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.     

Cardiac Autonomic Activity During Human Sleep: Analysis of Sleep Stages and Sleep Cycles

In this study characteristics of cardiac functioning were investigated in nine subjects during their nocturnal sleep. The pre-ejection period and the high frequency component of heart rate variability were used as indices of cardiac sympathetic and parasympathetic activity of the autonomic nervous system respectively. Heart rate and the autonomic indices were assessed across physiological determined sleep stages and consecutive temporal sleep cycles. Repeated measures ANOVA analyses indicated a significant pattern of heart rate as a function of sleep stages, which was mirrored by parasympathetic activity. Further, a significant decrease of heart rate as a function of sleep cycles was mirrored by an increase of sympathetic activity. Moreover, non-REM/REM differences revealed a dominant role of parasympathetic activity during sleep stages as well as sleep cycles. These findings demonstrate that sympathetic activity is influenced by time asleep, whereas parasympathetic activity is influenced by the depth of sleep.     

Cardiac Autonomic Activity During Human Sleep: Analysis of Sleep Stages and Sleep Cycles

In this study characteristics of cardiac functioning were investigated in nine subjects during their nocturnal sleep. The pre-ejection period and the high frequency component of heart rate variability were used as indices of cardiac sympathetic and parasympathetic activity of the autonomic nervous system respectively. Heart rate and the autonomic indices were assessed across physiological determined sleep stages and consecutive temporal sleep cycles. Repeated measures ANOVA analyses indicated a significant pattern of heart rate as a function of sleep stages, which was mirrored by parasympathetic activity. Further, a significant decrease of heart rate as a function of sleep cycles was mirrored by an increase of sympathetic activity. Moreover, non-REM/REM differences revealed a dominant role of parasympathetic activity during sleep stages as well as sleep cycles. These findings demonstrate that sympathetic activity is influenced by time asleep, whereas parasympathetic activity is influenced by the depth of sleep.     

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.     

Functional state of the cardiovascular system in 13-year-old adolescents with different types of autonomic nervous regulation

The features of the functional state of cardiovascular system in 13-year-old children with different types of autonomic nervous regulation were studied. Children with normotonic and parasympathetic types of autonomic regulation were found to have the highest adaptation capacities. The autonomic nervous system influences the bioelectrical processes in myocardium, the duration of cardiac cycle phases, and cerebral blood flow. Schoolchildren aged 13 years with higher sympathetic activity have shorter duration of the cardiac cycle, the phase of isometric contraction, and diastole. They have a lower pulse blood flow rate and a higher tone of large and medium cerebral vessels. No relationship was revealed between the initial autonomic nervous regulation of heart rate and the type of adaptation of myocardium to physical dynamic loads, as well as the type of adaptation of cerebral circulation to mental stress.     

Effect of Post-Weaning Individual Housing on Autonomic Responses in Male Rats to Sexually Receptive Female Rats

Post-weaning individual housing induces significant alterations in the reward system of adult male rats presented with sexually receptive female rats. In this study, we examined the effects of post-weaning individual housing on autonomic nervous activity in adult male rats during encounters with sexually receptive female rats to assess whether different affective states depending on post-weaning housing conditions are produced. Changes in heart rate and spectral parameters of heart rate variability indicated that in post-weaning individually housed male rats, both sympathetic and parasympathetic activity increased with no change in the sympathovagal balance, while in post-weaning socially housed male rats, both sympathetic and parasympathetic activity decreased with a predominance of parasympathetic activity. These two patterns of shifts in sympathovagal balances closely resembled changes in autonomic nervous activity with regard to classical appetitive conditioning in male rats. The autonomic changes in male rats housed individually after weaning corresponded to changes associated with the reward-expecting state evoked by the conditioned stimulus, and the autonomic changes observed in male rats housed socially after weaning corresponded to changes associated with the reward-receiving state evoked by the unconditioned stimulus. These results suggest that different affective states were induced in adult male rats during sexual encounters depending on male–male social interactions after weaning. The remarkable change caused by post-weaning individual housing may be ascribed to alteration of the reward system during sexual encounters induced by deficiency of intermale social communication after weaning.     

Phenotypic screening for heart rate variability in the mouse

We developed a technology for heart rate (HR) variability (HRV) analysis in the mouse for characterization of HR dynamics, modulated by vagal and sympathetic activity. The mouse is the principal animal model for studying biological processes. Mouse strains are now available harboring gene mutations providing fundamental insights into molecular mechanisms underlying cardiac electrical diseases. Future progress depends on enhanced understanding of these fundamental mechanisms and the implementation of methods for the functional analysis of mouse cardiovascular physiology. By telemetric techniques, standard time and frequency-domain measures of HRV were computed with and without autonomic blockade, and baroreflex sensitivity testing was performed. HR modulation in the high-frequency component is predominantly mediated by the parasympathetic nervous system, whereas the low-frequency component is under the influence of both the parasympathetic and sympathetic systems. The presented technology and protocol allow for assessment of autonomic regulation of the murine HR. Phenotypic screening for HR regulation in mice will further enhance the value of the mouse as a model of heritable electrophysiological human disease.     

