The switch that could turn off your nightmares and dreams

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When I was 13, I punched a wall. The act wasn’t due to adolescent rebellion. I was dreaming. As a lucid dreamer, my nocturnal adventures have two qualities: they’re vivid, and I can often manipulate the events. This dream was different. I lost control while boxing a faceless person — it was a fight for my life — and the episode ended with me hitting the wall. My throbbing fist woke me up.

science-wednesdaySometimes my dreams are so painfully detailed that I wake up exhausted, and I sometimes wonder if I’d be better off without them.

Thanks to emerging advances in neuroscience, I may one day have that option.

Experts say that a renaissance is happening right now in our understanding of REM — rapid eye movement — sleep. REM is the sleep stage associated with our most vivid dreams, but it is also believed to be important for learning and may influence migraines. The regulation of REM sleep plays a major role in sleep disorders, like narcolepsy, where the boundaries of being awake and the state of dreaming are melted together. And within the last couple of years, scientists have made major strides in unraveling the neural circuitry in control of REM sleep.

Three weeks ago, for instance, a study in the journal Nature highlighted how scientists had engineered a light switch to toggle REM sleep on and off in mice. The researchers, led by UC Berkeley neuroscientist Yang Dan, used optogenetics, a technique wherein individual neurons can be triggered to transmit signals using laser light from a fiber optic implant. In this case, the mice were genetically engineered to have light-sensitive neurons in their brain stem.

REM sleep was discovered in the early 1950s, and later that decade, pioneering work by [Michel] Jouvet concluded that the brain stem was important for REM sleep. Jouvet’s research showed how lesions in the brain could interrupt the neural pathways responsible for one of the classical features of REM sleep: muscle paralysis, otherwise known as muscle atonia.

Punching, kicking and aggressive motions are common during deep sleep for people with REM sleep behavior disorder. Photo by Westend61/via Getty Images

Punching, kicking and aggressive motions are common for people with REM sleep behavior disorder, wherein the boundaries between dreaming and real-life movements breakdown. Photo by Westend61/via Getty Images

REM sleep is the last of five stages that repeat in a cycle while we sleep. As normal people progress through the first four stages of non-REM sleep, our slumber deepens. Our muscle movements become less frequent, and our brain waves become slower with the occasional burst of rapid waves, called sleep spindles. We linger in deep, non-REM sleep until suddenly, our minds take a turn into REM sleep. Brain waves suddenly shift again, becoming fast and irregular. Our eyes dart around, and our muscles become completely paralyzed.

Muscle atonia keeps us from acting out our dreams, and in the past, it was believed that the brain stem neurons in charge of this paralysis were different from those responsible for inducing other aspects of REM sleep. However, Dan and her colleagues found a patch of neurons in the ventral medulla — a part of the brain stem — that could do both.

When activated by laser light, these neurons triggered the rapid induction of REM sleep within 30 seconds, as measured by electroencephalogram (EEG; brain) and electromyogram (EMG; muscle) scans.

“What’s surprising about their study is that when they activated and inactivated the area, they didn’t get what you expect: muscle paralysis or movement during REM,” said University of Toronto neuroscientist John Peever, who was not involved in the study. “Instead, they found that stimulation could actually change REM sleep length and frequency when they stimulated it.”

The scientists repeated this experiment in nearly 100 different mice and learned that toggling these neurons forced the transition from non-REM sleep to REM sleep 93 percent of time. The amount of time spent in REM sleep increased too. However, the light switch couldn’t force a mouse to slip from being awake directly to REM sleep, which is a characteristic of narcolepsy, a disorder where animals and people accidentally fall into deep sleep. These brain cells seem to be a causal switch for REM when mice are already sleeping, Dan said.

When REM walls crumble

Ok…ok…the mouse results are cool, but what does all of this mean for humans? And if my most vivid dreams occur during REM sleep, could this information be used to switch them off?

