Asleep somewhere new, one brain hemisphere keeps watch

April 21, 2016

Science Daily/Brown University

Have trouble sleeping on your first night in a new place? A new study explains what's going on in the brain during that 'first-night effect.'

https://images.sciencedaily.com/2016/04/160421133630_1_540x360.jpg

A rich array of electrodes in the sleep lab allowed for widespread but sensitive sensing of brain activity.

Credit: Michael Cohea/Brown University

The study in Current Biology explains what underlies the "first-night effect," a phenomenon that poses an inconvenience to business travelers and sleep researchers alike. Sleep is often noticeably worse during the first night in, say, a hotel or a sleep lab. In the latter context, researchers usually have to build an "adaptation night" into their studies to do their experiments. This time around, the team at Brown investigated the first-night effect, rather than factoring it out.

"In Japan they say, 'if you change your pillow, you can't sleep,'" said corresponding author Yuka Sasaki, research associate professor of cognitive linguistic and psychological sciences at Brown. "You don't sleep very well in a new place. We all know about it."

Sasaki and lead author Masako Tamaki wanted to figure out why. Over the course of three experiments their team used several methods to precisely measure brain activity during two nights of slumber, a week apart, among a total of 35 volunteers. They consistently found that on the first night in the lab, a particular network in the left hemisphere remained more active than in the right hemisphere, specifically during a deep sleep phase known as "slow-wave" sleep. When the researchers stimulated the left hemisphere with irregular beeping sounds (played in the right ear), that prompted a significantly greater likelihood of waking, and faster action upon waking, than if sounds were played in to the left ear to stimulate the right hemisphere.

In other sleep phases and three other networks tested on the first night, there was no difference in alertness or activity in either hemisphere. On the second night of sleep there was no significant difference between left and right hemispheres even in the "default-mode network" of the left hemisphere, which does make a difference on the first night. The testing, in other words, pinpointed a first-night-only effect specifically in the default-mode network of the left hemisphere during the slow-wave phase.

"To our best knowledge, regional asymmetric slow-wave activity associated with the first-night effect has never been reported in humans," the authors wrote.

To make the novel findings, the researchers used electroencephalography, magnetoencephelography, and magnetic resonance imaging to make unusually high-resolution and sensitive measurements with wide brain coverage.

Despite all that instrumentation, the volunteers did not report any unusual discomfort or anxiety in surveys. They were all screened for general mental health before enrollment in the research to ensure their typical sleep was likely to be normal.

Though the study evidence appears to document and explain the first-night effect, it doesn't answer all the questions about it, Sasaki acknowledged. The researchers only measured the first slow-wave sleep phase, for example. Therefore they don't know whether the left hemisphere keeps watch all night, or works in shifts with the right later in the night.

"It is possible that that the surveillance hemisphere may alternate," Sasaki said.

It's also not clear whether the default-mode network is a lonely watchman. In its day job, which some researchers associate with mind-wandering and daydreaming, it tends to keep running when the brain is otherwise fairly idle. There is evidence from prior studies that it remains more connected to other brain networks than most others during sleep. But because the researchers only measured four networks, they aren't sure what others the default-mode network may work with.

Finally, Sasaki said it's not known yet why the brain only maintains an alert state in just one hemisphere -- whether it's always the left or in alternation with the right. There are many examples among animals, however, of hemispheric asymmetry during slow-wave sleep. Marine mammals exhibit it, Sasaki said, presumably because they regularly need to resurface to breathe, even during sleep.

Now it's been found in humans as a first-night phenomenon.

"The present study has demonstrated that when we are in a novel environment, inter-hemispheric asymmetry occurs in regional slow-wave activity, vigilance and responsiveness, as a night watch to protect ourselves," the study concludes.

https://www.sciencedaily.com/releases/2016/04/160421133630.htm

Mitochondria affect stress responses Cell's powerhouse plays role in mind-body interactions, with long-term health effects

December 2, 2015
Science Daily/Children's Hospital of Philadelphia
Mitochondria, the tiny structures inside our cells that generate energy, may also play a previously unrecognized role in mind-body interactions. Based on new studies of stress responses in animals, this insight may have broad implications for human psychology and for the biology of psychiatric and neurological diseases.

A pioneering scientist in mitochondrial medicine has led research in animals showing how alterations in mitochondrial function lead to distinct physiological changes in hormonal, metabolic and behavioral systems in response to mild stress.

"Our findings suggest that relatively mild alterations in mitochondrial genes, and hence mitochondrial physiology, have large effects on how mammals respond to stressful changes in their environment," said Douglas C. Wallace, Ph.D., director of the Center for Mitochondrial and Epigenomic Medicine at The Children's Hospital of Philadelphia. "This has profound implications for the hereditary basis of neuropsychiatric diseases and for the role of stress in human health."

Wallace and colleagues published their study ahead of print on Nov. 16 in Proceedings of the National Academy of Sciences.

Wallace, who has investigated the genetics of mitochondria and their role in health for over 40 years, has long argued that a traditional biomedical approach focused on anatomy and thus, on the organ exhibiting the most prominent symptoms of a disease, overlooks the key role played by systematic bioenergetics in health. At the core of bioenergetics are the mitochondria, residing in large numbers outside the nucleus of every cell. Mitochondria contain their own DNA, which codes for essential energy genes and which exchanges biological signals with the more familiar DNA housed in the cell nucleus. Those interactions affect physiological networks essential for health.

In this current study, the researchers subjected the mice to a standardized psychological stress: placing them in restraint for a brief period. They then measured the effects of this stressor on the animals' neuroendocrine, inflammatory, metabolic and gene transcription systems. In humans, all of these systems are involved in behavioral responses to stress and long-term susceptibility to stress-related diseases.

Wallace and colleagues showed that in the mice, relatively mild mutations in mitochondrial genes, located in either mitochondrial DNA (mtDNA) or nuclear DNA, produced unique whole-body stress-response signatures, indicated by physiological and gene expression patterns. These differential responses to stress due to mitochondrial variation provide a physiological explanation for a 2012 observation by Wallace's laboratory team. That research, published in Cell, involved mixing two normal but different mtDNAs in a mouse model, thus thwarting the usual strict maternal inheritance of the mitochondrial DNA. Simply mixing those two mtDNAs resulted in hyper-excitable mice with severe learning and memory defects.

While researchers have long recognized individual differences in response to environmental cues such as stress, identifying the genetic and physiological basis for these individual differences has eluded scientists. Although he emphasizes that much more research remains to be done on the role of mitochondria on human behavior, Wallace postulates that the current study indicates that an important reason for our limited progress in understanding the genetic and biologic basis of psychology is our lack of appreciation for the importance of systematic alterations in energetic metabolism. "The brain, constituting only 2 percent of human body weight, consumes 20 percent of the body's energy," he said. "Hence, mild variations in mitochondrial bioenergetics will have significant effects on the brain."

It is well known that frequently activating stress responses can inflict long-term damage in mammals and humans. Under the framework of mind-body connections, stress researchers refer to allostatic load: the cumulative wear and tear on the body that can result in both psychological disorders and human diseases such as diabetes and age-related cognitive decline.

As Wallace and associates point out, "Scientists have long known that stressful experiences, on their own, do not cause disease; it's our responses to stress that have the potential to culminate in disease." They conclude, "In this emerging paradigm, mitochondria are at the interface of genetic and environmental factors contributing to disease trajectories."

One implication of this new study, said Wallace, is that identifying the altered mitochondrial states associated with neuropsychiatric diseases may help suggest new therapies. These may permit physicians to more effectively ameliorate the effects of environmental stressors on human health. This could make people more resilient in environmental changes, reduce the long-term burden of stress-related diseases and produce more effective therapies for psychiatric disorders.

