Unlocking the Riddle of REM Sleep

Eugene Aserinsky never wanted to study sleep. He tried being a social worker, a dental student, and even did a stint in the army as an explosives handler. He enrolled at the University of Chicago to pursue organ physiology, but all potential supervisors were too busy to take him on. His only choice was Nathaniel Kleitman, a middle-aged professor whom Aserinsky described as "always serious." Kleitman was doing research on sleep and so, grudgingly, Aserinsky followed suit.

Dr Mark Blumberg

Two years later, in 1953, the duo published a paper that shattered the way we saw sleep. They described a weird phenomenon Aserinsky later called REM sleep: periods of rapid eye movements paired with wakefulness-like activity in the brain. While seven decades have passed since Aserinsky's and Kleitman's discovery, the real essence of REM sleep and its function continue to elude us. "We are still at the very beginning of understanding this phenomenon," Mark Blumberg, PhD, professor of psychological and brain sciences at University of Iowa, told Medscape.

Before Aserinsky walked into Kleitman's lab, the widespread belief held that sleep was "the antithesis of wakefulness," as Kleitman wrote in his seminal 1939 book entitled Sleep and Wakefulness. Others saw it as a kind of a coma, a passive state. Another theory, developed in the early 20th century by French psychologist Henri Piéron, held that sleepiness is caused by an accumulation of 'hypnotoxins' in the brain.

In his 1913 study that would likely fail a contemporary ethics review, Piéron drew fluid from the brains of sleep-deprived dogs and injected it into other dogs to induce sleep. As he explained in an interview with The Washington Times in 1933, he believed that fatigue toxins accumulate in the brain throughout the wakeful hours, then slowly seep into the spinal column, promoting drowsiness. Once we fall asleep, Piéron claimed, the hypnotoxins burn away.

From Blinking to Rapid Eye Movement

In 1925 when Nathaniel Kleitman established the world's first sleep laboratory at the University of Chicago, sleep was a fringe science that most researchers avoided with a wide berth. Yet Kleitman was obsessed. The Moldova-born scientist famously worked famously worked 24/7 — literally. He not only stayed long hours in his lab, but also slept attached to a plethora of instruments to measure his brain waves, breathing, and heartbeat. At one point, Kleitman stayed awake for 180 hours (more than a week), to check how forced sleeplessness would affect his body (he later compared it to torture). He also lived 2 weeks aboard a submarine, moved his family north of the Arctic Circle, and spent over a month 119 feet below the surface in a cave in Kentucky, fighting rats, cold, and humidity to study circadian rhythms.

Kleitman was intrigued by an article in Nature in which the author asserted that he could detect the approach of slumber in train passengers by observing their blink frequencies. He instructed Aserinsky to observe sleeping infants (being monitored for a different study), to see how their blinking related to sleep. Yet Aserinsky was not amused. The project, he later wrote, "seemed about as exciting as warm milk."

Firstly, Aserinsky was uncertain whether eyelid movement with the eyes closed constituted a blink, then he noticed a 20-minute span in each hour when eye movement ceased entirely. Still short of getting his degree, Aserinsky decided to observe sleeping adults. He hauled a dusty clanker of a brain-wave machine out of the university's basement, and started registering the electrical activity of the brain of his dozing subjects. Soon, Aserinsky noticed something weird.

As he kept staring at the sleeping adults, he noticed that at times they'd have saccadic-like eye movements, just as the EEG machine would register a wake-like state of the brain. At first, he thought the machine was broken (it was ancient, after all). Then, that the subjects were awake and just keeping their eyes shut. Yet after conducting several sessions and tinkering with the EEG machine, Aserinsky finally concluded that the recordings and observations were correct: something was indeed happening during sleep that kept the cortex activated and made the subjects' eyes move in a jerky manner.

Dreams, Memory, and Thermoregulation

After studying dozens of subjects, including his son and Kleitman's daughter, and using miles of polygraph paper, the two scientists published their findings in September 1953 in the journal Science. Kleitman didn't expect the discovery to be particularly earth-shattering. When asked in a later interview how much research and excitement he thought the paper would generate, he replied: "none whatsoever." That's not how things went, though. "They completely changed the way people think," Blumberg says. Once and for all, the REM discovery put to rest the idea that sleep was a passive state where nothing interesting happens.

Aserinsky soon left the University of Chicago, while Kleitman continued research on rapid eye movements in sleep with his new student, William Dement. Together, they published studies suggesting that REM periods were when dreaming occurred — they reported that people who were awakened during REM sleep were far more likely to recall dreams than those awakened outside of that period. "REM sleep = dreams" became established dogma for decades, even though first reports of dreams during non-REM sleep came as early as Kleitman's and Dement's original research (they assumed these were recollections from the preceding REM episodes).

