Noninvasive cardiac psychophysiology as a tool for translational science with marmosets

The importance of marmosets for comparative and translational science has grown in recent years because of their relatively rapid development, birth cohorts of twins, family social structure, and genetic tractability. Despite this, they remain understudied in investigations of affective processes. In this methodological note, we establish the validity of using noninvasive commercially available equipment to record cardiac physiology and compute indices of autonomic nervous system activity—a major component of affective processes. Specifically, we recorded electrocardiogram and impedance cardiogram, from which we derived heart rate, respiration rate, measures of high‐frequency heart rate variability (indices of parasympathetic autonomic nervous system activity), and ventricular contractility (an index of sympathetic autonomic nervous system activity). Our methods produced physiologically plausible data, and further, animals with increased heart rates during testing were also more reactive to isolation from their social partner and presentation of novel objects, though no relationship was observed between reactivity and specific indices of parasympathetic or sympathetic nervous system activity.     

Rapid fluctuations in atrial fibrillatory electrophysiology detected during controlled respiration

Heart rate during sinus rhythm is modulated through the autonomic nervous system, which generates short-term oscillations. The high-frequency components in these oscillations are associated with respiration, causing sinus arrhythmia, mediated by the parasympathetic nervous system. In this study, we evaluated whether slow, controlled respiration causes cyclic fluctuations in the frequency of the fibrillating atria. Eight patients (four women; median age 63 yr, range 53-68 yr) with chronic atrial fibrillation (AF) and third-degree atrioventricular block treated by permanent pacemaker were studied. ECG was recorded during baseline rest, during 0.125-Hz frequency controlled respiration, and finally during controlled respiration after full vagal blockade. We calculated fibrillatory frequency using frequency analysis of the fibrillatory ECG for overlapping 2.5-s segments; spectral analysis of the resulting frequency trend was performed to determine the spectrum of variations of fibrillatory frequency. Normalized spectral power at respiration frequency increased significantly during controlled respiration from 1.4 (0.76-2.0) (median and range) at baseline to 2.7 (1.2-5.8) (P = 0.01). After vagal blockade, the power at respiration frequency decreased to 1.2 (0.23-2.8) (P = 0.01). Controlled respiration causes cyclic fluctuations in the AF frequency in patients with long-duration AF. This phenomenon seems to be related to parasympathetic modulations of the AF refractory period.     

Peculiarities of the Heart Rate Control during Competitive Entrance Examinations

A study was made of the dynamics of psychophysiological parameters and the activities of the systems regulating the heart rate in prospective post-secondary students taking competitive entrance examinations. The responses of the regulatory systems to examination stress were of two types, sympathetic and parasympathetic, depending on the initial state of the autonomic nervous system and the psychophysiological personality traits.     

Restoring the balance of the autonomic nervous system as an innovative approach to the treatment of rheumatoid arthritis

The immunomodulatory effect of the autonomic nervous system has raised considerable interest over the last decades. Studying the influence on the immune system and the role in inflammation of the sympathetic as well as the parasympathetic nervous system not only will increase our understanding of the mechanism of disease, but also could lead to the identification of potential new therapeutic targets for chronic immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). An imbalanced autonomic nervous system, with a reduced parasympathetic and increased sympathetic tone, has been a consistent finding in RA patients. Studies in animal models of arthritis have shown that influencing the sympathetic (via α- and β-adrenergic receptors) and the parasympathetic (via the nicotinic acetylcholine receptor α7nAChR or by electrically stimulating the vagus nerve) nervous system can have a beneficial effect on inflammation markers and arthritis. The immunosuppressive effect of the parasympathetic nervous system appears less ambiguous than the immunomodulatory effect of the sympathetic nervous system, where activation can lead to increased or decreased inflammation depending on timing, doses and kind of adrenergic agent used. In this review we will discuss the current knowledge of the role of both the sympathetic (SNS) and parasympathetic nervous system (PNS) in inflammation with a special focus on the role in RA. In addition, potential antirheumatic strategies that could be developed by targeting these autonomic pathways are discussed.     