Wallace concludes, "While human differences in behavior and its relation to predisposition to mental illness as well as to a wide varied of pediatric and adult neurological diseases has been the subject of intense investigations for over a century, we still have a rudimentary understanding of the physiological, genetic, and environmental factors that mediate mental health and illness. Our recent papers strongly suggest that by reorienting our investigations from the anatomy of the brain and brain-specific genes to the mitochondria and the bioenergetics genes, we may have a more productive conceptual framework to understand neuropsychiatric disease. If so, this will spawn a whole new generation of neuropsychiatric therapeutics."
http://www.sciencedaily.com/releases/2015/12/151202132521.htm

Sense of purpose in life linked to lower mortality and cardiovascular risk

December 3, 2015
Science Daily/Wolters Kluwer Health: Lippincott Williams and Wilkins
People who have a higher sense of purpose in life are at lower risk of death and cardiovascular disease, reports a pooled data analysis.
https://images.sciencedaily.com/2015/12/151203112844_1_540x360.jpg
An analysis showed a lower risk of death for people with a high sense of purpose in life.
Credit: © alexbrylovhk / Fotolia

"Possessing a high sense of purpose in life is associated with a reduced risk for mortality and cardiovascular events," according to the study by Drs. Randy Cohen and Alan Rozanski and colleagues at Mt. Sinai St. Luke's-Roosevelt Hospital, New York. While the mechanisms behind the association remain unclear, the findings suggest that approaches to strengthening a sense of purpose might lead to improved health outcomes.

How Does Purpose in Life Affect Health and Mortality Risks?

Using a technique called meta-analysis, the researchers pooled data from previous studies evaluating the relationship between purpose in life and the risk of death or cardiovascular disease. The analysis included data on more than 136,000 participants from ten studies -- mainly from the United States or Japan. The US studies evaluated a sense of purpose or meaning in life, or "usefulness to others." The Japanese studies assessed the concept of ikigai, translated as "a life worth living."

The study participants, average age 67 years, were followed up for an average of seven years. During this time, more than 14,500 participants died from any cause while more than 4,000 suffered cardiovascular events (heart attack, stroke, etc).

The analysis showed a lower risk of death for participants with a high sense of purpose in life. After adjusting for other factors, mortality was about one-fifth lower for participants reporting a strong sense of purpose, or ikigai.

A high sense of purpose in life was also related to a lower risk of cardiovascular events. Both associations remained significant on analysis of various subgroups, including country, how purpose in life was measured, and whether the studies included participants with pre-existing cardiovascular disease..

There is a well-documented link between "negative psychosocial risk factors" and adverse health outcomes, including heart attack, stroke, and overall mortality. "Conversely, more recent study provides evidence that positive psychosocial factors can promote healthy physiological functioning and greater longevity," according to the authors.

The new analysis assembles high-quality data from studies assessing the relationship between purpose life and various measures of health and adverse clinical outcomes. The researchers write, "Together, these findings indicate a robust relationship between purpose in life and mortality and/or adverse cardiovascular outcomes."

While further studies are needed to determine how purpose in life might promote health and deter disease, preliminary data suggest a few basic mechanisms. The association might be explained physiologically, such as by buffering of bodily responses to stress; or behaviorally, such as by a healthier lifestyle.

"Of note, having a strong sense of life purpose has long been postulated to be an important dimension of life, providing people with a sense of vitality motivation and resilience," Dr. Rozanski comments. "Nevertheless, the medical implications of living with a high or low sense of life purpose have only recently caught the attention of investigators. The current findings are important because they may open up new potential interventions for helping people to promote their health and sense of well-being."
http://www.sciencedaily.com/releases/2015/12/151203112844.htm

Lack of sleep tampers with your emotions Study pinpoints neural mechanism responsible for impaired neutrality due to sleep loss

December 8, 2015
Science Daily/American Friends of Tel Aviv University
The neurological changes sleep deprivation can impose on our ability to regulate emotions have been revealed by new research. The work also shows that we have the ability to allocate brain resources for cognitive processing.

A new Tel Aviv University study has identified the neurological mechanism responsible for disturbed emotion regulation and increased anxiety due to only one night's lack of sleep. The research reveals the changes sleep deprivation can impose on our ability to regulate emotions and allocate brain resources for cognitive processing.

The research was led by Prof. Talma Hendler of TAU's Sagol School of Neuroscience, Sackler Faculty of Medicine, and School of Psychological Sciences, and conducted by TAU graduate student Eti Ben-Simon at the Center for Brain Functions at Tel Aviv Sourasky Medical Center. It was published recently in the Journal of Neuroscience.

Nothing is neutral any more?

"Prior to our study, it was not clear what was responsible for the emotional impairments triggered by sleep loss," said Prof. Hendler. "We assumed that sleep loss would intensify the processing of emotional images and thus impede brain capacity for executive functions. We were actually surprised to find that it significantly impacts the processing of both neutral and emotionally-charged images.

"It turns out we lose our neutrality. The ability of the brain to tell what's important is compromised. It's as if suddenly everything is important," she said.

For the purpose of the study, Ben-Simon kept 18 adults awake all night to take two rounds of tests while undergoing brain mapping (fMRI and/or EEG), first following a good night's sleep and the second following a night of lack of sleep in the lab. One of the tests required participants to describe in which direction small yellow dots moved over distracting images. These images were "positively emotional" (a cat), "negatively emotional" (a mutilated body), or "neutral" (a spoon).

When participants had a good night's rest, they identified the direction of the dots hovering over the neutral images faster and more accurately, and their EEG pointed to differing neurological responses to neutral and emotional distractors. When sleep-deprived, however, participants performed badly in the cases of both the neutral and the emotional images, and their electrical brain responses, as measured by EEG, did not reflect a highly different response to the emotional images. This pointed to decreased regulatory processing.

"It could be that sleep deprivation universally impairs judgment, but it is more likely that a lack of sleep causes neutral images to provoke an emotional response," said Ben-Simon.

Losing a sense of proportion

The researchers conducted a second experiment testing concentration levels. Participants were shown neutral and emotional images while performing a task demanding their attention while ignoring distracting background pictures with emotional or neutral content -- the depression of a key or button at certain moments -- while inside an fMRI scanner. This time researchers measured activity levels in different parts of the brain as they completed the cognitive task.

The team found that participants after only one night of lack of sleep were distracted by every single image (neutral and emotional), while well-rested participants were only distracted by emotional images. The effect was indicated by activity change in the amygdala, a major limbic node responsible for emotional processing in the brain.

"We revealed a change in the emotional specificity of the amygdala, a region of the brain associated with detection and valuation of salient cues in our environment, in the course of a cognitive task." said Prof. Hendler.

"These results reveal that, without sleep, the mere recognition of what is an emotional and what is a neutral event is disrupted. We may experience similar emotional provocations from all incoming events, even neutral ones, and lose our ability to sort out more or less important information. This can lead to biased cognitive processing and poor judgment as well as anxiety," said Prof. Hendler.

The new findings emphasize the vital role sleep plays in maintaining good emotional balance in our life for promoting mental health. The researchers are currently examining how novel methods for sleep intervention (mostly focusing on REM sleep) may help reduce the emotional dysregulation seen in anxiety, depression, and traumatic stress disorders.
http://www.sciencedaily.com/releases/2015/12/151208133618.htm

Link between stress, unhealthy microbiomes discovered

January 6, 2016
Science Daily/University of Guelph
Red squirrels living in a low-stress environment harbor healthier communities of micro-organisms, a result that might hold implications for human health, according to a new study.
https://images.sciencedaily.com/2016/01/160106091735_1_540x360.jpg
Red squirrel in Algonquin Park, Ontario, Canada.
Credit: Colleen Bobbie - University of Guelph

Researchers tested squirrel microbiomes and analyzed the animals' stress hormones. Their study appears in the journal Biology Letters.

