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Section of Psychopharmacology and Sleep Research

Abstracts of papers published 1997


Low-frequency (< 1 Hz) oscillations in the human sleep EEG.

Achermann,P.; Borbély,A.A.

Low-frequency (< 1 Hz) oscillations in intracellular recordings from cortical neurons were first reported in the anesthetized cat and then also during natural sleep. The slow sequences of hyperpolarization and depolarization were reflected by slow oscillations in the EEG. The aim of the present study was to examine whether comparable low-frequency components are present in the human sleep EEG. All-night sleep recordings from 8 healthy young men were subjected to spectral analysis in which the low-frequency attenuation of the amplifier was compensated. During sleep stages with a predominance of slow waves and in the first two episodes of non-rapid-eye-movement (nonREM) sleep, the mean power spectrum showed a peak at 0.7-0.8 Hz (range 0.55-0.95 Hz). The typical decline in delta activity from the first to the second nonREM sleep episode was not present at frequencies below 2 Hz. To detect very low frequency components in the pattern of slow waves and sleep spindles, a new time series was computed from the mean voltage of successive 0.5-s epochs of the low-pass (< 4.5 Hz) or band-pass (12-15 Hz) filtered EEG. Spectral analysis revealed a periodicity of 20-30 s in the prevalence of slow waves and a periodicity of 4 s in the occurrence of activity in the spindle frequency range.

The results demonstrate that distinct components below 1 Hz are present also in the human sleep EEG spectrum. The differences in the dynamics between the component with a mean peak value at 0.7-0.8 Hz and delta waves above 2 Hz is in accordance with results from animal experiments.

Neuroscience 81 (1997): 213-222.


Dynamics of EEG spindle frequency activity during extended sleep in humans: relationship to slow-wave activity and time of day.

Aeschbach D., Dijk,D.J., Borbély A.A.

The dynamics of EEG spindle frequency activity (SFA; spectral power density in the 12.25-15.0 Hz range) and its relationship to slow-wave activity (SWA; 0.75-4.5 Hz) were investigated in long sleep episodes (>12 h). Young healthy men went to bed at either 19:00 h (early sleep; prior waking 36 h, N=9) or 24:00 h (late sleep; prior waking 17 h, N=8). In both nights, SWA in non-rapid-eye-movement sleep (NREMS) decreased over the first three to four 1.5-h intervals and remained at a low level in the subsequent five to six 1.5-h intervals. In contrast, the changes of SFA were more variable and differed between the lower (12.25-13.0 Hz), middle (13.25-14.0 Hz) and higher frequency bin (14.25-15.0 Hz). A pronounced influence of time of day was present in the lower and higher SFA bin, when the dynamics were analyzed with respect to clock time. In both the early and late sleep condition, power density in the lower bin was highest between 2:00 and 5:00 h in the morning and decreased thereafter. In the higher bin, power density was low in the early morning hours and increased as sleep was extended into the daytime hours. The results provide further evidence for a frequency-specific circadian modulation of SFA which becomes more evident at a time when SWA is low.

Brain Res. 748 (1997): 131-136


Pharmakologische Beeinflussung von Schlaf und Schlaf EEG durch Hypnotika.
[Pharmacological effects of hypnotics on sleep and the sleep EEG. Article in German]

Borbély A.A.

Benzodiazepine receptor agonists (BRA) are presently the hypnotics of first choice because of their favorable benefit-risk ratio. Their mechanisms of action on the molecular have been thoroughly investigated. BRA-hypnotics induce characteristic changes in the sleep EEG (“spectral benzodiazepine signature”) while leaving the sleep dynamics largely unaffected. The sleep EEG was shown to be a sensitive indicator of residual effects of sedative compounds (BRA-hypnotics, ethanol) and caffeine. Typical features of the sleep EEG (slow waves, spindles) are associated with variations of the membrane potential of thalamocortical neurones. The topographical analysis of the sleep EEG revealed time-dependent local changes which may be a consequence of the preferential use of brain areas during waking.

Somnologie 1 (1997): 42-45.


Chronic administration of melatonin reduces REM sleep in the Djungarian hamster (Phodopus sungorus).

Deboer T., Tobler I.

The prominent effects of photoperiod on sleep, electroencephalogram power spectra and cortical temperature in the Djungarian hamster may be mediated by melatonin. We investigated the effects of chronic subcutaneous melatonin application on these variables in Djungarian hamsters recorded in a short photoperiod (light:dark 8:16 hours). Melatonin abolished the light-dark difference in vigilance state distribution, reduced the amount of rapid eye movement (REM) sleep in the light period and the occurrence of REM sleep episodes. In contrast to the reduction of both cortical temperature and electroencephalogram power density in hamsters adapted to a short photoperiod these variables were unaffected by melatonin. Since the effects of chronic application of melatonin differ from those of shortening of the photoperiod it is improbable that melatonin mediates the effects.

