Brain changes linked to sleep need

June 14, 2018

Science Daily/UT Southwestern Medical Center

We've all experienced going to bed tired and waking up refreshed, yet how that happens at the molecular level remains a mystery. An international study sheds new light on the biochemistry of sleep need in the brain.

According to the American Sleep Association, 50 million to 70 million U.S. adults have a sleep disorder with almost 1 in 3 experiencing short-term insomnia and about 1 in 10 suffering from chronic insomnia. Sleep loss is known to compromise thinking and decision-making, which decreases work performance and productivity while increasing the risk of auto and industrial accidents. Understanding sleep regulators could benefit society by leading to the development of novel, more effective treatments for sleeplessness.

The new research reports the first whole-brain, quantitative study of a fundamental molecular process called phosphorylation in the context of sleep need. It features a clever comparison of two different groups of tired mice: sleep-deprived normal mice and Sleepy mutant mice, a variety with a genetic mutation that confers an unusually high sleep need despite increased sleep amount.

The Sleepy mouse was identified in a collaborative study between Dr. Masashi Yanagisawa and Dr. Joseph Takahashi initiated at UT Southwestern's Peter O'Donnell Jr. Brain Institute, where Dr. Takahashi is Chair of Neuroscience, a Howard Hughes Medical Institute Investigator, and holder of the Loyd B. Sands Distinguished Chair in Neuroscience. Dr. Yanagisawa, Director of the University of Tsukuba's International Institute for Integrative Sleep Medicine (WPI-IIIS) in Japan, is a Professor of Molecular Genetics at UT Southwestern. Dr. Yanagisawa and Dr. Qinghua Liu, an Associate Professor in UTSW's Center for the Genetics of Host Defense and of Neuroscience, are two of the study's three corresponding authors. Dr. Liu also has joint appointments at the WPI-IIIS and at the National Institute of Biological Sciences (NIBS) in Beijing.

"Although sleep exists in all animals, why sleep is needed and how sleep is regulated remain a mystery. We set out to investigate the molecules that govern sleep need (or sleep pressure)," said Dr. Liu, a W.A. "Tex" Moncrief Jr. Scholar in Medical Research. Sleep need is the feeling of tiredness that builds up during waking hours, he said.

Dr. Joseph Takahashi describes the 2016 study from the Peter O'Donnell Jr. Brain Institute that identified the Sleepy mouse.

"Each animal exhibits a set point of total sleep time. In adult humans, that usually means about 8 out of 24 hours. Everyone has experienced staying up too late and feeling a need to 'make up for lost sleep.' Even simple jellyfish need to rest longer after being forced to remain awake," he said, adding that it has been hypothesized that a substance accumulates in the brain during waking and dissipates during sleep.

"A long-term goal in sleep research is to identify the actual molecular factor or factors involved in sleep need," he said. Currently, the majority of sleep medicines are mimics of GABA, an inhibitory neurotransmitter that simply shuts off the brain, and they induce nonnatural sleep with many side effects. It would be nice to understand the natural molecules better in order to design improved treatments for sleep problems, he added.

To study the molecules involved in sleep need, researchers devised a novel strategy of comparing phosphorylation in the brains of the sleep-deprived normal mice and Sleepy mutant mice. Phosphorylation is a reversible process that modifies the functions of proteins by adding a phosphate group. The novel strategy comparing the two mice -- one sleepy by circumstance, the other sleepy by nature -- made it possible to exclude variables such as stress that could affect sleepiness, the researchers explained.

Using immunochemical assays and mass spectrometry, the researchers identified 80 proteins that were hyperphosphorylated in the brains of sleep-deprived and Sleepy mice, meaning that the proteins accumulated more phosphate groups the longer the mice stayed awake. They named these proteins Sleep-Need-Index-Phosphoproteins (SNIPPs). They found that the phosphorylation of SNIPPs increased with sleep need and dissipated, or dephosphorylated, throughout the brain during sleep.

"Previous studies suggested a close link between sleep need and synaptic plasticity (the strengthening and weakening of synaptic connections between neurons that is linked to thinking and learning). Intriguingly, the majority of SNIPPs are synaptic proteins, including many regulators of synaptic plasticity," Dr. Liu said.

He added that a literature search found that mutations of multiple SNIPPs have been linked to changes in sleep need. "Thus, we propose that SNIPPs constitute the molecular link between synaptic plasticity and regulation of sleep need or, in lay terms, between thinking and sleepiness," he said.

"The purpose of phosphorylation appears to be to maximize the duration and quality of cognitive (thinking) functions of the brain. While prolonged wakefulness leads to cognitive impairment and sleepiness, sleep refreshes the brain through multiple restorative effects and optimizes cognitive functions for the next waking period," he said. Therefore, the phosphorylation/dephosphorylation cycle of SNIPPs may be an important way for the brain to reset itself every night, restoring both synaptic and sleep-wake balance to maximize clear thinking, he added.

https://www.sciencedaily.com/releases/2018/06/180614212700.htm

Early birds less prone to depression

Largest study yet links chronotype to mental health

June 14, 2018

Science Daily/University of Colorado at Boulder

A study of 32,000 women found that those with an early chronotype, or sleep-wake preference, were significantly less likely to develop depression.

Middle-to-older aged women who are naturally early to bed and early to rise are significantly less likely to develop depression, according to a new study by researchers at University of Colorado Boulder and the Channing Division of Network Medicine at Brigham and Women's Hospital in Boston.

The study of more than 32,000 female nurses, published in the Journal of Psychiatric Research, is the largest and most detailed observational study yet to explore the link between chronotype, or sleep-wake preference, and mood disorders.