Microbiomes are communities of micro-organisms living in and on the bodies of all living things, including people. Found in the mouth and gut and on the skin, microbiomes consist of a mix of beneficial and potentially harmful bacteria that changes constantly and can affect their host's health.

"A diverse microbiome is generally a good thing for your health - it's why people take probiotics," said lead researcher Mason Stothart, a former undergraduate student in the Department of Integrative Biology.

"We wanted to understand the relationship between the microbiome and stress. The greater the stress in the squirrels, the less bacterial diversity they had, which can be an indicator of poor health."

Stothart and a Laurentian University graduate student trapped squirrels in Algonquin Park in Ontario. They took mouth swabs and fecal samples, which were then analyzed in a lab.

The researchers found that microbiomes were more diverse in squirrels with lower stress hormones.

"As a second part of the experiment, we captured the same squirrels two weeks later, and found that if stress levels increased, some bacteria that are potentially harmful also increased," said Stothart.

This study is the first of its kind to be conducted in a natural environment, said Prof. Amy Newman, senior author of the study and Stothart's supervisor.

"This is the first demonstration that there is a link between stress and microbiome diversity in the wild," Newman said.

"Conducting this study in a natural environment provides a more realistic look at the microbiome and its potential link to stress and health."

The researchers now plan to vary the microbiome to see whether it's impacted by stress, or the other way around, said Newman.

"Bacterial diversity within animals and people is emerging as an essential component of health, and this study provides data that shows the link between low stress and a healthy microbiome."
http://www.sciencedaily.com/releases/2016/01/160106091735.htm

The way you sound affects your mood

January 11, 2016
Science Daily/Lund University
Researchers have created a digital audio platform that can modify the emotional tone of people's voices while they are talking, to make them sound happier, sadder or more fearful. New results show that while listening to their altered voices, participants' emotional state change in accordance with the new emotion.
https://images.sciencedaily.com/2016/01/160111162659_1_540x360.jpg
Graphic depicting audio effects on human emotions.
Credit: Graph by science team

"Very little is known about the mechanisms behind the production of vocal emotion," says lead author Jean-Julien Aucouturier from the French National Centre for Scientific Research (CNRS), France.

"Previous research has suggested that people try to manage and control their emotions, for example hold back an expression or reappraise feelings. We wanted to investigate what kind of awareness people have of their own emotional expressions."

In an initial study using a novel digital audio platform, published in Proceedings of the National Academy of Sciences (PNAS), participants read a short story aloud while hearing their own altered voice, sounding happier, sadder or more fearful, through a headset.

The study found that the participants were unaware that their voices were being manipulated, while their emotional state changed in accordance with the manipulated emotion portrayed. This indicates that people do not always control their own voice to meet a specific goal and that people listen to their own voice to learn how they are feeling.

"The relationship between the expression and experience of emotions has been a long-standing topic of disagreement in the field of psychology," says Petter Johansson, one of the authors from Lund University, Sweden. "This is the first evidence of direct feedback effects on emotional experience in the auditory domain."

The emotional manipulations were created by digital audio processing algorithms that simulate acoustic components of emotional vocalisations. For example, the happy manipulation modifies the pitch of a speaker's voice using pitch shifting and inflection to make it sound more positive, modifies its dynamic range using compression to make it sound more confident, and modifies its spectral content using high pass filtering to make it sound more excited.

The researchers believe this novel audio platform opens up many new areas of experimentation.

"Previously, this kind of emotion manipulation has not been done on running speech, only on recorded segments," explains Jean-Julien Aucouturier. "We are making a version of the voice manipulation platform available as open-source on our website, and we invite anyone to download and experiment with the tools."

For applications outside academia, co-author Katsumi Watanabe from Waseda University and the University of Tokyo in Japan considers that the platform could be used for therapeutic purposes, for example for mood disorders by inducing positive attitude change from retelling affective memories or by redescribing emotionally laden events in a modified tone of voice. It might also be possible to enhance the emotional impact of Karaoke or live singing performances, or maybe to alter the emotional atmosphere of conversations in online meetings and gaming.

The study was conducted by researchers at the Science and Technology of Music and Sound Lab (STMS), (IRCAM/CNRS/UPMC) and the LEAD Lab (CNRS/University of Burgundy) in France, Lund University in Sweden, and Waseda University and the University of Tokyo in Japan.
http://www.sciencedaily.com/releases/2016/01/160111162659.htm

New study challenges 'mid-life crisis' theory

January 11, 2016
Science Daily/University of Alberta
A 25-year longitudinal study suggests the curve in happiness from early adulthood to midlife goes up, not down.

For half a century, the accepted research on happiness has shown our lives on a U-shaped curve, punctuated by a low point that we've come to know as the "mid-life crisis." A number of studies have claimed over the years that happiness declines for most from the early 20s to middle age (40 to 60). Today, the "mid-life crisis" is a generally accepted phenomenon, fodder for sitcoms and the subject of advertising propaganda the world over -- but does it actually exist?

The answer is no, according to "Up, Not Down: The Age Curve in Happiness from Early Adulthood to Midlife In Two Longitudinal Studies" -- a paper recently published in Developmental Psychology -- based on data drawn from two longitudinal studies by University of Alberta researchers Nancy Galambos, Harvey Krahn, Matt Johnson and their team.

Contrary to previous cross-sectional studies of life-span happiness, this new longitudinal data suggests happiness does not stall in midlife, but instead is part of an upward trajectory beginning in our teens and early twenties. And, according to Galambos and Krahn -- award-winning Faculty of Arts researchers -- this study is far more reliable than the research that came before it.

"I'm not trashing cross-sectional research, but if you want to see how people change as they get older, you have to measure the same individuals over time," sociologist Krahn said.

The team followed two cohorts -- one of Canadian high school seniors from ages 18 -- 43 and the other a group of university seniors from ages 23-37. Both showed happiness increased into the 30s, with a slight downturn by age 43 in the high school sample. After accounting for variations in participants' lives, such as changes in marital status and employment, both samples still demonstrated a general rise in happiness after high school and university.

Psychology professor Nancy Galambos -- first author on the study -- says it's crucial information, because happiness is important. It's associated with life span and overall well-being.

"We want people to be happier so that they have an easier life trajectory," she said. "And also they cost less to the health system, and society."

Background

"Up, Not Down: The Age Curve in Happiness from Early Adulthood to Midlife In Two Longitudinal Studies" by Nancy Galambos (Psychology), Shichen Fang (doctoral student/Psychology), Harvey Krahn (Sociology), Matthew Johnson (Human Ecology) and Margie Lachman (Brandeis University) was initially published online in Developmental Psychology on September 7, 2015. Researchers attribute the difference in results from other studies of life span happiness to longitudinal data, and find past efforts to report on the trajectory of life span happiness to be fundamentally flawed.