Neurosci. Lett. 231 (1997): 118-122.


Vigilance state episodes and cortical temperature in the Djungarian hamster: the influence of photoperiod and ambient temperature.

Deboer T., Tobler I.

The electroencephalogram, electromyogram and cortical temperature (TCRT) were recorded in seven Djungarian hamsters adapted to a short photoperiod at 16°C ambient temperature (TA; SP16). A baseline day was followed by 4 h sleep deprivation (SD) and 20 h recovery. The analysis included data obtained in earlier experiments at 22°C TA in a long (LP22) and short photoperiod (SP22).

In all three conditions the changes in TCRT during vigilance state episodes were a function of episode duration and, for waking and NREM sleep, of TCRT at episode onset. The increase in TCRT during REM sleep became progressively larger from LP22 to SP22 to SP16. After SD the mean TCRT decreased below baseline in the LP22 and stayed above baseline in the SP22. This difference in the effect of SD on TCRT was reflected in its increase during REM sleep, which was attenuated during recovery in LP22, but was enhanced in SP22. The time course of TCRT during NREM sleep or waking episodes was unaffected by SD. Therefore, the overall difference in TCRT between baseline and recovery in the LP22 and SP22 is due to changes in the increase in TCRT during REM sleep.

Pflügers Arch. 433, (1997): 230-237.


Selective and total sleep deprivation: effect on the sleep EEG in the rat.

Endo T., Schwierin B., Borbély A.A., Tobler I.

Although sleep deprivation is known to exert an antidepressant effect in depressed patients, the involvement of sleep regulation is still unknown. Selective sleep deprivation experiments were performed in the rat to investigate the interactions between non-REM sleep (NREMS) and REM sleep (REMS) in an animal model. A12-h total sleep deprivation (TD) period ending at lights on was followed by one of the following protocols: (1) recovery sleep (TD12); (2) 4-h total sleep deprivation (TD16); (3) 4-h slow-wave deprivation (SWD); (4) 4-h REMS deprivation (RD). In the SWD protocol, the reduction of EEG slow-wave activity (SWA; power density in the 0.75-4.0 Hz band) was obtained by curtailing NREMS episodes to 20 s. During RD the number of interventions required to prevent REMS increased during the first 2 h and then remained constant. While RD caused only a minor reduction of NREMS, it increasingly suppressed SWA in NREMS. The rebound of SWA occurred later and was less prominent after RD than after SWD. Whereas an REMS rebound occurred after all three 4-h sleep deprivation protocols, a persistent increase in the dark period was present only after TD16. It is concluded that (a) SWA in NREMS is inhibited by an increased level of REMS propensity; (b) the hypothesis that REMS propensity increases only during NREMS is not supported; and (c) the results are compatible with the hypothesis that the suppression of NREMS intensity is the common denominator of different antidepressive sleep manipulations in depressive patients.

Psychiatry Res. 66 (1997): 97-110.


Sleep and sleep regulation in normal and prion protein deficient mice.

Tobler,I.; Deboer,T.; Fischer,M.

Mice are the preferred mammalian species for genetic investigations of the role of proteins. The normal function of the prion protein (PrP) is unknown although it plays a major role in the prion diseases, including fatal familial insomnia. Most gene targeting experiments are performed in the 129 strain whose behavior is not well characterized. We compared sleep and the EEG spectrum before and after 6 h sleep deprivation in PrP knockout mice (129/SV) and wild-type controls (backcross 129/SV with C57BL/6). Although no difference was evident in the amount of vigilance states, the null mice exhibited a much larger degree of sleep fragmentation than the wild-type with almost double the amount of short waking episodes. As in other rodents, cortical temperature closely reflected the time course of waking. The increase of slow-wave activity (SWA; mean EEG power density in the 0.25-4.0 Hz range) within single non-rapid eye movement (NREM) sleep episodes was faster and reached a lower level in the null mice than in the wild-type. The contribution of the lower frequencies (0.25-5.0 Hz) to the spectrum was smaller than in other rodents in all three vigilance states and the distinction between NREM sleep and REM sleep was most marked in the theta band (6.0-8.5 Hz). After the sleep deprivation NREM sleep, REM sleep and SWA were increased in both genotypes. The change in EEG power density and in SWA was more prominent and lasted longer in the PrP-null mice. Our results suggest that PrP plays a role in promoting sleep continuity.

