Calming fear during sleep

First evidence that fear memories can be reduced during sleep

A fear memory was reduced in people by exposing them to the memory over and over again while they slept. It’s the first time that emotional memory has been manipulated in humans during sleep, report Northwestern Medicine® scientists.

The finding potentially offers a new way to enhance the typical daytime treatment of phobias through exposure therapy by adding a nighttime component. Exposure therapy is a common treatment for phobia and involves a gradual exposure to the feared object or situation until the fear is extinguished.

"It’s a novel finding," said Katherina Hauner, a postdoctoral fellow in neurology at Northwestern University Feinberg School of Medicine. "We showed a small but significant decrease in fear. If it can be extended to pre-existing fear, the bigger picture is that, perhaps, the treatment of phobias can be enhanced during sleep."

Hauner did the research in the lab of Jay Gottfried, associate professor of neurology at Feinberg and senior author of the paper.

The study will be published Sept. 22 in the journal Nature Neuroscience.

Previous projects have shown that spatial learning and motor sequence learning can be enhanced during sleep. It wasn’t previously known that emotions could be manipulated during sleep, Northwestern investigators said.

In the study, 15 healthy human subjects received mild electric shocks while seeing two different faces. They also smelled a specific odorant while viewing each face and being shocked, so the face and the odorant both were associated with fear. Subjects received different odorants to smell with each face such as woody, clove, new sneaker, lemon or mint.

Then, when a subject was asleep, one of the two odorants was re-presented, but in the absence of the associated faces and shocks. This occurred during slow wave sleep when memory consolidation is thought to occur. Sleep is very important for strengthening new memories, noted Hauner, also a research scientist at the Rehabilitation Institute of Chicago.

"While this particular odorant was being presented during sleep, it was reactivating the memory of that face over and over again which is similar to the process of fear extinction during exposure therapy," Hauner said.

When the subjects woke up, they were exposed to both faces. When they saw the face linked to the smell they had been exposed to during sleep, their fear reactions were lower than their fear reactions to the other face.

Fear was measured in two ways: through small amounts of sweat in the skin, similar to a lie detector test, and through neuroimaging with fMRI (functional magnetic resonance imaging). The fMRI results showed changes in regions associated with memory, such as the hippocampus, and changes in patterns of brain activity in regions associated with emotion, such as the amygdala. These brain changes reflected a decrease in reactivity that was specific to the targeted face image associated with the odorant presented during sleep.

Sleep Better, Look Better? New Research Says Yes

First scientific look at how sleep apnea treatment affects appearance — alertness, youthfulness & attractiveness — may help patients stick with care

Getting treatment for a common sleep problem may do more than help you sleep better – it may help you look better over the long term, too, according to a new research study from the University of Michigan Health System and Michigan Technological University.

The findings aren’t just about “looking sleepy” after a late night, or being bright-eyed after a good night’s rest.

It’s the first time researchers have shown specific improvement in facial appearance after at-home treatment for sleep apnea, a condition marked by snoring and breathing interruptions. Sleep apnea affects millions of adults – most undiagnosed — and puts them at higher risk for heart-related problems and daytime accidents.

Using a sensitive “face mapping” technique usually used by surgeons, and a panel of independent appearance raters, the researchers detected changes in 20 middle-aged apnea patients just a few months after they began using a system called CPAP to help them breathe better during sleep and overcome chronic sleepiness.

While the research needs to be confirmed by larger studies, the findings may eventually give apnea patients even more reason to stick with CPAP treatment – a challenge for some because they must wear a breathing mask in bed. CPAP is known to stop snoring, improve daytime alertness and reduce blood pressure.

Sleep neurologist Ronald Chervin, M.D., M.S., director of the U-M Sleep Disorders Center, led the study, which was funded by the Covault Memorial Foundation for Sleep Disorders Research and published in the Journal of Clinical Sleep Medicine.

Putting anecdote to the test

Chervin says the study grew out of the anecdotal evidence that sleep center staff often saw in sleep apnea patients when they came for follow-up visits after using CPAP. The team, including research program manager Deborah Ruzicka, R.N., Ph.D., sought a more scientific way to assess appearance before and after sleep treatment.

