In order to study both the prevalence of Primary Sleep Disorders (PSD) and sleepiness, and their association to the Chronic Fatigue Syndrome (CFS), 46 unselected outpatients (34 women, mean age 36.5) were examined clinically and underwent two nights of all-night polysomnography and multiple sleep latency tests (MSLT). Forty-six percent presented with a Sleep Apnea/Hypopnea Syndrome Index (AHI>=5), 5% with a Periodic Limb Movements syndrome. No subject received a diagnosis of Narcolepsy or Idiopathic Hypersomnia. Thirty percent showed the presence of objective sleepiness as measured by MSLT<10 minutes. Objective and subjective measures of sleepiness were not associated with CFS, nor with the double diagnosis of CFS and a PSD. The presence of PSD or sleepiness was not associated with any of the clinical scales that were used to measure anxiety, depression, somatisation, physical or mental fatigue, or functional status impairment. Fifty-four percent of CFS patients had no PSD, and 69% no sleepiness. These patients could not be distinguished clinically from patients having a PSD or from those with sleepiness. Therefore, it is unlikely that CFS is simply a somatic expression of any PSD observed in our sample or of sleepiness per se.
The "immediate-onset"-acting hypnotics (1-2 h after oral administration) (e.g., benzodiazepines) serve as the leading approach and great progress has been made in this century. They are exogenous from artificial synthesis and mainly fit for short-term insomnia. The "gradual-onset"-acting hypnotics (3-5 d after oral administration) are mild and gradually effective, but are very safe and without noticeable side or adverse effects. They are endogenous or endogenous-mimetic from natural isolation. It may serve as a more natural approach for the treatment of chronic or long-term insomnia, which is mainly gradually developed. This approach is especially useful in treating elderly people, whose numbers are rapidly increasing worldwide, especially in the next century. Sleep-Aid Tea (SAT) is a naturally processed Tea consisting of endogenous or endogenous-mimetic sleep-inducing substances isolated from specific natural and edible fruits and plants well known for the treatment of insomnia, e.g., Compendium of Materia Medica (Li, 1596) associated with modern knowledge and isolation technology (Liu, 1990, 1993). SAT is especially fit for the treatment of insomnia in aged people because it is mild, "gradual-onset"-acting (3-5 d after oral administration), natural, safe and without side effects.
Isolated Sleep Paralysis (SP) occurs at least once in a lifetime in 40-50% of normal subjects, while as a chronic complaint it is an uncommon and scarcely known disorder. A series of messages written by subjects who experienced at least one episode of SP, containing more or less detailed descriptions of this disorder, were collected from the Sleep Web site of the University of California in Los Angeles between January 1996 and July 1998. Two hundred and sixty-four messages fulfilling the International Classification of Sleep Disorders (ICSD) (Thorpy, 1990) minimal criteria for SP were analyzed. A wide spectrum of severity was evident, with a frequency of episodes ranging from one in a lifetime to almost every night, and a variety of emotional and hallucinatory experiences associated with SP episodes were reported. Clinical similarities between the recurrent form of isolated SP and channelopathies (in particular, periodic paralyses) are discussed. An activation of limbic system structures is suggested in order to explain some of the most common subjective experiences associated with SP.
The changes in brain temperature and sleep-wakefulness were studied in rats during their exposure to different ambient temperatures of 18 degrees C, 24 degrees C and 30 degrees C, before and after N-methyl D-aspartic acid lesion of the medial preoptic area. The medial preoptic area lesion produced a decrease in sleep, and increase in brain temperature except at 30 degrees C. Increase and decrease in brain temperature with slow wave sleep and paradoxical sleep respectively, were observed both in normal and lesioned rats. Sleep-wakefulness and brain temperature cycle durations were increased and their frequencies decreased at higher ambient temperature in normal rats. After the medial preoptic area lesion, sleep-wakefulness cycle duration was decreased and frequency increased at 30 degrees C. There was no significant change in brain temperature cycles at higher ambient temperature in lesioned rats. The medial preoptic area, in normal rats, possibly interlinks the neuronal circuits involved in regulating brain temperature and sleep-wakefulness cycles. The medial preoptic area is essential for increasing the sleep-wakefulness cycle duration with higher ambient temperature. The possible contribution of the increased brain temperature variation in producing sleep-wakefulness changes cannot be ruled out. The results of the study show that this area may serve as a fine tuning mechanism which helps to interlink the sleep-wakefulness with the thermoregulation.
