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.     

Nonlinear Dynamical Analysis of the Interdependence Between Central and Autonomic Nervous Systems in Neonates During Sleep

We present in this paper the results of a study of the interdependence between signal characteristic of the central nervous system (electroencephalography) and the autonomic nervous system (heart rate and respiration) in human neonates during sleep. By using methods from nonlinear dynamical systems theory, we show that there exist significant differences in this interdependence with the sleep stage and the electrodes considered. This paves the way for the application of this methodology in clinical practice to study pathologies where this interdependence is altered, such as the sudden infant death syndrome.     

The Role of the Suprachiasmatic Nucleus in Cardiac Autonomic Control during Sleep

Background

The suprachiasmatic nucleus (SCN) may play an important role in central autonomic control, since its projections connect to (para)sympathetic relay stations in the brainstem and spinal cord. The cardiac autonomic modifications during nighttime may therefore not only result from direct effects of the sleep-related changes in the central autonomic network, but also from endogenous circadian factors as directed by the SCN. To explore the influence of the SCN on autonomic fluctuations during nighttime, we studied heart rate and its variability (HRV) in a clinical model of SCN damage.

Methods

Fifteen patients in follow-up after surgical treatment for nonfunctioning pituitary macroadenoma (NFMA) compressing the optic chiasm (8 females, 26–65 years old) and fifteen age-matched healthy controls (5 females, 30–63 years) underwent overnight ambulatory polysomnography. Eleven patients had hypopituitarism and received adequate replacement therapy. HRV was calculated for each 30-second epoch and corrected for sleep stage, arousals, and gender using mixed effect regression models.

Results

Compared to controls, patients spent more time awake after sleep onset and in NREM1-sleep, and less in REM-sleep. Heart rate, low (LF) and high frequency (HF) power components and the LF/HF ratio across sleep stages were not significantly different between groups.

Conclusions

These findings suggest that the SCN does not play a dominant role in cardiac autonomic control during sleep.     

Cardiac Autonomic Nervous System Activity in Obese and Never-Obese Young Men

ARONNE, LOUIS J, RONALD MACKINTOSH, MICHAEL ROSENBAUM, RUDOLPH L LEIBEL, JULES HIRSCH. Cardiac autonomic nervous system activity in obese and never-obese young men. Autonomic nervous system (ANS) activity in age-matched, weight-stable, free-living, ad libitumfed, obese (OB) and never-obese (NO) young men (body mass index means [SD], 38.5 [3.9] and 22.0 [1.7], respectively) was evaluated by sequential blockade of cardiac autonomic innervation with weight-adjusted doses of parasympathetic (atropine) and sympathetic (esmolol) blockers so as to produce maximal effects on heart rate. Change in heart period (interbeat interval) from baseline, induced by atropine, defined parasympathetic control (PC), and the subsequent change, after esmolol administration, defined sympathetic control (SC). The heart period, after PC and SC blockade, defined intrinsic heart period (I). In the OB group, baseline heart period and PC were lower, and SC and I were higher, than in the NO group. The results in the OB, relative to the NO subjects, are similar to those reported in a previous study of NO subjects who had undergone a 10% weight gain by overfeeding. These findings suggest that the ANS of individuals with obesity is chronically altered in a way that would tend to oppose their excessive adiposity, and that these autonomic changes are more likely to be responses to other forces that induce obesity, rather than being primary agents in the production of the disease.     

Circadian Variation in Cardiac Autonomic Activity: Reactivity Measurements to Different Types of Stressors

The role of endogenous circadian rhythmicity in autonomic cardiac reactivity to different stressors was investigated. A constant routine protocol was used with repeated exposure to a dual task and a cold pressor test. The 29 subjects were randomly divided into two groups in order to manipulate prior wakefulness. Group 1 started at 09:00 h immediately after a monitored sleep period, whereas group 2 started 12 h later. Measures of interbeat intervals (IBI), respiratory sinus arrythmia (RSA, a measure of parasympathetic activity), pre-ejection period (PEP, a measure of sympathetic activity), as well as core body temperature (CBT) were recorded continuously. Multilevel regression analyses (across-subjects) revealed significant (mainly 24 h) sinusoidal circadian variation in the response to both stressors for IBI and RSA, but not for PEP. Individual 24 + 12 h cosine fits demonstrated a relatively large interindividual variation of the phases of the IBI and RSA rhythms, as compared to that of the CBT rhythm. Sinusoidal by group interactions were found for IBI and PEP, but not for RSA. These findings were interpreted as an indication for endogenous circadian and exogenous parasympathetic (vagal) modulation of cardiac reactivity, while sympathetic reactivity is relatively unaffected by the endogenous circadian drive and mainly influenced by exogenous factors.     

