TAG: "Sleep"

The mechanics of jet lag revealed

UC Irvine study shows how light shifts disrupt biological clocks.

Long the stuff of science fiction, the disembodied “brain in a jar” is providing science fact for UC Irvine researchers, who by studying the whole brains of fruit flies are discovering the inner mechanisms of jet lag.

To do this, Todd C. Holmes, professor of physiology & biophysics in the UC Irvine School of Medicine, and colleagues used imaging technology to make movies of fruit fly brains kept alive for six days in a petri dish. The scientists captured the activity of individual circadian clocks at single-cell resolution with an extremely sensitive low-light camera in order to determine how the circadian clock circuit is “reset” by light.

The study marks the first time researchers have seen in real time how specific neurons in intact circadian neural networks react to light cues that are comparable to rapid travel across time zones, such as flying from Los Angeles to Chicago. Study results appear online in Current Biology.

Most organisms make daily adjustments to their activity and metabolism to synchronize with environmental signals – daylight being the most powerful circadian cue. The scientists found that desynchronization of circadian neurons is a key feature of light-induced jet lag and suggest that treatments accelerating this desynchronization before travel may speed recovery afterward.

“Remarkably, our work indicates that the way you feel while jet-lagged exactly reflects what your nervous system is experiencing: a profound loss of synchrony,” Holmes said.

He explained that a single light pulse cues the biological clock of the fruit fly brain to shift two hours ahead of its original schedule through a process the researchers call “phase retuning.” This is characterized by a circadian circuit-wide pattern of brief desynchrony followed by the gradual emergence of a new state of network synchrony.

The scientists propose that temporarily weakening synchronization among neurons governed by circadian patterns allows for more rapid adaptation (an estimated two days) by enabling phase retuning to a new time zone’s cues. Normally, Holmes said, circadian circuit light response – i.e., jet lag recovery – takes place over four days for the time shift tested. A larger time shift, such as the one experienced in flying from Los Angeles to London, would likely require a longer time for recovery.

“That two-day difference is quite a bit if it means you feel great from the beginning of your arrival, say, in Italy,” Holmes noted. “You’re going to feel bad on the plane in any event, so it’s best to get the adjustment over with so you can enjoy your destination. I’m certain this will lead to treatments that’ll have a big impact on our travel practices.”

“These results literally and figuratively bring the inner workings of biological clocks ‘into the light,’” said Logan Roberts, a graduate student researcher in Holmes’ lab and the study’s first author.

“This work illustrates in real time how the network of daily clocks in the brain adjusts to synchronize with the local light cycle,” added Erik Herzog, a circadian biology expert at Washington University in St. Louis who was not involved in the study. “With extraordinary cellular resolution, the researchers show that some cells shift faster than others following a pulse of light. This might become a useful therapy in treating jet lag or the growing problem of ‘social jet lag,’ where people keep different schedules during the week than on the weekends.”

Alexis Galschiodt and Jerry Houl of UC Irvine; Takako Noguchi and David Welsh of UC San Diego; and Tanya Leise of Amherst College also contributed to the study, which was supported by the National Institutes of Health (grants NS046750, NS078434, GM102965 and GM107405) and the National Science Foundation (grants IBN-0323466 and DGE-1321846).

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A solution to sleepless nights for older adults

Mindfulness meditation may aid sleep, say UCLA researchers.

Michael Irwin, UCLA

By Mark Wheeler, UCLA

Everybody has a restless night now and again, but sleep disturbances among the elderly are a significant medical and public health concern.

An estimated 50 percent of people aged 55 and older suffer from some form of sleep problem, including not being able to fall asleep or not being able to stay asleep when they do. And those nighttime issues can carry over into the day, causing fatigue, depression and a diminished quality of life. Medications can help but they are, at best, temporary fixes, and they can cause daytime side effects and carry the risk of drug dependency.

All of which has created an urgent need for a way to help older adults sleep better without a pill.

