1. To improve chronic pain, get more sleep (coffee helps too)

    May 15, 2017 by Ashley

    From the Boston Children’s Hospital press release:

    New research from Boston Children’s Hospital and Beth Israel Deaconess Medical Center (BIDMC) shows that chronic sleep loss increases pain sensitivity. It suggests that chronic pain sufferers can get relief by getting more sleep, or, short of that, taking medications to promote wakefulness such as caffeine. Both approaches performed better than standard analgesics in a rigorous study in mice, described in the May 8, 2017 issue of Nature Medicine.

    Pain physiologist Alban Latremoliere, PhD, of Boston Children’s and sleep physiologist Chloe Alexandre, PhD, of BIDMC precisely measured the effects of acute or chronic sleep loss on sleepiness and sensitivity to both painful and non-painful stimuli. They then tested standard pain medications, like ibuprofen and morphine, as well as wakefulness-promoting agents like caffeine and modafinil. Their findings reveal an unexpected role for alertness in setting pain sensitivity.

    Keeping mice awake, through custom entertainment

    The team started by measuring normal sleep cycles, using tiny headsets that took electroencephalography (EEG) and electromyography (EMG) readings. “For each mouse, we have exact baseline data on how much they sleep and what their sensory sensitivity is,” says Latremoliere, who works in the lab of Clifford Woolf, PhD, in the F.M. Kirby Neurobiology Center at Boston Children’s.

    Next, unlike other sleep studies that force mice to stay awake walking treadmills or falling from platforms, Alexandre, Latremoliere and colleagues deprived mice of sleep in a way that mimics what happens with people: They entertained them.

    “We developed a protocol to chronically sleep-deprive mice in a non-stressful manner, by providing them with toys and activities at the time they were supposed to go to sleep, thereby extending the wake period,” says Alexandre, who works in the lab of Thomas Scammell, MD, at BIDMC. “This is similar to what most of us do when we stay awake a little bit too much watching late-night TV each weekday.”

    To keep the mice awake, researchers kept vigil, providing the mice with custom-made toys as interest flagged while being careful not to overstimulate them. “Mice love nesting, so when they started to get sleepy (as seen by their EEG/EMG pattern) we would give them nesting materials like a wipe or cotton ball,” says Latremoliere. “Rodents also like chewing, so we introduced a lot of activities based around chewing, for example, having to chew through something to get to a cotton ball.”

    In this way, they kept groups of six to 12 mice awake for as long as 12 hours in one session, or six hours for five consecutive days, monitoring sleepiness and stress hormones (to make sure they weren’t stressed) and testing for pain along the way.

    Pain sensitivity was measured in a blinded fashion by exposing mice to controlled amounts of heat, cold, pressure or capsaicin (the agent in hot chili peppers) and then measuring how long it took the animal to move away (or lick away the discomfort caused by capsaicin). The researchers also tested responses to non-painful stimuli, such as jumping when startled by a sudden loud sound.

    “We found that five consecutive days of moderate sleep deprivation can significantly exacerbate pain sensitivity over time in otherwise healthy mice,” says Alexandre. “The response was specific to pain, and was not due to a state of general hyperexcitability to any stimuli.”

    Analgesics vs. wake-promoting agents

    Surprisingly, common analgesics like ibuprofen did not block sleep-loss-induced pain hypersensitivity. Even morphine lost most of its efficacy in sleep-deprived mice. These observations suggest that patients using these drugs for pain relief might have to increase their dose to compensate for lost efficacy due to sleep loss, thereby increasing their risk for side effects.

    In contrast, both caffeine and modafinil, drugs used to promote wakefulness, successfully blocked the pain hypersensitivity caused by both acute and chronic sleep loss. Interestingly, in non-sleep-deprived mice, these compounds had no analgesic properties.

    “This represents a new kind of analgesic that hadn’t been considered before, one that depends on the biological state of the animal,” says Woolf, director of the Kirby Center at Boston Children’s. “Such drugs could help disrupt the chronic pain cycle, in which pain disrupts sleep, which then promotes pain, which further disrupts sleep.”

    A new approach to chronic pain?

    The researchers conclude that rather than just taking painkillers, patients with chronic pain might benefit from better sleep habits or sleep-promoting medications at night, coupled with daytime alertness-promoting agents to try to break the pain cycle. Some painkillers already include caffeine as an ingredient, although its mechanism of action isn’t yet known. Both caffeine and modafinil boost dopamine circuits in the brain, so that may provide a clue.

    “This work was supported by a novel NIH program that required a pain scientist to join a non-pain scientist to tackle a completely new area of research,” notes Scammel, professor of neurology at BIDMC. “This cross-disciplinary collaboration enabled our labs to discover unsuspected links between sleep and pain with actionable clinical implications for improving pain management.”

