Forced Awakening Research Articles

Psychological distress, forced awakening, and morning blood pressure surge.

Morning blood pressure surge (MBPS) has been recognized as an independent predictor of cardiovascular disease events. Psychological distress, including anxiety, depression, and perceived stress, and behavioral risk factors, such as poor sleep quality, have been associated with increased MBPS. Elevations in sympathetic activity induced by forced awakening may also contribute to further increases in MBPS. Yet, no examination of the interrelationships among psychological distress, sleep quality, awakening mode (natural vs. forced awakenings), and MBPS has been undertaken. This pilot study aimed: (1) to examine if MBPS differs by awakening mode and (2) to investigate whether psychological distress is associated with MBPS difference between natural and forced awakenings, independent of sleep quality. Thirty-two healthy adults were included in this cross-sectional study. Blood pressure was measured using a beat-to-beat blood pressure monitor over two nights, consisting of one night of natural awakening and one night of forced awakening. Psychological distress and sleep quality were assessed using questionnaires. We conducted paired t-tests (aim 1) and multiple linear regressions (aim 2). MBPS was significantly greater during forced awakening compared with natural awakening. In addition, the MBPS difference between natural and forced awakenings was significantly greater in participants with higher anxiety levels, independent of sleep quality. We found that augmentation of MBPS by forced awakening was significantly greater in individuals who reported higher anxiety levels. Additional research is needed to examine the potential impacts of forced awakening and anxiety on MBPS in a larger sample of individuals at risk for cardiovascular disease.

The impact of forced awakening on morning blood pressure surge

BackgroundPoor sleep quality can cause an increase in morning blood pressure surge (MBPS), an independent risk factor of cardiovascular disease (CVD) events. Awakening induced by external factors such as alarm clocks, may also contribute to increased MBPS. ObjectivesTo (1) compare the MBPS and sleep quality parameters between natural and forced awakenings and (2) examine the potential impact of forced awakening on MBPS, independent of sleep quality. MethodsThirty-two healthy adults participated in this pilot study, which included one night of natural awakening and one night of forced awakening (i.e., sleep was interrupted by an alarm after five hours). Objective and self-reported sleep quality parameters were measured using a multisensory wristband and sleep diaries, respectively, and beat-to-beat blood pressure variability was assessed using a continuous blood pressure monitor. Analyses included a paired t-test (objective 1) and linear mixed models (objective 2). ResultsParticipants predominantly consisted of young, healthy, and highly educated Asian adults. During the night of sleep with forced awakening, significantly higher MBPS, lower objective wakefulness after sleep onset, and lower self-reported sleep latency were observed, compared to the night with natural awakening. Forced awakening was significantly associated with increased MBPS after controlling for age, sex, mean arterial pressure, and sleep quality. ConclusionsForced awakening may significantly increase MBPS, consequently heightening the risk of CVD events. Study findings should be validated in a larger sample. Further research is also warranted to examine the impact of forced awakening on MBPS in individuals with CVD.

Kleine-Levin syndrome

Kleine-Levin syndrome (KLS) is manifested by periodic hypersomnolence with an increased appetite and psychopathological symptoms (psychomotor agitation, hallucinations, hypersexuality). The duration of the attack ranges from several days to several weeks. A forced awakening can provoke severe aggressive behavior. The disease occurs for an unknown reason, mainly in adolescence and mostly affects males. Lack of awareness among doctors about the disease leads to an incorrect diagnosis, often of a psychopathological disorder. This article presents modern data on the causes, clinical symptoms, diagnostic methods of KLS and provides a case of a 18 year-old man, whose disease manifested at the age of 16 years.

Sexual assault facilitated by the reduced response to sensory stimuli during sleep

The reports of women who wake during non-consensual penile-vaginal penetration often indicate that a male has entered the room and moved her clothing before she wakes. Sleep involves reduced sensitivity to sensory stimuli including touch, light, sound, and pain1,2 and the operation of a gating system which filters stimuli not recognised as meaningful. In a sexual assault involving forced awakening, this reduced sensitivity is additive to the effect of sleep inertia: the performance impairment and confusional state characteristic of the normal transition phase from sleep to waking. In a retrospective study of 305 adult females (median age 26, range 18–68), who presented for a forensic examination at the RPA Sexual Assault service,1 38/305 (12%) (median age 27, range 18–51) woke to find sexual acts already in progress including 25/305 (8%) who woke to find penile-vaginal penetration already occurring. 9/38 (24% of those who woke) were non-intoxicated prior to going to sleep. In 4/38 the only recall was of non-penetrative touching despite other indicators of penetration (vaginal injury, DNA evidence). Another 68/305 women (22%) had no memory of waking during an alleged or suspected sexual assault and may have slept throughout.

