Classical conditioning and conditionability of insulin and glucose effects in healthy humans

We examined whether the effects of intravenously injected insulin and glucose (the physiological endogenous insulin production stimulus) could be classically conditioned in healthy humans. We expected a conditioned blood glucose decrease to a conditioned stimulus (CS) previously paired with insulin and an, albeit lower, blood glucose decrease to a CS paired with glucose injection. In addition, we analyzed glucoregulatory hormone and symptom conditionability. Thirty healthy males were divided into three groups and were given the CS and an intravenous injection of either insulin (0.05 IU/kg) in Group 1, glucose (15%, 0.5 g/kg) in Group 2, or placebo [physiological saline (0.9%)] in Group 3 during the acquisition phase on 4 days. All participants were given the olfactory CS (rosewood-peppermint smell) and placebo injection on Day 5 (test). On Day 5, the total blood glucose decrease tended to be higher in Group 1 than in Group 3 (P<.10), especially at CS presentation (P<.10) and previous unconditioned hypoglycemia time-point (P<.05). The conditioned blood glucose decrease was statistically nonsignificant in Group 2, but shortly after CS presentation, insulin level and blood glucose changes were negatively correlated in Groups 1 and 2 in contrast to positive correlation in Group 3. Furthermore, Group 1 showed an increase in noradrenaline (P<.05), a temporarily delayed increase in growth hormone (GH; P<.05), and an increase of autonomic and neuroglycopenic symptoms, reaching a medium and small effect size, respectively. Group 2 responded with an increase in cortisol (P<.01) and neuroglycopenic symptoms (P<.05) at the time-point of the previous unconditioned blood glucose minimum. To conclude, the effects of exogenously applied insulin can be conditioned in a reliable way. In correspondence with the lower intensity of the unconditioned stimulus (US), conditioning effects with glucose-and, thus, endogenously produced insulin-are weaker but also reflect the actions of central insulin. Future studies will examine the diverse actions of insulin within the brain further.     

The reinforcing effects of vagal stimulation on classically conditioned heart rate in rats

Classically conditioned heart rate was examined in 4 groups of restrained rats using a 2 × 2 factorial design in which one of the factors was type of US (electric shock vs inhalation of ammonia fumes) and the other whether the US was presented alone or in combination with direct stimulation of the intact vagus nerve. All of the groups demonstrated conditioned decelerations in heart rate with the magnitudes of the CRs of the two compound-US groups being larger than those shown by the single-US groups. The detailed topographies of the CRs were essentially the same for all groups with maximum cardiodecelerations occurring just prior to the presentation of the US(s). Magnitude and direction of the CRs were not systematically related to the URs elicited by the various USs. Augmentation of conditioning in the compound-US groups was discussed in terms of the possible effects of vagal stimulation on motivational level and on a central system coordinating cardiac and somato-motor activities.     

The effect of eccentric strength training on heart rate and on its variability during isometric exercise in healthy older men

The purpose of this study was to investigate if chronic eccentric strength training (ST) affects heart rate (HR) and heart rate variability (HRV) during sub-maximal isometric voluntary contractions (SIVC). The training group (TG) (9 men, 62 ± 2) was submitted to ST (12 weeks, 2 days/week, 2–4 sets of 8–12 repetitions at 75–80% peak torque (PT). The control group (CG) (8 men, 64 ± 4) did not perform ST. The HR and the HRV (RMSSD index) were evaluated during SIVC of the knee extension (15, 30 and 40% of PT). ST increased the eccentric torque only in TG, but did not change the isometric PT and the duration of SIVC. During SIVC, the HR response pattern and the RMSSD index were similar for both groups in pre- and post-training evaluations. Although ST increased the eccentric torque in the TG, it did not generate changes in HR or HRV.     

Baroreceptor involvement in classically conditioned heart rate responses of restrained rats

A group (N = 8) of restrained, baroreceptor denervated rats and a sham-operated-control group (n = 8) received discriminated classical conditioning consisting of 30 reinforced trials in which a CS+ was paired with an electric shock US and 30 non-reinforced trials in which a different CS (CS-) was presented alone. The control group displayed a decelerative heart rate CR and a biphasic pressor-depressor blood pressure CR. The denervated group failed to show a heart rate CR but did show a pressor-only blood pressure CR. The URs of the denervated group consisted of a major depressor change in blood pressure and a slight tachycardia whereas the URs of the control group consisted of a slight pressor response and tachycardia. The results indicated that centrally initiated activity in the efferent vagal pathways mediating the decelerative HR CR in rats may be blocked by the absence of normal afferent baroreceptor neural discharge. An integrating role of baroreceptor input was also suggested for the URs.     