    “Many patients with chronic pain suffer from poor sleep and daytime fatigue, and some pain medications themselves can contribute to these co-morbidities,” notes Kiran Maski, MD, a specialist in sleep disorders at Boston Children’s. “This study suggests a novel approach to pain management that would be relatively easy to implement in clinical care. Clinical research is needed to understand what sleep duration is required and to test the efficacy of wake-promoting medications in chronic pain patients.”


  2. Surprise communication found between brain regions involved in infant motor control

    May 12, 2017 by Ashley

    From the University of Iowa press release:

    A newborn’s brain is abuzz with activity.

    Day and night, it’s processing signals from all over the body, from recognizing the wriggles of the child’s own fingers and toes to the sound of mommy’s or daddy’s voice.

    Though much of how the infant brain works and develops remains a mystery, University of Iowa researchers say they have uncovered a new mode of communication between two relatively distant regions. And, it turns out that sleep is key to this communication.

    When two areas of the brain communicate, their rhythms will often synchronize. One well-known brain rhythm, the theta rhythm, is most closely associated with the hippocampus, a region in the forebrain important for consolidating memories and navigation, among other functions. In experiments with infant rats, the researchers showed for the first time that the hippocampus oscillates in lockstep with the red nucleus, a brain-stem structure that plays a major role in motor control. Importantly, the hippocampus and red nucleus synchronize almost exclusively during REM (active) sleep.

    Rats and humans both spend much of their early lives in REM sleep. In human newborns, eight hours of every day is occupied by REM sleep alone. And because rat brains and human brains have the same basic structure, UI researchers believe the same communication, between the same regions, is likely occurring in human infants. They also suspect disruptions to that linkage may contribute to the motor-control problems that often accompany disorders such as autism and schizophrenia.

    “Our findings provide a possible route to understanding the early emergence of motor problems in human infants. Because we found that communication between the hippocampus and red nucleus occurred primarily during REM sleep, disrupting normal sleep in early infancy could interfere with the strengthening of the communication links among forebrain and brainstem structures,” says Mark Blumberg, a professor in the UI Department of Psychological and Brain Sciences and corresponding author on the study, published in the journal Current Biology.

    “We feel this work opens new doors to a host of important questions that have been largely overlooked,” Blumberg says.

    Carlos Del Rio-Bermudez, a Fulbright Scholar who joined Blumberg’s lab for his doctoral studies, says he was surprised by the findings.

    “Although a lot is known about the theta rhythm in the hippocampus and other forebrain structures, no one seems to have suspected that it might also be involved in communication between the hippocampus and a brain-stem structure like the red nucleus,” Del Rio-Bermudez says.

    According to Blumberg, this discovery supports the idea that REM sleep is important for early brain development and that brain rhythms play a significant role in this process.

    The researchers point out that an infant’s red nucleus and other similar structures contribute heavily to motor control at a time in development when other brain structures, including the motor cortex, are still developing.

    Considering the many similarities in the brain and behavior of infant rats and humans, “it would be extraordinary if similar events are not also happening in us,” Blumberg says.


  3. Alternating skimpy sleep with sleep marathons hurts attention, creativity in young adults

    May 2, 2017 by Ashley

    From the Baylor University press release:

    Skimping on sleep, followed by “catch-up” days with long snoozes, is tied to worse cognition — both in attention and creativityin young adults, in particular those tackling major projects, Baylor University researchers have found.

    “The more variability they showed in their night-to-night sleep, the worse their cognition declined across the week,” said study co-author Michael Scullin, Ph.D., director of Baylor’s Sleep Neuroscience and Cognition Laboratory and assistant professor of psychology and neuroscience in Baylor’s College of Arts & Sciences.

    “When completing term projects, students restrict sleep, then rebound on sleep, then repeat,” he said. “Major projects which call for numerous tasks and deadlines — more so than for tests — seem to contribute to sleep variability.”

    The study of interior design students is published online in the Journal of Interior Design. It also has implications for art, architecture, graphic design and other disciplines that use a model of design studio-based instruction, researchers said.

    Interior design is “a strange culture, one where sleep deprivation is almost a badge of honor,” said lead author Elise King, assistant professor of interior design in Baylor’s Robbins College of Health and Human Sciences.

    Staying up late to work on a project is not seen as procrastination but considered by some students and faculty members to be a tradition and a normal part of studio-based curricula to prepare them for their careers, she said.

    “Since the general public still doesn’t understand the profession of interior design, and mistakenly thinks we’re the same as decorators, there is a sense that you want to work harder and prove them wrong,” King said. “But recently, we’ve seen the consequences of that type of thinking: anxiety, depression and other mental health issues — and also the dangers of driving while sleep deprived.”

    The study challenges a common myth — that “the best design ideas only come in the middle of the night,” King said. But researchers found the opposite — that “consistent habits are at least as important as total length of sleep,” Scullin said.

    Irregular sleep is a negative for “executive attention” — intense focus for planning, making decisions, correcting errors and dealing with novelty. Erratic sleep also has a negative effect on creativity, the study found.