Effects of using a snooze alarm on sleep inertia after morning awakening

BackgroundMany people use the snooze function of digital alarm clocks for morning awakening, but the effects of a snooze alarm on waking are unclear. We examined the effects of a snooze alarm on sleep inertia, which is a transitional state characterized by reduced arousal and impaired cognitive and behavioral performance immediately upon awakening.MethodsIn study 1, healthy Japanese university students responded to a sleep survey during a psychology class (study 1), and we collected 293 valid responses. In study 2, we compared a separate sample of university students (n = 10) for the effects of using or not using a snooze alarm on sleep inertia immediately after awakening from normal nocturnal sleep in a sleep laboratory.ResultsOf 293 valid respondents in study 1, 251 often used a tool to wake up in the morning (85.7%). Moreover, 70.5% reported often using the snooze function of their mobile phones, mainly to reduce anxiety about oversleeping. Study 2 indicated no differences in the sleep quality or quantity before awakening with or without the snooze alarm, except in the last 20 min. However, during the last 20 min of sleep with snooze alarm, the snooze alarm prolonged waking and stage N1 sleep. Stage N1 sleep is non-rapid eye movement sleep that is primarily defined as a drowsy state. Furthermore, Global Vigor values were enhanced after awakening compared to pre-sleep in the no-snooze condition.ConclusionsUsing a snooze alarm prolongs sleep inertia compared to a single alarm, possibly because snooze alarms induce repeated forced awakenings.

092 Effect of the dual orexin receptor antagonist (DORA) daridorexant on behaviour upon awakening in rats and dogs

Abstract Introduction The ability to be fast alert and to interact with the environment without motor impairment upon waking up, is a critical feature of natural sleep. DORAs represent a new class of insomnia medications that specifically inhibit the wake-promoting effects of orexin neuropeptides. Daridorexant is a potent and selective DORA under late stage development for the treatment of insomnia. Here, we assessed the impact of sleep-promoting doses of daridorexant on rats’ and dogs’ behaviour upon forced awakening. Zolpidem (a positive GABAA receptor modulator) was used as active comparator in rats because of its known negative impact on motor functions. Methods Rats were woken up at different time points after oral administration of daridorexant (10, 30, 100 mg/kg) or zolpidem (30, 100 mg/kg) during their inactive phase, and repeatedly subjected to two motor tasks: 1) the rotating rod test (lasting 120 sec, at each time point) assessing gross motor skills and coordination, and 2) the forepaw grip strength test assessing fine motor skills and muscle strength. Dogs were presented with food as an external, salient stimulus, three hours after administration of daridorexant in gelatin capsules (10, 30 or 90 mg/dog) during their active phase. Behaviour and signs of muscle weakness, after having woken up, were assessed by manual inspection of video recordings and concomitant electroencephalogram/electromyogram recordings. Results In both the rotarod and grip tests, daridorexant treatment had no effect on motor behavior at any dose or time point tested, while zolpidem significantly reduced the time spent on the rotarod and the grip strength in a dose and time-dependent manner (N=12/group; p<0.001;) (e.g. at 30 min post-dose, time spent on the rotarod was 84, 79–89 and 10–19 sec for vehicle, daridorexant and zolpidem, respectively). Dogs treated with daridorexant were able to wake up easily upon food presentation. They behaved and ate normally and did not show any signs of muscle weakness. Conclusion The type of sleep promoted by daridorexant is surmountable in rats and dogs and similar to physiological sleep. It allows animals to easily wake up, to behave normally without motor impairment and to respond efficiently to the environmental conditions. Support (if any) Funded by Idorsia Pharmaceuticals Ltd

Experimental sleep disruption attenuates morphine analgesia: findings from a randomized trial and implications for the opioid abuse epidemic

