Prediction of Tonic Parasympathetic Cardiac Control Using Respiratory Sinus Arrhythmia: The Need for Respiratory Control

Respiratory sinus arrhythmia (RSA) has received much attention in recent years due to the large body of evidence indicating that variations in this phenomenon represent alterations in parasympathetic cardiac control. Although it appears that respiratory sinus arrhythmia is mediated by vagal mechanisms, the extent to which the well-known respiratory influences (i.e., rate and tidal volume) on respiratory sinus arrhythmia (in altering its magnitude) may moderate the relationship between RSA and cardiac vagal tone has never been systematically studied. We addressed this issue by examining intraindividual relationships among RSA magnitude, respiration (rate and tidal volume), and heart period among six healthy male adults after intravenous administration of 10 mg propranolol, a beta-adrenergic blocker. Subjects were exposed to various behavioral tasks which altered all physiological variables measured. Variations in heart period after beta blockade were assumed to be predominantly vagally mediated. Within-subject regression analyses consistently showed that respiratory parameters influenced RSA magnitude, but not tonic variations in beta-blocked heart period, suggesting that respiratory-mediated RSA alterations are not associated with changes in cardiac vagal tone. Only when respiratory variables were statistically controlled was there evidence of a reasonable correspondence between beta-blocked heart period and RSA amplitude, providing support for the idea that respiratory parameters need to be controlled when using RSA amplitude as an index of cardiac vagal tone. Repeated-measures analyses of variance of mean levels of heart period and respiratory sinus arrhythmia across subjects supplemented and supported the intraindividual results. These findings point to the importance of controlling for respiratory parameters when using respiratory sinus arrhythmia as a cardiac vagal index.     

Respiratory sinus arrhythmia, cardiac vagal tone, and respiration: Within- and between-individual relations

Respiratory sinus arrhythmia (RSA) is frequently employed as an intra- and interindividual index of cardiac parasympathetic tone, although the relationship of RSA to interindividual differences in cardiac vagal tone remains questionable. Our study examined between- and within-subject relations among RSA, cardiac vagal tone, and respiratory parameters. Twenty-nine young adults performed two sessions of tasks under no medication and single and double autonomic blockade (intravenously administered propranolol and atropine). Parasympathetic tone was determined from heart period responses to complete vagal blockade. Results indicated the following. Resting RSA does not accurately predict individual differences in cardiac vagal tone. However, RSA and heart period together do predict such individual differences reasonably well. The relationship between individual variations in RSA and vagal tone is not improved by controlling respiratory parameters. Substantial cardiac vagal activity occurs during inspiration, and intraindividual variations in respiratory measures confound the association between RSA and cardiac vagal tone.     

Respiratory Sinus Arrhythmia and Cardiovascular Responses to Stress

The parasympathetic nervous system provides mechanisms that could attenuate sympathetically mediated heart rate stress responses and might have even more general antagonistic actions on stress reactivity. Individuals characterized by higher levels of parasympathetic tone might, through such mechanisms, be less reactive when stimuli elicit sympathetically mediated responses. Respiratory sinus arrhythmia (RSA) is considered to be a noninvasive index of cardiac parasympathetic (vagal) tone. The present study investigated whether individual differences in RSA level at rest could predict variations among individuals in the magnitude of cardiovascular responses to psychological stress. None of the measures of resting respiratory sinus arrhythmia, derived from spectral analysis of beat-to-beat changes in resting heart rate, predicted the observed variations in cardiovascular task reactivity. However, scores reflecting respiratory sinus arrhythmia as the percentage of total heart rate variability (RSAnorm) were negatively correlated with blood pressure levels, both at rest and during the task. Furthermore, subjects with higher scores for RSAnorm demonstrated a faster adaptation of heart rate responses during stress, which suggests the development of parasympathetic antagonism to ongoing sympathetic arousal. Although a simple relationship between respiratory sinus arrhythmia and reactivity was not observed, these results encourage further investigation of RSA measures as psychophysiological indices of individual differences in parasympathetic (vagal) cardiac tone, or perhaps of general parasympathetic/sympathetic balance, which could modulate the expression of potentially pathogenic stress responses.     