Additional Factoids

•    People are happier in their early 40s (midlife) than they were at age 18
•    Happiness rises fastest between age 18 and well into the 30s
•    Happiness is higher in years when people are married and in better physical health, and lower in years when people are unemployed
•    The rise in happiness between the teens and early 40s is not consistent with a midlife crisis
•    The rise in happiness to midlife refutes the purported "u-bend" in happiness, which assumes that happiness declines between the teens and the 40s
http://www.sciencedaily.com/releases/2016/01/160111162712.htm

People who experience rage attacks have smaller 'emotional brains'

January 12, 2016
Science Daily/Elsevier
Neuroimaging studies suggest that frontolimbic regions of the brain, structures that regulate emotions, play an important role in the biology of aggressive behavior. A new article reports that individuals with intermittent explosive disorder (IED) have significantly lower gray matter volume in these frontolimbic brain structures. In other words, these people have smaller "emotional brains."
https://images.sciencedaily.com/2016/01/160112091812_1_540x360.jpg
Individuals with intermittent explosive disorder (IED) have significantly lower gray matter volume in certain frontolimbic brain structures. In other words, these people have smaller "emotional brains."
Credit: © Minerva Studio / Fotolia

A new article published in the inaugural issue of the journal Biological Psychiatry: Cognitive Neuroscience and Neuroimaging reports that individuals with intermittent explosive disorder (IED) have significantly lower gray matter volume in these frontolimbic brain structures. In other words, these people have smaller "emotional brains."

"Intermittent explosive disorder is defined in DSM-5 as recurrent, problematic, impulsive aggression," explained Dr. Emil Coccaro, the article's lead author. "While more common than bipolar disorder and schizophrenia combined, many in the scientific and lay communities believe that impulsive aggression is simply 'bad behavior' that requires an 'attitude adjustment.' However, our data confirm that IED, as defined by DSM-5, is a brain disorder and not simply a disorder of 'personality.'" Dr. Coccaro is the E.C. Manning Professor and Chair of Psychiatry and Behavioral Neuroscience at the University of Chicago.

Dr. Coccaro and his colleagues also report a significant inverse correlation between measures of aggression and frontolimbic gray matter volume.

The investigators collected high-resolution magnetic resonance imaging (MRI) scans in 168 subjects, including 57 subjects with IED, 53 healthy control subjects, and 58 psychiatric control subjects. The team found a direct correlation between history of actual aggressive behavior and the magnitude of reduction in gray matter volume, linking both in a dimensional relationship.

"Across all subjects, reduced volume in frontolimbic brain structures was associated with increased aggressiveness," commented Dr. Cameron Carter, Professor of Psychiatry and Behavioral Sciences at University of California, Davis and Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. "These important findings suggest that disrupted development of the brain's emotion-regulating circuitry may underlie an individual's propensity for rage and aggression."
http://www.sciencedaily.com/releases/2016/01/160112091812.htm

Weekend catch-up sleep can reduce diabetes risk associated with sleep loss

January 18, 2016
Science Daily/University of Chicago Medical Center
Two consecutive nights of extended sleep, a typical weekend occurrence, appears to counteract the increased risk of diabetes associated with short-term sleep restriction during the work week, at least in lean, healthy, young men eating a controlled diet.
https://images.sciencedaily.com/2016/01/160118184342_1_540x360.jpg
A sleep study in process is shown.
Credit: The University of Chicago Medicine

The finding, based on a study performed at the University of Chicago sleep laboratory published early online by the journal Diabetes Care, could affect large numbers of people who work long hours.

The pattern of cutting back on sleep during the work week followed by catching up on sleep over the weekend is common. Even short-term sleep restriction, with four or five hours of sleep per night, can increase the risk of developing diabetes by about 16 percent--comparable to the increase in risk caused by obesity.

"In this short-term study, we found that two long nights spent catching up on lost sleep can reverse the negative metabolic effects of four consecutive nights of restricted sleep," said study author Josiane Broussard, PhD, now an assistant research professor in the Department of Integrative Physiology at the University of Colorado, Boulder.

The researchers recruited 19 volunteers, all healthy young men. On one occasion, they were allowed to sleep normally, spending 8.5 hours in bed for four nights. On another occasion, the same volunteers were first sleep deprived, allowed only 4.5 hours in bed for four consecutive nights. They spent an average of 4.3 of those hours asleep each night. Subsequently, they were allowed 2 nights of extended sleep, during which they averaged 9.7 hours of sleep.

Investigators then determined the subjects' insulin sensitivity--the ability of insulin to regulate blood sugars--and the disposition index, a predictor of diabetes risk. After four nights of sleep restriction, the volunteers' insulin sensitivity decreased by 23 percent and their diabetes risk increased by 16 percent.

After two nights of extended sleep, however, insulin sensitivity and the risk of diabetes returned to normal sleep levels.

"The metabolic response to this extra sleep was very interesting and encouraging," said senior author Esra Tasali, MD, associate professor of medicine at the University of Chicago. "It shows that young, healthy people who sporadically fail to get sufficient sleep during the work week can reduce their diabetes risk if they catch up on sleep during the weekend."

"Though this is evidence that weekend catch-up sleep may help someone recover from a sleep-deprived week," Broussard said, "this was not a long-term study and our subjects went through this process only once. Going forward we intend to study the effects of extended weekend sleep schedules in people who repeatedly curtail their weekday sleep."

Increased risk of developing diabetes is not the only drawback associated with inadequate sleep, the authors point out. The volunteers in this study were given a calorie-controlled diet, but sleep-deprived adults outside the laboratory setting tend to eat more, with a strong preference for sweets and high-fat foods. Chronically sleep deprived people are more likely to develop other health problems such as increased inflammation and high blood pressure. They also show cognitive problems, tend to be less alert and have difficulty concentrating, reasoning and solving problems. They are prone to traffic accidents. The impact of extra weekend sleep on other adverse health and safety outcomes remains to be determined.
http://www.sciencedaily.com/releases/2016/01/160118184342.htm

Chronic stress, anxiety can damage the brain, increase risk of major psychiatric disorders

January 21, 2016
Science Daily/Baycrest Centre for Geriatric Care
People need to find ways to reduce chronic stress and anxiety in their lives or they may be at increased risk for developing depression and even dementia, a new scientific review paper warns.

Led by the Rotman Research Institute at Baycrest Health Sciences, the review examined brain areas impacted by chronic anxiety, fear and stress in animal and human studies that are already published. The authors concluded that there is "extensive overlap" of the brain's neurocircuitry in all three conditions, which may explain the link between chronic stress and the development of neuropsychiatric disorders, including depression and Alzheimer's disease.

The paper is posted online this month in the journal Current Opinion in Psychiatry.

Experiencing anxiety, fear and stress is considered a normal part of life when it is occasional and temporary, such as feeling anxious and stressed before an exam or a job interview. However, when those acute emotional reactions become more frequent or chronic, they can significantly interfere with daily living activities such as work, school and relationships. Chronic stress is a pathological state that is caused by prolonged activation of the normal acute physiological stress response, which can wreak havoc on immune, metabolic and cardiovascular systems, and lead to atrophy of the brain's hippocampus (crucial for long-term memory and spatial navigation).

"Pathological anxiety and chronic stress are associated with structural degeneration and impaired functioning of the hippocampus and the prefrontal cortex (PFC), which may account for the increased risk of developing neuropsychiatric disorders, including depression and dementia," said Dr. Linda Mah, clinician scientist with Baycrest's Rotman Research Institute and lead author of the review.

The review paper examined recent evidence from studies of stress and fear conditioning in animal models, and neuroimaging studies of stress and anxiety in healthy individuals and in clinical populations.

Dr. Mah and colleagues looked specifically at key structures in the neurocircuitry of fear and anxiety (amygdala, medial prefrontal cortex, hippocampus) which are impacted during exposure to chronic stress. The researchers noted similar patterns of abnormal brain activity with fear/anxiety and chronic stress -- specifically an overactive amygdala (associated with emotional responses) and an under-active PFC (thinking areas of the brain that help regulate emotional responses through cognitive appraisal). This see-saw relationship was first identified in a landmark study by world-renowned neurologist and depression researcher Dr. Helen Mayberg over a decade ago.