It shows that even after accounting for environmental factors like light exposure and work schedules, chronotype -- which is in part determined by genetics -- appears to mildly influence depression risk.

"Our results show a modest link between chronotype and depression risk. This could be related to the overlap in genetic pathways associated with chronotype and mood," said lead author Céline Vetter, director of the Circadian and Sleep Epidemiology Laboratory (CASEL) at CU Boulder.

Previous studies have shown that night owls are as much as twice as likely to suffer from depression. But because those studies often used data at a single time-point and didn't account for many other factors that influence depression risk, it has been hard to determine whether depression leads people to stay up later or a late chronotype boosts risk of depression.

To shed light on the question, researchers used data from 32,470 female participants, average age 55, in the Nurses' Health Study, which asks nurses to fill out health questionnaires biennially.

In 2009, all the participants included in the study were free of depression. When asked about their sleep patterns, 37 percent described themselves as early types, 53 percent described themselves as intermediate types, and 10 percent described themselves as evening types.

The women were followed for four years to see who developed depression.

Depression risk factors like body weight, physical activity, chronic disease, sleep duration, or night shift work were also assessed.

The researchers found that late chronotypes, or night owls, are less likely to be married, more likely to live alone and be smokers, and more likely to have erratic sleep patterns.

After accounting for these factors, they found that early risers still had a 12 -- 27 percent lower risk of being depressed than intermediate types. Late types had a 6 percent higher risk than intermediate types ( this modest increase was not statistically significant.)

"This tells us that there might be an effect of chronotype on depression risk that is not driven by environmental and lifestyle factors," said Vetter.

Genetics play a role in determining whether you are an early bird, intermediate type, or night owl, with research showing 12-42 percent heritability. And some studies have already shown that certain genes (including PER2 and RORA), which influence when we prefer to rise and sleep, also influence depression risk.

"Alternatively, when and how much light you get also influences chronotype, and light exposure also influences depression risk. Disentangling the contribution of light patterns and genetics on the link between chronotype and depression risk is an important next step" Vetter said.

Vetter stresses that while the study does suggest that chronotype is an independent risk factor for depression, it does not mean night owls are doomed to be depressed.

"Yes, chronotype is relevant when it comes to depression but it is a small effect," she says, noting that her study found a more modest effect than previous ones have.

Her advice to night owls who want to lower their risk?

"Being an early type seems to beneficial, and you can influence how early you are" she said. Try to get enough sleep, exercise, spend time outdoors, dim the lights at night, and try to get as much light by day as possible.

https://www.sciencedaily.com/releases/2018/06/180614212658.htm

Sleeping too much or not enough may have bad effects on health

June 12, 2018

Science Daily/BioMed Central

Fewer than six and more than ten hours of sleep per day are associated with metabolic syndrome and its individual components, according to a new study.

Researchers at Seoul National University College of Medicine found that compared to individuals who slept six to seven hours per day, men who slept fewer than six hours were more likely to have metabolic syndrome and higher waist circumference. Women who slept fewer than six hours were more likely to have higher waist circumference. Sleeping more than ten hours per day was associated with metabolic syndrome and increased levels of triglycerides in men, and with metabolic syndrome, higher waist circumference, higher levels of triglycerides and blood sugar, as well as low levels of 'good' cholesterol (HDL-C) in women. The authors found that nearly 11% of men and 13% of women slept less than six hours, while 1.5% of men and 1.7% of women slept more than ten hours.

Claire E. Kim, lead author of the study said: "This is the largest study examining a dose-response association between sleep duration and metabolic syndrome and its components separately for men and women. Because we were able to expand the sample of our previous study, we were able to detect associations between sleep and metabolic syndrome that were unnoticed before. We observed a potential gender difference between sleep duration and metabolic syndrome, with an association between metabolic syndrome and long sleep in women and metabolic syndrome and short sleep in men."

Based on common definitions, participants were considered to have metabolic syndrome if they showed at least three of the following: elevated waist circumference, high triglyceride levels, low levels of 'good' cholesterol, hypertension, and high fasting blood sugar. The prevalence of metabolic syndrome was just over 29% in men and 24.5% in women. The authors suggest that as the prevalence of metabolic syndrome in Korea is high, it is critical to identify modifiable risk factors such as sleep duration.

The authors used data from the HEXA study, a large-scale community-based study conducted in Korea during the years 2004-2013, which included information on socio-demographic characteristics, medical history, medication use, family history, lifestyle factors, diet, physical activity, and reproductive factors for women. As part of the HEXA study, samples of plasma, serum, buffy coat, blood cells, genomic DNA, and urine were collected, and participants underwent physical examinations by medical professionals. Sleep duration was assessed by asking the question: "In the past year, on average, how many hours/minutes of sleep (including daytime naps) did you take per day?"

Although the biological mechanisms that underlie the association between sleep duration and metabolic syndrome remain unclear, several potential processes have been reported. These include elevated levels of hormones which increase appetite and caloric intake or reduce energy expenditure in people who sleep less than seven hours per day, which may lead to increased waist circumference and development of obesity.

The authors caution that the cross-sectional, observational nature of this study does not allow for conclusions about cause and effect. Estimates of sleep duration were based on self-report data rather than objective measures and may reflect 'time in bed', actual time spent asleep or time people believed they slept. Also, as the study did not distinguish between daytime naps and nighttime sleep, their impact on health could not be assessed separately.

https://www.sciencedaily.com/releases/2018/06/180612201800.htm

People who deeply grasp pain or happiness of others, process music differently in brain

Higher empathy people appear to process music like a pleasurable proxy for a human encounter -- in the brain regions for reward, social awareness and regulation of social emotions

June 12, 2018

Science Daily/Southern Methodist University

People who deeply grasp the pain or happiness of others also process music differently, say researchers. The study in Frontiers in Behavioral Neuroscience compared MRI scans of low- and high-empathy people. Higher empathy people process music like a pleasurable proxy for a human encounter -- in brain regions for reward and social awareness. The findings may have implications for the function of music now and in our evolutionary past.