Involvement of the sympatho-vagal balance in the formation of respiration-dependent oscillations in the human cardiovascular system

The effect of deep breathing controlled in both rate and amplitude on the heart rate variability (HRV) and respiration-dependent blood flow oscillations was studied in the forearm and finger-pad skin of healthy 18- to 25-year-old volunteers. In order to reveal the effects of the divisions of the autonomic nervous system on the amplitudes of respiratory sinus arrhythmia (RSA) and skin blood flow oscillations, we studied the indices of the cardiovascular system in two groups of subjects with respectively lower and higher values of the sympatho-vagal balance. This index was calculated as a ratio of low frequency and high frequency HRV spectral power (LF/HF) under the conditions of spontaneous breathing. It was found that, in subjects with a predominant parasympathetic tone, the amplitudes of RSA and the rate of blood flow in the finger-pad skin were higher compared to subjects with a predominant sympathetic tone during respiration with the frequency lower than 4 cycle/min. In the forearm skin, where sympathetic innervation is weaker compared to the finger-pad skin, there were no significant differences in respiration-dependent oscillations of the rate of blood flow in two groups of subjects.     

Evidence of dominant parasympathetic nervous activity of great cormorants (<Emphasis Type="Italic">Phalacrocorax carbo</Emphasis>)

The characteristics of autonomic nervous activity were examined on captive great cormorants Phalacrocorax carbo hanedae, using a power spectral analysis of heart rate variability. Heart rates were calculated from recordings of the electrocardiograms of the birds via embarked data loggers. We investigated the effects of blockades of the sympathetic or parasympathetic nervous systems using the indices of autonomic nervous activity such as high frequency (0.061–1.5 Hz) component, low frequency (0.02–0.060 Hz) component and the low frequency power component to high frequency power component ratio. Resting heart rate (85.5 ± 6.1 bpm) was lower than the intrinsic heart rate (259.2 ± 15.3 bpm). The heart rate drastically increased after the injection of the parasympathetic nervous blocker, on the other hand it slightly decreased after the injection of the sympathetic nervous blocker. The sympathetic, parasympathetic and net autonomic nervous tones calculated from heart rate with and without blockades were 40.9 ± 27.6, −44.5 ± 7.4 and −29.5 ± 9.0%, respectively. The effect of the parasympathetic nervous blockade on low frequency and high frequency power was greater than that of the sympathetic nervous blockade. Those data suggested that the parasympathetic nervous activity was dominant for great cormorants.     

Quantifying cardiac sympathetic and parasympathetic nervous activities using principal dynamic modes analysis of heart rate variability

The ratio between low-frequency (LF) and high-frequency (HF) spectral power of heart rate has been used as an approximate index for determining the autonomic nervous system (ANS) balance. An accurate assessment of the ANS balance can only be achieved if clear separation of the dynamics of the sympathetic and parasympathetic nervous activities can be obtained, which is a daunting task because they are nonlinear and have overlapping dynamics. In this study, a promising nonlinear method, termed the principal dynamic mode (PDM) method, is used to separate dynamic components of the sympathetic and parasympathetic nervous activities on the basis of ECG signal, and the results are compared with the power spectral approach to assessing the ANS balance. The PDM analysis based on the 28 subjects consistently resulted in a clear separation of the two nervous systems, which have similar frequency characteristics for parasympathetic and sympathetic activities as those reported in the literature. With the application of atropine, in 13 of 15 supine subjects there was an increase in the sympathetic-to-parasympathetic ratio (SPR) due to a greater decrease of parasympathetic than sympathetic activity (P=0.003), and all 13 subjects in the upright position had a decrease in SPR due to a greater decrease of sympathetic than parasympathetic activity (P<0.001) with the application of propranolol. The LF-to-HF ratio calculated by the power spectral density is less accurate than the PDM because it is not able to separate the dynamics of the parasympathetic and sympathetic nervous systems. The culprit is equivalent decreases in both the sympathetic and parasympathetic activities irrespective of the pharmacological blockades. These findings suggest that the PDM shows promise as a noninvasive and quantitative marker of ANS imbalance, which has been shown to be a factor in many cardiac and stress-related diseases.     

