The nature of arousal in sleep

The role of arousals in sleep is gaining interest among both basic researchers and clinicians. In the last 20 years increasing evidence shows that arousals are deeply involved in the pathophysiology of sleep disorders. The nature of arousals in sleep is still a matter of debate. According to the conceptual framework of the American Sleep Disorders Association criteria, arousals are a marker of sleep disruption representing a detrimental and harmful feature for sleep. In contrast, our view indicates arousals as elements weaved into the texture of sleep taking part in the regulation of the sleep process. In addition, the concept of micro-arousal (MA) has been extended, incorporating, besides the classical low-voltage fast-rhythm electroencephalographic (EEG) arousals, high-amplitude EEG bursts, be they like delta-like or K-complexes, which reflects a special kind of arousal process, mobilizing parallely antiarousal swings. In physiologic conditions, the slow and fast MA are not randomly scattered but appear structurally distributed within sleep representing state-specific arousal responses. MA preceded by slow waves occurs more frequently across the descending part of sleep cycles and in the first cycles, while the traditional fast type of arousals across the ascending slope of cycles prevails during the last third of sleep. The uniform arousal characteristics of these two types of MAs is supported by the finding that different MAs are associated with an increasing magnitude of vegetative activation ranging hierarchically from the weaker slow EEG types (coupled with mild autonomic activation) to the stronger rapid EEG types (coupled with a vigorous autonomic activation). Finally, it has been ascertained that MA are not isolated events but are basically endowed with a periodic nature expressed in non-rapid eye movement (NREM) sleep by the cyclic alternating pattern (CAP). Understanding the role of arousals and CAP and the relationship between physiologic and pathologic MA can shed light on the adaptive properties of the sleeping brain and provide insight into the pathomechanisms of sleep disturbances. Functional significance of arousal in sleep, and particularly in NREM sleep, is to ensure the reversibility of sleep, without which it would be identical to coma. Arousals may connect the sleeper with the surrounding world maintaining the selection of relevant incoming information and adapting the organism to the dangers and demands of the outer world. In this dynamic perspective, ongoing phasic events carry on the one hand arousal influences and on the other elements of information processing. The other function of arousals is tailoring the more or less stereotyped endogenously determined sleep process driven by chemical influences according to internal and external demands. In this perspective, arousals shape the individual course of night sleep as a variation of the sleep program.     

The cardiorespiratory activation response at an arousal from sleep is independent of the level of CO(2)

Arousal from sleep is associated with transient cardiorespiratory activation. Traditionally, this response has been understood to be a consequence of state-dependent changes in the homeostatic control of ventilation. The hypothesis predicts that the magnitude of ventilatory and cardiac responses at an arousal will be a function of the intensity of concurrent respiratory stimuli (primarily PCO(2)). Alternatively, it has been proposed that increased cardiorespiratory activity is due to reflex activation. This hypothesis predicts that the magnitude of the cardiorespiratory response will be independent of respiratory stimuli. To compare these hypotheses we measured minute ventilation (V(i)), heart rate (HR) and blood pressure (BP) during wakefulness and stage 2 sleep, while manipulating P(et)CO(2). Further, we assessed the magnitude of the response of these variables to an arousal from sleep at the various levels of P(et)CO(2). The subjects were male aged 18-25 years. P(et)CO(2) was manipulated by clamping it at four levels during wakefulness [wake eucapnic, sleep eucapnic (Low), and sleep eucapnic +3 mmHg (Medium) and +6 mmHg (High)] and three levels during sleep (Low, Medium and High). The average number of determinations for each subject at each level was 14 during wakefulness and 25 during sleep. Arousals were required to meet American Sleep Disorders Association criteria and were without body movement. The results indicated that average increases in V(i), HR and BP at arousal from sleep did not significantly differ as a function of the level of P(et)CO(2) present at the time of the arousal (all P > 0.05). Further, the magnitude of the ventilatory response to an arousal was significantly less than the values predicted by the homeostatic hypothesis (P < 0.05). We conclude that, in normal subjects, the cardiorespiratory response to an arousal from sleep is not because of a homeostatic response, but of a reflex activation.     