The researchers found that compared to low empathy people, those with higher empathy process familiar music with greater involvement of the reward system of the brain, as well as in areas responsible for processing social information.

"High-empathy and low-empathy people share a lot in common when listening to music, including roughly equivalent involvement in the regions of the brain related to auditory, emotion, and sensory-motor processing," said lead author Zachary Wallmark, an assistant professor in the SMU Meadows School of the Arts.

But there is at least one significant difference.

Highly empathic people process familiar music with greater involvement of the brain's social circuitry, such as the areas activated when feeling empathy for others. They also seem to experience a greater degree of pleasure in listening, as indicated by increased activation of the reward system.

"This may indicate that music is being perceived weakly as a kind of social entity, as an imagined or virtual human presence," Wallmark said.

Researchers in 2014 reported that about 20 percent of the population is highly empathic. These are people who are especially sensitive and respond strongly to social and emotional stimuli.

The SMU-UCLA study is the first to find evidence supporting a neural account of the music-empathy connection. Also, it is among the first to use functional magnetic resonance imaging (fMRI) to explore how empathy affects the way we perceive music.

The new study indicates that among higher-empathy people, at least, music is not solely a form of artistic expression.

"If music was not related to how we process the social world, then we likely would have seen no significant difference in the brain activation between high-empathy and low-empathy people," said Wallmark, who is director of the MuSci Lab at SMU, an interdisciplinary research collective that studies -- among other things -- how music affects the brain.

"This tells us that over and above appreciating music as high art, music is about humans interacting with other humans and trying to understand and communicate with each other," he said.

This may seem obvious.

"But in our culture we have a whole elaborate system of music education and music thinking that treats music as a sort of disembodied object of aesthetic contemplation," Wallmark said. "In contrast, the results of our study help explain how music connects us to others. This could have implications for how we understand the function of music in our world, and possibly in our evolutionary past."

The researchers reported their findings in the peer-reviewed journal Frontiers in Behavioral Neuroscience, in the article "Neurophysiological effects of trait empathy in music listening."

The co-authors are Choi Deblieck, with the University of Leuven, Belgium, and Marco Iacoboni, UCLA. The research was carried out at the Ahmanson-Lovelace Brain Mapping Center at UCLA.

"The study shows on one hand the power of empathy in modulating music perception, a phenomenon that reminds us of the original roots of the concept of empathy -- 'feeling into' a piece of art," said senior author Marco Iacoboni, a neuroscientist at the UCLA Semel Institute for Neuroscience and Human Behavior.

"On the other hand," Iacoboni said, "the study shows the power of music in triggering the same complex social processes at work in the brain that are at play during human social interactions."

Comparison of brain scans showed distinctive differences based on empathy

Participants were 20 UCLA undergraduate students. They were each scanned in an MRI machine while listening to excerpts of music that were either familiar or unfamiliar to them, and that they either liked or disliked. The familiar music was selected by participants prior to the scan.

Afterward each person completed a standard questionnaire to assess individual differences in empathy -- for example, frequently feeling sympathy for others in distress, or imagining oneself in another's shoes.

The researchers then did controlled comparisons to see which areas of the brain during music listening are correlated with empathy.

Analysis of the brain scans showed that high empathizers experienced more activity in the dorsal striatum, part of the brain's reward system, when listening to familiar music, whether they liked the music or not.

The reward system is related to pleasure and other positive emotions. Malfunction of the area can lead to addictive behaviors.

Empathic people process music with involvement of social cognitive circuitry

In addition, the brain scans of higher empathy people in the study also recorded greater activation in medial and lateral areas of the prefrontal cortex that are responsible for processing the social world, and in the temporoparietal junction, which is critical to analyzing and understanding others' behaviors and intentions.

Typically, those areas of the brain are activated when people are interacting with, or thinking about, other people. Observing their correlation with empathy during music listening might indicate that music to these listeners functions as a proxy for a human encounter.

Beyond analysis of the brain scans, the researchers also looked at purely behavioral data -- answers to a survey asking the listeners to rate the music afterward.

Those data also indicated that higher empathy people were more passionate in their musical likes and dislikes, such as showing a stronger preference for unfamiliar music.

Precise neurophysiological relationship between empathy and music is largely unexplored

A large body of research has focused on the cognitive neuroscience of empathy -- how we understand and experience the thoughts and emotions of other people. Studies point to a number of areas of the prefrontal, insular, and cingulate cortices as being relevant to what brain scientists refer to as social cognition.

Activation of the social circuitry in the brain varies from individual to individual. People with more empathic personalities show increased activity in those areas when performing socially relevant tasks, including watching a needle penetrating skin, listening to non-verbal vocal sounds, observing emotional facial expressions, or seeing a loved one in pain.

In the field of music psychology, a number of recent studies have suggested that empathy is related to intensity of emotional responses to music, listening style, and musical preferences -- for example, empathic people are more likely to enjoy sad music.

"This study contributes to a growing body of evidence," Wallmark said, "that music processing may piggyback upon cognitive mechanisms that originally evolved to facilitate social interaction."

https://www.sciencedaily.com/releases/2018/06/180612185148.htm

Loneliness is bad for the heart

June 9, 2018

Science Daily/European Society of Cardiology

Loneliness is bad for the heart and a strong predictor of premature death, according to a new study. The study found that feeling lonely was a stronger predictor of poor outcomes than living alone, in both men and women.