Use of a Physiological Monitoring Model for Comprehensive Evaluation of Adaptive Capacities in Schoolchildren during Learning: I. Influence of Various Motor Activity Regimens on Cardiac Rhythm Indices in Junior Schoolchildren

The dynamics of changes in the indices of the autonomic regulation of cardiac rhythm was studied in junior schoolchildren during adaptation to physical exercise. An analysis of variation pulsometry parameters throughout the school year showed the role of the sympathetic and parasympathetic parts of the autonomic nervous system in the formation of body adaptive reactions to various motor activity regimens.     

Autonomic nervous system activity in Macaca fascicularis

This study was performed to determine the contributions of the sympathetic and parasympathetic nervous systems to cardiovascular control. Hexamethonium was administered to block the autonomic ganglia, propranolol to block beta adrenergic receptors of the sympathetic nervous system, and methylatropine to block the parasympathetic nervous system. The results of this study indicate high sympathetic tone and low parasympathetic tone in resting Macaca fascicularis. These findings are different from those in man but are similar to other nonhuman primates.     

Autonomic Dysregulation in Headache Patients

To analyze autonomic nervous system activity in headache subjects, measurements of heart rate variability (HRV), skin temperature, skin conductance, and respiration were compared to a matched control group. HRV data were recorded in time and frequency domains. Subjects also completed self-report questionnaires assessing psychological distress, fatigue, and sleep dysfunction. Twenty-one headache and nineteen control subjects participated. In the time domain, the number of consecutive R-to-R intervals that varied by more than 50 ms and the standard deviation of the normalized R-to-R intervals, both indices of parasympathetic nervous system activity, were significantly lower in the headache group than the control group. Groups did not differ statistically on HRV measures in the frequency domain. Self-report measures showed significantly increased somatization, hostility, anxiety, symptom distress, fatigue, and sleep problems in the headache group. The results suggest headache subjects have increased sympathetic nervous system activity and decreased parasympathetic activity compared to non-headache control subjects. Headaches subjects also showed greater emotional distress, fatigue, and sleep problems. The results indicate an association between headaches and cardiovascular functioning suggestive of sympathetic nervous system activation in this sample of mixed migraine and tension-type headache sufferers.     

Respiratory influences on non-linear dynamics of heart rate variability in humans

 The goal of our study was to determine whether evidence for chaos in heart rate variability (HRV) can be observed when the respiratory input to the autonomic controller of heart rate is forced by the deterministic pattern associated with periodic breathing. We simultaneously recorded, in supine healthy volunteers, RR intervals and breathing volumes for 20 to 30 min (1024 data point series) during three protocols: rest (control), fixed breathing (15 breath/min) and voluntary periodic breathing (3 breaths with 2 s inspiration and 2 s expiration followed by an 8 s breath hold). On both the RR interval and breathing volume series we applied the non-linear prediction method (Sugihara and May algorithm) to the original time series and to distribution-conserved isospectral surrogate data. Our results showed that, in contrast to the control test, during both fixed and voluntary periodic breathing the variability of breathing volumes was clearly deterministic non-chaotic. During all the three protocols, the RR-interval series’ non-linear predictability was consistent with one of a chaotic series. However, at rest, no clear difference was observed between the RR-interval series and their surrogates, which means that no clear chaos was observed. During fixed breathing a difference appeared, and this difference seemed clearer during voluntary periodic breathing. We concluded that HRV dynamics were chaotic when respiration was forced with a deterministic non-chaotic pattern and that normal spontaneous respiratory influences might mask the normally chaotic pattern in HRV. Received: 7 August 1995 / Accepted in revised form: 20 March 1997     

Newly raised anti‐VAChT and anti‐ChAT antibodies detect cholinergic cells in chicken embryos