Preclinical studies demonstrate that sleep disruption diminishes morphine analgesia and modulates reward processing. We sought to translate these preclinical findings to humans by examining whether sleep disruption alters morphine’s analgesic and hedonic properties. We randomized 100 healthy adults to receive morphine versus placebo after two nights of undisturbed sleep (US) and two nights of forced awakening (FA) sleep disruption. Sleep conditions were counterbalanced, separated by a two-week washout. The morning after both sleep conditions, we tested cold pressor pain tolerance before and 40-min after double-blind injection of .08 mg/kg morphine or placebo. The primary outcome was the analgesia index, calculated as the change in cold pressor hand withdrawal latency (HWL) before and after drug injection. Secondary outcomes were ratings of feeling “high,” drug “liking,” and negative drug effects. We found a significant sleep condition by drug interaction on the analgesia index (95% CI − 0.57, − 0.001). After US, subjects receiving morphine demonstrated significantly longer HWL compared to placebo (95% CI 0.23, 0.65), but not after FA (95% CI − 0.05, 0.38). Morphine analgesia was diminished threefold under FA, relative to US. After FA, females (95% CI − 0.88, − 0.05), but not males (95% CI − 0.23, 0.72), reported decreased subjective “high” effects compared to US. After FA, females (95% CI 0.05, 0.27), but not males (95% CI − 0.10, 0.11), administered morphine reported increased negative drug effects compared to US. These data demonstrate that sleep disruption attenuates morphine analgesia in humans and suggest that sleep disturbed males may be at greatest risk for problematic opioid use.

0548 Overnight Memory Consolidation in Insomnia versus Normal and Experimentally Disrupted Sleep

Abstract Introduction Healthy sleep is assumed to play an important role in the consolidation of newly acquired memories. Evidence suggest that periods of sleep after learning facilitates memory consolidation relative to wakefulness. Insomnia is associated with cognitive impairment but few studies have assessed overnight memory consolidation. We compared overnight consolidation in people with insomnia to a group of good sleepers who were randomised to either a normal night of sleep (uninterrupted sleep, US) or one night of sleep continuity disruption via forced awakenings (FA). Methods 51 good sleepers (37 female; mean age: 24 years, SD: 3.63), randomised to either one night of US (n=24) or one night of FA (n=27), were compared to 27 participants meeting criteria for insomnia disorder (23 female; mean age: 53 years, SD: 8.34) who were assessed at baseline as part of a randomised controlled trial of digital cognitive-behavioural therapy. Overnight memory consolidation (difference in correctly recalled word pairs between evening and morning recall) was assessed using the same word-pair task and protocol in the two lab-based studies. Results Overnight memory consolidation was significantly lower in the insomnia (mean: 5.4, SD: 5.8, p=0.001) and the FA (mean: 6.7, SD: 4.1, p<0.001) group compared to the US group (mean: 11.6, SD: 5.3). However, when adjusted for age only the FA group, but not the insomnia group, showed significantly lower memory performance than the US group. Conclusion While our findings suggest that overnight memory consolidation is impaired in insomnia relative to normal sleep we cannot rule out an age-related explanation given the difference in ages between the study samples. Future work will assess whether overnight consolidation improves following cognitive behavioural therapy. Support The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) and the Dr Mortimer and Theresa Sackler Foundation. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Different Effects of orexin receptor antagonist and gabaa agonist on physical and cognitive functions after forced awakening

Different Effects of orexin receptor antagonist and gabaa agonist on physical and cognitive functions after forced awakening

Distinct effects of orexin receptor antagonist and GABAA agonist on sleep and physical/cognitive functions after forced awakening