Cardiac Autonomic Mechanisms Associated with Borderline Hypertension under Varying Behavioral Demands: Evidence for Attenuated Parasympathetic Tone but Not for Enhanced Beta-Adrenergic Activity

Elevated blood pressure in psychophysiological studies of borderline hypertension is frequently attributed to the effects of increased sympathetic tone, and with few exceptions, the potential parasympathetic contributions have not been considered. Furthermore, of the investigations that have addressed vagal influences upon blood pressure, most have employed invasive pharmacological assessment of parasympathetic tone. In this study, cardiac parasympathetic and beta-adrenergic influences in borderline hypertension were evaluated noninvasively employing respiratory sinus arrhythmia as a vagal index and preejection period as a sympathetic index of cardiac functioning. Subjects were 30 borderline hypertensive and 23 normotensive males (age range, 24-45 years). The ECG, blood pressure, impedance cardiography, and respiration were measured during two baselines (initial and post-task), a memory-comparison reaction time task, the cold pressor, and CO2-rebreathing. Results indicated tonic differences between groups in all cardiovascular variables across tasks, with the exception of pre-ejection period, which showed no group effects at all. Hypertensives additionally manifested somewhat heightened systolic blood pressure reactivity and attenuated cardiac parasympathetic responsivity to specific tasks. Our findings provide no support for an exaggerated cardiac beta-adrenergic tonic level or reactivity in borderline hypertensives. On the other hand, the consistently lower magnitude of respiratory sinus arrhythmia in our hypertensives suggests that reduced parasympathetic control may be involved in the pathophysiology of hypertension.     

Respiratory Sinus Arrhythmia as an Index of Parasympathetic Cardiac Control During Active Coping

Psychophysiological studies concerning tonic cardiac responses to stressor tasks have tended to emphasize beta-adrenergic effects and to neglect parasympathetic influences and sympathetic-parasympathetic interactions. Much recent evidence indicates that both within- and between-individual variations in cardiac parasympathetic heart rate (HR) control can be easily and reliably assessed by measuring the magnitude of respiratory sinus arrhythmia (RSA). Therefore, we used RSA to index cardiac vagal responses to two active coping tasks. Both tasks consisted of the same video game, in one condition with threat of shock for inferior performance, and in the other without such threat. Twenty subjects underwent both tasks (counterbalanced over subjects), plus a preceding resting baseline period. HR and RSA were continuously measured. Results suggested that cardiac parasympathetic activity was diminished from rest to task, contributing to heart rate responses. Exaggerated HR responses were also associated with extreme parasympathetic withdrawal. Furthermore, task condition X sequence of presentation interaction effects showed that threat of shock was particularly effective in elevating HR and reducing RSA when the threat was presented during the first task condition. A repeated-measures analysis of covariance of HR, attempting to remove the effects of parasympathetic influences upon HR, suggested that sympathetic influences upon HR exceeded any reciprocal vagal effects during the threat condition for those subjects exposed to the threat task first. The findings indicate the importance of considering stress-related parasympathetic effects upon HR as well as sympathetic-vagal interactions.     

Patterns of Autonomic Response During Laboratory Stressors

The present study was designed to include an index reflecting the influence of parasympathetic nervous system activity on the heart, respiratory sinus arrhythmia, in addition to measures reflecting primarily sympathetic nervous system activity. The inclusion of the parasympathetic index was considered important for two reasons:(a) Past studies have suggested different patterns of autonomic response to qualitatively different laboratory stressors but have had to infer parasympathetic influences more indirectly, and (b) there is evidence that borderline hypertensives may have reduced vagal tone at rest when compared to normotensives. This last point is important for the study of individual differences in cardiovascular reactivity because excessive responsiveness in young normotensives (beta-adrenergic reactors) has been suggested as a model for studying the precursors of some types of hypertension. Fifty-one male college students were given a reaction time task, a mental arithmetic task, a cold pressor task, and graded bicycle exercise. A variety of cardiovascular and respiratory measures were collected on each subject. Results indicated significant differences in levels of respiratory sinus arrhythmia during the three tasks and the rest period, giving additional evidence for parasympathetic differences (along with sympathetic differences) in these conditions. Additionally, high beta-adrenergic reactors did not differ in mean level of respiratory sinus arrhythmia from low reactors either at rest or during the task periods. These results are discussed in the context of previous research.     

