Models of human sleep regulation

Non-REM sleep deprivation and REM sleep deprivation both lead to specific rebounds, suggesting that these states fulfil physiological needs. In view of impaired performance after sleep deprivation, a recovery function of sleep seems likely. The timing of this recovery is restricted to a narrow time interval within the 24 hour day, i.e. the night. Generally, nocturnal sleep in humans is considered a consequence of the impact of the circadian pacemaker in the hypothalamus on sleep propensity. The interaction between the homeostatic recovery process and the circadian pacemaker has been modelled in the two-process model of sleep regulation. This model is used as a starting point in the present review. A series of refinements and several alternative models are discussed, both with respect to the quality of fit of theory and data, as well as with respect to the concepts behind the models

Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling

Circadian rhythms are fundamental to life. In mammals, these rhythms are generated by pacemaker neurons in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is remarkably consistent in structure and function between species, yet mammalian rest/activity patterns are extremely diverse, including diurnal, nocturnal, and crepuscular behaviors. Two mechanisms have been proposed to account for this diversity: (i) modulation of SCN output by downstream nuclei, and (ii) direct effects of light on activity. These two mechanisms are difficult to disentangle experimentally and their respective roles remain unknown. To address this, we developed a computational model to simulate the two mechanisms and their influence on temporal niche. In our model, SCN output is relayed via the subparaventricular zone (SPZ) to the dorsomedial hypothalamus (DMH), and thence to ventrolateral preoptic nuclei (VLPO) and lateral hypothalamus (LHA). Using this model, we generated rich phenotypes that closely resemble experimental data. Modulation of SCN output at the SPZ was found to generate a full spectrum of diurnal-to-nocturnal phenotypes. Intriguingly, we also uncovered a novel mechanism for crepuscular behavior: if DMH/VLPO and DMH/LHA projections act cooperatively, daily activity is unimodal, but if they act competitively, activity can become bimodal. In addition, we successfully reproduced diurnal/nocturnal switching in the rodent Octodon degu using coordinated inversions in both masking and circadian modulation. Finally, the model correctly predicted the SCN lesion phenotype in squirrel monkeys: loss of circadian rhythmicity and emergence of ∼4-h sleep/wake cycles. In capturing these diverse phenotypes, the model provides a powerful new framework for understanding rest/activity patterns and relating them to underlying physiology. Given the ubiquitous effects of temporal organization on all aspects of animal behavior and physiology, this study sheds light on the physiological changes required to orchestrate adaptation to various temporal niches

What is the Best Measure of Daytime Sleepiness in Adults With Heart Failure?

Purpose To identify the best screening measure of daytime sleepiness in adults with heart failure (HF). Data sources A total of 280 adults with HF completed the Epworth Sleepiness Scale, the Stanford Sleepiness Scale, and a single Likert item measuring daytime sleepiness. The sensitivity and specificity of these self-report measures were assessed in relation to a measure of daytime dysfunction from poor sleep quality. Conclusions Only 16% of the sample reported significant daytime dysfunction because of poor sleep quality. Those reporting daytime dysfunction were likely to be younger (p \u3c .001), to be unmarried (p = .002), to have New York Heart Association (NYHA) functional class IV HF (p = .015), and to report low income (p = .006) and fewer hours of sleep (p = .015). The measure of daytime sleepiness that was most sensitive to daytime dysfunction was a single Likert item measured on a 10-point (1–10) scale. Patients with a score ≥4 were 2.4 times more likely to have daytime dysfunction than those with a score \u3c4. Implications for practice Complaints of daytime dysfunction because of poor sleep are not common in adults with HF. Routine use of a single question about daytime sleepiness can help nurse practitioners to identify those HF patients with significant sleep issues that may require further screening

Quantitative Physiologically-Based Sleep Modeling: Dynamical Analysis and Clinical Applications