    The National Sleep Foundation recommends that young adults have seven to nine hours of sleep each day. But for the 28 interior design students in the Baylor study, sleep was short and fragmented. Only one participant slept seven hours or more nightly; 79 percent slept fewer than seven hours at least three nights during the week.

    “Most students think they’re getting about four more hours of sleep each week than they actually are,” Scullin said.

    “Projects are often lengthy, with final due dates looming weeks or months in the future,” King said. “The stress of juggling several projects, each with multiple deadlines, is likely to contribute to students’ tendency to cycle between several days of poor sleep leading up to a project due date, followed by a catch-up day with 10 or more sleep hours.”

    Researchers measured sleep patterns through actigraphy, with students wearing wristbands to track movement. Students also kept daily diaries on the quantity and quality of their sleep.

    “The wristband is somewhat similar to Fitbit devices, but much more reliable in detection, including the many brief awakenings during sleep that affect sleep quality,” Scullin said.

    All participants completed two cognitive testing sessions for creativity and executive attention — each about an hour long and in a laboratory. The sessions were done on the first and last day of the study at the same time of day.

    “What we call ‘creativity’ is often people’s ability to see the link between things that at first glance seem unrelated, and one of the tests taps into that ability,” Scullin said.

    An example: participants are given three words that are loosely connected — such as “sore,”‘ “shoulder” and “sweat” — and asked to figure out a fourth word that would connect them all.

    “What first comes to mind are words related to exercise, but in this case, no single exercise word really works. Instead, the ‘creative’ and correct answer is ‘cold,'” Scullin said.

    Meanwhile, executive attention — “working” memory — enables people to hold memories for a short time while doing a separate task. In the study, participants completed a task in which they saw a grid with black and white squares.

    “They had to decide very quickly whether that grid was symmetrical or not. Symmetry decisions by themselves are easy,” Scullin said. “But after each decision, participants were shown a grid with one square highlighted in red. Then they made another symmetry decision, followed by a different square highlighted in red. They repeat that cycle up to five times before being asked to recall all the square locations in the correct order. It’s very challenging to cycle between those two tasks and keep the square locations in mind.”

    Further investigation with a greater range of students across multiple studio-based majors and multiple universities would be valuable, researchers said.

    “Interior design programs are changing,” King said. “People are open to the conversation and willing to discuss ways to reduce that pressure on our students and encourage them to be healthier.”


  4. Poor sleep due to anxiety or depression may make it harder to think positive

    April 22, 2017 by Ashley

    From the University of Illinois at Chicago press release:

    A lack of sleep makes everything harder. Focusing, finishing assignments, and coping with everyday stress can become monumental tasks.

    People with anxiety and depression often have sleep problems. But little has been known about whether or how their poor sleep affects a specific region of the brain known to be involved in regulating negative emotional responses.

    Researchers at the University of Illinois at Chicago College of Medicine have found that this area of the brain, the dorsal anterior cingulate cortex, may have to work harder to modify negative emotional responses in people with poor sleep who have depression or anxiety. The finding is reported in the journal Depression and Anxiety.

    The research team, led by Heide Klumpp, assistant professor of psychiatry at UIC, used functional MRI to measure the activity in different regions of the brain as subjects were challenged with an emotion-regulation task. Participants were shown disturbing images of violence — from war or accidents — and were asked to simply look at the images and not to try to control their reaction or to “reappraise” what they saw in a more positive light.

    An example of reappraisal would be to see an image of a woman with a badly bruised face and imagine her as an actress in makeup for a role, rather than as a survivor of violence, Klumpp said.

    Reappraisal is something that requires significant mental energy,” she said. “In people with depression or anxiety, reappraisal can be even more difficult, because these disorders are characterized by chronic negativity or negative rumination, which makes seeing the good in things difficult.”

    The participants — 78 patients, 18 to 65 years of age, who had been diagnosed with an anxiety disorder, a major depressive disorder, or both — also completed a questionnaire to assess their sleep over the previous month. A motion-sensing device called an actigraph measured their awake time in bed, or “sleep efficiency,” over a six-day period. The questionnaire results indicated that three out of four participants met criteria for significant sleep disturbance, and the actigraph results suggested the majority had insomnia.

    Participants who reported poorer sleep on the questionnaire were seen to have less brain activity in the dorsal anterior cingulate cortex during the reappraisal task, while those with lower sleep efficiency based on the actigraph data had higher activity in the DACC.

    “Because the questionnaire and actigraph measure different aspects of the sleep experience, it is not surprising that brain activity also differed between these measures,” said Klumpp. “The questionnaire asks about sleep over the previous month, and answers can be impacted by current mood. Plus, respondents may not be able to accurately remember how they slept a month ago. The actigraph objectively measures current sleep, so the results from both measurements may not match.”