Dr Jerome Siegel

"It turns out that you can have a perfectly good dream when you haven't had a previous REM sleep period," says Jerome Siegel, PhD, professor of psychiatry and biobehavioral sciences at UCLA's Center for Sleep Research, pointing out that equating REM sleep with dreams is still "a common misconception."

By the 1960s, REM sleep seemed to be well defined as the combination of rapid eye movement with EEG showing brain activation, first noted by Aserinsky, as well as muscle atonia — a state of near-total muscle relaxation or paralysis. Today, however, Blumberg says, things are considerably less clear cut. In one recent paper, Blumberg and his colleagues went as far as to question whether REM sleep is even "a thing." REM sleep is prevalent across terrestrial vertebrates, but they found that it is also highly nuanced, messing up old definitions.

Take the platypus, for example, the animal with the most REM sleep (as far as we know): they have rapid eye movements and their bills twitch during REM (stillness punctuated by sudden twitches is typical of that period of sleep), but they don't have the classic brain activation on EEG. Owls have EEG activation and twitching, but no rapid eye movements, since their eyes are largely immobile. Geese, meanwhile, are missing muscle atonia — that's why they can sleep standing. And new studies are still coming in, showing, for instance, that even jumping spiders may have REM sleep, complete with jerky eye movements and limb twitching.

For Siegel, the findings on REM sleep in animals point to the potential explanation of what that bizarre stage of sleep may be all about: thermoregulation. "When you look at differences in sleep among the groups of warm-blooded animals, the correlation is almost perfect, and inverse. The colder they are, the more REM sleep they get," Siegel says. During REM sleep, body thermoregulation is basically suspended, and so, as Siegel argued in Lancet Neurology last fall, REM sleep could be a vital player in managing our brain's temperature and metabolic activity during sleep.

Wallace Mendelson, MD, professor emeritus of psychiatry at the University of Chicago, says it's likely, however, that REM sleep has more than one function. "There is no reason why one single theory has to be an answer. Most important physiological functions have multiple functions," he says. The ideas are many, including that REM sleep helps consolidate our memories and plays an important role in emotion regulation But it's not that simple. A Swiss study of nearly 1000 healthy participants did not show any correlation between sleep stage and memory consolidation. Sleep disruption of any stage can prevent memory consolidation and quiet wakefulness with closed eyes can be as effective as sleep for memory recall.

In 1971, researchers from the National Institute of Mental Health published results of their study on total suppression of REM sleep. For as long as 40 days, they administered the monoamine oxidase inhibitor (MAOI) phenelzine, a type of drug that can completely eliminate REM sleep, to six patients with anxiety and depression. They showed that suppression of REM sleep could improve symptoms of depression, seemingly without impairing the patients' cognitive function. Modern antidepressants, too, can greatly diminish REM sleep, Siegel says. "I'm not aware that there is any dramatic downside in having REM sleep reduced," he says.

So do we even need REM sleep for optimal performance? Siegel believes that there is a lot of exaggeration about how great REM sleep is for our health. "People just indulge their imaginations," he says. Blumberg points out that, in general, as long as you get enough sleep in the first place, you will get enough REM. "You can't control the amount of REM sleep you have," he explains.

REM Sleep Behavior Disorder

Even though we may not need REM sleep to function well, REM sleep behavior disorder (RBD) is a sign that our health may be in trouble. In 1986, scientists from the University of Minnesota reported a bizarre REM sleep pathology in four men and one woman who would act out their dreams. One 67-year-old man, for example, reportedly punched and kicked his wife at night for years. One time he found himself kneeling alongside the bed with his arms extended as if he were holding a rifle (he dreamt he was in a shootout). His overall health, however, seemed unaffected apart from self-injury during some episodes.

However, in 1996 the same group of researchers reported that 11 of 29 men originally diagnosed with RBD went on to develop a parkinsonian disorder. Combined data from 24 centers of the International RBD Study Group puts that number as high as 74% at 12-year follow-up. These patients get diagnosed with Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Scientists believe that the protein alpha-synuclein forms toxic clumps in the brain, which are responsible both for malfunctioning of muscle atonia during REM sleep and subsequent neurodegenerative disorders.

While some researchers say that RBD may offer a unique window into better understanding REM sleep, we're still a long way off from fully figuring out this biological phenomenon. According to Blumberg, the story of REM sleep has arguably become more muddled in the seven decades since Aserinsky and Kleitman published their original findings, dispelling myths about 'fatigue toxins' and sleep as a passive, coma-like state. Mendelson concurred: "It truly remains a mystery."

Blumberg, Mendelson, and Siegel reported no relevant disclosures.

Marta Zaraska is a Polish-Canadian journalist whose science writing has appeared in The Washington Post, Scientific American, Newsweek, Los Angeles Times, and New Scientist, among others, and is the author of Growing Young: How Friendship, Optimism, and Kindness Can Help You Live To 100

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