Cardiac vagal activity is associated with gut-microbiome patterns in women-An exploratory pilot study.

Introduction: A functional reciprocity between the gut microbiome and vagal nerve activity has been suggested, however, human studies addressing this phenomenon are limited. Methods: Twenty-four-hour cardiac vagal activity (CVA) was assessed from 73 female participants (aged 24.5 ± 4.3 years). Additionally, stool samples were subjected to 16SrRNA gene analysis (V1-V2). Quantitative Insights Into Microbial Ecology (QIIME) was used to analyse microbiome data. Additionally, inflammatory parameters (such as CRP and IL-6) were derived from serum samples. Results: Daytime CVA correlated significantly with gut microbiota diversity (r sp = 0.254, p = 0.030), CRP (r sp = -0.348, p = 0.003), and IL-6 (r sp = -0.320, p = 0.006). When the group was divided at the median of 24 h CVA (Mdn = 1.322), the following features were more abundant in the high CVA group: Clostridia (Linear discriminant analysis effect size (LDA) = 4.195, p = 0.029), Clostridiales (LDA = 4.195, p = 0.029), Lachnospira (LDA = 3.489, p = 0.004), Ruminococcaceae (LDA = 4.073, p = 0.010), Faecalibacterium (LDA = 3.982, p = 0.042), Lactobacillales (LDA = 3.317, p = 0.029), Bacilli (LDA = 3.294, p = 0.0350), Streptococcaceae (LDA = 3.353, p = 0.006), Streptococcus (LDA = 3.332, p = 0.011). Based on Dirichlet multinomial mixtures two enterotypes could be detected, which differed significantly in CVA, age, BMI, CRP, IL-6, and diversity. Conclusions: As an indicator of gut-brain communication, gut microbiome analysis could be extended by measurements of CVA to enhance our understanding of signalling via microbiota-gut-brain-axis and its alterations through psychobiotics.

Driver drowsiness estimation using EEG signals with a dynamical encoder-decoder modeling framework.

Drowsiness is a leading cause of accidents on the road as it negatively affects the driver's ability to safely operate a vehicle. Neural activity recorded by EEG electrodes is a widely used physiological correlate of driver drowsiness. This paper presents a novel dynamical modeling solution to estimate the instantaneous level of the driver drowsiness using EEG signals, where the PERcentage of eyelid CLOSure (PERCLOS) is employed as the ground truth of driver drowsiness. Applying our proposed modeling framework, we find neural features present in EEG data that encode PERCLOS. In the decoding phase, we use a Bayesian filtering solution to estimate the PERCLOS level over time. A data set that comprises 18 driving tests, conducted by 13 drivers, has been used to investigate the performance of the proposed framework. The modeling performance in estimation of PERCLOS provides robust and repeatable results in tests with manual and automated driving modes by an average RMSE of 0.117 (at a PERCLOS range of 0 to 1) and average High Probability Density percentage of 62.5%. We further hypothesized that there are biomarkers that encode the PERCLOS across different driving tests and participants. Using this solution, we identified possible biomarkers such as Theta and Delta powers. Results show that about 73% and 66% of the Theta and Delta powers which are selected as biomarkers are increasing as PERCLOS grows during the driving test. We argue that the proposed method is a robust and reliable solution to estimate drowsiness in real-time which opens the door in utilizing EEG-based measures in driver drowsiness detection systems.

Cardiorespiratory Interaction and Autonomic Sleep Quality Improve during Sleep in Beds Made from Pinus cembra (Stone Pine) Solid Wood.

Cardiorespiratory interactions (CRIs) reflect the mutual tuning of two important organismic oscillators-the heartbeat and respiration. These interactions can be used as a powerful tool to characterize the self-organizational and recreational quality of sleep. In this randomized, blinded and cross-over design study, we investigated CRIs in 15 subjects over a total of 253 nights who slept in beds made from different materials. One type of bed, used as control, was made of melamine faced chipboard with a wood-like appearance, while the other type was made of solid wood from stone pine (Pinus cembra). We observed a significant increase of vagal activity (measured by respiratory sinus arrhythmia), a decrease in the heart rate (as an indicator of energy consumption during sleep) and an improvement in CRIs, especially during the first hours of sleep in the stone pine beds as compared to the chipboard beds. Subjective assessments of study participants' well-being in the morning and sub-scalar assessments of their intrapsychic stability were significantly better after they slept in the stone pine bed than after they slept in the chipboard bed. Our observations suggest that CRIs are sensitive to detectable differences in indoor settings that are relevant to human health. Our results are in agreement with those of other studies that have reported that exposure to volatile phytochemical ingredients of stone pine (α-pinene, limonene, bornyl acetate) lead to an improvement in vagal activity and studies that show a reduction in stress parameters upon contact with solid wood surfaces.

