Our nightly rest affects our mind and health more than previously thought / Robert Stickgold
The article is published with the approval of Scientific American Israel and the Ort Israel network
in brief
- Many studies, as well as general life experience, support the connection between a good night's sleep and improved mood, memory and learning.
- Many experiments conducted in the last two decades have also revealed that the sleep mechanism directly affects the body's activity, starting with hormonal balance and ending with the protection of the immune system.
- Despite these findings, researchers still don't understand why exactly we need to sleep every day, but they are discovering a lot of information about what exactly happens when we sleep.
Do you really need to sleep?" During the sleep lectures I give around the world, I get asked this question over and over again. The answer was always clear: "Yes, everyone must sleep. Just like hunger, thirst and sexual desire, the need to sleep is a physiological drive." However, scientists have long wondered why we need to spend a third of our lives unconscious.
Acknowledging the lack of a satisfactory answer, Alan Rechtshafen, one of the world's leading sleep researchers, said in 1978: "If sleep does not serve a completely essential function, it is the biggest mistake evolution has ever made" (emphasis mine). In the 90s, J. Alan Hobson, also a leading sleep researcher, noted that the only known function of sleep is to cure sleepiness.
Research conducted over the past 20 years has finally begun to provide at least a partial explanation for our need for sleep. The most obvious finding is that sleep does not fulfill a single purpose, but is also needed for the optimal functioning of a variety of biological processes: from the activity of the immune system and hormonal balance to mental and emotional health, from learning and memory to eliminating toxins from the brain. At the same time, none of these activities fail completely in the absence of sleep. In general, sleep seems to improve the functioning of these systems, but is not absolutely necessary. Still, anyone who goes months without sleep will die.
Even this partial understanding has evolved over many decades. The ancient explanations about the causes of sleep claimed that it was caused by the withdrawal of blood from the surface of the skin or by the accumulation of hot vapors from the stomach. At the end of the 20th century, researchers replaced these hypotheses with detailed measurements of brain wave activity, breathing patterns, and daily fluctuations in the amount of hormones and other molecules in the blood. Recently, researchers have begun to identify the exact aspects of sleep that are important for each of its benefits. But ironically, as much as researchers reveal the uncompromising need for a good night's sleep for the proper functioning of the mind and body, the citizens of the 21st century rarely actually spend time in the comforting arms of Morpheus, the Greek god of dreams.
Fatal lack of sleep
The clearest evidence regarding our absolute need for sleep comes from a study published in 1989 by Carol Everson while working in Rechtshafen's laboratory. Everson, now at the Medical College of Wisconsin, found that rats that were completely deprived of sleep died within a month. In fact, all she had to do to achieve the lethal result was to prevent the animals from entering a stage of sleep characterized by rapid eye movement (REM). But a quarter of a century later, researchers still can't explain why the rats died. A series of experiments conducted in the past years only made it possible to rule out possible causes. For example: increased stress response, excess energy consumption or failure of the internal heat regulation of the body or of the immune system.
Death due to sleep deprivation is not unique to rats. Fatal Familial Insomnia, a disease first described 30 years ago, is a hereditary disease in humans, and as its name suggests, first causes permanent sleeplessness and eventually death. A group of Italian researchers, then at the University of Bologna School of Medicine, reported it in 1986. The group, led by Elio Lugresi and Rosella Madori, told the story of a 53-year-old man who died within months of suffering from untreatable insomnia - like many of his relatives over two generations. Postmortem brain analysis showed massive loss of brain cells in two areas of the thalamus, a walnut-sized structure located in the midbrain that generally functions as a transit station for sensory input reaching the brain. But these two particular areas are better known for their role in regulating emotional memory and producing what are known as sleep spindles, a key pattern of brain waves that can be seen in electroencephalograms of the brain during sleep.
It is not clear how this deterioration in the thalamus can lead to sleeplessness or alternatively death. But the immediate cause of the damage itself is now known. In the early 90s, Madori, who by then had already moved to Case Western Reserve University, and her colleagues discovered that an abnormal protein, called prion, was responsible for the destruction. Prions also cause scrapie disease in sheep, and Creutzfeldt-Jakob disease ("mad cow disease") in humans. Although in the case of fatal familial insomnia, the prion protein is inherited from generation to generation and does not come from food, as in the case of the other two diseases.
Fortunately, there are no other reports of human deaths from sleep deprivation (except for random accidents when, for example, tired drivers fall asleep at the wheel). But there are also no other reports of people living months without sleep. If so, we are left with two examples of complete and prolonged sleep deprivation that causes death: sleep deprivation in an experiment in rats, and a hereditary disease of prions in humans, and without any understanding of the exact cause of death in either case.
