University of Zürich - Institute of Pharmacology and Toxicology Section of Psychopharmacology and Sleep Research

Abstracts of papers published 1998

Achermann,P.; Borbély,A.A.

Animal studies have shown that the sleep-related oscillations in the frequency range of spindles and slow waves, and in the gamma band occur synchronously over large parts of the cerebral cortex. Coherence analysis was used to investigate these oscillations in the human sleep EEG. In all-night EEG recordings from 8 young subjects power and coherence spectra within and between cerebral hemispheres were computed from bipolar derivations placed bilaterally along the antero-posterior axis. The 0.75 - 50 Hz range was examined with a resolution of 0.25 Hz. Distinct peaks in coherence were present in nonREM sleep but not in REM sleep. The most prominent and consistent peak was seen in the range of sleep spindles (13-14 Hz), and additional peaks were present in the alpha band (9-10 Hz) and low delta band (1-2 Hz). Whereas coherence in the spindle range was highest in stage 2, the alpha peak was most prominent in slow wave sleep (stages 3 and 4). Interhemispheric coherence at 30 Hz was higher in REM sleep than in nonREM sleep. There were also marked sleep state-independent regional differences. Coherence between homologous interhemispheric derivations was high in the low frequency range and declined with increasing frequencies, whereas coherence of intrahemispheric and non-homologous interhemispheric derivations was at a low level throughout the spectra. It is concluded that coherence analysis may provide insights into large-scale functional connectivities of brain regions during sleep. The high coherence of sleep spindles is an indication for their wide-spread and quasi-synchronous occurrence throughout the cortex and may point to their specific role in the sleep process.

Neuroscience 85 (1998): 1195-1208.

Achermann,P.; Borbély,A.A.

Coherence analysis of the human sleep EEG was used to investigate relations between brain regions. In all-night EEG recordings from 8 young subjects the temporal evolution of power and coherence spectra within and between cerebral hemispheres was investigated from bipolar derivations along the antero-posterior axis. Distinct peaks in the power and coherence spectra were present in nonREM sleep but not in REM sleep. They were situated in the frequency range of sleep spindles (13-14 Hz), alpha band (9-10 Hz) and low delta band (1-2 Hz). Whereas the peaks coincided in the power and coherence spectra, a dissociation of their temporal evolution was observed. In the low delta band only power but not coherence showed a decline across successive nonREM sleep episodes. Moreover, power increased gradually in the first part of a nonREM sleep episode, whereas coherence showed a rapid rise. The results indicate that the intrahemispheric and interhemispheric coherence of EEG activity attains readily a high level in nonREM sleep and is largely independent of the signal amplitude.

J. Sleep Res. 7(1998) Suppl 1: 36-41.

Borbély,AA.

Sleep is regulated by homeostatic, circadian and ultradian processes. Slow waves and sleep spindles are EEG markers of sleep processes which have counterparts at the cellular level. The interaction of homeostatic and circadian sleep regulation has been formalized in the two-process model and validated in experiments. Sleep is not only a global brain phenomenon but also a regional cerebral process whose intensity may be influenced by prior activity during waking.

Hormone Research 49 (1998): 114-117.

Deboer,T.

In animals, changes in brain temperature induce a shift in frequencies in the electroencephalogram (EEG). Given the large decreases in body and brain temperature that occur during hibernation, putative functions that were previously ascribed to certain EEG frequencies are no longer valid because of the progressive shift away from the original frequency. In the present review it is proposed that even moderate temperature changes in humans and animals, such as those across the circadian or menstrual cycle or induced by drugs, have a significant effect on EEG frequencies and the corresponding power spectrum. Alterations in the relative EEG power spectrum, in studies where body temperature also changes, may not be a direct cause of the treatment under investigation, but a consequence of unspecific effects on body or brain temperature. However, these effects on the EEG power spectrum are usually interpreted to result directly from the experimental treatment.

J. Sleep Res. 7 (1998): 254-262.

Endo,T.; Roth,C.; Landolt,H.P.; Werth,E.; Aeschbach,D.; Achermann,P.; Borbély,A.A.

In the framework of a selective sleep deprivation study, eight young men were repeatedly awakened during 3 nights from nonREM sleep (nonREMS). The mean number of awakenings per night was 27.4, 29.5 and 32.8. In order to avoid excessive suppression of slow wave sleep, no awakening occurred in the first nonREMS episode. Compared to baseline, cycle 2 was significantly prolonged in all 3 nights, and cycle 3 in night 3 only. However, after subtracting the waking intervals, the differences from baseline was eliminated. The results show that the mechanisms underlying sleep cycle control keep track of sleep time and disregard epochs of waking.