The autonomic nervous system consists of sympathetic and parasympathetic nerves, which functionally antagonize each other to control physiology and homeostasis of organs. However, it is largely unexplored how the autonomic nervous system is established during development. In particular, early formation of parasympathetic network remains elusive because of its complex anatomical structure. To distinguish between parasympathetic (cholinergic) and sympathetic (adrenergic) ganglia, vesicular acetylcholine transporter (VAChT) and choline O‐acetyltransferase (ChAT), proteins associated with acetylcholine synthesis, are known to be useful markers. Whereas commercially available antibodies against these proteins are widely used for mammalian specimens including mice and rats, these antibodies do not work satisfactorily in chickens, although chicken is an excellent model for the study of autonomic nervous system. Here, we newly raised antibodies against chicken VAChT and ChAT proteins. One monoclonal and three polyclonal antibodies for VAChT, and one polyclonal antibody for ChAT were obtained, which were available for Western blotting analyses and immunohistochemistry. Using these verified antibodies, we detected cholinergic cells in Remak ganglia of autonomic nervous system, which form in the dorsal aspect of the digestive tract of chicken E13 embryos. The antibodies obtained in this study are useful for visualization of cholinergic neurons including parasympathetic ganglia.     

Autonomic Activity Assessed by Heart Rate Spectral Analysis Varies with Fat Distribution in Obese Women

Obesity in humans has been associated with altered autonomic nervous system activity. The objective of this study was to examine the relationship between autonomic function and body fat distribution in 16 obese, postmenopausal women using power spectrum analysis of heart rate variability. Using this technique, a low frequency peak (0.04-0.12 Hz) reflecting mixed sympathetic and parasympathetic activity, and a high frequency peak (0.22-0.28 Hz) reflecting parasympathetic activity, were identified from 5-minute consecutive heart rate data (both supine and standing). Autonomic activity in upper body (UBO) vs. lower body obesity (LBO)(by waist-to-hip ratio) and subcutaneous vs. visceral obesity (by CT scan) was evaluated. Power spectrum data were log transformed to normalize the data. The results showed that standing, low-frequency power (reflecting sympathetic activity) and supine, high-frequency power (reflecting parasympathetic activity) were significantly greater in UBO than in LBO, and in visceral compared to subcutaneous obesity. Women with combined UBO and visceral obesity had significantly higher cardiac sympathetic and parasympathetic activity than any other subgroup. We conclude that cardiac autonomic function as assessed by heart rate spectral analysis varies in women depending on their regional body fat distribution.     

Cardiac rhythm effects of .125-Hz paced breathing through a resistive load: Implications for paced breathing therapy and the polyvagal theory

This study examined the psychophysiological effects of slow-paced breathing while subjects breathed through external respiratory resistive loads. Twenty-four normal volunteers completed four 5-min trials of paced breathing (.125 Hz) through an inspiratory resistive wire mesh screen (0 to 25 cm H₂O/L/s). Each trial was followed by a 5-min rest trial. There was evidence for hyperventilation and/or fatigue during paced breathing. Also, respiratory sinus arrhythmia (RSA) was elevated in the first minute of paced breathing, and then declined toward baseline. Heart period decreased during paced breathing trials, and fell significantly below baseline during rest periods. These data suggest decreased vagus nerve activity and/or sympathetic activation, following an initial increase in parasympathetic activity during paced breathing. They are not consistent with the use of .125-Hz paced breathing as a relaxation technique, particularly during respiratory resistive stress. Finally, although RSA and average heart period changed synchronouslywithin paced breathing and rest conditions, they diverged incomparisons between pacing and rest. This dissociation suggests that different mechanisms mediate these two cardiac parameters. These data are consistent with Porges' theory that vagal influences on tonic heart rate are mediated by the combined effect of vagal projections from both the nucleus ambiguus and the dorsal motor nucleus, while RSA is mediated only through the nucleus ambiguus alone.     

Parasympathetic Stimuli on Bronchial and Cardiovascular Systems in Humans

Background

It is not known whether parasympathetic outflow simultaneously acts on bronchial tone and cardiovascular system waxing and waning both systems in parallel, or, alternatively, whether the regulation is more dependent on local factors and therefore independent on each system. The aim of this study was to evaluate the simultaneous effect of different kinds of stimulations, all associated with parasympathetic activation, on bronchomotor tone and cardiovascular autonomic regulation.