Researchers at UCLA’s Semel Institute for Neuroscience and Human Behavior say they’ve found a relatively simple mind–body intervention that fits the bill. Working with collaborators at the University of Southern California’s Keck School of Medicine, the scientists found that mindfulness meditation promotes sleep quality in older adults who suffer from moderate sleep complaints.

Their research appears in the Feb. 12 online edition of the Journal of the American Medical Association, Internal Medicine.

Dating back thousands of years, the practice of mindfulness meditation involves paying attention to — but not reacting to, judging or being distracted by — one’s own moment-by-moment thoughts, emotions, and physiological responses and sensations.

Mindful awareness has scientific support as a means to reduce stress, improve attention, boost the immune system, reduce emotional reactivity and promote a general sense of health and well-being.

Essentially, that means “staying in the present and not judging your thoughts or observations,” said Dr. Michael Irwin, the study’s senior author, a UCLA professor of psychiatry and director of the Cousins Center for Psychoneuroimmunology at the Semel Institute.

Previous studies by Cousins Center researchers showed that tai chi, a Chinese martial art based on slow movement and meditation, can improve sleep quality in older adults. In the current study, the researchers tested whether meditation involving mental practices alone would have similar benefits.

The randomized control trial involved 49 volunteers 55 and older, divided into two groups. One group completed a six-week, two-hour-per-week program during which participants were taught about sleep biology, sleep problems, stress biology and stress reduction; relaxation methods for improving sleep; and modifying poor sleep habits and establishing a bedtime routine.

The second group participated in a mindfulness meditation course of similar duration. In addition to lectures and group discussions, weekly sessions covered experiential mindfulness exercises, including an “appreciation meditation” that focused on expressing gratitude, along with mindful movement and sitting meditations.

The researchers evaluated participants’ changes in sleep quality using the Pittsburgh Sleep Quality Index, a commonly used questionnaire that assesses sleep quality and disturbances. They found that, compared with people whose program focused only on sleep hygiene education, participants in the mindfulness meditation group showed a greater improvement in their quality of sleep — similar in magnitude to the sleep improvements reported in other studies using standard behavioral treatment or sleeping aids.

In addition to better sleep quality, the mindfulness group also reported fewer insomnia symptoms, less fatigue and less depression than the sleep hygiene education group.

The researchers note that more research is needed to validate the findings and determine the longer-term effects of mindfulness meditation on sleep.

“All of us have had sleepless nights and we’ve all experienced what that does to us the day after,” Irwin said. “Imagine if you were living with this day in and day out; it can be exhausting, and certainly detrimental to your health, particularly for the elderly population. The practice of mindfulness appears to promote a good night’s sleep.”

Other authors were Richard Olmstead and Elizabeth Breen of UCLA; and first author David S. Black and Gillian O’Reilly of USC.

The work was supported by the UCLA Older Americans Independence Center (AG028748), the UCLA Clinical and Translational Science Institute (UL1TR000124), the National Institute of Mental Health (5T32-MH019925, R01-AG034588, R01-AG026364, R01-CA160245-01, R01-CA119159, R01-HL095799, R01-DA032922-01, and P30-AG028748), the Furlotti Family Foundation, the Petit Foundation and the Cousins Center for Psychoneuroimmunology.

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‘Sleepless in America’ documentary to feature UC Berkeley research

Documentary to air Nov. 30 on National Geographic Channel.

UC Berkeley neuroscientist Matthew Walker is featured in “Sleepless in America,” a documentary that airs this Sunday, Nov. 30, on the National Geographic Channel (Photo by National Geographic)

We spend one-third of our lives sleeping, and yet it is only in the last decade or so that scientists have begun to really understand why. Among other things, UC Berkeley sleep researcher Matthew Walker has linked sleep deprivation to psychiatric disorders, obesity, risky behavior, post-traumatic stress disorder, learning and memory loss in old age.

This Sunday, Nov. 30,  Walker and other scientists will be featured in the captivating documentary “Sleepless in America,” on the National Geographic Channel.