The effect of a single nucleotide polymorphism, a glutamine to arginine amino acid substitution in the human Timeless gene (Q831R, A2634G), on diurnal preferences was studied in a random sample of normal volunteers enrolled in a population-based epidemiology study of the natural history of sleep disorders. We genotyped 528 subjects for this single nucleotide polymorphism and determined morningness-eveningness tendencies using the Horne-Ostberg questionnaire. Our results indicate that Q831R Timeless has no influence on morningness- eveningness tendencies in humans.
Severity of negative esophageal pressure (Pes) and apnea hypopnea index (AHI) were investigated in 34 patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). The OSAHS patients were diagnostically classified as having obstructive sleep apnea syndrome (OSAS) or upper airway resistance syndrome (UARS). Diagnosis of OSAS was based on an AHI of more than 5, and that of UARS on an AHI of less than 5, EEG arousals which were associated with apnea, hypopnea and/or respiratory effort occurring more than 10 times per hour, and daytime sleepiness. Negative Pes was represented by the greatest peak (NPes Max) and the number of increased (more than 13.5 cmH2O) episodes per hour (NPesI13.5). There was no significant correlation between the AHI and Pes indices, but NPes Max and NPesI13.5 showed significant correlation (p<0.01). NPes Max and NPesI13.5 showed no significant differences among the severe OSAS (AHI>50; 8 cases), moderate OSAS (50>AHI>15; 10 cases), mild OSAS (15>AHI>5; 9 cases) and UARS (7 cases) groups. We conclude that AHI does not reflect the severity of the increase in negative Pes, which is an important aspect of the pathophysiology of OSAHS. Assessment of OSAHS based on AHI alone may therefore underestimate the risk of increased negative Pes in cases with reduced AHI.
In depression and aging an increase in nocturnal cortisol secretion and a blunted nocturnal growth hormone (GH) surge have been described. In normal young men, growth hormone-releasing hormone (GHRH) promotes GH release and reduces plasma cortisol. Here, we examined whether GHRH could help to restore sleep-endocrine regulation in patients with depression and aging. GHRH (4x50 microgram, at 2200, 2300, 2400 and 0100 h) or saline (placebo) was injected intravenously to 42 patients with depression (19 females, 23 males) and matched controls (age range 19-76 years). Blood samples were withdrawn at 20 min intervals between 2200-0700 h and analysed using Manova (D.F. 1, 72). Patients compared to controls had significantly higher levels of ACTH and cortisol, particularly during the first half of the night (F=9 and F=11.8, each p<0.05). GHRH reduced ACTH during the first and cortisol secretion during the second half of the night in males, regardless of diagnosis, but enhanced it in females (F=5.1 and F=4.0, each p<0.05). ACTH and cortisol secretion were inversely related to NREM and stage 2 sleep in patients (r= -0.42, -0.42 and r= -0.36, -0.39, respectively, each p<0.05) but not in controls. Our data suggest that: 1) female gender, depression and aging add-on to enhance HPA activity, and 2) hyperactivity of the HPA system and the decrease in NREM and in particular stage 2 sleep in depression are interrelated. In men, GHRH can restore some of the sleep-endocrine alterations associated with depression and aging.
The aim of this experiment was to compare the characteristics of mental activity during REM and Slow Wave Sleep (SWS). Forty dream reports and their mnemonic associations were collected from twenty subjects. The reports were analyzed for structure (number of temporal units, number of report multi-units, and narrative continuity), awareness (reality testing, subjective time), and content (self, setting, laboratory references, number of non-self characters, implausibility, body feelings, number and intensity of emotions, vividness). Associations were classified as episodic and semantic memories. Results showed that REM reports were significantly longer than SWS reports. Minor content SWS-REM differences were also detected, which were more quantitative than qualitative. The collected observations might support the tentative hypothesis that dreaming is a continuous process, which is not unique to REM sleep. Different levels of engagement of the cognitive system are responsible for the SWS-REM differences that were detected.