Autonomic Nervous System Activity During Actual and Mentally Simulated Preparation for Movement

The aim of this study was to compare actual versus mentally simulated preparation for a complex motor skill. Two behavioral periods are observed during weightlifting: (i) an initial phase in which the subject standing behind the bar is thought to focus his attention on forthcoming execution and (ii) a second phase between hands/bar contact and execution during which the subject is thought to increase activation. Such mental processes accompanying behavioral sequences are correlated with autonomic nervous system activity, phasic responses corresponding to allocation of attentional resources, and tonic variations related to increasing general activation. To study mental processes during preparation for action, 12 subjects performed actual and imagined preparation phases of execution. Six autonomic variables were measured continuously. Skin potential (² = 0.16), skin temperature amplitude (Z = –0.66) and duration (Z = –1.78), skin blood flow amplitude (Z = –0.56) and duration (Z = –1.51), respiratory frequency amplitude (Z = –0.14) and duration (Z = –0.13), and duration of heart rate response (Z = –1.25) were shown to be comparable (p >.05), whatever the modality of preparation. However, during mentally simulated preparation, skin resistance response was shorter than in actual preparation (Z = –2.12, p <.05), thus attesting to a weaker load, whereas lower decrease in heart rate was elicited (Z = –1.96, p <.05). This may be explained by this particular experimental condition because mental preparation would not lead to actual action. Such autonomic variables could be used as feedback to improve performance.     

Involvement of Autonomic Nervous Activity Changes in Gastroesophageal Reflux in Neonates during Sleep and Wakefulness

Background

It has been suggested that disturbed activity of the autonomic nervous system is one of the factors involved in gastroesophageal reflux (GER) in adults. We sought to establish whether transient ANS dysfunction (as assessed by heart rate variability) is associated with the occurrence of GER events in neonates during sleep and wakefulness.

Methods

Nineteen neonates with suspected GER underwent simultaneous, synchronized 12-hour polysomnography and esophageal multichannel impedance-pH monitoring. We compared changes in HRV parameters during three types of periods (control and prior to and during reflux) with respect to the vigilance state.

Results

The vigilance state influenced the distribution of GER events (P<0.001), with 53.4% observed during wakefulness, 37.6% observed during active sleep and only 9% observed during quiet sleep. A significant increase in the sympathovagal ratio (+32%, P=0.013) was observed in the period immediately prior to reflux (due to a 15% reduction in parasympathetic activity (P=0.017)), relative to the control period. This phenomenon was observed during both wakefulness and active sleep.

Conclusion

Our results showed that GER events were preceded by a vigilance-state-independent decrease in parasympathetic tone. This suggests that a pre-reflux change in ANS activity is one of the factors contributing to the mechanism of reflux in neonates.     

Application of Chaos Theory in Analyzing the Cardiac Rhythm in Healthy Subjects at Different Sleep Stages

The changes in the chaotic element of the cardiac rhythm (CR) were quantitated at different sleep stages by calculating the correlation dimension (D2) in 26 healthy subjects of both sexes (mean age 29.2 years), including 7 trained and 19 untrained subjects. Three untrained subjects took part in tests with autonomic nervous system blockers (atropine and propranolol). The study demonstrated a correlation between the changes in D2 at different sleep stages and the level of the autonomic regulation of CR. As the influence of the parasympathetic system on CR increased from one stage of slow wave sleep to another, D2 increased; during rapid eye movement (REM) sleep, this influence weakened and D2 decreased. The character of changes differed in the trained and untrained subjects and depended on the initial level of the autonomic regulation of CR. In the trained subjects, characterized by predominance of the parasympathetic regulation of CR, the initial and subsequent D2 values were higher than in the untrained subjects. Both during wakefulness and at all stages of sleep, D2 increased when the sympathetic regulation of CR was blocked, decreased when the parasympathetic regulation was blocked, and reached the lowest level when both of them were blocked. This showed that the chaotic element of CR, expressed numerically by D2, depends on the regulating effects of the autonomic nervous system.     

