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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.

Arousal↗

Respiratory arousal from sleep: mechanisms and significance.

The mechanisms by which respiratory stimuli induce arousal from sleep and the clinical significance of these arousals have been explored by numerous studies in the last two decades. Evidence to date suggests that the arousal stimulus in nonrapid eye movement sleep (NREM) is related to the level of inspiratory effort rather than the individual stimuli that contribute to ventilatory drive. A component of the arousal stimulus proportional to the level of inspiratory effort may originate in mechanoreceptors either in the upper airway or respiratory pump. Medullary centers responsible for ventilatory drive may also send a signal proportionate to the level of drive to higher centers in the brain which are responsible for arousal. Thus, the arousal stimulus may consist of multiple components, each increasing as inspiratory effort increases. The level of effort triggering arousal is an index of the arousability of the brain (arousal threshold). A deeper stage of sleep, central nervous system depressants, prior sleep fragmentation, and the presence of obstructive sleep apnea (OSA) have been observed to increase the arousal threshold to airway occlusion. Less information is available concerning the mechanisms of arousal from rapid eye movement (REM) sleep. While REM sleep is associated with the longest obstructive apneas in patients with OSA, normal human subjects appear to have a similar or lower arousal threshold to respiratory stimuli in REM compared to NREM sleep. Recent studies have challenged the assumption that the termination of all obstructive apnea is dependent on arousal from sleep. Improvements in methods to detect and quantitate changes in the cortical electroencephalogram (EEG) may better define the relationship between arousal and apnea termination. This may result in improved criteria for identifying EEG changes of clinical significance. While little is known concerning the mechanisms of arousal in central sleep apnea, arousal may play an important role in inducing this type of apnea in some patients.

Arousal↗

Infant polysomnography: reliability and validity of infant arousal assessment.

Infant arousal scoring based on the Atlas Task Force definition of transient EEG arousal was evaluated to determine (1). whether transient arousals can be identified and assessed reliably in infants and (2). whether arousal and no-arousal epochs scored previously by trained raters can be validated reliably by independent sleep experts. Phase I for inter- and intrarater reliability scoring was based on two datasets of sleep epochs selected randomly from nocturnal polysomnograms of healthy full-term, preterm, idiopathic apparent life-threatening event cases, and siblings of Sudden Infant Death Syndrome infants of 35 to 64 weeks postconceptional age. After training, test set 1 reliability was assessed and discrepancies identified. After retraining, test set 2 was scored by the same raters to determine interrater reliability. Later, three raters from the trained group rescored test set 2 to assess inter- and intrarater reliabilities. Interrater and intrarater reliability kappa's, with 95% confidence intervals, ranged from substantial to almost perfect levels of agreement. Interrater reliabilities for spontaneous arousals were initially moderate and then substantial. During the validation phase, 315 previously scored epochs were presented to four sleep experts to rate as containing arousal or no-arousal events. Interrater expert agreements were diverse and considered as noninterpretable. Concordance in sleep experts' agreements, based on identification of the previously sampled arousal and no-arousal epochs, was used as a secondary evaluative technique. Results showed agreement by two or more experts on 86% of the Collaborative Home Infant Monitoring Evaluation Study arousal scored events. Conversely, only 1% of the Collaborative Home Infant Monitoring Evaluation Study-scored no-arousal epochs were rated as an arousal. In summary, this study presents an empirically tested model with procedures and criteria for attaining improved reliability in transient EEG arousal assessments in infants using the modified Atlas Task Force standards. With training based on specific criteria, substantial inter- and intrarater agreement in identifying infant arousals was demonstrated. Corroborative validation results were too disparate for meaningful interpretation. Alternate evaluation based on concordance agreements supports reliance on infant EEG criteria for assessment. Results mandate additional confirmatory validation studies with specific training on infant EEG arousal assessment criteria.

Arousal↗

Hierarchy of micro-arousals and the microstructure of sleep.

