Simulation of human sleep: ultradian dynamics of electroencephalographic slow-wave activity

The typical declining trend of electroencephalographic (EEG) slow-wave activity (SWA) within a sleep period is represented in the two-process model of sleep regulation by an exponentially decaying process (Process S). The model has been further elaborated to simulate not only the global changes of SWA, but also the dynamics within non-rapid-eye-movement (non-REM) sleep episodes. In this new model, the initial intraepisodic buildup of SWA is determined by the combined action of an exponentially increasing process and a saturation process, whereas its fall at the end of an episode is due to an exponentially decreasing process. The global declining trend of SWA over consecutive episodes results from the monotonic decay of the intraepisodic saturation level. In contrast to Process S in the two-process model, this decay is not represented by an exponential function, but is proportional to the momentary level of SWA. REM sleep episodes are triggered by an external function. The model allows one to simulate the ultradian pattern of SWA for baseline nights as well as changes induced by a prolonged waking period, a daytime nap, a partial slow-wave sleep deprivation, or an antidepressant drug.     

Long photoperiod restores the 24-h rhythm of sleep and EEG slow-wave activity in the Djungarian hamster (Phodopus sungorus)

Photoperiod influences the distribution of sleep and waking and electroencephalogram (EEG) power density in the Djungarian hamster. In an experimental procedure combining short photoperiod (SP) and low ambient temperature, the light-dark difference in the amount of sleep was decreased, and the changes in slow-wave activity (SWA) (mean EEG power density between 0.75 and 4.0 Hz) in nonrapid eye movement (NREM) sleep within 24 h were abolished. These findings, obtained in three different groups of animals, suggested that at the lower ambient temperature, the influence of the circadian clock on sleep-wake behavior was diminished. However, it remained unclear whether the changes were due to the photoperiod, ambient temperature, or both. Here, the authors show that EEG and electromyogram recordings in a single group of animals sequentially adapted to a short and long photoperiod (LP) at low ambient temperature (approximately 15 degrees C) confirm that EEG power is reduced in SP. Moreover, the nocturnal sleep-wake behavior and the changes in SWA in NREM sleep over 24 h were restored by returning the animals to LP and retaining ambient temperature at 15 degrees C. Therefore, the effects cannot be attributed to ambient temperature alone but are due to a combined effect of temperature and photoperiod. When the Djungarian hamster adapts to winter conditions, it appears to uncouple sleep regulation from the circadian clock.     

Interaction of systems generating spindles and delta waves as a possible mechanism for the development of slow-wave sleep

Certain correlations between spindling and delta-activity during slow-wave sleep (SWS) development have been studied in experiments on man and animals. Interaction between systems of delta-activity and spindling generation is discussed as a possible mechanism underlying development of SWS. Amplitude-modulated stimulation of non-specific thalamic structures has been shown to influence this interaction and development of sleep processes.     

Loss of Gnas imprinting differentially affects REM/NREM sleep and cognition in mice

It has been suggested that imprinted genes are important in the regulation of sleep. However, the fundamental question of whether genomic imprinting has a role in sleep has remained elusive up to now. In this work we show that REM and NREM sleep states are differentially modulated by the maternally expressed imprinted gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and complex cognitive processes are enhanced while REM and REM-linked behaviors are inhibited. This is the first demonstration that a specific overexpression of an imprinted gene affects sleep states and related complex behavioral traits. Furthermore, in parallel to the Gnas overexpression, we have observed an overexpression of Ucp1 in interscapular brown adipose tissue (BAT) and a significant increase in thermoregulation that may account for the REM/NREM sleep phenotypes. We conclude that there must be significant evolutionary advantages in the monoallelic expression of Gnas for REM sleep and for the consolidation of REM-dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave activity in NREM sleep, and this results in a reduction of uncertainty in temporal decision-making processes.     

Alterations in EEG activity and sleep after influenza viral infection in GHRH receptor-deficient mice.

