Section of Psychopharmacology and Sleep Research
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University of Zürich - Institute of Pharmacology and Toxicology Section of Psychopharmacology and Sleep Research |
Napping benefits and sustains subsequent performance. Prophylactic naps have been recommended as a means to maintain performance during extended wakefulness, as required during shiftwork. However, napping may cause short-term performance impairments, because awakening from sleep is followed by sleep inertia, a period of hypovigilance and impaired cognitive and behavioral performance. We investigated sleep inertia after an afternoon nap. Healthy 18–28 year-olds (n=50, not sleep deprived) were assigned to sleep, active wake or rest groups for a 2-h experimental phase with polysomnography starting either at 14:00 or 16:00 for half of each group. Before (baseline, 12:30 or 14:30) and in five sessions during the hour after the experimental phase (16:00–17:00 or 18:00–19:00), subjects completed an addition task, an auditory reaction time task, and the Stanford Sleepiness Scale. In session one, addition speed in the sleep group was reduced compared with baseline and with active wake controls, whereas calculation accuracy did not change. Addition speed in the sleep and rest groups increased substantially from session one to session two and reached a level similar to that of the active wake group by the fifth session. In the first session, auditory reaction speed of the sleep group was reduced compared with baseline and with rest controls but did not differ from the active wake group. The slowest reaction times showed significant recovery after 20 min. The groups reported similar increases in subjective sleepiness after the experimental period. These findings provide evidence for performance slowing and recovery during the hour following a 2-h nap opportunity. They highlight the importance of employing multiple control groups and various objective and subjective measures to assess sleep inertia.
Brain Research. Cognitive Brain Research 2005, 22:323-331
Objectives: One of the early hypotheses relating sleep disturbances in depression to a model of sleep regulation is the S-deficiency hypothesis. It is postulated that, in depressed patients, sleep propensity during wakefulness does not rise to the level attained by nondepressed subjects, resulting in altered sleep structure or changes in the electroencephalogram during sleep. We aimed to test this hypothesis by assessing topographic
changes in the sleep electroencephalogram associated with depression.
Design: Cross-sectional clinical study.
Setting: Mental Health Clinical Research Center.
Participants: Sixteen unmedicated depressed outpatients (mean age: 41.2 years) and 16 pair-matched healthy controls (mean age: 41.1 years).
Interventions: None.
Measurements: Baseline sleep electroencephalogram recordings were obtained from a central referential electrode and from 3 bipolar derivations (frontocentral, centroparietal, parietooccipital) along the anteroposterior axis.
Results: Symptoms of depression at the time of sleep recordings were moderate (24-item Hamilton Rating Scale of Depression range: 16–31). No differences between patients and controls were found in sleep variables and all-night electroencephalogram spectra in non-rapid-eye-movement and rapid-eye-movement sleep. The ultradian modulation of slowwave activity (power within 0.75-4.5 Hz), as well as the exponential decline of slow-wave activity, during sleep did not differ between the groups. The statistical analyses of electroencephalogram power gradients between adjacent derivations revealed no Group × Derivation interactions. An anterior dominance in non-rapid-eye-movement sleep power
was present in the 0.75- to 2-Hz range, which diminished throughout the night.
Conclusions: These findings in moderately depressed patients do not support the existence of an S-deficiency during sleep. Because the build
up of sleep propensity during waking can be dissociated from its decline, future studies need to investigate the waking electroencephalogram spectra in depression..
Sleep, 28:239-247 (2005).
We investigated the effects of radio frequency electromagnetic fields (RF EMF) similar to those emitted by mobile phones on waking regional cerebral blood flow (rCBF) in 12 healthy young men. Two types of RF EMF exposure were applied: a "base-station-like" and a "handset-like" signal. Positron emission tomography scans were taken after 30 min unilateral head exposure to pulse-modulated 900 MHz RF EMF (10 g tissue-averaged spatial peak-specific absorption rate of 1 W/kg for both conditions) and sham control. We observed an increase in relative rCBF in the dorsolateral prefrontal cortex on the side of exposure. The effect depended on the spectral power in the amplitude modulation of the RF carrier such that only "handset-like" RF EMF exposure with its stronger low frequency components but not the "base-station-like" RF EMF exposure affected rCBF. This finding supports our previous observation that pulse modulation of RF EMF is necessary to induce changes in the waking and sleep EEG, and substantiates the notion that pulse modulation is crucial for RF EMF-induced alterations in brain physiology.