The role, if any, of exercise training in the management of individuals with obstructive sleep apnea syndrome (OSAS) is unclear. Anecdotally, patients have reported improvement in symptoms with regular participation in an exercise regime. In this study, we evaluated the effects of an exercise training program and weight loss on physical and subjective measures associated with OSAS. Nine subjects with mild to moderate OSAS completed a six month supervised exercise program. Pre and post-training measures on polysomnographic testing, physical training, anthropometric measures, quality of life (QOL), daytime somnolence and mood states were assessed. A significant decrease in the AHI (p=0.002) was noted along with improvements (p<0.05) in total sleep time, sleep efficiency, number of awakenings/hour, arousals/hour, apnea index and mean exercise training workloads. Significant decreases (p<.001) in weight (-6.2 kg) and body mass index (-1.6) were observed. Evaluation of QOL measures by the Health Status Questionnaire, Profile of Mood States and Epworth Sleepiness Scale showed significant changes in health status, affective state, and a decrease in daytime somnolence. Regular exercise training had a positive impact on the AHI, aerobic capacity, body mass index and QOL. However, exercise training alone was not an adequate intervention strategy for most individuals with OSAS but may serve well as an adjunct treatment strategy in the conservative management of individuals with mild to moderate OSAS.
Recent work has implicated the hypocretin (orexin) system in the genesis of narcolepsy. In the current study we demonstrate that systemically administered hypocretin-1 (Hcrt-1) produces an increase in activity level, longer waking periods, a decrease in REM sleep without change in nonREM sleep, reduced sleep fragmentation and a dose dependent reduction in cataplexy in canine narcoleptics. Repeated administration of single daily doses of Hcrt-1 led to consolidation of waking and sleep periods and to a complete loss of cataplexy for periods of three or more days after treatment in animals that were never asymptomatic under control conditions. Systemic administration of Hcrt-1 may be an effective treatment for narcolepsy.
From the accumulated results, we hypothesize that neurons in the central processor systems of the brain generally exhibit a common state-dependency in slow dynamics of their spontaneous activities during sleep. In this paper, activities of relay cells in the cat's lateral geniculate nucleus (LGN) were studied to see if our hypothesis can be applied in this thalamic region. Data segments in polygraphically steady states were strictly extracted in order to sample the activities whose stationarity was guaranteed in a statistical sense. During slow wave sleep (SWS), the discharge pattern was characterized by short bursts. In contrast, the rather tonic discharge pattern was observed to prevail during rapid eye movement (REM) sleep. Spectral analyses showed white noise-like spectra in the low frequency range of 0.04-1.0 Hz during SWS, and 1/f noise-like spectra in the same frequency range during REM sleep. This state-dependency of the slow dynamics was consistently characterized by the other statistical parameters concerning the second-order moment as well. In contrast, the fast dynamics over 1.0 Hz tended to exhibit neuron-specific changes associated with the sleep state in terms of the Markovian dependency analysis. Consequently, our working hypothesis was not rejected for the LGN relay cells. The result here extends the possibility that the state-dependency of the slow dynamics we found is a general rule concerning single neuronal dynamics in widespread areas of the brain during sleep. The state-dependency of the slow dynamics of the LGN relay cells could be understood according to the proposed mechanism that a state-associated alteration in the global biasing input to a neural network during sleep induces the phenomenon with which we are concerned. The slow dynamics of neuronal activities might provide a novel framework defining SWS and REM sleep states instead of the polygraphic characteristics.
The present study sought to evaluate concomitant alterations of behavioral and sleep patterns of arthritic rats. Rats were implanted with electrodes for polysomnographic recordings and submitted to the model of arthritis by a subcutaneous (s.c.) administration of Freund adjuvant in the posterior right paw and saline in the posterior left paw. The SHAM group was injected with saline in both paws, whereas the control group (CTL) was not submitted to any manipulation. Behavioral tests were carried out twice before induction of arthritis, on the second day of arthritis, and once a week afterwards until the eighth week. Body weight, colonic temperature, and measurements of the injured paw were carried out on the same days. Arthritic rats presented a reduction of total sleep time, increased latency to synchronized sleep, augmented number of episodes of synchronized sleep, reduction of sleep efficiency, more stage shifts, and increased total alert time. Moreover, these animals presented a lower pain threshold than control and SHAM animals. This reduction was observed on the second day of arthritis and remained so reduced until the end of the study. The data appear to indicate a relationship between altered sleep pattern and increased pain sensitivity in arthritic rats.