The majority of patients with insomnia are treated with hypnotic agents. In the present study, we evaluated the side-effect profile of an orexin receptor antagonist and γ-aminobutyric acid A (GABAA) receptor agonist on physical/cognitive functions upon forced awakening. This double-blind, randomized, placebo-controlled, cross-over study was conducted on 30 healthy male subjects. Fifteen minutes before bedtime, the subjects took a pill of suvorexant (20 mg), brotizolam (0.25 mg), or placebo and were forced awake 90 min thereafter. Physical- and cognitive-function tests were performed before taking the pill, after forced awakening, and the next morning. Polysomnographic recordings revealed that the efficacies of the hypnotic agents in prolonging total sleep time (∼30 min) and increasing sleep efficiency (∼6%) were comparable. When the subjects were allowed to go back to sleep after the forced awakening, the sleep latency was shorter under the influence of hypnotic agents (∼2 min) compared to the placebo trial (24 min), and the rapid eye movement latency was significantly shorter under suvorexant (98.8, 81.7, and 48.8 min for placebo, brotizolam, and suvorexant, respectively). Although brotizolam significantly impaired the overall physical/cognitive performance (sum of z score) compared with placebo upon forced awakening, there was no significant difference in the total z score of performance between suvorexant and placebo. Notably, the score for static balance with the eyes open was higher under suvorexant compared to brotizolam administration. The energy expenditure was lower under suvorexant and brotizolam compared with the placebo. The effect size of brotizolam (d = 0.24) to reduce the energy expenditure was larger than that of suvorexant (d < 0.01).

Experimental sleep disruption and reward learning: moderating role of positive affect responses.

Sleep disturbances increase vulnerability for depression, but the mechanisms underlying this relationship are not well known. We investigated the effects of experimental sleep disruption on response bias (RB), a measure of reward learning previously linked to depression, and the moderating role of positive affect responses. Participants (N = 42) were healthy adults enrolled in a within-subject crossover sleep disruption experiment that incorporated one night of uninterrupted sleep (US) and one night of forced awakenings (FA) in random order. On the day following each experimental sleep night, participants completed a probabilistic reward task to assess RB, and the Positive and Negative Affect Schedule-X. Participants were subgrouped according to positive affect responses: Preserved Positive Affect (i.e. positive affect scores maintained or increased; n = 15) or Reduced Positive Affect (i.e. positive affect scores decreased; n = 27) following FA. Contrary to our hypotheses, across participants, RB did not significantly differ between the US and FA sleep conditions (p = .67). However, the effect of sleep condition on RB was moderated by positive affect response (p = .01); those with preserved positive affect showed heightened RB following FA, whereas those with reduced positive affect showed diminished RB following FA. Changes in negative affect between US and FA did not moderate RB. The inability to preserve positive affect through periods of sleep disruption may be a marker of diminished reward learning capability. Understanding how sleep disruption impacts positive affect responses and reward learning identifies a pathway by which sleep disturbances may confer risk for depression.

Sleep structure and awakening threshold in delayed sleep-wake phase disorder patients compared to healthy sleepers

Study ObjectivesDifficult early morning awakening is a primary symptom of delayed sleep-wake phase disorder (DSWPD), however, it remains poorly investigated. Our main objective was to quantify the awakening threshold in DSWPD-patients and healthy controls as well as investigate a possible relationship with sleep stages. A secondary objective was to compare habitual sleep measured by polysomnography and actigraphy between patients and controls. MethodsTwenty DSWPD patients and 16 controls had two polysomnographic recordings at a sleep laboratory. Participants followed their habitual sleep-wake schedule on the first night and a forced sleep-wake schedule (00:00–07:00 h) on the second night. We used a custom-made alarm clock was for the forced-night awakening, starting at 72 dB sound intensity which increased up to 104 dB. ResultsMean awakening threshold in dB was higher in patients compared to controls; 75.5 vs. 72.6, p = 0.01, and the difference could not be explained statistically by sleep-time. Patients who were in REM sleep upon attempted awakening had a higher awakening threshold compared to patients who were in NREM sleep; 80.0 vs 74.7, F = 6.4, p = 0.02. Patients had increased sleep onset latency both at home with actigraphy and by PSG during the first laboratory night (20.6 vs 12.1 min, p = 0.004), however no further differences between the groups were observed regarding sleep structure. ConclusionsA high early-morning forced awakening threshold in DSWPD was related to REM sleep. Sleep onset problems, even with habitual bedtimes, may also be an integral feature of DSWPD.

Partial Sleep Deprivation Attenuates the Positive Affective System: Effects Across Multiple Measurement Modalities.