J. Neurosci. 17 (1997): 1869-1879.


Sleep deprivation increases Somatostatin and Growth hormone-releasing hormone messenger RNA in the rat hypothalamus.

Toppila,J.; Alanko,L.; Asikainen,M.; Tobler,I.; Stenberg,D.; Porkkaheiskanen,T.

We studied the effect of sleep deprivation (SD) on the amount of somatostatin (SRIF) and growth hormone-releasing hormone (GHRH) mRNA in rat hypothalamic nuclei. According to earlier studies SRIF possibly facilitates REM sleep and GHRH slow-wave sleep. Adult male rats were sleep deprived by the gentle handling method either for 6 h during the first half of the light phase or for 12 h during the dark phase. Undisturbed rats sacrificed at the same time as the SD rats served as controls. After oligonucleotide in situ hybridization the amount of SRIF and GHRH mRNA was measured in brain sections by image analysis and cell count. SD increased the amount of SRIF mRNA in the arcuate nucleus (ARC). In the periventricular nucleus (PE) there was no effect. The amount of GHRH mRNA increased in the paraventricular nucleus (PA) in the 6 h SD group but no effect was detected in ARC. In the periventromedial hypothalamic area (pVMH) the amount of GHRH mRNA was higher in the control rats sacrificed in the morning (09.00 hours) than in the afternoon (15.00 hours), and SD had no effect. We conclude that SRIF cells in ARC and GHRH cells in PA are modulated by sleep loss, which is in accordance with the possible sleep regulatory function of these neuropeptides.

J. Sleep Res. 6 (1997): 171-178.


Fronto-occipital EEG power gradients in human sleep.

Werth,E.; Achermann,P.; Borbély,A.A.

The brain topography of power spectra along the antero-posterior (A-P) axis was studied in the all-night human sleep EEG. Spectra (0.25-25.0 Hz) were computed for an anterior (A; F3-C3), a middle (M; C3-P3), and a posterior (P; P3-O1) bipolar derivation, and the spectral gradients between two adjacent derivations were expressed by power ratios (A/M and M/P). At nonREM-REM sleep transitions a power shift from A to M was present over almost the entire frequency range, while the direction of shifts between M and P differed between frequency bands. Within nonREM sleep, frequency specific power gradients were present: In the low delta band power in both A (0.25 Hz bin) and P (0.25-1.0 Hz bins) was higher than in M. In the 4-9 Hz range, the relation was A>M>P, and in the 15-25 Hz range, power was largest in M. Power in the spindle frequency range was highest at 11.75 Hz in M, and at 13.5-13.75 Hz in A. Topographical differences were seen also in the temporal changes of power across and within nonREM sleep episodes. Whereas nonREM sleep power in the 2-Hz bin was higher in A than in M in the first episode, this difference vanished in the course of the night. This result points to a specific involvement of frontal parts of the cortex in sleep homeostasis. The regional differences in sleep EEG spectra indicate that sleep is not only a global phenomenon but also a local brain process with a different regional involvement of neuronal populations.

J. Sleep Res. 6 (1997): 102-112.


Spindle frequency activity in the sleep EEG: individual differences and topographical distribution.

Werth,E.; Achermann,P.; Dijk,D.J.; Borbély,A.A.

The brain topography of EEG power spectra in the frequency range of sleep spindles was investigated in 34 sleep recordings from 20 healthy young men. Referential (F3-A2, C3-A2, P3-A2 and O1-A2) and bipolar derivations (F3-C3, C3-P3 and P3-O1) along the antero-posterior axis were used. Sleep spindles gave rise to a distinct peak in the EEG power spectrum. The distribution of the peak frequencies pooled over subjects and derivations showed a bimodal pattern with modes at 11.5 and 13.0 Hz, and a trough at 12.25 Hz. The large inter-subject variation in peak frequency (range: 1.25 Hz) contrasted with the small intra-subject variation between derivations, nonREM sleep episodes and different nights. In some individuals and/or some derivations, only a single spindle peak was present. The topographical distributions from referential and bipolar recordings showed differences. Power showed a declining trend over consecutive nonREM sleep episodes in the low range of spindle frequency activity and a rising trend in the high range. The functional and topographic heterogeneity of sleep spindles in conjunction with the intra-subject stability of their frequency are important characteristics for the analysis of sleep regulation on the basis of the EEG.

Electroenceph. clin. Neurophysiol. 103 (1997): 535-542.


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