Biomedical subjects
Publications and source records attributed to P Achermann.
Different models have been proposed to account for processes underlying the regulation of sleep and alertness. Specific models have addressed sleep homeostasis, the nonREM-REM sleep cycle, the circadian sleep/wake rhythm, and changes of daytime alertness. We show that the different models are not mutually exclusive but that they can be integrated as 'modules' in a combined model.
A single bedtime dose of the benzodiazepine hypnotics, flunitrazepam (2 mg), triazolam (0.5 mg) or flurazepam (30 mg), was administered to young, healthy subjects. Abortive first rapid eye movement sleep (REMS) episodes, characterized by a low level of EEG slow-wave activity (spectral power density in the 0.75-4.5 Hz band) without rapid eye movements and/or muscle atonia, were more frequent in the drug night than in the placebo night or in the drug-free night following upon the drug night. The benzodiazepine hypnotics depressed slow-wave activity in non-REM sleep (NREMS) in the drug night and the subsequent drug-free night. However, the typical declining trend of slow-wave activity over the first three NREMS-REMS cycles, and the cyclic ultradian pattern of slow-wave activity were little affected by the hypnotics. The results indicate that benzodiazepine hypnotics depress the generation of slow EEG waves without disrupting the homeostatic and ultradian processes of sleep regulation.
Wakefulness, nonrapid eye movement sleep (nonREMS) and REMS of rats were scored in 4-s epochs during the first 8 h of the 12-h light period of a baseline (BL) day and during recovery (REC) from 24-h sleep deprivation (SD). Vigilance state continuity was investigated by analyzing the distribution of state episodes. After SD, state continuity was enhanced. The reduced occurrence of short wake episodes resulted in a consolidation of sleep states. The distribution of the REM-nonREM cycle length showed a mode at 10-13 min for both BL and REC. The variability of the cycle length was reduced after SD. The mean cycle length was markedly influenced by the criteria of minimum REMS episode duration and maximal allowed REMS episode interruption.
The typical declining trend of electroencephalographic (EEG) slow-wave activity (SWA) within a sleep period is represented in the two-process model of sleep regulation by an exponentially decaying process (Process S). The model has been further elaborated to simulate not only the global changes of SWA, but also the dynamics within non-rapid-eye-movement (non-REM) sleep episodes. In this new model, the initial intraepisodic buildup of SWA is determined by the combined action of an exponentially increasing process and a saturation process, whereas its fall at the end of an episode is due to an exponentially decreasing process. The global declining trend of SWA over consecutive episodes results from the monotonic decay of the intraepisodic saturation level. In contrast to Process S in the two-process model, this decay is not represented by an exponential function, but is proportional to the momentary level of SWA. REM sleep episodes are triggered by an external function. The model allows one to simulate the ultradian pattern of SWA for baseline nights as well as changes induced by a prolonged waking period, a daytime nap, a partial slow-wave sleep deprivation, or an antidepressant drug.
Sleep initiation and sleep intensity in humans show a dissimilar time course. The propensity of sleep initiation (PSI), as measured by the multiple sleep latency test, remains at a relatively constant level throughout the habitual period of waking or exhibits a midafternoon peak. When waking is extended into the sleep period, PSI rises rapidly within a few hours. In contrast, sleep intensity, as measured by electroencephalographic slow-wave activity during naps, shows a gradual increase during the period of habitual waking. In the two-process model of sleep regulation, it corresponds to the rising limb of the homeostatic Process S. We propose that PSI is determined by the difference between Process S and the threshold H defining sleep onset, which is modulated by the circadian process C. In contrast to a previous version of the model, the parameters of H (amplitude, phase, skewness) differ from those of threshold L, which defines sleep termination. The present model is able to simulate the time course of PSI under baseline conditions as well as following recovery sleep after extended sleep deprivation. The simulations suggest that during the regular period of waking, a circadian process counteracts the increasing sleep propensity induced by a homeostatic process. Data obtained in the rat indicate that during the circadian period of predominant waking, a circadian process prevents a major intrusion of sleep.
The dynamics of EEG slow wave activity during sleep were investigated in two subjects recorded for 14 consecutive nights, and in 14 subjects recorded for one night after placebo administration. In addition, records were obtained after a single bedtime dose of the benzodiazepine hypnotics flurazepam (30 mg), flunitrazepam (2 mg), triazolam (0.5 mg) and midazolam (15 mg). Mean slow wave activity (i.e. spectral power density in the 0.75-4.5 Hz band) invariably declined from the first to the third nonREM sleep episode. Within episodes, slow wave activity showed initially a gradual buildup over a period of offroximately 35 min, and in the end a rapid decline. Both the rise rates and fall rates decreased over the first three nonREM sleep episodes. The benzodiazepines typically attenuated mean slow wave activity within episodes as well as the rise and fall rates. For three compounds, residual effects were demonstrated in the drug-free post-drug night. We conclude that a homeostatically regulated sleep process determines the buildup rate of slow wave activity within nonREM sleep episodes.