Classical conditioning of heart rate in rats using direct vagal stimulation as a US

Classically conditioned heart-rate deceleration was established in rats using a 2-sec stimulation of the intact cervical vagus nerve as the US. Although small in magnitude, changes in the form of the CR over training indicated that there may have been inhibition of delay similar to that obtained using a traditional painful shock US. Independent assessments of motivational potency revealed that the vagal US did not lead to conditioned lever-press suppression in a CER procedure, but did produce reliable escape responding in a shuttle-box preference situation. It was suggested that the mildly aversive motivational effects of vagal stimulation may have stemmed from the activation of a vagally mediated system involved in the regulation of hunger.     

Spectral evaluation of aging effects on blood pressure and heart rate variations in healthy subjects

The background to heart rate variability (HRV) and blood pressure variability (BPV), and their determinants and physiological correlates, remain obscure. The impact of age must be taken into account if HRV and BPV are used for predictive purposes in clinical settings. Healthy subjects show wide inter-individual variation in their heart rate behaviour and the factors affecting heart rate dynamics are not well known. This paper has undertaken to evaluate heart rate variability (HRV) and baroreflex sensitivity (BRS) in a random sample of subjects without evidence of heart disease, and to estimate the relation of HRV and BPV behaviour to age. The aim of this study was to analyse the effects of ageing on HRV and BPV for simultaneous recordings of electrocardiograph (ECG) and blood pressure (BP) signals at rest in healthy subjects. We studied eight young (21 – 34 years old) and eight elderly (68 – 85 years old) rigorously screened subjects from the Fantasia Database to make the reproducibility and comparability of the results more extensive. Time- and frequency-domain analysis of HRV and BPV was performed on 5-minute ectopic-free recordings. BRS on the heart was estimated by frequency-domain analysis of spontaneous variability of systolic blood pressure (SBP) and RR interval. It has been observed that compared to young the elderly subjects have (i) diminished HRV; (ii) a shift in the power spectral density and median frequency to low frequency side for HRV and to higher frequency side for BPV; and (iii) increased low-frequency alpha index and decreased high-frequency alpha index of BRS with overall alpha index augmented. The results convey that normal ageing in the absence of disease is associated with lesser parasympathetic regulation of heart rate. Thus it is concluded that the age is an important factor to be considered for prognosis and diagnosis by HRV and BPV. For reliable clinical applications, more research needs to be done on a broad spectrum of subjects. In addition, these observations will prove to be useful for dynamic modelling of cardiovascular regulation for testing the authentication of new techniques for analysis purposes.     

A comparison of photoplethysmography and ECG recording to analyse heart rate variability in healthy subjects

Measures of heart rate variability (HRV) are widely used to assess autonomic nervous system (ANS) function. The signal from which they are derived requires accurate determination of the interval between successive heartbeats; it can be recorded via electrocardiography (ECG), which is both non-invasive and widely available. However, methodological problems inherent in the recording and analysis of ECG traces have motivated a search for alternatives. Photoplethysmography (PPG) constitutes another means of determining the timing of cardiac cycles via continuous monitoring of changes in blood volume in a portion of the peripheral microvasculature. This technique measures pulse waveforms, which in some instances may prove a practical basis for HRV analysis. We investigated the feasibility of using earlobe PPG to analyse HRV by applying the same analytic process to PPG and ECG recordings made simultaneously. Comparison of 5-minute recordings demonstrated a very high degree of correlation in the temporal and frequency domains and in nonlinear dynamic analyses between HRV measures derived from PPG and ECG. Our results confirm that PPG provides accurate interpulse intervals from which HRV measures can be accurately derived in healthy subjects under ideal conditions, suggesting this technique may prove a practical alternative to ECG for HRV analysis. This finding is of particular relevance to the care of patients suffering from peripheral hyperkinesia or tremor, which make fingertip PPG recording impractical, and following clinical interventions known to introduce electrical artefacts into the electrocardiogram.     

Cognitive depressive symptoms associated with delayed heart rate recovery following interpersonal stress in healthy men and women

Among cardiac patients, research suggests that somatic depressive symptoms are more strongly associated with altered cardiovascular responses to stress than cognitive depressive symptoms. This study sought to determine whether this was also the case in healthy individuals. One hundred and ninety-nine adults from the community completed the Beck Depression Inventory II (BDI-II) and underwent psychological laboratory stressors while their blood pressure, heart rate, and heart rate variability were monitored. A cognitive-affective factor and somatic-affective factor were identified within the BDI-II, but only the cognitive factor was associated with reduced heart rate recovery following the stressors in multivariate analyses examining both factors simultaneously. This suggests that cognitive depressive symptoms may be more strongly related to altered stress physiology following psychological stressors.     