Viral infections induce excess non-rapid eye movement sleep (NREMS) in mice. Growth hormone-releasing hormone receptor (GHRH receptor) was previously identified as a candidate gene responsible for NREMS responses to influenza challenge in mice. The dwarf lit/lit mouse with a nonfunctional GHRH receptor was used to assess the role of the GHRH receptor in viral-induced NREMS. After influenza A virus infection the duration and intensity [electroencephalogram (EEG) delta power] of NREMS increased in heterozygous mice with the normal phenotype, whereas NREMS and EEG delta power decreased in homozygous lit/lit mice. Lit/lit mice developed a pathological state with EEG slow waves and enhanced muscle tone. Other influenza-induced responses (decreases in rapid eye movement sleep, changes in the EEG high-frequency bands during the various stages of vigilance, hypothermia, and decreased motor activity) did not differ between the heterozygous and lit/lit mice. GH replacement failed to normalize the NREMS responses in the lit/lit mice after influenza inoculation. Decreases in NREMS paralleled hypothermia in the lit/lit mice. Lung virus levels were similar in the two mouse strains. Lit/lit mice had a higher death rate after influenza challenge than the heterozygotes. In conclusion, GHRH signaling is involved in the NREMS response to influenza infection.     

Role of biological membranes in slow-wave sleep

Two involvements of cellular membranes in slow-wave sleep (SWS) are discussed. In the first the endoplasmic reticulum (ER) is focussed upon, and in the second, the plasmalemma, where specific binding sites (receptors?) for promoters of slow-wave sleep are believed to be located. The study concerning the ER focusses on an enzyme in the brain, glucose-6-phosphatase, which, although present at low levels, manifests greatly increased activity during SWS compared to the waking state. The work on the plasmalemma has to do with the specific binding of muramyl peptides, inducers of slow-wave sleep, to various cells, and membrane preparations of various sorts, including those from brain tissue. Such cells as macrophages from mice, B-lymphocytes from human blood, and cells from a cell line (C-6 glioma) have been examined in this context.     

Sleep: sequential reduction of paradoxical (REM) and elevation of slow-wave (NREM) sleep by a non-convulsive dose of insulin in rats

Administration of a single non-convulsive dose of insulin (1.0, I.U./kg., I.P.) which produced no observable gross behavioral changes in rats, reduced rapid eye movement (REM) sleep time 100% in the first 3 hrs. and 82% by the 4th hr., reaching control subject levels (saline-treated) by the 6th hr. In contrast, slow-wave sleep (NREM) time in insulin treated animals exceeded control subject levels by 49% by the end of the 2nd hr., returning to normal by the 5th hr. Although there was no difference between insulin and saline treated rats for the total 8 hr. post-injection recording period for total percentage of time awake, or slow-wave sleep time, a 44% reduction in REM sleep time was observed in insulin treated animals compared to that of a saline treated control. The significance of these findings are discussed in terms of known neurochemical changes i.e., an increase of both brain tryptophan and serotonin in rats, induced by a subconvulsive dose of exogenous insulin.     

Effect of cold stimulation during slow-wave sleep on sleep cycle

To clarify the effect of cold stimulation during slow-wave sleep (SWS) on the sleep cycle, we conducted a sleep experiment. Five healthy males slept on a bedding system we developed to make the inside of bedding cooler. When the subject was sleeping deeply in the second and fourth SWS, the system cooled their bedding. When the subject's sleep condition shifted toward arousal, the cold air was stopped. As a result, all subjects’ sleep stage shifted to light sleep and reached arousal. After stopping stimulation, they immediately returned to the SWS at the first stimulation. But at the second stimulation, the sleep state did not return to the SWS.     

Regional slow waves and spindles in human sleep

The most prominent EEG events in sleep are slow waves, reflecting a slow (<1 Hz) oscillation between up and down states in cortical neurons. It is unknown whether slow oscillations are synchronous across the majority or the minority of brain regions--are they a global or local phenomenon? To examine this, we recorded simultaneously scalp EEG, intracerebral EEG, and unit firing in multiple brain regions of neurosurgical patients. We find that most sleep slow waves and the underlying active and inactive neuronal states occur locally. Thus, especially in late sleep, some regions can be active while others are silent. We also find that slow waves can propagate, usually from medial prefrontal cortex to the medial temporal lobe and hippocampus. Sleep spindles, the other hallmark of NREM sleep EEG, are likewise predominantly local. Thus, intracerebral communication during sleep is constrained because slow and spindle oscillations often occur out-of-phase in different brain regions.     