Psychiatry and Clinical Neurosciences 52 (1998): 129-130.

Endo,T.; Roth,C.; Landolt,H.P.; Werth,E.; Aeschbach,D.; Achermann,P.; Borbély,A.A.

To investigate rapid eye movement (REM) sleep regulation, 8 healthy young men were deprived of REM sleep for 3 consecutive nights. In a 3-night control sleep deprivation (CD) session two weeks later, the subjects were repeatedly awakened from nonREM sleep in an attempt to match the awakenings during the REM sleep deprivation (RD) nights. During the RD nights the number of sleep interruptions required to prevent REM sleep increased within and across consecutive nights. REM sleep was reduced to 9.2 % of baseline (CD nights: 80.7 %) and rose to 140.1% in the first recovery night. RD gave rise to changes in the EEG power spectra of REM sleep. Power in the 8.25-11 Hz range was reduced in the first recovery night, an effect that gradually subsided but was still present in the third recovery night. The rising REM sleep propensity as reflected by the increase of interventions within and across RD nights, and the moderate REM sleep rebound during recovery can be accounted for by a compensatory response which serves REM sleep homeostasis. The changes in the EEG power spectra which were observed during enhanced REM sleep propensity, may be a sign of an altered quality of REM sleep.

American Journal of Physiology 274 (1998): R1186-R1194.

Huber,R.; Deboer,T.; Schwierin,B.; Tobler,I.

The effect of a single dose of melatonin (3-5 mg/kg i.p.) on sleep, electroencephalographic power density, and cortical temperature (TCRT) was investigated. Melatonin was administered to Djungarian hamsters 4 h or 12 h after lights on in a 16 h light - 8 h dark cycle (LD 16:8) and to rats at dark onset in a LD 12:12. The effects in both species were short lasting and depended on the time of day. Sleep latency was prolonged in the late light period, sleep fragmentation was enhanced in the early light period and TCRT was elevated in all three conditions. Rapid eye-movement sleep was reduced in the first post-drug hour after the late light period treatment in the hamsters and in post-drug hours 2 and 3 after dark onset treatment in the rat. Therefore we have no evidence for a sleep inducing effect of 3-5 mg/kg melatonin in the hamster or rat. In view of some data which indicate that melatonin may exert a sleep inducing effect in humans, it is suggested that melatonin induces changes that are typical for the dark period of each species, i.e. waking in the nocturnal Djungarian hamster and rat, and sleepiness in the diurnal human.

Physiol. Behav. 65 (1998): 77-82.

Lugaresi,E.; Tobler,I.; Gambetti,P.; Montagna,P.

The key clinical aspects of FFI, i,e, hypovigilance and attention deficit, inability to generate EEG sleep patterns, sympathetic hyperactivity and attenuation of vegetative and hormonal circadian oscillations, are related to selective atrophy of the anteroventral and mediodorsal thalamic nuclei, These nuclei constitute the limbic part of the thalamus interconnecting limbic and paralimbic regions of the cortex and other subcortical structures in the limbic system including the hypothalamus, The hypothalamus released from cortico-limbic control is shifted to a prevalence of activating, as opposed to deactivating, functions including loss of sleep, sympathetic hyperactivity and the attendant attenuation of autonomic circadian and endocrine oscillations. These findings document that the limbic thalamus has a strategic position in the central autonomic network running from the limbic cortical regions to the lower brain stem which regulates the body's homeostasis in an integrated fashion.

Brain Pathology 8 (1998): 521-526.

McKeown,MJ.; Humphries,C.; Achermann,P.; Borbély,AA.; Sejnowski,TJ.

A new statistical method is described for detecting state changes in the electroencephalogram (EEG), based on the ongoing relationships between electrode voltages at different scalp locations. An EEG sleep recording from one NREM-REM sleep cycle from a healthy subject was used for exploratory analysis. A dimensionless function defined at discrete times t(i), u(t(i)), was calculated by determining the log-likelihood of observing all scalp electrode voltages under the assumption that the data can be modeled by linear combinations of stationary relationships between derivations. The u(t(i)), calculated by using independent component analysis, provided a sensitive, but non-specific measure of changes in the global pattern of the EEG. In stage 2, abrupt increases in u(t(i)) corresponded to sleep spindles, In stages 3 and 4, low frequency (approximate to 0.6 Hz) oscillations occurred in u(t(i)) which may correspond to slow oscillations described in cellular recordings and the EEG of sleeping cats, In stage 4 sleep, additional irregular very low frequency (approximate to 0.05-0.2 Hz) oscillations were observed in u(t(i)) consistent with possible cyclic changes in cerebral blood flow or changes of vigilance and muscle tone. These preliminary results suggest that the new method can detect subtle changes in the overall pattern of the EEG without the necessity of making tenuous assumptions about stationarity.

