The Basics of Sleep/Sleep Deprivation as a Stressor

[cutthecashflow]

This may need additional work/citations as I have not fine combed it yet, but nonetheless here it is...

The Basics of Sleep

All things considered, sleeping is pretty creepy. For a third of your life, you’re just not there, floating in this suspended state, everything slowed down. Except, at points, your brain is more active than when you’re awake, making your eyelids all twitchy, and it’s consolidating memories from the day and solving problems for you. Except when it’s dreaming, when it’s making no sense and then you sometimes walk or talk in your sleep. Or drool. And then there’s those mysterious penile or clitoral erections that occur intermittently during the night.
Weird, what’s going on here? To start, sleep is not a monolithic process, a uniform phenomenon. Instead, there are different types of sleep--- shallow (also known as stages and 2) sleep, where you are easily awakened. Deep sleep (also known as stages 3 and 4, or “slow wave sleep”). Rapid Eye Movement (REM) sleep, where the puppy’s paws flutter and our eyes dart around and dreams happen. There are not only these different stages, but a structure, an architecture to them. You start off shallow, gradually sleep your way down to slow wave sleep, followed by REM, then back up again, and then repeat the whole cycle about every ninety minutes.

Not surprisingly, the brain works differently in different stages of sleep. This can be studied by having people sleep in a brain scanner, while you measure the activity of different brain regions. Take some volunteers, sleep-deprive them for some godawful length of time, stick them in one of these imaging machines, poke them awake a little more while you get a measure of their brains’ activity when they’re awake, and then, snug as a bug in a scanner, let them go to sleep with the scanner running.

The picture during slow wave sleep makes a lot of sense. Parts of the brain associated with arousal activity slow down. Ditto for brain regions involved in controlling muscle movement. Interestingly, brain regions involved in the consolidation and retrieval of memories don’t have much of a decrease in metabolism. However, the pathways that bring information to and from these pathways shutdown dramatically, isolating them. The parts of the brain that first respond to sensory information have somewhat of a metabolic shutdown, but the more dramatic changes are in downstream brain areas that integrate, associate those bytes of sensory information, and give them meaning. What you’ve got is a metabolically quiescent, sleeping brain. This makes sense, as deep slow wave sleep is when energy restoration occurs. This is shown by the fact that the extent of sleep deprivation is not a great predictor of the total amount you will ultimately sleep, but it is a good predictor of how much slow wave sleep there’ll be---a very active brain or sleep deprived brain tends to consume a lot of a particular form of energy; the breakdown product of that depleted form of energy is the signal that biases toward slow wave sleep.

A very different picture emerges during REM sleep. Overall, there’s an increase in activity. Some brain regions become even more metabolically active than when you’re awake. Parts of the brain that regulate muscle movement, brain stem regions that control breathing and heart rate---all increase their metabolic rate. In the part of the brain called the limbic system, which is involved in emotion, there is an increase as well. The same for areas involved in memory and sensory processing, especially those involved in vision and hearing.
Something particularly subtle goes on in the visual processing regions. The part of the cortex that processes the first bits of visual information does not show much of an increase in metabolism, whereas there is a big jump in the downstream regions that integrate simple visual information. How can this be, when on top of it, your eyes are closed? This is dreaming!

That tells us something about how dream imagery arises. But something else happens in the brain that tells us something about the content of dreams. There’s a part of the brain, called the frontal cortex. It’s the most recently evolved part of the human brain, it is disproportionately huge in primates, and is the last part of our brain to fully mature. The frontal cortex is the nearest thing we have to a superego. Starting from toilet training, it helps you to do the harder, rather than easier thing—for example, thinking in a logical, sequential manner, rather than bouncing all over the place cognitively. It keeps you from murdering someone just because you feel like it, stops you from telling someone exactly what you think of their hideous outfit and instead finds something complimentary. The frontal cortex does all this disciplining of you by inhibiting that frothy, emotional limbic system. If you damage your frontal cortex, someone gets “frontally disinhibited”—doing and saying things we may think about, but never act upon. During REM sleep, metabolism in the frontal cortex goes way down, disinhibiting the limbic system to come up with the most outlandish ideas. That’s why dreams are dreamlike—illogical, nonsequential, hyperemotional. You breathe underwater, fly in the air, communicate telepathically; you announce your love to strangers, invent languages, rule kingdoms, have sexual encounters, star in musicals, etcetera.

So those are the nuts and bolts of sleep. But what is sleep for you? You die without it. Even fruit flies do. The most obvious answer is to have a stretch where your brain is going at half speed, in order to build up supplies of energy. Your brain consumes phenomenal amounts of energy to pull off all that calculus and symphony writing that you do—the brain constitutes something like 3 percent of your body weight, but needs nearly a quarter of the energy. So stores tend to decline during the day and some solid slow wave sleep is needed to restock these stores (mostly a molecule called glycogen, which is also an energy store in liver and muscle).