Thalamic T-type Ca2+ channels and NREM sleep

T-type Ca2+ channels play a number of different and pivotal roles in almost every type of neuronal oscillation expressed by thalamic neurones during non-rapid eye movement (NREM) sleep, including those underlying sleep theta waves, the K-complex and the slow (<1 Hz) sleep rhythm, sleep spindles and delta waves. In particular, the transient opening of T channels not only gives rise to the 'classical' low threshold Ca2+ potentials, and associated high frequency burst of action potentials, that are characteristically present during sleep spindles and delta waves, but also contributes to the high threshold bursts that underlie the thalamic generation of sleep theta rhythms. The persistent opening of a small fraction of T channels, i.e. I(Twindow), is responsible for the large amplitude and long lasting depolarization, or UP state, of the slow (<1 Hz) sleep oscillation in thalamic neurones. These cellular findings are in part matched by the wake-sleep phenotype of global and thalamic-selective CaV3.1 knockout mice that show a decreased amount of total NREM sleep time. T-type Ca2+ channels, therefore, constitute the single most crucial voltage-dependent conductance that permeates all activities of thalamic neurones during NREM sleep. Since I(Twindow) and high threshold bursts are not restricted to thalamic neurones, the cellular neurophysiology of T channels should now move away from the simplistic, though historically significant, view of these channels as being responsible only for low threshold Ca2+ potentials.     

Determinants of long-term facilitation in humans during NREM sleep.

Long-term facilitation (LTF) is a prolonged increase in ventilatory motor output after episodic peripheral chemoreceptor stimulation. We have previously shown that LTF is activated during sleep following repetitive hypoxia in snorers (Babcock MA and Badr MS. Sleep 21: 709-716, 1998). The purpose of this study was 1) to ascertain the relative contribution of inspiratory flow limitation to the development of LTF and 2) to determine the effect of eliminating inspiratory flow limitation by nasal CPAP on LTF. We studied 25 normal subjects during stable non-rapid eye movement sleep. We induced 10 episodes of brief repetitive isocapnic hypoxia (inspired O(2) fraction = 8%; 3 min) followed by 5 min of room air. Measurements were obtained during control and at 20 min of recovery (R(20)). During the episodic hypoxia study, inspiratory minute ventilation (Vi) increased from 6.7 +/- 1.9 l/min during the control period to 8.2 +/- 2.7 l/min at R(20) (122% of control; P < 0.05). Linear regression analysis confirmed that inspiratory flow limitation during control was the only independent determinant of the presence of LTF (P = 0.005). Six subjects were restudied by using nasal continuous positive airway pressure to ascertain the effect of eliminating inspiratory flow limitation on LTF. Vi during the recovery period was 97 +/- 10% (P > 0.05). In conclusion, 1) repetitive hypoxia in sleeping humans is followed by increased Vi in the recovery period, indicative of development of LTF; 2) inspiratory flow limitation is the only independent determinant of posthypoxic LTF in sleeping human; 3) elimination of inspiratory flow limitation abolished the ventilatory manifestations of LTF; and 4) we propose that increased Vi in the recovery period was a result of preferential recruitment of upper airway dilators by repetitive hypoxia.     

The dynamics of EEG entropy

The scaling properties of human EEG have so far been analyzed predominantly in the framework of detrended fluctuation analysis (DFA). In particular, these studies suggested the existence of power-law correlations in EEG. In DFA, EEG time series are tacitly assumed to be made up of fluctuations, whose scaling behavior reflects neurophysiologically important information and polynomial trends. Even though these trends are physiologically irrelevant, they must be eliminated (detrended) to reliably estimate such measures as Hurst exponent or fractal dimension. Here, we employ the diffusion entropy method to study the scaling behavior of EEG. Unlike DFA, this method does not rely on the assumption of trends superposed on EEG fluctuations. We find that the growth of diffusion entropy of EEG increments of awake subjects with closed eyes is arrested only after approximately 0.5 s. We demonstrate that the salient features of diffusion entropy dynamics of EEG, such as the existence of short-term scaling, asymptotic saturation, and alpha wave modulation, may be faithfully reproduced using a dissipative, first-order, stochastic differential equation—an extension of the Langevin equation. The structure of such a model is utterly different from the “noise+trend” paradigm of DFA. Consequently, we argue that the existence of scaling properties for EEG dynamics is an open question that necessitates further studies.     

