Sleep disturbances due to exposure to tone pulses throughout the night

Sleep electroencephalograms (EEGs) and subjective reports data were obtained from six subjects (male college students) during 2 nights of baseline observation and 5 experimental nights of exposure to a 90-100 dB, 25 ms, 1,000 c/s tone pulse with various interstimulus intervals. The first of the 5 experimental nights started with an intertone interval of 80 s. On each of the following 4 nights, the intertone interval was fixed at 40-, 10-, 2.5-, or 1-s intervals, respectively. With the intensification of noise stimulus by shortening the intervals of tone pulses, a progressive disruption of nightly EEG sleep patterns was observed as follows: (a) increased frequency of awakenings and sleep stage changes during the night, (b) prolonged sleep latency, and (c) increased percentage of time spent in stage 1 sleep. However, total sleep time, REM latency, inter-REM intervals, and the percentages of time in stages 2, 3, 4, and REM sleep did not change significantly. The degree of subjective sleep disturbance was highly associated with objective measures of nightly EEG sleep patterns.     

The relationship of sleep and anxiety in anxious subjects

The present study provided polysomnographic corroboration of the frequently reported relationship between anxiety and subjective sleep disturbance. When compared to normals, anxious individuals were found to have significantly less sleep period time, total sleep time, percent stage REM and percent stage 4; shorter latency to stage REM; and greater percent stage 1. Partial correlations (holding depression constant) showed significant positive relationships between anxiety rating and number of awakenings, latency to stage 1, and percent stage 2. A significant negative relationship was found between anxiety and percent stage 4, and a nonsignificant negative trend was found between anxiety and latency to stage REM. Overall there was a tendency toward less sleep and lighter sleep in subjects with anxiety, thus validating subjective reports. The decreased latency to stage REM and its negative relation to anxiety, raised the possibility that this variable may not be specifically indicative of depression.     

Sleep polygraphic variables in anorexia nervosa and depression: a comparative study in adolescents.

Sleep EEG variables were compared in an adolescent population consisting of 11 anorectic girls, 11 young depressed patients and 11 healthy volunteers matched for age and sex. Anorectic patients differed from depressed patients in a greater number and a higher length of awakenings. In comparison with controls, anorectic patients showed less sleep efficiency, a higher length of awakenings and less REM sleep. When anorectic patients were divided in restricting and bulimic subtypes, the bulimic anorectics showed an increase in stage 3 of sleep. These results do not support a direct association between eating disorders and affective disorders. Sleep EEG variables were not significantly correlated to the Body Mass Index.     

Spontaneous eyelid movements (ELMS) during sleep are related to dream recall on awakening

The present study aimed to test whether spontaneous eyelid movements (ELMs) during stage 2 and rapid eye movement (REM) sleep are related to more frequent and vivid reports of visual mentation on awakening. Participants were awakened 15 s after an ELM was observed during ongoing REM and stage 2 sleep and immediately asked for a mentation report and to rate the visual vividness of any imagery they could remember. These reports were compared with control reports collected after a period of ELM quiescence before awakening (noELM). Significantly greater frequencies of imagery reports were collected after ELM awakenings compared with noELM awakenings from stage 2, but not REM sleep. When imagery was reported, imagery ratings were not significantly different between ELM and noELM conditions, regardless of sleep stage. The average amount of electroencephalogram (EEG) arousal 15 s after stage 2 awakenings was significantly higher in the ELM compared with noELM conditions. In addition, within the stage 2 ELM condition, EEG arousal was significantly higher when visual imagery was reported compared with reports without imagery; suggesting that the observed increase in imagery reporting from the stage 2 ELM condition could have been mediated by the level of brain arousal. Such arousal possibly provides better conditions to attend and recall previous mental activity from NREM sleep. However, there was no ELM/arousal effect within REM sleep, possibly because this state is already at maximum sleeping levels of arousal, attention and resulting dream recall.     