A co-production of the Public Good Projects and the National Institutes of Health, the documentary lays out in sometimes gripping detail the perils of getting too little sleep. For more details about sleep research at UC Berkeley, click on the following links.

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Sleep apnea is linked to poor aerobic fitness

People with sleep apnea have lower peak oxygen uptake during aerobic activity, study finds.

People with moderate to severe obstructive sleep apnea may have an intrinsic inability to burn high amounts of oxygen during strenuous aerobic exercise, according to a new study led by researchers at the UC San Diego School of Medicine.

The study, reported in the current issue of Journal of Clinical Sleep Medicine, shows that people with sleep apnea, in which breathing repeatedly starts and stops during slumber, have a lower peak oxygen uptake during aerobic activity than those who do not suffer from the sleep disorder.

People who suffer from apnea are more likely to be obese and thus would be expected to be less fit as well. The researchers, however, found that apnea patients had a reduced aerobic fitness, even compared with those of similar body mass indices.

“Encouraging patients to exercise more is part of the story, but that is not the whole story,” said lead author Jeremy Beitler, M.D., assistant clinical professor in pulmonary and critical care medicine. “We believe the sleep apnea itself causes structural changes in muscle that contributes to their difficulty exercising.”

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Tai chi reduces inflammation in breast cancer survivors

Practicing the ancient Chinese martial art could potentially lower risk for cancer recurrence.

UCLA researchers have discovered that the Chinese practice of tai chi can reduce inflammation in people who have had breast cancer, thereby reducing a risk factor for the recurrence of the cancer.

Current research indicates that women diagnosed with breast cancer in the past 10 years are three times more likely to suffer from lack of sleep. Insomnia can lead to increases in inflammation, which places breast cancer survivors at risk for cancer recurrence as well as cardiovascular disease.

Led by UCLA Jonsson Comprehensive Cancer Center member Dr. Michael Irwin, researchers conducted a five-year randomized clinical trial from April 2007 to August 2013. His team analyzed blood samples from 90 participants between 30 to 85 years old, before and after they started the tai chi routine.

“When people practice tai chi, there is a decrease in the stress hormones produced by the sympathetic nervous system,” said Irwin, who is professor of psychiatry and biobehavioral sciences at UCLA.

Irwin and his colleagues also discovered that tai chi relaxes the body to a certain point that it can reduce inflammation, which is commonly seen in most breast cancer survivors after treatment.

“We saw that tai chi reversed cellular inflammation, by producing a down-regulation of the genes that lead to inflammation,” said Dr. Irwin. “Tai chi is a movement meditation, and we have found that similar anti-inflammatory effects occur when people practice other forms of meditation.”

Irwin said that he hopes the exercise will gain in popularity, particularly in low-income communities where many do not have immediate access to breast cancer treatment.

Two-time breast cancer survivor Linda Tucker has had many sleepless nights until recently.

“I absolutely did not sleep, my eyes would not stay asleep, my body just would not relax and I found myself awake until six in the morning,” said Tucker.

Desperate to find a cure for her sleeping problems, Tucker decided to participate in Irwin’s tai chi study at UCLA despite her initial skepticism.

“I said to myself, this has to be a joke, this is not going to work or do anything. But after two sessions the insomnia started going away,” she said. “I just felt a sense of peacefulness.”

The study was published online Nov. 4 in the Journal of the National Cancer Institute.

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Sleep researcher awarded federal grants totaling $2.7M

Research has implications for improving sleep and memory for aging adults, college students.

Sara Mednick, UC Riverside

UC Riverside psychologist Sara C. Mednick has been awarded nearly $2.7 million in federal grants to continue researching the neural mechanisms of learning and memory, which has implications for improving sleep and memory for aging adults and the health of college students who pop so-called “smart drugs.”

Mednick previously led a team whose groundbreaking research confirmed the mechanism that enables the brain to consolidate memory and found that Ambien, a commonly prescribed sleep aid, enhances the process.

