fluctuations in position-specific DNA base pairs are involved in regulating helicase movement into the replication fork

We previously used changes in the near-UV circular dichroism and fluorescence spectra of DNA base analogue probes placed site specifically to show that the first three base pairs at the fork junction in model replication fork constructs are significantly opened by "breathing" fluctuations under physiological conditions. Here, we use these probes to provide mechanistic snapshots of the initial interactions of the DNA fork with a tight-binding replication helicase in solution. The primosome helicase of bacteriophage T4 was assembled from six (gp41) helicase subunits, one (gp61) primase subunit, and nonhydrolyzable GTPγS. When bound to a DNA replication fork construct this complex advances one base pair into the duplex portion of the fork and forms a stably bound helicase "initiation complex." Replacement of GTPγS with GTP permits the completion of the helicase-driven unwinding process. Our spectroscopic probes show that the primosome in this stable helicase initiation complex binds the DNA of the fork primarily via backbone contacts and holds the first complementary base pair of the fork in an open conformation, whereas the second, third, and fourth base pairs of the duplex show essentially the breathing behavior that previously characterized the first three base pairs of the free fork. These spectral changes, together with dynamic fluorescence quenching results, are consistent with a primosome-binding model in which the lagging DNA strand passes through the central hole of the hexagonal helicase, the leading strand binds to the "outside" surfaces of subunits of the helicase hexamer, and the single primase subunit interacts with both strands.

The dissolution of intact airway responsiveness from breathing fluctuations: what went wrong?

the dynamic pressure fluctuations of breathing do not reduce the responsiveness of an excised, intact human airway. Surprisingly, this is the main result presented by Noble et al. ([10][1]) in this issue of the Journal of Applied Physiology . How could this result stand in the face of piles of

Reduction of global interference in functional multidistance near-infrared spectroscopy using empirical mode decomposition and recursive least squares: a Monte Carlo study

Functional near-infrared spectroscopy (fNIRS) is a sensitive technique that has the potential to detect haemodynamic changes during the performance of specific activation tasks. However, in real situations, fNIRS recordings are often corrupted by physiological phenomena, especially by cardiac contraction, breathing and blood pressure fluctuations, and these forms of interference can severely limit the utility of fNIRS. We present a novel fNIRS enhancement based on the multidistance fNIRS method with short-distance and long-distance optode pairs. With this method empirical mode decomposition (EMD) is applied to decompose the short-distance fNIRS measurement into a series of intrinsic mode functions (IMFs). By utilizing the weighting coefficients for the IMFs, we derive an estimate for global interference in the long-distance fNIRS measurements. We recover the evoked brain activity by minimizing least squares between the long-distance measurements and the estimated global interference. To accelerate the computation we adopt the recursive least squares (RLS) to decrease the computation complexity due to the matrix inversion. Monte Carlo simulations of photon propagation through a five-layered slab model of a human adult head were implemented to evaluate our methodology. The results demonstrate that the EMD-RLS method can effectively remove contamination from the evoked brain activity.

SU‐GG‐T‐539: Quantitative Analysis of Dosimetric Effects Due to Irregular Respiratory Motion in Stereotactic Body Radiotherapy of Lung Cancer

