Ancient Indian sages, Egyptians and Greeks, and Romans, have all described sleep in various ways, including naming the gods who brought dreams to sleepers. It was also well known that many people experienced sleep in two shifts, with an hour or three of intervening wakefulness, when one could have quiet time alone or visit one’s neighbors, or complete some task.
Around 450 BC, a Greek physician, Alcmaeon, postulated that sleep was a spell of unconsciousness brought on by the lack of circulation to the brain, because of blood draining from the body surface. Similarly, circa 400 BC, it was thought that the drop in the surface temperature of a sleeping person was the cause of sleep.
About 50 years later, Aristotle commented that sleep was an arrest of consciousness, in the heart (thought to be the seat of sense and sensibility), so it would last longer. He connected the digestive process with the onset of sleep as well
It was in 162 AD that Galen identified the brain, rather than the heart, as the seat of consciousness. Over the next 1600 years, however, little progress was made in understanding the nature of sleep. It is important to note that sleep was thought of as a detoxifying process, one which shut down some bodily mechanisms, or as being brought on by the lack of blood.
In the Age of Enlightenment, some science experts started the practice of interpreting their own dreams. The bedroom slowly became a place for sleep and sexual intimacy alone, and sleep itself became regulated. By the 1800s, excessive sleep was regarded as a mark of slothfulness.
In the 1900s, neurons were discovered to be the individual units of the nervous system. The year 1903 marked the formulation of the first sleeping pill, barbital. Within 30 years, it had become one of the most abused drugs in the USA. A still more momentous discovery was that of Circadian rhythms in the body.
In 1911, Henri Piéron et al found that sleep-deprived animals apparently secreted a sleep-inducing molecule into the cerebrospinal fluid which could make alert dogs fall into a deep sleep when injected into them. This was termed ‘hypnotoxin’. Two years later, he published the first book to attempt to deal with the physiology of sleep.
Constantin von Economo, a physician, studied patients with encephalitis who displayed sleep abnormalities, and identified the region of the brain called the hypothalamus as the center of sleep and wake activity in 1916 and following years.
The year 1925 was the start of the research of one of the most distinguished workers in the field, Nathaniel Kleitman. He discovered the existence of rapid eye movement (REM) sleep, and went on to study sleep and wakefulness; cerebral cortical activity in mentation, consciousness, and voluntary movement; and the effects of sleep deprivation.
In 1924, the electroencephalogram (EEG) was invented, but it was published only after 5 years in which the concept was validated. The differing brain electrical waves during sleep and wakefulness were discovered during this process. Around this time, stimulants began to be used to promote wakefulness in narcolepsy patients.
In 1935, the German researcher Bunning recognized the existence of the biological clock, and found that it is inherited in each species. Just two years later, the team of Loomis, Harvey, and Hobart discovered the five stages of sleep, and named the brain waves characteristic of each, as alpha, low voltage, spindles, spindles plus random, and random waves. The structure of sleep was being unveiled.
In 1939, Kleitman’s Sleep and Wakefulness was published, covering many years of sleep research, sleep disorders, temperature changes during sleep, and sleep-wake cycles. Further work established the role of the brainstem in skeletal muscle relaxation during sleep, which advanced the understanding of the neurophysiology of sleep.
It was in 1953 that REM sleep was first detected, in a young boy, which was startling to the researcher involved, because it contradicted the general impression that brain activity dropped to a low during sleep. The next year, it was found that night-time sleep consists of several repeating cycles. Melatonin was discovered in 1958 and proved to be key in regulating sleep.
In 1959, a crucial distinction was made between REM and NREM sleep by Michel Jouvet, because the former was not light sleep, but ‘paradoxical sleep’, with the increased brain activity being accompanied by skeletal muscle inhibition which prevents the body from acting out the vivid images and sounds in the dreams experienced during REM. In NREM, this inhibition is not seen, and brain activity is low. The same year, Circadian rhythms were named as such by Halberg, who identified and studied them in humans for the first time, thus becoming the father of chronobiology.
In 1962 Jouvet discovered that the pons regulates REM sleep. Obstructive sleep apnea became the poster boy of sleep medicine, with physiological changes being described and studied in detail in connection with sleep and awakening in 1965. This was extended to a systematic study of temperature, circulatory, and breathing changes during sleep.
Parasomnias and bed-wetting were identified to be products of confusional awakening from slow-wave sleep rather than REM sleep, in a 1968 paper by Roger Broughton. The following decade saw the setting up of the first sleep research center at Stanford in 1970, the identification of a genetic (‘per’ gene) and physical locus (suprachiasmatic nucleus) for the Circadian rhythms, and the evolution of reliable sleepiness measures such as the multiple sleep latency test (MSLT). Models were put forth to explain dreams (the activation-synthesis model) apart from psychoanalytical and supernatural explanations, and sleep stage switching, such as the reciprocal-interaction hypothesis for REM-NREM alternation.
In the 1980s, the connection between the Circadian rhythm and the duration of sleep was determined, as well as with other cues. The relationship between sleep and learning was studied, and the absolute physiological necessity of sleep to life was finally confirmed. Molecular biology started to play a major role in this field. The most authoritative book on sleep research, Principles and Practice of Sleep Medicine, was published in 1989.
The 1990s saw the emergence of numerous working theories of sleep, including the neuronal group theory and the brain energy metabolism theory. The so-called sleep switch, in the ventrolateral pre-optic area, was identified by Saper and his team. Deficiency of orexin receptor, a molecule whose absence produces narcolepsy, was discovered and van Cauter et al started to explore the effects of sleep deprivation on carbohydrate metabolism. The role of light and melanopsin, a retinal pigment, in setting the biological clock, was uncovered, shedding fascinating light upon the process of sleep regulation.
In 2003, Tononi and Cirelli proposed the synaptic homeostasis theory, which stated that sleep allowed synaptic networks to recoup and reduce their activation level, so as to conserve their strength. Sleep and memory consolidation, as well as sleep deprivation and the risk of poor judgment and motor errors, were studied and data published. The search for a single unified theory of the cause and effects of sleep in human life went on, with hundreds of sleep centers in the US alone. Work is currently going on to establish the genetic, environmental, and psychosocial aspects of sleep disorders.
Reviewed by Susha Cheriyedath, MSc