The National Institute on Aging, the National Science Foundation and the Department of Defense-Office of Naval Research have awarded Mednick grants to support research into sleep processes that are important for learning and memory, and how those processes might be manipulated to improve both.

Supported by a five-year, $1.25 million grant from the National Institutes of Health-National Institute on Aging, Mednick is expanding on research published last year which demonstrated for the first time the critical role that sleep spindles play in consolidating memory in the hippocampus region of the brain. Her team also showed that pharmaceuticals could significantly improve that process, far more than sleep alone.

Sleep spindles are bursts of brain activity that last for a second or less during a specific stage of sleep. The hippocampus, part of the cerebral cortex, is important in the consolidation of information from short-term to long-term memory, and spatial navigation. The hippocampus is one of the first regions of the brain damaged by Alzheimer’s disease.

The new study, which began in fall 2013, will investigate doses of Ambien needed to boost sleep spindles and whether declarative memory – the ability to recall facts and knowledge – improves as well. The next study will test the same question in older adults.

“Older adults have poorer sleep and less sleep spindles. They also experience decreases in verbal memory,” Mednick explained. “Maybe these decreases in cognition are related to less sleep. A question we hope to answer is, can we slow the cognitive aging process?”

In another project, Mednick and UC Berkeley neuroscientist Michael Silver will share a $450,000, three-year grant from the National Science Foundation to study the role of neural transmitters that are known to be important for brain plasticity and memory consolidation.

The researchers will study whether a prescription drug used to treat dementia associated with Alzheimer’s disease and Parkinson’s disease – Rivastigmine – can improve declarative memory. Rivastigmine is known to activate acetylcholine, a neuromodulator known as the “memory molecule.” Acetylcholine plays a role in attention and arousal and works to activate muscles.

A $995,381 grant from the Office of Naval Research will support a study of the effects of psychostimulants such as Adderall and Ritalin – used to treat attention deficit hyperactivity disorder (ADHD) – on cognition and sleep.

“Off-label use of these drugs has been increasing dramatically in the college population, and there has been very little research on their impacts on healthy populations and on sleep,” Mednick said. “I am interested in how these drugs may be influencing sleep-dependent memory consolidation.”

The military is interested out of concern that the practice of giving so-called “go” and “no-go” pills to keep servicemen and women alert for long periods of time may affect cognition.

About one-third of college students – approximately 11 million young adults – take the ADHD medications without prescriptions, assuming that these so-called “smart drugs” will make them smarter and take the place of sleep, Mednick explained.

“Research shows they aren’t getting better grades, but they believe they will,” she said. This study will help determine if these drugs can replace sleep, “or if there is something so important about sleep that no pharmacological intervention can replace. What are the links between sleep disruption and cognitive decline?”

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Treating insomnia in elderly reduces inflammation

Study finds a common form of psychotherapy is most effective at alleviating sleeplessness.

Michael Irwin, UCLA

Lack of sleep can make you sick. And while everybody has the occasional restless night, for those who suffer from chronic insomnia — some 15 percent of older adults in the United States — that sleep loss can increase the risk for cardiovascular disease, hypertension, weight gain, type 2 diabetes and even lead to an earlier death.

The reason for the increased risk of health problems is thought to be an association between insomnia and an increase in inflammation throughout the body that becomes chronic. Though inflammation can be a good thing — part of a robust immune response that heals injury and fights infection, chronic inflammation can damage and kill healthy cells, leading to disease.

What hasn’t been known is whether treating insomnia could reduce inflammation, thereby lowering the risk for chronic disease in older adults. Nor has it been known what the most effective therapy is to treat insomnia.

Now UCLA researchers have answered both these questions. In a new study, they demonstrate that reducing insomnia can indeed lead to decreases in inflammation, and second, that a form of psychotherapy called cognitive behavioral therapy proved superior to other forms of treatment.

The study appears in the September issue of the journal Sleep.