Sleepiness and REM Sleep Recurrence: The Effects of Stage 2 and REM Sleep Awakenings

Determinants of daytime sleepiness include sleep length, sleep continuity, and circadian factors. Sleep stage composition has not been seen as influencing subsequent daytime functioning; however, earlier studies did not focus explicitly on sleepiness. The present experiment studied the effects of selective sleep-stage restriction on an objective measure of sleep tendency, and explored the relationship between sleepiness and subsequent REM recurrence during REM deprivation. Daytime sleep latency was measured by a modified Multiple Sleep Latency Test prior to and following two nights of awakenings from either REM or Stage 2 sleep in 16 normal young adults. Sleep latency following these awakenings was also measured. REM sleep and Stage 2 awakenings produced comparable levels of sleepiness, both during the Awakening Nights and subsequent daytime Multiple Sleep Latency Testing. Pooling the groups, daytime and nocturnal sleepiness measures were correlated within individuals. In the REM-Awakening Group, Pre-Awakening daytime sleepiness was associated with the tendency for REM sleep to recur following experimental awakenings. Comparable levels of sleepiness may result from nonspecific processes such as sleep curtailment and fragmentation, or alternatively from separate REM and Stage 2 mechanisms. The relationship between REM sleep and sleepiness is discussed in the context of both state and trait models.     

Heart rate variability during sleep in children with partial epilepsy

Alterations in autonomic control of cardiac activity in epileptic patients have been reported by several studies in the past, and both ictal and interictal modifications of heart rate regulation have been described. Alterations of autonomic control of cardiac activity can play an important role in sudden unexplained death in patients with epilepsy (SUDEP). However, the presence of specific changes in heart rate variability (HRV) during sleep, not correlated with seizures, has not been assessed in children with epilepsy; for this reason, we evaluated features of cardiac autonomic function during sleep without ictal epileptiform electroencephalogram (EEG) activity in a group of children with partial epilepsy. Eleven patients (five males and six females; mean age 11.5 years, SD: 3.65 years) affected by partial epilepsy were admitted to this study; 11 normal subjects (five males and six females; mean age 12.9 years, SD: 2.72 years) served as a control group. All subjects slept in the laboratory for two consecutive nights. The data were analyzed during the second night. Sleep was polygraphically recorded [including one electrocardiography (ECG) channel] and signals were digitally stored. A series of 5-min ECG epochs were chosen from each sleep stage, during periods without evident ictal epileptiform activity in the EEG. Electrocardiography signals were analyzed for automatic detection of R-waves and, subsequently, a series of time- and frequency-domain measures were calculated. Epileptic subjects tended to show an overall lower HRV in both time- and frequency-domain parameters, principally during rapid eye movement (REM) sleep and, to a lesser extent, during sleep stage 2. Among the different bands, this decrease was most evident for the high-frequency band (HF) absolute power. For this reason, the ratio between the low-frequency band (LF) and HF was always higher in epileptic patients than in normal controls and the difference was statistically significant during sleep stages 3 and/or 4 and REM sleep. Our results indicate that during sleep, a particular condition of basal modification in autonomic characteristics occurs (mostly during REM sleep) in partial epilepsy patients. This finding might represent an important factor contributing to the complex mechanism of SUDEP which takes place most often during sleep and supports the need of studying HRV specifically during this state in subjects with seizures.     

Sleep EEG recordings in generalized anxiety disorder with significant depression

After one accommodation night, sleep EEG recordings were performed during three consecutive nights in ten drug-free inpatients presenting generalized anxiety disorder (GAD) with significant depression, compared with a age- and sex-matched group of patients with GAD and a group of primary major depressive disorder (MDD) patients. GAD patients with depression did not differ from GAD patients in any sleep variable. Patients with MDD showed more stage shifts and a greater number of awakenings than patients with GAD. REM latency was significantly shorter in MDD patients than in the other groups, and may thus help to differentiate anxious from depressed patients.     