"Loneliness is more common today than ever before, and more people live alone," said Anne Vinggaard Christensen, study author and PhD student, The Heart Centre, Copenhagen University Hospital, Denmark. "Previous research has shown that loneliness and social isolation are linked with coronary heart disease and stroke, but this has not been investigated in patients with different types of cardiovascular disease."

The study investigated whether poor social network was associated with worse outcomes in 13,463 patients with ischaemic heart disease, arrhythmia (abnormal heart rhythm), heart failure, or heart valve disease. Data from national registers was linked with the DenHeart survey, which asked all patients discharged from April 2013 to April 2014 from five heart centres in Denmark to answer a questionnaire about their physical and mental health, lifestyle factors such as smoking, and social support.

Social support was measured using registry data on living alone or not, and survey questions about feeling lonely -- Do you have someone to talk to when you need it? Do you feel alone sometimes even though you want to be with someone? "It was important to collect information on both, since people may live alone but not feel lonely while others cohabit but do feel lonely," explained Ms Vinggaard Christensen.

Feeling lonely was associated with poor outcomes in all patients regardless of their type of heart disease, and even after adjusting for age, level of education, other diseases, body mass index, smoking, and alcohol intake. Loneliness was associated with a doubled mortality risk in women and nearly doubled risk in men. Both men and women who felt lonely were three times more likely to report symptoms of anxiety and depression, and had a significantly lower quality of life than those who did not feel lonely.

"Loneliness is a strong predictor of premature death, worse mental health, and lower quality of life in patients with cardiovascular disease, and a much stronger predictor than living alone, in both men and women," said Ms Vinggaard Christensen.

Ms Vinggaard Christensen noted that people with poor social support may have worse health outcomes because they have unhealthier lifestyles, are less compliant with treatment, and are more affected by stressful events. But she said: "We adjusted for lifestyle behaviours and many other factors in our analysis, and still found that loneliness is bad for health."

She concluded: "We live in a time when loneliness is more present and health providers should take this into account when assessing risk. Our study shows that asking two questions about social support provides a lot of information about the likelihood of having poor health outcomes."

European guidelines on cardiovascular prevention state that people who are isolated or disconnected from others are at increased risk of developing and dying prematurely from coronary artery disease. The guidelines recommend assessment of psychosocial risk factors in patients with established cardiovascular disease and those at high risk of developing cardiovascular disease.

https://www.sciencedaily.com/releases/2018/06/180609124652.htm

One in four Americans develop insomnia each year: 75 percent of those with insomnia recover

June 5, 2018

Science Daily/University of Pennsylvania School of Medicine

About 25 percent of Americans experience acute insomnia each year, but about 75 percent of these individuals recover without developing persistent poor sleep or chronic insomnia, according to a new study.

The new study offers the latest data on the prevalence of acute insomnia, which is characterized by difficulty falling asleep or staying asleep for as little as three nights per week for at least two consecutive weeks up to three months. Insomnia becomes chronic when it occurs at least three nights a week for more than three months.

"Whether caused by stress, illness, medications, or other factors, poor sleep is very common," said senior author Michael Perlis, PhD, an associate professor of Psychiatry and director of the Behavioral Sleep Medicine program. "These findings reveal new insights about the paths that acute insomnia takes and can inform interventions that target poor sleep and help people recover sustained sufficient sleep."

The findings, (#0359) will be presented at SLEEP 2018, the 32nd Annual Meeting of the Associated Professional Sleep Societies LLC (APSS) in Baltimore.

Although some studies have offered the prevalence of insomnia symptoms in large populations, to date this is the first study to offer data on transitions of good sleepers (GS) -- defined as those needing fewer than 15 minutes to fall asleep and/or who spend fewer than 15 minutes awake during the night on five or more nights per week. The study specifically determines how GS transition to acute insomnia (AI), to persistent poor sleep (PPS) -- i.e., recurring bouts of AI without sustained recovery or turning to chronic insomnia (CI), to chronic insomnia, and how many of those affected by AI recover.

A total of 1,435 adults were recruited nationwide and tracked for one year during 2015-2017. They were verified as good sleepers over the first three months of the study and assessed on a daily, weekly and monthly basis for one full year. The subjects kept a daily sleep diary for the duration of the study, allowing for a uniquely detailed level of insight into how sleep varies from day to day. Also, regular assessments were made regarding participants' daytime function, stress and life events, and medical and mental health.

Among the 25 percent experiencing acute insomnia, about 75 percent of subjects recovered good sleep within 12 months, while 21 percent remained poor sleepers with recurring bouts of AI, and about 6 percent developed chronic insomnia. No significant differences were observed along racial, ethnic, or gender lines, or among people of varying incomes or BMI.

The new data provides researchers with how many people experience AI each year, as well as how those cases progress, laying the groundwork for additional research now underway to assess what factors predict recovery (resilience) and non-recovery (persistent poor sleep or the new onset of chronic insomnia).

The findings will be presented during the poster session on Tuesday, June 5, from 3:15-3:30 pm in room 337 at the Baltimore Convention Center.

Previous research from the Perlis team has shown that suicides are more likely to occur after midnight than during the daytime or evening and another study showing that more sleep reduces suicide risk in those with insomnia.

https://www.sciencedaily.com/releases/2018/06/180605154114.htm

Short and long sleep durations lnked with excess heart age

Sleep duration and heart age may be a simplified way to express cardiovascular disease risk

June 4, 2018

Science Daily/American Academy of Sleep Medicine

Preliminary results from a new study show that excess heart age (EHA) appeared to be lowest among adults who reported sleeping seven hours per 24-hour period.