The results were obtained from a randomized clinical trial of 123 adults older than 55, and showed that treating insomnia led to decreases in a known marker of inflammation called C-reactive protein (CRP). The protein is found in blood plasma, and its levels rise in response to an acute inflammatory stimulus. The CRP levels were measured at the beginning of the study, again after treatment, and again in a follow-up 16 months later.

“What we found particularly intriguing was that the levels of the CRP inflammatory marker remained low even 16 months after treating the insomnia,” said Michael Irwin, first author, and a professor of psychiatry and director of the Cousins Center for Psychoneuroimmunology at the UCLA Semel Institute for Neuroscience and Human Behavior.

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Study finds sleep disorders widely undiagnosed in individuals with MS

More than 70 percent of study participants screened positive for at least one sleep disorder.

Steven Brass, UC Davis

In what may be the largest study of sleep problems among individuals with multiple sclerosis (MS), researchers at UC Davis have found that widely undiagnosed sleep disorders may be at the root of the most common and disabling symptom of the disease: fatigue.

Conducted in over 2,300 individuals in Northern California with multiple sclerosis, the large, population-based study found that, overall, more than 70 percent of participants screened positive for one or more sleep disorders.

The research highlights the importance of diagnosing the root causes of fatigue among individuals with MS, as sleep disorders may affect the course of the disease as well as the overall health and well-being of sufferers, the authors said.

The study “The Underdiagnosis of Sleep Disorders in Patients with Multiple Sclerosis,” is published online today (Sept. 12) in the Journal of Clinical Sleep Medicine.

“A large percentage of MS subjects in our study are sleep deprived and screened positive for one or more sleep disorders,” said Steven Brass, associate clinical professor and director of the Neurology Sleep Clinical Program and co-medical director of the UC Davis Sleep Medicine Laboratory.

“The vast majority of these sleep disorders are potentially undiagnosed and untreated,” he said. “This work suggests that patients with MS may have sleep disorders requiring independent diagnosis and management.”

Fatigue is the hallmark of multiple sclerosis, an inflammatory disease affecting the white matter and spinal cord of sufferers. MS symptoms include loss of vision, vertigo, weakness and numbness. Patients also may experience psychiatric symptoms. Disease onset generally is between the ages of 20 and 50 years. The cause of MS is not known, although it is believed to be an autoimmune condition.

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Study shows evidence that sleep apnea hurts brain

UCLA researchers find that people suffering from sleep apnea have weaker brain blood flow.

This brain scan shows that the brain blood flow in a subject with obstructive sleep apnea (left) is markedly lower compared to a subject without the sleep disorder.

Employing a measure rarely used in sleep apnea studies, researchers at the UCLA School of Nursing have uncovered evidence of what may be damaging the brain in people with the sleep disorder — weaker brain blood flow.

In the study, published Aug. 28 in the peer-reviewed journal PLOS ONE, researchers measured blood flow in the brain using a non-invasive MRI procedure: the global blood volume and oxygen dependent (BOLD) signal. This method is usually used to observe brain activity.  Because previous research showed that poor regulation of blood in the brain might be a problem for people with sleep apnea, the researchers used the whole-brain BOLD signal to look at blood flow in individuals with and without obstructive sleep apnea (OSA).

“We know there is injury to the brain from sleep apnea, and we also know that the heart has problems pumping blood to the body, and potentially also to the brain,” said Paul Macey, associate dean for Information Technology and Innovations at the UCLA School of Nursing and lead researcher for the study. “By using this method, we were able to show changes in the amount of oxygenated blood across the whole brain, which could be one cause of the damage we see in people with sleep apnea.”

Obstructive sleep apnea is a serious disorder that occurs when a person’s breathing is repeatedly interrupted during sleep, hundreds of times a night. Each time breathing stops, the oxygen level in the blood drops, which damages many cells in the body. If left untreated, it can lead to high blood pressure, stroke, heart failure, diabetes, depression and other serious health problems. Approximately 10 percent of adults struggle with obstructive sleep apnea, which is accompanied by symptoms of brain dysfunction, including extreme daytime sleepiness, depression and anxiety, and memory problems.