Toward understanding respiratory sinus arrhythmia: relations to cardiac vagal tone, evolution and biobehavioral functions

Respiratory sinus arrhythmia (RSA, or high-frequency heart-rate variability) is frequently employed as an index of cardiac vagal tone or even believed to be a direct measure of vagal tone. However, there are many significant caveats regarding vagal tone interpretation: 1. Respiratory parameters can confound relations between RSA and cardiac vagal tone.2. Although intraindividual relations between RSA and cardiac vagal control are often strong, interindividual associations may be modest.3. RSA measurement is profoundly influenced by concurrent levels of momentary physical activity, which can bias estimation of individual differences in vagal tone.4. RSA magnitude is affected by beta-adrenergic tone.5. RSA and cardiac vagal tone can dissociate under certain circumstances.6. The polyvagal theory contains evolution-based speculations that relate RSA, vagal tone and behavioral phenomena. We present evidence that the polyvagal theory does not accurately depict evolution of vagal control of heart-rate variability, and that it ignores the phenomenon of cardiac aliasing and disregards the evolution of a functional role for vagal control of the heart, from cardiorespiratory synchrony in fish to RSA in mammals. Unawareness of these issues can lead to misinterpretation of cardiovascular autonomic mechanisms. On the other hand, RSA has been shown to often provide a reasonable reflection of cardiac vagal tone when the above-mentioned complexities are considered. Finally, a recent hypothesis is expanded upon, in which RSA plays a primary role in regulation of energy exchange by means of synchronizing respiratory and cardiovascular processes during metabolic and behavioral change.     

Whither vagal tone

Measures of respiratory sinus arrhythmia (RSA) have been widely applied in the physiological and psychophysiological literature as an index of vagal control of the heart. Despite an extensive literature, however, differences in interpretation remain within the field. A guiding conception for several contributions in this issue is the notion of separate brainstem centers involved in parasympathetic control, with distinct evolutionary origins and significance and with divergent influences on cardiac vagal tone as it relates to psychological and behavioral processes. We here consider the biological foundations for this view, discuss some methodological and interpretative caveats for RSA applications and offer suggestions for further development of the field.     

A Comparison of Three Quantification Methods for Estimation of Respiratory Sinus Arrhythmia

The empirical literature has shown that respiratory sinus arrhythmia is a sensitive noninvasive index of parasympathetic cardiac control. Nevertheless there has been no general agreement among investigators as to the most preferable quantification technique for assessing respiratory sinus arrhythmia, although there has been much speculation that specific estimation techniques are more or less reflective of vagal processes and could be more or less contaminated by other influences upon heart period variability unrelated to respiration. This study compared three quantification procedures for estimating respiratory sinus arrhythmia (RSA): (1) a spectral analytic technique, (2) a complex detrending approach removing periodic and aperiodic cardiac variations unrelated to respiration, and (3) a time-domain, peak-valley procedure employing inspiratory and expiratory periods as windows for determining range of cardiac-interval fluctuations associated with respiratory phase. Measures derived from these techniques were intra- and interindividually compared using three different samples of male subjects, including students, adult normotensives, and adult hypertensives. All interindividual correlations between measures yielded coefficients above .92 and the mean within-subject correlation across 42 individuals was .96, thus indicating a marked degree of comparability between measures. Additionally, given that much evidence indicates lawful within-individual relations between RSA amplitude and respiratory parameters, we employed respiratory period as an external criterion and compared intraindividual correlations between this variable and (2) and (3); results showed that (3) was significantly more highly associated with respiration than was (2), although the mean r's for the two measures did not diverge greatly (.91 vs. .84). Finally, inspection of the data and further regression analyses did not suggest that any of the RSA estimates were differentially contaminated by other components of cardiac variability. Our findings suggest that the three techniques are almost equivalent as indices of cardiac vagal tone and would appear to ease concerns about the inferiority of any of the procedures. Choice of a quantification procedure should therefore be tailored to the specific empirical needs of an investigation. The advantages and disadvantages of each method are discussed.     