Results show that mean adjusted EHA was lowest among adults who reported sleeping seven hours per 24-hour period. Sleeping times less than or greater than seven hours were associated with increased excess heart age, and the highest elevations in EHA were noted in short sleepers. Sleep duration coupled with EHA may prove helpful for communicating the cardiovascular risks and benefits associated with sleep duration.

"These results are important because they demonstrate a quantitative method for the inclusion of sleep duration in the establishment and communication of cardiovascular risk for individuals. This could have utility in the clinical care of patients with cardiovascular risk, and for public health researchers interested in adding a sleep metric to future studies," said primary researcher and study author Julia Durmer, BS candidate, Emory University, the Center for the Study of Human Health and student researcher, Emory University, Rollins School of Public Heath in Atlanta, Ga.

The study involved 12,775 adults ranging in age from 30-74 years who responded to the 2007-2014 National Health and Nutrition Examination Survey (NHANES). Self-reported sleep duration was classified into five categories (5 or less, 6, 7, 8, and 9 or more hours of sleep per night). They used the sex-specific Framingham heart age algorithm to calculate each individual's heart age and used multivariable linear or logistic regression to examine the association between sleep duration and EHA or risk of EHA 10 years or more.

https://www.sciencedaily.com/releases/2018/06/180604093121.htm

Inadequate sleep could cost countries billions

June 4, 2018

Science Daily/Oxford University Press USA

Inadequate sleep is a public health problem affecting more than one in three adults worldwide. A new study suggests that insufficient sleep could also have grave economic consequences.

Community sleep surveys suggest that inadequate sleep is substantial and increasing. Surveys performed several years ago demonstrated that complaints of inadequate sleep were common, with between 20 and 30 percent of respondents complaining of inadequate sleep on a regular basis across several Western nations. Recent surveys suggest this proportion is increasing; between 33 and 45 percent of Australian adults now have this complaint.

The growth of the problem over time is shared by other nations with similar demographics. Some 35 percent of U.S. adults are not getting the recommended 7 hours of sleep each night. About 30 percent of Canadians don't feel they're getting enough sleep. Some 37 percent of those in the UK, 28 percent of people in Singapore, and 26 percent of French people also report insufficient sleep.

Insufficient sleep is associated with lapses in attention and the inability to stay focused; reduced motivation; compromised problem solving; confusion, irritability and memory lapses; impaired communication; slowed or faulty information processing and judgment; diminished reaction times; and indifference and loss of empathy. Furthermore, short sleep increases the risk of heart attacks, stroke, hypertension, obesity, diabetes, and depression.

Here researchers attempted to measure the economic consequences of limited sleep times -- defined as "difficulties with sleep initiation, maintenance or quality associated with the presence of impaired daytime alertness" at least several days a week -- in Australia. Researchers evaluated financial and non-financial cost data derived from national surveys and databases. Costs considered included: financial costs associated with health care, informal care provided outside the healthcare sector, productivity losses, non-medical work and vehicle accident costs, deadweight loss through inefficiencies relating to lost taxation revenue and welfare payments; and nonfinancial costs of a loss of well-being.

The financial cost component was $17.88 billion, comprised of: direct health costs of $160 million for sleep disorders and $1.08 billion for associated conditions; productivity losses of $12.19 billion ($5.22 billion reduced employment, $0.61 billion premature death, $1.73 billion absenteeism, $4.63 billion lost through workers showing up for work but not actually performing work on the job); non-medical accident costs of $2.48 billion; informal care costs of $0.41 billion; and deadweight loss of $1.56 billion. The non-financial cost of reduced well-being was $27.33 billion. Thus, the estimated overall cost of inadequate sleep in Australia in 2016-17 (population: 24.8 million) was $45.21 billion.

The financial and non-financial costs associated with inadequate sleep are substantial. The estimated total financial cost of $17.88 billion represents 1.55% of Australian gross domestic product. The estimated non-financial cost of $27.33 billion represents 4.6% of the total Australian burden of disease for the year. The researchers argue that these costs warrant substantial investment in preventive health measures to address the issue through education and regulation.

In setting national health priorities, governments have attempted to identify issues that involve high communal illness and injury burden with associated high costs for attention through public education, regulation, and other initiatives to effect improvements in health status. The authors say that governments have been remarkably successful in targeting diabetes, depression, and smoking, for example. These data presented above suggest that sleep health may merit similar attention. The situation is likely to be similar in equivalent economies.

Researcher quote: "We are in the midst of a worldwide epidemic of inadequate sleep, some from clinical sleep disorders, some through pressure from competing work, social and family activities and some from failure to give sleep sufficient priority through choice or ignorance. Apart from its impact on well-being, this problem comes at a huge economic cost through its destructive effects on health, safety and productivity. Addressing the issue by education, regulation and other initiatives is likely to deliver substantial economic as well as health benefits."

https://www.sciencedaily.com/releases/2018/06/180604093111.htm

Effects of night-time light on internal body clock

April 30, 2018

Science Daily/The Physiological Society

New research published in The Journal of Physiology has illuminated the effects of night-time light exposure on internal body clock processes. This is important for helping those who have poor quality sleep, such as shift workers, and could help improve treatments for depression.

The body has an internal clock that causes various physiological processes to oscillate in 24-h cycles, called circadian rhythms, which includes daily changes in sleepiness. Light is the strongest environmental time cue that resets the body's internal 24-h clock. Melatonin is a hormone produced in the brain at night that regulates this body clock and exposure to light before bedtime may reduce sleep quality by suppressing its production. The research team aimed to explore the link between the physiological process that enables our internal body clock to synchronise to external time cues (i.e. day and night) -- called circadian phase resetting -- and suppression of melatonin.

