Daniel P. Brunner

A model of human sleep homeostasis based on EEG slow-wave activity: Quantitative comparison of data and simulations

EEG slow-wave activity (SWA; spectral power in the 0.75-4.5 Hz band) is a function of the duration of prior waking and, thereby, an indicator of sleep homeostasis. We present a model that accounts for both the declining trend of SWA during sleep and for its variation within the successive nonrapid eye movement (non-REM) sleep episodes. The values of the model parameters were estimated by an optimization procedure in which empirical SWA of baseline nights (16 subjects, 26 nights) served as a reference. A sensitivity analysis revealed the model to be quite robust to small changes (+/- 5%) of the parameter values. The estimated parameter values were used to simulate data sets from three different experimental protocols (sleep in the evening or sleep in the morning after prolonged waking, or extended sleep initiated at the habitual bedtime; n = 8 or 9). The timing of the REM trigger parameter was derived from the empirical data. A close fit was obtained between the simulated and empirical SWA data, and even the occasional late SWA peaks during extended sleep could be reproduced. Minor discrepancies suggest indirect or direct circadian influences on SWA. The simulations demonstrate that the concept of sleep homeostasis as proposed in the two-process model of sleep regulation can be refined to account in quantitative terms for empirical data and to predict the changes induced by the prolongation of waking or sleep.

Effect of zolpidem on sleep and sleep EEG spectra in healthy young men.

A single 10 mg dose of zolpidem, an imidazopyridine hypnotic, was administered to young, healthy male volunteers prior to bedtime. The drug reduced REM sleep but did not significantly affect other sleep stages and subjective sleep parameters. All-night spectral analysis of the EEG revealed that power density in nonREM sleep was reduced in the low-frequency range (1.25–2.5 Hz; 5.25–10.0 Hz) and increased in the spindle frequency range (12.25–13.0 Hz). Significant changes in the EEG spectrum were present in the first 4 h of sleep. The pattern of the spectral changes was similar to those induced by other hypnotics that bind to the GABAA/benzodiazepine receptor complex. There were no residual effects of zolpidem on psychomotor performance in the morning, on the self-rated state in the morning and at noon, and on sleep and EEG parameters in the subsequent drug-free night.

Dynamics of slow-wave activity and spindle frequency activity in the human sleep EEG: effect of midazolam and zopiclone.

Electroencephalographic slow-wave activity (SWA; power density in the 0.75 to 4.5 Hz band) and spindle frequency activity (SFA; 11.25 to 15.0 Hz) exhibit a typical time course and a distinct mutual relationship during sleep. Because benzodiazepines (BDZ) suppress SWA and enhance SFA, we investigated the effect of two BDZ-receptor agonists on the dynamics of these EEG parameters. A single dose of midazolam (15 mg), zopiclone (7.5 mg), or placebo was administered before bedtime to healthy young men. Although the two drugs reduced SWA and enhanced SFA, their time course across and within sleep cycles as well as their mutual relationship were little affected. The results constitute further evidence that hypnotics acting as BDZ-receptor agonists do not substantially interfere with the homeostatic aspect of sleep regulation.

EEG power density during recovery sleep in the morning

Sleep was recorded under baseline conditions (waking prior to sleep 16 h; lights off 23.00 h) and during recovery sleep in the morning (waking prior to sleep 24 h; lights off 07.00 h). Slow-wave activity (SWA; EEG power density in the range of 0.75-4.5 Hz) declined progressively over consecutive nonREM-REM cycles in both conditions despite the different circadian phase at which sleep occurred. SWA in nonREM sleep in the first 5 h of sleep was significantly higher in recovery than in baseline. Also SWA within the first 20 min of nonREM-episodes 2 and 3 was significantly higher in recovery sleep, and a tendency in the same direction was seen for nonREM-episode 1. These data show that homeostatic processes are expressed in the EEG also when sleep is initiated at a circadian phase where REM sleep propensity is high. However, comparison of the power spectrum in the first cycle of day-time recovery sleep with published data on recovery sleep at various circadian phases suggests that circadian factors influence the EEG spectra.

Behavioural evidence for polarization vision in crickets

ABSTRACT. Tethered field crickets, Gryllus campestris L., walking on an air‐suspended bail exhibit a spontaneous response to the e‐vector of polarized light presented from above: E‐vector orientation controls strength and direction of turning tendency. Experiments in which different eye regions are covered with paint suggest that this response is mediated by the anatomically and physiologically specialized dorsal rim area of the compound eye. We conclude that crickets have polarization vision and that the dorsal rim area of the eye plays a key role in this sensory capacity.