“The common lore, that people ‘look sleepy’ because they are sleepy, and that they have puffy eyes with dark circles under them, drives people to spend untold dollars on home remedies,” notes Chervin, the Michael S. Aldrich Collegiate Professor of Sleep Medicine and professor of Neurology at the U-M Medical School. “We perceived that our CPAP patients often looked better, or reported that they’d been told they looked better, after treatment. But no one has ever actually studied this.”

They teamed with U-M plastic and reconstructive surgeon Steven Buchman, M.D., to use a precise face-measuring system called photogrammetry to take an array of images of the patients under identical conditions before CPAP and a few months after. Capable of measuring tiny differences in facial contours, the system helps surgeons plan operations and assess their impact.

“One of the breakthroughs in plastic surgery over the last decade has been our aim to get more objective in our outcomes,” says Buchman. “The technology used in this study demonstrates the real relationship between how you look and how you really are doing, from a health perspective.”

The research team also included longtime collaborators at the Michigan Tech Research Institute, led by signal analysis expert and engineer Joseph W. Burns, Ph.D., who developed a way to precisely map the colors of patients’ facial skin before and after CPAP treatment.

The researchers also used a subjective test of appearance: 22 independent raters were asked to look at the photos, without knowing which were the “before” pictures and which the “after” pictures of each patient. The raters were asked to rank attractiveness, alertness and youthfulness – and to pick which picture they thought showed the patient after sleep apnea treatment.

Results show improvement

About two-thirds of the time, the raters stated that the patients in the post-treatment photos looked more alert, more youthful and more attractive. The raters also correctly identified the post-treatment photo two-thirds of the time.

Meanwhile, the objective measures of facial appearance showed that patients’ foreheads were less puffy, and their faces were less red, after CPAP treatment. The redness reduction was especially visible in 16 patients who are Caucasian, and was associated with the independent raters’ tendency to say a patient looked more alert in the post-treatment photo. The researchers also perceived, but did not have a way to measure, a reduction in forehead wrinkles after treatment.

However, the researchers note, they didn’t see a big change in facial characteristics that popular lore associates with sleepiness. “We were surprised that our approach could not document any improvement, after treatment, in tendency to have dark blue circles or puffiness under the eyes,” says Chervin. “Further research is needed, to assess facial changes in more patients, and over a longer period of CPAP treatment.”

He notes that this initial study wouldn’t have been possible without the generosity of donors who have supported U-M sleep research as a way of honoring the memory of Jonathan Covault, a promising attorney who died young, and whose undertreated sleep apnea may have contributed to his premature death. The Covault family was aware of the research study, and of the importance of research that might encourage others to seek and stay with apnea treatment.

Chervin and his colleagues hope to continue to study the effect of sleep apnea treatment on many aspects of a person’s life, including further research on appearance. “We want sleep to be on people’s minds, and to educate them about the importance of getting enough sleep and getting attention for sleep disorders,” he says.

Sleep Boosts Production of Brain Support Cells

Animal study shows genes involved in brain repair, growth turned on during slumber

Sleep increases the reproduction of the cells that go on to form the insulating material on nerve cell projections in the brain and spinal cord known as myelin, according to an animal study published in the September 4 issue of The Journal of Neuroscience. The findings could one day lead scientists to new insights about sleep’s role in brain repair and growth.

Scientists have known for years that many genes are turned on during sleep and off during periods of wakefulness. However, it was unclear how sleep affects specific cells types, such as oligodendrocytes, which make myelin in the healthy brain and in response to injury. Much like the insulation around an electrical wire, myelin allows electrical impulses to move rapidly from one cell to the next.

In the current study, Chiara Cirelli, MD, PhD, and colleagues at the University of Wisconsin, Madison, measured gene activity in oligodendrocytes from mice that slept or were forced to stay awake. The group found that genes promoting myelin formation were turned on during sleep. In contrast, the genes implicated in cell death and the cellular stress response were turned on when the animals stayed awake.

“These findings hint at how sleep or lack of sleep might repair or damage the brain,” said Mehdi Tafti, PhD, who studies sleep at the University of Lausanne in Switzerland and was not involved with this study.

