Section of Psychopharmacology and Sleep Research
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University of Zürich - Institute of Pharmacology and Toxicology Section of Psychopharmacology and Sleep Research |
Objective: To assess age-related topographic changes in the sleep electroencephalogram (EEG). Methods: The sleep EEG records of young (mean age 22.3 years) and middle-aged (mean age 62.0 years) healthy men were compared. The EEG was obtained from 3 bipolar derivations (frontal-central (FC), central-parietal (CP) and parietal-occipital (PO)) along the anteroposterior axis. Results: The total sleep time, sleep efficiency, stage 2 and slow wave sleep (SWS) were lower in the middle-aged group, while sleep latency, stage I and wakefulness after sleep onset were higher. Spectral analysis documented the age-related reduction of EEG power in non-REM sleep (0.25-14 Hz) and REM sleep (0.75-10 Hz). However, the reduction was not uniform over the 3 derivations but was most pronounced in the anterior derivation (FC) in the theta (both sleep states) and high-alpha/low-sigma bands (non-REM sleep). Conclusions: These changes can be interpreted as age-related shifts of power from the anterior (FC) towards the middle derivation (CP). Aging not only reduces power in the sleep EEG but causes frequency-specific changes in the brain topography. The results are consistent with the notion of sleep as a local process.
Clin. Neurophysiol., 112, 369-377 (2001).
Study Objectives: The mole rat, Spalax ehrenbergi, is an interesting species for sleep because of its pronounced specialization to a fossorial life. These rodents spend most of their life-time underground, and are less exposed to many of the environmental stimuli and challenges that are common to non-fossorial rodents. A prominent adaptation is their blindness, which is due to an atrophy of the eyes. Design: Continuous 24-h recordings of EEG, EMG and cortical temperature, and EEG spectral analysis were performed in six individuals caught in the wild and adapted to the laboratory for several months. Setting: N/A Patients or Participants: N/A Interventions: N/A Measurements and Results: Total sleep time (52% of recording time) and the amount of REM sleep (8% of recording time) in these subterranean rodents are in the range of values found in the laboratory rat. mouse and hamster recorded under similar conditions. In contrast to these species, the polyphasic sleep-wakefulness distribution in mole rats was more distinct. A predominance of sleep in the dark period was only minor and not present in all individuals, which resembles sleep in the guinea pig. As in all other mammals investigated, the daily time course of EEG slow-wave activity (SWA) in nonREM sleep closely followed the polyphasic sleep-wake pattern and the light-dark preference. The transitions from non REM sleep to REM sleep were characterized, as in other rodents. by a gradual increase in EEG activity in the theta and sigma frequency bands before the transition. However, the power surge in these frequencies massively exceeded that found in other rodents. This feature may be related to adaptations of the brain to the requirements of the subterranean habitat. Conclusions: It is remarkable that large ecological differences between species within the same order have relatively small effects on many sleep features. The time course of SWA confirmed its predictability on the basis of the previous sleep-wake history. [References: 44] 44
Sleep, 24, 147-154 (2001).
EEG power spectra exhibit site-specific and state-related differences in specific frequency bands. In the present study we investigated the effect of total sleep deprivation on sleep EEG topography. Eight healthy, young, right-handed subjects were recorded during baseline sleep and recovery sleep after sleep deprivation. Forty hours of sleep deprivation affected power spectra in all derivations. However, hemispheric asymmetries were observed in the delta range. Sleep deprivation enhanced the anterior predominance of delta activity in the left hemisphere but not in the right one. This effect may reflect a functional asymmetry between the dominant and non-dominant hemisphere. The results provide further evidence for the presence of both global and local aspects of sleep regulation.