Blood phobia and spider phobia: two specific phobias with different autonomic cardiac modulations

Cardiac reactions to two fear-related and one control film were compared in individuals high in spider or blood/injury fear. Twelve subjects in each phobic group were selected on the basis of their scores in the Spider or Mutilation Questionnaires and a semi-structured interview. Cardiac responses and self-reported affective ratings to the films were investigated. Sympathetic and parasympathetic cardiac influences were indexed by T-wave amplitude and respiratory sinus arrhythmia measured during film viewing. Basal parasympathetic cardiac control was also assessed during a paced breathing task. Results indicate differential autonomic modulation of cardiac responses for blood and spider phobics. Although each group reacted with marked cardiac activation to its feared stimulus, a sympathetic increase followed by withdrawal over time was found in blood phobics. Greater vagal tone at rest was present in blood phobics compared with spider phobics.     

Respiratory sinus arrhythmia: Autonomic origins, physiological mechanisms, and psychophysiological implications

Respiratory sinus arrhythmia (RSA) is being used increasingly in psychophysiological studies as an index of vagal control of the heart and may be among the most selective noninvasive indices of parasympathetic control of cardiac functions. A comprehensive understanding of RSA, however, requires an appreciation of its multiple autonomic and physiological origins. We review the physiological bases of RSA and show that RSA arises from multiple tonic and phasic processes of both central and peripheral origin. These underlying mechanisms are at least partially differentiated, have distinct dynamics and consequences, and may be differentially sensitive to behavioral and cognitive events. These multiple mechanisms are relevant for psychophysiological studies of RSA, and a thorough understanding of RSA can only be achieved through an appreciation of the dynamics of its underlying origins. There is a distinction between the psychophysiological and neurophysiological domains, and conceptual and empirical bridges between these domains are needed.     

Studying noninvasive indices of vagal control: the need for respiratory control and the problem of target specificity

Respiratory sinus arrhythmia (RSA) is a popular index of cardiac vagal control; however, research has rarely adequately addressed respiratory influences on RSA. In addition, simplistic views of the parasympathetic system have resulted in an overinterpretation of RSA as a general indicator of vagal control. Research using a respiration-corrected time-domain index of RSA has yielded plausible findings that substantially deviate from uncorrected RSA. Paced breathing, which is used for baseline calibration of RSA in this correction procedure, allows for a representative sampling of respiratory influences on RSA and has minimal impact on autonomic regulation. Past research has largely focused on cardiac vagal activity and ignored the extent of target specificity in the parasympathetic system. More research is needed on new noninvasive indices of vagal control at other organ sites. Studies also need to address muscarinic receptor sensitivity before noninvasive vagal indices can be interpreted as markers of central vagal outflow.     

Infant regulation of the vagal “brake” predicts child behavior problems: A psychobiological model of social behavior

Cardiac vagal tone is a construct that describes the functional relationship between the brainstem and the heart. Cardiac vagal tone is measured by quantifying the amplitude of respiratory sinus arrhythmia, a component of heart rate variability reflecting the functional output of vagal pathways on the heart. Although there is an extensive literature evaluating baseline vagal tone and its relation to behavior, the relation between individual differences in the ability to regulate cardiac vagal tone and behavior has been theoretically vague. This article introduces a theoretical model to explain the relation between vagal tone during steady states and vagal reactivity (i.e., the vagal brake) in response to environmental challenges. Based upon the proposed model, it was hypothesized that infants who had difficulties in regulating the vagal brake (i.e., decreasing cardiac vagal tone) during social/attention tasks would have difficulties developing appropriate social interactions requiring reciprocal engagement and disengagement strategies. Data from 24 infants are presented. The findings support the model and demonstrate that infants with difficulties in decreasing vagal tone during a social/attention task at 9 months of age had significantly more behavioral problems at 3 years of age. © 1996 John Wiley & Sons, Inc.     

