Normal Human Sleep Research Articles

Novel polymorphism in the promoter region of the tumor necrosis factor alpha gene: No association with narcolepsy.

The striking evidence of almost 100% association of narcolepsy with human leukocyte antigens (HLA) DR2(DR15) antigen is an important clue to elucidate the molecular basis of this sleep disorder. The gene for tumor necrosis factor alpha (TNF alpha) is located in the HLA class II gene cluster. Recent studies have indicated that TNF alpha plays an important role in the regulation of normal human sleep, and regulation of this cytokine may be disturbed in narcolepsy. We searched for a mutation associated with narcolepsy in the promoter region of the TNF alpha gene by single-strand conformation polymorphism analysis. A novel polymorphism, C-850T, was found in narcoleptic patients. Genotype frequency was examined by restriction fragment length polymorphism method. No significant difference of genotype distribution was found between 92 patients with narcolepsy and 91 normal controls. These results do not support our hypothesis that genetic abnormality of TNF alpha production is pathogenetic for narcolepsy.

A search for a mutation in the tumour necrosis factor-alpha gene in narcolepsy.

The discovery of almost 100% association of narcolepsy with human leukocyte antigens (HLA) DR2 antigen prompted molecular biological research of this disorder. In the HLA class II gene cluster, the gene for tumour necrosis factor-alpha (TNF-alpha), which plays a role in the regulation of normal human sleep, is located. The present study searched for a mutation in the TNF-alpha gene by single-strand conformation polymorphism analysis (SSCP) in patients with narcolepsy. No mutation was detected in exons and introns of the TNF-alpha gene by SSCP and sequencing.

Ellen R. Grass Guest Lecture: Sleep Disorders and Epilepsy: Things That Go Bump in the Night … and Day

ABSTRACT.It has long been known that sleep and sleep deprivation affect epilepsy; therefore, many sleep disorders may affect epilepsy as well as mimic epilepsy. The two most common symptoms that must be differentiated are confusional arousals from sleep and abnormal movements in sleep. In this presentation, we review the components of normal human sleep, common sleep disorders, and their effects on and differentiation from seizures. The combination of video monitoring, digital EEG, and the patient's history must be used to formulate the diagnosis.

Dynamics of cerebral blood flow velocities during normal human sleep

Bilateral flow patterns of the middle cerebral artery (MCA) were recorded continuously throughout the night in 18 healthy male subjects (mean age 27.4 years) by a computer-assisted pulsed Doppler (2 MHz) system together with simultaneous polysomnography. After inception of sleep, mean flow velocity (MFV) decreased steadily during deepening sleep stages reaching − 15.0 ± 3.6% ( p < 0.001) in the right MCA and −16.2 ± 3.4% in the left MCA ( p < 0.001) in stage 4 of the first sleep cycle compared to the waking state. Lowest MFV values were found in stage 2 preceding the last REM period (right MCA: − 19.2 ± 4.1%: left MCA: − 19.7 ± 5.1%). Changing from non-REM into REM sleep, a sudden rise of MFV, which varied from 8.9% (first sleep cycle, left MCA) to 18% (last sleep cycle, right MCA), could be consistently detected indicating a coupling of cerebral electrical activity and cerebral perfusionin REM sleep. During non-REM sleep this concomitant change of MFV and EEG activity was only found in the first sleep cycle, whereas no parallel changes could be observed in later sleep cycles. These results indicate a decoupling of EEG measured cerebral electrical activity and perfusion and suggest that factors other than metabolic mechanisms contribute to the regulation of cerebral perfusion during human non-REM sleep.

Sleep architecture in agenesis of the corpus callosum: laboratory assessment of four cases.