This review is aimed at providing an overview concerning the hierarchy of different kinds of micro-arousals (without awakening) during slow wave sleep (SWS), and to summarize available data on the dynamic interplay of phasic events constituting the microstructural web of sleep EEG. K-complexes are considered elementary forms of arousal during SWS. They carry characteristics of evoked potentials, which provide subattentive information processing and have at the same time level-setting sleep maintenance functions. Micro-arousals are more complex arousal-dependent phasic events in the hierarchy. One class of recurring micro-arousals are preceded by K-complexes, while others, such as phases of spontaneous transitory activation--type micro-arousals-- represent higher levels of arousal, and are associated with EEG desyncronization, increased muscle activity and signs of autonomous arousal. All types of micro-arousals function in a complex interrelationship with another phasic event--sleep spindles--interpreted as microstates inhibiting sensory inflow through the thalamic relay system. Lastly the CAP (cyclic alternating pattern) phenomenon offers a global framework for characterizing and measuring arousal instability. Appearance of CAP sequences reflects arousal instability in a higher duration range than individual micro-arousals. They represent an arousal control mechanism reflecting that all arousing influences set into motion an oscillatory level setting system around the referential state providing a flexible adaptation for the system to defend it against perturbations. The whole arousal (without awakening) hierarchy thus seems to play an essential role in sleep regulation, serving both cyclicity and maintenance of sleep and providing at the same time flexible contact between sleeper and environment--preserving the possibility to wake up in case of any biological danger, and tailoring sleep program according to actual environmental or inner demands. Although at present there are no accepted rules for microstructural evaluation of sleep, microstructural aspects provide a more dynamic picture both about the preprogrammed and reactive changes in sleep. This approach gives us some clues to better understand sleep disorders as well. Several studies concerning microstructural analysis of certain sleep disorders are also reviewed.

Arousal↗

Arousal responses to somatosensory and mild hypoxic stimuli are depressed during quiet sleep in healthy term infants.

STUDY OBJECTIVES: To compare arousal responses to somatosensory and hypoxic stimuli in sleeping human infants and to determine whether sleep state and postnatal age exerted similar changes in these arousal responses. DESIGN: We delivered somatosensory (nasal air-jet) stimulation and mild hypoxia (15% oxygen) to 10 healthy term infants aged 2 to 4 weeks, 2 to 3 months, and 5 to 6 months during identified sleep states. Hypoxic challenges were terminated at arousal, when the oxygen saturation fell below 85%, or at 5 minutes (failure to arouse). RESULTS: Infants failed to arouse to a greater percentage of hypoxia tests during quiet sleep (QS) than during active sleep (AS) at 2 to 3 months and 5 to 6 months of age (P < 0.01). Infants failed to arouse to a greater percentage of hypoxic challenges during QS at 2 to 3 months and 5 to 6 months than at 2 to 4 weeks of age. Arousal latency to hypoxia was significantly longer in QS than in AS at each study age; however, arousal latency was not affected by postnatal age. Arousal thresholds to somatosensory stimulation were significantly greater in QS than in AS, except at 2 to 4 weeks of age. In AS, arousability to the air-jet was greater at 2 to 3 months compared to 2 to 4 weeks of age (P < 0.05); in QS it was lower at 5 to 6 months compared to 2 to 4 weeks of age (P < 0.05). Arousal latency to hypoxia and arousal thresholds to air-jet stimulation were not correlated within infants. CONCLUSION: We conclude that arousal responses of infants to somatosensory and respiratory stimuli are similarly affected by sleep state and postnatal age. Infants are less arousable to both stimulus modalities in QS than in AS, and less arousable at 5 to 6 months of age than at 2 to 4 weeks in QS.

Arousal↗

Arousals and obstructive sleep apnea syndrome in children.

