June 24, 2019History of Medicine
Sleep has been seen in culture as similar to death since antiquity; in Greek mythology, Hypnos (the god of sleep) and his half-brother, Thanatos (the god of death) were both said to be the children of Nyx (the goddess of night).
Galen: On Diagnosis in Dreams
The vision-in-sleep, in my opinion, indicates a disposition of the body. Someone dreaming a conflagration is troubled by yellow bile, but if he dreams of smoke, or mist, or deep darkness, by black bile. Rainstorm indicates that cold moisture abounds; snow, ice, and hail, cold phlegm. It is necessary also to pay attention to the stage [kairos] of the disease and to the nourishment that has been taken. If, for example, someone who thinks that he is being covered with snow has this impression at the onset of an attack accompanied by trembling, shivering, or chills, one must assign this for the most part to the stage of the disease, not to the disposition of the body. But someone who has such a dream when the disease is past its crisis will provide us with a firmer indication of the coldness of his prevailing humors, all the more so if he has not eaten any of the phlegmatic foods, which, when they are encompassed in the stomach, make possible the coming-into-being of such an impression, even though the disposition in the whole body is not similar. But since in sleep the soul does not produce impressions based on dispositions of the body only, but also from the things habitually done by us day by day, and some from what we have thought - and indeed some things are revealed by it in fashion of prophesy (for even this is witnessed by experience) - the diagnosis of the body from the visions-in-sleep that arise from the body becomes difficult.
Now if it were necessary only to distinguish this cause from the things done or thought by day, it would not be at all difficult to conclude that whatever has not been done or thought is arising from the body. But since we concede that there are also prophetic dreams, it is not easy to say how these might be distinguished from the ones arising from the body. At all events, a man dreamed that one of his legs had turned to stone, and many of those clever about such matters judged that the dream pertained to his slaves, but the man was paralyzed in that leg, although none of us expected that. We established, for example, that the wrestler who seemed to be standing in a receptacle of blood and to keep above it with difficulty had an abundance of blood and was in need of purging. And some who were about to sweat critically seemed to be bathing and swimming in receptacles of hot water. So also the impression of drinking without being filled befalls those who thirst exceedingly, just as also that of eating without fulfillment befalls the famished, and that of making love, those who are full of semen.
For it is likely that in sleep the soul, having gone into the depths of the body and retreated from the external perceptions, perceives the dispositions throughout the body and forms an impression of all that it reaches out to, as though these things were already present. And if this is the case, it would in no way be marvelous, whenever the psychic faculty, weighed down by an excess of humors, is troubled, that those moving themselves with difficulty have that impression in a dream and bear some vexations; or on the other hand, whenever the disposition of the body is light and unsuperfluous, that those who are so disposed have a dream that they are flying or running swiftly, the impressions of the soul always agreeing with the dispositions of the body, even to the point of seeming to smell bad or good odors. For those who have this impression that they are passing time in dung and mire either have their internal humors in bad condition, foul-smelling, and putrid, or they have an excess of dung encompassed in their bowels. One must conclude that those who are disposed in the reverse of this way and seem to be passing time in fragrant places have the opposite disposition in their body. So what our patients see in their visions-in-sleep and seem to do often indicates to us both the shortage or abundance and the quality of their humors.
Disposition: Greek diathesis. In Galen's medical theory, a disease is not a distinct entity, but rather the result of an interaction between the diathesis or state of an organism and an affected part or peponthos topos. 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 BCE, 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 BCE, 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 CE 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 Pieron 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. Over a decade later, neuroscience research has discovered that while the brain sleeps, (and only during sleep), it clears out harmful toxins, a process that may reduce the risk of Alzheimer's.
During sleep, the flow of cerebrospinal fluid in the brain increases dramatically, washing away harmful waste proteins that build up between brain cells during waking hours, a study of mice found. The results appear to offer the best explanation yet of why animals and people need sleep. If this proves to be true in humans as well, it could help explain a mysterious association between sleep disorders and brain diseases, including Alzheimer's. Neuroscientists noticed that during sleep, the system that circulates cerebrospinal fluid through the brain and nervous system was pumping fluid into the brain and removing fluid from the brain in a very rapid pace. Based on research out of the University of Rochester, it was discovered that this increased flow was possible in part because when mice went to sleep, their brain cells actually shrank, making it easier for fluid to circulate. When an animal woke up, the brain cells enlarged again and the flow between cells slowed to a trickle; almost like opening and closing a faucet, It's that dramatic.
Previous research showed that this fluid was carrying away waste products that build up in the spaces between brain cells. The brain cleansing process is important because what's getting washed away during sleep are waste proteins that are toxic to brain cells. This could explain why we don't think clearly after a sleepless night and why a prolonged lack of sleep can actually kill an animal or a person. It's speculated that the brain only cleans itself at night and not during the day because cleaning takes a lot of energy. It's probably not possible for the brain to both clean itself and simultaneously be aware of the surroundings and talk and move and think, etc. The brain-cleaning process has been observed in rats and baboons, but not yet in humans. Even so, it could offer a new way of understanding human brain diseases including Alzheimer's. That's because one of the waste products removed from the brain during sleep is beta amyloid, the substance that forms sticky plaques associated with the disease. This is probably not a coincidence; and interesting that Alzheimer's and all other diseases associated with dementia, they are linked to sleep disorders. Researchers who study Alzheimer's say that this research could help explain a number of recent findings related to sleep. One of these involves how sleep affects levels of beta amyloid. Beta amyloid concentrations continue to increase while a person is awake. Then after people go to sleep that concentration of beta amyloid decreases.
This important research provides a beautiful mechanism by which this may be happening. The report also offers a tantalizing hint of a new approach to Alzheimer's prevention. It does raise the possibility that one might be able to actually control sleep in a way to improve the clearance of beta amyloid and help prevent amyloidosis that we think can lead to Alzheimer's disease. Sources: https://www.npr.org/sections/health-shots: https://www.news-medical.net,; nih.gov; ScienceDaily, Wikipedia