Dr. Mah, an assistant professor of Psychiatry in the Department of Geriatric Psychiatry at the University of Toronto, concluded her review on a hopeful note by suggesting that stress-induced damage to the hippocampus and PFC is "not completely irreversible." Anti-depressant treatment and physical activity have both been found to increase hippocampal neurogenesis, she said.

"Looking to the future, we need to do more work to determine whether interventions, such as exercise, mindfulness training and cognitive behavioural therapy, can not only reduce stress but decrease the risk of developing neuropsychiatric disorders," said Dr. Mah

The scientific review paper follows on the heels of a major study Dr. Mah published in the American Journal of Geriatric Psychiatry (first posted online in October 2014), which found some of the strongest evidence yet that anxiety may accelerate conversion to Alzheimer's disease in people diagnosed with mild cognitive impairment.

Dr. Alexandra Fiocco, a psychologist with the Institute for Stress and Wellbeing Research, Ryerson University, contributed to the review paper in Current Opinion in Psychiatry. The work was supported in part by the Ministry of Health and Long-Term Care AFP Innovation Fund.
http://www.sciencedaily.com/releases/2016/01/160121121818.htm

Stress inhibits spatial perception

January 27, 2016
Science Daily/Ruhr-Universitaet-Bochum
Neuroscientists have investigated the effects of stress on the perception of scenes and faces. In a behavioral study, they compared the results of stressed participants with those of an unstressed control group. They were able to show that stress inhibits the perception of complex spatial information. The reason for this lies in the processing of this information in the hippocampus, an area in the temporal lobe of the brain, which is influenced by the stress hormone cortisol.

Research builds on previous studies

Previous studies within Collaborative Research Centre 874 have shown that the release of the stress hormone cortisol influences long-term memory in the hippocampus. Other research revealed that the hippocampus is not only responsible for memory, but that it is also involved in the perception of scenes. Faces are processed in adjacent regions of the temporal lobe. In their study the research teams of Prof. Dr. Oliver T. Wolf (Cognitive Psychology) and Prof. Dr. Boris Suchan (Clinical Neuropsychology) combined these two strains of research and investigated how stress effects the perception of scenes and faces.

Behavioural study induces stress

In a behavioural study with young men the scientists investigated how the perception of scenes and faces under stress differs to non-stressful perception. To induce stress and the release of the corresponding hormone cortisol, the scientists administered the socially evaluated cold-pressor test, a method well-established in stress research. During this procedure the participant is asked to immerse their hand in ice water for up to three minutes, while being filmed and instructed by a female researcher.

Impaired perception of scenes under stress

The evaluation of the following visual tasks showed that the stressed participants did less well in the discrimination of complex scenes than the non-stressed control group. For the perception of faces there was no significant difference between the groups. "Our results confirm the notion that whereas scenes are processed in the hippocampus, faces are processed in adjacent areas of the temporal lobe," explains PhD student Marcus Paul. "Stress has a deciding influence on the hippocampus. It not only affects memory, but also spatial perception." To confirm these findings, further research using magnetic resonance imaging must now be conducted to investigate activity patterns in the hippocampus during stress.
http://www.sciencedaily.com/releases/2016/01/160127101616.htm

Stress could help activate brown fat

February 8, 2016
Science Daily/The Physiological Society
Mild stress stimulates the activity and heat production by brown fat associated with raised cortisol, according to a study. Brown adipose tissue (BAT), also known as brown fat, is one of two types of fat found in humans and other mammals. Initially only attributed to babies and hibernating mammals, it was discovered in recent years that adults can have brown fat too. Its main function is to generate body heat by burning calories (opposed to white fat, which is a result of storing excess calories. People with a lower body mass index (BMI) therefore have a higher amount of brown fat.

To induce a mild psychological stress, five healthy lean women had to solve a short maths test in the first run, but in the second run, the test was substituted with a relaxation video. To assess stress responses, the scientists measured cortisol in the saliva. To measure the activity of brown fat, the researchers used infrared thermography to detect changes in temperature of the skin overlying the main area of brown fat in humans (in the neck (supraclavicular) region).

Although the actual maths tests did not elicit an acute stress response, the anticipation of being tested did, and led to raised cortisol and warmer brown fat. Both were positively correlated, with higher cortisol linked with more fat activity and thus more potential heat production.

Prof Michael E Symonds from The School of Medicine, University of Nottingham and Co-author of the study comments,

'Our research indicates that the variation in brown fat activity between individuals may be explained by differences in their response to psychological stress. This is important as brown fat has a unique capacity to rapidly generate heat and metabolise glucose.

'Most adults only have between 50-100 g of brown fat but because its capacity to generate heat is 300 times greater (per unit mass) than any other tissue, brown fat has the potential to rapidly metabolise glucose and lipids. There is an inverse relationship between the amount of brown fat and BMI, and whether this is a direct consequence of having more active fat remains to be fully established.

'A better understanding of the main factors controlling brown fat activity, which include diet and activity, therefore has the potential to introduce sustainable interventions designed to prevent obesity and diabetes. In future, new techniques to induce mild stress to promote brown fat activity could be incorporated alongside dietary and/or environmental interventions. This is likely to contrast with the negative effects of chronic and more severe stress that can contribute to poor metabolic health.'
http://www.sciencedaily.com/releases/2016/02/160208213648.htm

Experiencing financial stress may lead to physical pain

February 22, 2016
Science Daily/Association for Psychological Science
People who feel that their financial outlook is shaky may actually experience more physical pain than those who feel financially secure, according to new research. The findings indicate that the link may be driven, at least in part, by feeling a lack of control over one's life.

"Overall, our findings reveal that it physically hurts to be economically insecure," explains researcher and lead study author Eileen Chou of the University of Virginia. "Results from six studies establish that economic insecurity produces physical pain, reduces pain tolerance, and predicts over-the-counter painkiller consumption."

The research, led by Chou and colleagues Bidhan Parmar (University of Virginia) and Adam Galinsky (Columbia University), stemmed from an observation of two co-occurring trends: increasing economic insecurity and increasing complaints of physical pain.

The researchers hypothesized that these trends might actually be linked. They surmised that feelings of economic insecurity would lead people to feel a lack of control in their lives, which would, in turn, activate psychological processes associated with anxiety, fear, and stress. These psychological processes have been shown to share similar neural mechanisms to those underlying pain.

Initial findings provided support for the hypothesized link. Data from a diverse consumer panel of 33,720 individuals revealed that households in which both adults were unemployed spent 20% more on over-the-counter painkillers in 2008 compared with households in which at least one adult was working. And an online study with 187 participants indicated that two measures of economic insecurity -- participants' own unemployment and state-level insecurity -- were correlated with participants' reports of pain, as measured by a four-item pain scale.

In another online study, participants who recalled a period of economic instability reported almost double the amount of physical pain than did participants who recalled an economically stable period. This pattern of findings remained even after the researchers took other factors -- including age, employment status, and negative emotion -- into account.

Evidence from a lab-based study suggested that economic insecurity might be also linked with tolerance for pain. Student participants who were prompted to think about an uncertain job market showed a decrease in pain tolerance, measured by how long they could comfortably keep their hand in a bucket of ice water; students who were prompted to think about entering a stable job market showed no change in pain tolerance.

And the researchers found that the degree to which participants felt in control of their lives helped to account for the association between feelings of economic insecurity and reports of physical pain.

Together, the results highlight the importance of distinguishing between subjective and objective experience:

"Individuals' subjective interpretation of their own economic security has crucial consequences above and beyond those of objective economic status," Chou and colleagues write.