Sleep Cystometrography: A Preliminary Study of Bladder Function During Sleep

Bladder function during sleep was studied by the use of a cystometer which recorded detrusor contractions and intravesical pressure as urine accumulated in the bladder during diuresis. The cystometrographic tracing was obtained while the patient was awake. A detrusor contraction can occur during sleep. Results of such studies on five patients are presented, with photographs of representative cystometrographic tracings.The general pattern of the cystometrogram during sleep was found to be different from that obtained while the patient was awake. A detrusor contraction can occur during sleep and may subsequently: (a) subside without awakening the patient; (b) be associated with the involuntary escape of urine or flatus; or (c) cause the patient to awaken. It is suggested that detrusor contractions rather than increases in urinary volume are responsible for the individual''s awakening at night to urinate.In the light of these observations, further study of patients with enuresis and those with non-obstructive nocturia is required.     

Elevated Variance in Heart Rate During Slow-Wave Sleep After Late-Night Physical Activity

This study investigates the effect of mild physical activity before bedtime on the sleep pattern and heart rate during the night. Nine healthy subjects underwent a habituation night, a reference night, and a physical induction night. The physical induction night did not alter the sleep pattern. Physical activity before bedtime resulted in higher heart rate variance during slow-wave sleep. The low-frequency/high-frequency component (LF/HF) ratio during slow-wave sleep in the physical induction night was significantly higher than during the reference night. Increased mean heart rate and higher LF/HF ratio are related to decreased parasympathetic dominance. Exercise up to 1?h before bedtime thus seems to modify the quality of sleep. (Author correspondence: Daniel.Berckmans@biw.kuleuven.be)     

Expression of Clock Genes in Human Peripheral Blood Mononuclear Cells throughout the Sleep/Wake and Circadian Cycles

The rhythmic expression of circadian clock genes in the neurons of the suprachiasmatic nucleus (SCN) underlies the manifestation of endogenous circadian rhythmicity in behavior and physiology. Recent evidence demonstrating rhythmic clock gene expression in non‐SCN tissues suggests that functional clocks exist outside the central circadian pacemaker of the brain. In this investigation, the nature of an oscillator in peripheral blood mononuclear cells (PBMCs) is evaluated by assessing clock gene expression throughout both a typical sleep/wake cycle (LD) and during a constant routine (CR). Six healthy men and women aged (mean±SEM) 23.7±1.6 yrs participated in this five‐day investigation in temporal isolation. Core body temperature and plasma melatonin concentration were measured as markers of the central circadian pacemaker. The expression of HPER1, HPER2, and HBMAL1 was quantified in PBMCs sampled throughout an uninterrupted 72 h period. The core body temperature minimum and the midpoint of melatonin concentration measured during the CR occurred 2:17±0:20 and 3:24 ±0:09 h before habitual awakening, respectively, and were well aligned to the sleep/wake cycle. HPER1 and HPER2 expression in PBMCs demonstrated significant circadian rhythmicity that peaked early after wake‐time and was comparable under LD and CR conditions. HBMAL1 expression was more variable, and peaked in the middle of the wake period under LD conditions and during the habitual sleep period under CR conditions. For the first time, bi‐hourly sampling over three consecutive days is used to compare clock gene expression in a human peripheral oscillator under different sleep/wake conditions.     

Autonomic Cardiac Rhythm Regulation and Temperament in Infancy

The specific features of the cardiac rhythm (CR) and temperament were studied in 92 children aged from 15 to 31 months. The average cardiac interval in a recumbent position and its variability (standard deviation) were determined. The parasympathetic tone (PT) was determined by analyzing the CR wave structure according to CR spectrum power within the range of 0.2 to 1.2 Hz. The sympathetic tone was measured by subtracting the PT contribution from the spectrum power within the range of 0 to 0.2 Hz by means of regression. The children's temperament was measured using their parents' questionnaires. Repeated examination showed the stability of the CR characteristics. The PT was shown to correlate with the children's motor activity (0.52), approaching a new subject (0.39), distraction (–0.34), and the age of entering a nursery (–0.35). The results evidenced a relationship between the parasympathetic tone and the behavioral activity during the first years of life and the role of the parasympathetic tone in physiological regulation of approach/avoidance responses and sustained attention.     