In this thesis, a recently developed physiologically-based model of the sleep-wake switch is analyzed and applied to a variety of clinically-relevant protocols. In contrast to phenomenological models, which have dominated sleep modeling in the past, the present work demonstrates the advantages of the physiologically-based approach. Dynamical and linear stability analyses of the Phillips-Robinson sleep model allow us to create a general framework for determining its response to arbitrary external stimuli. The effects of near-stable wake and sleep ghosts on the model’s dynamics are found to have implications for arousal during sleep, sleep deprivation, and sleep inertia. Impulsive sensory stimuli during sleep are modeled modeled according to their known physiological mechanism. The predicted arousal threshold variation matches experimental data from the literature. In simulating a sleep fragmentation protocol, the model simultaneously reproduces the body temperature and arousal threshold variation measured in another existing clinical study. In the second part of the thesis, we simulate sleep deprivation by introducing a wake-effort drive that is required to maintain wakefulness during normal sleeping periods. We interpret this drive both physiologically and psychologically, and demonstrate quantitative agreement between the model’s output and experimental subjective fatigue-related data. As well as subjective fatigue, the model is simultaneously able to reproduce adrenaline excretion and body temperature variations. In the final part of the thesis, the model is extended to include the orexinergic neurons of the lateral hypothalamic area. Due to the dynamics of the orexin group, the extended model exhibits sleep inertia, and an inhibitory circadian projection to the orexin group produces a postlunch dip in performance – both of which are well-known behavioral features. Including both homeostatic and circadian inputs to the orexin group, the model produces a waking arousal variation that quantitatively matches published clinical data

The two-process model of sleep regulation: a reappraisal

In the last three decades the two-process model of sleep regulation has served as a major conceptual framework in sleep research. It has been applied widely in studies on fatigue and performance and to dissect individual differences in sleep regulation. The model posits that a homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C), with time-courses derived from physiological and behavioural variables. The model simulates successfully the timing and intensity of sleep in diverse experimental protocols. Electrophysiological recordings from the suprachiasmatic nuclei (SCN) suggest that S and C interact continuously. Oscillators outside the SCN that are linked to energy metabolism are evident in SCN-lesioned arrhythmic animals subjected to restricted feeding or methamphetamine administration, as well as in human subjects during internal desynchronization. In intact animals these peripheral oscillators may dissociate from the central pacemaker rhythm. A sleep/fast and wake/feed phase segregate antagonistic anabolic and catabolic metabolic processes in peripheral tissues. A deficiency of Process S was proposed to account for both depressive sleep disturbances and the antidepressant effect of sleep deprivation. The model supported the development of novel non-pharmacological treatment paradigms in psychiatry, based on manipulating circadian phase, sleep and light exposure. In conclusion, the model remains conceptually useful for promoting the integration of sleep and circadian rhythm research. Sleep appears to have not only a short-term, use-dependent function; it also serves to enforce rest and fasting, thereby supporting the optimization of metabolic processes at the appropriate phase of the 24-h cycle

Obstructive sleep apnoea and driver performance: prevalence, correlates and implications for driver fatigue

Obstructive sleep apnoea (OSA) is characterised by repetitive reductions or pauses in breathing during sleep due to upper airway narrowing or closure. Due to disruption to normal sleep patterns, many patients with OSA suffer from increased daytime sleepiness. Epidemiological studies have established a link between OSA and driver fatigue and accidents, generally showing a two to seven times increased risk of road traffic accidents in non-commercial drivers with OSA. There is emerging evidence that commercial drivers have a higher prevalence of OSA than the general population, being predominately male, middle-aged and overweight, three important risk factors for OSA. However, little is known about the relationship between OSA and driver sleepiness in commercial drivers, whether road accidents are increased in commercial drivers with OSA, and whether OSA interacts with other fatigue promoting factors, such as sleep deprivation, to further escalate road accident risk. One thousand randomly selected commercial drivers were surveyed in the field. In addition, 61 randomly selected NSW commercial drivers had in hospital sleep studies and daytime performance testing, including a PC based driving simulator task. The prevalence of OSA, defined as Respiratory Disturbance Index (RDI) < 10, was approximately 50% in NSW commercial drivers. Approximately one quarter of the drivers reported pathological daytime sleepiness, and 12-14% had both OSA and pathological daytime sleepiness. A diagnosis of OSA was the most important factor predicting excessive daytime sleepiness in these drivers: OSA was more important than 15 other work-related, lifestyle and medical factors that could be expected to promote, or be associated with, daytime sleepiness. Drivers with sleep apnoea syndrome (both OSA and pathological daytime sleepiness) had an increased driving accident risk, using driving simulator and daytime performance testing as proxy measures for accident risk. These results demonstrate the importance of OSA as a cause of driver fatigue in commercial drivers and suggest that all commercial drivers should be screened for the presence of sleep apnoea syndrome in order to potentially reduce road accident risk through treatment. A separate, but related body of work examined the combined effects of mild OSA and other fatigue promoting factors (sleep deprivation and circadian influences) on driving performance. Twenty nine subjects, consisting of a group with mild OSA and a group of non-OSA controls, were tested on several occasions throughout the night and day using an intensive performance battery, under both baseline conditions and after a period of 36 hours of total sleep deprivation. The results suggest that drivers with mild OSA are not different to the control group in their response to sleep deprivation or time of day influences. However, the subjects with mild OSA were less aware of their impairment due to sleep deprivation, which is of concern if drivers with OSA are relying on their subjective awareness of fatigue to make decisions about when to stop driving. A final perspective on OSA and driver fatigue is provided through a clinical case series of seven fall-asleep fatality associated MVA�s associated with unrecognised or under-treated sleep disorders. As well as demonstrating the day to day potential for devastating road accidents due, at least in part, to un-recognised or untreated sleep disorders, these cases also serve to highlight some of the current medico-legal controversies and difficulties in this area of driver fatigue. In conclusion, this body of work has provided novel information about the epidemiology and implications of OSA in commercial drivers, and about how OSA interacts with other fatigue promoting factors. Finally, it has explored some of the medico-legal issues that relate to sleep disorders and driver fatigue. As well as providing much needed information in the area of driver fatigue, at the same time this work raises many more questions and suggests areas of future research. For instance, such research should examine the relationship between objective accident rates and OSA/sleep apnoea syndrome in commercial drivers, the interaction between mild sleep apnoea syndrome and other fatigue risk factors, and driver perception of sleepiness prior to sleep onset in drivers with sleep disorders