Purpose: A dosimetric analysis of respiratory motion irregularities is presented for stereotactic body radiotherapy (SBRT) of lung cancer. The changes in target dosimetric coverage is quantified in terms of random and systematic variations in the respiratory motion and correlated with average tumor motion. Method and Materials: Treatment plans and respiratory motion data of 12 lung cancer patients treated under SBRT protocols are retrospectively analyzed. In addition to actual respiratory motion data, a set of simulated motion data is also generated demonstrating irregularities in form of random fluctuations as well as systematic variations. Delineated clinical target volumes (CTV) of patients are subjected to the motion pattern while the target voxels are individually tracked in three dimensions. These trajectories are finally used to map the dose accumulated in the voxels of CTV in its own frame‐of‐reference enabling dosimetric evaluation. Results: The reduction in target minimum dose (Dmin) due to irregular respiratory motion was −1.1% (s=0.7%) for mean target motion of 1.0 cm and −2.6% (s=1.4%) for 2.0 cm. Changes in tumor control probability (TCP) associated with these reductions were negligible. When investigated separately, random fluctuations in the respiratory motion accounted for no change in Dmin (s=0.2%) for 1.0 cm target motion and only −0.8% (s=0.4%) for 2.0 cm. However, systematic variations in the respiratory motion such as a change in the average target motion between the simulation and treatment sessions was observed to play a greater role, with −1.6% and −3.7% changes in Dmin for 1.0 and 2.0 cm target motions respectively. Conclusions: Dosimetric impact of irregular respiratory motion was observed to be minimal in the use of SBRT for lung cancer treatments. When individual types of uncertainties are evaluated, the systematic shifts in breathing pattern were observed to have larger effect than commonly observed random breathing fluctuations.

Cheyne-Stokes Respiration in Patients with Heart Failure

Cheyne-Stokes respiration (CSR) is a form of central sleep-disordered breathing (SDB) in which there are cyclical fluctuations in breathing that lead to periods of central apneas/hypopnea, which alternate with periods of hyperpnea. The crescendo-decrescendo pattern of respiration in CSR is a compensation for the changing levels of blood oxygen and carbon dioxide. Severe congestive heart failure seems to be the most important risk factor for the development of CSR. A number of pathophysiologic changes, such as sleep disruption, arousals, hypoxemia-reoxygenation, hypercapnia/hypocapnia, and changes in intrathoracic pressure have harmful effects on the cardiovascular system, and the presence of CSR is associated with increased mortality and morbidity in subjects with variable degrees of heart failure. The management of CSR involves optimal control of underlying heart failure, oxygen therapy, and positive airway pressure support. In this review, we initially define and describe the epidemiology of central sleep apnea (CSA) and CSR, its pathogenesis, clinical presentation, diagnostic methods, and then discuss the recent developments in the management in patients with heart failure.

Acute reverse microdialysis (MD) of atropine into the pontine respiratory group (PRG) of goats at night has no affect on breathing, but does tend to increase NREM and REM sleep

Acetylcholine is an important neurotransmitter in the PRG (Respir. Physiol. Neurobiol. 2004 Nov 15;143(2‐3):235‐49). Tonic pontine influences may have increased importance during sleep to stabilize and prevent large fluctuations in breathing. Abnormalities in this tonic facilitation, such as attenuation of cholinergic modulation (Respir. Physiol. Neurobiol. 131:135‐144, 2002.), may contribute to sleep‐disordered breathing. Accordingly, we chronically implanted microtubules into the PRG of 7 goats to assess the response of MD of atropine (50mM) into the PRG at night. MD of atropine at night did not have a significant effect on pulmonary ventilation (VI), breathing frequency, or tidal volume compared to MD of mock cerebral spinal fluid (mCSF). However, a normal state‐dependent respiratory depression was observed, where VI during REM &lt; VI during NREM &lt; VI during wakefulness. The percent of NREM and REM sleep tended to increase from the first night of ipsilateral MD, to the second night of contralateral MD, and to the third night of bilateral MD. We conclude that MD of atropine into the PRG at night does not affect breathing, but does tend to increase both NREM and REM sleep. Supported by the Department of Veterans Affairs and NIH 25739.

Point:Counterpoint: Respiratory sinus arrhythmia is due to a central mechanism vs. respiratory sinus arrhythmia is due to the baroreflex mechanism

Blood pressure and heart periods fluctuate at respiratory frequencies in healthy humans. Some researchers ([8][1], [23][2]) explain this as a cause-and-effect relation: blood pressure changes trigger baroreflex-mediated R-R interval changes. Here I make the case that respiratory sinus arrhythmia is