Ample behavioral and neurobiological evidence links sleep and affective functioning. Recent self-report evidence suggests that the affective problems associated with sleep loss may be stronger for positive versus negative affective state and that those effects may be mediated by changes in electroencepholographically measured slow wave sleep (SWS). In the present study, we extend those preliminary findings using multiple measures of affective functioning. In a within-subject randomized crossover experiment, we tested the effects of one night of sleep continuity disruption via forced awakenings (FA) compared to one night of uninterrupted sleep (US) on three measures of positive and negative affective functioning: self-reported affective state, affective pain modulation, and affect-biased attention. The study was set in an inpatient clinical research suite. Healthy, good sleeping adults (N = 45) were included. Results indicated that a single night of sleep continuity disruption attenuated positive affective state via FA-induced reductions in SWS. Additionally, sleep continuity disruption attenuated the inhibition of pain by positive affect as well as attention bias to positive affective stimuli. Negative affective state, negative affective pain facilitation, nor negative attention bias were altered by sleep continuity disruption. The present findings, observed across multiple measures of affective function, suggest that sleep continuity disruption has a stronger influence on the positive affective system relative to the negative affective affective system.

A growth spurt in pediatric sleep research.

A growth spurt in pediatric sleep research.

(190) Effects of sleep continuity disruption on cold pain tolerance and accompanying pain catastrophizing in healthy, good sleepers

Chronic sleep problems, such as those associated with insomnia, have been shown to increase vulnerability for chronic pain at the population level. However, there is limited understanding of the mechanisms linking sleep and pain. Cold pain tolerance (CPT) is a predictor of clinical pain severity in chronic pain patients. Pain catastrophizing, a maladaptive cognitive coping strategy, is associated with lower pain tolerance and higher clinical pain. In the present study, we investigated the effects of sleep continuity disruption -- an experimental model of sleep deprivation with ecological validity for comorbid chronic pain and insomnia -- on CPT and accompanying catastrophizing cognitions. Healthy good sleepers underwent one night of uninterrupted sleep (US) and one night of forced awakenings (FA) in a randomized, within-person, counter-balanced design. On the day following each sleep condition, participants placed their dominant hand palm-down in a 4°C circulating water bath for a maximum of 300 seconds and were instructed to remove their hand when the pain became intolerable. CPT was measured as the time to withdrawal. Participants completed a self-report pain catastrophizing scale immediately following CPT. A total of 33 subjects provided usable data on these measures. Results indicated that CPT was significantly lower following FA compared to US (p<0.05). Pain catastrophizing was not significantly different between sleep conditions. Together these findings indicate that a single night of sleep continuity disruption is associated with a reduction in CPT that does not appear to be driven by catastrophizing. The present data suggest that the association of sleep continuity disruption and pain tolerance may be one avenue through which chronic sleep disorders, such as insomnia, increase vulnerability to chronic pain.

The borderlands of waking: Quantifying the transition from reflective thought to hallucination in sleep onset.

We lose waking consciousness spontaneously and regularly over the circadian cycle. It seems that every time we fall asleep, reflective thinking gradually gives way to our interactions with an imaginary, hallucinatory world that brings multimodal experiences in the absence of adequate external stimuli. The present study investigates this transition, proposing a new measure of hallucinatory states. Reflective thinking and motor imagery were quantified in 150 mentation reports provided by 16 participants after forced awakenings from different physiology-monitored time intervals after sleep onset. Cognitive agency analysis and motor agency analysis--which are objective (grammatical-semantic) tools derived from linguistic theories--show (i) a decrease in reflective thinking which sleepers would need to acknowledge the hallucinatory quality of their state, and (ii) an increase in motor imagery, indicating interactions with a hallucinatory world. By mapping these spontaneous changes in human consciousness onto physiology, we can in the long run explore the conditions of its decline, and possibilities for treatment.

Sleep Disruption and Mood Disruption

Insomnia, affecting 10% of the population, is associated with increased risk for depression. Investigators examined possible mechanisms for this association in 62 healthy men and women (39 women; mean age, 26) who demonstrated good sleep and did not have psychiatric or substance use disorders. Participants were randomized to one of three conditions for 3 nights: forced awakenings for 20 …

Can we still dream when the mind is blank? Sleep and dream mentations in auto-activation deficit