European Journal of Neuroscience, 21:1000-1006 (2005).
Sleep deprivation is accompanied by the progressive development of an irresistible need to sleep, a phenomenon whose mechanism has remained elusive. Here, we identified for the first time a reflection of that phenomenon in vitro by showing that, after a short 2 h period of total sleep deprivation, the action of noradrenaline on the wake-promoting hypocretin/orexin neurons changes from an excitation to an inhibition. We propose that such a conspicuous modification of responsiveness should contribute to the growing sleepiness that accompanies sleep deprivation.
Journal of Neuroscience, 25:4127-4130 (2005).
THIP is a GABAA agonist with hypnotic properties consisting in reducing sleep latency and prolonging and consolidating sleep. THIP has been reported to increase EEG slow-wave activity (SWA; EEG power in the 0.75-4 Hz band) in non-REM (NREM) sleep in both rats and humans. We investigated the effects of THIP on sleep in C57BL/6 mice. EEG recordings were performed after 2, 4 and 6 mg/kg THIP and saline control. The results were compared with analyses of recordings obtained after 6 h of sleep deprivation (SD) in the same strain of mice. The two higher doses of THIP induced an abnormal EEG pattern both in waking and NREM sleep. The EEG was characterized by sporadic asymmetric high-voltage potentials recurring at a low-frequency (<1 Hz) on the background of a low-amplitude EEG pattern. In contrast, after SD the typical regular synchronous high amplitude delta waves predominated. THIP at 4 and 6 mg/kg led to a prominent enhancement of spectral power in the low-frequency range of the waking and sleep EEG which was much higher than the increase attained after 6 h SD. This effect was particularly prominent in the waking EEG. In NREM sleep the increase of spectral power after THIP reflected the frequency of recurrence of the high-voltage potentials, and was restricted to a narrower frequency band than after SD. The EEG changes after 2 mg/kg differed little from saline control. Sleep latency was not affected by the two lower doses of THIP, and was prolonged after 6 mg/kg. REM sleep was suppressed after the two higher doses. In contrast to previous results reported in other species, THIP did not have a hypnotic action in mice. The changes induced by THIP in the waking and sleep EEG differed from those caused by enhanced physiological sleep pressure encountered after SD. Considering the abnormal EEG pattern and the similarity of the spectral changes in the sleep and waking EEG, THIP does not seem to exert a specific effect on mechanisms involved in sleep regulation.
Neuropharmacology, 48:617-626 (2005).
Slow, rhythmic oscillations (<5 Hz) in the sleep electroencephalogram may be a sign of synaptic plasticity occurring during sleep. The oscillations, referred to as slow-wave activity (SWA), reflect sleep need and sleep intensity. The amount of SWA is homeostatically regulated. It is enhanced after sleep loss and declines during sleep. Animal studies suggested that sleep need is genetically controlled, yet the physiological mechanisms remain unknown. Here we show in humans that a genetic variant of adenosine deaminase, which is associated with the reduced metabolism of adenosine to inosine, specifically enhances deep sleep and SWA during sleep. In contrast, a distinct polymorphism of the adenosine A(2A) receptor gene, which was associated with interindividual differences in anxiety symptoms after caffeine intake in healthy volunteers, affects the electroencephalogram during sleep and wakefulness in a non-state-specific manner. Our findings indicate a direct role of adenosine in human sleep homeostasis. Moreover, our data suggest that genetic variability in the adenosinergic system contributes to the interindividual variability in brain electrical activity during sleep and wakefulness.
Proc. Natl. Acad. Sci. U.S.A., 102(43): 15676-15681 (2005).
