Sleep Deprivation

Basic Science, Physiology and Behavior

Clete A. Kushida, Clete A. Kushida

• Publisher: CRC Press
• Year: 2004
• ISBN:
  9781135519346
• Edition: 1
• Topic: Medicina
• Subtopic: Teoría, práctica y referencia médicas

Analyzing ground-breaking research, this reference highlights the impact of sleep deprivation on the well-being of the individual and society-presenting current theories on the function of sleep, the effects of sleep deprivation on patients with medical and psychiatric conditions, as well as providing interpretative and methodological results in co

1
Perspectives

WYNNE CHEN AND CLETE A. KUSHIDA
Stanford University, Stanford, California, U.S.A.

“The term ‘function’ in the biological literature is a slippery idea. Whether we think in terms of genes, cells or organisms, these entities are not functionally discrete. Despite their differences, each operates seamlessly within a system to achieve survival in the face of environmental challenges, while also carrying the constraints of the evolutionary past and the capacity of future change.”

Kenneth S. Kosik—Beyond phrenology, at last (1)

I. Introduction

What is sleep? Sleep scientists might define sleep as a period of behavioral quiescence and non-responsiveness to the environment that is electroencephalographically, physiologically, and behaviorally distinct from the waking state. Sleep is divided into two states, rapid-eye-movement (REM, or “paradoxical” sleep in animals) and non-REM (NREM) sleep that are also electroencephalographically, physiologically, and behaviorally distinct from one another. NREM sleep is further subdivided into four stages 1–4 (or I-IV), corresponding to the depth of sleep, and the presence of specific electrophysiologic markers.

What is sleep deprivation? The deprivation of sleep is the partial or near-complete removal of sleep in an organism. There can never be a complete absence of sleep, due to the fact a “perfect” sleep deprivation procedure has not been developed that is technologically capable of eliminating all sleep. With sleep deprivation, especially over a long period, there is a progressively-accumulating sleep debt that results in greater and greater efforts, bordering on the heroic, to maintain wakefulness in the subject. Microsleeps, which are often too brief to detect and prevent, are an inevitable consequence of sleep deprivation, and the accumulation of these very brief sleep periods may add up to significant amounts of sleep as the deprivation period progresses. There are several types of sleep deprivation. Besides “total” sleep deprivation, there is partial sleep deprivation, which typically can refer to two different paradigms. The first is where sleep is restricted to a level less than baseline sleep amounts, irrespective of sleep state or stage. For example, partial sleep deprivation may involve restricting a human subject to 4 hours of sleep per night, in contrast to his or her baseline sleep amounts of 8.5 hours of sleep per night. The second paradigm for partial sleep deprivation refers to the following. Sleep deprivation may be sleep state specific, where the subject may be specifically deprived of NREM or REM sleep, or sleep stage specific, where the subject may be specifically deprived of any of the stages of NREM sleep. It is impossible to deprive a subject of a state or stage of sleep without affecting the other state or stages of sleep. For example, deprivation of REM sleep will inevitably result in a decrease in NREM sleep amounts, and vice versa. Subjects may also be acutely or chronically sleep deprived, with increased effort required, as discussed earlier, for the longer periods of deprivation. Sleep fragmentation, a different method of sleep deprivation, involves awakening the subject during their sleep, and can either be sleep state/stage specific (e.g., awaking a subject only during REM sleep) or not. A subject can also be naturally deprived of sleep by the presence of sleep disorders or medical conditions that disrupt or fragment sleep.

What it is the function of sleep? In the field of behavioral neurosciences, this question is rather unique in being so familiar, yet so difficult to define scientifically (2). It is clear that sleep has an important physiologic function, given its widespread presence in the animal kingdom, and its persistence among species despite the attendant risks taken during such recurrent periods of reduced awareness, which is characteristic of the sleep state (3). Molecular and behavioral conservation indicate that sleep likely conferred a selective advantage in ancestral mammals, and sleep deprivation experiments in animals have clearly shown that sleep is required for survival (4). However, the specific function or functions of sleep have not been so easily defined, as evidenced by the several reviews and conferences on the subject (2,5,6). While several putative functions for sleep have been proposed, as Rechtschaffen has opined (5), such theories have suffered from a lack of parsimony; it has been difficult to explain diverse data gathered by different methods among different populations. Indeed, the evidence on sleep function may be inconsistent and incongruous because sleep makes several partial contributions to several different functions. No single contribution may be so essential or ubiquitous across species and age groups, that a succinct statement about its function can be made (5). Furthermore, such functions may not be well reflected at the organ or system level. Specifically, the observable system characteristics of sleep might be relevant only in that it permits more essential molecular processes to occur (4). For example, it has been proposed that the muscular hypotonia of sleep may allow for the endogenous reinforcement of motor circuits by synaptic activation (7).