Dynamics of Vagal Activity Due to Surgery and Subsequent Rehabilitation.

BACKGROUND: Vagal activity is critical for maintaining key body functions, including the stability of inflammatory control. Its weakening, such as in the aftermatch of a surgery, leaves the body vulnerable to diverse inflammatory conditions, including sepsis. METHODS: Vagal activity can be measured by the cardiorespiratory interaction known as respiratory sinus arrhythmia or high-frequency heart-rate variability (HRV). We examined the vagal dynamics before, during and after an orthopedic surgery. 39 patients had their HRV measured around the period of operation and during subsequent rehabilitation. Measurements were done during 24 h circadian cycles on ten specific days. For each patient, the circadian vagal activity was calculated from HRV data. RESULTS: Our results confirm the deteriorating effect of surgery on vagal activity. Patients with stronger pre-operative vagal activity suffer greater vagal withdrawal during the peri-operative phase, but benefit from stronger improvements during post-operative period, especially during the night. Rehabilitation seems not only to efficiently restore the vagal activity to pre-operative level, but in some cases to actually improve it. DISCUSSION: Our findings indicate that orthopedic rehabilitation has the potential to strengthen the vagal activity and hence boost inflammatory control. We conclude that providing a patient with a vagal reinforcement procedure prior to the surgery ("pre-habilitation") might be a beneficial strategy against post-operative complications. The study also shows the clinical usefulness of quantifying the cardiorespiratory interactions.

Heart Rhythm Analyzed via Shapelets Distinguishes Sleep From Awake.

Automatically determining when a person falls asleep from easily available vital signals is important, not just for medical applications but also for practical ones, such as traffic safety or smart homes. Heart dynamics and respiration cycle couple differently during sleep and awake. Specifically, respiratory modulation of heart rhythm or respiratory sinus arrhythmia (RSA) is more prominent during sleep, as both sleep and RSA are connected to strong vagal activity. The onset of sleep can be recognized or even predicted as the increase of cardio-respiratory coupling. Here, we employ this empirical fact to design a method for detecting the change of consciousness status (sleep/awake) based only on heart rate variability (HRV) data. Our method relies on quantifying the (self)similarity among shapelets - short chunks of HRV time series - whose "shapes" are related to the respiration cycle. To test our method, we examine the HRV data of 75 healthy individuals recorded with microsecond precision. We find distinctive patterns stable across age and sex, that are not only indicative of sleep and awake, but allow to pinpoint the change from awake to sleep almost immediately. More systematic analysis along these lines could lead to a reliable prediction of sleep.

Disentangling respiratory sinus arrhythmia in heart rate variability records.

OBJECTIVE: Several different measures of heart rate variability, and particularly of respiratory sinus arrhythmia, are widely used in research and clinical applications. For many purposes it is important to know which features of heart rate variability are directly related to respiration and which are caused by other aspects of cardiac dynamics. APPROACH: Inspired by ideas from the theory of coupled oscillators, we use simultaneous measurements of respiratory and cardiac activity to perform a nonlinear disentanglement of the heart rate variability into the respiratory-related component and the rest. MAIN RESULTS: The theoretical consideration is illustrated by the analysis of 25 data sets from healthy subjects. In all cases we show how the disentanglement is manifested in the different measures of heart rate variability. SIGNIFICANCE: The suggested technique can be exploited as a universal preprocessing tool, both for the analysis of respiratory influence on the heart rate and in cases when effects of other factors on the heart rate variability are in focus.

Investigation of a Micro-test for Circulatory Autonomic Nervous System Responses.