Melatonin suppression and circadian phase resetting are often correlated such that high levels of melatonin suppression can be associated with large shifts of the body clock. This association between the two responses has often been assumed to represent a functional relationship, resulting in the acceptance that one could be used as a proxy measure for the other. Circadian phase resetting is more difficult to measure than melatonin suppression, meaning the latter has often been used to assess disruption to the body clock caused by light exposure at night. However, this research has found that the magnitude of the shift in internal body clock is functionally independent from melatonin suppression. This casts doubt on the use of melatonin suppression as a proxy for circadian phase resetting. This knowledge may shape future research designed to improve treatments for depression and shift work sleep disorder.

The researchers tested the association between melatonin suppression and circadian phase resetting in participants who received either continuous or intermittent bright light exposure at night. This research procedure involved each participant completing a 9-10 day inpatient study at Brigham and Women's Hospital, Boston, under highly controlled laboratory conditions with strict control over their sleep/wake, activity and light/dark schedules. Intermittent exposure patterns were found to show significant phase shifts with disproportionately less melatonin suppression. Moreover, each and every intermittent bright light pulse induced a similar degree of melatonin suppression, but did not appear to cause an equal magnitude of phase shift.

Despite the results of this study suggesting functional independence in circadian phase resetting and melatonin suppression responses to exposure to light at night, the study's conclusions may be restricted by the limited sample size in each light exposure condition.

Lead author Dr Shadab Rahman is excited by his team's findings, and is looking forward to investigating new avenues of interest they have opened up:

"Overall, our data suggest that melatonin suppression and phase resetting are sometimes correlated, but ultimately are regulated by separate neurophysiological processes. Therefore melatonin suppression is not a reliable surrogate for phase resetting. This is an important consideration for developing light-therapy treatments for people who have poor quality sleep and biological clock disruption, such as shift workers, or disorders such as depression. Additional work is needed to optimize light therapy protocols used as treatment."

https://www.sciencedaily.com/releases/2018/04/180430075635.htm

Dark chocolate consumption reduces stress and inflammation

Data represent first human trials examining the impact of dark chocolate consumption on cognition and other brain functions

Science Daily/April 24, 2018

Loma Linda University Adventist Health Sciences Center

New research shows there might be health benefits to eating certain types of dark chocolate. Findings from two studies being presented today at the Experimental Biology 2018 annual meeting in San Diego show that consuming dark chocolate that has a high concentration of cacao (minimally 70% cacao, 30% organic cane sugar) has positive effects on stress levels, inflammation, mood, memory and immunity. While it is well known that cacao is a major source of flavonoids, this is the first time the effect has been studied in human subjects to determine how it can support cognitive, endocrine and cardiovascular health.

Lee S. Berk, DrPH, associate dean of research affairs, School of Allied Health Professions and a researcher in psychoneuroimmunology and food science from Loma Linda University, served as principal investigator on both studies.

"For years, we have looked at the influence of dark chocolate on neurological functions from the standpoint of sugar content -- the more sugar, the happier we are," Berk said. "This is the first time that we have looked at the impact of large amounts of cacao in doses as small as a regular-sized chocolate bar in humans over short or long periods of time, and are encouraged by the findings. These studies show us that the higher the concentration of cacao, the more positive the impact on cognition, memory, mood, immunity and other beneficial effects."

The flavonoids found in cacao are extremely potent antioxidants and anti-inflammatory agents, with known mechanisms beneficial for brain and cardiovascular health. The following results will be presented in live poster sessions during the Experimental Biology 2018 meeting:

Dark Chocolate (70% Cacao) Affects Human Gene Expression: Cacao Regulates Cellular Immune Response, Neural Signaling, and Sensory Perception

·     This pilot feasibility experimental trial examined the impact of 70 percent cacao chocolate consumption on human immune and dendritic cell gene expression, with focus on pro- and anti-inflammatory cytokines. Study findings show cacao consumption up-regulates multiple intracellular signaling pathways involved in T-cell activation, cellular immune response and genes involved in neural signaling and sensory perception -- the latter potentially associated with the phenomena of brain hyperplasticity.

Dark Chocolate (70% Organic Cacao) Increases Acute and Chronic EEG Power Spectral Density (μv2) Response of Gamma Frequency (25-40Hz) for Brain Health: Enhancement of Neuroplasticity, Neural Synchrony, Cognitive Processing, Learning, Memory, Recall, and Mindfulness Meditation

·     This study assessed the electroencephalography (EEG) response to consuming 48 g of dark chocolate (70% cacao) after an acute period of time (30 mins) and after a chronic period of time (120 mins), on modulating brain frequencies 0-40Hz, specifically beneficial gamma frequency (25-40Hz). Findings show that this superfood of 70 percent cacao enhances neuroplasticity for behavioral and brain health benefits.

Berk said the studies require further investigation, specifically to determine the significance of these effects for immune cells and the brain in larger study populations. Further research is in progress to elaborate on the mechanisms that may be involved in the cause-and-effect brain-behavior relationship with cacao at this high concentration.

https://www.sciencedaily.com/releases/2018/04/180424133628.htm

Sitting is bad for your brain -- not just your metabolism or heart

Thinning in brain regions important for memory linked to sedentary habits

April 12, 2018

Science Daily/University of California - Los Angeles

Studies show that too much sitting, like smoking, increases the risk of heart disease, diabetes and premature death. Researchers found sedentary behavior is linked to thinning in regions of the brain that are critical to memory formation.

UCLA researchers recruited 35 people ages 45 to 75 and asked about their physical activity levels and the average number of hours per day they spent sitting over the previous week. Each person had a high-resolution MRI scan, which provides a detailed look at the medial temporal lobe, or MTL, a brain region involved in the formation of new memories.