Effect of growth hormone treatment on sleep EEGs in growth hormone-deficient children

Total sleep time, sleep stages 1-4, REM, REM latency, and sleep efficiency were analyzed in seven children with growth hormone deficiency (GHD) before and after growth hormone (GH) therapy. Before GH therapy, GHD children spent 19.5% of their total sleep time in REM sleep, 9.7% in stage 1, 41.0% in stage 2, 10.0% in stage 3, and 19.7% in stage 4. GHD children had more stage 1 and 3 sleep and less REM as compared with age-matched normal children reported by Williams et al. After GH therapy was initiated, six of the seven patients had decreases in the duration of stage 3 sleep, with an average decrease of 21.8 min. The difference between stage 3 sleep before and during GH treatment was significant, with a p value of less than 0.025. When the results were expressed as the percentage of the total sleep period, the difference was also significant, (10.0 +/- 2.0 to 7.5 +/- 3.1%, mean +/- SD; p less than 0.05). No other sleep parameters were significantly affected by GH therapy. The changes observed in stage 3 sleep, non-REM sleep, and the lack of any other changes in sleep before and after GH therapy have not been described before in GH-deficient children. They differ from studies in normal humans and animals which showed that REM sleep increased with administration of growth hormone. These differences suggest that GH deficiency is associated with a specific sleep EEG anomaly that is corrected in part by GH therapy.     

Alexithymia and polysomnographic measures of sleep in healthy adults

OBJECTIVE: This study examined associations between alexithymia and objective characteristics of sleep (latencies, stages, and amount and patterning of REM sleep) that may contribute to subjective reports of poor sleep quality and impaired dream recall among alexithymic people. METHODS: Fifty healthy, normally sleeping adults from the community completed the 20-item Toronto Alexithymia Scale and slept uninterrupted for one night in the laboratory while polysomnography was conducted. Various measures of sleep latency, sleep stages, and REM sleep-related variables were obtained, and analyses correlated these sleep measures with alexithymia, controlling for age, sex, and level of depressed affect. RESULTS: Higher alexithymia scores were significantly related to increased stage 1 (light) sleep and decreased stage 3/4 (deep) sleep. Alexithymia was unrelated to overall sleep efficiency or percentage of stage 2 sleep. Alexithymia was related to more frequent REM episodes and more stage 1 sleep during and immediately after REM episodes but was unrelated to the absolute amount of REM sleep. Alexithymia was also related to an earlier onset of the first REM episode. CONCLUSIONS: Alexithymia is associated with more light sleep and less deep sleep, which may contribute to subjective reports of poor sleep and increased sleepiness, fatigue, and somatic symptoms. Although alexithymia is not associated with an overall reduction of REM sleep, the increased frequency of episodes of REM that are interrupted and followed by light sleep rather than complete awakenings may contribute to limited dream recall.     

Comparison of subjective and objective measures of insomnia in monozygotic twins discordant for chronic fatigue syndrome

STUDY OBJECTIVES: To examine the objective and subjective measures of insomnia in chronic fatigue syndrome (CFS). DESIGN: Monozygotic co-twin control study. SETTING: Academic medical center. PATIENTS OR PARTICIPANTS: Twenty-two pairs of monozygotic twins where 1 member of the pair had CFS and the other did not. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Twenty-two CFS-discordant twin pairs completed a Sleep Disorders Questionnaire, overnight polysomnography, and a postpolysomnography sleep survey. Mean and percent differences in the sleep measures were compared between the CFS and healthy twins using matched-pair methods of analysis. Compared with their healthy co-twins, the CFS twins more frequently endorsed 8 subjective measures of insomnia and poor sleep (all p < or = 0.05). However, the CFS and healthy twins did not differ in objective polysomnographic measures of insomnia, including sleep latency, total sleep time, sleep efficiency, arousal number, arousal index, hypnogram awakenings, rapid eye movement (REM)-sleep latency, and percent stages 1, 2, and 3-4 (delta). Percent stage REM sleep was increased in the CFS twins compared with the healthy twins (27.7% vs. 24.4%, p < or = 0.05). On the postpolysomnography survey, CFS twins reported that they had slept fewer hours (6.2 vs. 6.7; p < or = 0.05), and were less well rested (p < or = 0.001) compared to their co-twins. CONCLUSIONS: CFS patients had worse subjective sleep than their co-twins despite little objective data supporting this discrepancy, suggesting they suffer from an element of sleep-state misperception. The higher percentage of REM sleep in the CFS twins implies that REM sleep may play a role in this illness.     

Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment

OBJECTIVE: Evaluate the efficacy of ramelteon, an MT/1MT2-receptor agonist, for the treatment of transient insomnia in healthy adults. DESIGN: Randomized, double-blind, placebo-controlled design using a model of transient insomnia related to sleeping in a novel environment. SETTING: Fourteen sleep research centers. PARTICIPANTS: Healthy adults (N=375; 228 women), aged 35 to 60 years, who had never previously slept in a sleep laboratory and had a reported usual sleep duration of 6.5 to 8.5 hours and usual bedtime between 8:30 PM and midnight. INTERVENTIONS: Single administration of ramelteon (16 or 64 mg) or placebo 30 minutes before bedtime. OUTCOME MEASURES: Primary efficacy measure was latency to persistent sleep. Also evaluated were total sleep time, wake after sleep onset, percentage of each sleep stage, subjective estimates of sleep from postsleep questionnaire, number of awakenings, and subjective number of awakenings. Residual effects were assessed via Digit Symbol Substitution Test and postsleep questionnaire. RESULTS: Participants in ramelteon-treated groups had significantly shorter latency to persistent sleep relative to placebo. They also were associated with significantly longer total sleep time. Wake after sleep onset and time spent in each sleep stage were not significantly different from placebo. The use of ramelteon (16 mg) was associated with a shorter subjective sleep latency compared to placebo. Other subjective measures of sleep did not differ significantly from placebo. Digit Symbol Substitution Test scores did not differ significantly among the 3 groups, but the use of the 64-mg [corrected] dose was associated with subjective reports of impairment in the morning. CONCLUSIONS: Ramelteon significantly improved latency to persistent sleep and total sleep time in this model of transient insomnia in healthy adults. No dose-related differences in latency to persistent sleep were observed, and both doses were well tolerated.     

Subjective versus objective evaluation of hypnotic efficacy: experience with zolpidem.

There is little published literature on the correlation between subjective and objective efficacy of hypnotics. We wanted to determine whether there was a correlation between the patient's subjective evaluation of the efficacy of the hypnotic with the polysomnographic (PSG) findings. We studied 16 patients with chronic insomnia (sleep latency, greater than or equal to 30 minutes; total sleep time, greater than 240 but less than 420 minutes) for 11 nights who took placebos on nights 1 and 2, zolpidem (imidazopyridine) on nights 3-9 and placebo on nights 10 and 11. Patients completed a questionnaire each morning following PSG, which evaluated subjective sleep quality, sleep latency and total sleep time. These data were compared to PSG findings to answer specific questions about sleep latency reduction, efficacy of the hypnotic after a week's use, sleep quality after discontinuing the drug, and any correlation between subjective and objective measures. PSG findings indicated a shortened sleep latency, increased total sleep time, decreased total wake time and increased sleep efficiency when patients ingested zolpidem 30 minutes before bedtime. We found that after 7 nights (nights 3-9) the drug was still effective in reducing sleep latency and increasing total sleep time. Upon withdrawal (nights 10 and 11) sleep returned to baseline (nights 1 and 2). Subjectively, the patients confirmed those findings on the questionnaire, as well as a subjective reduction in the number of awakenings and, interestingly, a subjective increase in the time spent awake after sleep. Many of the objective variables we examined correlated highly with the subjective variables. While on zolpidem, subjects believed and were objectively shown to have a decreased sleep latency, increased total sleep time and decreased time awake before persistent sleep, although they tended to overestimate sleep latency and time spent awake before persistent sleep and underestimated total sleep time. Although the correlation between objective and subjective measures was high for the group, in individual patients there was an impressive difference between the two, and the highest coefficient of variation between a subjective and objective measures was 0.453. No correlations were found with subjective measures of refreshing quality of sleep, decrease in number of awakenings, how sleepy patients felt in the morning or their ability to concentrate in the morning. Thus, we believe the PSG remains the keystone in the evaluation of hypnotic efficacy.     