Others speculate that sleep is for decreasing brain temperature, letting it cool off from all that daytime brainstorming, or for detoxifying the brain. Weirdly, another major reason to sleep is to dream. If you skip a nights sleep, when you finally get to sleep the next night, you have more REM sleep than normal, suggesting that you’ve built up a real deficit of dreaming. Some extremely difficult studies that are queasy in nature just to contemplate deprive people or animals of REM sleep preferentially, and the study subjects go to pieces much faster than they do for the equivalent amount of deprivation of other types of sleep.

Thus, this begs the question of what dreaming is for. To work out unresolved issues about your mother? To provide a living for surrealists and Dadaists? So you can have a sex dream about some unlikely person in your waking life and then act all weird around the person around that person the next morning by the water cooler? Well, maybe. The marked increase in metabolic activity during REM sleep, and in some of the most inhibited areas of the brain during waking, have suggested to some a sort of “use it or lose it” scenario in which dreaming gives some aerobic exercise to otherwise underutilitized brain pathways (that is, the oft-neglected starring in musicals brain pathway).

What has become clear is that sleep plays a role in cognition. For example, sleep can facilitate problem solving. This is the realm of “sleeping on a problem,” and then suddenly discovering a solution the next morning while you’re cleaning crud out of the corners of your eyes. The neurobiologists Robert Stickgold of Harvard has emphasized that this type of problem solving is the kind where a morass of unhelpful facts are broken through to get to feelings. As he says, you don’t forget a phone number and then “sleep on it” to remember it. You do it for some complex, ambiguous problem.

Both slow wave and REM sleep also seem to play roles in the formation of new memories, the consolidation of information from the previous day, even information that became less accessible to you while awake over the course of the day. One type of evidence supporting this is the fact that if you teach an animal some task and disrupt its sleep that night, the new information isn’t consolidated. While this has been shown in many different ways, the interpretation remains controversial. Stress can also disrupt memory consolidation, and sleep deprivation is stressful. Maybe sleep deprivation disrupts memory consolidation merely because of the stress, which wouldn’t prove that sleep normally helps memory consolidation. But the pattern of memory disruption caused by sleep deprivation is different from that caused by stress.

Another type of evidence is correlative. Being exposed to lots of new information during the day is associated with more REM sleep that night. Moreover, the amount of certain subtypes of sleep at night predicts how well new information is recalled the next day. For example, lots of REM sleep during the night predicts better consolidation of emotional information from the day before, while lots of stage 2 sleep predicts better consolidation of a motor task, and a combination of lots of REM sleep and slow wave sleep predicts better retention of perceptual information. Others have taken this further, reporting that it’s not just the amount of some subtype of sleep that predicts some subtype of learning, but whether it occurs early or late in the night.

Another style of evidence for the “sleep helps you consolidate memories” story was first obtained by Bruce McNaughton of the University of Arizona. As we should all know, the hippocampus has a central role in explicit learning. McNaughton recorded the activity of single hippocampal neurons in rats, identifying ones that became particularly busy while the rat was learning some new explicit information. That night, during slow wave sleep, it would be those same neurons that would be particularly busy. Taking that one step further, he showed that patterns of activation of hippocampal neurons that occur during learning are then repeated when the animal is sleeping. Brain-imaging studies with humans have shown something similar. There’s even evidence that when consolidation is going on during REM, genes are activated that help form new connections between neurons. During slow wave sleep, metabolism remains surprisingly high in areas like the hippocampus. It’s as if sleep is the time when the brain practices those new memory patterns over and over, centering them into place.

Weirdly, amid this general picture of sleep deprivation disrupting cognition, at least one type of learning is facilitated by sleep deprivation, as shown in some recent work of a graduate student by the name of Ilana Hairston. Suppose you have some unlikely task where you have to learn to recite the months of the year backward as quickly as possible. Why is this going to be so hard? Because there will repeatedly be the pull to recite the months in the way that you have done your entire life, which is forward; the previous, over learned version of the task interferes with this new reversal task. Who would excel at this task? Someone who has never learned to do January, February, March, etc., automatically in that direction. If you sleep deprive some rats and give them a rat’s equivalent of a reversal task, they do better than do control animals. Why? Because they can’t remember the prior overlearned version of the task well enough for it to intrude now.