Additional analysis revealed that the reproduction of oligodendrocyte precursor cells (OPCs) — cells that become oligodendrocytes — doubles during sleep, particularly during rapid eye movement (REM), which is associated with dreaming.

“For a long time, sleep researchers focused on how the activity of nerve cells differs when animals are awake versus when they are asleep,” Cirelli said. “Now it is clear that the way other supporting cells in the nervous system operate also changes significantly depending on whether the animal is asleep or awake.”

Additionally, Cirelli speculated the findings suggest that extreme and/or chronic sleep loss could possibly aggravate some symptoms of multiple sclerosis (MS), a disease that damages myelin. Cirelli noted that future experiments may examine whether or not an association between sleep patterns and severity of MS symptoms exists.

How sleep helps brain learn motor task

Sleep helps the brain consolidate what we’ve learned, but scientists have struggled to determine what goes on in the brain to make that happen for different kinds of learned tasks. In a new study, researchers pinpoint the brainwave frequencies and brain region associated with sleep-enhanced learning of a sequential finger tapping task akin to typing, or playing piano.

You take your piano lesson, you go to sleep and when you wake up your fingers are better able to play that beautiful sequence of notes. How does sleep make that difference? A new study helps to explain what happens in your brain during those fateful, restful hours when motor learning takes hold.

"The mechanisms of memory consolidations regarding motor memory learning were still uncertain until now," said Masako Tamaki, a postdoctoral researcher at Brown University and lead author of the study that appears Aug. 21 in the Journal of Neuroscience. “We were trying to figure out which part of the brain is doing what during sleep, independent of what goes on during wakefulness. We were trying to figure out the specific role of sleep.”

In part because it employed three different kinds of brain scans, the research is the first to precisely quantify changes among certain brainwaves and the exact location of that changed brain activity in subjects as they slept after learning a sequential finger-tapping task. The task was a sequence of key punches that is cognitively akin to typing or playing the piano.

Specifically, the results of complex experiments performed at Massachusetts General Hospital and then analyzed at Brown show that the improved speed and accuracy volunteers showed on the task after a few hours sleep was significantly associated with changes in fast-sigma and delta brainwave oscillations in their supplementary motor area (SMA), a region on the top-middle of the brain. These specific brainwave changes in the SMA occurred during a particular phase of sleep known as “slow-wave” sleep.

Scientists have shown that sleep improves many kinds of learning, including the kind of sequential finger-tapping motor tasks addressed in the study, but they haven’t been sure about why or how. It’s an intensive activity for the brain to consolidate learning and so the brain may benefit from sleep perhaps because more energy is available or because distractions and new inputs are fewer, said study corresponding author Yuka Sasaki, a research associate professor in Brown’s Department of Cognitive, Linguistic & Psychological Sciences.

"Sleep is not just a waste of time," Sasaki said.

The extent of reorganization that the brain accomplishes during sleep is suggested by the distinct roles the two brainwave oscillations appear to play. The authors wrote that the delta oscillations appeared to govern the changes in the SMA’s connectivity with other areas of the cortex, while the fast-sigma oscillations appeared to pertain to changes within the SMA itself.

Meticulous measurements

Possible roles for fast-sigma and delta brainwaves and for the SMA had suggestive support in the literature before this study, but no one had obtained much proof in part because doing so requires a complex experimental protocol.

To make their findings, Sasaki, Tamaki and their team asked each of their 15 subjects to volunteer for the motor learning experiments. For the first three nights, nine subjects simply slept at whatever their preferred bedtime was while their brains were scanned both with magnetoencephalography (MEG), which measures the oscillations with precise timing, and polysomnography, which keeps track of sleep phase. By this time the researchers had good baseline measurements of their brain activity and subjects had become accustomed to sleeping in the lab.

On day 4, the subjects learned the finger-tapping task on their non-dominant hand (to purposely make it harder to learn). The subjects were then allowed to go to sleep for three hours and were again scanned with PSG and MEG. Then the researchers woke them up. An hour later they asked the subjects to perform the tapping task. As a control, six other subjects did not sleep after learning the task, but were also asked to perform it four hours after being trained. Those who slept did the task faster and more accurately than those who did not.