The maturational trajectories of NREM and REM sleep durations differ across adolescence on both school-night and extended sleep

We recorded sleep electroencephalogram longitudinally across ages 9-18 yr in subjects sleeping at home. Recordings were made twice yearly on 4 consecutive nights: 2 nights with the subjects maintaining their ongoing school-night schedules, and 2 nights with time in bed extended to 12 h. As expected, school-night total sleep time declined with age. This decline was entirely produced by decreasing non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep durations increased slightly but significantly. NREM and REM sleep durations also exhibited different age trajectories when sleep was extended. Both durations exceeded those on school-night schedules. However, the elevated NREM duration did not change with age, whereas REM durations increased significantly. We interpret the adolescent decline in school-night NREM duration in relation to our hypothesis that NREM sleep reverses changes produced in plastic brain systems during waking. The "substrate" produced during waking declines across adolescence, because synaptic elimination decreases the intensity (metabolic rate) of waking brain activity. Declining substrate reduces both NREM intensity (i.e., delta power) and NREM duration. The absence of a decline in REM sleep duration on school-night sleep and its age-dependent increase in extended sleep pose new challenges to understanding its physiological role. Whatever their ultimate explanation, these robust findings demonstrate that the two physiological states of human sleep respond differently to the maturational brain changes of adolescence. Understanding these differences should shed new light on both brain development and the functions of sleep.     

Circadian rhythms of slow-wave sleep and paradoxical sleep are in opposite phase in genetically hypoprolactinemic rats

In eleven genetically hypoprolactinemic rats (IPL nude rats) and five control rats (OFA), the sleep-waking cycle was continuously registered for 14 days at two ambient temperatures. At 23 degrees C, the slow wave sleep (SWS) duration of IPL rats was significantly higher (+6.8%, t = 5.4, p less than 0.001) than that of control rats, while the paradoxical sleep (PS) duration was lowered by 31.8% (t = 9.4, p less than 0.001). The circadian rhythm of PS disappeared while that of SWS persisted unchanged. At 30 degrees C, both sleep durations reached the level of control rats. The circadian rhythm of PS was however completely reversed: the PS acrophase was at 01 h while that of SWS was at 12 hrs. This first observation of spontaneous dissociation of the two states of sleep supports the hypothesis of two distinct circadian clocks, one for SWS, another for PS. It is suggested that hypothalamic prolactin and/or other still unknown genetic alterations might be responsible for the observed change in the PS circadian rhythm.     

The spectral dynamics and its applications in EEG

The method of spectral dynamics is introduced to process slow changes in EEG. This method is based on evaluation of distance between EEG spectra. The typical application field is pharmaco-EEG after single dose drug administration, where distances between pre and post drug EEG spectra are computed. The distance between two spectra may be, however, defined in several different ways. The paper deals with the well known L _p metrics and with the metrics that plays an important role in discriminating stationary processes with different spectra. The L _p and metrics are non-equivalent and their properties, consistency and robustness, are studied in a simple statistical model.     

A double-blind investigation of the relationship between seizure activity and the sleep EEG following EEG biofeedback training

The sleep EEGs of eight medically refractory epileptic patients were examined as part of a double-blind, ABA crossover study designed to determine the effectiveness of EEG biofeedback for the control of seizures. The patients were initially reinforced for one of three EEG criteria recorded from electrodes placed over sensorimotor cortex: (a) suppression of 3- to 7-Hz activity, (b) enhancement of 12- to 15-Hz activity, or (c) simultaneous suppression of 3- to 7-Hz and enhancement of 11- to 19-Hz activity. Reinforcement contingencies were reversed during the second or B phase, and then reinstated in their original form during the final A′ phase. All-night polysomnographic recordings were obtained at the end of each conditioning phase and were subjected to both visual and computer-based power spectral analyses. Four of the patients showed changes in their nocturnal paroxysmal activity that were either partially or totally consistent with the ABA′ contingencies of the study. The spectral data proved difficult to interpret, though two trends emerged from the analyses. Decreases in nocturnal 4- to 7-Hz activity were correlated with decreases in seizure activity, and increases in 8- to 11-Hz activity were correlated with decreases in seizure activity. These findings were shown to strengthen the hypothesis that EEG biofeedback may produce changes in the sleep EEG that are related to seizure incidence.