Noninvasive cardiovascular markers of acoustically induced arousal from non-rapid-eye-movement sleep

STUDY OBJECTIVES: Changes in cardiovascular measures such as heart rate (HR) and pulse transit time (PTT) have been advocated as sensitive markers of autonomic arousal from sleep. In animal studies, alerting stimuli produce particularly marked skin vascular responses. We hypothesized that changes in skin vascular conductance would provide more sensitive markers of autonomic arousal during sleep compared to central cardiovascular response measures such as HR and PTT. DESIGN: Cardiovascular responses to auditory-induced arousals were recorded during overnight sleep studies. SETTING: Sleep disorders unit in a 270-bed teaching hospital. PARTICIPANTS: Eleven young healthy male subjects. INTERVENTIONS: Throughout ovemight sleep studies, auditory tones (5-second duration, 54-90 decibels, 22-56 per subject) were presented during non-rapid-eye-movement sleep. Beat-by-beat HR, PTT, laser-Doppler fingertip skin blood flow (SBF) and finger and ear photoplethysmogram pulse wave amplitudes (PWA) were measured in the 20 seconds preceding and 30 seconds following each tone and compared to control measurements obtained during 50-second periods of recording with no stimulus (no tone, 6-22 per subject). Electroencephalographic (EEG) arousals were scored according to standard criteria (American Sleep Disorders Association) into no discemible, 3- to 10-second duration, or 10- to 15-second duration arousals. Poststimulus cardiovascular measurements were expressed as a percentage of the prestimulus mean and response magnitudes quantified from peak responses and the area under the poststimulus response curve. The ability of each cardiovascular response measure to discriminate EEG arousals (EEG changes lasting more than 3 seconds) was assessed from the area under the receiver operating characteristic (ROC) curve. MEASUREMENTS AND RESULTS: There were no significant changes in any cardiovascular parameter during control recordings. In contrast to all other parameters, finger PWA and SBF decreased following tones that produced no discernible EEG arousal (P < 0.05). A significant HR rise and decreases in all cardiovascular measures occurred with greater than 3-second arousals, with longer duration arousals generally exhibiting larger responses. Conventional EEG arousals (greater than 3 seconds) were relatively poorly detected from HR responses (ROC area HR rise 0.80 +/- 0.04) compared to changes in SBF (0.85 +/- 0.02), PTT (0.85 +/- 0.03) and finger PWA (0.90 +/- 0.01). CONCLUSIONS: Decreases in skin vascular conductance (finger PWA and SBF) provide sensitive markers of autonomic arousal during sleep. They are at least as sensitive as PTT for detecting conventionally scored EEG arousals and may be more sensitive in detecting "subcortical" arousals.     

On arousal from sleep: time-frequency analysis

Time-frequency analysis of the heart rate variability during arousal from sleep, with and without EMG activation, coming from five obese healthy subjects was performed. Additionally, a comparative analysis of three time-frequency distributions, smooth pseudo Wigner–Ville (SPWVD), Choi–Williams (CWD) and Born–Jordan distribution (BJD) is presented in this study. SPWVD showed higher capacity for eliminating the cross terms independently of the signal. After applying Hilbert transformation to real signals BJD and CWD lost some important mathematic properties as marginals, on the contrary PSWVD remains unchanged. BJD showed results comparable with CWD. During arousal episodes, analogous energy distribution and spectral indexes were obtained by the three time-frequency representations. Arousals with chin activity presented stronger changes in RR intervals and LF (related to sympathetic activity) component, being statistically different with respect to arousal without chin activity, only around the period of maximum change in β activity on the EEG. These results suggest a more evident stress for the heart when an arousal is related to external muscular activity.     