低体温与心率变异性和血压变异性的关系

目的: 研究低体温与自主神经功能变化的关系。方法: 采用体表物理降温法逐步降低直肠温度,直肠温度变化范围为19-37 ℃。分别记录不同直肠温度下大鼠动态心电和血压信号。应用心率变异性和血压变异性分析系统评价低体温对心率变异性和收缩压变异性的影响。结果: 心率变异分析表明，直肠温度下降到29 ℃以下,R-R间期均延长（P<0.01）,提示心率明显降低;当直肠温度下降到19-21 ℃时,心率变异归一化低频功率降低（P<0.05）和归一化高频功率增加（P<0.05），而且自主神经的平衡向心迷走神经张力增强的方向发生了转移（P<0.05）。血压变异性分析表明，体温下降到31℃时与呼吸有关的归一化高频功率开始增加（P<0.01）；直肠温度下降到29 ℃以下(除27 ℃外),与呼吸有关的归一化高频功率增加（P<0.05或P<0.01），同时自主神经的平衡也发生了改变（P<0.05）。结论： 随着体温的降低，心血管迷走神经活性增加，自主神经的平衡向迷走神经张力增强的方向转移。低体温对血压变异性的影响敏感于心率变异性。     

Modulation of heart rate variability by estrogen in young women undergoing induction of ovulation

Estrogens are involved in the modulation of the cardiovascular system, yet their effects in young women remains largely unknown. Women who undergo ovulation induction treatments attain extremely high estrogen concentrations during a very short time period. The aim of the present study was to evaluate the effects of an acute increase in estrogens on the autonomic nervous system modulation of heart rate variability (HRV). A total of 27 women undergoing ovulation induction and 14 normally menstruating women were prospectively studied. HRV was assessed during nadir and peak estrogen using time domain and power spectral density analyses. A significant increase in high-frequency spectral power (243 ± 77 vs. 188 ± 73 ms²/Hz, P < 0.01) with a significant decrease in the ratio of low to high-frequency power was observed during estrogen peak in women undergoing induction of ovulation. The acute increase in estrogen in women undergoing ovulation induction was associated with vagal activation and altered sympathovagal balance.     

Effects of mental and physical demands on heart rate variability during computer work

The aim of the study was to evaluate the effect of physical and mental demands on heart rate variability- (HRV-) derived indices of autonomic activity. Ten healthy, female subjects performed two computer tasks: one with combined mental and physical demands and a reference task primarily consisting of physical demands. The combined task, which was performed once with a keyboard and once with a computer mouse, was a computerized version of the colour word conflict task (CWT). The CWT is highly mentally demanding due to the inherent perceptual conflict between a word stimulus and a colour stimulus. In the reference task (REF) the physical demands were comparable to CWT, while the mental demands were low. Finally, the subjects rested at the workplace (REST). Data on performance, heart rate (HR), mean arterial blood pressure (MAP), HRV, and urinary concentrations of catecholamines were obtained. The following frequency bands were applied for HRV: very low frequency (VLF, 0.00–0.04 Hz), low frequency (LF, 0.05–0.15 Hz), high frequency (HF, 0.16–0.40 Hz) and total power (TP, 0.00–0.40 Hz). Indices of sympathetic nervous activity (I_SNS) and parasympathetic nervous activity (I_PNS) were estimated as normalized powers in LF and HF bands: I_SNS=LF/(TP–VLF) and I_PNS=HF/(TP–VLF). Values are expressed as normalised units (nu). There was an increase in I_SNS during CWT [mouse: 0.490 (0.052) nu [ave (SEM)] and keyboard: 0.476 (0.039) nu] and REF [mouse: 0.453 (0.059) nu and keyboard: 0.489 (0.047) nu] compared to REST [0.397 (0.047) nu], but no difference between CWT and REF. Corresponding decreases were observed for I_PNS. HR and MAP were higher during CWT compared to REST. No effects were observed for excreted amounts of catecholamines. There were no differences between the computer mouse and the keyboard condition for I_SNS and I_PNS. In conclusion, an increase in I_SNS and a decrease in I_PNS were found in response to a physically demanding reference computer task. Addition of mental demands did not elicit any further effect on I_SNS and I_PNS, suggesting a significant influence of the physical rather than the mental demands during computer work. Electronic Publication     