On day 5, the researchers scanned each volunteer with an magnetic resonance imaging machine, which maps brain anatomy, so that they could later see where the MEG oscillations they had observed were located in each subject’s brain.

In all, the experimenters tracked 5 different oscillation frequencies in eight brain regions (four distinct regions on each of the brain’s two sides). Sasaki said she expected the most significant activity to take place in the “M1” brain region, which governs motor control, but instead the significant changes occurred in the SMA on the opposite side of the trained hand.

What was especially important about the delta and fast-sigma oscillations was that they fit two key criteria with statistical significance: they changed substantially after subjects were trained in the task and the strength of that change correlated with the degree of the subject’s performance improvement on the task.

After performing the experiments, the team of Sasaki, Tamaki and co-author Takeo Watanabe moved from MGH to Brown, where they have set up a new sleep lab. They have since begun a project to further study how the brain consolidates learning. In this case they’re looking at visual learning tasks.

"Will we see similar effects?" Sasaki asked. "Would it be with similar frequency bands and a similar organization of neighboring brain areas?"

To find out, some volunteers will just have to sleep on it.

Why Some Remember Dreams, Others Don’t

People who tend to remember their dreams also respond more strongly than others to hearing their name when they’re awake, new research suggests.

Everyone dreams during sleep, but not everyone recalls the mental escapade the next day, and scientists aren’t sure why some people remember more than others.

To find out, researchers used electroencephalography to record the electrical activity in the brains of 36 people while the participants listened to background tunes, and occasionally heard their own first name. The brain measurements were taken during wakefulness and sleep. Half of the participants were called high recallers, because they reported remembering their dreams almost every day, whereas the other half, low recallers, said they only remembered their dreams once or twice a month.

When asleep, both groups showed similar changes in brain activity in response to hearing their names, which were played quietly enough not to wake them.

However, when awake, high recallers showed a more sustained decrease in a brain wave called the alpha wave when they heard their names, compared with the low recallers.

"It was quite surprising to see a difference between the groups during wakefulness," said study researcher Perrine Ruby, neuroscientist at Lyon Neuroscience Research Center in France.

The difference could reflect variations in the brains of high and low recallers that could have a role in how they dream, too, Ruby said.

Who remembers their dreams

A well-established theory suggests that a decrease in the alpha wave is a sign that brain regions are being inhibited from responding to outside stimuli. Studies show that when people hear a sudden sound or open their eyes, and more brain regions become active, the alpha wave is reduced.

In the study, as predicted, both groups showed a decrease in the alpha wave when they heard their names while awake. But high recallers showed a more prolonged decrease, which may be a sign their brains became more widely activated when they heard their names.

In other words, high recallers may engage more brain regions when processing sounds while awake, compared with low recallers, the researchers said.

While people are asleep, the alpha wave behaves in the opposite way —it increases when a sudden sound is heard. Scientists aren’t certain why this happens, but one idea is that it protects the brain from being interrupted by sounds during sleep, Ruby said.

Indeed, the study participants showed an increase in the alpha wave in response to sounds during sleep, and there was no difference between the groups.

One possibility to explain the lack of difference, the researchers said, could be that perhaps high recallers had a larger increase in alpha waves, but it was so high that they woke up.

Time spent awake, during the night

The researchers saw that high recallers awoke more frequently during the night. They were awake, on average, for 30 minutes during the night, whereas low recallers were awake for 14 minutes. However, Ruby said “both figures are in the normal range, it’s not that there’s something wrong with either group.”

Altogether, the results suggest the brain of high recallers may be more reactive to stimuli such as sounds, which could make them wake up more easily. It is more likely a person would remember their dreams if they are awakened immediately after one, Ruby said.

However, waking up at night can account for only a part of the differences people show in remembering dreams. “There’s still much more to understand,” she said.

The study is published online (Aug. 13) in the journal Frontiers in Psychology.

Baby owls sleep like baby humans

Researchers at the Max Planck Institute for Ornithology and the University of Lausanne have discovered that the sleeping patterns of baby birds are similar to that of baby mammals. What is more, the sleep of baby birds appears to change in the same way as it does in humans. Studying barn owls in the wild, the researchers discovered that this change in sleep is strongly correlated with the expression of a gene involved in producing dark, melanic feather spots, a trait known to covary with behavioral and physiological traits in adult owls. These findings raise the intriguing possibility that sleep-related developmental processes in the brain contribute to the link between melanism and other traits observed in adult barn owls and other animals.

