Section of Psychopharmacology and Sleep Research
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University of Zürich - Institute of Pharmacology and Toxicology Section of Psychopharmacology and Sleep Research |
The two-process model of sleep regulation postulates that a homeostatic and a circadian process underlie sleep regulation. The timing of sleep and waking is accounted for by the interaction of these two processes. The assumptions of two separate processes or of a single process resulting from their additive interaction are mathematically equivalent but conceptually different. Based on an additive interaction, subjective alertness ratings in a forced desynchrony protocol and subjective sleepiness ratings in a photoperiod experiment were simulated. The correspondence between empirical and simulated data supports the basic assumption of the model.
Biol. Cybern. 71 (1994): 115-121.
EEG signals have been considered to be generated either by stochastic processes or by non-linear deterministic systems exhibiting chaotic behavior. To address this problem, the correlation dimension of the EEG was computed and compared to the correlation dimension of an artificial signal with identical power spectrum. By using a new type of personal super computer we were able for the first time to calculate the correlation dimension for the sleep episode of an entire night as well as for the corresponding artificial signal. The correlation dimension was high in episodes of rapid eye movement (REM) sleep, declined progressively within each non-REM sleep episode, and reached a low level at times when EEG slow waves (0.75-4.5 Hz) were dominant. The correlation dimension of the artificial signal and the EEG changed largely in parallel, although on average the values of the artificial signal were 7.3% higher. These results do not support the hypothesis that the sleep EEG is generated by a chaotic attractor.
Electroencephalogr. Clin. Neurophysiol. 90 (1994): 384-387.
The complexity of the electroencephalogram (EEG) during human sleep can be estimated by calculating the correlation dimension. Due to the large number of calculations required by this approach, only selected short (4-164 s) segments of the sleep EEG have been analysed previously. By using a new type of personal supercomputer, we were able to calculate the correlation dimension of overlapping 1 min EEG segments for the entire sleep episode (480 min) of 11 subjects and thereby delineate the time course of the changes. The correlation dimension was high in episodes of rapid eye movement (REM) sleep, declined progressively within each non-REM sleep episode, and reached a low level at times when EEG slow waves (0.75-4.5 Hz) were dominant. However, whereas slow- wave activity showed its typical progressive decline from non-REM/REM sleep cycle 1 to 4, no such trend was present for the correlation dimension. By providing an estimate of the complexity of a signal and being independent of amplitude and frequency measures, the correlation dimension represents a novel approach to exploring the dynamics of sleep and the processes underlying its regulation.
Eur. J. Neurosci. 6 (1994): 497-500.
The effect of triazolam (0.25 mg) and placebo was investigated in healthy, male subjects who slept in a sitting position. After the intake of placebo, sleep efficiency, rapid eye movement (REM) sleep and subjective sleep quality were lower than in the preceding sleep episode in bed, while stage 1 and REM sleep latency were higher. Triazolam did not prevent this impairment of sleep. However, in comparison with the placebo condition, the percentage of slow wave sleep was higher in the first third of the night, and in the morning sleep was rated as more quite. EEG power density in nonREM sleep was reduced in the frequency range of 1.25-10.0 Hz and enhanced in the range of sleep spindles (12.25-13.0 Hz). These changes were still present in the last third of the night. In REM sleep, triazolam reduced spectral activity in some frequency bins between 4.25 and 10.0 Hz. The sitting position itself affected the nonREM sleep spectra, since the placebo level in the 2.25-21.0-Hz range exceeded the baseline level. We conclude that a 0.25 mg dose of triazolam does not effectively counteract a posture-induced sleep disturbance, but induces changes in the EEG spectra which are typical for benzodiazepine receptor agonists.
Psychopharmacol. (Berl.) 114 (1994): 209-214.
Electroencephalographic slow-wave activity (SWA; power density in the 0.75 to 4.5 Hz band) and spindle frequency activity (SFA; 11.25 to 15.0 Hz) exhibit a typical time course and a distinct mutual relationship during sleep. Because benzodiazepines (BDZ) suppress SWA and enhance SFA, we investigated the effect of two BDZ-receptor agonists on the dynamics of these EEG parameters. A single dose of midazolam (15 mg), zopiclone (7.5 mg), or placebo was administered before bedtime to healthy young men. Although the two drugs reduced SWA and enhanced SFA, their time course across and within sleep cycles as well as their mutual relationship were little affected. The results constitute further evidence that hypnotics acting as BDZ-receptor agonists do not substantially interfere with the homeostatic aspect of sleep regulation.
