Section of Psychopharmacology and Sleep Research
|
University of Zürich - Institute of Pharmacology and Toxicology Section of Psychopharmacology and Sleep Research |
OBJECTIVE: The relevance of the dimensional complexity (DC) for the analysis of sleep EEG data is investigated and compared to linear measures. METHODS: We calculated DC of artifact-free 1 min segments of all-night sleep EEG recordings of 4 healthy young subjects. Non- linearity was tested by comparing with DC values of surrogate data. Linear properties of the segments were characterized by estimating the self-similarity exponent alpha based on the detrended fluctuation analysis which quantifies the persistence of the signal and by calculating spectral power in the delta, theta, alpha and sigma bands, respectively. RESULTS: We found weak nonlinear signatures in all sleep stages, but most pronounced in sleep stage 2. Strong correlations between DC and linear measures were established for the self-similarity exponent alpha and delta power, respectively. CONCLUSIONS: The dimensional complexity of the sleep EEG is influenced by both linear and nonlinear features. It cannot be directly interpreted as a nonlinear synchronization measure of brain activity, but yields valuable information when combined with the analysis of linear measures.
Clinical Neurophysiology 114, 199-209 (2003).
In two previous studies we demonstrated that radiofrequency electromagnetic fields (RF EMF) similar to those emitted by digital radiotelephone handsets affect brain physiology of healthy young subjects exposed to RF EMF (900 MHz; spatial peak specific absorption rate [SAR] 1 W/kg) either during sleep or during the waking period preceding sleep. In the first experiment, subjects were exposed intermittently during an 8 h nighttime sleep episode and in the second experiment, unilaterally for 30 min prior to a 3 h daytime sleep episode. Here we report an extended analysis of the two studies as well as the detailed dosimetry of the brain areas, including the assessment of the exposure variability and uncertainties. The latter enabled a more in depth analysis and discussion of the findings. Compared to the control condition with sham exposure, spectral power of the non-rapid eye movement sleep electroencephalogram (EEG) was initially increased in the 9-14 Hz range in both experiments. No topographical differences with respect to the effect of RF EMF exposure were observed in the two experiments. Even unilateral exposure during waking induced a similar effect in both hemispheres. Exposure during sleep reduced waking after sleep onset and affected heart rate variability. Exposure prior to sleep reduced heart rate during waking and stage 1 sleep. The lack of asymmetries in the effects on sleep EEG, independent of bi- or unilateral exposure of the cortex, may indicate involvement of subcortical bilateral projections to the cortex in the generation of brain function changes, especially since the exposure of the thalamus was similar in both experiments (approx. 0.1 W/kg).
Bioelectromagnetics 24:262-276, (2003).
Several investigators of EEG time series reported a rejection of the null hypothesis of linear stochastic dynamics for epochs longer than 10 s. We examine whether this rejection is related to nonlinearity or to nonstationarity. Our approach is a combination of autoregressive (AR-) modeling and surrogate data testing. It is shown that the fraction of subsegments, for which the null hypothesis has to be rejected, increases with the length of the subsegments and can be related to fluctuations of the AR-coeficients on time scales in the range from 2 to 30 s.
Neurocomputing: 857-862, 2003.
The level of EEG slow-wave activity (SWA) is determined by the duration of prior sleep and waking. SWA is a marker of nonREM sleep intensity and may serve as an indicator of sleep homeostasis. The two-process model of sleep regulation posits the interaction of the homeostatic Process S and the circadian Process C. Also models of neurobehavioral functions (three-process model; interactive models of alertness and cognitive throughput) are based on the concept of an interaction between homeostatic and circadian factors. Whether the interaction is linear or nonlinear is still unresolved. Models may serve as a guiding principle for specifying the relationship between processes occurring at the macroscopic and microscopic level of analysis.