Antibodies and hormones
In the meantime, we do know that even one night of complete or even partial lack of sleep can interfere with a variety of bodily processes, such as hormonal activity and protection against infections. Two studies that examined the body's response to a vaccine against jaundice show how dramatic the effect of sleep deprivation on the immune system can be. In the first experiment, from 2003, a small group of students were vaccinated in the morning with a standard formulation for hepatitis A, containing a killed virus, after which the researchers allowed half of them to sleep normally, while the other half remained awake during the night.
The insomniac subjects were not allowed to sleep until the next night. Four weeks later, the researchers took blood samples from the students and measured the amount of protective antibodies that their immune system produced in response to the virus in the composition. Higher levels of antibodies indicate a better response to the vaccine and are therefore expected to provide better protection against future infection with disease-causing hepatitis viruses. After the four weeks, the group that enjoyed a good night's sleep had 97% higher antibody levels than the sleep-deprived group.
Negative effects are also obtained when you sleep less than a full night. In the second study, adults received a hepatitis B vaccine. The subjects received three doses of a standard component over the course of six months, a repeat vaccination is needed to build up full immune protection, and during that time the researchers monitored their sleep at home using a clock-shaped motion detector. After that, the researchers examined the average amount of sleep of the participants in the week after the first injection and compared the results to the level of antibodies in their blood after the second injection. The researchers found that antibody levels increased by 56% with each additional hour of sleep. Six months after the last vaccine dose, participants who slept less than six hours on average during the week after the first injection were seven times more likely than others to develop a level of antibodies in the blood that is considered too low to provide protection against the hepatitis B virus.
Impressive evidence of poor hormonal activity was obtained from a series of studies conducted by Karin Spiegel, who was working at the time with Yvonne Kotter at the University of Chicago. In one of the experiments, the researchers allowed 11 young, healthy men to sleep only four hours a night. After five nights of sleep deprivation, the subjects' ability to remove glucose from the blood, a process dependent on the hormone insulin, decreased by 40%. In another study, Spiegel and her colleagues similarly restricted the sleeping hours of 12 men for two nights. The scientists measured the level of the hormone ghrelin, which stimulates appetite, in the subjects' blood, and saw that it increased by 28%. At the same time, the blood level of another hormone, called leptin, which inhibits hunger by signaling to the brain that there is no need to eat, decreased by 18%. Not surprisingly, the hunger level of the sleep-deprived men increased by 23% on average, according to their reports.
Illustration of the human body with an emphasis on the central nervous system, the immune system and the endocrine system. Credit: Brian Christie
Findings - don't cut back on sleep:
Studies have revealed many mechanisms by which lack of sleep harms our mental and physical health. Some of the most studied and important effects are listed here. (Illustration: Brian Christie)
The general picture that emerges from studies on human physiology shows that reduced sleep can lead to weight gain: a conclusion currently supported by at least 50 studies. In several studies, it was found that the risk of children aged nine to eleven, who sleep less than 10 hours a night, to become overweight was one and a half to two times higher than that of children who slept more. Whereas studies in adults indicate a 50% increase in obesity in participants who sleep less than six hours a night. Studies also point to a correlation between little sleep and the development of type 2 diabetes.
A bomb of negativity
Although limited sleep has such an acute effect on hormonal activity and the activity of the immune system, its greatest effect probably occurs in the brain. In a 2006 study I conducted with Matthew P. Walker, now at UC Berkeley, we looked at how sleep deprivation for one night affects our emotional memories. We presented 26 subjects, half of whom had not slept the night before, words with a positive, negative or neutral meaning (for example, "calm", "sorrow" or "willow tree") and asked them to rate the degree of emotion they evoke. After two nights of restful sleep, they underwent a surprise memory test.
Subjects who did not sleep before seeing the words for the first time showed a 40% deterioration in their ability to remember the words compared to subjects who slept properly. But more impressive was the relative effect of sleep deprivation on recalling words from the three different categories. In the sleep-deprived subjects, the ability to remember the positive or neutral words deteriorated by 50%. But their ability to remember words with a negative meaning deteriorated by only 20%. On the other hand, if the subjects had a normal sleep, no difference was found in the extent to which they remembered words with a negative or positive meaning, although they remembered these words better than they remembered words with a neutral meaning. In other words, the memory of words with a negative meaning was at least twice as strong as that of positive or neutral words after the study participants were forced to give up sleep.
These results raise the rather horrifying possibility that when we are sleep deprived, we actually create twice as many memories of negative events in our lives as memories of positive events, creating a biased and depressing memory of our day. Indeed, several studies conducted in the last 25 years have shown that poor sleep can, under certain conditions, lead to depression severe enough to be defined as clinical depression and may also contribute to the development of other psychiatric illnesses.