The squirrel monkey (Saimiri sciureus) exhibits a robust daily rhythm of sleep-wakefulness that is under circadian control, but the nature of homeostatic sleep regulation in this diurnal primate is poorly understood. Since delta frequency (0.5-2.0 Hz) activity in the electroencephalogram (EEG) during non-Rapid Eye Movement (NREM) sleep is thought to reflect homeostatic factors contributing to sleep tendency, we measured EEG delta power density and slow wave incidence and amplitude during NREM sleep during spontaneous sleep, occurring when monkeys were housed undisturbed in a 24-hour light-dark (LD) cycle and in constant light (LL). In LD and LL conditions, monkeys exhibited circadian rhythms in delta power density, wave incidence and wave amplitude that peaked in the middle of the subjective night, several hours after consolidated sleep onset. These results differ from predictions of a purely homeostatic model of sleep that would include maximal levels of delta activity at sleep onset.
Investigations concerning the temporal organization of the sleep/wake cycle (SWC) in healthy active elderly, specially focusing possible relationships between regular daily routines, sleep fragmentation and sleep quality in aging are still scarce. We studied the SWC of 23 healthy active elderly (65-76 years old) of both sexes (15 female, 8 male), engaged in an exercise program for old people, considering that physical exercise sessions could represent a strategy for keeping structured daily routines. We report the relationships between SWC characteristics and performance of physical exercises viewed as time cues. We collected SWC data by means of sleep logs and data about light exposition by means of actigraphy during 23 consecutive days. Individuals who chose earlier times for exercising showed longer exposition to natural bright light and reported better sleep quality. Indications that physical exercises could be beneficial upon sleep were scarce (better subjective sleep quality). Strength of semicircadian component of the SWC was greater for subjects who exercised longer, suggesting they have advantageously used naps as part of their active and healthy lifestyle, and indicating the need for studying more closely the temporal organization of naps.
The time-courses of power in the different frequency bands (1-40 Hz) within the non-rapid-eye-movement (NREM) episode of the human sleep electroencephalogram have provided for many years a fascinating window into the sleep process. Here our analysis of the slow-wave band (1-4 Hz) reveals a hitherto unrecognized very slow oscillation of power with mean period ~15 minutes, an instability that appears to be an integral characteristic of the early NREM episode. The neuronal transition probability (NTP) model has already given a mechanism explaining how power in the spindle band peaks consistently before that of slow wave activity. Here we show that an extension of the model, with the hypothesis of a population of sleep neurons alternating between two steady probability states, can simulate the very slow oscillation. In doing so it gives not only the time course of power in the slow wave band, but also the simultaneous time-courses in the spindle and in the fast frequency bands. Animal data suggest that a brainstem neuronal population, toggled by an external switching source, generates these time-courses and dictates them to the thalamus and thence to the cortex. The discovery of the very slow oscillation and the success of the NTP model in interpreting the overall NREM structure may have important implications for both clinical and fundamental sleep research.
This study investigated the effects of a short afternoon nap (<30 min) in the elderly on subjective mood, performance and electroencephalograms (EEG). Ten healthy elderly persons who habitually napped in the afternoon three or more times a week participated in the present study. They participated in two experimental conditions with an interval of more than five days. In the nap condition, the participants went to bed at 13:00 hours and slept for 30 min, whereas they just had a rest while watching television in the no-nap condition. In both conditions, subjective sleepiness, fatigue, performance and EEG activities with eyes opened and closed were repeatedly measured before and after the nap or rest. The nap significantly reduced subjective sleepiness and fatigue in the afternoon. It also improved performance levels and EEG theta, alpha 1 or alpha 2 band activities with eyes opened and closed. These findings suggest that a short afternoon nap is useful for the elderly in maintaining their daytime psychological, behavioral and physiological arousal at an adequate level.