STUDY OBJECTIVES: To examine the effects of total sleep deprivation on adolescent sleep and the sleep electroencephalogram (EEG) and to study aspects of sleep homeostasis. DESIGN: Subjects were studied during baseline and recovery sleep after 36 hours of wakefulness. SETTING: Four-bed sleep research laboratory. PARTICIPANTS: Seven prepubertal or early pubertal children (pubertal stage Tanner 1 or 2 = Tanner 1/2; mean age 11.9 years, SD +/- 0.8, 2 boys) and 6 mature adolescents (Tanner 5; 14.2 years, +/- 1.4, 2 boys). INTERVENTIONS: Thirty-six hours of sleep deprivation. MEASUREMENTS: All-night polysomnography was performed. EEG power spectra (C3/A2) were calculated using a Fast Fourier transform routine. RESULTS: In both groups, sleep latency was shorter, sleep efficiency was higher, non-rapid eye movement (NREM) sleep stage 4 was increased, and waking after sleep onset was reduced in recovery relative to baseline sleep. Spectral power of the NREM sleep EEG was enhanced after sleep deprivation in the low-frequency range (1.6-3.6 Hz in Tanner 1/2; 0.8-6.0 Hz in Tanner 5) and reduced in the sigma range (11-15 Hz). Sleep deprivation resulted in a stronger increase of slow-wave activity (EEG power 0.6-4.6 Hz, marker for sleep homeostatic pressure) in Tanner 5 (39% above baseline) than in Tanner 1/2 adolescents (18% above baseline). Sleep homeostasis was modeled according to the two-process model of sleep regulation. The build-up of homeostatic sleep pressure during wakefulness was slower in Tanner 5 adolescents (time constant of exponential saturating function 15.4 +/- 2.5 hours) compared with Tanner 1/2 children (8.9 +/- 1.2 hours). In contrast, the decline of the homeostatic process was similar in both groups. CONCLUSION: Maturational changes of homeostatic sleep regulation are permissive of the sleep phase delay in the course of adolescence.
Sleep, 2005 Nov 1;28(11):1446-54.
The different brain states during sleep are characterized by the occurrence of distinct oscillatory patterns such as spindles or delta waves. Using a new algorithm to detect oscillatory events in the electroencephalogram (EEG), we studied their properties and changes throughout the night. The present approach was based on the idea that the EEG may be described as a superposition of stochastically driven harmonic oscillators with damping and frequency varying in time. This idea was implemented by fitting autoregressive models to the EEG data. Oscillatory events were detected, whenever the damping of one or more frequencies was below a predefined threshold. Sleep EEG data of eight healthy young males were analyzed (four nights per subject). Oscillatory events occurred mainly in three frequency ranges, which correspond roughly to the classically defined delta (0-4.5 Hz), alpha (8-11.5 Hz) and sigma (11.5-16 Hz) bands. Their incidence showed small intra- but large inter-individual differences, in particular with respect to alpha events. The incidence and frequency of the events was characteristic for sleep stages and non-rapid eye movement (REM)-REM sleep cycles. The mean event frequency of delta and sigma (spindle) events decreased with the deepening of sleep. It was higher in the second half of the night compared with the first one for delta, alpha and sigma oscillations. The algorithm provides a general framework to detect and characterize oscillatory patterns in the EEG and similar signals.
J Sleep Res., 2005 Dec;14(4):337-46.
Regional aspects of sleep homeostasis were investigated in mice provided with a running wheel for several weeks. Electroencephalogram (EEG) spectra of the primary motor (frontal) and somatosensory cortex (parietal) were recorded for three consecutive days. On a single day (day 2) the wheel was locked to prevent running. Wheel running correlated negatively with the frontal-parietal ratio of slow-wave activity (EEG power between 0.75 and 4.0 Hz) in the first 2 h after sleep onset (r = -0.60; P < 0.01). On day 2 frontal EEG power (2.25-8.0 Hz) in non-rapid eye movement sleep exceeded the level of the previous day, indicating that the diverse behaviors replacing wheel-running elicited more pronounced regional EEG differences. The frontal-parietal power ratio of the lower frequency bin (0.75-1.0 Hz) in the first 2 h of sleep after dark onset correlated positively with the duration of the preceding waking (r = 0.64; P < 0.001), whereas the power ratio in the remaining frequencies of the delta band (1.25-4.0 Hz) was unrelated to waking. The data suggest that in mice EEG power in the lower frequency, corresponding to the slow oscillations described in cats and humans, is related to local sleep homeostasis.