Whether the corpus callosum is essential for normal human sleep cannot be decided from current knowledge. We thus studied sleep architecture in four subjects with agenesis of the corpus callosum (ACC) and four control subjects matched for age, gender, and hand preference. All-night EEG, EOG, and EMG activity were monitored in the laboratory for one adaptation night and one data acquisition night. Standard sleep variables were calculated for the second night. Agenesis subjects were found to have a greater percentage of stage 3 + 4 sleep and a lower percentage of stage 2 sleep than control subjects. Agenesis subjects also tended to have more REM sleep periods and a shorter REM cycle length than controls. The pattern of results is similar to that produced by partial callosotomy. It is also relevant to two hypotheses about the function of the corpus callosum in sleep. First, the corpus callosum may facilitate synchronization of activity between homologous regions in the two hemispheres but interfere with synchronization of neuronal populations within each hemisphere. Its absence may thus explain both an augmentation of slow-wave activity (and thus more slow-wave sleep) and a decrease in interhemispheric EEG coherence. Secondly, the corpus callosum may play a role in the regulation of the ultradian rhythm which underlies timing and duration of REM sleep.

Lack of Effect of External Warming on Sleep Architecture in Sleep Apnea/Hypopnea Syndrome

Sleep apnea/hypopnea syndrome (SAHS) is characterized by nocturnal apneas (A) and/or hypopneas (H) occurring in various sleep stages. However, these disordered breathing events (DBE) occur rarely in slow-wave sleep (SWS) and are most severe in rapid eye movement (REM) sleep when severe hypoxemia results. Several studies have shown that a rise in body temperature by external warming, induced according to a specific protocol, affects normal human sleep architecture by diminishing the time spent in REM and increasing the time spent in SWS. The purpose of this study was to determine if external warming is as effective in sleep apneic patients in decreasing REM and increasing SWS, hoping that DBE and hypoxemia may diminish. Seven newly diagnosed patients were studied two more nights, on one of which (selected randomly) the sleep study was preceded by sitting in a warm bathtub with temperature of 41 degrees C for 1/2 h, 2 1/2 h before the start of sleep study. The mean maximum rise in oral temperature with warm bath was 2.0 +/- 0.4 degrees C. Total bed time (min) and sleep efficiency, REM, and SWS (%) were, respectively, 320 +/- 17 (SD), 81 +/- 8, 19 +/- 7, and 1.2 +/- 1.1 for the control (C) and 339 +/- 33, 79 +/- 11, 19 +/- 5, and 2.4 +/- 1.6 for the bath (B) night. In both C and B, the lowest O2 saturation (%) occurred in REM sleep and was 78 +/- 7 and 77 +/- 9, respectively. Comparing respective paired values between C and B, no significance was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the antidepressant Org 3770 on human sleep

The effect of a single dose (30 mg) of Org 3770 (metirzapine) on human sleep was assessed in a double blind, placebo controlled, cross over study in 6 young, healthy male volunteers. The sleep stage classification was based on visual scoring of 24 h electroencephalographic recordings according to the criteria of Rechtschaffen and Kales. Org 3770 30 mg p.o. given 2 h before bedtime had a sleep promoting action in all subjects, resulting in a shortened time to the onset of sleep. Bedtime waking and dozing (Stage 1) were reduced in favour of deep, slow wave sleep (Stages 3 and 4). Org 3770 increased the latency of REM sleep with respect to Stage 2 sleep in all subjects. It also caused a minor reduction in waking periods during REM sleep and a lower frequency of awakenings after periods of movement. No effect of Org 3770 was observed in reaction and vigilance tests on the post treatment day. The observed effects of Org 3770 on normal human sleep suggest that it might ameliorate the sleep disturbances encountered in endogenous depression, which are characterized by a reduction in slow wave sleep, an increase in nighttime awakenings and shortening of REM sleep latency.

A method of quantitative analysis of the regularity of the REM episodes distribution in normal human sleep

A method of quantitative analysis of the regularity of the REM episodes distribution in normal human sleep

Patterns in the distribution of REM sleep in normal human sleep.