心肌缺血中心率变异性的符号动力学分析

目的基于心率变异性（HRV）研究,分析心肌缺血发生过程中心率的动态变化特性以探讨自主神经活动的变化和影响。方法从长时ST段一T波终点（Long．term ST-T）数据库中,选取13个记录中共193个心肌缺血时段及其前后各5min的对照时段。选用符号动力学方法分析不同时段的RR间期序列,利用重复测量的方差分析对缺血前和缺血中以及缺血后结果进行检验;以线性拟合的方式,分析心肌缺血时自主神经响应模式随缺血持续时间的分布。结果较之心肌缺血前后,心肌缺血过程中0v％的显著增加和2UV％的显著减小反映了交感神经活性的增加和迷走神经活性的减弱,但这种自主神经平衡向交感神经更占优移动的趋势随着缺血持续时间的延长而减小,提示可能存在的对心脏的保护作用。结论符号动力学分析为研究心肌缺血中自主神经的调制提供了一个敏感的工具。     

Heart rate variability in acute psychosis

Heart rate variability (HRV) provides reliable tools to assess the integrity and reactivity of autonomic nervous function. Our aim was to examine HRV in the resting condition and during different mental loads in acute psychosis compared to healthy controls. HRV was measured in 17 first-episode drug-naive patients with psychosis and 21 healthy controls during oddball tasks and while performing the Wisconsin Card Sorting Test. A discrete event series was constructed by an adaptive QRS detector algorithm and power spectrum estimation was carried out. The RMSSD (representing interval differences of successive heartbeats) and the amount of high frequency (HF) power were significantly reduced in patients. Moreover, the patients' HRV remained unaltered during the tasks, whereas in controls the HRV diminished with increasing mental load of the task. Patients with psychosis displayed less short-term HR reactivity than healthy controls. They also failed to adapt HRV according to the task-connected strain. Acute psychosis is characterized by a limited capacity to respond to external demands at the level of autonomic nervous system.     

Linear and nonlinear analysis of heart rate variability in healthy subjects and after acute myocardial infarction in patients

The objectives of this study were to evaluate and compare the use of linear and nonlinear methods for analysis of heart rate variability (HRV) in healthy subjects and in patients after acute myocardial infarction (AMI). Heart rate (HR) was recorded for 15 min in the supine position in 10 patients with AMI taking β-blockers (aged 57 ± 9 years) and in 11 healthy subjects (aged 53 ± 4 years). HRV was analyzed in the time domain (RMSSD and RMSM), the frequency domain using low- and high-frequency bands in normalized units (nu; LFnu and HFnu) and the LF/HF ratio and approximate entropy (ApEn) were determined. There was a correlation (P < 0.05) of RMSSD, RMSM, LFnu, HFnu, and the LF/HF ratio index with the ApEn of the AMI group on the 2nd (r = 0.87, 0.65, 0.72, 0.72, and 0.64) and 7th day (r = 0.88, 0.70, 0.69, 0.69, and 0.87) and of the healthy group (r = 0.63, 0.71, 0.63, 0.63, and 0.74), respectively. The median HRV indexes of the AMI group on the 2nd and 7th day differed from the healthy group (P < 0.05): RMSSD = 10.37, 19.95, 24.81; RMSM = 23.47, 31.96, 43.79; LFnu = 0.79, 0.79, 0.62; HFnu = 0.20, 0.20, 0.37; LF/HF ratio = 3.87, 3.94, 1.65; ApEn = 1.01, 1.24, 1.31, respectively. There was agreement between the methods, suggesting that these have the same power to evaluate autonomic modulation of HR in both AMI patients and healthy subjects. AMI contributed to a reduction in cardiac signal irregularity, higher sympathetic modulation and lower vagal modulation.     

Effects of low ambient temperature on heart rate variability during sleep in humans

The effects of cold exposure on heart rate variability (HRV) during sleep were examined. Eight male subjects slept under three different conditions: 3°C, 50–80% relative humidity (RH) [3]; 10°C, 50% RH [10]; and 17°C 50% RH [17]. No significant differences were observed in HRV during rapid eye movement sleep (REM) and wakefulness. The ratio of the low frequency (LF) to high frequency component (HF) of HRV (LF/HF) significantly differed among the conditions during stage 2 and slow wave sleep (SWS) that decreased as the ambient temperature decreased. The normalized LF [LF/(LF + HF)] significantly decreased in 3 and 10 than in 17 during SWS. In low ambient temperature, predominant cardiac parasympathetic activity during stage 2 with no significant difference during REM and wakefulness may cause variations in HRV at transition from stage 2 to REM and wakefulness. These results may partly explain the peak in adverse cardiac events during winter.     