睡眠剥夺中感觉运动皮层和视觉皮层神经活动及警觉水平的改变

在睡眠剥夺(sleep deprivation, SD)过程中,人类大脑的神经活动和警觉水平如何受到影响,尤其是感觉运动和视觉系统,目前仍是研究的热点。静息状态功能磁共振成像(resting state functional magnetic resonance imaging,rfMRI)作为一种反映人脑自发活动的非侵入式成像技术,在睡眠剥夺的研究中得到了广泛应用。本研究采用9次重复rfMRI和心理运动警觉任务(psychomotor vigilance task,PVT),以探索23名志愿者在整个36小时的睡眠剥夺过程中神经活动和警觉水平的变化。我们采用基于PVT的平均反应时间(mean reaction time, MRT)和失效率(lapses ratio, LR)评估警觉水平的变化。我们采用基于rfMRI的区域同质性(region homogeneity,ReHo)和低频波动幅度(amplitude of low frequency fluctuation,ALFF)评估大脑神经活动变化。结果表明,感觉运动网络(sensorimotor network, SMN)和视觉区域(visual network, VN)是受到睡眠剥夺影响最严重的区域。我们采用组独立成分分析(Group Independent component analysis, GICA)将视觉相关区域划分为视觉I区、视觉II区、视觉关联区,并从解剖自动标记(Anatomical automatic labeling,AAL)模板中提取运动感觉相关区域,包括中央前/中央后回、中央旁小叶和辅助运动区。我们发现,睡眠剥夺后16 - 30小时脑神经活动及警惕性下降。我们采用2×3重复测量方差分析,探讨睡眠压力、昼夜节律及其交互作用对感觉运动相关和视觉相关脑区神经活动的影响。我们观察到睡眠压力与交互作用对感觉运动相关区域和视觉相关区域有显著影响。我们采用皮尔逊相关系数评估警觉水平变化与感觉运动相关和视觉相关脑区神经活动变化的关系。睡眠剥夺期间所有感觉运动相关区域的神经活动变化与警觉变化均存在显著的相关关系。我们的研究结果证实,睡眠剥夺从第一天24：00开始改变SMN和VN的警戒水平和神经活动,睡眠压力和昼夜节律在睡眠剥夺期间调节SMN和VN的神经活动。此外,昼夜节律的效应受到睡眠压力的显著调节。感觉运动相关区域和视觉相关区域的增强导致他们远程连接的减弱,这可能是睡眠剥夺期间响应时间变慢的原因。     

Assessment of Cardiac Autonomic Modulation during Adolescent Obesity

Objective: To investigate the cardiovascular autonomic function in pediatric obesity of different duration by using standard time domain, spectral heart rate variability (HRV), and nonlinear methods. Research Methods and Procedures: Fifty obese children (13.9 ± 1.7 years) were compared with 12 lean subjects (12.9 ± 1.6 years). Obese children were classified as recent obese (ROB) (<4 years), intermediate obese (IOB) (4 to 7 years), and long‐term obese (OB) (>7 years). In all participants, we performed blood pressure (BP) measurements, laboratory tests, and 24‐hour electrocardiogram/ambulatory BP monitoring. The spectral power was quantified in total power, very low‐frequency (LF) power, high‐frequency (HF) power, and LF to HF ratio. Total, long‐term, and short‐term time domain HRV were calculated. Poincaré plot and quadrant methods were used as nonlinear techniques. Results: All obese groups had higher casual and ambulatory BP and higher glucose, homeostasis model assessment, and triglyceride levels. All parameters reflecting parasympathetic tone (HF band, root mean square successive difference, proportion of successive normal‐to‐normal intervals, and scatterplot width) were significantly and persistently reduced in all obese groups in comparison with lean controls. LF normalized units, LF/HF, and cardiac acceleration (reflecting sympathetic activation) were significantly increased in the ROB group. In IOB and OB groups, LF, but not nonlinear, measures were similar to lean controls, suggesting biphasic behavior of sympathetic tone, whereas nonlinear analysis showed a decreasing trend with the duration of obesity. Long‐term HRV measures were significantly reduced in ROB and IOB. Discussion: Autonomic nervous system changes in adolescent obesity seem to be related to its duration. Nonlinear methods of scatterplot and quadrant analysis permit assessment of autonomic balance, despite measuring different aspects of HRV.