Assessment of autonomic function by the spectral analysis of heart rate variability: an examination in a mirror drawing task]

The effect of an experimental task on autonomic function was investigated by spectral analysis of heart rate variability in 13 male college students. Power spectral density of heart rate variability has been said to contain two significant components: respiratory sinus arrhythmia (RSA) as an index of cardiac vagal activity, and Mayer wave related sinus arrhythmia (MWSA) as an index of sympathetic activity with vagal modulation. Those two components were examined during a task of mirror drawing on the CRT. In order to eliminate the effect of respiratory rate on RSA, the respiratory rate was controlled at 15 breaths/min. Furthermore, the coefficient of variance of R-R interval (CV-RR) and the fluctuation of plethysmograph (PTG) were calculated simultaneously. Results indicated that, while RSA decreased significantly, MWSA did not change during the task. On the other hand, neither CV-RR nor PTG showed any significant differences during the task. These findings indicated that cardiac parasympathetic activity was diminished in the mirror drawing task. The significance of spectral analysis of heart rate variability were discussed.     

Effects of Eating on Vection-Induced Motion Sickness, Cardiac Vagal Tone, and Gastric Myoelectric Activity

This study investigated the effect of food ingestion on motion sickness severity and its physiological mechanisms. Forty-six fasted subjects were assigned either to a meal group or to a no-meal group. Electrogastrographic (EGG) indices (normal 3 cpm activity and abnormal 4-9 cpm tachyarrhythmia) and respiratory sinus arrhythmia (RSA) were measured before and after a meal and during a subsequent exposure to a rotating drum in which illusory self-motion was induced. The results indicated that food intake enhanced cardiac parasympathetic tone (RSA) and increased gastric 3 cpm activity. Postprandial effects on motion sickness severity remain equivocal due to group differences in RSA baseline levels. During drum rotation, dysrhythmic activity of the stomach (tachyarrhythmia) and vagal withdrawal were observed. Furthermore, high levels of vagal tone prior to drum rotation predicted a low incidence of motion sickness symptoms, and were associated positively with gastric 3 cpm activity and negatively with tachyarrhythmia. These data suggest that enhanced levels of parasympathetic activity can alleviate motion sickness symptoms by suppressing, in part, its dysrhythmic gastric underpinnings.     

Respiratory and cardiac rhythms as windows to central and autonomic biobehavioral regulation: selection of window frames, keeping the panes clean and viewing the neural topography.

Respiratory and cardiovascular processes figure importantly in biobehavioral regulation. Various cardiac and respiratory measures may, furthermore, index the activity of relatively distinct central and autonomic mechanisms. In this regard, I consider ventilatory indices of central drive and timing of respiration, and rhythmic cardiac-interval fluctuations as reflections of parasympathetic and sympathetic cardiac influences. Particular emphasis is placed upon the phenomenon of respiratory sinus arrhythmia (RSA). A number of conceptual and methodological questions are addressed concerning quantification and inference. Among others, these include the following issues: (1) What is the evidence that the three cardiac periodicities slower than heart rate reflect distinct autonomic mechanisms? (2) Does RSA reflect tonic or phasic parasympathetic regulation of heart rate? (3) Do specific quantification procedures for measuring these rhythms provide superior estimates? (4) What are some potential pitfalls for quantification and inference.     

