Mysteries of sleep

Frank Knower knew something was wrong when he kept having conversations with co-workers and later couldn't remember a thing that was said. He couldn't even remember what he'd said.

Later, after he retired, he discovered another problem: He got irresistibly drowsy during long drives.

None of the usual stay-awake tricks like turning up the radio or rolling down the window could keep him awake. He had to pull over for naps.

These days, his wife handles a lot of the driving. And while the 74-year-old Knower can still nod off during the day at his home in Tappan, N.Y., treatment for his sleep-disrupting condition, apnea, and a daytime alertness pill help keep his problems in check.

For Knower, it's a story with a happy ending. For scientists, though, it's a story full of mystery.

Why would a sleep-deprived brain fail to absorb conversations? Just how does it produce drowsiness while a person is driving? Indeed, how does it know it needs more sleep in the first place?

These aren't just esoteric ponderings. The answers to these and related mysteries about the sleepy brain could lead to improved drugs to help people fall asleep or stay awake. They could help drowsy people find the most effective time to drink coffee or take a nap.

Scientists may even find safe and reliable ways to skip slumber entirely for days without the usual mental glitches.

"You could have soldiers who could fight a war 24 hours a day and maybe not sleep, at least for a few days," said Dr. Clifford Saper of Harvard Medical School. "If you knew what was making the brain sleepy, you could get at it at a fundamental level ... I think once we learn how the system operates we'll be able to successfully manipulate it."

Of course, in an economy with such potentially perilous round-the-clock workplaces as trucks, airplanes, nuclear power plants and supertankers, even helping people sleep and function well one day at a time would be a benefit.

An estimated 70 million people in the United States suffer from sleep problems, either because of disorders such as apnea and insomnia or just a lack of time devoted to slumber, the federal government says. At least 100,000 auto crashes and 1,550 traffic deaths a year are caused by falling asleep at the wheel.

And sleep deprivation leads to reduced productivity, poor performance in school or the workplace, and possibly medical problems like high blood pressure, heart disease, depression and reduced resistance to viruses.

"Sleep is as important to our overall health as exercise and a healthy diet," says Dr. Carl Hunt, director of the government's National Center on Sleep Disorders Research.

Getting enough sleep

So how much sleep is enough? The typical recommendation is at least eight hours a night for adults. But in the February issue of the journal Sleep, an expert called on doctors to abandon that blanket prescription.

"It appears seven hours or even five or six is safe for people who aren't sleepy during the day," said Dr. Daniel Kripke of the School of Medicine of the University of California, San Diego.

Kripke cited large studies that tracked death rates in people who habitually slept different lengths of time. But "if someone is sleepy during the day with less than eight hours, as I am myself, then I think it might be wise to get eight hours sleep," he said.

Hunt said sleep studies overall indicate that adults generally need seven to eight hours a night to be well-rested. "As you ratchet down from seven hours to six or five or four, there's a progressively greater price" in illness, accidents and mental malfunctioning, Hunt said.

Studies show people can sleep too little and still feel fine during the day, but that's because people stop realizing they're impaired if they sleep too little night after night, Hunt said. So while there probably are some people who truly function well on six hours a night, they can't just rely on how they feel, he said.

Teenagers need around 8.5 hours of sleep a night, and younger children should aim for about nine hours, he said.

When the brain runs on too little sleep, it malfunctions in a wide variety of areas:

Your reaction time slows and you have trouble paying sustained attention. Driving is "the worst kind of thing," especially in bumper-to-bumper situations or lonely roads, said Edward Stepanski of the Rush University Medical Center in Chicago. "You're forced to sit still, so you can't move around and do things people ordinarily do to keep awake, and you're staring at the road."

You have trouble keeping tabs on multiple sources of information. So you ignore some of them to focus on a few, and "you fail to notice that you're running out of gas," said David Dinges at the University of Pennsylvania School of Medicine.

Creativity suffers. You get stuck on bad solutions and can't think of better ones.