    “Higher DACC activity in participants with lower levels of sleep efficiency could mean the DACC is working harder to carry out the demanding work of reappraisal,” Klumpp said.

    “Our research indicates sleep might play an important role in the ability to regulate negative emotions in people who suffer from anxiety or depression.”


  5. Early school starts pit teens in a conflict between society, biology

    April 18, 2017 by Ashley

    From the Brown University press release:

    The idea of sleep is supposed to evoke feelings of peace, relaxation and refreshment, but when expert Mary Carskadon talks about teen sleep in school districts with early start times, she uses far less comfortable words.

    “Social policy clashes with what we see from the biology,” said Carskadon, a professor of psychiatry and human behavior at the Warren Alpert Medical School of Brown University. “For teens, when they have not gotten enough sleep and they have to get up too early, they are crushed in the morning.”

    Over decades of study, Carskadon has shown that two systems that regulate sleep, circadian rhythms and sleep pressure, both change as children grow up. While they still need the same amount of sleep throughout childhood — ideally 9 to 10 hours — older kids naturally become inclined to go to sleep later (as their circadian rhythms skew later). That means they become biologically predisposed to sleep later, too, to fully relieve that sleep pressure – or biological need to sleep. Yet society frequently requires that they wake early.

    “They are incredibly sleepy from the sleep pressure, but also they have to be at school at a time when their circadian system wants them to be asleep,” she said.

    Carskadon will share the insights from her research as one of many speakers at “Adolescent Sleep, Health, and School Start Times,” a national conference in Washington, D.C., from April 27 to 28. Co-organized by Dr. Judy Owens, director of sleep medicine at Boston Children’s Hospital and former professor at Brown University, the event will feature scientists, physicians and K-12 educators from across the country who will gather to discuss the health, educational and controversial policy implications of the issue.

    The issue is a hot button in several states, including Rhode Island where a newly proposed law would set a statewide high school start time of 8:30 a.m. Carskadon, meanwhile, has been invited to address the Rhode Island Association of School Committees in May even as she gears up for a new study this summer.

    The biology of bedtime

    Carskadon’s work began in the 1970s when she was a graduate student at Stanford University. She surveyed teens about their sleep habits and preferences. Perhaps not surprisingly, the results showed that teens stayed up later and slept less than when they were younger. The prevailing assumption was that they needed less sleep. But when she experimentally put teens on a schedule that allowed them to sleep longer, they did. Teens didn’t need less sleep than younger kids, she concluded. The fact that they also stopped waking on their own was apparent in the data, but was not Carskadon’s focus at the time.

    “We kind of missed that clue until we started looking at it in different ways,” she said.

    In a nationwide round of surveys in the early 1990s, she asked sixth graders when they felt best during the day and what their sleep preferences were. She also asked them to rate their maturity. She found an interesting trend.

    “The more mature they rated themselves, the more evening type they rated themselves,” she said. “There was a hint that maybe something was going on around the time of pubertal development that has to do with the circadian system.”

    In her Bradley Hospital sleep lab located on the campus of Butler Hospital in Rhode Island, Carskadon began to expand her research to incorporate biomarkers such as saliva levels of melatonin, a natural hormone driven by circadian rhythms that cues the onset of sleepiness. She found that given the same light/dark schedule, teens will produce melatonin at later times than younger kids, indicating their circadian rhythm grows fundamentally later as they age.

    One of her most seminal findings came in the late 1990s, when she studied 10th graders who had a high school start time of about 7:20 a.m. Wrist-worn sleep monitors showed they were getting about 7 hours of sleep a night. When she brought them into the lab, she’d wake them up for their regular school start time but then let them go back to sleep starting at 8:30 — a time when in school they’d be expected to be well underway with taking exams or listening intently to lectures.

    “About half of them looked like they had a major sleep disorder — narcolepsy,” she said. “At 8:30, half of the kids fell asleep in under a minute and went directly into REM sleep which means that their brains were set up

    in a very strong way to be asleep. When you are trying to teach and learn, it’s a non-starter.”

    As her lab grew and she added expertise to the team, she also began to look at brain wave patterns of teens as they slept. That helped her observe the buildup of sleep pressure. Her lab’s finding was that sleep pressure builds up more slowly in older kids. It’s easier for them to stay awake longer. But what doesn’t change is how quickly they relieve sleep pressure: they need just as much sleep.

    Her studies have continued all along. In 2014, she added more to the evidence of a later shift in sleep schedules with age, not by comparing groups of differently aged kids as before, but by comparing kids to themselves as they aged. Carskadon and colleagues published a study in PLOS ONE tracking the same children for more than two years. The data clearly showed that as they got older, they went to bed later.

    A recurring theme in Carskadon’s studies is that later-to-bed and later-to-rise is not entirely a behavioral choice — it’s a physiological imperative.

    “The force behind the change that we see behaviorally is in the biology,” she said.