Neuropsychopharmacology 11 (1994): 237-244.
The impairment of sleep quality is a common complaint during pregnancy. To investigate the changes in sleep in the course of pregnancy, the sleep electroencephalogram (EEG) was recorded and analyzed in nine healthy women on 2 consecutive nights during each trimester of pregnancy. Waking after sleep onset increased from the second (TR2) to the third (TR3) trimester, whereas rapid eye movement (REM) sleep decreased from the first trimester (TR1) to TR2. Spectral analysis of the EEG in nonrapid eye movement (NREM) sleep revealed a progressive reduction of power density in the course of pregnancy. In comparison to TR1, the values in TR2 were significantly lower in the 10.25-11.0-Hz and 14.25-17.0-Hz bands. In TR3, the significant reduction extended over the ranges of 1.25-12.0 Hz and 13.25-16.0 Hz. The largest decrease (30%) occurred in the 14.25-15.0-Hz band. In REM sleep, the spindle frequency range was not affected, and a minor reduction of power density in some frequency bins below 12 Hz was present only in TR3. The study documents major alterations of the sleep EEG that are not evident from the sleep scores and that may be associated with the characteristic hormonal changes occurring during pregnancy.
Sleep 17 (1994): 576-582.
To investigate the dynamics of heart rate in the course of sleep and to relate cardiac activity to sleep intensity, the electrocardiogram was recorded concomitantly with the polysomnogram in healthy young males. Heart rate was assessed across consecutive non-REM sleep (NREMS)-REM sleep (REMS) cycles as well as within individual episodes of NREMS and REMS. Within a sleep cycle, heart rate was lower in the NREMS episode than in the subsequent REMS episode. A global declining trend was present over successive NREMS episodes and over successive REMS episodes. A rapid increase of heart rate at the NREMS-REMS transitions was followed by a slow decline that started within the REMS episodes. Heart rate variability was higher in REMS than in NREMS and showed an increasing trend over successive REMS episodes but not over successive NREMS episodes. EEG slow-wave activity (spectral power density in the 0.75-4.5 Hz band), an intensity measure of NREMS, declined across NREMS episodes and was not correlated with heart rate. The global trends and ultradian variations of heart rate may represent sleep state-dependent modulations and circadian variations of the autonomic nervous system, which are not fully reflected in the sleep EEG.
Physiol. Behav. 55 (1994): 769-774.
The Djungarian hamster (Phodopus sungorus) is a markedly photoperiodic rodent which exhibits daily torpor under short photoperiod. Normative data were obtained on vigilance states, electroencephalogram (EEG) power spectra (0.25- 25.0 Hz), and cortical temperature (TCRT) under a 16:8 h light-dark schedule, in 7 Djungarian hamsters for 2 baseline days, 4 h sleep deprivation (SD) and 20 h recovery. During the baseline days total sleep time amounted to 59% of recording time, 67% in the light period and 43% in the dark period. The 4 h SD induced a small increase in the amount of non-rapid eye movement (NREM) sleep and a marked increase in EEG slow-wave activity (SWA; mean power density 0.75-4.0 Hz) within NREM sleep in the first hours of recovery. TCRT was lower in the light period than in the dark period. It decreased at transitions from either waking or rapid eye movement (REM) sleep to NREM sleep, and increased at the transition from NREM sleep to waking or REM sleep. After SD, TCRT was lower in all vigilance states. In conclusion, the sleep-wake pattern, EEG spectrum, and time course of TCRT in the Djungarian hamster are similar to other nocturnal rodents. Also in the Djungarian hamster the time course of SWA seems to reflect a homeostatically regulated process as was formulated in the two-process model of sleep regulation.
J. Comp. Physiol. A 174 (1994): 145-155.
Sleep, daily torpor and hibernation are considered to be homologous processes. However, during periodic arousals from hibernation, ground squirrels spent most of the euthermic period in non-REM sleep. Therefore, it has been proposed that animals arouse regularly from hibernation to recover from a sleep deprivation (SD) incurred during hibernation. We demonstrate in the Djungarian hamster that EEG slow-wave activity (EEG power density in the 0.75-4-Hz range), which is increased after SD, is enhanced in a similar way after an episode of daily torpor. The results support the hypothesis that daily torpor is incompatible with the restorative function of sleep.
Neurosci. Lett. 166 (1994): 35-38.