The evidence for a causal link to depression has strengthened considerably in recent years and is largely due to studies on sleep apnea syndrome, a disturbance in the flow of air to the lungs during sleep. The disorder can lead to snoring, choking and other breathing disorders. Whenever people with sleep apnea stop breathing, they wake up for a moment to start breathing again. As a result, people with severe apnea may wake up every minute or two during the night. A 2012 study conducted by the US Centers for Disease Control and Prevention (CDC) revealed that men and women diagnosed with sleep apnea are 2.4 and 5.2 times more likely to develop clinical depression, respectively, relative to people who sleep well.
Several studies conducted over the past 25 years have concluded that poor sleep can, under certain conditions, lead to depression severe enough to be defined as clinical depression.
It is understood that there is no law of correlation between the two situations as law of proof that one causes the other. But a recent data analysis of 19 studies revealed that treating sleep apnea using devices called CPAP (short for continuous positive airway pressure), which improve breathing and sleep, significantly reduces symptoms of depression. Indeed, one of the studies, which happened to initially include a higher proportion of depressed patients than other studies have shown, found a 26% reduction in depressive symptoms in those using CPAP.
These results still do not conclusively prove that disturbed sleep can cause depression, nor has a comparison been made between the effect of CPAP treatment and the use of antidepressants. Nevertheless, it seems worthwhile to continue to explore this direction. Similarly, a 2007 study found that treating apnea in children who also have attention, concentration and hyperactivity disorder caused a 36% decrease in the rating of hyperactivity symptoms: a significant reduction compared to reduction rates of only 24%, obtained with ADHD medications.
Future memories
Although researchers still do not know the physiological mechanism by which sleep and the lack of sleep affect mental health, they suspect that there is much to do with the role that sleep plays in helping the brain turn the day's events into memories. In the last two decades, there has been a sharp increase in findings that have shown that sleep participates in the processing of memories in everyone, regardless of their mental state. In the findings: sleeping after learning causes stabilization, strengthening assimilation and selective analysis of new memories. Because of this, it controls the content of our memories and the way we remember.
In the late 19th and early 20th centuries, scientists believed that memories are fragile until the moment they undergo a crystallization process, which transforms them into a stable form that can survive for a lifetime. More recent studies have shown that memories can change even after the brain records and consolidates them. And indeed, restarting a memory can return it to an unstable state long after it was first created, a state in which recrystallization is necessary. When the memory is in this vulnerable state, it can change and even disappear completely. This finding is both a curse and a blessing. A curse, because previously accurate information can be destroyed, and a blessing, because inaccurate information can be corrected. This is why researchers today talk about the evolution of memories instead of the consolidation of memories, especially when discussing the processing of memories in sleep.
The era of modern research on sleep and memory began only about 20 years ago, when Avi Karni and his colleagues in Israel showed that the performance of subjects trained to perform a visual discrimination task improved after a night's sleep, but only if they were allowed to sink into REM sleep. (By the way, most dreams occur during REM sleep.) Their experiment showed that sleep not only stabilizes memories and prevents them from deteriorating over time, it actually improves them.
In 2000, Walker walked into my office brandishing a scientific journal article and predicted: "This too depends on sleep!" The article described a task in which the subjects learned to drum their fingers to a certain rhythm, which became easier to perform over time even without additional training. But the researchers didn't look at how sleep might contribute to improvement. Within two weeks, Walker had an answer. He found that sleep did improve performance, and then showed another stage of light sleep, other than REM sleep, improved that performance more than REM sleep did in Carney's vision experiments. The conclusion was inevitable: the brain reinforces different types of memory during different stages of sleep.
Further studies have shown that not all memories are stabilized in sleep. In 2008, Jessica Payne, now at the University of Notre Dame, conducted a study in which she presented volunteers with various images with disturbing details, such as a dead cat on the side of the road. She found that after a night's sleep, the subjects could accurately identify the picture of the dead cat, but they forgot the road in the background. What was most impressive was that this selective forgetting of background details did not occur when she trained the subjects in the morning and tested them on it in the evening after they had been awake for the day. And it didn't happen if the central figure in the picture was unobtrusive, for example just a cat crossing the road. That is, sleep, but not wakefulness, causes the subjects' brains to preserve images with high emotional value in preference to neutral images (a cat crossing the road) or background details.
But not only emotional memories are enhanced during sleep. Apparently, everything that seems important to us will be preserved in a selective way while we sleep. Two research groups in Europe have shown that when trainers are tested to perform a certain task, the processes that occur in their sleep are different if they are told that they will be tested on the information. As you might expect, only the information subjects are told they will be tested on improves the next day. On the other hand, when the subjects are trained in the morning, the knowledge that they will or will not be tested in the evening does not matter at all. Sleep, rather than being awake, selectively reinforces memories that our brain classifies as important.