    Even the newest threat to teen sleep — the temptations of portable screens lit up with games and social media — has direct and specific biological impact on sleep. In a 2015 study she found that the sleep biology of boys and girls aged 9 to 15 who were in the earlier stages of puberty was especially sensitive to light at night compared to older teens, meaning that late-night gadget use is particularly disruptive for young teens.

    The clash with policy

    For all the scientific evidence she has found, Carskadon acknowledges that policy is driven by many factors. Her studies have identified significant overall trends, but individuals vary widely, she said, and there are no doubt many households where teens are managing early school days just fine.

    Meanwhile, there are a lot of reasons why school districts start when they do, she said. For some families, for example, having older kids home from school before younger kids allows parents to be sure that younger kids have an older sibling to come home to.

    “The school system is central to community life,” she acknowledged.

    But the biological evidence for letting teens sleep in longer is overwhelming, she said. So long as school starts at a time when they physiologically still need to be asleep, she said, teenagers on average may be consigned to suffer from a “social jetlag” in which the timing of life is not the timing of the body.


  6. Study suggests college students study best later in the day

    April 17, 2017 by Ashley

    From the University of Nevada, Reno press release:

    A new cognitive research study used two new approaches to determine ranges of start times that optimize functioning for undergraduate students. Based on a sample of first and second year university students, the University of Nevada, Reno and The Open University in the United Kingdom used a survey-based, empirical model and a neuroscience-based, theoretical model to analyse the learning patterns of each student to determine optimum times when cognitive performance can be expected to be at its peak.

    “The basic thrust is that the best times of day for learning for college-age students are later than standard class hours begin,” Mariah Evans, associate professor of sociology at the University of Nevada, Reno and co-author of the study, said. “Especially for freshmen and sophomores, we should be running more afternoon and evening classes as part of the standard curriculum.”

    Prior research has demonstrated that late starts are optimal for most high school students, and this study extends that analysis to freshmen and sophomores in college. The analysis by Evans, Jonathan Kelley, fellow University sociology professor, and Paul Kelley, honorary associate of sleep, circadian and memory neuroscience at The Open University, assessed the preferred sleeping times of the participants and asked them to rate their fitness for cognitive activities in each hour of the 24-hour day.

    “Neuroscientists have documented the time shift using biological data — on average, teens’ biologically ‘natural’ day begins about two hours later than is optimal for prime age adults,” Evans said. “The survey we present here support that for college students, but they also show that when it comes to optimal performance, no one time fits all.”

    The study showed that much later starting times of after 11 a.m. or noon, result in the best learning. It also revealed that those who saw themselves as “evening” people outnumbered the “morning” people by 2:1, and it concluded that every start time disadvantages one or more of the chronotypes (propensity for the individual to be alert and cognitively active at a particular time during a 24-hour period).

    “Thus, the science supports recent moves by the University to encourage evening classes as part of the standard undergraduate curriculum,” Evans said. “It also supports increasing the availability of asynchronous online classes to enable students to align their academic work times with their optimal learning times.”

    The results, “Identifying the best times for cognitive functioning using new methods: Matching university times to undergraduate chronotypes”, were published in Frontiers in Human Neuroscience March 31, 2017.

    “This raises the question as to why conventional universities start their lectures at 9 a.m. or even earlier when our research reveals that this limits the performance of their students,” Kelley said. “This work is very helpful for asynchronous online learning as it allows for the student to target their study time to align with their personal rhythm and at the time of day when they know they are most effective.”


  7. Gene mutation helps explain night owl behavior

    April 11, 2017 by Ashley

    From the Cell Press press release:

    Some people stay up late and have trouble getting up in the morning because their internal clock is genetically programmed to run slowly, according to a study published April 6 in Cell. A mutation in a gene called CRY1 alters the human circadian clock, which dictates rhythmic behavior such as sleep/wake cycles. Carriers of the gene variant experienced nighttime sleep delays of 2-2.5 hours compared to non-carriers.

    “Carriers of the mutation have longer days than the planet gives them, so they are essentially playing catch-up for their entire lives,” says first author Alina Patke, a research associate in the lab of principal investigator Michael Young, Richard and Jeanne Fisher Professor and Head of the Laboratory of Genetics at The Rockefeller University.

    Night owls are often diagnosed at sleep clinics with delayed sleep phase disorder (DSPD). This study is the first to implicate a gene mutation in the development of DSPD, which affects up to 10% of the public, according to clinical studies.

    People with DSPD often struggle to fall asleep at night, and sometimes sleep comes so late that it fractures into a series of long naps. DSPD and other sleep disorders are associated with anxiety, depression, cardiovascular disease, and diabetes. People with DSPD also have trouble conforming to societal expectations and morning work schedules.

    “It’s as if these people have perpetual jet lag, moving eastward every day,” says Young. “In the morning, they’re not ready for the next day to arrive.”