OBJECTIVE: Observations of children with obstructive sleep apnea syndrome (OSAS) show a restless sleep. But there is no significant disturbance of sleep macrostructure as in adult OSAS patients. It will be proved, whether the analysis of arousals permits a comprehensive characterization of this respiratory related sleep disturbance. Considering the problems in EEG-arousals detection in dependence of age and maturation we will compare the results of analysis of EEG- and movement arousals to find out a more practicable way for arousal analysis in childhood. METHODS: Twenty OSAS pediatric patients (aged 3.1-14.3 years, median 7.5 years) and 20 age matched children with no OSAS (aged 3.3-13.9 years, median 7.9 years) were examined polysomnographically. Clinically confirmed OSAS patients with an apnea/hypopnea index (AHI) > or = 5/h TST (total sleep time) were examined during 1 whole night before treatment (diagnostic night - baseline) and after/under receiving therapy. Various polygraphic parameters to describe the macrostructure of sleep (sleep efficiency, NREM 1-4, REM) and the microstructure of sleep (EEG- and movement arousals) were analyzed. Furthermore the AHI, heart rate and oxygen saturation were evaluated. RESULTS: Patients with clinically and polysomnographically confirmed OSAS had significantly more EEG (median 21.0/interquartile range 9.31 /h TST) and movement arousals (20.4/13.1 /h TST) before therapy than after/under therapy (EEG: 9.9/6.3 /h TST; movement: 9.2/3.8/h TST). The frequency of arousals was comparable in OSAS children after/under treatment and controls (EEG: 9.0/4.2/h TST; movement 9.3/3.4/h TST). In the 3 groups there was no significant correlation between AHI and number of EEG-arousals and movement arousals. AHI was significantly higher in OSAS children in comparison to controls and treated OSAS. In contrast to adults, sleep efficiency and macrostructure of sleep were not different in controls and OSAS children with or without treatment. Also, oxygen saturation and heart rate, had the same values in controls, OSAS children and OSAS children after/under treatment. CONCLUSIONS: OSAS in children is characterized by a restless sleep, i.e. by an enhanced number of movement and EEG-arousals. The microstructure of sleep but not the macrostructure is changed. There is a high coincidence between EEG arousals and movement arousals. The evaluation of arousals especially the analysis of movement arousals is helpful to estimate treatment effect in OSAS patients.

Adolescent↗

False physiological feedback and persuasion: effect of fear arousal vs. fear reduction on attitude change.

Two experiments tested the hypothesis that increases in false physiological feedback of fear arousal will enhance persuasion and that reduction in the arousal feedback is unnecessary for increased persuasion to occur. Prior research has usually found a positive relation between level of arousal and persuasion, but support for the drive reduction hypothesis is tenuous. However, Harris and Jellison (1971) claimed support for such a hypothesis. They manipulated subjects' fear arousal cognitively via false physiological feedback while the subjects listened to a persuasive communication. The present experiments used a similar procedure in an attempt to test an "arousal only" against an "arousal reduction" hypothesis. Subjects listened to a persuasive speech while receiving false feedback via a meter concerning their fear arousal. In Experiment I half of the subjects received high arousal and half received moderate arousal information. Within each of these conditions half of the subjects had their arousal reduced, and the other half did not. In Experiment II subjects received either low arousal, high arousal, or high then low arousal feedback while listening. The results of the two studies generally provided support for the "arousal only" hypothesis. An interpretation in terms of Bem's attribution theory was tentatively suggested.

Arousal↗

The influence of gender and upper airway resistance on the ventilatory response to arousal in obstructive sleep apnoea in humans.

