Monday, August 08, 2005

Deep into Sleep

Deep into Sleep:

"When people make the unlikely claim that they get by on four hours of sleep per night, Stickgold often asks if they worry about what they are losing. “You get a blank look,” he says. “They think that sleep is wasted time.” But sleep is not merely “down time” between episodes of being alive. Within an evolutionary framework, the simple fact that we spend about a third of our lives asleep suggests that sleep is more than a necessary evil. Much transpires while we are asleep, and the question is no longer whether sleep does something, but exactly what it does. Lack of sleep may be related to obesity, diabetes, immune-system dysfunction, and many illnesses, as well as to safety issues such as car accidents and medical errors, plus impaired job performance and productivity in many other activities.

Although the modern era of sleep research started in the 1950s with the discovery of REM (Rapid Eye Movement) sleep, the field remained, well, somnolent until recently. Even 20 years ago, “The dominant paradigm in sleep research was that ‘Sleep cures sleepiness,’” says Stickgold. Since then, researchers have developed a far more complex picture of what happens while we snooze. The annual meetings in sleep medicine, which only this year became a recognized medical specialty, now draw 5,000 participants. Harvard has long been a leader in the area. The Medical School’s Division of Sleep Medicine, founded in 1997 and chaired by Baldino professor of sleep medicine Charles Czeisler, has 61 faculty affiliates. The division aims to foster collaborative research into sleep, sleep disorders, and circadian biology, to educate physicians and the lay public, to influence public policy, and to set new standards of clinical practice, aiming, as its website (www.hms.harvard.edu/sleep) declares, to create “a model program in sleep and circadian biology.”



A Culture of “Sleep Bulimia”

Imagine going on a camping trip without flashlights or lanterns. As the sun sets at the end of the day, daylight gradually gives way to darkness, and once the campfire burns down, you will probably go to sleep. At sunrise, there’s a similar gradient in reverse; from the beginning of time, human beings have been entrained to these cycles of light and dark.

Homo sapiens is not a nocturnal animal; we don’t have good night vision and are not especially effective in darkness. Yet in an instant on the evolutionary time scale, Edison’s invention of the light bulb, and his opening of the first round-the-clock power plant on Pearl Street in Manhattan in 1882, shifted our time-and-light environment in the nocturnal direction. At the snap of a switch, a whole range of nighttime activity opened up, and today we live in a 24-hour world that is always available for work or play. Television and telephones never shut down; the Internet allows you to shop, gamble, work, or flirt at 3 a.m.; businesses stay open ever-longer hours; tens of millions of travelers cross multiple time zones each year, worldwide; and with the growth of global commerce and communication, Wall Street traders may need to rise early or stay up late to keep abreast of developments on Japan’s Nikkei exchange or at the Deutsche Bundesbank.

Consequently most of us now sleep less than people did a century ago, or even 50 years ago. The National Sleep Foundation’s 2005 poll showed adult Americans averaging 6.8 hours of sleep on weeknights—more than an hour less than they need, Czeisler says. Not only how much sleep, but when people sleep has changed. In the United States, six to eight million shift workers toil regularly at night, disrupting sleep patterns in ways that are not necessarily amenable to adaptation. Many people get only five hours per night during the week and then try to catch up by logging nine hours nightly on weekends. “You can make up for acute sleep deprivation,” says David P. White, McGinness professor of sleep medicine and director of the sleep disorders program at Brigham and Women’s Hospital. “But we don’t know what happens when people are chronically sleep-deprived over years.”

“We are living in the middle of history’s greatest experiment in sleep deprivation and we are all a part of that experiment,” says Stickgold. “It’s not inconceivable to me that we will discover that there are major social, economic, and health consequences to that experiment. Sleep deprivation doesn’t have any good side effects.”"

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Sleeping well helps keep you alive longer. Among humans, death from all causes is lowest among adults who get seven to eight hours of sleep nightly, and significantly higher among those who sleep less than seven or more than nine hours. (“Those who sleep more than nine hours have something wrong with them that may be causing the heavy sleep, and leads to their demise,” White notes. “It is not the sleep itself that is harmful.”)

Sleep is essential to normal biological function. “The immune system doesn’t work well if we don’t sleep,” says White. “Most think sleep serves some neurological process to maintain homeostasis in the brain.” Rats totally deprived of sleep die in 17 to 20 days: their hair starts falling out, and they become hypermetabolic, burning lots of calories while just standing still.