The REM neurocircuits in the brain stem aren’t likely involved in the content of dreams, Peever said, but these nerves do seem to induce or restrict the occurrence of REM sleep. Also, he said, clinical data from postmortem brains suggests the area manipulated by Dan’s group is degenerated in people with REM sleep behavior disorder. People with this condition lose muscle paralysis during REM and then act out their dreams, often with intricate motions.

“You see that they have these amazingly elaborate movements during sleep,” Peever said. “Some people can smoke. Others will sit in their beds and quack like ducks.” Patients with this condition may talk or make gestures while dreaming. And as Peever wrote in a 2014 review article, the muscle movements can turn violent:

There is a link between dream content and motor behaviors in REM sleep behavior disorder. Common dream content includes fighting off animals or unknown people, which may explain violent behaviors. Fear and anger are the most common emotions during dreams. Aggressive behaviors are prevalent and this contrasts with the typically mild-mannered temperament of patients during wakefulness.

Peever writes that REM sleep behavior disorder isn’t the same thing as sleepwalking, because REM sleep and sleepwalking happen in a separate brain state and manifest in different ways. Sleepwalking occurs during non-REM stages of sleep, and people are often able to orient themselves within their environment.

“They can walk down a flight of stairs or open the fridge,” Peever said. “REM sleep behavior disorder, in contrast, happens exclusively during REM sleep, and even though the movements are very elaborate, they’re often quite uncoordinated in terms of moving in the context of your environment.”

In other words, my painful wall punch may have occurred during REM sleep, Peever said, since I lacked an awareness of my surroundings.

Peever said he too experienced “horrific” behaviors during REM sleep when he was young that including yelling and screaming in bed.

“Most evidence suggests that if it starts when you’re extremely young, then there isn’t a link with neurodegeneration, but the jury is really out,” he said.

This video shows a patient with REM sleep behavior disorder who is saying a phrase — “You’re a little [censored] because you go hanging about in the streets” — which refers to a news story read earlier by the patient about a poor mother wandering the Chicago streets looking for a job, who eventually killed her baby. Video by Uguccioni G et al. PLOS ONE. 2013.

Dan’s study offers clarity into the neurocircuits that may go awry and lead to REM sleep behavior disorder. The patch of neurons tweaked by Dan and her colleagues weren’t only linked by location, but by the chemical neurotransmitter GABA that the cells use to send nerve signals. Using optogenetics, her team isolated 20 or so GABA-producing — or “GABAergic” — neurons that were most in tune with the transition from non-REM to REM sleep.

And according to Peever, Dan’s work comes on the heels of a slate of studies defining individual groups of neurons involved in the REM sleep circuit. In January, a study in PNAS showed that stimulating a separate patch of acetylcholine-producing cells in the brain stem could induce REM sleep more easily.

Another recent study showed if you activate cells in the hypothalamus that contain a chemical called MCH or melanin concentrating hormone, you can also produce REM sleep more easily and it lasts longer,” Peever said.

The neuron in the hypothalamus, an area that governs wakefulness and behaviors like eating, are physically linked by nerve connections to the brain stem regions associated with REM sleep.

Defining the neurocircuitry of REM could be crucial to determining whether or not a person truly has REM sleep behavior disorder. Things like intoxication, alcohol withdrawal and long-term antidepressant use can cause unrestful REM sleep symptoms similar to the sleep behavior disorder. Also, normal people may occasionally move during REM sleep without necessarily having the disorder. The same applies to patients with PTSD.

“I think that there is something special about the REM sleep circuit that makes it vulnerable to stressful conditions, whether they be emotional or physical, such as withdrawal from alcohol.” Peever said. “PTSD patients will often have vivid nightmarish dreams where they move, but they don’t have REM sleep behavior disorder.”

The distinction is valuable because 80 percent of REM sleep behavior disorder cases end up developing synucleinopathies, a class of neurodegenerative disorders that includes Parkinson’s diseases. Moreover, REM sleep behavior disorder can predict the development of synucleinopathies close to two decades before they manifest.

Peever emphasizes that REM sleep behavior disorder is rare, affecting less than 0.5 percent of the population. Also, most cases affect older adults. The prevalence increases to 2 percent over the age of 60 and to 6 percent over the age of 70.