The effects on cardiovascular autonomic control of repetitive arousal from sleep

STUDY OBJECTIVES: To quantitatively assess autonomic cardiovascular control in normal young adults following exposure to repetitive acoustically-induced arousals from sleep. DESIGN: Respiration, R-R interval (RRI) and noninvasive measurements of continuous arterial blood pressure were monitored in subjects during the transition from relaxed wakefulness to stable Stage 2 sleep. These measurements were made under undisturbed conditions or conditions in which transient arousals were induced repetitively by acoustic stimulation. A mathematical model was used to partition the fluctuations in RRI into a component ("RSA") correlated with respiration and a component ("A representing baroreflex control of heart rate. The magnitudes and forms of each component before and after exposure to repetitive arousals were compared SETTING: Sleep disorders laboratory in a university setting. PATIENTS OR PARTICIPANTS: Ten healthy young adults (5 male, 5 female) with an average age of 20.4 +/- 2.0 y and mean body-mass index of 23.8 +/- 2.9 kg/m2. INTERVENTIONS: Each subject participated in multiple sleep studies consisting of 4 conditions with 2 nights in each condition. The first condition consisted of undisturbed sleep (control), while in the other 3 conditions, the subjects were aroused from sleep by repetitive auditory stimuli applied continuously over a duration of 50 minutes, with periodicities of 30 seconds, 1 minute, and 2 minutes of sleep. MEASUREMENTS AND RESULTS: Exposure to repetitive arousal (RA) did not alter mean heart rate or blood pressure. However, ABR and RSA gains estimated using the model, increased from the onset of Stage 1 sleep to the start of stable Stage 2 sleep under the control condition, but remained unchanged in all RA conditions. There were also significant increases in low-frequency oscillations of systolic blood pressure in the RA conditions versus no change in the control condition. CONCLUSIONS: Exposure to RA over durations approximating an hour produces cumulative effects on autonomic control that are subtle and can only be detected when advanced signal processing methods are employed. More specifically, the increases in ABR and RSA gains that accompany increasing sleep depth in normal sleep are prevented from occurring.     

Respiratory paradox as an indicator of arousal from non-REM sleep

Increasing respiratory effort is the likely stimulus for arousal in patients with sleep-disordered breathing. Changes in the phase angle waveform (an indirect measure of respiratory effort) may provide a useful non-EEG indicator of respiratory-related arousal. The aim of this study was to investigate the relationship between phase angle change (using a continuous measurement technique) and EEG arousal. Polysomnographic sleep recordings (including: EEG, EOG, EMG, respiratory effort [ribcage and abdominal movement], respiratory paradox [continuous phase angle measurement], oral-nasal airflow, and oxygen saturation) were performed in a purpose built laboratory on 30 patients with sleep-disordered breathing (15 patients with obstructive sleep apnoea/hypopnoea syndrome [OSAHS]; 15 chronic heavy snorers without OSAHS) and 15 age and weight matched, non-snoring normal subjects. All data, including the temporal relationship between phase angle change and EEG arousal, were analyzed manually (4,545 phase angle changes and 6,473 EEG arousals). There was a highly significant correlation (p<0.001) between phase angle index (changes/hour of sleep) and EEG arousal index (arousals/hour of sleep). However, mean phase angle index allowed a much clearer differentiation between the three subject groups, with the mean phase angle index providing a six-fold difference between normal and OSAHS groups, while the EEG arousal index gave only a two-fold difference. In support of the suggestion that phase angle changes represent respiratory-related sleep disruption, more than twice as many EEG arousals were associated with a change in the phase angle waveform in patients with sleep-disordered breathing than in normal subjects. This study highlights the limitations of EEG arousal scoring in the assessment of patients with sleep-disordered breathing and provides further evidence to support phase angle change as an indicator of respiratory-related sleep disruption.     