The researchers found that sedentary behavior is a significant predictor of thinning of the MTL and that physical activity, even at high levels, is insufficient to offset the harmful effects of sitting for extended periods.

This study does not prove that too much sitting causes thinner brain structures, but instead that more hours spent sitting are associated with thinner regions, researchers said. In addition, the researchers focused on the hours spent sitting, but did not ask participants if they took breaks during this time.

The researchers next hope to follow a group of people for a longer duration to determine if sitting causes the thinning and what role gender, race, and weight might play in brain health related to sitting.

MTL thinning can be a precursor to cognitive decline and dementia in middle-aged and older adults. Reducing sedentary behavior may be a possible target for interventions designed to improve brain health in people at risk for Alzheimer's disease, researchers said.

https://www.sciencedaily.com/releases/2018/04/180412141014.htm

Night owls have higher risk of dying sooner

Evening types have 10 percent higher risk of dying than morning counterparts

April 12, 2018

Science Daily/Northwestern University

Night owls -- people who prefer to stay up late and sleep late -- have 10 percent higher risk of dying sooner than larks, people who go to bed early and rise early, reports a new study. This is the first study to show 'owls' have higher risk of mortality. Owls also suffer from more diseases and disorders than morning larks. Employers should allow greater flexibility in working hours for owls, scientists said.

The study, on nearly half a million participants in the UK Biobank Study, found owls have a 10 percent higher risk of dying than larks. In the study sample, 50,000 people were more likely to die in the 6½ -year period sampled.

"Night owls trying to live in a morning lark world may have health consequences for their bodies," said co-lead author Kristen Knutson, associate professor of neurology at Northwestern University Feinberg School of Medicine.

Previous studies in this field have focused on the higher rates of metabolic dysfunction and cardiovascular disease, but this is the first to look at mortality risk.

The study will be published April 12 in the journal Chronobiology International.

The scientists adjusted for the expected health problems in owls and still found the 10 percent higher risk of death.

"This is a public health issue that can no longer be ignored," said Malcolm von Schantz, a professor of chronobiology at the University of Surrey. "We should discuss allowing evening types to start and finish work later, where practical. And we need more research about how we can help evening types cope with the higher effort of keeping their body clock in synchrony with sun time."

"It could be that people who are up late have an internal biological clock that doesn't match their external environment," Knutson said. "It could be psychological stress, eating at the wrong time for their body, not exercising enough, not sleeping enough, being awake at night by yourself, maybe drug or alcohol use. There are a whole variety of unhealthy behaviors related to being up late in the dark by yourself."

In the new study, scientists found owls had higher rates of diabetes, psychological disorders and neurological disorders?

Can owls become larks?

Genetics and environment play approximately equal roles in whether we are a morning or a night type, or somewhere in between, the authors have previously reported.

"You're not doomed," Knutson said. "Part of it you don't have any control over and part of it you might."

One way to shift your behavior is to make sure you are exposed to light early in the morning but not at night, Knutson said. Try to keep a regular bedtime and not let yourself drift to later bedtimes. Be regimented about adopting healthy lifestyle behaviors and recognize the timing of when you sleep matters. Do things earlier and be less of an evening person as much as you can.

Society can help, too

"If we can recognize these chronotypes are, in part, genetically determined and not just a character flaw, jobs and work hours could have more flexibility for owls," Knutson said. "They shouldn't be forced to get up for an 8 a.m. shift. Make work shifts match peoples' chronotypes. Some people may be better suited to night shifts."

In future research, Knutson and colleagues want to test an intervention with owls to get them to shift their body clocks to adapt to an earlier schedule. "Then we'll see if we get improvements in blood pressure and overall health," she said.

The switch to daylight savings or summer time is already known to be much more difficult for evening types than for morning types.

"There are already reports of higher incidence of heart attacks following the switch to summer time," says von Schantz. "And we have to remember that even a small additional risk is multiplied by more than 1.3 billion people who experience this shift every year. I think we need to seriously consider whether the suggested benefits outweigh these risks."

How the study worked

For the study, researchers from the University of Surrey and Northwestern University examined the link between an individual's natural inclination toward mornings or evenings and their risk of mortality. They asked 433,268 participants, age 38 to 73 years, if they are a "definite morning type" a "moderate morning type" a "moderate evening type" or a "definite evening type." Deaths in the sample were tracked up to six and half years later.

The study was supported by the University of Surrey Institute?of Advanced Studies Santander fellowship and the National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK095207 from the National Institutes of Health.

https://www.sciencedaily.com/releases/2018/04/180412085736.htm

Brain activity can predict success of depression treatment

April 11, 2018

Science Daily/McLean Hospital

Researchers believe they have uncovered a method that could be useful in predicting a depressed patient's treatment prognosis, prior to starting treatment.

McLean Hospital and Harvard Medical School researchers believe they have uncovered a method that could be useful in predicting a depressed patient's treatment prognosis, prior to starting treatment.

In the paper "Pretreatment Rostral Anterior Cingulate Cortex Activity in Relation to Symptom Improvement in Depression: A Randomized Clinical Trial," currently available online and scheduled to appear in the June 2018 edition of JAMA Psychiatry, the investigative team details its work in identifying whether certain markers in the brain could allow clinicians to identify patients with a high or low likelihood of responding to certain treatments for depression.