    Patke is a night owl and usually works late into the night. She, however, does not carry the CRY1 variant. Not all cases of DSPD are attributable to this gene mutation. However, Young and Patke found it in 1 in 75 of individuals of non-Finnish, European ancestry in a gene database search. “Our variant has an effect on a large fraction of the population,” she says.

    Young, who has studied the genes involved in the circadian clock of the fruit fly, connected with clinical researchers at the Weill Cornell Medical College to understand the molecular underpinnings of human sleep disorders. By studying the skin cells of people with DSPD, he and Patke discovered a mutation in CRY1, which helps drive the circadian clock.

    The circadian clock is a fundamental element of life on Earth and has remained more or less the same, genetically, throughout the evolution of animals. “It’s basically the same clock from flies to humans,” Young says.

    Normally the clock begins its cycle by building up proteins, call activators, in a cell. These activators produce their own inhibitors that, over time, cause the activators to lose their potency. When all the activators in the cell have been silenced, inhibitors are no longer produced and eventually degrade. Once they’ve all gone, the potency of the activators surges, and the cycle begins again.

    The CRY1 protein is one of the clock’s inhibitors. The mutation Young and Patke found is a single-point mutation in the CRY1 gene, meaning just one letter in its genetic instructions is incorrect. Yet this change causes a chunk of the gene’s resulting protein to be missing. That alteration causes the inhibitor to be overly active, prolonging the time that the activators are suppressed and stretching the daily cycle by half an hour or more.

    In addition to their initial study of a multigenerational family in the U.S., Young and Patke collaborated with clinical researchers at Bilkent University to analyze the sleep patterns of six families of Turkish individuals, 39 carriers of the CRY1 variant and 31 non-carriers. The carriers had delayed sleep onset times and some had fractured, irregular sleep patterns. The mid-point of sleep for non-carriers was about 4 a. m. But for carriers, the mid-point was shifted to 6-8 a.m.

    Because the mutation does not disable the protein, it can have an effect on individuals whether they carry one or two copies of the gene. Of the 39 Turkish carriers studied, 8 had inherited the mutation from both parents, and 31 had inherited only one copy of the mutation.

    The circadian clock responds to external environmental cues, so it is possible for people to manage the effects of the mutation on sleep. For instance, one carrier in the study reported maintaining a sleep routine through self-enforced regular sleep and wake times and exposure to bright light during the day. “An external cycle and good sleep hygiene can help force a slow-running clock to accommodate a 24-hour day,” says Patke. “We just have to work harder at it.”


  8. Deep sleep may act as fountain of youth in old age

    April 10, 2017 by Ashley

    From the UC Berkeley press release:

    As we grow old, our nights are frequently plagued by bouts of wakefulness, bathroom trips and other nuisances as we lose our ability to generate the deep, restorative slumber we enjoyed in youth.

    But does that mean older people just need less sleep?

    Not according to UC Berkeley researchers, who argue in an article published April 5 in the journal Neuron that the unmet sleep needs of the elderly elevate their risk of memory loss and a wide range of mental and physical disorders.

    “Nearly every disease killing us in later life has a causal link to lack of sleep,” said the article’s senior author, Matthew Walker, a UC Berkeley professor of psychology and neuroscience. “We’ve done a good job of extending life span, but a poor job of extending our health span. We now see sleep, and improving sleep, as a new pathway for helping remedy that.”

    Unlike more cosmetic markers of aging, such as wrinkles and gray hair, sleep deterioration has been linked to such conditions as Alzheimer’s disease, heart disease, obesity, diabetes and stroke, he said.

    Though older people are less likely than younger cohorts to notice and/or report mental fogginess and other symptoms of sleep deprivation, numerous brain studies reveal how poor sleep leaves them cognitively worse off.

    Moreover, the shift from deep, consolidated sleep in youth to fitful, dissatisfying sleep can start as early as one’s 30s, paving the way for sleep-related cognitive and physical ailments in middle age.

    And, while the pharmaceutical industry is raking in billions by catering to insomniacs, Walker warns that the pills designed to help us doze off are a poor substitute for the natural sleep cycles that the brain needs in order to function well.

    “Don’t be fooled into thinking sedation is real sleep. It’s not,” he said.

    For their review of sleep research, Walker and fellow researchers Bryce Mander and Joseph Winer cite studies, including some of their own, that show the aging brain has trouble generating the kind of slow brain waves that promote deep curative sleep, as well as the neurochemicals that help us switch stably from sleep to wakefulness.

    “The parts of the brain deteriorating earliest are the same regions that give us deep sleep,” said article lead author Mander, a postdoctoral researcher in Walker’s Sleep and Neuroimaging Laboratory at UC Berkeley.

    Aging typically brings on a decline in deep non-rapid eye movement (NREM) or “slow wave sleep,” and the characteristic brain waves associated with it, including both slow waves and faster bursts of brain waves known as “sleep spindles.”