The cardiovascular response to arousal from sleep decreases with age in healthy adults

STUDY OBJECTIVES: To investigate age and gender effects on the acute blood pressure (BP) and heart rate (HR) response to arousal from sleep in healthy adults. DESIGN: Healthy young and older male and female adults were aroused from stage 2 sleep throughout the night using an auditory tone. The magnitude of the cardiovascular responses to arousal were assessed using 2 (young v older) by 2 (male v female) ANOVAs with repeated measures over time. SETTING: Sleep laboratory at the Royal Brompton Hospital, London. PATIENTS OR PARTICIPANTS: 25 healthy young (< or = 40 years, n = 15 males) and 20 healthy older adults (> or = 60 years, n = 11 males). INTERVENTIONS: Arousals (> 10 seconds) from undisturbed stage 2 sleep were induced by an auditory tone throughout the night. MEASUREMENTS AND RESULTS: Overnight polysomnography (PSG) with HR, continuous beat-by-beat arterial BP and respiratory measurements was performed. Older adults had smaller and delayed initial mean BP and HR responses to arousal compared to young adults (both P < 0.001), whereas changes in ventilation and tidal volume responses to arousal were similar between age groups (P = 0.3 and P = 0.6 respectively).There were no differences between females and males in the cardiovascular or respiratory responses to arousal from sleep. CONCLUSION: The cause of the smaller and delayed response in healthy older adults is unknown; however, we speculate that for older people with sleep apnea, in whom nocturnal arousals occur frequently, the reduced cardiovascular response may be protective against the link between sleep apnea and hypertension.     

Acute cardiovascular responses to arousal from non-REM sleep during normoxia and hypoxia.

STUDY OBJECTIVES: There is uncertainty concerning the relative contribution of arousal, chemoreceptor stimulation, and their potentially interactive effects, to the acute cardiovascular changes observed during sleep in patients with sleep-disordered breathing. The purpose of this study was to compare cardiovascular responses (heart rate, skin blood flow, and pulse transit time, a non-invasive measure of arterial wall stiffness) to auditory induced arousal from stage 2 sleep under conditions of normoxia and overnight mild hypoxia. DESIGN: Randomised crossover. SETTING: Sleep Disorders Unit in a 270-bed teaching hospital. PARTICIPANTS: Eleven healthy male subjects. INTERVENTIONS: Subjects slept wearing a facemask and breathed room air (one night; SaO2 approximately 98%) or an hypoxic gas mixture (two nights; SaO2 approximately 92%). Once in stage 2 sleep, subjects were administered one of 10 auditory tones (500 Hz, range 54-90 dB, 5-sec duration) via earphones or a sham tone (recording with no tone). MEASUREMENTS AND RESULTS: Cardiovascular responses were examined beat-by-beat for 20 seconds before and 30 seconds after auditory tones associated with arousals (3-10 second EEG changes) and after sham tones. Sleep efficiency and the percentage of sleep spent in each stage were not different between hypoxia and normoxia nights. Baseline heart rate was elevated on hypoxia nights compared with normoxia nights (59.5+/-1.7 vs. 54.4+/-1.6 b x min(-1), p=0.007). Heart rate, pulse transit time, and skin blood flow showed significant changes after arousal consistent with rapid parasympathetic withdrawal and sympathetic nervous system activation. No changes were observed after sham tones. There were no differences in time course or magnitude of cardiovascular responses between hypoxia and normoxia nights. CONCLUSIONS: We conclude that while mild hypoxia stimulates autonomic activity it does not augment the cardiovascular response to arousal from stage 2 sleep in normal subjects.     

Cerebrovascular response to arousal from NREM and REM sleep

STUDY OBJECTIVE: To determine the effect of arousal from sleep on cerebral blood flow velocity (CBFV) in relation to associated ventilatory and systemic hemodynamic changes. PARTICIPANTS: Eleven healthy individuals (6 men, 5 women). MEASUREMENTS: Pulsed Doppler ultrasonography was used to measure CBFV in the middle cerebral artery with simultaneous measurements of sleep state (EEG, EOG, and EMG), ventilation (inductance plethysmography), heart rate (ECG), and arterial pressure (finger plethysmography). Arousals were induced by auditory tones (range: 40-80 dB; duration: 0.5 sec). Cardiovascular responses were examined beat-by-beat for 30 sec before and 30 sec after auditory tones. RESULTS: During NREM sleep, CBFV declined following arousals (-15% +/- 2%; group mean +/- SEM) with a nadir at 9 sec after the auditory tone, followed by a gradual return to baseline. Mean arterial pressure (MAP; +20% +/- 1%) and heart rate (HR; +17% +/- 2%) increased with peaks at 5 and 3 sec after the auditory tone, respectively. Minute ventilation (VE) was increased (+35% +/- 10%) for 2 breaths after the auditory tone. In contrast, during REM sleep, CBFV increased following arousals (+15% +/- 3%) with a peak at 3 sec. MAP (+17% +/- 2%) and HR (+15% +/- 2%) increased during arousals from REM sleep with peaks at 5 and 3 sec post tone. VE increased (+16% +/- 7%) in a smaller, more sustained manner during arousals from REM sleep. CONCLUSIONS: Arousals from NREM sleep transiently reduce CBFV, whereas arousals from REM sleep transiently increase CBFV, despite qualitatively and quantitatively similar increases in MAP, HR, and VE in the two sleep states.     