Frontiers in Bioscience 8, s683-693, May 1, 2003 PDF-File of the whole paper can be downloaded
Benzodiazepines reduce EEG slow-wave activity in non-REM sleep by potentiating GABAergic neurotransmission at GABAA receptors via a modulatory binding site. However, the mechanisms of action underlying the effects of benzodiazepines on sleep and the sleep EEG are still unknown. Slow waves during sleep are generated by the corticothalamic system and synchronized by the inhibitory GABAergic neurons of the reticular thalamic nucleus. This region contains exclusively a3-containing GABAA receptors. We investigated the role of these receptors in the mediation of diazepam effects on the sleep EEG by studying point-mutated mice in which the a3-GABAA receptor is diazepam-insensitive [a3(H126R)]. Sleep was recorded for 12 h after i. p. injection of 3 mg/kg diazepam or vehicle at light onset in a3(H126R) and wild-type controls (n = 13 - 17 per genottype). The main effect was a marked reduction of slow-wave activity (EEG power density in 0.75-4.00 Hz) in non-REM sleep and a concomitant increase in frequencies above 15.00 Hz in non-REM sleep and waking in both genotypes. Neither effect of diazepam differed significantly between the genotypes. Despite the exclusive expression of a3-containing a3-GABAA receptors in the reticular thalamic nucleus, these receptors do not seem to be critical for the mediation of the effects of diazepam on the sleep EEG.
Eur J Neurosci, 17 (2003) 2226-2230.
In mammals, circadian rhythms are driven by a pacemaker located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The firing rate of neurons within the SCN exhibits a circadian rhythm. There is evidence that individual neurons within the SCN act as circadian oscillators. Rhythm generation in the SCN was therefore modeled by a system of self-sustained oscillators. The model is composed of up to 10 000 oscillatory elements arranged in a square array. Each oscillator has its own (randomly determined) intrinsic period reflecting the widely dispersed periods observed in the SCN. The model behavior was investigated mainly in the absence of synchronizing zeitgebers. Due to local coupling the oscillators synchronized and an overall rhythm emerged. This indicates that a locally coupled system is capable of integrating the output of individual clock cells with widely dispersed periods. The period of the global output (average of all oscillators) corresponded to the average of the intrinsic periods and was stable even for small amplitudes and during transients. Noise, reflecting biological fluctuations at the cellular level, distorted the global rhythm in small arrays. The period of the rhythm could be stabilized by increasing the array size, which thus increased the robustness against noise. Since different regions of the SCN have separate output pathways, the array of oscillators was subdivided into four quadrants. Sudden deviations of periodicity sometimes appeared in one quadrant, while the periods of the other quadrants were largely unaffected. This result could represent a model for splitting, which has been observed in animal experiments. In summary, the multi-oscillator model of the SCN showed a broad repertoire of dynamic patterns, revealed a stable period (even during transients) with robustness against noise, and was able to account for such a complex physiological behavior as splitting.
J Theor Biol, 224 (2003) 63-78
Background: Changes in photoperiod and ambient temperature trigger seasonal adaptations in the physiology and behaviour of many species, including the Djungarian hamster. Exposure of the hamsters to a short photoperiod and low ambient temperature leads to a reduction of the polyphasic distribution of sleep and waking over the light and dark period. In contrast, a long photoperiod enhances the daily sleep-wake amplitude leading to a decline of slow-wave activity in NREM sleep within the light period. It is unknown whether these changes can be attributed specifically to photoperiod and/or ambient temperature, or whether endogenous components are contributing factors. The influence of endogenous factors was investigated by recording sleep in Djungarian hamsters invariably maintained at a low ambient temperature and fully adapted to a short photoperiod. The second recording was performed when they had returned to summer physiology, despite the maintenance of the 'winter' conditions. Results: Clear winter-summer differences were seen in sleep distribution, while total sleep time was unchanged. A significantly higher light-dark cycle modulation in NREM sleep, REM sleep and waking was observed in hamsters in the summer physiological state compared to those in the winter state. Moreover, only in summer, REM sleep episodes were longer and waking bouts were shorter during the light period compared to the dark period. EEG power in the slow-wave range (0.75–4.0 Hz) in both NREM sleep and REM sleep was higher in animals in the summer physiological state than in those in the 'winter' state. In winter SWA in NREM sleep was evenly distributed over the 24 h, while in summer it decreased during the light period and increased during the dark period. Conclusion: Endogenous changes in the organism underlie the differences in sleep-wake redistribution we have observed previously in hamsters recorded in a short and long photoperiod.