Sleep in mammals and birds consists of two phases, REM sleep (“Rapid Eye Movement Sleep”) and non-REM sleep. We experience our most vivid dreams during REM sleep, a paradoxical state characterized by awake-like brain activity. Despite extensive research, REM sleep’s purpose remains a mystery. One of the most salient features of REM sleep is its preponderance early in life. A variety of mammals spend far more time in REM sleep during early life than when they are adults. For example, as newborns, half of our time asleep is spent in REM sleep, whereas last night REM sleep probably encompassed only 20-25% percent of your time snoozing.Although birds are the only non-mammalian group known to clearly engage in REM sleep, it has been unclear whether sleep develops in the same manner in baby birds. Consequently, Niels Rattenborg of the MPIO, Alexandre Roulin of Unil, and their PhD student Madeleine Scriba, reexamined this question in a population of wild barn owls. They used an electroencephalogram (EEG) and movement data logger in conjunction with minimally invasive EEG sensors designed for use in humans, to record sleep in 66 owlets of varying age. During the recordings, the owlets remained in their nest box and were fed normally by their parents. After having their sleep patterns recorded for up to five days, the logger was removed. All of the owlets subsequently fledged and returned at normal rates to breed in the following year, indicating that there were no long-term adverse effects of eves-dropping on their sleeping brains.

Despite lacking significant eye movements (a trait common to owls), the owlets spent large amounts of time in REM sleep. “During this sleep phase, the owlets’ EEG showed awake-like activity, their eyes remained closed, and their heads nodded slowly”, reports Madeleine Scriba from the University of Lausanne (see video). Importantly, the researchers discovered that just as in baby humans, the time spent in REM sleep declined as the owlets aged.

In addition, the team examined the relationship between sleep and the expression of a gene in the feather follicles involved in producing dark, melanic feather spots. “As in several other avian and mammalian species, we have found that melanic spotting in owls covaries with a variety of behavioral and physiological traits, many of which also have links to sleep, such as immune system function and energy regulation”, notes Alexander Roulin from the University of Lausanne. Indeed, the team found that owlets expressing higher levels of the gene involved in melanism had less REM sleep than expected for their age, suggesting that their brains were developing faster than in owlets expressing lower levels of this gene. In line with this interpretation, the enzyme encoded by this gene also plays a role in producing hormones (thyroid and insulin) involved in brain development.

Although additional research is needed to determine exactly how sleep, brain development, and pigmentation are interrelated, these findings nonetheless raise several intriguing questions. Does variation in sleep during brain development influence adult brain organization? If so, does this contribute to the link between behavioral and physiological traits and melanism observed in adult owls? Do sleep and pigmentation covary in adult owls, and if so how does this influence their behavior and physiology? Finally, Niels Rattenborg from the Max Planck Institute for Ornithology in Seewiesen hopes that “this naturally occurring variation in REM sleep during a period of brain development can be used to reveal exactly what REM sleep does for the developing brain in baby owls, as well as humans.”

Bad night’s sleep? The moon could be to blame

Many people complain about poor sleep around the full moon, and now a report appearing in Current Biology, a Cell Press publication, on July 25 offers some of the first convincing scientific evidence to suggest that this really is true. The findings add to evidence that humans—despite the comforts of our civilized world—still respond to the geophysical rhythms of the moon, driven by a circalunar clock.

"The lunar cycle seems to influence human sleep, even when one does not ‘see’ the moon and is not aware of the actual moon phase," says Christian Cajochen of the Psychiatric Hospital of the University of Basel.

In the new study, the researchers studied 33 volunteers in two age groups in the lab while they slept. Their brain patterns were monitored while sleeping, along with eye movements and hormone secretions.

The data show that around the full moon, brain activity related to deep sleep dropped by 30 percent. People also took five minutes longer to fall asleep, and they slept for twenty minutes less time overall. Study participants felt as though their sleep was poorer when the moon was full, and they showed diminished levels of melatonin, a hormone known to regulate sleep and wake cycles.