The termination of obstructive respiratory events is typically associated with arousal from sleep. The ventilatory response to arousal may be an important determinant of subsequent respiratory stability/instability and therefore may be involved in perpetuating obstructive respiratory events. In healthy subjects arousal is associated with brief hyperventilation followed by more prolonged hypoventilation on return to sleep. This study was designed to assess whether elevated sleeping upper airway resistance (R(UA)) alters the ventilatory response to arousal and subsequent breathing on return to sleep in patients with obstructive sleep apnoea (OSA). Inspired minute ventilation (V(I)), R(UA) and end-tidal CO(2) pressure (P(ET,CO(2))) were measured in 22 patients (11 men, 11 women) with OSA (mean +/-s.e.m., apnoea-hypopnoea index (AHI) 48.9 +/- 5.9 events h(-1)) during non-rapid eye movement (NREM) sleep with low R(UA) (2.8 +/- 0.3 cmH(2)O l(-1) s; optimal continuous positive airway pressure (CPAP) = 11.3 +/- 0.7 cmH(2)O) and with elevated R(UA) (17.6 +/- 2.8 cmH(2)O l(-1) s; sub-optimal CPAP = 8.4 +/- 0.8 cmH(2)O). A single observer, unaware of respiratory data, identified spontaneous and tone-induced arousals of 3-15 s duration preceded and followed by stable NREM sleep. V(I) was compared between CPAP levels before and after spontaneous arousal in 16 subjects with tone-induced arousals in both conditions. During stable NREM sleep at sub-optimal CPAP, P(ET,CO(2)) was mildly elevated (43.5 +/- 0.8 versus 42.5 +/- 0.8 Torr). However, baseline V(I) (7.8 +/- 0.3 versus 8.0 +/- 0.3 l min(-1)) was unchanged between CPAP conditions. For the first three breaths following arousal, V(I) was higher for sub-optimal than optimal CPAP (first breath: 11.2 +/- 0.9 versus 9.3 +/- 0.6 l min(-1)). The magnitude of hypoventilation on return to sleep was not affected by the level of CPAP and both obstructive and central respiratory events were rare following arousal. Similar results occurred after tone-induced arousals which led to larger responses than spontaneous arousals. V(I) for the first breath following arousal under optimal CPAP was greater in men than women (11.0 +/- 0.4 versus 7.6 +/- 0.6 l min(-1)). These results demonstrate that the ventilatory response to arousal is influenced by pre-arousal airway resistance and gender. Whether this contributes to the perpetuation of respiratory events and the pathogenesis of OSA is unclear.

Adult↗

Pathophysiological interactions of ventilation, arousals, and blood pressure oscillations during cheyne-stokes respiration in patients with heart failure.

Arousals from sleep can be associated with increases in blood pressure (BP). However, it is uncertain whether this is due to a direct effect of arousals on BP, or is secondary to respiratory stimuli present at the time of the arousal. Cheyne-Stokes respiration (CSR) in patients with congestive heart failure (CHF) provides unique conditions that may allow these two possibilities to be distinguished. In CSR, the apnea-hyperpnea cycle can be dissociated from arousals because when CSR occurs during wakefulness, it does so in the absence of arousals, and when it occurs during sleep, arousals occur either at the termination of apnea (early arousals) or several breaths after the onset of hyperpnea (late arousals). We therefore measured BP during wakefulness and non-rapid eye movement (NREM) sleep in eight patients with CHF and CSR. During wakefulness, CSR was associated with wide fluctuations in systolic BP (mean +/- SD, 11.3 +/- 6.0 mm Hg) synchronous with the apnea-hyperpnea cycle, in the absence of arousals. Similar fluctuations in BP were observed during CSR with early arousals (13. 7 +/- 7.0 mm Hg) in NREM sleep. However, late arousals during CSR were associated with a small, but significant additional effect on systolic BP (14.2 +/- 7.1 mm Hg, p < 0.05). Furthermore, the degree of BP increase following arousals was directly related to the associated increase in ventilation (r = 0.70, p < 0.05). We conclude that BP fluctuations during CSR in patients with CHF are primarily related to oscillations in ventilation during the CSR cycle and can occur in the absence of arousals. Arousals augment these BP oscillations, but only when they occur late in hyperpnea.

Aged↗

Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: a randomised controlled trial.