Effects of sleep on spinal nociceptive reflexes in humans

Controversy continues to surround the monosynaptic and polysynaptic spinal reflexes during the different stages of sleep. In animal studies both of these reflexes were found to be depressed during desynchronized sleep. In humans, the H reflex was unchanged whereas the second component of the nociceptive flexion reflex was increased. However, abolition of the H reflex and F waves during REM sleep has also been reported. The aim of this investigation was to examine the effects of different sleep stages on the polysynaptic nociceptive flexion reflex. Six healthy volunteers were studied. The RIII reflex was studied according to Willer's method (1977) during the different stages of NREM and REM sleep. The RIII reflex threshold was found to increase during stage 2 of NREM sleep. It remained higher during stages 3 and 4. During REM sleep a further increase in the reflex threshold was observed. The reflex latency was prolonged during stage 4 of NREM sleep. There was evidence of further latency prolongation during REM sleep. It was also during REM sleep that the maximum increase in the amplitude and duration of the reflex were recorded.     

The estimation of sleep quality in different stages and cycles of sleep

Dream content in NREM and REM sleep correlates with the subjective experience of having slept immediately before awakening. The estimation of depth of sleep depends on the quality of the NREM sleep stages. The presence of dreaming in a given sleep stage is more important for the subjective experience of having slept than the duration of the sleep episode before the awakening. Neurotic insomniac patients more often deny mental activity when awoken from NREM and REM sleep, than do healthy subjects. These data suggest that spontaneous awakenings in different sleep stages, especially in the first sleep cycle, correlate with the insomniac's tendency to underestimate sleep duration and quality.     

The effect of transdermal nicotine patches on sleep and dreams

This study was undertaken to determine the effect of 24-h transdermal nicotine patches on sleep and dream mentation in 15 smokers aged 20 to 33. Utilising a repeated measures design, it was found that more time awake and more ASDA micro-arousals occurred while wearing the nicotine patch compared to placebo. Also, the percentage of REM sleep decreased, but REM latency and the proportion of time spent in NREM sleep stages did not change significantly. Dream reports containing visual imagery, visual imagery ratings and the number of visualizable nouns were significantly greater from REM compared to Stage 2 awakenings, regardless of patch condition. However, a general interaction effect was observed. Stage 2 dream variables remained equivalent across nicotine and placebo conditions. Within REM sleep, more dream reports containing visual imagery occurred while wearing the nicotine patch, and these were rated as more vivid. The greater frequency of visual imagery reports and higher imagery ratings specifically from REM sleep suggests that previously reported dreaming side effects from 24-h nicotine patches may be specific to REM sleep. Combined with previous animal studies showing that transdermally delivered nicotine blocks PGO activity in REM sleep, the current results do no appear consistent with PGO-based hypotheses of dreaming, such as the Activation-Synthesis (AS) or Activation, Input and Modulation (AIM) models.     

Effects of intravenous catheter on sleep in healthy men and in depressed patients

The effects of intravenous catheter and nocturnal blood samplings at frequent intervals on sleep electroencephalogram (EEG) variables were investigated in 8 male healthy controls and 12 depressed patients, who were studied in the same experimental conditions. After one night of habituation, sleep was recorded during 4 consecutive nights in the sleep laboratory. A catheter was inserted around noon the day before the fourth night, and blood was sampled every 15 min for 25 h. The night-to-night comparison of sleep EEG variables did not show significant sleep continuity modifications in the control subjects, other than a weak trend toward an increase in nocturnal awakenings during the night with the catheter. A lengthening of sleep onset latency during the fourth night was found in the depressed patients. No significant changes were detected in percentage of rapid eye movement (REM) sleep in the two groups. However, a gradual increase in Stage 3 was observed across the 4 nights in the control subjects. These results indicate that intravenous blood sampling via a catheter can be performed without inducing significant disruption of sleep length and structure.     