Effects of cognitive arousal and physiological arousal on sleep perception

STUDY OBJECTIVES: Two experiments were conducted to investigate the effect of presleep arousal on sleep perception. Experiment 1 examined the link between presleep cognitive arousal and distorted perception of sleep and compared the relative effect of anxious and neutral cognitive arousal on sleep perception. Experiment 2 compared the relative effect of anxious cognitive arousal and physiological arousal on sleep perception. DESIGN: Participants completed a nap session. Just prior to the nap, the participants were randomly assigned to 1 of 3 groups to receive different arousal manipulations. They were then allowed to go to sleep and were asked to report their sleep perception upon waking. SETTING: Sleep laboratory. PARTICIPANTS: Fifty-four healthy good sleepers in each experiment. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Self-reported sleep, actigraphy-defined sleep, and the discrepancy between them were indexed. In Experiment 1, participants who were experimentally manipulated to experience anxious cognitive arousal during the presleep period reported longer sleep-onset latency. Both the Anxious Cognitive Arousal Group and the Neutral Cognitive Arousal Group exhibited a greater discrepancy between self-reported and actigraphy-defined sleep, relative to participants who received no manipulation. In Experiment 2, participants who were experimentally manipulated to experience anxious cognitive arousal or physiological arousal during the presleep period reported longer sleep-onset latency and shorter total sleep time, and both groups exhibited a greater discrepancy between the self-reported and actigraphy-defined sleep, relative to participants who received no manipulation. CONCLUSIONS: Results suggest that both presleep cognitive arousal and presleep physiological arousal contribute to distorted perception of sleep.     

Effect of cognitive arousal on sleep latency, somatic and cortical arousal following partial sleep deprivation

Emerging research has shown that sleepiness, defined as the tendency to fall asleep, is not only determined by sleep pressure and time of day, but also by physiological and cognitive arousal. In this study we evaluated (i) the impact of experimentally induced cognitive arousal on electroencephalogram (EEG) defined sleep latency, and subjective, somatic and cortical arousal, and (ii) whether experimentally induced cognitive arousal enhances performance on a driving simulator test. Twelve healthy sleepers each spent three nights and the following day in the sleep laboratory: an adaptation, a cognitive arousal and a neutral testing day. In the cognitive arousal condition, a visit of a television camera crew took place and subjects were asked to be interviewed. On each testing day, a 5-min heart rate recording, subjective sleepiness and arousal scales, Multiple Sleep Latency Test and a 25-min driving simulator task were scheduled three times at 2-h intervals. Experimentally induced cognitive arousal resulted in significant increases in objective sleep latency. Significantly elevated levels of subjective and somatic arousal--as indexed by a subjective arousal scale and heart rate--were also evidenced following cognitive arousal induction. A marginally significant trend for increased cortical arousal, measured by EEG beta activity, was also found. No effects were found on driving simulator performance. These findings support the concept of cognitive arousal as a significant component in determining sleep latency. In addition, it was illustrated that cognitively induced arousal can provoke increases in somatic and possibly even cortical arousal in normal sleepers. However, this was not accompanied by an enhanced ability to perform adequately on a driving simulator test.     