OBJECTIVE: Some postmenopausal women lose genital sexual responsivity despite preserved subjective sexual arousal from non-genital stimuli. When oestrogen replacement is without benefit, both the underlying pathophysiology and management of this acquired genital female sexual arousal disorder are unclear. We aimed to study the effect of sildenafil on sexual arousal and orgasmic functioning of such women. Secondly, we aimed to explore the concordance between a detailed historical assessment of genital response in real life, with laboratory vaginal photoplethysmographic assessment of genital vasocongestion. DESIGN: Session one consisted of a semi-structured clinical interview to assess real life sexual arousal. Session two employed vaginal pulse amplitude and self-report questionnaire assessment of erotica-induced sexual arousal. Sessions three and four were a randomised, double-blind, placebo-controlled crossover administration of sildenafil on orgasm latency, intensity, perception of genital congestion and subjective arousal to erotica plus clitoral vibrostimulation. SETTING: University associated Sexual Medicine Clinic and Psychophysiology Laboratory. SAMPLE: Volunteer sample of 34 oestrogenised postmenopausal women with acquired genital female sexual arousal disorder and impaired orgasm. METHODS: Sildenafil (50 mg) or placebo administered over two laboratory sessions. MAIN OUTCOME MEASURES: Orgasm latency and intensity during drug sessions; subjective and psychophysiological sexual arousal during photoplethysmography session. RESULTS: The erotic video significantly increased subjective sexual arousal in all women. Vaginal pulse amplitude responses varied from robust to absent. Although across all women, sildenafil improved neither arousal nor orgasm, subsequent analyses comparing high versus low vaginal pulse amplitude responders revealed significantly reduced latency to orgasm, and increased subjective sexual arousal and perception of genital arousal in the latter group of women. CONCLUSION: The data suggest that oestrogenised postmenopausal women with genital female sexual arousal disorder and orgasmic impairment based only on clinical assessment do not benefit from sildenafil. However, the photoplethysmograph had predictive value-those women showing low vaginal pulse amplitude response benefited from sildenafil compared with women with a higher response. Thus, oestrogenised women diagnosed with acquired genital female sexual arousal disorder may be a heterogeneous group and the photoplethysmograph might be useful in their further characterisation.

Adult↗

Alcohol and erectile response: the effects of high dosage in the context of demands to maximize sexual arousal.

Although drinking often precedes men's sexual activity, basic questions about alcohol's effects on men's sexual arousal remain unanswered. Inconsistencies in findings from studies examining subjective and physiological effects on erectile functioning suggest these effects are context specific, for example, dependent on whether a man wants to maximize or suppress his arousal. To address unresolved questions about alcohol and erectile functioning, the authors evaluated the effects of high blood alcohol concentrations (BACs) and arousal instructional demands on indices of penile circumference change and self-reported sexual arousal. In Study 1, a target BAC of .10% (vs. .00%) attenuated peak circumference change from a neutral baseline but did not affect mean change, latency to arousal onset (a 5% increase in circumference from baseline), latency to peak achieved arousal, or subjective arousal, which correlated moderately with physiological indices. In Study 2, instructions to maximize (vs. suppress) arousal increased peak and mean circumference change and interacted with a target BAC of .08% (vs. .00%) to influence latency to arousal onset. Sober men instructed to maximize showed a shorter latency to arousal onset than did those instructed to suppress arousal; however, intoxicated men did not show a differential pattern. Moreover, compared with intoxicated counterparts, sober men instructed to maximize arousal showed a marginally shorter latency to arousal onset. Overall, alcohol and arousal instructions had small but discernible effects. Findings highlight the importance of contextual factors in alcohol's impact on erectile functioning.

Adult↗

How to score arousals in preterm infants? Can we use recommendations of the Pediatric Wake-up Club?

Infants' arousals from sleep reflect the activation of various brain stem and cortical structures and their characteristics change with age. Arousal scoring based on the Pediatric Wake-up Club definition of arousal in infants was evaluated to determine whether arousals could be reliably identified and assessed in preterm infants also. Polygraphic recordings were made in seven stable preterm infants with a mean postconceptional age of 34.4 +/- 1.2 weeks. Fifty-two arousals were scored according to the guidelines of the Pediatric Wake-up Club (Consensus meeting in Brussels, 2002). Values of interest were assessed during the arousal period and during the 30-second periods before and after the arousal. The latter periods were subdivided into 10-second intervals and compared with the arousal period. The mean duration of arousal was 7 +/- 3 seconds. Respiratory rate was higher (35 +/- 15 bpm) during the arousal than in the periods preceding (29 +/- 14 bpm; p < 0.01) and following (29 +/- 11 bpm; p < 0.001) it. Heart rate decreased during the arousal (131 +/- 30 bpm) when compared with the preceding 10-second period (140 +/- 14 bpm; p < 0.05). We found that arousals in preterm infants can be reliably identified and assessed using the Pediatric Wake-up Club's arousal definition for term infants.