During wakefulness, the cerebral cortex, which is responsible for generating mental activities, is activated by brain stem ascending influences. This is evidenced by classic electrophysiological field and unitary activities, gamma range activity and cortical blood flow. However, aminergic ascending neurons exert mainly diffuse inhibitory influences. These two kinds of influences together support reflective and rational psychological activities. During slow wave sleep, both kinds of ascending influences decrease and the mental content comprises low-intensity thought-like activities, similar to the waking mode of functioning, although dreams have been described. During rapid eye movement sleep, the principal dreaming stage, the cortex is activated but significantly disinhibited since all aminergic neurons are silent except the dopaminergic ones. We hypothesize that, in addition to this unusual state, the persistent release of dopamine associated with the specific silence of noradrenergic neurons could explain the characteristics of dream mental activity which are somewhat similar to psychotic symptoms.
The present study investigated the distribution of neurons implicated in the regulation of sleep in three species generally used in sleep research, i.e., mice, rats and cats. We focused on sleep active neurons in the ventral lateral preoptic (VLPO) area and the hypocretin/orexin-containing neurons in the lateral hypothalamus. The latter groups of neurons were found recently to play an important role in the regulation of REM sleep. The expression of the transcription factor, c-Fos, was used to identify the VLPO. In mice and rats, in response to sleep, a discrete cluster of c-Fos positive cells was found in the VLPO. In mice, this cluster was located more medially compared to the rat, and as in the rat, galanin immunostained neurons were found in the VLPO. In the cat, c-Fos positive cells did not segregate to a specific location but were more diffusely represented in the preoptic area. In all three species, orexin/hypocretin-containing neurons were located only in the lateral hypothalamus with the distribution being more diffuse in the cat. The grouping of sleep-active cells in rodents makes it feasible to extract these cells for tissue culture and molecular analysis. Moreover, given that rodents have a distinct circadian distribution of sleep-wakefulness, the connectivity with the suprachiasmatic nucleus can also be determined.
The P1/P50 midlatency auditory evoked potential is a sleep state-dependent waveform present during waking and rapid eye movement (REM) sleep and absent during slow-wave sleep. The P50 potential was studied in normal male and female subjects of various ages including post-pubertal adolescents (12-19 yrs), young adults (24-39 yrs), middle-aged adults (40-55 yrs) and older adults (55-78 yrs). There were no statistically significant differences in the mean peak amplitude or mean peak latency of the P50 potential between males and females or between age groups. Using a paired stimulus paradigm, the degree of sensory gating of the P50 potential was tested at three different interstimulus intervals (ISIs), 250, 500 and 1000 msec. There were no statistically significant differences in the sensory gating of the P50 potential between males and females. However, there was a significant decrease in sensory gating of the P50 potential in the adolescent group compared to each of the other age groups at the 250 msec ISI, but not at the 500 or 1000 msec ISI. These results suggest the presence of decreased sensory gating in normal adolescents compared to normal, older age groups.
In the transition from NREM to REM sleep, as in other instances of brain activation, a marked increase in cerebral blood flow and glucose uptake is observed, together with a lesser increase in O2 uptake. Brain activation also entails an increase in capillary PO2 and lactate production. The hypothesis of saturation of the oxidative machinery was advanced to explain anaerobic glycolysis and lactate production in the presence of high PO2, but data are available that cannot be explained by this hypothesis: hypoxic spots exist in the brain, augmenting in arterial hypoxia and disappearing in arterial hyperoxia, while tissue [H+] lowers as arterial PO2 increases beyond 100 mmHg. Additional hypotheses are thus required. We suggest that O2 diffusion limitation exists in the brain: microregions lying at mid-distance between capillaries may become hypoxic and partly resort to anaerobic glycolysis. These microregions are thought to enlarge with increasing metabolic rate or arterial hypoxia and give rise to vasodilatatory signals regulating local blood flow. REM sleep time is strongly reduced by hypoxic and increased by hyperoxic atmosphere, in accordance with the existence of an O2 diffusion limitation. Any pathological decrease in arterial PO2 and/or O2 delivery creates a specific risk in REM sleep.
