SUMMARY  The dynamics of the sleep EEG were investigated by all‐night spectral analysis of 51 sleep records. Power density was calculated for 1‐Hz bins in the 0.25–25.0 Hz range. Values in non‐rapid‐eye‐movement sleep (NREMS) were higher than in REMS in the 0.25–16.0 Hz range, and lower in the 18.25–22.0 Hz range. Power density in the 0.25–12.0 Hz range showed a declining trend over the first four NREMS episodes, which, depending on the frequency bin, could be approximated by non‐linear or linear decay functions. In the frequency range of sleep spindles (12.25–15.0 Hz), power density in the 13.25–15.0 Hz band showed an increasing trend between NREMS episode 2 and NREMS episode 4. A correlation matrix of 25 1‐Hz bins revealed for NREMS a negative correlation between slow‐wave activity (SWA; 0.25–4.0 Hz) and activity in the spindle frequency range. This negative correlation was highest in the first NREMS episode and diminished progressively over the subsequent NREMS episodes. Within NREMS episodes, the values in the spindle frequency range showed a U‐shaped time course, the trough coinciding with a high level of SWA. By contrast, in both the early and late part of the episode the two types of activity changed in the same direction. The results are consistent with recent electrophysiological studies indicating that the establishment of NREMS is associated with a progressive hyperpolarization of thalamocortical neurons during which the membrane potential exhibits oscillations first in the spindle frequency range and then in the range of SWA.

Summary: The two‐process model serves as a major conceptual framework in sleep science. Although dating back more than four decades, it has not lost its relevance for research today. Retracing its origins, I describe how animal experiments aimed at exploring the oscillators driving the circadian sleep–wake rhythm led to the recognition of gradients of sleep states within the daily sleep period. Advances in signal analysis revealed that the level of slow‐wave activity in non‐rapid eye movement sleep electroencephalogram is high at the beginning of the 12‐light period and then declines. After sleep deprivation, the level of slow‐wave activity is enhanced. By scheduling recovery sleep to the animal's activity period, the conflict between the sleep–wake‐dependent and the circadian influence resulted in a two‐stage recovery pattern. These experiments provided the basis for the first version of the two‐process model. Sleep deprivation experiments in humans showed that the decline of slow‐wave activity during sleep is exponential. The two‐process model posits that a sleep–wake‐dependent homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C). At present, homeostatic and circadian facets of sleep regulation are being investigated at the synaptic level as well as in the transcriptome and proteome domains. The notion of sleep has been extended from a global phenomenon to local representations, while the master circadian pacemaker has been supplemented by multiple peripheral oscillators. The original interpretation that the emergence of sleep may be viewed as an escape from the rigid control imposed by the circadian pacemaker is still upheld.

The two-process model of sleep regulation has served as a conceptual framework in the last four decades for understanding sleep physiology. In the 1970s, long-term recordings of sleep in rats were obtained thanks to EEG telemetry. NonREM sleep and REM sleep were found to differ in their time course and response to light-dark protocols. There were indications for their coupling to the circadian system, in particular the light-dark and the dark-light transitions. With the advent of quantitative EEG analysis, slow-wave activity in nonREM sleep was recognized as a sleep-wake-dependent variable. The term “sleep homeostasis” was coined to specify the regulated balance between sleep and waking. The regulatory homeostatic process was designated as “Process S”. In the two-process model, its interaction with the circadian pacemaker “Process C” can account for sleep duration under various experimental protocols. Local, use-dependent slow-wave activity changes were demonstrated in both humans and rats by the selective, unilateral activation of a cortical region prior to sleep. Finding that rest in invertebrates has sleep-like regulatory properties opened a new realm of animal studies. Comparative sleep studies in a broad variety of animal species confirmed the validity of the basic concepts of the two-process model. Recent studies have addressed sleep-related changes of brain temperature as an indicator of brain metabolism; the application of the model to Drosophila; the divergence of cortical and subcortical states; and sleep in an increasing number of species and taxa.