    Youthful, healthy slow waves and spindles help transfer memories and information from the hippocampus, which provides the brain’s short-term storage, to the prefrontal cortex, which consolidates the information, acting as the brain’s long-term storage.

    “Sadly, both these types of sleep brain waves diminish markedly as we grow old, and we are now discovering that this sleep decline is related to memory decline in later life,” said Winer, a doctoral student in Walker’s lab.

    Another deficiency in later life is the inability to regulate neurochemicals that stabilize our sleep and help us transition from sleep to waking states. These neurochemicals include galanin, which promotes sleep, and orexin, which promotes wakefulness. A disruption to the sleep-wake rhythm commonly leaves older adults fatigued during the day but frustratingly restless at night, Mander said.

    Of course, not everyone is vulnerable to sleep changes in later life: “Just as some people age more successfully than others, some people sleep better than others as they get older, and that’s another line of research we’ll be exploring,” Mander said.

    Meanwhile, non-pharmaceutical interventions are being explored to boost the quality of sleep, such as electrical stimulation to amplify brain waves during sleep and acoustic tones that act like a metronome to slow brain rhythms.

    However, promoting alternatives to prescription and over-the-counter sleep aids is sure to be challenging.

    “The American College of Physicians has acknowledged that sleeping pills should not be the first-line kneejerk response to sleep problems,” Walker said. “Sleeping pills sedate the brain, rather than help it sleep naturally. We must find better treatments for restoring healthy sleep in older adults, and that is now one of our dedicated research missions.”

    Also important to consider in changing the culture of sleep is the question of quantity versus quality.

    “Previously, the conversation has focused on how many hours you need to sleep,” Mander said. “However, you can sleep for a sufficient number of hours, but not obtain the right quality of sleep. We also need to appreciate the importance of sleep quality.

    “Indeed, we need both quantity and quality,” Walker said.


  9. Mathematicians predict delaying school start times won’t help sleep deprived teenagers

    April 5, 2017 by Ashley

    From the University of Surrey press release:

    Delaying school start times in the UK is unlikely to reduce sleep deprivation in teenagers, research from the University of Surrey and Harvard Medical School has found. The research, conducted in collaboration between mathematicians and sleep scientists, predicts that turning down the lights in the evening would be much more effective at tackling sleep deprivation.

    Teenagers like to sleep late and struggle to get up in time to go to school. The commonly accepted explanation for this is that adolescents’ biological brain clocks are delayed. It has been suggested that to remedy this, school start times should be delayed for older teenagers so that they are again in tune with their biological clock.

    The study, which is published today in Scientific Reports, used a mathematical model that takes into account whether people are naturally more of a morning or evening person, the impact of natural and artificial light on the body clock and the typical time of an alarm clock, to predict the effects of delaying school start times.

    The mathematical model showed that delaying school start times in the UK would not help reduce sleep deprivation. Just as when clocks go back in the autumn, most teenagers’ body clocks would drift even later in response to the later start time, and in a matter of weeks they would find it just as hard to get out of bed. The results did, however, lend some support to delaying school start in the US, where many schools start as early as 7am.

    The mathematical explanation has its roots in the work of the 17th century Dutch mathematician Huygens. He saw that clocks can synchronise, but it depends on both the clocks and how they influence each other. From research over the last few decades we know that body clocks typically run a little slow, so they need to be regularly ‘corrected’ if they are to remain in sync with the 24-hour day. Historically, this correcting signal came from our interaction with the environmental light/dark ‘clock’.

    The mathematical model shows that the problem for adolescents is that their light consumption behaviour interferes with the natural interaction with the environmental clock — getting up late in the morning results in adolescents keeping the lights on until later at night. Having the lights on late delays the biological clock, making it even harder to get up in the morning. The mathematics also suggests that the biological clocks of adolescents are particularly sensitive to the effects of light consumption.

    The model suggests that an alternative remedy to moving school start times in the UK is exposure to bright light during the day, turning the lights down in the evening and off at night. For very early start times, as in some US regions, any benefit gained from delaying school start times could be lost unless it is coupled with strict limits on the amount of evening artificial light consumption.

    Lead author Dr Anne Skeldon said: “The power of the mathematics is that we are able to use existing knowledge about how light interacts with the biological clock to make predictions about different interventions to help reduce ‘social jetlag’.

    “It highlights that adolescents are not ‘programmed’ to wake up late and that by increasing exposure to bright light during the day, turning lights down in the evening and off at night should enable most to get up in time for work or school without too much effort and without changing school timetables.”

    Co-author Dr Andrew Phillips said: “The most interesting part of this analysis for me was the counter-intuitive finding that the most extreme evening types are predicted to derive the least benefit from a delay in school start times, because they tend to use evening artificial light for a longer interval of time.

    “For evening types, it is critical to keep evening light levels low to derive any of the potential benefits of a delay in morning alarm times, otherwise their bed time is very prone to shifting later. Understanding these individual differences, and how they are influenced by light consumption, is necessary to maximize the effects of any policy change.”