Methods

Respiratory system resistance (Rrs, forced oscillation technique) and cardio-vascular activity (heart rate, oxygen saturation, tissue oxygenation index, blood pressure) were assessed in 13 volunteers at baseline and during a series of parasympathetic stimuli: O₂ inhalation, stimulation of the carotid sinus baroreceptors by neck suction, slow breathing, and inhalation of methacholine.

Results

Pure cholinergic stimuli, like O₂ inhalation and baroreceptors stimulation, caused an increase in Rrs and a reduction in heart rate and blood pressure. Slow breathing led to bradycardia and hypotension, without significant changes in Rrs. However slow breathing was associated with deep inhalations, and Rrs evaluated at the baseline lung volumes was significantly increased, suggesting that the large tidal volumes reversed the airways narrowing effect of parasympathetic activation. Finally inhaled methacholine caused marked airway narrowing, while the cardiovascular variables were unaffected, presumably because of the sympathetic activity triggered in response to hypoxemia.

Conclusions

All parasympathetic stimuli affected bronchial tone and moderately affected also the cardiovascular system. However the response differed depending on the nature of the stimulus. Slow breathing was associated with large tidal volumes that reversed the airways narrowing effect of parasympathetic activation.     

Use of Controlled Diaphragmatic Breathing for the Management of Motion Sickness in a Virtual Reality Environment

Evidence indicates that activation of the parasympathetic nervous system (PNS) suppresses physiological responses associated with motion sickness. Research also shows paced breathing increases PNS activation; the current study examines the use of paced diaphragmatic breathing (DB) training to quell motion sickness symptoms. Healthy participants (N = 60) were pre-screened for motion sickness susceptibility. Participants were then randomly assigned to either a control condition, focusing on environmental awareness, or to an experimental condition implementing paced DB. Following this, participants were exposed to a virtual reality (VR) motion sickness experience, while heart rate variability, breathing rate (RPM), and motion sickness ratings were collected. Results demonstrated participants in the DB condition had higher PNS activation and reported fewer motion sickness symptoms during the VR experience than the participants in the control condition. Results suggest that the DB protocol can be used to significantly increase PNS tone and decrease the development of motion sickness symptoms.     

Macaque Cardiac Physiology Is Sensitive to the Valence of Passively Viewed Sensory Stimuli

Autonomic nervous system activity is an important component of affective experience. We demonstrate in the rhesus monkey that both the sympathetic and parasympathetic branches of the autonomic nervous system respond differentially to the affective valence of passively viewed video stimuli. We recorded cardiac impedance and an electrocardiogram while adult macaques watched a series of 300 30-second videos that varied in their affective content. We found that sympathetic activity (as measured by cardiac pre-ejection period) increased and parasympathetic activity (as measured by respiratory sinus arrhythmia) decreased as video content changes from positive to negative. These findings parallel the relationship between autonomic nervous system responsivity and valence of stimuli in humans. Given the relationship between human cardiac physiology and affective processing, these findings suggest that macaque cardiac physiology may be an index of affect in nonverbal animals.     

Age-related changes in the innervation of the prostate gland

The adult prostate gland grows and develops under hormonal control while its physiological functions are controlled by the autonomic nervous system. The prostate gland receives sympathetic input via the hypogastric nerve and parasympathetic input via the pelvic nerve. In addition, the hypogastric and pelvic nerves also provide sensory inputs to the gland. This review provides a summary of the innervation of the adult prostate gland and describes the changes which occur with age and disease. Growth and development of the prostate gland is age dependent as is the occurrence of both benign prostate disease and prostate cancer. In parallel, the activity and influence of both the sympathetic and parasympathetic nervous system changes with age. The influence of the sympathetic nervous system on benign prostatic hyperplasia is well documented and this review considers the possibility of a link between changes in autonomic innervation and prostate cancer progression.