Field studies of sleep and performance in operational settings

Sleep loss leads to degraded alertness and cognitive performance. The management of factors influencing performance (time on task, sleep/wake history, and circadian rhythm) is important to workplace effectiveness. Contemporary work schedules limit sleep opportunities, leading to chronic sleep restriction. The present studies sought to examine the relationship between extended work hours, sleep, and subsequent performance. In Study 1, equipment maintenance personnel were studied during normal and extended work hours. Objective measures of sleep and performance demonstrated that extending work hours was associated with sleep loss. In this study, for each additional hour worked, an hour of sleep was lost. Contrary to expectations, objectively measured performance improved in the extended work hours condition. In Study 2, medical residents were studied while working both day shifts and a one month "night float" (extended night shift) rotation. In addition to the sleep and performance measures obtained in Study 1, two measures of learning and memory performance were administered. Medical residents obtained nearly equal amounts of objectively measured sleep while working both day and night float shifts; however, how this sleep was obtained differed between the day shift and night float conditions. Day shift sleep was obtained in a single, off shift, night time sleep bout. For the night float, some sleep was obtained in an off shift, daytime sleep bout. This daytime sleep bout was supplemented in the night float condition by napping on shift, while working the night float. By thus augmenting their truncated daytime sleep with night time, on shift naps, residents obtained near equivalent amounts of total sleep/24 hours working day shift and night float. Consistent with equivalent total sleep times between conditions, no differences in objective performance working day shift or night float were found. Field studies such as the ones presented here will be instrumental to forming the evidence-base of a fatigue risk management system. Such a system would allow for the management of sleep and duty times to sustain optimal performance in the work

ОБОБЩЕННАЯ МОДЕЛЬ ТРЕХ ПРОЦЕССОВ ЦИКЛИЧЕСКОЙ РЕГУЛЯЦИИ СНА-БОДРСТВОВАНИЯ

The most-known model of sleep-wake regulation includes different formulae describing the kinetics of three separate processes, i.e., homeostatic, circadian, and ultradian. We tried to explain all these processes within a more parsimonious modeling framework and to use the EEG recordings of baseline night sleep for derivation of the model’s parameters and for prediction of the effects of experimental manipulations with sleep-wake regimen.Самая известная модель цикла «сон-бодрствование» включает три различные формулы для описания динамики трех регуляторных процессов – гомеостатического, циркадианного и ультрадианного. Предложена модель, позволяющая применять одну простую формулу для описания всех трех процессов. Электроэнцефалографические записи обычного ночного сна были использованы для определения параметров модели и предсказания эффектов экспериментальных манипуляций режимом сна-бодрствования