Results are reported of four analyses of the distribution of REM sleep across nights of two subjects who slept for 50 consecutive nights on a regimented, but normal, sleep schedule. We found (a) a strong phase-setting effect of sleep onset on the distribution of REM sleep within nights, (b) no systematic change in the phase of the distribution of REM sleep across nights, and (c) a relationship between the nocturnal temperature minimum and the distribution of REM sleep within nights. Our results are consistent with the notion that the nightly distribution of REM sleep may be determined by an oscillatory process, the phase of which is reset at sleep onset, but which may be subject to other influences, such as the circadian temperature rhythm. These results are in general agreement with those found by investigators studying subjects on free-running or other abnormal sleep schedules.

The effect of naloxone on normal human sleep

Placebo and naloxone (4, 8, and 12 mg) were infused on seperation nights in a double-blind fashion over a 20-min period between the 25th and 45th min of sleep in normal volunteers. Naloxone produced a dose-dependent increase in REM latency (the time from onset of sleep until the first REM period), and duration of the first REM period and second NREM period. The number of REM periods was also reduced.

The time-dependent induction of REM sleep and arousal by physostigmine infusion during normal human sleep

The time-dependent induction of REM sleep and arousal by physostigmine infusion during normal human sleep

Studies of information processing in sleep.

ABSTRACTTwo studies of information processing in normal human sleep are reported. In Experiment I it was found that subjects responded differentially in stage 2 sleep to “own name,”“other name,” and tone stimuli (decreasing in that order) as reflected in both the finger plethysmograph (FP)and heart rate (HR) and to some extent the EEG K‐complex response, and similarly in REM sleep as reflected in the FP measure and to some extent the HR measure, but not in sleep stage 3–4. In Experiment II it was found that conditioned discrimination acquired during wakefulness persisted in sleep stage 4, as reflected in the FP and HR measures, and sleep stage 2, as reflected in the K‐complex response, but not in REM sleep. Results are compared to other studies of information processing in sleep. It is concluded that the results appear to indicate differential availability of the mechanisms of long‐term memory, short‐term memory, and stimulus preprocessing in the various stages of sleep. The authors further noted a bifurcation of the autonomic nervous system in sleep into two discrete effector limbs: electrodermal and cardiovascular.

Electroencephalography (EEG) of Human Sleep: Clinical Applications

This monograph describes the normative pattern of electroencephalographic and polygraphic physiological recording of normal human nocturnal sleep and represents work carried out in the authors' laboratory during a period of 13 years. The 6,000 recordings of several hundred subjects span the age range from the neonate to more than 70 years. Approximately two thirds of the monograph is composed of tables and figures. The authors emphasize that their studies provide a normative base for the future characterization of sleep disorders and include one chapter that discusses present concepts of disorders of sleep. With the increasing number of sleep disorder clinics in the United States, this monograph is, therefore, timely and is an important contribution to the field. Two aspects of their report represent a particularly significant contribution. The authors find a significant and consistent difference of sleep stage patterns between men and women from puberty through age 70. Women have

Human cerebral blood flow during sleep and waking.

Human cerebral blood flow during sleep and waking.

Spontaneous middle ear muscle activity in man: a rapid eye movement sleep phenomenon.

Changes in compliance of the tympanic membrane have been detected in normal human sleep, presumably due to spontaneous contraction of the stapedius and tensor tympani muscles of the middle ear. In the waking state, these muscles generally respond to loud sound (middle ear reflex). Middle ear muscle activity typically erupts before or at the onset of rapid eye movement (REM) sleep and persists throughout the REM period in a discontinuous pattern resembling that exhibited by rapid eye movements. Approximately 80 percent of all nocturnal middle ear muscle activity is contained in REM sleep. Half of the remaining 20 percent occurs in the 10-minute intervals just prior to the onset of REM sleep. Middle ear muscle activity is often associated with other phasic events such as momentary enhancement of electromyogram inhibition, apnea, and K complexes. Rapid eye movements and middle ear muscle activity, though significantly correlated in REM sleep, are not always simultaneous.