Brain Research, 913, 220–223 (2001)
Repetitive transcranial magnetic stimulation rTMS is a novel research tool in neurology and psychiatry. It is currently being evaluated as a conceivable alternative to electroconvulsive therapy for the treatment of mood disorders. Eight healthy young age range 2125 years right-handed men without sleep complaints participated in the study. Two sessions at a 1-week interval, each consisting of an adaptation night sham stimulation and an experimental night rTMS in the left dorsolateral prefrontal cortex or sham stimulation; crossover design , were scheduled. In each subject, 40 trains of 2-s duration of rTMS inter-train interval 28 s were applied at a frequency of 20 Hz i.e. 1600 pulses per session and at an intensity of 90% of the motor threshold. Stimulations were scheduled 80 min before lights off. The waking EEG was recorded for 10-min intervals 30 min prior to and after the 20-min stimulations, and polysomnographic recordings were obtained during the subsequent sleep episode 23.0007.00 h . The power spectra of two referential derivations, as well as of bipolar derivations along the antero-posterior axis over the left and right hemispheres, were analyzed. rTMS induced a small reduction of sleep stage 1 in min and percentage of total sleep time over the whole night and a small enhancement of sleep stage 4 during the first non-REM sleep episode. Other sleep variables were not affected. rTMS of the left dorsolateral cortex did not alter the topography of EEG power spectra in waking following stimulation, in the all-night sleep EEG, or during the first non-REM sleep episode. Our results indicate that a single session of rTMS using parameters like those used in depression treatment protocols has no detectable side effects with respect to sleep in young healthy males.
Psychiatry Research: Neuroimaging Section,107,1-9 (2001)
Ligands acting at the benzodiazepine (BZ) site of g-aminobutyric acid type A (GABAA) receptors currently are the most widely used hypnotics. BZs such as diazepam (Dz) potentiate GABAA receptor activation. To determine the GABAA receptor subtypes that mediate the hypnotic action of Dz wild-type mice and mice that harbor Dz-insensitive a1 GABAA receptors [a1 (H101R) mice] were compared. Sleep latency and the amount of sleep after Dz treatment were not affected by the point mutation. An initial reduction of rapid eye movement (REM) sleep also occurred equally in both genotypes. Furthermore, the Dz-induced changes in the sleep and waking electroencephalogram (EEG) spectra, the increase in power density above 21 Hz in non-REM sleep and waking, and the suppression of slow-wave activity (SWA; EEG power in the 0.75- to 4.0-Hz band) in non-REM sleep were present in both genotypes. Surprisingly, these effects were even more pronounced in a1(H101R) mice and sleep continuity was enhanced by Dz only in the mutants. Interestingly, Dz did not affect the initial surge of SWA at the transitions to sleep, indicating that the SWA-generating mechanisms are not impaired by the BZ. We conclude that the REM sleep inhibiting action of Dz and its effect on the EEG spectra in sleep and waking are mediated by GABAAreceptors other than a1, i.e., a2, a3, or a5 GABAA receptors. Because a1 GABAA receptors mediate the sedative action of Dz, our results provide evidence that the hypnotic effect of Dz and its EEG ‘‘fingerprint’’ can be dissociated from its sedative action. BZ hypnotics have distinct effects both on sleep and the sleep electroencephalogram (EEG). They induce dose-dependent increases of non-rapid eye movement (NREM) sleep, a reduction of REM sleep in humans and a typical BZ ‘‘fingerprint,’’ consisting of a reduction in delta activity in humans and rats, an increase of sigma activity in humans, and high-frequency activity in rats (8–15). These effects are common for agonists acting at the BZ site, irrespective of whether they are BZ or non-BZ compounds such as zolpidem and zopiclone (15–17). To assess whether the a1 GABAA receptors mediate not only the sedative action of Dz but also its effects on sleep, the sleep EEG and motor activity were compared in a1(H101R) and wild-type mice. Surprisingly, we found that the BZ fingerprint in the sleep EEG was present in both genotypes, indicating that these changes in the sleep EEG are mediated by GABAA receptors other than a1, in contrast to the sedative action, which is mediated by a1 receptors (5, 6).