Mild hypoxia does not suppress auditory arousal from NREM sleep

STUDY OBJECTIVES: The depressive effects of hypoxia on the central nervous system are well known. The purpose of this study was to determine the influence of mild overnight hypoxia on the ability of healthy individuals to arouse from non-rapid-eye-movement (NREM) sleep to auditory tones. DESIGN: Randomized cross-over. SETTING: Participants slept in a sound-insulated room with the physiologic recordings and experimental interventions controlled from a separate room. PARTICIPANTS: Eleven healthy men aged 18 to 24 years. Interventions: On separate nights, participants were exposed to mild overnight hypoxia (SaO2 approximately 90%) or medical air in single-blind fashion. During established sleep, subjects were administered 1 of 10 auditory tones (500 Hz, 54-90 dB, 5 seconds duration) via earphones, or a sham tone (recording period with no tone). MEASUREMENTS AND RESULTS: The probability and intensity of arousal responses in the 30 seconds following tones or shams were compared between gas conditions and between stage 2 and slow-wave sleep. Arousal probability and intensity increased with tone intensity and were significantly lower during slow-wave compared with stage 2 sleep but were not different between hypoxia and normoxia nights. CONCLUSION: These data suggest that mild overnight hypoxia does not impair the neural mechanisms involved in arousal from sleep to auditory stimuli.     

Self-report and cardiovascular measures of arousal: fractionation during residual arousal

Residual arousal has been conceptualized as a state of physiological activation that is amenable to misattribution-like processes because individuals are unaware of their aroused physiological state (Zillmann, 1978). Although there is considerable evidence showing that people in the state labeled "residual arousal" rate excitatory stimuli in a more polarized fashion (see review by Zillmann, 1983), the available evidence for the notion that residual arousal is imperceptible can alternatively be interpreted as evidence of an inability to discriminate the cause of the residual arousal. To determine the nature of the cognitive representation of residual arousal (and, hence, whether excitation transfer is likely to be a nonconscious rather than conscious misattributional process), cardiac activity and reported arousal were tracked before, during, and following exercise. Results replicated previous research showing that exercise-induced cardiac activity remained significantly elevated when subjects ceased to report feeling aroused due to the exercise. These findings were extended through the joint use of magnitude estimation and psychophysiological procedures to index what level of exercise-induced bodily activation was reportable. Results indicated that residual arousal is unperceived rather than perceived and mistaken as to its cause. Implications of the present research range from theories of arousal and of misattribution to the effects of stress-related variations in cardiac performance on cardiac detection.     

Effects of age and sleeping position on arousal from sleep in preterm infants

STUDY OBJECTIVES: Preterm infants are at increased risk of sudden infant death syndrome (SIDS). We investigated whether the prone sleeping position impaired arousal from sleep in healthy preterm infants and whether this impairment was related to cardiorespiratory variables, temperature or postnatal age. DESIGN: Longitudinal SETTING/PARTICIPANTS: 14 healthy preterm infants (mean 32 +/- 0.4 weeks) were studied using daytime polysomnography on 4 occasions: 36-38 weeks postconception age, 2 to 3 weeks postterm, 2 to 3 months postterm, and 5 to 6 months postterm. Interventions: N/A. MEASUREMENTS: Multiple measurements of arousal threshold (cm H2O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep and quiet sleep when infants slept both prone and supine. RESULTS: Arousal thresholds were significantly higher in both AS and QS when infants slept prone at 36 to 38 weeks postconception age and 2 to 3 months postterm but not at 2 to 3 weeks or 5 to 6 months postterm. These increases were independent of any sleep position-related changes in either rectal or abdominal skin temperature, respiratory rate, oxygen saturation or heart rate. CONCLUSIONS: At the age when the risk of SIDS is highest, the prone position significantly impairs arousal from both active sleep and quiet sleep in healthy infants born prematurely. This impairment in arousability occurred with no clinically significant changes in cardiorespiratory parameters or body temperature. Decreased arousability from sleep in the prone position may explain its role as a risk factor for SIDS.     