SLEEP DEPRIVATION AS A STRESSOR

As we glide down into slow wave sleep, some obvious things occur to facets of the stress-response system. For starters, the sympathetic nervous system shuts down, in favor of that calm, vegetative parasympathetic nervous system. In addition, gluccocortocoid levels go way down. Corticotropin Releasing Hormone (CRH) is the hypothalamic hormone that gets the pituitary to release Adreno Corticotropin Releasing Hormone (ACTH) in order to trigger adrenal release of gluccocortocoids. Some of the hypothalamic control of pituitary hormone release consists of an accelerator and brake—a releasing factor and an inhibiting factor. For years, there’s been evidence floating around for a hypothalamic “corticotropin inhibiting factor” (CIF) that would inhibit the release of ACTH, counteracting the effects of CRH. No one’s sure what CIF is, or if it really exists, but there’s some decent evidence that CIF is a brain chemical that helps bring on slow wave sleep (called “delta sleep-inducing factor”). Thus, sleep deeply, and you turn off gluccocortocoid secretion.

In contrast, during REM, as you’re mobilizing all that energy to generate the outlandish dream imagery and to move your eyes rapidly, gluccocortocoid secretion and the sympathetic nervous system revs up again. But given that most of what counts as a good night’s sleep consists of slow wave sleep, sleep is predominantly a time when the stress response is turned off. This is seen in species whether they’re nocturnal or diurnal (that is, sleeping during the dark hours, like us). About an hour before you wake up, levels of CRH, ACTH, and glucocorticoids begin to rise. This is not just because merely rousing from a slumber is a mini-stressor, requiring mobilization of some energy, but because those rising stress hormone levels play a role in terminating sleep.

So deprive yourself of sleep, and the sleep-induced decline in the levels of those stress hormones doesn’t occur. And, no surprise, they rise instead. Glucocorticoid levels increase and the sympathetic nervous system is activated; down go the levels of growth hormone and various sex hormones. Sleep deprivation definitely stimulates glucocorticoid secretion, although not a massive extent in most studies (unless the sleep deprivation is really prolonged; however, “it is postulated that these increases [in response to sleep deprivation] are due to the stress of dying rather than to sleep loss,” dryly noted one journal article.

The elevated glucocortocoid levels during sleep deprivation play a role in breaking down some of the stored forms of energy in the brain. This, along with many of the glucocortocoid effects on memory, could have something to do with why learning and memory are so lousy when sleep deprived. That’s something we all learned when we were doing an all nighter and discovering the next morning during the final exam that we can barely recall what month it was, let alone any of the factoids crammed in our heads the previous night. A recent study demonstrated one way in which our brains become impaired when we try to think hard on no sleep. Take a normally rested subject, stick her in a brain imager, and ask her to solve some “working memory” problems (holding on to some facts and manipulating them—like adding sequences of three-digit numbers). As a result, her frontal cortex lights up metabolically. Now, take someone who is sleep deprived and he’s awful at the working memory task. And what’s going on in his brain? What you might have guessed is that frontal metabolism would be inhibited, too groggy to get activated in response to the task. Instead, the opposite occurs—the frontal cortex is activated, but so are large parts of the rest of the cortex. It’s as if sleep deprivation has reduced this gleaming computer of a frontal cortex to a bunch of unshaven gibbering neurons counting on their toes, having to ask the rest of the cortical neurons to help out with this tough math problem.

So why care if sleep deprivation is a stressor? It’s obvious. We’re accustomed to all sorts of amenities in our modern lives: overnight deliveries of packages, advice nurses who can be called at two in the morning, round-the-clock technical support staff. Therefore, people are required to work under conditions of sleep deprivation. We’re not a nocturnal species and if a person works at night or works swing shifts, regardless of how many total hours of sleep she’s getting, it’s going against her biological nature. People who work those sorts of hours tend to over activate the stress response, and there’s little habituation (learning) that goes on. It’s not surprising that night work or shift work increases the risk of cardiovascular disease, gastrointestinal disorders, immune suppression, and fertility problems.

A widely reported study a few years back really brought this into focus. Prolonged stress and glucocorticoids can damage the hippocampus and impair hippocampal-dependent explicit memory. Kei Choi of the University of Bristol studied flight attendants working for two different airlines. On one airline, after you worked a transcontinental flight with major jet lag, you’d have a 15-day break until being scheduled for the next transcontinental flight. In contrast, on airline #2, presumably with a weaker union, you got a 5-day break before the next transcontinental flight. Cho controlled for total amount of flying time and total number of time zones shifted in the course of flying. Thus, Airline #2’s crews didn’t experience more total jet lag, just less time to recover. Finally, Cho considered only employees who had been doing this for more than five years. He found that airline #2’s attendants had, on average, impaired explicit memory, higher glucocortocoid levels, and a smaller temporal lobe (the part of the brain that contains the hippocampus). This is obviously not a good thing for the employees working under these conditions. And this may make it less likely that the flight attendant will remember that 17C requested a mixture of ginger ale and skim milk with ice. But it kind of makes one wonder whether the back-to-the-grind-after-5-days pilot is having trouble remembering whether or not this little ol’ switch turns the engine on or off.