There once was a fair amount of research on total sleep deprivation, like that which killed the rats. Doctors would keep humans awake for 48, 72, or even 96 hours, and watch their performance deteriorate while their mental states devolved into psychosis. For several reasons, such studies rarely happen any more
[...]

In this context, it is important to distinguish between acute and chronic sleep deprivation. Someone who misses an entire night of sleep but then gets adequate sleep on the following three days “will recover most of his or her normal ability to function, ” Czeisler says. “But someone restricted to only five hours of nightly sleep for weeks builds up a cumulative sleep deficit. In the first place, their performance will be as impaired as if they had been up all night. Secondly, it will take two to three weeks of extra nightly sleep before they return to baseline performance. Chronic sleep deprivation’s impact takes much longer to build up, and it also takes much longer to recover.” The body is eager to restore the balance; Harvard undergraduates, a high-achieving, sleep-deprived population, frequently go home for Christmas vacation and pretty much sleep for the first week. Stickgold notes that “When you live on four hours a night, you forget what it’s like to really be awake.”

Sleep researcher Eve van Cauter at the University of Chicago exposed sleep-deprived students (allowed only four hours per night for six nights) to flu vaccine; their immune systems produced only half the normal number of antibodies in response to the viral challenge. Levels of cortisol (a hormone associated with stress) rose, and the sympathetic nervous system became active, raising heart rates and blood pressure. The subjects also showed insulin resistance, a pre-diabetic condition that affects glucose tolerance and produces weight gain. “[When] restricted to four hours [of sleep] a night, within a couple of weeks, you could make an 18-year-old look like a 60-year-old in terms of their ability to metabolize glucose,” Czeisler notes. “The sleep-deprived metabolic syndrome might increase carbohydrate cravings and the craving for junk food.”

Van Cauter also showed that sleep-deprived subjects had reduced levels of leptin, a molecule secreted by fat cells that acts in the brain to inhibit appetite. “During nights of sleep deprivation, you feel that your eating goes wacky,” says Stickgold. “Up at 2 a.m., working on a paper, a steak or pasta is not very attractive. You’ll grab the candy bar instead. It probably has to do with the glucose regulation going off. It could be that a good chunk of our epidemic of obesity is actually an epidemic of sleep deprivation.”

Furthermore, “Many children in our society don’t get adequate amounts of sleep,” Czeisler says. “Contrary to what one might expect, it’s common to see irritability and hyperactivity in sleep-deprived children. Is it really surprising that we treat them with wake-promoting drugs like Ritalin?” Schools and athletic programs press children to stay awake longer, and some children may be chronically sleep-deprived. Czeisler once took his daughter to a swim-team practice that ran from eight to nine o’clock at night, and told the coaches that this was too late an hour for children. “They looked at me like I was from another planet,” he recalls. “They said, ‘This is when we can get the pool.’”

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Students often wonder whether to pull an all-nighter before an exam. Will the extra studying time outweigh the exhaustion? Robert Stickgold, who has studied sleep’s role in cognition for the past 10 years, reports that it depends on the exam. “If you are just trying to remember simple facts—listing all the kings of England, say—cramming all night works, ” he explains. “That’s because it’s a different memory system, the declarative memory system. But if you expect to be hit with a question like ‘Relate the French Revolution to the Industrial Revolution,’ where you have to synthesize connections between facts, then missing that night of sleep can be disastrous. Your ability to do critical thinking takes a massive hit—just as with alcohol, you’re knocking out the frontal-cortex functions.

“It’s a version of ‘sleeping on a problem,’” Stickgold continues. “If you can’t recall a phone number, you don’t say, ‘Let me sleep on it.’ But if you can’t decide whether to take a better-paying job located halfway across the country—where you have all the information and just have to weigh it—you say, ‘Let me sleep on it.’ You don’t say, ‘Give me 24 hours.’ We realize that it’s not just time; we understand at a gut level that the brain is doing this integration of information as we sleep, all by itself.”

Not only mental and emotional clarification, but the improvement of motor skills can occur while asleep. “Suppose you are trying to learn a passage in a Chopin piano ├ętude, and you just can’t get it,” says Stickgold. “You walk away and the next day, the first try, you’ve got it perfectly. We see this with musicians, and with gymnasts. There’s something about learning motor-activity patterns, complex movements: they seem to get better by themselves, overnight.”