EEG and subjective sleepiness during extended wakefulness in seasonal affective disorder: circadian and homeostatic influences

BACKGROUND Seasonal affective disorder (SAD) may reflect a disturbance of circadian phase relationships or a disturbance of sleep-wake dependent processes, both of which change daytime energy and sleepiness levels. METHODS Under the unmasking conditions of a 40-hour constant routine protocol (CR), self-rated sleepiness and waking electroencephalogram (EEG) power density were assessed in women with SAD (n = 8) and in age-matched healthy control subjects (n = 9). RESULTS There was no significant effect of season or light treatment in any of the measures. The time course of subjective sleepiness was characterized by a circadian modulation and an overall increase during extended wakefulness in both SAD patients and control subjects. A prominent circadian rhythm of subjective sleepiness was not different in SAD patients and control subjects; however, the progressive buildup of sleepiness, as quantified by nonlinear regression analysis, was significantly reduced in SAD patients, mainly because they were sleepier than control subjects during the first 12 hours of the CR. The time course of waking EEG theta-alpha activity showed a more rapid increase during the first 10 hours of the CR in SAD patients. In contrast to control subjects who showed a progressive increase in the course of the 40-hour episode of extended wakefulness, EEG theta-alpha activity in SAD patients did not further increase over the remainder of the CR. CONCLUSIONS The data suggest that SAD patients may have a trait (rather than state) deficiency in the homeostatic buildup of sleep pressure during extended wakefulness as indexed by subjective sleepiness and EEG theta-alpha activity.

A quantitative analysis of phasic and tonic submental EMG activity in human sleep

Submental muscle activity and slow-wave activity in the EEG (mean power density in the 0.75-4.5-Hz band) were determined for consecutive 20-sec epochs in 34 all-night recordings of human sleep. Muscle activity was quantified by calculating the statistical variance of the digitized electromyogram (EMG). The tonic level of muscle activity was lower in REM sleep (REMS) than in nonREMS, and higher in the first nonREMS episode but an increasing trend within all subsequent nonREMS episodes. EEG slow-wave activity increased in the first part of all nonREMS episodes and decreased in the first part of all REMS episodes. The absolute or relative difference in muscle activity between two consecutive 20-sec intervals was used for defining EMG arousals. The density of arousals did not differ significantly among nonREMS episodes. Weak and moderate arousals showed an increasing density over consecutive REMS episodes. While arousals were uniformly distributed within REMS episodes, they were concentrated at the beginning and the end of nonREMS episodes.

Sleep electroencephalogram in seasonal affective disorder and in control women: Effects of midday light treatment and sleep deprivation

The role of sleep regulation in Seasonal Affective Disorder (SAD) was studied in 11 female SAD patients and eight controls in winter before and after light treatment (LT, 6000 lux, 10-14h, 5 days). The sleep electroencephalogram (EEG) was recorded at baseline and after the total sleep deprivation (TSD) of a 40-h constant routine. The well-known effects of TSD on sleep parameters and on EEG power spectra were replicated, indicating normal homeostatic sleep regulation in SAD. Sleep improved after LT in both groups. Since the condition following LT was the second session, these improvements may be an order effect and/or an effect of LT itself. After LT, sleep EEG spectra of SAD patients, but not of controls, showed modifications resembling those of recovery sleep. Since only SAD patients curtailed their sleep while remitting during the LT period, these EEG modifications can be explained by normal sleep regulation alone. We conclude that the robust antidepressant effect of LT in SAD is unlikely to be mediated by changes in sleep, and that sleep regulatory mechanisms are not a crucial factor in the pathogenesis of winter depression.

Accelerated post-glucose glycaemia and altered alliesthesia-test in Seasonal Affective Disorder

BACKGROUND Little is known about the link between mood, food and metabolic function in Seasonal Affective Disorder (SAD). METHODS We investigated this link in a combined glucose tolerance-alliesthesia test in eight SAD patients in winter before and after one week light therapy, and in summer. RESULTS SAD patients exhibited faster post-glucose glycaemic and insulin responses (p <0.05), and increased hedonic ratings of high concentrated sucrose solutions (p <0.035) when depressed in winter than when euthymic (one week after light treatment or in summer). CONCLUSIONS The rapid glycaemic and insulin responses to an oral glucose load may be a result of accelerated gastric emptying. LIMITATIONS The number of studied patients was rather small and no control group was studied in parallel. CLINICAL RELEVANCE the more rapid post-glucose glycaemia may impair glucose homeostasis in depressed SAD patients.

Effect of Light on Unmasked Circadian Rhythms in Winter Depression

Abstract Nine women with winter depression carried out a “constant routine” protocol of 40 hours sustained wakefulness to measure endogenous circadian rhythms (rectal temperature, mood, alertness, performance). Bright light given in the middle of the day reduced depressive symptoms and improved mood, as did the sleep deprivation of the constant routine protocol itself. Mood and alertness showed a bimodal rhythm under unmasked conditions, with both a nocturnal and afternoon trough. Light did not modify the endogenous rhythm of alertness but did improve a simple performance task at all circadian phases both in winter and in summer.