These worries about sleep deprivation are relevant to even those whose 9-to-5 job is 9-5 during daylight hours. We have an unprecedented number of ways to make us sleep deprived, beginning with something as simple as indoor lighting. In 1910, the average American slept nine hours a night, disturbed only by the occasional Model T backfiring. We now average 7.5 and declining. When there’s the lure of 24-hour-a-day fun, activities, and entertainment, or for the workaholic, the knowledge that somewhere, in some time zone, someone else is working while you indulge yourself in sleep, that pull of “just a few more minutes,” of pushing yourself, becomes irresistible and damaging.

Special Thanks

I would like to give thanks to the following researchers/authors who provided me with the necessary material to write this report.

Benington, J., & Heller, H. (1995). Restoration of brain energy metabolism as the function of sleep. Progress in Neurobiology, 45, 347.
Braun, A., Balkin, T., Wesensten, N., Gwardy, F., Carson, R., Varga, M., Baldwin, P., Belenky, G., & Herscovitch, P. (1998). Dissociated patterns of activity in visual cortices and their projections during human rapid eye movement sleep. Science, 279, 91.
Cauter, E., & Spiegel, K. (1999). Sleep as a mediator of the relationship between socioeconomic status and health: a hypothesis. Annals of the New York Academy of Sciences, 896,, 254.
Cho, K. (2001). Chronic ‘jet lag’ produces temporal lobe atrophy and spatial cognitive deficits. Nature Neuroscience, 4, 567.
Drummond, S., Brown, G., Gillin, J., Stricker, J., Wong, E. & Buxton, R. (2000). Altered brain response to verbal learning following sleep deprivation. Nature, 403 655.
Fenn, K., Nusbaum, H., & Margoliash, D. (2003). Consolidation during sleep of perceptual learning of spoken language. Nature, 425, 614.
Gip, P., Hagiwara, G., Sapolsky, R., Cao, V., Heller, H., & Ruby, N. Glucocortocoids influence brain glycogen levels during sleep deprivation. American Journal of Physiology in press.
Hairston, I., Little, M., Scanlon,M., Lutan, C., Barakat, M., Palmer, T., Sapolsky, R., & Heller, H. (2003). Sleep deprivation enhances memory? Society for Neuroscience Annual Meeting, 616.
Meerlo, P., Koehl, M., van der Brought, K., & Turek, F. (2002). Sleep restriction alters the HPA response to stress. Journal of Neuroendocrinology, 14, 397-402.
Okajima, T. & Hertting, G. (1986). Delta sleep induced peptide inhibited CRF-induced ACTH secretion from rat anterior pituitary gland in vitro. Hormones and Metabolic Research, 18 497.
Maquet, P. (2001). The role of sleep in learning and memory. Science, 294, 1048.
Mednick, S., Nakayama, K., & Stickgold, R. (2003). Sleep-dependent learning: a nap is as good as a night. Nature Neuroscience, 6, 697.
Pace-Schott, E., & Hobson, J. (2002) The neurobiology of sleep; genetics; cellular physiology and subcortical networks. Nature Reviews Neuroscience, 3, 591.
Sapolsky, R. (2001). Wild dreams. Discover, 22, 36.
Shaw, P., Tononni, G., Greenspan, R., & Robinson, D. (2002). Stress response genes protect against lethal effects of sleep deprivation in Drosophila. Nature, 417, 287.
Skaggs, W., & McNaughton, B. (1996). Replay of neuronal firing sequences in rat hippocampus during sleep following spatial experience. Science, 271, 1870.
Siegel, J. (2003). Why we sleep. Scientific American, 92
VanReeth, O., Weibel, L., Spiegel, K., Leproult, R., Dugovic, C., & Maccari, S. (2000). Interactions between stress and sleep: from basic research to clinical situations. Sleep Medicine Reviews, 4, 201.
Vgontzas, A., Bixler. E., & Kales, A. (2000). Sleep, sleep disorders, and stress. Encyclopedia of Stress vol 3., 449.
Wagner, U., Gais, S., & Borm, J. (2001). Emotional memory formation is enhanced across sleep intervals with high amounts of rapid eye movement sleep. Learning and Memory, 8, 112.
Wilson, M., & McNaughton, B. (1994). Reactivation of hippocampal ensemble memories during sleep. Science, 265, 676.

[SpRi7e]

Once I finish this, I'll get back to it with a discussion.. dreams are extremely interesting so I'm sort of using this as a reminder to read it

[emilyblunt]

That was a very long post man but I'll try to read everything. I'll get back to you when I'm done.

[AbbyRoad]

i am on the boat of people that are going to read this and get back to you