PNAS, vol. 98, no.11, 6464-6469 (2001)
The sleep EEG of healthy young men was recorded during baseline and recovery sleep after 40 h of waking. To analyse the EEG topography, power spectra were computed from 27 derivations. Mean power maps of the nonREM sleep EEG were calculated for 1-Hz bins between 1.0 and 24.75 Hz. Cluster analysis revealed a topographic segregation into distinct frequency bands which were similar for baseline and recovery sleep, and corresponded closely to the traditional frequency bands. Hallmarks of the power maps were the frontal predominance in the delta and alpha band, the occipital predominance in the theta band, and the sharply delineated vertex maximum in the sigma band. The effect of sleep deprivation on EEG topography was determined by calculating the recovery/baseline ratio of the power spectra. Prolonged waking induced an increase in power in the low-frequency range (1-10.75 Hz) which was largest over the frontal region, and a decrease in power in the sigma band (13-15.75 Hz) which was most pronounced over the vertex. The topographic pattern of the recovery/baseline power ratio was similar to the power ratio between the first and second half of the baseline night. These results indicate that changes in sleep propensity are reflected by specific regional differences in EEG power. The predominant increase of low-frequency power in frontal areas may be due to a high 'recovery need' of the frontal heteromodal association areas of the cortex.
European Journal of Neuroscience, vol. 13, no. 12, 2282-2290 (2001)
The sleep EEG of eight healthy young men was recorded from 27 derivations during a baseline night and a recovery night after 40 h of waking. Individual power maps of the nonREM sleep EEG were calculated for the delta, theta, alpha, sigma and beta range. The comparison of the normalized individual maps for baseline and recovery sleep revealed very similar individual patterns within each frequency band. This high correspondence was quantified and statistically confirmed by calculating the Manhattan distance between all pairs of maps within and between individuals. Although prolonged waking enhanced power in the low-frequency range (0.75-10.5 Hz) and reduced power in the high-frequency range (13.25-25 Hz), only minor effects on the individual topography were observed. Nevertheless, statistical analysis revealed frequency-specific regional effects of sleep deprivation. The results demonstrate that the pattern of the EEG power distribution in nonREM sleep is characteristic for an individual and may reflect individual traits of functional anatomy.
Neuropsychopharmacology, vol. 25 (5 Suppl 1):S57-62 (2001)
Antidepressants belonging to the class of monoamine oxidase inhibitors (MAOI) such as phenelzine have long been known to drastically suppress REM sleep. Sleep and the electroencephalogram (EEG) in sleep and waking were studied in three depressed patients at regular time intervals before, during and after 6 to 18 months of phenelzine treatment. While REM sleep was initially eliminated in all patients, short REM sleep episodes reappeared after 3 to 6 months of medication. Total sleep time and EEG slow-wave activity (SWA, spectral power within 0.75-4.5 Hz) in non-REM sleep (stages 1-4) were not changed. In contrast, EEG theta frequency activity (TFA, power within 4.75-8.0 Hz) during a 5-min wake interval recorded prior to the sleep episodes was initially enhanced, and tended to correlate negatively with the percentage of REM sleep (p=0.06). This observation indicates that compensatory REM sleep mechanisms may occur in wakefulness during chronic MAOI treatment.
Neuropsychopharmacology, vol. 25, no. S5:63-67 (2001).
Multichannel EEG of an advanced meditator was recorded during four different, repeated meditations. Locations of intracerebral source gravity centers as well as Low Resolution Electromagnetic Tomography (LORETA) functional images of the EEG ‘gamma’ (35-44 Hz) frequency band activity differed significantly between meditations. Thus, during volitionally self-initiated, altered states of consciousness that were associated with different subjective meditation states, different brain neuronal populations were active. The brain areas predominantly involved during the self-induced meditation states aiming at visualization (right posterior) and verbalization (left central) agreed with known brain functional neuroanatomy. The brain areas involved in the self-induced, meditational dissolution and reconstitution of the experience of the self (right fronto-temporal) are discussed in the context of neural substrates implicated in normal self-representation and reality testing, as well as in depersonalization disorders and detachment from self after brain lesions.
Psychiatry Res: Neuroimaging Section, vol. 108, 111-121(2001).