You can't remember as much, and "a sleepy brain is just not very good at learning new information," Stepanski said.

Your brain just can't do some critical things in a hurry.

If given the luxury of time, it actually does pretty well with tasks like making decisions and solving complicated problems, says Hans Van Dongen at the University of Pennsylvania. That's because the brain has "an almost stunning ability to find tricks" to get around some hurdles imposed by sleep loss, he said.

Much of the overall problem in the sleepy brain is what scientists call microsleeps, repeated periods of a second or two, or maybe 10, when you just zone out and don't process information.

Microsleeps reflect "a kind of struggle inside the brain at the most fundamental biological level" between sleep and wakefulness, producing a sort of in-between state of reverie or inattentiveness, Dinges said. A person might look awake to a casual observer during microsleeps of a couple seconds, or the episodes can be more obvious.

Think of trying to stay awake at a meeting after partying all night. As Dinges observes in lab experiments, the eyeballs try to roll, the eyelids move unusually slowly and neck muscles start to go limp, which suggests that even muscle-control parts of the brain participate in sleepiness.

Work in Dinges' lab has shown that after a few nights of too little sleep, people stop realizing their daytime performance is suffering. So researchers are studying whether machines can do a better job of spotting sleep-deprived people.

Dinges said federal investigators are now seeing whether specialized monitors can track slowly closing eyelids in truckers. Studies suggest that's a reliable sign of impairment, he said.

Along with researchers from the National Aeronautics and Space Administration, Dinges has studied how much benefit a sleepy person gets from taking a break and moving around. The results suggest it might buy 10 to 20 minutes of wakefulness. Napping can be more effective as long as you doze at least 10 minutes, he said.

How about coffee? "Caffeine is not buying you a lot when you've taken it first thing in the morning after you've first awakened," said James Wyatt of the Rush University Medical Center in Chicago. At that point, coffee is probably just treating symptoms of caffeine withdrawal, which include sleepiness, confusion and irritability, he said.

For fighting effects of sleep deprivation, caffeine helps a lot more when it's taken after at least eight hours of wakefulness, he said.

To come up with better drugs to help people sleep or stay awake, scientists are studying just what happens in the sleep-deprived brain itself.

The brain has at least two major systems that govern sleep. One is the well-known pacemaker that keeps our bodies on a 24-hour rhythm. It's found in the hypothalamus, and it drives the sleep-wake cycle. Scientists aren't sure yet just how it sends its timing signals to the body.

But people can obviously override the pacemaker, staying up through most of the night. That's when a second, "homeostatic" system kicks in. It basically keeps track of how short you are on sleep, either from one bad night or a buildup of sleep deprivation over time. And it does its best to make sure you pay this "sleep debt" off.

Much less is known about this system. Where is it? How does it keep track of your sleep debt, especially if the debt builds night after night? And how does sleep debt impair the brain?

One apparent actor in this system is a substance called adenosine, which brain cells give off as a waste product.

The theory goes like this: as brain cells function during wakefulness, they give off adenosine, which mounts up outside the cells in the basal forebrain. There, the adenosine acts to inhibit brain cells that normally promote wakefulness and play key roles in brain function. So you feel sleepy and your mental functioning declines. When you finally fall asleep, your brain cells work less hard and adenosine is taken back into cells, relieving its pressure on the wakefulness circuitry of the brain.

Caffeine blocks drowsiness by interfering with adenosine's ability to affect brain cells, says Robert McCarley, a researcher at the VA Medical Center in Brockton, Mass., and Harvard Medical School. Further studies of how the brain responds to adenosine might lead to more effective wake-up agents and better sleeping pills, McCarley said.

To really understand how lack of sleep alters the brain, Dinges said, scientists will need to develop a few more tools. They'll need to find a way to mimic those mental and behavioral changes in animals, for example. And they'll need more detailed brain scans that can capture the very tiny brain structures that play a role in the process.

But such advances are nearly at hand, Dinges said.

"Over the next five years," he said, "there will be an exciting amount of work."