br Disclosure statement br Acknowledgements

Disclosure statement
Acknowledgements The authors thank Australian Wool Innovation Ltd (AWI) for financial support for the project that yielded material discussed in this article.
Introduction Scientific study of human sleep has been initiated by the discovery that sleep progresses through a series of stages in which different purchase (±)-Nutlin-3 wave patterns are displayed (e.g., [6]). Indeed, visual analysis of most of polysomnographic sleep records reveals that human sleep begins in stage 1 (N1) and progresses into stages 2 (N2) and 3 (N3) of Non-Rapid-Eye-Movement (NREM) sleep. The conventional methodology of such subdivision of the sleep records into intervals each of which is allocated to one of a few all-or-nothing variables called “sleep stages” has been first introduced in 1968 in the publication of the standard sleep scoring rules [20]. Since some of these rules, especially with respect to stage boundaries, are difficult to follow, this standard system of sleep description faces practical problems of definition and demarcation of sleep stages [24,23]. Nevertheless, the criteria for distinction between stages 1 and 3 of NREM sleep had remained almost unchanged after rare attempts to revise these criteria [3,24]. One of the major shortcomings of the standard scoring rules is their relying on arbitrarily-defined thresholds for separation of NREM sleep stages. For instance, the most powerful component of the electroencephalographic (EEG) signal, delta activity (slow waves with frequencies 0.5–4.5Hz), exhibits a gradual increase in the course of sleep deepening that starts with a short transitional interval known as stage 1 (N1), continues through the following much longer interval of stage 2(N2) that is viewed as the first unequivocal stage of sleep and reaches its peak during stage 3 (N3) that is usually named slow wave sleep (SWS) due to predominance of relatively high-voltage (more than 75μV) low-frequency waves (0.5–2.0Hz). The arbitrarily-defined threshold criteria that were recommended for defying stage 3 (N3 or SWS) include three (amount, frequency and amplitude) thresholds, i.e., more than 20% of <2Hz activity with amplitude >75μV during a given epoch of sleep [20,3]. Therefore, subjective assessment of the EEG epochs is necessary and this can lead to unreliable results and poor agreement between scorers [4]. Particularly, Norman et al. [10] reported that stages N1 and N3 are most prone to disagreement, and that, overall, 88.4% of the scoring disagreements are associated with scoring adjacent stages (wake/N1, N1/N2, and N2/SWS). Until recently, SWS and slow-wave activity have been simply viewed as useful objective markers of sleep deepness and intensity. However, most recent studies showed that they might be of particular importance for analysis of the sleep process due to their unique vital functions. For example, these studies point to their essential role in learning and memory (e.g., [7,19,5,26,25]). Since the presence and integrity of SWS was found to be linked to the ability to form and retain memories, the diminished levels of conventionally scored stage 3 sleep can explain some cognitive impairment in primary insomnia and older age (e.g., [1,9]). Therefore, one of the questions that need to be answered in the light of such recent findings might be: where is the true neurophysiological boundary between stages 2 and 3 (N2/N3)? Earlier we showed that principal component structuring of the EEG spectrum provides a theoretically sound method of relating the quantitative descriptions of spectral power densities to quantitative changes (i.e., from negative to positive) in scores on the largest principal components of the EEG spectrum [11–15,17,16,18]. It was hypothesized that the rise of the 1st score reflects the switch-like change in the sleep-promoting processes that usually delays relative to the change in the wake-promoting processes represented by the decline of the 2nd score [11,16]. Consequently, stage 1 sleep might be viewed as “no man׳s land” between the opponent driving forces for wake and sleep [14,15]. It was also shown that, like it occurs during diurnal sleep-wake transitions, the 1st and 2nd components of the EEG spectrum might also represent alternations between competing drives for sleep and wakefulness throughout the whole episode of all-night sleep, whereas time courses of the next pair of component scores (3rd and 4th) might reflect the within-sleep alternations between sub-sates of light and deep sleep, respectively [11,12]. At least, the time course of the 4th score during each ultradian sleep cycle pointed to its link to deep sleep, i.e., its rapid raise always delayed relative to changes in the 1st and 2nd scores in the beginning of the first sleep cycle, but its maximum was reached already in the middle of the cycle, and its fall during the second half of the cycle occurred earlier compared to changes in other scores [11,12].