Aims and Objectives: The autonomic nervous system plays an important role in homeostasis and organismic recreation, control of immune function, inflammation, and bone growth. It also regulates blood pressure and orthostasis via vagal and sympathetic pathways. Besides recording of heart rate variability (HRV), which characterizes medium (1-5 min) and long term (circadian) autonomic tone or modulation, no gentle tests of short-term autonomic reactivity and control are available. In 1976 Nogier described a short time cardiovascular response ("Réflexe Auriculo Cardiaque", RAC) which could be used to investigate short term autonomic reactions without changing system characteristics and thus being repeatable in short intervals. In this paper, we investigated the possible application of the Nogier reaction as a micro-test for the identification of a disturbed sensitivity or reactivity of the autonomic nervous system. Methods: We statistically analyzed cardiovascular signals derived during the application of small repeated stimuli utilizing methods of signal averaging to characterize the physiological background. Specifically, the Nogier reaction was investigated using simultaneous recordings of ECG, pulse waves, and respiration. Results: Significant fast (delay 1-5 s) and slower (delay 6-12 s) cardio-autonomic responses to different stimuli which characterize short term were observed. From time characteristics and type of signals where they occur we deduce that fast changes observed in heart rate are vagal reactions to the small stimuli whereas slower changes observed in pulse waves stem from sympathetic nervous system responses. Conclusions: The investigated autonomic micro-test opens the possibility to differentially investigate both limbs of the autonomic nervous system with minimal stimuli. It can be performed within seconds and does not change the set point of the system in opposition to less subtle tests such as Valsalva maneuver. Therefore, it is well-suited for quick, repeated measurements of autonomic nervous system reactivity.

In vivo cardiac phase response curve elucidates human respiratory heart rate variability.

Recovering interaction of endogenous rhythms from observations is challenging, especially if a mathematical model explaining the behaviour of the system is unknown. The decisive information for successful reconstruction of the dynamics is the sensitivity of an oscillator to external influences, which is quantified by its phase response curve. Here we present a technique that allows the extraction of the phase response curve from a non-invasive observation of a system consisting of two interacting oscillators--in this case heartbeat and respiration--in its natural environment and under free-running conditions. We use this method to obtain the phase-coupling functions describing cardiorespiratory interactions and the phase response curve of 17 healthy humans. We show for the first time the phase at which the cardiac beat is susceptible to respiratory drive and extract the respiratory-related component of heart rate variability. This non-invasive method for the determination of phase response curves of coupled oscillators may find application in many scientific disciplines.

Multimodal therapy concept and aerobic training in breast cancer patients with chronic cancer-related fatigue.

UNLABELLED: HYPOTHESE: Cancer-related fatigue (CRF) and sleep disorders are some of the most wearing and common symptoms in disease-free breast cancer patients (BC). Aerobic training (AT) is the treatment with the best available evidence, even though it seems to be insufficient with regards to improvements in cognitive fatigue. We introduced a new multimodal therapy concept (MM) consisting of psycho-, sleep-education and new approaches based on anthroposophic medicine such as eurythmy and painting therapy. STUDY DESIGN: This pilot study will test the implementation of MM and yield first results of the MM and AE in our centres. METHODS: 31 out of 34 patients suffering from BC and CRF were fully assessed in a ten-week intervention study. 21 patients chose MM and 10 decided on AT. CRF was measured with the help of the Cancer Fatigue Scale (CFS-D), and the global quality of sleep was measured with the Pittsburgh Sleep Quality Index (PSQI). We also captured autonomic regulation (aR) and patients' satisfaction with questionnaires. Statistical analysis was done with SAS 9.1.3 for windows. RESULTS: The new MM therapy can be implemented with high satisfaction among patients. Significant improvements were found in the MM group with regards to CFS-D, global quality of sleep, sleep efficiency (PSQI), aR and rest/activity regulation compared to baseline (all p<0.05). In the AT group aR orthostatic-circulatory and rest/activity regulation improved significantly (p<0.05), too. However, no improvement in cognitive fatigue was seen in either group. CONCLUSION: The multimodal therapy concept was feasible and improved cancer fatigue, sleep quality, autonomic and rest-/activity regulation in breast cancer patients. It may therefore constitute a valuable treatment option in addition to aerobic training for BC patients with CRF. A further study with larger sample size needs to be carried out to assess the efficacy of combined multimodal-aerobic therapy.

Comparison of respiratory rates derived from heart rate variability, ECG amplitude, and nasal/oral airflow.

It would often be desirable to obtain the respiratory rate during everyday conditions without obtaining an additional respiratory trace. This study investigates the agreement between respiratory rate assessed from the electrocardiogram (ECG) and the reference respiratory rate derived from a nasal/oral airflow (AF). Nasal/oral airflow and a Holter ECG were recorded in 52 healthy subjects (26 males, age range: 25.4-85.4 years) during everyday conditions for at least 10 h, including night-time sleep. The respiratory rate was assessed for each 5-min epoch (1) using respiratory sinus arrhythmia (RSA), (2) utilizing the respiration induced variations of the R-wave amplitude (ECG derived respiration (EDR)). The agreement with respect to AF was quantified using the average/std and the concordance correlation coefficient rho(c). For RSA and EDR the difference with respect to AF was 0.2 cpm (std: 0.6 cpm) during sleep and -0.2 cpm (std: 1.0 cpm) during wake time. During sleep the RSA-approach performed best for subjects < or =50 years (rho(c) = 0.79) and worst for subjects >50 years (rho(c) = 0.41). The correlation of the EDR-approach was rho(c) = 0.73 for both groups. In conclusion, the respiratory rate may be assessed with reasonable agreement by both methods in younger subjects, but EDR should be preferred in the elderly.