Cereb Cortex., 2005 May 18
In humans, EEG power in the theta frequency band (5-8 Hz) during quiet waking increases during sleep deprivation (SD), and predicts the subsequent homeostatic increase of sleep slow-wave activity (SWA; EEG power between 0.5 and 4.0 Hz). These findings indicate that theta power in waking is an EEG variable, which reflects the rise in sleep propensity. In rodents, a number of short sleep attempts, as well as SWA in the waking EEG increase in the course of SD, but neither variable predicts the subsequent homeostatic increase of EEG SWA during recovery sleep. To investigate whether there is an EEG marker for sleep propensity also in rodents, the EEG of the rat was recorded during 6 h SD in the first half of the light period (SDL, n = 7). During SDL, power of the waking EEG showed an increase in the delta (1.5-4 Hz) and low theta (5-6.5 Hz) band. Based on the neck muscle EMG, wakefulness was subdivided into active (high EMG activity) and quiet (low EMG activity) waking. During quiet waking, the theta peak occurred at 5.5 Hz, the frequency at which the increase of EEG power during SD was most pronounced. This increase was due to higher amplitude of theta waves, while wave incidence (frequency) was unchanged. Correlation analysis showed that the rise in EEG power in the 5-7 Hz band during SD predicted the subsequent enhancement of SWA in non-rapid eye movement sleep. The analysis of data of a further batch of rats which were sleep deprived for 6 h after dark onset (SDD, n = 7) revealed a significant increase in theta-wave amplitude during the SD and a tendency for a similar, positive correlation between the increase of theta power (5-7 Hz) and subsequent SWA. The results indicate that in rats, as in humans, a specific waking EEG frequency, i.e., theta power in quiet waking is a marker of sleep propensity.
Brain Res., 2005 Jul 19;1050(1-2):64-71.
Topographic differences in the sleep EEG have been repeatedly found in humans and rodents. A frontal predominance of EEG slow-wave activity (0.75-4 Hz; delta band) during non-rapid eye movement (NREM) sleep is particularly evident under conditions of increased sleep propensity. Local aspects of neuronal connectivity in the neocortex that are modified by specific neuronal stimulation may underlie these differences. To investigate the role of altered neuronal connectivity on anterior-posterior EEG topography, sleep was recorded in mice with congenital dysgenesis of the corpus callosum (B1 strain) during baseline and after 6 h sleep deprivation (SD). In these mice neuronal connections within a hemisphere are increased due to the longitudinal Probst bundle, a structure of re-routed callosal fibers. After SD the frequencies above 1.5 Hz within the delta band in NREM sleep were reduced in B1 mice compared with control C57BL/6 mice, a strain that has a normal corpus callosum, while power in the lowest frequency band (0.75-1.0 Hz) was enhanced in B1 mice. The differences between the strains subsided in the course of recovery. The redistribution of EEG power within the delta band in the frontal region in mice with a well developed Probst bundle, suggests a role of intracortical connectivity in local sleep regulation.
J Sleep Res., 2005 Sep;14(3):299-304.
A huge amount of knowledge about sleep has accumulated during the last 5 decades following the discovery of rapid eye movement (REM) sleep. Nevertheless, there are numerous areas of considerable ignorance. One of these concerns the particularities of sleep in women. Most basic and clinical studies have been performed in male subjects, and only very recently research groups around the world have addressed women's sleep in health and disease. In this review, we summarize the present knowledge on the influence of oestrogens on the brain and on the distinctive changes of sleep across the menstrual cycle, during pregnancy and menopause. In addition, studies in female rodents are reviewed as well as the knowledge on female peculiarities regarding the interactions between sleep regulation and age-related changes in circadian rhythms. We also address specific aspects of sleep loss and sleep disorders in women. Finally, very recent studies on the sociology of sleep are summarized and future directions in the field are discussed.
J Psychiatr Res., 2005 Jan;39(1):55-76.