Yet, the past decade has proven an especially exciting time in the field of sleep research, characterized by intense investigation into the biochemical and genetic mechanisms of sleep (8). Innovations in technology have allowed researchers to examine the sleeping brain using quantitative electrophysiology, functional neuroimaging, and genetic techniques. Furthermore, the ability to monitor and record the awake and sleeping brain with electroencephalography (EEG) outside of the laboratory setting, has led to knowledge, which would have been impossible to acquire previously (9). It has been possible to map upwards from the level of neuromodulatory systems to the functional geography of the human brain and, finally to cognition (10–12). We now know that the control mechanisms of sleep are manifested at every level of biological organization, from genes and intracellular processes, to neuronal cell networks, and involve systems that control movement, behavior, cognition, and autonomic functions (13). Studies utilizing sleep deprivation protocols have been instrumental in much of this progress, and what follows will be an overview of the role of sleep deprivation in this ongoing search for the function(s) of sleep. In the end, while no one prevailing theory about the function of sleep emerges the victor, how and why the various theories emerged and evolved should become evident, as should how the aforementioned technological advances have made basic sleep deprivation techniques more powerful than the earliest researchers in the field of sleep medicine, could have ever imagined.

II. Methods and Limitations of Sleep Deprivation

The very first sleep deprivation studies (see also Chap. 2) were conducted in puppies (14), but were soon followed by human studies. In 1896, three young subjects (15) were crudely studied while being kept awake for 88 to 90 hours. Physiological and psychological assessments revealed increases in weight; impairments in reaction time and voluntary motor ability; and memory deficits. One participant also experienced visual hallucinations and a gradual decrease in body temperature, although circadian rhythmicity was preserved. Recovery sleep lasted 10.5 to 12 hours, and all subjects seemed to be normal after their recovery night of sleep. However, more than fifty years would pass until more sophisticated methods of physiologic monitoring allowed the discovery of REM sleep (16). Soon after, Dement (17) performed the first human selective REM sleep deprivation experiment in which more frequent attempts at entering REM sleep and an increased percentage of REM sleep rebounds during recovery sleep were observed, as well as psychological disturbances, which included anxiety, irritability, and difficulty in verbal communication. This led to more refined techniques in selective REM sleep deprivation in animal models, which have included the cat, mouse and rat; the rat being the most extensively studied to date. The rat is perhaps the most ideal animal model for physiologists (18); three major procedures have been used to enforce sleep deprivation in the rat (19). Requiring relatively modest labor and instrumentation, the most commonly employed method has been that involving continuously enforced locomotion. However, there has been controversy over whether this method of stimulation—locomotion—contributes to rebounds from short-term total sleep deprivation (20–24). Yet, subsequent studies using “gentler” methods of sleep deprivation, such as “hand-deprivation” (21,25), proved equally if not more problematic. It seemed impractical if not impossible to enforce chronic total sleep deprivation with such a method, as it required several experimenters, and rats could adapt quickly even to the most novel of methods of gentle stimulation. For example, one study maintained deprivation by “non-putative” procedures, but ultimately, immersion in water was frequently required to help maintain wakefulness (26); even then, there was some evidence of decreased attentiveness on the part of the experimenters themselves.

Therefore, in an attempt to reduce both the motor activity and sensory stimulation necessary to induce sleep deprivation, Rechtschaffen and colleagues (27,28) at the University of Chicago, devised the “disk-over-water” (DOW) method (Figures 1 and 2; see also chapters 4,5). In this method, both experimental and control rats were subjected to similar sensory stimulation and a similar light locomotor load (i.e., the disk usually rotated at only about 20–30% of the day for a total of about 1.0 kilometers per day, which was comparatively less than the daily 3.0 kilometers per day that the rats would normally run) (24). Therefore, an advantage of the DOW method was that the effects of the deprivation method were controlled for by the use of a yoked-control rat, which received almost the exact type of physical stimulation as the sleep-deprived rat. Whatever stress was induced by the deprivation method per se would theoretically be experienced by both the sleep-deprived and control rats, and would equally affect their sleep patterns during recovery sleep (19). Indeed, sleep-deprived rats studied in this manner showed either minimal or none of the traditional “stress” indicators. These include the development of stomach ulcers, adrenal hypertrophy, increases in ACTH and corticosterone, decreased food intake, expression of stress-response genes, an initial decrease in metabolic rate, or initial hypothermia and later fever (totally sleep-deprived rats showed the opposi...