By elucidating the relationship between social phenomena, psychological processes, and physical experiences, these studies provide important insights to researchers and policymakers alike, the researchers argue:

"By showing that physical pain has roots in economic insecurity and feelings of lack of control, the current findings offer hope for short-circuiting the downward spiral initiated by economic insecurity and producing a new, positive cycle of well-being and pain-free experience," they conclude.
https://www.sciencedaily.com/releases/2016/02/160222090652.htm

Let it go: Reaction to stress more important than its frequency

February 25, 2016
Science Daily/Penn State
How you perceive and react to stressful events is more important to your health than how frequently you encounter stress, according to health researchers.

It is known that stress and negative emotions can increase the risk of heart disease, but the reasons why are not well understood. One potential pathway linking stress to future heart disease is a dysregulation of the autonomic nervous system -- a case of a person's normally self-regulated nervous system getting off track.

Nancy L. Sin and colleagues wanted to find out if daily stress and heart rate variability -- a measure of autonomic regulation of the heart -- are linked. Heart rate variability is the variation in intervals between consecutive heartbeats.

"Higher heart rate variability is better for health as it reflects the capacity to respond to challenges," said Sin, postdoctoral fellow in the Center for Healthy Aging and in the department of biobehavioral health at Penn State. "People with lower heart rate variability have a greater risk of cardiovascular disease and premature death."

Depression and major stressful events are known to be harmful for health, but less attention has been paid to the health consequences of frustrations and hassles in everyday life. Prior to this research, very few studies have looked at the relationship between heart rate variability and daily stressful events.

Sin and colleagues analyzed data collected from 909 participants, including daily telephone interviews over eight consecutive days and the results from an electrocardiogram. They report their findings online in Psychosomatic Medicine. The participants were between the ages of 35 and 85 and were drawn from a national study.

During the daily phone interviews, participants were asked to report the stressful events they had experienced that day, rating how stressful each event was by choosing "not at all," "not very," "somewhat" or "very." They were also asked about their negative emotions that day, such as feeling angry, sad and nervous. On average, participants reported having at least one stressful experience on 42 percent of the interview days, and these experiences were generally rated as "somewhat" stressful.

The researchers found that participants who reported a lot of stressful events in their lives were not necessarily those who had lower heart rate variability. No matter how many or how few stressful events a person faces it was those who perceived the events as more stressful or who experienced a greater spike in negative emotions that had lower heart rate variability -- meaning these people may be at a higher risk for heart disease.

"These results tell us that a person's perceptions and emotional reactions to stressful events are more important than exposure to stress per se," said Sin. "This adds to the evidence that minor hassles might pile up to influence health. We hope these findings will help inform the development of interventions to improve well-being in daily life and to promote better health."

David M. Almeida, professor of human development and family studies, Penn State; Richard P. Sloan, professor, and Paula S. McKinley, assistant professor, both of behavioral medicine in psychiatry, Columbia University Medical Center also worked on this project. The National Institute on Aging supported this work.
https://www.sciencedaily.com/releases/2016/02/160225140246.htm

Quick thinking and feeling healthy predict longer life

February 29, 2016
Science Daily/Association for Psychological Science
Suffering from chronic medical conditions and engaging in unhealthy behaviors are known risk factors for early death, but findings from a longitudinal study of over 6,000 adults suggests that certain psychological factors may be even stronger predictors of how long we'll live.

The findings are published in Psychological Science, a journal of the Association for Psychological Science.

"Our study shows that two psychological variables, lower self-rated health and age-related decrements in processing speed, appear to be especially important indicators of elevated mortality risk in middle-age and older adults," says psychological scientist Stephen Aichele of the University of Geneva in Switzerland. "This information may facilitate diagnostic accuracy and timely interventions."

Aichele and colleagues Patrick Rabbitt (University of Oxford, UK) and Paolo Ghisletta (University of Geneva, Switzerland) were interested in investigating the relative influence of cognitive, demographic, health, and lifestyle variables in predicting mortality risk. While previous research had provided some clues as to the roles played by these variables, comprehensive longitudinal studies were few and far between.

"It has been long known that particular factors such as illnesses, socio-economic disadvantage, cognitive decline, and social support determine how long we survive in old age," explains Aichele. "The problem has been that these and other markers for mortality have been tested separately, rather than together. Given that they are strongly associated with each other, it makes it difficult to determine which variables most influence mortality risk."

To address this gap in the available research, Aichele and colleagues turned to the Manchester Longitudinal Study of Cognition, examining 29 years' worth of data collected from 6,203 adults who ranged in age from 41 to 96 years old when they began the study.

Aggregating data from 15 different tasks, the researchers looked at participants' cognitive performance across five domains of ability: crystallized intelligence, fluid intelligence, verbal memory, visual memory, and processing speed. The tasks--all well-established measures of cognitive ability--were administered up to four times over a 12-year period, allowing the researchers to assess participants' baseline performance and change in performance over time for each domain.

To gauge participants' health, the researchers used the Cornell Medical Index, a measure that includes detailed checklists of a total of 195 pathological symptoms related to physical and psychological disorders.

Finally, the researchers looked at participants' subjective reports of various lifestyle factors, including perceived health, number of prescribed medicines, sleep patterns, hobbies, leisure activities, and social interactions.

Using two types of statistical analysis, the researchers were able to assess the relative importance of a total of 65 different variables in predicting participants' mortality risk.

The results revealed subjective health and mental processing speed to be two of the strongest predictors -- that is, better perceived health and smaller decreases in processing speed over time were associated with reduced mortality risk.

Being a woman was also associated with reduced mortality risk, while years of smoking tobacco was linked with an increased risk of early death.

The influence of the two psychological factors relative to known medical risk factors, such as cardiovascular symptoms, came as a surprise:

"The result that psychological variables are so strongly linked to mortality risk is very surprising because much extant evidence supports the hypothesis that the strongest predictors of survival in old age are of medical or physiological nature," explains Aichele.

These findings may provide useful insights to health professionals, who need better methods for identifying individuals at risk of early death.

"Addressing the needs of an aging global population will require accounting for numerous morbidity and mortality risk factors, such as demographic variables, health conditions, functional capacities, mental abilities, and social support," the researchers conclude.
https://www.sciencedaily.com/releases/2016/02/160229081913.htm

How much sleep do you really need, and what happens when you don’t get enough?

March 1, 2016
Science Daily/Valley Health System
Every March, we are all faced with the arrival of Daylight Saving Time and its impact on our circadian rhythms, our sleep-wake pattern. The 1-hour shift in time can even temporarily disrupt our ability to fall asleep at night and to wake up in the morning. We not only lose an hour of sleep, but the time change disrupts the body’s biological clock and circadian rhythm. The effect is the same as jetlag in plane travel, in which our bodies remain on the prior schedule for a period of time.

"People who sleep well can usually adjust to the time shift with little difficulty," says Jeffrey P. Barasch, M.D., Medical Director of The Valley Hospital Center for Sleep Medicine in Ridgewood, NJ. However, if someone has been coping with chronic difficulty sleeping, daylight saving time can worsen or uncover an undiagnosed and untreated sleep disorder, such as insomnia or sleep apnea.

It is important to keep in mind that the required amount of sleep per day changes with age, and studies indicate the following recommended sleep durations:

• Newborns -- 16 to 18 hours a day

• Preschool-aged children -- 11 to 12 hours a day

• School-aged children -- at least 10 hours a day

• Teens -- 9 to 10 hours a day

• Adults (age 20-64) -- 7 to 9 hours a day

• Elderly (age 65 and over) -- 7 to 8 hours a day

"Unfortunately, as you well know, sometimes life can prevent us from going to bed when we want to and many of us have experienced the frustration of not being able to fall asleep or stay asleep once we are in bed," Dr. Barasch says. "Luckily, our bodies can adjust to occasional instances when we do not get enough sleep."