Changes in resting heart rate variability across the menstrual cycle

Heart rate variability (HRV) is a noninvasive indicator of autonomic control. This study examines HRV changes across a normal menstrual cycle and proposes a novel piecewise function controlling for the effects of breathing on HRV spectral parameters. A resting ECG was collected from 13 women at five points in their menstrual cycle. Both heart rate and breathing rate increased across the cycle (p < .01) while time‐domain variability decreased (p = .04). Use of the piecewise function for breathing rate in HRV spectral analysis was confirmed by a substantial increase in model goodness‐of‐fit. HRV spectral parameters, controlled for breathing with the piecewise function, confirm that the decrease in variability is likely due to a parasympathetic withdrawal, since high frequency HRV decreases (p = .02).     

Effects of dynamic resistance training on heart rate variability in healthy older women

Twenty healthy women aged between 65 and 74 years, trained three times a week, for 16 weeks, on a cycle ergometer, to determine the effects of dynamic resistance training on heart rate variability (HRV). Subjects were allocated to two training groups, high (HI, n=10) and low (LO, n=10) intensity. The HI group performed eight sets of 8 revolutions at 80% of the maximum resistance to complete 2 pedal revolutions (2RM); the LO group performed eight sets of 16 pedal revolutions at 40% of 2RM. Subjects were tested twice before, as control period (−4 weeks and 0 weeks) and once after training (16 weeks) for HRV, maximum voluntary contraction (MVC) of knee extensors and peak power (P _p) of lower limbs by jumping on a force platform. HRV was measured using time and frequency domain parameters. Two-way ANOVA for repeated measures was performed on all variables (P<0.05). Results showed no differences between training groups. Following training HRV was not modified, while MVC and P _p significantly increased. The two proposed forms of dynamic resistance training were appropriate to improve muscle power and strength in elderly females without affecting HRV. More research should verify the effects of an isometric and more prolonged training stimulus on HRV in older subjects. Electronic Publication     

Resting high‐frequency heart rate variability is related to resting brain perfusion

We examined the neural correlates of resting cardiac vagal activity in a sample of 432 participants (206 male; 61 African American; mean age 42 years). Pulsed arterial spin labeling was used to quantify whole brain and regional cerebral blood flow at rest. High‐frequency heart rate variability (HF‐HRV) was used to measure cardiac vagal activity at rest. The primary aim was to determine whether brain regions implicated in regulating cardiac vagal reactions were also related to cardiac vagal activity at rest, and whether these associations varied by sex or race. Brain areas previously related to vagal reactivity were related to resting HF‐HRV. Directionality of relationships differed between overall and regional flows. Some relationships were only observed in women and African Americans. There appears to be communality between brain regions associated with task‐induced vagal reactivity and those associated with resting cardiac vagal activity.     

Women with posttraumatic stress disorder have larger decreases in heart rate variability during stress tasks

The relationship between posttraumatic stress disorder (PTSD) and high frequency heart rate variability (HF-HRV) was investigated during a resting baseline period and two 4-minute laboratory speech tasks. Participants were 20 women with PTSD and 20 age- and gender-matched controls. Parasympathetic nervous system (PNS) cardiac control was measured as HF-HRV (0.12–0.40 Hz) using power spectrum analysis. Participants with PTSD had significantly greater reductions in HF-HRV during two speech tasks (trauma recall and mental arithmetic) than control. These results suggest that PTSD is related to the magnitude of decrease in parasympathetic cardiac control during stress in women. Health implications of altered PNS activity associated with PTSD deserve further study.     

Moderate alcohol intake is related to increased heart rate variability in young adults: Implications for health and well‐being

Epidemiological literature indicates that the relationship between alcohol consumption and health outcomes reflects a J‐shaped curve such that moderate alcohol consumption confers a protective effect in comparison to abstinence, while heavy consumption is associated with poorer health. While heart rate variability (HRV) may underpin the relationship between drinking and poor health in heavy drinkers, it is unclear whether HRV is increased in moderate, habitual drinkers relative to nonhabitual drinkers. HRV and drinking habits were assessed in 47 volunteers. Results supported hypotheses suggesting that moderate, habitual drinking increases HRV. Although not supported by a significant interaction between drinking group and sex, planned follow‐up analysis also revealed that these findings may be specific to males. Regardless, results highlight HRV as a candidate mechanism for the findings reported in the epidemiological literature.