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How sleep impacts PTSD

Fragmented REM sleep may hinder effective treatment of post-traumatic stress disorder.

The effectiveness of post-traumatic stress disorder (PTSD) treatment may hinge significantly upon sleep quality, report researchers at the UC San Diego School of Medicine and Veterans Affairs San Diego Healthcare System in a paper published today (Aug. 26) in the Journal of Neuroscience.

“I think these findings help us understand why sleep disturbances and nightmares are such important symptoms in PTSD,” said Sean P.A. Drummond, Ph.D., professor of psychiatry and director of the Behavioral Sleep Medicine Program at the VA San Diego Healthcare System. “Our study suggests the physiological mechanism whereby sleep difficulties can help maintain PTSD. It also strongly implies a mechanism by which poor sleep may impair the ability of an individual to fully benefit from exposure-based PTSD treatments, which are the gold standard of interventions.

“The implication is that we should try treating sleep before treating the daytime symptoms of PTSD and see if those who are sleeping better when they start exposure therapy derive more benefit.”

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Teen night owls likely to perform worse academically, emotionally

Results present compelling argument for later middle and high school start times.

Lauren Asarnow, UC Berkeley

Lauren Asarnow, UC Berkeley

Teenagers who go to bed late during the school year are more prone to academic and emotional difficulties in the long run, compared to their earlier-to-bed counterparts, according to a new study from UC Berkeley.

Berkeley researchers analyzed longitudinal data from a nationally representative cohort of 2,700 U.S. adolescents of whom 30 percent reported bedtimes later than 11:30 p.m. on school days and 1:30 a.m. in the summer in their middle and high school years.

By the time they graduated from high school, the school-year night owls had lower GPA scores, and were more vulnerable to emotional problems than teens with earlier bedtimes, according to the study published online today (Nov.10) in the Journal of Adolescent Health.

The results present a compelling argument in favor of later middle and high school start times in the face of intense academic, social and technological pressures, researchers said.

“Academic pressures, busy after-school schedules, and the desire to finally have free time at the end of the day to connect with friends on the phone or online make this problem even more challenging,” said Lauren Asarnow, lead author of the study and a graduate student in UC Berkeley’s Golden Bear Sleep and Mood Research Clinic.

On a positive note, she said the findings underscore how a healthy sleep cycle promotes the academic and emotional success of adolescents.

“The good news is that sleep behavior is highly modifiable with the right support,” said Asarnow, citing  UC Berkeley’s Teen Sleep Study, a treatment program designed to reset the biological clocks of adolescents who have trouble going to sleep and waking up.

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Sleep apnea study uncovers more hidden dangers for women

UCLA researcher: “We now know that sleep apnea is a precursor to bigger health issues.”

Paul Macey, UCLA

Paul Macey, UCLA

There’s more bad news for women with sleep apnea. A new study from the UCLA School of Nursing shows that the body’s autonomic responses — the controls that impact such functions as blood pressure, heart rate and sweating — are weaker in people with obstructive sleep apnea but are even more diminished in women.

Women with obstructive sleep apnea may appear to be healthy — having, for instance, normal resting blood pressure — and their symptoms also tend to be subtler, which often means their sleep problem is missed and they get diagnosed with other conditions.

“We now know that sleep apnea is a precursor to bigger health issues,” said Paul Macey, lead researcher on the study, which appears today (Oct. 23) in the peer-reviewed journal PLOS ONE. “And for women in particular, the results could be deadly.”

Obstructive sleep apnea is a serious disorder that occurs when a person’s breathing is repeatedly interrupted during sleep, sometimes hundreds of times. Each time, the oxygen level in the blood drops, eventually resulting in damage to many cells in the body. The condition affects more that 20 million adults in the U.S. and is associated with a number of serious health consequences and early death. Women are much less likely to be diagnosed than men.

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