"This is the first reliable evidence that a lunar rhythm can modulate sleep structure in humans when measured under the highly controlled conditions of a circadian laboratory study protocol without time cues," the researchers say.

Cajochen adds that this circalunar rhythm might be a relic from a past in which the moon could have synchronized human behaviors for reproductive or other purposes, much as it does in other animals. Today, the moon’s hold over us is usually masked by the influence of electrical lighting and other aspects of modern life.

The researchers say it would be interesting to look more deeply into the anatomical location of the circalunar clock and its molecular and neuronal underpinnings. And, they say, it could turn out that the moon has power over other aspects of our behavior as well, such as our cognitive performance and our moods.

Helping SAD Sufferers Sleep Soundly

Lying awake in bed plagues everyone occasionally, but for those with seasonal affective disorder, sleeplessness is routine.University of Pittsburgh researchers report in the Journal of Affective Disorders that individuals with seasonal affective disorder (SAD)—a winter depression that leads to loss of motivation and interest in daily activities—have misconceptions about their sleep habits similar to those of insomniacs. These findings open the door for treating seasonal affective disorder similar to the way doctors treat insomnia.

Kathryn Roecklein, primary investigator and assistant professor in Pitt’s Department of Psychology within the Kenneth P. Dietrich School of Arts and Sciences, along with a team of researchers from Pitt’s School of Medicine and Reyerson University, investigated why, according to a previously published sleep study by the University of California, Berkeley, individuals with seasonal affective disorder incorrectly reported that they slept four more hours a night in the winter. 

“We wondered if this misreporting was a result of depression symptoms like fatigue and low motivation, prompting people to spend more time in bed,” said Roecklein. “And people with seasonal affective disorder have depression approximately five months a year, most years. This puts a significant strain on a person’s work life and home life.”

Roecklein and her team interviewed 147 adults between the ages of 18 and 65 living in the Pittsburgh metropolitan area during the winters of 2011 and 2012. Data was collected through self-reported questionnaires and structured clinical interviews in which participants were asked such questions as: “In the past month, have you been sleeping more than usual?” and “How many hours, on average, have you been sleeping in the past month? How does that compare to your normal sleep duration during the summer?” 

In order to understand participants’ ideas about sleep, Roecklein’s team asked them to respond to questions such as “I need at least 8 hours of sleep to function the next day” and “Insomnia is dangerous for health” on a scale from 0 to 7, where 7 means “strongly agree” and 0 means “disagree completely.”

Roecklein and her team found that SAD participants’ misconceptions about sleep were similar to the “unhelpful beliefs” or personal misconceptions about sleep that insomniacs often hold. Due to depression, individuals with SAD, like those with insomnia, may spend more time resting in bed, but not actually sleeping—leading to misconceptions about how much they sleep. These misconceptions, said Roecklein, play a significant role in sleep cognition for those with seasonal affective disorder.

“We predict that about 750,000 people in the Pittsburgh metro area suffer from seasonal affective disorder, making this an important issue for our community and the economic strength and vitality of our city,” said Roecklein. “If we can properly treat this disorder, we can significantly lower the number of sufferers in our city.”

Roecklein’s research data suggests that addressing, understanding, and managing these “unhelpful beliefs” about sleep by way of psychotherapy could lead to improved treatments for seasonal affective disorder. One of the most effective treatment options for insomnia, said Roecklein, is cognitive behavioral therapy for insomnia (known as CBT-I), which aims to help people take control of their thinking to improve their sleep habits as well as mood, behavior, and emotions.

Roecklein’s next research project aims to improve treatment for seasonal affective disorder by studying light perception and biological clock synchronization. Light from the environment synchronizes internal biological rhythms with the timing of dawn and dusk, which naturally changes with the seasons. This synchronization allows people to be awake and alert during the day and to sleep at night. Roecklein will examine whether people with seasonal affective disorder perceive this light from the environment differently because of changes in the function of neurological pathways from the eye to the brain. This could help uncover reasons why people suffer from seasonal affective disorder and could suggest new treatment options.

(Image: Shutterstock)