Bilateral damage to the basal ganglia causes auto-activation deficit, a neuropsychological syndrome characterized by striking apathy, with a loss of self-driven behaviour that is partially reversible with external stimulation. Some patients with auto-activation deficit also experience a mental emptiness, which is defined as an absence of any self-reported thoughts. We asked whether this deficit in spontaneous activation of mental processing may be reversed during REM sleep, when dreaming activity is potentially elicited by bottom-up brainstem stimulation on the cortex. Sleep and video monitoring over two nights and cognitive tests were performed on 13 patients with auto-activation deficit secondary to bilateral striato-pallidal lesions and 13 healthy subjects. Dream mentations were collected from home diaries and after forced awakenings in non-REM and REM sleep. The home diaries were blindly analysed for length, complexity and bizarreness. A mental blank during wakefulness was complete in six patients and partial in one patient. Four (31%) patients with auto-activation deficit (versus 92% of control subjects) reported mentations when awakened from REM sleep, even when they demonstrated a mental blank during the daytime (n = 2). However, the patients' dream reports were infrequent, short, devoid of any bizarre or emotional elements and tended to be less complex than the dream mentations of control subjects. The sleep duration, continuity and stages were similar between the groups, except for a striking absence of sleep spindles in 6 of 13 patients with auto-activation deficit, despite an intact thalamus. The presence of spontaneous dreams in REM sleep in the absence of thoughts during wakefulness in patients with auto-activation deficit supports the idea that simple dream imagery is generated by brainstem stimulation and is sent to the sensory cortex. However, the lack of complexity in these dream mentations suggests that the full dreaming process (scenario, emotions, etc.) require these sensations to be interpreted by higher-order cortical areas. The absence of sleep spindles in localized lesions in the basal ganglia highlights the role of the pallidum and striatum in spindling activity during non-REM sleep.

Discriminating neurological from psychiatric hypersomnia using the forced awakening test

Sleep inertia refers to the inability to attain full alertness following awakening from sleep and is a major component of hypersomnia. As event-related potentials (ERPs) are correlated to the degree of consciousness, they allow exploring information processing in transitional states of vigilance. Their modifications during forced awakening (FA) context have been shown to reflect sleep inertia. To assess the diagnostic value of a FA test using an oddball stimulation protocol during a nap in a representative sample of patients with excessive daytime sleepiness (EDS). One hundred and seventy three patients [30 narcolepsy, 62 idiopathic hypersomnia, 33 sleep apnoea syndrome, and 48 other (mainly psychiatric) hypersomnia] performed an auditory target detection stimulation task during pre-, post-nap wakefulness, and during two successive intra-nap FA while the EEG was simultaneously recorded. Both the accuracy of target detection and the ERPs were evaluated. ERPs during forced awakening test were considered to reflect sleep inertia if they presented with a P300 delay and/or sleep negativities (N350/N550). Pre-nap behavior and ERPs were normal in all patients. Behavioral results were significantly worse during FA than during wakefulness for all groups of patients. P300 latencies were significantly delayed on FA conditions in each group of patients except the psychiatric group. Sensitivity and specificity for detection of sleep inertia were 64% and 94%, respectively, with predictive values of 96% (positive) and 50% (negative). Our results suggest that the FA test could be helpful as a diagnostic procedure for discriminating neurological from psychiatric hypersomnia.

Longitudinal study of self-awakening and sleep/wake habits in adolescents

Self-awakening is the ability to awaken without external assistance at a predetermined time. Cross-sectional studies reported that people who self-awaken have sleep/wake habits different from those of people who use external means to wake from sleep. However, no longitudinal study has examined self-awakening. The present study investigated self- awakening, both habitual and inconsistent, compared to awakening by external means in relation to sleep/wake schedules for five consecutive years in 362 students (starting at mean age 15.1 ± 0.3 years). Students who self-awakened consistently for five consecutive years (5% of all students) went to bed earlier than those who inconsistently self-awakened (mixed group, 40%) or consistently used forced awakening by external means (56%). Awakening during sleep was more frequent and sleep was lighter in the consistently self-awakened group than in the mixed and consistently forced-awakened groups. However, daytime dozing was less frequent and comfort immediately after awakening was greater for the consistently self-awakened group than for the mixed and consistently forced-awakened groups. These results indicate that the three groups have different sleep/wake habits. Previous studies of self-awakening using cross-sectional survey data may have confounded both consistent and inconsistent self-awakening habits. A longitudinal study is necessary to clarify the relationship between the self-awakening habit and sleep/wake patterns.