BMC Neuroscience, 4 (2003) 9
Sleep was investigated in 10 captive gelada baboons (Theropithecus gelada), belonging to two harem groups by continuous infrared video recording (n = 4 males, n = 3 females, n = 3 juveniles). The aim was to investigate the relation between sleep and social status. Social status was assessed during daytime activities, when the two harem groups interacted. Three behavioral states (waking, transitional sleep and relaxed sleep) as well as sleep fragmentation were scored based on movements and body posture. The individuals belonging to each of the harem groups spent most of the night huddled closely together within a sleeping cluster. Sleep was considerably fragmented in all adult and subadult individuals. No relation was found between sleep latency or sleep fragmentation and social rank. Total sleep time was 11.4 ± 0.5 h per night (n = 10) and was negatively correlated with age. In the four males sleep duration was unrelated to their social rank, whereas both within the females and the juveniles it increased with decreasing rank. The amount of relaxed sleep was lower in the dominant males and the dominant females compared to the corresponding low-ranking ones. In contrast, dominant males had the highest amount of transitional sleep, while in the females no rank-association was evident. These results indicate that the high-ranking geladas engaging less in a relaxed sleeping posture may be maintaining a larger degree of alertness that would enable them to react quickly to nocturnal dangers.
Behav. Brain Res., 147 :9-15 (2003).
Study Objectives: Emerging from daily torpor, Djungarian hamsters (Phodopus sungorus) show an initial increase in electroencephalographic
slow-wave activity (power density between 0.75 and 4.0 Hz) during sleep that gradually declines. This feature is typical for sleep following prolonged
waking and supports the hypothesis that sleep pressure increases during daily torpor. After hamsters were subjected to sleep deprivation or
partial non-rapid eye movement sleep deprivation immediately following torpor, slow-wave activity remained high and decreased only when sleep
was allowed. An analysis of the dynamics of the process underlying the build-up of sleep pressure during episodes of waking and torpor may provide
insights into the regulation of normal sleep and wakefulness. We have analyzed in more detail the timecourse of the process that is common
for waking and daily torpor and that could account for the subsequent increase in slow-wave activity.
Design: Continuous 24-hour recordings of electroencephalography, electromyography, cortical temperature, and electroencephalographic spectral
analysis were performed. Torpor data of 28 hamsters and sleep-deprivation data of diverse durations collected previously in 15 hamsters wereanalyzed.
Interventions: Sleep deprivation.
Measurements and Results: Slow-wave activity invariably increased as a function of the duration of both prior waking and torpor. However, the
time constant of the build-up of slow-wave activity was approximately 2.75 times slower during torpor compared to sleep deprivation. Brain temperature
recorded during the torpor bouts was 10º to 12ºC below euthermic brain temperature. Therefore, the temperature coefficient of the time constant
for the slow–wave-activity increase is between 2.3 and 2.8, a range typical for biochemical processes.
Conclusions: We conclude that the processes occurring during daily torpor in the Djungarian hamster are similar to those occurring during sleep
deprivation, but the build-up of sleep pressure during torpor appears to be slowed down by the lower brain temperature.
Sleep 26:567-572 (2003).
Treatment with the monoamine oxidase inhibitor phenelzine completely suppressed rapid eye movement (REM) sleep in five depressed patients. Hypothesizing that increased serotonergic neurotransmission eliminated REM sleep, we administered a tryptophan-free amino acid drink (TFD) known to reduce plasma tryptophan and brain levels of serotonin. The TFD reversed the REM sleep suppression, while the control drink (TFD plus tryptophan) had virtually no effect on sleep. Neither TFD nor control drink affected mood, total sleep time, sleep efficiency or the all-night electroencephalogram power spectra in non- rapid eye movement (NREM) sleep. We report the first non-disruptive, double-blind method for studying human subjects overnight with and without REM sleep. It opens up a novel strategy for investigating the functions of REM sleep, and the roles of serotonin and REM sleep in the regulation of NREM sleep and mood.
Journal of Sleep Research 12:13-18 (2003)