But what happens when we are consistently not getting enough sleep? According to Dr. Barasch, sleep deprivation can impact the brain and every organ in the body. During sleep, a newly discovered network of water channels in the brain, called the glymphatic system, becomes active and functions as a waste disposal system, carrying toxins away which would otherwise accumulate and damage brain cells. The accumulation of one of those toxins, amyloid-beta, is associated with Alzheimer's disease.

Dr. Barasch warns that those who suffer from chronic sleep deprivation, regardless of the reason, can experience adverse effects in many aspects of their lives. The lack of crucial restorative sleep can lead to daytime sleepiness, irritability, difficulty focusing, deterioration in work or school productivity, and impaired creativity and decision making. Sleep deprivation also affects performance and reaction time. Losing two hours of sleep is similar to the effect of alcohol intoxication. Sleep deprivation is also involved in many automobile, truck and airplane crashes. Lack of sleep also promotes weight gain and may lead to long term health consequences, such as depression, diabetes, hypertension, gastrointestinal disorders and colon cancer.

So what do you do if your struggle with sleep isn't limited to a change in the clocks? If you are having difficulty sleeping, the National Institute of Health suggests incorporating some of the following strategies into your nighttime routine: • Go to bed and wake up at the same time every day. • Try to keep the same sleep schedule on weeknights and weekends. • Use the hour before bed for quiet time. • Avoid heavy and/or large meals within a couple hours of bedtime. • Avoid alcoholic drinks, nicotine and caffeine before bed. • Spend time outside every day (when possible) and be physically active. • Keep your bedroom quiet, cool, and dark (a dim night light is fine, if needed). • Take a hot bath or use relaxation techniques before bed.

If you regularly experience daytime drowsiness, fatigue or disturbed sleep, consider consulting with a sleep medicine specialist to evaluate and treat the problem.
https://www.sciencedaily.com/releases/2016/03/160301175006.htm

Can’t sleep? Street lights may be keeping you awake

March 1, 2016
Science Daily/American Academy of Neurology (AAN)
If your neighborhood is well-lit at night, you may not be sleeping well, according to a new study.

"Our world has become a 24/7 society. We use outdoor lighting, such a street lights, to be more active at night and to increase our safety and security," said study author Maurice Ohayon, MD, DSC, PhD, of Stanford University in Stanford, Calif. "The concern is that we have reduced our exposure to darkness and it could be affecting our sleep."

For the study, 15,863 people were interviewed by phone over an eight-year period. They were asked about sleep habits, quality of sleep as well as medical and psychiatric disorders. Then, with nighttime data from the Defense Meteorological Satellite Program, the researchers looked at how much outdoor light those people were exposed to at night. People living in urban areas of 500,000 people or more were exposed to nighttime lights that were three to six times more intense than people living in small towns and rural areas.

The study shows that nighttime light affects sleep duration and was significantly associated with sleep disturbances. People living in more intense light areas were six percent more likely to sleep less than six hours per night than people in less intense light areas. People living in more intense light areas were more likely to be dissatisfied with their sleep quantity or quality than people in less intense light areas, with 29 percent dissatisfied compared to 16 percent.

People with high light exposure were also more likely to report fatigue than those with low light exposure, with 9 percent compared to 7 percent. People with high light exposure also slept less per night than those with low light exposure, with an average of 412 minutes per night compared to 402 minutes per night.

In addition, people with high light exposure were more likely to wake up confused during the night than people with low light exposure, with 19 percent experiencing this compared to 13 percent. They were also more likely to have excessive sleepiness and impaired functioning, at 6 percent compared to 2 percent.

"Light pollution can be found in any sizable city in the world. Yet, excessive exposure to light at night may affect how we function during the day and increase the risks of excessive sleepiness," said Ohayon. "If this association is confirmed by other studies, people may want to consider room darkening shades, sleep masks or other options to reduce their exposure."
https://www.sciencedaily.com/releases/2016/03/160301175008.htm

Shedding light on the day-night cycle Scanning fruit fly brains helps understanding of neural signaling involved in some circadian behaviors

March 2, 2016
Science Daily/Washington University School of Medicine
New research sheds light on how the rhythms of daily life are encoded in the brain. Scientists have discovered that different groups of neurons, those charged with keeping time, become active at different times of day despite being on the same molecular clock.
https://images.sciencedaily.com/2016/03/160302132538_1_540x360.jpg
Living fruit flies' brains were scanned every 10 minutes for 24 hours to help understand the master circadian clock in the brain and how it helps coordinate body rhythms.
Credit: Taghert lab/Washington University

The findings are published Feb. 26 in Science.

Life on Earth follows the rising and setting of the sun. Daily cycles have been found in animals, plants, fungi and even bacteria. For humans, sleeping and waking as well as hormone levels, body temperature and cognitive performance, follow a daily cycle.

"The influence of our circadian rhythms can be substantial -- for example, some of us are night owls and others are morning larks," said senior investigator Paul Taghert, PhD, professor of neuroscience. "It's important to understand how such fundamental timing information is translated into actual neuronal signals in the brain that control daily rhythms, including rhythmic behavior."

The biological control for these daily cycles is known as the circadian clock. In animals, a master circadian clock in the brain helps coordinate most of these body rhythms, including the sleep-wake cycle.

The biochemical basis of the circadian clock has been conserved through evolution. It involves a small number of "clock proteins" whose levels go up and down in a controlled manner once a day.

But scientists long have puzzled over how some circadian-controlled behaviors and physiological changes that occur two or more times a day correspond to the once-daily rise and fall of clock proteins. The fruit fly Drosophila, for example, is behaviorally active twice a day, in the morning and evening.

Taghert, along with graduate student Xitong Liang and Timothy Holy, associate professor of neuroscience, asked how one biochemical peak in clock proteins could lead to two distinct peaks of activity at different times of day. They wondered whether the neuronal time-keeping circuit produces a single daily signal or generates multiple signals throughout the day.

To answer that question, Liang performed whole brain scans of living fruit flies every 10 minutes for 24 hours. Fruit flies are widely used in circadian research because the clock in each fly's tiny brain is represented by only 150 time-keeping or so-called pacemaker neurons, making it much easier to dissect than the clock in larger animals. Even in mice, for example, the circadian system involves about 20,000 pacemaker neurons in a part of the brain called the suprachiasmatic nucleus.

The experiments measured calcium levels inside pacemaker cells to assess the cells' activities -- higher calcium levels indicate higher levels of neuronal activation. Unexpectedly, each pacemaker group displayed a distinct phase of activity. These activity patterns were sensitive to environmental signals, such as day length, and also to the circadian clock. The researchers found that one specific group of pacemaker neurons was active about four hours before the fly's morning peak in activity, and another specific group was active about four hours before the fly's evening activity.

"Essentially, groups of neurons decide to take different parts of the clock," explained Holy. "One group says, 'We'll be active in the morning, to make the fly active that time of day,' and this other group of neurons says, 'Even though our molecular clock is peaking here in the morning, we're going to wait to be most active until later on in the day.'"

Studying the genes of mutant fruit flies, the research team identified a chemical signal called pigment-dispersing factor (PDF). This neuropeptide is secreted by the morning pacemakers to help diversify the timing of pacemakers that control behaviors at other times of day.

"PDF is secreted by cells that are most active at dawn," Liang said. "In the flies with a mutation in the PDF receptor, we found that two other groups of neurons normally active at other times of day instead become active at dawn." The activity of the pacemaker neurons become more synchronous in the mutant flies, and the regular morning-evening pattern of fly activity is thrown off, the researcher said.