    Co-author Prof Derk-Jan Dijk said: “Just as mathematical models are used to predict climate change, they can now be used to predict how changing our light environment will influence our biological rhythms.

    “It shows that modern lifestyles make it hard for body clocks to stay on 24 hours, which shifts our rhythm of sleepiness and alertness to later times — meaning we are sleepy until late in the morning and remain alert until later in the evening.

    “As a result, during the working week our alarm clocks go off before the body clock naturally wakes us up. We then get insufficient sleep during the week and compensate for it during the weekend. Such patterns of insufficient and irregular sleep have been associated with various health problems and have been termed ‘social jet lag’.”

    The mathematical understanding of biological clocks suggests that adolescents are particularly sensitive to the effects of light consumption. However, the model can be applied to other age-groups as well. It can be used to design new interventions not only for sleepy teenagers but also for adults who suffer from delayed sleep phase disorders or people who are not synchronised to the 24-hour day at all.

    The research draws attention to light, light consumption and darkness as important environmental and behavioural factors influencing health. This has implications for how we design the light environment at work and at home in our modern light-polluted societies.


  10. Sleep deprivation impairs ability to interpret facial expressions

    March 29, 2017 by Ashley

    From the University of Arizona press release:

    After a rough night’s sleep, your ability to recognize whether those around you are happy or sad could suffer, according to a study led by a University of Arizona psychologist.

    The research, published in the journal Neurobiology of Sleep and Circadian Rhythms, found that study participants had a harder time identifying facial expressions of happiness or sadness when they were sleep deprived versus well-rested.

    The sleepy participants’ ability to interpret facial expressions of other emotions — anger, fear, surprise and disgust — was not impaired, however. That’s likely because we’re wired to recognize those more primitive emotions in order to survive acute dangers, said lead researcher William D.S. Killgore, a UA professor of psychiatry, psychology and medical imaging.

    While emotions such as fear and anger could indicate a threat, social emotions such as happiness and sadness are less necessary for us to recognize for immediate survival. When we’re tired, it seems we’re more likely to dedicate our resources to recognizing those emotions that could impact our short-term safety and well-being, Killgore said.

    “If someone is going to hurt you, even when you’re sleep deprived you should still be able to pick up on that,” Killgore said. “Reading whether somebody is sad or not is really not that important in that acute danger situation, so if anything is going to start to degrade with lack of sleep it might be the ability to recognize those social emotions.”

    The data used in the study was part of a larger research effort on sleep deprivation’s effects on social, emotional and moral judgment. Killgore began the project while working as a research psychologist for the U.S. Army.

    The current study is based on data from 54 participants, who were shown photographs of the same male face expressing varying degrees of fear, happiness, sadness, anger, surprise and disgust. Participants were asked to indicate which of those six emotions they thought was being expressed the most by each face.

    In order to assess participants’ ability to interpret more subtle emotional expressions, the images presented were composite photos of commonly confused facial expressions morphed together by a computer program. For example, a face might show 70 percent sadness and 30 percent disgust or vice versa. Participants saw a total of 180 blended facial expressions at each testing session.

    Participants’ baseline responses to the images were compared to their responses after they were deprived of sleep for one night.

    Researchers found that blatant facial expressions — such as an obvious grin or frown (90 percent happy or 90 percent sad) — were easily identifiable regardless of how much sleep a participant got. Sleep deprived participants had a harder time, however, correctly identifying more subtle expressions of happiness and sadness, although their performance on the other emotions was unchanged.

    When participants were tested again after one night of recovery sleep, their performance on happiness and sadness improved, returning to its baseline level.

    While the difference in performance was not overwhelming, it’s enough that it could have a significant impact in critical social interactions, Killgore said.

    “As a society, we don’t get the full seven to eight hours of sleep that people probably need to be getting. The average American is getting a little less than six hours of sleep on average, and it could affect how you’re reading people in everyday interactions,” Killgore said. “You may be responding inappropriately to somebody that you just don’t read correctly, especially those social emotions that make us human. Or you may not be as empathic. Your spouse or significant other may need something from you and you’re less able to read that. It’s possible that this could lead to problems in your relationships or problems at work. To me, that is one of the biggest problems — how this affects our relationships.”

    Killgore’s research builds on existing work on the effects of sleep deprivation on the brain’s ventromedial prefrontal cortex — an area that helps people make judgments and decisions using their emotions.

    A prior study, published by Harvard’s Seung-Schik Yoo and colleagues, showed that when people are sleep deprived, a disconnect occurs between the prefrontal cortex and the amygdala — one of the key emotionally responsive areas of the brain.

    “So, in simplistic terms, the part of the brain that controls your emotions and the part that sees faces and responds to the emotional content basically start to lose their ability to communicate,” Killgore said. “We wanted to test that out and see if it plays out in terms of how people read facial expressions — and, in fact, it looks like it does.”