Arousal↗

The effect of CNS activation versus EEG arousal during sleep on heart rate response and daytime tests.

OBJECTIVE: To induce a heart rate change in normal subjects using auditory stimulation without inducing EEG arousals and to assess the effects on daytime functioning and compare results to auditory stimulation leading to short EEG arousals. METHODS: Six normal young men initially randomized into two groups (A and B) underwent 4 nights of nocturnal polysomnography (normal sleep on night 1, auditory stimulation without EEG arousal or normal sleep on nights 2 and 3 using Latin square design, and auditory stimulation with EEG arousal on night 4). MSLT and PVT were performed during days following nights 2-4. RESULTS: MSLT and PVT results showed significant differences after EEG arousal compared to stimulation without EEG arousal and to normal sleep; there were no significant differences after normal sleep compared to stimulation without EEG arousal. RR interval showed significant differences during undisturbed sleep compared to stimulation without EEG arousal and to stimulation with EEG arousal; RR interval without EEG arousal also differed significantly from RR interval with EEG arousal. CONCLUSION: Activation of the brain-stem can lead to autonomic nervous system (ANS) response without objective consequences the next day. SIGNIFICANCE: ANS responses induced by auditory stimulation during sleep without EEG arousal do not have the same effects on daytime sleepiness and performance as sleep fragmentation associated with EEG arousals.

Acoustic Stimulation↗

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.

Acoustic Stimulation↗

Spontaneous arousability in prone and supine position in healthy infants.

STUDY OBJECTIVE: Compared with control infants, those who will be future victims of sudden infant death syndrome (SIDS) show a decreased arousability during sleep, with fewer cortical arousals and more-frequent subcortical activations. These findings suggest an incomplete arousal process in victims of SIDS. Prone sleep position, a major risk factor for SIDS, has been reported to reduce arousal responses during sleep. The present study was undertaken to evaluate whether the prone sleep position impairs the arousal process in healthy infants. METHODS: Twenty-four healthy infants were studied polygraphically during 1 night; 12 infants regularly slept supine and 12 infants regularly slept prone. Infants were matched for sex, gestational age, and age at recording. Arousals were differentiated into subcortical activations or cortical arousals, according to the presence of autonomic and/or electroencephalographic changes. Frequencies of subcortical activations and cortical arousals were compared in the prone- and the supine-sleeping infants. RESULTS: Compared with supine sleepers, prone sleepers had significantly fewer cortical arousals during rapid eye movement (REM) sleep (p = .043). There were no significant differences in cortical arousals between the 2 groups during non-REM sleep. No significant differences were seen in the frequencies of subcortical activations during both REM and non-REM sleep between supine and prone sleepers. The ratio of cortical arousal to subcortical activation showed no significant differences between the prone and the supine sleepers. CONCLUSIONS: Prone sleep position decreased the frequency of cortical arousals but did not change the frequency of subcortical activations, as has been previously found in SIDS victims. These results suggest specific pathways for impairment of the arousal process in SIDS victims.

Arousal↗

Arousal responses to hypertension in lambs: effect of sinoaortic denervation.