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.     

Statistical coding and decoding of heartbeat intervals

The heart integrates neuroregulatory messages into specific bands of frequency, such that the overall amplitude spectrum of the cardiac output reflects the variations of the autonomic nervous system. This modulatory mechanism seems to be well adjusted to the unpredictability of the cardiac demand, maintaining a proper cardiac regulation. A longstanding theory holds that biological organisms facing an ever-changing environment are likely to evolve adaptive mechanisms to extract essential features in order to adjust their behavior. The key question, however, has been to understand how the neural circuitry self-organizes these feature detectors to select behaviorally relevant information. Previous studies in computational perception suggest that a neural population enhances information that is important for survival by minimizing the statistical redundancy of the stimuli. Herein we investigate whether the cardiac system makes use of a redundancy reduction strategy to regulate the cardiac rhythm. Based on a network of neural filters optimized to code heartbeat intervals, we learn a population code that maximizes the information across the neural ensemble. The emerging population code displays filter tuning proprieties whose characteristics explain diverse aspects of the autonomic cardiac regulation, such as the compromise between fast and slow cardiac responses. We show that the filters yield responses that are quantitatively similar to observed heart rate responses during direct sympathetic or parasympathetic nerve stimulation. Our findings suggest that the heart decodes autonomic stimuli according to information theory principles analogous to how perceptual cues are encoded by sensory systems.     

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.     

The Power of an Infant's Smile: Maternal Physiological Responses to Infant Emotional Expressions

Infant emotional expressions, such as distress cries, evoke maternal physiological reactions. Most of which involve accelerated sympathetic nervous activity. Comparatively little is known about effects of positive infant expressions, such as happy smiles, on maternal physiological responses. This study investigated how physiological and psychological maternal states change in response to infants’ emotional expressions. Thirty first-time mothers viewed films of their own 6- to 7-month-old infants’ affective behavior. Each observed a video of a distress cry followed by a video showing one of two expressions (randomly assigned): a happy smiling face (smile condition) or a calm neutral face (neutral condition). Both before and after the session, participants completed a self-report inventory assessing their emotional states. The results of the self-report inventory revealed no effects of exposure to the infant videos. However, the mothers in the smile condition, but not in the neutral condition, showed deceleration of skin conductance. These findings demonstrate that the mothers who observed their infants smiling showed decreased sympathetic activity. We propose that an infant’s positive emotional expression may affect the branch of the maternal stress-response system that modulates the homeostatic balance of the sympathetic and parasympathetic nervous systems.     

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.     

Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans

Glucagon-like peptide-1 (GLP-1), an incretin, which is used to treat diabetes mellitus in humans, inhibited vagal activity and activated nitrergic pathways. In rats, GLP-1 also increased sympathetic activity, heart rate, and blood pressure (BP). However, the effects of GLP-1 on sympathetic activity in humans are unknown. Our aims were to assess the effects of a GLP-1 agonist with or without alpha(2)-adrenergic or -nitrergic blockade on autonomic nervous functions in humans. In this double-blind study, 48 healthy volunteers were randomized to GLP-1-(7-36) amide, the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine acetate (l-NMMA), the alpha(2)-adrenergic antagonist yohimbine, or placebo (i.e., saline), alone or in combination. Hemodynamic parameters, plasma catecholamines, and cardiac sympathetic and parasympathetic modulation were measured by spectral analysis of heart rate. Thereafter, the effects of GLP-1-(7-36) amide on muscle sympathetic nerve activity (MSNA) were assessed by microneurography in seven subjects. GLP-1 increased (P = 0.02) MSNA but did not affect cardiac sympathetic or parasympathetic indices, as assessed by spectral analysis. Yohimbine increased plasma catecholamines and the low-frequency (LF) component of heart rate power spectrum, suggesting increased cardiac sympathetic activity. l-NMMA increased the BP and reduced the heart rate but did not affect the balance between sympathetic and parasympathetic activity. GLP-1 increases skeletal muscle sympathetic nerve activity but does not appear to affect cardiac sympathetic or parasympathetic activity in humans.     