These findings provide elegant support for Daniel Schechter of Harvard University's contention that memory deals with the future and not the past. He argued that we evolved memory systems not to recall past memories but so that we could use previous experience to improve our future functioning. So, it's no wonder that when we sleep, our brain pays special attention to information that may be of future importance. When we say that you need to "sleep on it" to solve a problem, we are not asking the old brain to simply remember something. We want our brain to take information already stored in it and do some calculation, to take into account different possibilities and find the best solution to the problem. Lucky for us, he does!
An example of this analytical ability is the weather prediction experiment developed by Barbara J. Knowlton and her colleagues at the University of California at Los Angeles (UCLA). Knowlton showed subjects one or more cards from a series of four cards that each had a certain geometric shape (circle, diamond, square, or triangle). Before the subjects began the task, the researchers assigned each card to rainy or sunny weather and did not share the information with the patients. Then, based on the cards presented, the researchers asked the subjects to predict whether the cards indicate rainy or sunny weather. Over time, subjects developed a sense of how the cards were associated with the weather. In the first experiment, for example, a diamond card was shown, and the subjects were told that the weather was sunny. In the second experiment, the circle and triangle cards were shown and the subjects were told that the weather was rainy. Already after these two experiments, the subjects, without exception, began to develop hypotheses about the connections, for example that Moin means sun. But then, on the third trial, the diamond card appeared again, followed by rain.
The trick was that the cards were related to the weather in a probabilistic relationship. Thus, the diamond card predicts sunshine 80% of the time, but the remaining 20% will be followed by rain. Other cards predict sunshine only 20% to 60% of the time. In Knowlton's study, even after 200 repetitions, subjects still did not master the task, guessing the most likely outcome only 75% of the time.
The use of such tasks allowed the researchers to distinguish between different memory systems in the brain: systems related to the memory of facts (the "what" system), versus systems related to the memory of skills (the "how" system). When subjects practice the weather forecasting task, they slowly move from using the what system to the how system. When researcher Ina Dzunlejic from my lab asked what happens to this information during sleep, she got an amazing result. When volunteers who practiced in the morning were re-tested that evening, they also guessed about 75% of the results, and apparently fully retained the information they learned in the morning. But when other subjects trained in the evening and were tested after a night of sleep, their result improved by 10% relative to the previous evening. Somehow the old brain managed to improve the subjects' understanding of the connection between the cards and the weather they were predicting. They formed a better model of how the world works.
As researchers investigate more about what happens when we sleep, they discover additional benefits of a good night's sleep. The last addition to the list is the elimination, apparently, of waste materials from the brain. In 2013, Lulu Sia and her colleagues at the University of Rochester Medical Center reported that the spaces between brain cells widen during sleep, allowing for better passage of cerebrospinal fluid between the brain and the spinal cord. When researchers injected beta-amyloid (the precursor protein to the amyloid layers found between nerve cells in Alzheimer's disease) into mice, they found that it was cleared from the brain during sleep twice as fast as in awake animals. Apparently the increased flow of cerebrospinal fluid helped remove the potentially toxic molecule from the brain, away from the areas where the damage may be greatest. Now researchers are trying to find out if the increased flow during sleep is impaired in people with Alzheimer's.
In light of all the recent research on the many roles of sleep and the likelihood that many more roles will be discovered, cutting back on sleep seems like a very poor strategy for dealing with the day-to-day tasks of life. The picture that emerges is that the results of studies examining the effect of sleep on hormonal activity, on the immune system and on memory indicate that if we do not get enough sleep, we will not only be tired, but also sick, fat, forgetful and very sad.
About the writers
Robert Stickgold is the director of the Sleep and Cognition Center at Beth Israel Deaconess Medical Center and an associate professor at Harvard Medical School.
- for further reading
- Sleep Deprivation in the Rat: An Update of the 1989 Paper. Allan Rechtschaffen and Bernard M. Bergmann in Sleep, Vol. 25, no. 1, pages 18–24; 2002
- Sleep and the Epidemic of Obesity in Children and Adults. Eve Van Cauter and Kristen L. Knutson in European Journal of Endocrinology, Vol. 159, Supplement No. 1, pages S59–S66; December 2008
- To Sleep, to Strive, or Both: How Best to Optimize Memory. Matthew A. Tucker et al. in PLOS ONE, Vol. 6, no. 7, Article No. e21737; July 20, 2011.
- Insufficient Sleep Is a Public Health Problem, CDC
- Sleep to Prune, Giulio Tononi and Chiara Chiarli, Scientific American Israel, December 2013
- The biological clock and nutrition, Dorit Ferns, interview with Professor Oren Frey, Scientific American Israel, October 2015