Why life oscillates--from a topographical towards a functional chronobiology.

Chronobiology has identified a multitude of rhythms within our body as well as within each living cell. Some of these rhythms, such as the circadian and circannual, interact with our environment, while others run on their own, but are often coupled to the circadian or to other body rhythms. Recent evidence shows that these rhythms might be more important for our health than expected: Disturbance of the circadian rhythms by jet lag or shift work not only evokes autonomic disturbances but also increases the incidence of cancer, as shown in this issue of Cancer Causes and Control. The occurrence of rhythms in the organism obviously bears several advantages: (1) It increases organismic stability by calibrating the system's characteristics: Regulation curves in time and space are crucial for controlling physiological long-term stability. To determine its properties continuously the system varies its parameters slightly over several time scales at different frequencies-akin to what our body does, e.g. in heart-rate variability. (2) Tuning and synchronization of rhythms saves energy: It was Huygens who observed that clocks on a wall tend to synchronize their beats. It turned out later that synchronisation is a very common phenomenon observed in bodies' rhythms and can be found, for example, when we relax or sleep. At such times energy consumption is minimal, our body working most efficiently. (3) Temporal compartmentalization allows polar events to occur in the same space unit: there are polarities in the universe of our body, which cannot happen simultaneously. Systole and diastole, inspiration and expiration, work and relaxation, wakefulness and sleep, reductive and oxidative states cannot be performed efficiently at the same time and place. Temporal compartmentalization is probably the most efficient way to mediate between these polarities. Chronobiology and chronomedicine are opening a new and very exciting understanding of our bodies' regulation. The biological time and its oscillations gain more attention and importance as these interrelations are understood.

Changes of respiratory sinus arrhythmia during the menstrual cycle depend on average heart rate.

To evaluate the complex time course of changes in respiratory sinus arrhythmia (RSA) during the menstrual cycle, daily beat-to-beat morning recordings of heart rate (HR) were carried out in 26 healthy female subjects (age 20-29 years) during two menstrual cycles. For determination of fast, vagally mediated variations of HR we used a robust time-domain measure of RSA (logRSA). We found pronounced changes in HR during the menstrual cycle with a minimum in the early follicular phase and a maximum in the late luteal phase. There were large differences between individuals in the fluctuations of logRSA during the menstrual cycle that were related to average HR: subjects with a low HR exhibited higher values of logRSA in the luteal compared to the follicular phase, whereas the trend was reversed in subjects with a high HR. The difference of extreme points of logRSA fluctuations (early follicular and mid luteal phase) was correlated to average HR (r=-0.64, P < 0.001). We conclude that different patterns of RSA fluctuations occur depending on the level of average HR.

Effects of speech therapy with poetry on heart rate rhythmicity and cardiorespiratory coordination.

Our objective was to study the effects of guided rhythmic speech with poetry, referred to as anthroposophical therapeutic speech (ATS), on binary differential heart rate dynamics (also called musical heart rate rhythmicity or HRR) as well as on classical spectral parameters during the 15 min after a speech exercise had ended. A total of 105 1-h sessions with speech or control exercises were performed in seven healthy subjects, with 15 sessions each. Heart rate was recorded with ambulatory solid state recorders. Sessions were divided into a 15-min baseline measurement (S1), 30 min of exercise and a 15-min effect measurement (S2). The overall binary pattern predominance (PP) as well as the frequency of predominant and cyclically recurrent cardiorespiratory phase locking patterns were calculated from HRR and their changes from S1 to S2 were compared with the changes in low and high frequency heart rate variability. The results showed that: (i) ATS provokes alterations in heart rate dynamics which are different from those after control exercises and which persist at least for 15 min following exercise; (ii) in comparison to spectral parameters of heart rate variability, pattern predominance discloses the effects of rhythmic speech exercises best; and (iii) cardiorespiratory phase locking patterns, which contribute most to the rhythm pattern predominance, are more prominent after ATS.