J. Sleep Res. 7 (1998) Suppl 1: 48-56.

Roth,C.; Landolt,H.P.; Achermann,P.; Teuscher,A.; Borbély,A.A.

To investigate whether porcine insulin (PI) and human insulin (HI) have different effects on brain functions outside of hypoglycemia, sleep and the sleep EEG was recorded in 8 insulin-dependent diabetes mellitus (IDDM) patients in 3 separate sessions of 2 consecutive nights. Near-normoglycemia was confirmed by measurements of capillary blood glucose before and after sleep and at 0145 h. The treatment effect (PI compared to HI) consisted in a change of the nonREM sleep EEG in the spindle frequency range. Spectral power density in the 14-Hz bin was reduced upon transfer from PI (session 1) to HI (session 2) in all subjects, and increased upon reversal to PI (session 3) in all but one subject. There were no significant treatment effects on any other sleep EEG variable or on sleep stages. The subjects rated their sleep as more sound and their state in the morning as more relaxed during PI treatment. However, they were not blinded to the type of insulin they were using. PI and HI may exert differential effects on spindle generating mechanisms in the thalamocortical system. The results indicate that human insulin may affect brain functions differently compared to animal insulin under near-normoglycemic conditions.

Sleep 21 (1998): 92-100.

Tobler,I.; Herrmann,M.; Cooper,H.M.; Negroni,J.; Nevo,E.; Achermann P

The mole rat is a solitary, subterranean and photoperiodic rodent. We investigated its rest activity behavior under several lighting conditions, complemented our observations with light-induced c-fos expression, and compared the activity behavior of two chromosomal forms (2n = 58 and 60). The 26 mole rats had a clear overall preference for activity in the light or dark period, but prolonged recordings in five individuals showed that the initial preference was not stable in the nocturnal animals, they became diurnal. A 6-h advance of the light-dark (LD) cycle induced a shift of activity and the previous LD preference was reestablished. The large daily variability of activity onset did not allow this study to determine whether the animals were entrained to the LD cycle upon release into constant darkness (DD) or whether activity had been masked by light. The period of the motor activity rhythm in DD free ran in more than 50% of the animals. No differences in activity were observed between the two karyotypes. Immunohistochemistry for c-fos expression in the nucleus suprachiasmaticus at different circadian times showed that c-fos was induced only in animals exposed to a 1-h light pulse during the subjective night, but not during the subjective day or in control animals in the absence of a light pulse. The large intra- and inter-individual variability in daily motor activity both in LD and in DD suggest only a weak photic entrainment of the circadian clock to light of approximately 100 lux, and possibly a weak regulation of behavior by the circadian clock.

Behav. Brain Res. 96 (1998): 173-183.

Schwierin,B.; Borbély,A.A.; Tobler,I.

To investigate whether sleep homeostasis in the female rat is modulated by the estrous cycle, the vigilance states, EEG power spectra and cortical temperature (TCRT) were assessed on the basis of 4-day continuous recordings. A regulatory response was elicited by 6-h sleep deprivation (SD) during the proestrous (PRO) and the estrous (EST) day and compared to the baseline recordings. The vigilance states varied across the estrous cycle. In the PRO dark period the amount of sleep was reduced. The decrease in rapid-eye-movement (REM) sleep was already evident towards the end of the preceding light period, and an increased fragmentation of sleep was present throughout PRO. Compared to the other days of the estrous cycle, slow-wave activity (SWA; EEG power density 0.75-4.75 Hz) in nonREM (NREM) sleep was lower in PRO at the end of the light period and in the beginning of the dark period. High-frequency activity (HFA; EEG power density 10.25-25.0 Hz) was increased in the dark period of PRO. The SD performed during the first 6 h of the light period of PRO and EST enhanced SWA in NREM sleep and reduced sleep fragmentation during the subsequent 6 h. The extent and time course of the response to SD did not differ between the two phases of the estrous cycle. It is concluded that despite the marked baseline variations of the vigilance states and the EEG, homeostatic regulation is little affected by the estrous cycle.

Brain Res. 811 (1998): 96-104.