Behavioral Sleep States in Very Low Birth Weight Preterm Neonates: Relation to Neonatal Health and Vagal Maturation

Assessed the relation of behavioral codes of quiet versus activesleep state to neonatal health status in 62 very low birth weightpreterm neonates. Sleep sessions (12 min) were coded for percentagetime in active versus quiet sleep at 33, 34, and 35 weeks conceptionalage. ECG was monitored during each sleep session to derive measuresof heart rate, heart rate variability, and an index of cardiacvagal lone derived from respiratory sinus arrhythmia. Higherrisk neonates spent more sleep session time in active sleepthan healthier preterm neonates. Cardiac vagal tone showed amaturational change during the study weeks, whereas percentageof sampled sleep time in active sleep did not. Vagal maturationmeasured by age-related increases in the amplitude of respiratorysinus arrhythmia was associated with less active sleep overall,although weekly measures of respiratory sinus arrhythmia andsleep state were not related. Follow-up data on 30 of the neonatesindicated that heart rate variability and cardiac vagal tone,but not sleep state measures, were related to better outcomesin mental processing, social skills, and motor skills, and tofewer behavior problems. Results are discussed in terms of thelack of coupling between behavioral and physiological componentsof preterm sleep states at this age as compared with that seenin full-term sleep states.     

呼吸性窦性心律不齐定量分析研究进展

呼吸性窦性心律不齐(RSA)是一种心率随呼吸周期性波动的生理现象。近年来在临床上常被用作心迷走神经张力的非侵入式检测指征。但它的定量分析受呼吸参数、体位、体动等因素影响,使得至今还没有建立起一个通用的定量分析标准和校准方法。本文主要介绍了五种常见的定量分析方法:相邻R-R间期差值均方根(RMSSD)法、峰谷(pvRSA)法、逐次呼吸余弦拟合(cosinor fitting)法、谱分析(spectral analysis)法以及时频联合分析(JTFA)法;同时本文介绍了定量分析中常见的呼吸参数校准方法:引导呼吸法、协方差分析统计学控制法、相对呼吸参数残余量法以及潮气量修正法。最后,对如何解决现阶段RSA定量估计中存在的问题做了展望。     

Parasympathetic nervous system control of heart rate responses to stress in offspring of hypertensives

The elevated heart rate response to stress in normotensive offspring of hypertensives (PH+) has been suggested to be a function of sympathetic nervous system activity. This study examined whether parasympathetic nervous system activity may also underlie familial differences in the heart rate response. Twenty-four subjects, half of whom were PH+, were exposed to four stressor tasks administered in counterbalanced order. Stressors were chosen based on previous research that suggested vagal contributions to the heart rate response. Stressors were a cold pack to the forehead, isometric hand grip, a noxious film, and a shock-avoidance video game task. Physiological measures included heart rate (HR), respiration rate (RR), and respiratory sinus arrhythmia (RSA). RSA values were corrected for corresponding RR by analysis of covariance. Familial differences in HR were observed in response to the hand grip and video game tasks. However, in both cases analyses suggest that familial differences in reactivity were a function of primarily sympathetic as opposed to parasympathetic influences. Familial differences in RSA were not observed for rest or tasks. This study found no evidence for parasympathetic mediation of familial differences in the heart rate response to the stressors employed.     

Contribution of tonic vagal modulation of heart rate,central respiratory drive,respiratory depth,and respiratory frequency to respiratory sinus arrhythmia during mental stress and physical exercise

This study tested various sources of changes in respiratory sinus arrhythmia (RSA). Twenty-two healthy participants participated in three experimental conditions (mental stress, relaxation, and mild physical exercise) that each consisted of three breathing parts (normal breathing, breathing compressed room air, and breathing compressed 5% CO2-enriched air). Independent contributions to changes in RSA were found for changes in tonic vagal modulation of heart rate, central respiratory drive (i.e., PaCO2), respiratory depth, and respiratory frequency. The relative contributions to changes in RSA differed for mental stress and physical exercise. It is concluded that uncorrected RSA will suffice to index within-subject changes in tonic vagal modulation of heart rate in most situations. However, if the central respiratory drive is expected to change, RSA should ideally be corrected for changes in PaCO2, respiratory depth, and respiratory frequency.