Stickgold’s colleague Matthew Walker, an instructor in psychiatry, studied a simple motor task: typing the sequence “41324” as rapidly and accurately as possible. After 12 minutes of training, subjects improved their speed by 50 to 60 percent, but then reached a plateau. Those who trained in the morning and came back for another trial the same evening showed no improvement. But those who trained in the evening and returned for a retest the following morning were 15 to 20 percent faster and 30 to 50 percent more accurate. “Twenty percent improvement—what’s that?” asks Stickgold, rhetorically. “Well, it’s taking a four-minute mile down to three minutes and 10 seconds, or raising a five-foot high jump to six feet.”

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The origins of humans’ consolidated sleep take us to the beginnings of terrestrial life, since even prokaryotes—one-celled organisms like bacteria, lacking a nucleus—have built-in 24-hour rhythms. It is not surprising that these biological clocks are so universal, as they reflect the entrainment of all living things to the primeval 24-hour cycles of light and darkness created by the rotation of Earth.

“The light and dark cycle is the most powerful synchronizer of the internal circadian clock that keeps us in sync with the 24-hour day,” Czeisler says. As late as 1978, when he published a paper demonstrating this effect, many still believed that “social interaction was the most important factor in synchronizing physiological cycles—that we had evolved beyond light,” he says. “But much of our subsequent research shows that our daily cycles are more like those of cockroaches than we want to believe. We are very sensitive to light.”

Light strongly affects the suprachiasmatic nucleus (SCN), a biological clock in the anterior region of the hypothalamus that directs circadian cycles. All cells have internal clocks—even cells in a tissue culture run on 24-hour cycles. “They all oscillate like violins and cellos, but the SCN is the conductor that synchronizes them all together, ” Czeisler explains.

While the homeostatic pressure to sleep starts growing the moment we awaken, the SCN calls a different tune. Late in the afternoon, its circadian signal for wakefulness kicks in. “The circadian system is set up in a beautiful way to override the homeostatic drive for sleep,” Czeisler says. The circadian pacemaker’s signal continues to increase into the night, offsetting the build-up of homeostatic pressure and allowing us to stay awake well into the evening and so achieve our human pattern of consolidated sleep and wakefulness. (There is often a dip in the late afternoon, when the homeostatic drive has been building for hours but the circadian signal hasn’t yet kicked in; Czeisler calls this “a great time for a nap.”) The evolutionary benefit of consolidated sleep and wakefulness is a subject of speculation; Czeisler says that long bouts of wakefulness may enable us to “take advantage of our greater intellectual capacity by focusing our energy and concentration. Frequent catnaps would interrupt that.”

The circadian pacemaker’s push for wakefulness peaks between about 8 and 10 p.m., which makes it very difficult for someone on a typical schedule to fall asleep then. “The period from two to three hours before one’s regular bedtime, we call a ‘wake maintenance zone,’ ” Czeisler says. But about an hour before bedtime, the pineal gland steps up its secretion of the hormone melatonin, which quiets the output from the SCN and hence paves the way for sleep.

Some years ago, melatonin supplements became popular as a natural sleeping pill, but as Czeisler’s research has proven, light is a more powerful influence on the biological clock than melatonin. Mangelsdorf professor of natural sciences J. Woodland Hastings has shown that even a split-second of light exposure can shift the circadian cycle of a single-celled organism by a full hour. Light interferes with sleep, at least partly because it inhibits melatonin secretion and thus resets the biological clock. For this reason, those seeking a sound sleep should probably keep their bedroom as dark as possible and by all means avoid midnight trips to brightly lit bathrooms or kitchens; blue light, with its shorter wavelength—and its resemblance to the sunlit sky—has the most powerful resetting effect.

Light resets the pacemaker even in the case of some completely blind people, who generally lose circadian entrainment and suffer recurrent insomnia. “The eye has two functions, just as the ear does, with hearing and balance,” says Czeisler. “The eye has vision, and also circadian photoreception.” A subset of about 1,000 photosensitive retinal ganglion cells connects by a direct neural pathway to the SCN; these cells are sometimes active even in those who are blind to light. Exposure to bright light will decrease melatonin levels in some blind persons, and this subset, unlike other blind people, generally do not suffer from insomnia and are biologically entrained to the 24-hour day.

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