Central nervous system involvement in the autonomic responses to psychological distress

Psychological distress can trigger acute coronary syndromes and sudden cardiac death in vulnerable patients. The primary pathophysiological mechanism that plays a role in stress-induced cardiac events involves the autonomic nervous system, particularly disproportional sympathetic activation and parasympathetic withdrawal. This article describes the relation between psychological distress and autonomic nervous system function, with a focus on subsequent adverse cardiovascular outcomes. The role of the central nervous system in these associations is addressed, and a systematic review is presented of studies examining the association between stress-induced central nervous system responses measured by neuroimaging techniques and autonomic nervous system activation. Results of the systematic review indicate that the primary brain areas involved in the autonomic component of the brain-heart association are the insula, medial prefrontal cortex, and cerebellum (based on 121 participants across three studies that fitted the inclusion criteria). Other areas involved in stress-induced autonomic modulation are the (anterior) cingulate cortex, parietal cortex, somatomotor cortex/precentral gyrus, and temporal cortex. The interaction between central and autonomic nervous system responses may have implications for further investigations of the brain-heart associations and mechanisms by which acute and chronic psychological distress increase the risk of myocardial infarction, cardiac arrhythmias, and sudden cardiac death.     

Autonomic Nervous Responses According to Preference for the Odor of Jasmine Tea

The effect of jasmine tea odor on the autonomic nervous system was investigated by a power spectral analysis of the heart rate variability. We assigned eight volunteers to two groups with either a predilection for or antipathy toward the jasmine tea odor. We tested both high- and low-intensity jasmine tea odors. The low-intensity odor was produced by diluting 20-fold the jasmine tea used for the high-intensity odor test. The low-intensity odor produced an increase in parasympathetic nervous activity in both the predilection and antipathy groups. The high-intensity odor produced an increase in parasympathetic nervous activity in the predilection group, but an increase in sympathetic nervous activity in the antipathy group. The odor of Chinese green tea, a basic ingredient of jasmine tea, produced no effects similar to those of the jasmine tea odor. These results suggest that the jasmine tea odor activated the parasympathetic nerve, whereas the higher-intensity odor activated the sympathetic nerve in those subjects who disliked the odor.     

Autonomic nervous responses according to preference for the odor of jasmine tea

The effect of jasmine tea odor on the autonomic nervous system was investigated by a power spectral analysis of the heart rate variability. We assigned eight volunteers to two groups with either a predilection for or antipathy toward the jasmine tea odor. We tested both high- and low-intensity jasmine tea odors. The low-intensity odor was produced by diluting 20-fold the jasmine tea used for the high-intensity odor test. The low-intensity odor produced an increase in parasympathetic nervous activity in both the predilection and antipathy groups. The high-intensity odor produced an increase in parasympathetic nervous activity in the predilection group, but an increase in sympathetic nervous activity in the antipathy group. The odor of Chinese green tea, a basic ingredient of jasmine tea, produced no effects similar to those of the jasmine tea odor. These results suggest that the jasmine tea odor activated the parasympathetic nerve, whereas the higher-intensity odor activated the sympathetic nerve in those subjects who disliked the odor.     

Meal-induced insulin secretion in dogs is mediated by both branches of the autonomic nervous system

We investigated the relationship between autonomic activity to the pancreas and insulin secretion in chronically catheterized dogs when food was shown, during eating, and during the early absorptive period. Pancreatic polypeptide (PP) output, pancreatic norepinephrine spillover (PNESO), and arterial epinephrine (Epi) were measured as indexes for parasympathetic and sympathetic nervous activity to the pancreas and for adrenal medullary activity, respectively. The relation between autonomic activity and insulin secretion was confirmed by autonomic blockade. Showing food to dogs initiated a transient increase in insulin secretion without changing PP output or PNESO. Epi did increase, suggesting beta(2)-adrenergic mediation, which was confirmed by beta-adrenoceptor blockade. Eating initiated a second transient insulin response, which was only totally abolished by combined muscarinic and beta-adrenoceptor blockade. During absorption, insulin increased to a plateau. PP output showed the same pattern, suggesting parasympathetic mediation. PNESO decreased by 50%, suggesting withdrawal of inhibitory sympathetic neural tone. We conclude that 1) the insulin response to showing food is mediated by the beta(2)-adrenergic effect of Epi, 2) the insulin response to eating is mediated both by parasympathetic muscarinic stimulation and by the beta(2)-adrenergic effect of Epi, and 3) the insulin response during early absorption is mediated by parasympathetic activation, with possible contribution of withdrawal of sympathetic neural tone.     

John Newport Langley and His Construction of the Autonomic (Vegetative) Nervous System

The paper describes the scientific career of Professor John Newport Langley, an outstanding English physiologist and histologist, member of the London Royal Society and its Vice-President. The main scientific achievements of Langley are dealing with anatomy and physiology of the autonomic (vegetative) nervous system that he considered as an entirely efferent system. The autonomic nervous system was divided by Langley into three parts: sympathetic, parasympathetic, and enteral (intestinal) systems. He has also established functional differences of the autonomic nervous system from the somatic one. He suggested the presence of synaptic contacts on muscle and secretory cells, as well as the existence in these synaptic structures of a peculiar receptor substance providing interaction of nerve fibers with postganglionic neurons and effector cells of visceral organs. The examples of development of several Langley's concepts at present are given.