Newborn lambs were subjected to hypertensive stimuli of 1-min duration to examine features of hypertension-induced arousal from sleep. Reflex mechanisms involved were studied by performing the same tests after sinoaortic denervation (SAD). In intact lambs, hypertension increased the probability of arousal from both quiet sleep (QS) and rapid-eye-movement (REM) sleep. Hypertension resulted in arousal in 51% (QS) and 50% (REM) of tests. Arousal time was significantly longer in REM (29.3 +/- 0.9 s, mean +/- SE) than in QS (22.6 +/- 0.6 s, P less than 0.01). Arterial oxygen saturation (So2) and partial pressure of oxygen (Po2) measured at the point of arousal, or after 60 s if arousal failed to occur, were unchanged from control values. After SAD hypertension did not increase the probability of arousal. Arousals significantly decreased (P less than 0.001) to 31% (QS) and 10% (REM). These findings indicate that acute hypertension, mediated via arterial baroreceptors, is a potent stimulus for arousal. In intact lambs, the arousal probability increased and arousal time decreased with increasing stimulus strength (1-30 mmHg), but the arousal time difference between QS and REM remained constant. Consideration of these findings in terms of a simple baroreflex threshold model suggests that the slower response in REM sleep is explained by slower neural processes after the achievement of a critical arousal input rather than by a higher threshold for baroreceptor input in this state.

Aging↗

The influence of increasing ventilatory effort on arousal from sleep.

Arousal from sleep in response to asphyxia can be a lifesaving event. However, the mechanisms responsible for this important arousal response are uncertain. A unifying hypothesis is that arousal results from the increased respiratory effort that occurs as a result of ventilatory stimulation. If this is true, the magnitude of this effort during the breaths immediately preceding arousal from sleep should be similar regardless of the stimulus. Therefore, the negative inspiratory pleural pressure during the breaths preceding arousal would be similar, whether stimulated by added inspiratory resistive load, hypoxia, or hypercapnia. To test this hypothesis, we studied eight young, healthy men during full-night sleep studies. We measured their electroencephalography (EEG), electromyography (EMG), electrooculography (EOG), inspired ventilation (VI), end tidal PCO2 (PETCO2), O2 saturation, and esophageal pressure (esophageal balloon) while inducing arousal from non-REM sleep using (1) a 30-cm H2O/L/s added resistive load, (2) progressive hypoxia, and (3) progressive hyperoxic hypercapnia. All subjects were eventually aroused following the addition of the 30-cm H2O/L/s added load and during progressive hypercapnia. However, only six of the eight men were aroused when the O2 saturation was reduced to a minimum of 70%. For each stimulus, arousal occurred at very different levels of ventilation and arterial chemistry (SaO2 and CO2). However, ventilatory effort for each subject was similar at the point of arousal regardless of the stimulus. The peak-negative esophageal pressure for the single inspiration preceding arousal (for the six subjects arousing with all three stimuli) was 16.8 +/- 1.4 cm H2O for added resistive load, 15.0 +/- 2.4 cm H2O for hypoxia, and 14.7 +/- 2.1 cm H2O for hypercapnia. We conclude that increasing ventilatory effort may be the stimulus to arousal from sleep independent of the source of this rising drive to breathe.

Adult↗

Role of arousals in the pathogenesis of obstructive sleep apnea.

Arousal is believed to be needed for upper airway opening in obstructive hypopneas-apneas, without compelling evidence to support this notion. The association may be incidental. I studied the temporal relation between arousal and opening and impact of arousal on flow response at opening in 82 patients (apnea-hypopnea index, 46 +/- 35/hour). Obstructive apneas-hypopneas were induced by dial-down of continuous positive airway pressure. Obstructions and hypopneas occurred in 44 and 56% of dial-downs, respectively. When arousal occurred (83% of dial-downs), the temporal relation between arousal and opening was inconsistent between and within patients. Frequency of opening without or before arousal increased with milder obstructions (p < 10(-9)) and with delta power of EEG (p < 10(-6)). Time of opening was unaffected by whether arousal occurred before or after opening (18.0 +/- 9.8 vs. 18.1 +/- 10.5 seconds). Flow response was already excessive when opening occurred without or before arousal (180 +/- 148% of initial flow decline) and was considerably higher when arousal occurred (267 +/- 154%, p < 10(-10)). Flow undershoot after first ventilatory response was greater if arousal occurred (p < 0.01). It is concluded that arousals are incidental events that occur when thresholds for arousal and for arousal-independent opening are close. They are not needed to initiate opening or to obtain adequate flow and they likely increase the severity of the disorder by promoting greater ventilatory instability.

Airway Resistance↗