“The simplest way to remember is if you’re older and you’re repeatedly acting out your violent dreams, then you may have REM sleep behavior disorder. However, if you scream and act out the odd time in bed, then you probably don’t have REM sleep behavior disorder,” Peever said. By mapping the REM neurocircuitry, he added, scientists may be able to create clinical tests to spot those with bonafide disorders.

A “future” life without REM

Dreamer. Photo by Colin Anderson/via Getty Images

Dreamer. Photo by Colin Anderson/via Getty Images

“The big next step in understanding REM sleep is learning how these different areas control each other, how they communicate with each other,” Peever said, and optogenetics may one day serve as a way to tweak these circuits in humans. “That’s effectively the goal of these technologies. It’s not only investigating how those particular brain cells control behavior, but how we are going to be able to control those cells to manipulate behaviors, so we can alleviate certain pathologies, for example, REM sleep behavior disorder and narcolepsy.”

At first, that idea sounds more like science fiction than science, because it requires using non-lethal viruses to genetically modify brain cells so they can be activated by light — in the case of optogenetics — or by a drug.

But professor Dan agreed, and she highlighted an upcoming clinical trial that plans on using optogenetics to turn on neurons in the eye to treat blindness. The U.S. Food and Drug Administration gave the trial, which is being led by the biopharmaceutical company RetroSense Therapeutics, a green light to proceed in late August.

It will be years before this technology can be used for a condition like narcolepsy, REM sleep behavior disorder or as a tool to switch off vivid or traumatic dreams, so Peever believes the key goal now is discerning as much about the REM circuit as possible, so future techniques can be put to good use.

“It’s not a matter of ‘if.’ It’s a matter of when we’ll able to target brain cells for whatever disease that we’re trying to cure,” Peever said.

But if we shut off REM sleep, will our minds and bodies suffer?

Sleep, overall, seems critical for survival. “There are studies in rats where if you deprive them of sleep completely, they die in two weeks,” Dan said. “There’s also a horrible neurodegenerative disease in humans, where people can’t sleep called fatal familial insomnia. They die within a year or two.”

But I don’t want to lose sleep entirely. I want to shut the valve on my vivid dreams by tweaking or wiping my REM sleep. That, by comparison, appears less hazardous.

Antidepressants are known to eradicate REM sleep by upping the brain levels of monoaminergic neurotransmitters, like noreadrenaline and serotonin.

“These neurons in the monoaminergic system are really anti-REM. So for people who take certain types of antidepressants, REM is almost completely gone,” Dan said. “Yet if you look at those people, they still seem intelligent, and they don’t have gross defects.”

“There’s no evidence that REM sleep deprivation by itself will kill anyone,” sleep psychiatrist Jerome Siegel of UCLA, told LiveScience after an expert witness during a 2013 trial suggested a lack of REM sleep led to Michael Jackson’s death. The same article cited a case of a patient who lost REM sleep after a brain injury, but then went to law school and became the puzzle editor for a Tel Aviv newspaper.

However, there could be side-effects of losing REM. REM and non-REM sleep seem to help solidify what we learn and our memories from the day.

“If you’re doing a complicated task — like exercise or a word association, it involves some basic skills, but sometimes you have to make a mental connection that isn’t entirely obvious,” Dan said. “There is some evidence that if you have REM sleep between the time that you practice a complicated task and the time that you’re retested, then you can gain these hidden insights.”

A dip in learning might be a dealbreaker for some folks, like kids prepping for an exam, but there might be people willing to sacrifice such learning for a loss of their dreams, such as war veterans who suffer from vivid nightmares due to post-traumatic stress disorder.

For now though, my dreams (and my nightmares), are my own, as I ponder a dreamless future. To borrow a line from the blockbuster Hook, “You know that place between sleep and awake? That place where you still remember dreaming?…That’s where I’ll be waiting.”

For more on neuroscience, check out the new PBS series The Brain with David Eagleman.