Previously, scientists had thought that cellular activity was closely coupled to the peak levels of the clock molecules.

"The idea was, as the clock goes, so goes the activity," Taghert said. "But here, we're suggesting that there may be a disconnect in some cells, and the reason for that disconnect is to space out the timing signals.

"We would never have been able to measure this activity 10 years ago," he said. Until a few years ago, it would not have been possible to monitor the activity of groups of neurons in a living animal in distant parts of the brain over extended time periods.

"One of the important new tools in neuroscience is the ability to measure brain activity with light," Holy explained. "However, too much light can be damaging to brain cells, especially if you're imaging for a long time. A few years ago, my lab developed a microscope that can illuminate the brain very gently, yet still get very high-quality pictures of what's happening over time. The trick is to shine light on just the part of the brain that's in focus so you avoid damaging any part you're not looking at. After snapping one picture, you move the microscope and take another picture of a different part of the brain. By doing that very quickly, you can cover the whole brain of the fly in a second or less."

"This is very much an example of techniques allowing you to answer questions that weren't answerable before," Taghert added.

Because many principles of circadian time-keeping are conserved across distant species, this neuronal mechanism discovered in Drosophila also may indicate a general clock principle. Naturally, time will tell.
https://www.sciencedaily.com/releases/2016/03/160302132538.htm

Brain tune-up may aid self-motivation Allowing people to see their own brain activity might help them motivate themselves

March 3, 2016
Science Daily/Duke University
Volition powers us through innumerable daily tasks. Could we lead healthier, more productive lives if we could learn to control the parts of our brain most essential to volition? A new spin on a technique called 'neurofeedback' has allowed scientists to take the first step in understanding how to manipulate neurotransmitter circuits involved in volition using thoughts and imagery. The methods may one day inform the treatment of depression or ADHD.
https://images.sciencedaily.com/2016/03/160303132957_1_540x360.jpg
This illustration shows an experiment in which subjects received real-time feedback during an MRI scan that showed activity in a reward center of their brain. Without feedback, they were unable to reliably increase activity in the Ventral Tegmental Area (VTA, in red), but the fluctuating thermometer helped them learn and adopt effective strategies by thinking about motivating themselves. Their self-generated boosts in VTA activation then worked even after the thermometer display was removed.
Credit: Jeff MacInnes, Duke University

If we could learn to control the motivational centers of our brains that drive volition, would it lead us toward healthier, more productive lives? Using a new brain imaging strategy, Duke University scientists have now taken a first step in understanding how to manipulate specific neural circuits using thoughts and imagery.

The technique, which is described in the March 16 issue of the journal Neuron, is part of a larger approach called 'neurofeedback,' which gives participants a dynamic readout of brain activity, in this case from a brain area critical for motivation.

"These methods show a direct route for manipulating brain networks centrally involved in healthy brain function and daily behavior," said the study's senior investigator R. Alison Adcock, an assistant professor of psychiatry and behavioral sciences and associate director of the Center for Cognitive Neuroscience in the Duke University Institute for Brain Sciences.

Neurofeedback is a specialized form of biofeedback, a technique that allows people to monitor aspects of their own physiology, such as heart rate and skin temperature. It can help generate strategies to overcome anxiety and stress or to cope with other medical conditions.

Neurofeedback has historically relied on electroencephalography or EEG, in which patterns of electrical activity are monitored noninvasively by electrodes attached to the scalp. But these measures provide only rough estimates of where activity occurs in the brain.

In contrast, the new study employed functional magnetic resonance imaging (fMRI), which measures changes in blood oxygen levels, allowing more precisely localized measurements of brain activity.

Adcock's team has been working on ways to use thoughts and behavior to tune brain function for the past eight years. In this time, they've developed tools allowing them to analyze complex brain imaging data in real time and to display it to participants as neurofeedback while they are in the fMRI scanner.

This study focused on the ventral tegmental area (VTA), a small area deep within the brain that is a major source of dopamine, a neurochemical well known for its role in motivation, experiencing rewards, learning, and memory.

According to Adcock's previous research, when people are given incentives to remember specific images, an increase in VTA activation before the image appears predicts whether the participants are going to successfully remember the image.

External incentives like money work well to stimulate the VTA, but it was unclear whether people could exercise this area on their own, said co-author Jeff MacInnes, a postdoctoral researcher in Adcock's lab.

In the new study, the team encouraged participants in the scanner to generate feelings of motivation -- using their own personal strategies -- during 20-second intervals. They weren't able to raise their VTA activity consistently on their own.

But when the scientists provided participants with neurofeedback from the VTA, presented in the form of a fluctuating thermometer, participants were able to learn which strategies worked, and ultimately adopt more effective strategies. Compared to control groups, the neurofeedback-trained participants successfully elevated their VTA activity.

Participants reported using a variety of different motivational strategies, from imagining parents or coaches encouraging them, to playing out hypothetical scenarios in which their efforts were rewarded, said co-author Kathryn Dickerson, a postdoctoral researcher in Adcock's group.

The self-generated boost in VTA activation worked even after the thermometer display was removed. Only the participants who had received accurate neurofeedback were able to consistently raise their VTA levels.

"Because this is the first demonstration of its kind, there is much still to be understood," Adcock added. "But these tools could offer benefits for everyone, particularly those with depression or attention problems."

The neurofeedback training also activated other regions involved in learning and experiencing rewards, confirming that, at least in the short term, the brain changes its activity more broadly as a result of neurofeedback, Dickerson said.

Adcock said one caveat of the study is that the team has not tested whether the neurofeedback drove changes in behavior. The group is working on those studies now and also plans to conduct the same study in participants with depression and attention deficit hyperactivity disorder (ADHD).
https://www.sciencedaily.com/releases/2016/03/160303132957.htm

Light exposure improves depressive symptoms among cancer survivors

March 10, 2016
Science Daily/The Mount Sinai Hospital / Mount Sinai School of Medicine
Light therapy decreased depressive symptoms and normalized circadian rhythms among cancer survivors, according to researchers, who add that those exposed to a dim red light experienced no change in symptoms.

Researchers from Icahn School of Medicine at Mount Sinai, Northwestern University in Chicago, University of Iowa, University of California in San Diego and Reykjavik University in Iceland randomly divided 54 cancer survivors into a bright white light or a dim red light group. Participants were provided with a light box and asked to use it for 30 minutes every morning for four weeks. Depressive symptoms and circadian activity rhythms were measured before, during and three months after completing the light exposures to determine the effectiveness of light therapy.

"Depressive symptoms are common among cancer survivors even years after treatment has ended," said Heiddis Valdimarsdottir, PhD, Associate Professor of Oncological Sciences, Icahn School of Medicine at Mount Sinai and lead author of the study. "This interferes with overall quality of life and puts survivors at risk for poor outcomes including death."

Patients exposed to the bright light experienced improvement in depressive symptoms while those exposed to the dim red light experienced no change in symptoms.

"Our findings suggest light therapy, a rather non-invasive therapy, may provide an innovative way to decrease depression among cancer survivors," said William Redd, PhD, Professor of Oncological Sciences at Icahn School of Medicine at Mount Sinai and co-author of the study.

Most patients face some degree of depression, anxiety, and fear when cancer becomes part of their lives. According to the American Cancer Society, 1 in 4 people with cancer have clinical depression.

"The good news is that depression can be treated, and bright light therapy is a potentially effective new treatment option," said Dr. Valdimarsdottir.
https://www.sciencedaily.com/releases/2016/03/160310214145.htm