Narcolepsy and depression and the neurobiology of gammahydroxybutyrate

A voluminous literature describes the relationship between disturbed sleep and depression. The breakdown of sleep is one of the cardinal features of depression and often also heralds its onset. Frequent arousals, periods of wakefulness and a short sleep onset REM latency are typical polysomnographic features of depression. The short latency to REM sleep has been attributed to the combination of a monoaminergic deficiency and cholinergic supersensitivity and these irregularities have been proposed to form the biological basis of the disorder. A similar imbalance between monoaminergic and cholinergic neurotransmission has been found in narcolepsy, a condition in which frequent awakenings, periods of wakefulness and short sleep onset REM latencies are also characteristic findings during sleep. In many cases of narcolepsy, this imbalance appears to result from a deficiency of hypocretin but once established, whether in depression or narcolepsy, this disequilibrium sets the stage for the dissociation or premature appearance of REM sleep and for the dissociation of the motor inhibitory component of REM sleep or cataplexy. In the presence of this monoaminergic/cholinergic imbalance, gammahydroxybutyrate (GHB) may acutely further reduce the latency of REM sleep and induce cataplexy, in both patients with narcolepsy or depression. On the other hand, the repeated nocturnal application of GHB in patients with narcolepsy improves the continuity of sleep, prolongs the latency to REM sleep and prevents cataplexy. Evidence to date suggests that GHB may restore the normal balance between monoaminergic and cholinergic neurotransmission. As such, the repeated use of GHB at night and the stabilization of sleep over time makes GHB an effective treatment for narcolepsy and a potentially effective treatment for depression.     

The role of presleep negative emotion in sleep physiology

Although daytime emotional stressful events are often presumed to cause sleep disturbances, the few studies of stressful life events on sleep physiology have resulted in various and contradictory findings. As research has focused in particular on stress in itself, the present study is the first to investigate the effect using polysomnography (PSG). Results indicate a significant increase in sleep fragmentation, as expressed by decreased sleep efficiency, total sleep time, percentage of rapid eye movement (REM) sleep, and an increased wake after sleep onset latency, total time awake, latency to SWS, number of awakenings and number of awakenings from REM sleep. The results demonstrate that negative emotion correlates with enhanced sleep fragmentation helping us to understand why sleep patterns change and how sleep disturbances may develop.     

The Effects of Continuous, High Intensity, White Noise on the Human Sleep Cycle

Eight male college students slept for 8 consecutive nights under conditions of 93 ± 2 dB white noise (N) and under normal quiet conditions (Q). On N nights the percentage of total sleep time spent in stage REM was decreased (p < .001), the percentages of stages 1 and 2 were increased (p < .05, p < .001, respectively) and REM latency was increased (p < .02) compared to Q nights prior to N nights. On Q nights following N nights the percentages of stage REM increased above baseline levels indicating compensatory recovery effects from REM sleep deprivation on the prior N nights. Stages 3 and 4 remained unchanged throughout the study. The reduction in stage REM on N nights was directly attributed to the effects of noise on the CNS and not a secondary result of an increased number of awakenings on N nights.     

Corticospinal excitability and sleep: a motor threshold assessment by transcranial magnetic stimulation after awakenings from REM and NREM sleep

Transcranial magnetic stimulation (TMS) is a recently established technique in the neurosciences that allows the non-invasive assessment, among other parameters, of the excitability of motor cortex. Up to now, its application to sleep research has been very scarce and because of technical problems it provided contrasting results. In fact delivering one single suprathreshold magnetic stimulus easily awakes subjects, or lightens their sleep. For this reason, in the present study we assessed motor thresholds (MTs) upon rapid eye movement (REM) and non-rapid eye movement (NREM) sleep awakenings, both in the first and in the last part of the night. Taking into account that a full re-establishment of wake regional brain activity patterns upon awakening from sleep needs up to 20-30 min, it is possible to make inferences about the neurophysiological characteristics of the different sleep stages by analyzing the variables of interest immediately after provoked awakenings. Ten female volunteers slept in the lab for four consecutive nights. During the first night the MTs were collected, following a standardized procedure: 5 min before lights off, upon stage 2 awakening (second NREM period), upon REM sleep awakening (second REM period), upon the final morning awakening (always from stage 2). Results showed that MTs increased linearly from presleep wakefulness to REM sleep awakenings, and from the latter to stage 2 awakenings. There was also a time-of-night effect on MTs upon awakening from stage 2, indicating that MTs decreased from the first to the second part of the night. The increase in corticospinal excitability across the night, which parallels the fulfillment of sleep need, is consistent with the linear decrease of auditory arousal thresholds during the night. The maximal reduction of corticospinal excitability during early NREM sleep can be related to the hyperpolarization of thalamocortical neurons, and is in line with the decreased metabolic activity of motor cortices during this sleep stage. On the contrary, the increase of MTs upon REM sleep awakenings should reflect peripheral factors. We conclude that our findings legitimate the introduction of the TMS technique as a new proper tool in sleep research.