In view of the reports that in the human magnetoencephalogram, 40-Hz oscillations are more abundant in waking and REM sleep than in non-REM sleep, we performed a 24-h broad-band (0.25-64 Hz) spectral analysis of the electrocorticogram in unrestrained rats. Spectral power above 33 Hz was higher in waking and REM sleep than in non-REM sleep, and in the range of 6-38 Hz it was higher in REM sleep than in waking. Consistent frequency-specific changes in spectral power marked the transitions between vigilance states. The study demonstrates that the rat EEG exhibits state- and frequency-specific changes over a large frequency range.
Neurosci. Lett. 167 (1994): 89-92.
The hypothesis that local activation of brain regions during wakefulness affects the EEG recorded from these regions during sleep was tested by applying vibratory stimuli to one hand prior to sleep. Eight subjects slept in the laboratory for five consecutive nights. During a 6-h period prior to night 3, either the left or the right hand was vibrated intermittently (20 min on -8 min off), while prior to night 5 the same treatment was applied to the contralateral hand. The sleep EEG was recorded from frontal, central, parietal and occipital derivations and subjected to spectral analysis. The interhemispheric asymmetry index (IAI) was calculated for spectral power in nonREM sleep in the frequency range of 0.25-25.0 Hz for 0.5-Hz or 1-Hz bins. In the first hour of sleep following right-hand stimulation, the IAI of the central derivation was increased relative to baseline, which corresponds to a shift of power towards the left hemisphere. This effect was most prominent in the delta range, was limited to the first hour of sleep and was restricted to the central derivation situated over the somatosensory cortex. No significant changes were observed following left-hand stimulation. Although the effect was small, it is consistent with the hypothesis that the activation of specific neuronal populations during wakefulness may have repercussions on their electrical activity pattern during subsequent sleep.
J. Sleep Res. 3 (1994): 159-164.
Since the rat is a nocturnal animal sleep experiments in this species are commonly performed during the light period of the 24-h light-dark (LD) cycle. To examine whether light itself affects sleep, chronically implanted albino rats were continuously recorded for a day under a 12-h light-12-h dark cycle (light intensity approx. 300 lx) and on the subsequent day in constant darkness (DD). In the absence of light, EEG slow-wave activity (0.75-4.0 Hz) in non-REM sleep and sleep continuity were significantly enhanced, while total sleep time and cortical temperature were not affected. The results show that in the albino rat room light impairs sleep by reducing its intensity and continuity.
Behav. Brain Res. 63 (1994): 205-211.
To investigate the relationship between thermoregulation and sleep regulation, rats were sleep-deprived for 3 hours at two different ambient temperatures. Sleep deprivations (SD) were performed at 23 degrees C (SD-23) and at 32 degrees C (SD-32) in the beginning of the 12-h light period in animals chronically implanted with ECoG and EMG electrodes, and with epidural and hypothalamic thermistors. SD-32 enhanced cerebral temperature more than SD-23 at both brain sites. The SD-induced hyperthermia was followed by a fall of brain temperature below baseline. During recovery from either SD procedure, waking was reduced and sleep continuity increased. REM sleep was increased after SD-32. EEG slow-wave activity (spectral power density in the 0.75-4.0 Hz band) exceeded the baseline level in the first 3-h interval of recovery; however, the effects of SD-23 and SD-32 did not differ. In the same time interval, power density in the 1.25-1.5 Hz bin as well as in some bins in the theta and alpha band was higher after SD-32 than after SD-23. The increase in hypothalamic temperature during SD did not correlate with the increase in SWA during recovery. It is concluded that even a brief SD has major repercussions on recovery sleep whereas the extent of cerebral hyperthermia during SD is only a minor factor.
Arch. Ital. Biol. 132 (1994): 39-52.
The effects of melatonin (3 mg/kg i.p.) and the melatonin receptor agonist S-20098 (3 mg/kg i.p.) on the vigilance states, electroencephalogram power spectra (0.25-25.0 Hz), and cortical temperature were determined in eight rats in the first 6-hr interval of the 12-hr light period. Compared to the vehicle injection both compounds reduced the power density in non-rapid eye movement sleep in the low frequency range (1-8 Hz) but did not affect the vigilance states and brain temperature. The present findings do not indicate that the stimulation of the melatonin receptor exerts a hypnotic effect at doses that had been shown to affect the circadian rest-activity rhythm.
J. Pineal. Res. 16 (1994): 26-32.