Disorders of arousal from sleep and violent behavior: the role of physical contact and proximity

STUDY OBJECTIVES: To review medical and legal case reports to determine how many appear to support the belief that violence against other individuals that occurs during Disorders of Arousal - sleepwalking, confusional arousal, and sleep terrors - is triggered by direct physical contact or close proximity to that individual and does not occur randomly or spontaneously. DESIGN: Historical review of case reports in the medical and legal literature. MEASUREMENTS AND RESULTS: A total of 32 cases drawn from medical and legal literature were reviewed. Each case contained a record of violence associated with Disorders of Arousal; in each, details of the violent behavior were available. Violent behaviors associated with provocations and/or close proximity were found to be present in 100% of confusional arousal patients and 81% of sleep terror patients. Violent behaviors were associated with provocation or close proximity in 40%-90% of sleepwalking cases, depending on whether the legal verdict and other factors were taken into account. Often the provocation was quite minor and the response greatly exaggerated. The specific manner in which the violence was triggered differed among sleepwalking, confusional arousals, and sleep terrors. CONCLUSIONS: In the cases reviewed, violent behavior directed against other individuals associated with Disorders of Arousal most frequently appeared to follow direct provocation by, or close proximity to, another individual. Sleepwalkers most often did not seek out victims, but rather the victims sought out or encountered the sleepwalker. These conclusions are tempered by several limitations: the selection of cases was not random and may not represent an accurate sample of violent behaviors associated with Disorders of Arousal. Also, final verdicts by juries in reported legal cases should not be confused with scientific proof of the presence or absence of sleepwalking. The pathophysiology of Disorders of Arousal with and without violent behavior could be associated with normally occurring deactivation of the frontal lobes during slow wave sleep (SWS) connected via atypically active thalamocortical pathways to the limbic areas. It is not known if the violent sleepwalker, confusional arousal patient, or sleep terror patient differs from other patients with these disorders. The conclusions of this case series await confirmation by the results of future sleep laboratory based studies.     

The nature of the paradoxical phase of sleep

Summary 1. Paradoxical sleep is a complex phenomenon which can be divided into three stages: 1) the stage of general activation, or desynchronization of slow activity in all areas of the brain, 2) the stage of predominance of the hippocampal -rhythm and 3) the stage of predominance of the hippocampal -rhythm.These stages are considered to have their neurophysiological mechanisms subcortically. The stage of general activation would be determined by excitation of the reticular formation, the stage of hippocampal -rhythm by excitation of the hippocampal centers of motivation, and the stage of hippocampal -rhythm by excitation of the hypothalamic centers causing inhibition of drives.     

Caffeine affects cardiovascular and neuroendocrine activation at work and home

OBJECTIVE: This study investigated the effects of moderate doses of caffeine on ambulatory blood pressure and heart rate, urinary excretion of epinephrine, norepinephrine, and cortisol, and subjective measures of stress during normal activities at work and at home in the evening. METHODS: Healthy, nonsmoking, habitual coffee drinkers (N = 47) participated in 3 days of ambulatory study. After a day of ad lib caffeine consumption, caffeine (500 mg) and placebo were administered double-blind in counter-balanced order on separate workdays. Ambulatory blood pressure and heart rate were monitored from the start of the workday until bedtime. Urinary excretion of catecholamines and cortisol was assessed during the workday and evening. RESULTS: Caffeine administration significantly raised average ambulatory blood pressure during the workday and evening by 4/3 mm Hg and reduced average heart rate by 2 bpm. Caffeine also increased by 32% the levels of free epinephrine excreted during the workday and the evening. In addition, caffeine amplified the increases in blood pressure and heart rate associated with higher levels of self-reported stress during the activities of the day. Effects were undiminished through the evening until bedtime. CONCLUSIONS: Caffeine has significant hemodynamic and humoral effects in habitual coffee drinkers that persist for many hours during the activities of everyday life. Furthermore, caffeine may exaggerate sympathetic adrenal-medullary responses to the stressful events of normal daily life. Repeated daily blood pressure elevations and increases in stress reactivity caused by caffeine consumption could contribute to an increased risk of coronary heart disease in the adult population.