The study was jointly first-authored by Diego A. Pizzagalli, PhD, and Christian A. Webb, PhD. "Our work shows that we could predict a patient's response to an antidepressant by looking at the activation level of the rostral anterior cingulate cortex (ACC) region of the brain by using a non-invasive monitoring system to test brain activity called an electroencephalogram -- also known as an EEG," said Diego A. Pizzagalli, director of the McLean Imaging Center as well as the hospital's Center For Depression, Anxiety and Stress Research and Laboratory for Translational and Affective Neuroscience. Webb, assistant professor at Harvard Medical School and director of the Treatment and Etiology of Depression in Youth Laboratory, noted that this is the first study to "demonstrate the 'incremental predictive validity' of this neural marker, that is, the fact that activity in this brain region predicts the likelihood of treatment response above and beyond the contribution of a range of low-cost and easily administered clinical and demographic characteristics previously shown to predict treatment outcome."

For this study, the team built upon Pizzagalli's previous work showing that EEG recordings of rostral ACC activity could predict the eventual response. "In that prior study, we saw that the higher the activity before the start of the treatment, the better the clinical response months later," noted Pizzagalli, who is also a professor of psychiatry at Harvard Medical School.

For the new study, more than 300 patients were tested at four sites in the United States -- using sertraline for the treatment group. "We showed that the rostral ACC marker predicted clinical response eight weeks later, even when statistically controlling for demographics and clinical variables previously linked to treatment response," said Pizzagalli. "For those with the marker of good response, a clinician could tell patients that they have a high chance of benefitting from the intervention, and they should stay engaged in treatment," he explained. Conversely, he said, for patients with the marker of low response, "clinicians could decide to start with more aggressive treatment at the outset, such as a combination of pharmacology and psychotherapy, and importantly, monitor these patients more closely."

Soon, Webb, Pizzagalli, and their colleagues plan to deploy these approaches on patients at McLean Hospital to determine whether they can lead to treatment-specific predictions. "Our vision is to determine if an optimal combination of markers -- including brain-based but also clinical and demographic characteristics -- might allow us to predict response to drug A but not drug B or psychotherapy, for example," Webb explained.

Also, if an ACC marker predicts better response, researchers might develop cognitive training that specifically targets this region, which could increase brain activation to accelerate or boost response to more traditional intervention. Pizzagalli and his team hope to engage in further research into this concept by testing patients with major depressive disorder.

https://www.sciencedaily.com/releases/2018/04/180411111103.htm

Lingering negative responses to stress linked with health a decade later

April 9, 2018

Science Daily/Association for Psychological Science

People whose negative emotional responses to stress carry over to the following day are more likely to report health problems and physical limitations later in life compared with peers who are able to 'let it go.'

"Our research shows that negative emotions that linger after even minor, daily stressors have important implications for our long-term physical health," says psychological scientist Kate Leger of the University of California, Irvine.

"When most people think of the types of stressors that impact health, they think of the big things, major life events that severely impact their lives, such as the death of a loved one or getting divorced," Leger says. "But accumulating findings suggest that it's not just the big events, but minor, everyday stressors that can impact our health as well."

Evidence from previous studies suggests a clear association between same-day responses to stress and long-term well-being, but the impact of lingering emotional responses remained unclear. That is, does it make a difference if a stressor -- such as a flat tire, a bad grade, or an argument -- leads to negative emotions that spill over into the following day?

To find out, Leger and colleagues Susan T. Charles and David M. Almeida analyzed data from the Midlife in the United States Survey, a nationally representative, longitudinal study of adults.

As part of the study, participants completed an 8-day survey of negative emotion; each day, they reported how much of the time over the previous 24 hours they had felt a variety of emotions (e.g., lonely, afraid, irritable, and angry). They also reported the stressors that they experienced each day.

In a subsequent part of the study that took place 10 years later, the participants completed surveys that assessed their chronic illnesses and functional limitations. Participants reported the degree to which they were able to carry out basic and everyday tasks, such as dressing themselves, climbing a flight of stairs, carrying groceries, and walking several blocks.

As expected, people tended to report higher negative emotion if they had experienced a stressor the previous day compared with if they hadn't experienced any stressor the day before.

Critically, analyses revealed that lingering negative emotions in response to a stressor were associated with a greater number of health problems, including chronic illnesses, functional impairments, and difficulties with everyday tasks, a decade later.

These associations emerged independently of participants' gender, education, and baseline health and they held even after the researchers took participants' same-day emotional responses and average number of stressors into account.

"This means that health outcomes don't just reflect how people react to daily stressors, or the number of stressors they are exposed to -- there is something unique about how negative they feel the next day that has important consequences for physical health," explains Leger.

Leger and colleagues hypothesize that this link could play out through activation of stress-related systems or through health behaviors, two potential mechanisms that offer avenues for future research.

"Stress is common in our everyday lives. It happens at work, it happens at school, it happens at home and in our relationships," says Leger. "Our research shows that the strategy to 'just let it go' could be beneficial to our long term physical health."

https://www.sciencedaily.com/releases/2018/04/180409161315.htm

Study found people would rather pop a pill or sip tea than exercise to treat high blood pressure

April 8, 2018

Science Daily/American Heart Association

Survey respondents were more likely to choose a daily cup of tea or a pill over exercise to 'treat' high blood pressure in an imaginary scenario, but many didn't think the interventions were worth the benefits. When the perceived gain of treating hypertension was higher -- one or five extra years of life versus one extra month, for example -- survey respondents were more likely to say they would.

Researchers wanted to find out how people weigh the benefits of high blood pressure treatment options against its inconvenience. They asked survey respondents to imagine that they had high blood pressure and then asked about their willingness to adopt any of four "treatments" to gain an extra month, year or five years of life. In this survey, the "treatments" proposed were: a daily cup of tea, exercise, pills or monthly or semi-annual injections.

Results showed that taking a pill or drinking a daily up of tea were the preferred treatments, though some were unwilling to adopt any intervention even if it meant gaining an additional year or five years of life. For each treatment, participants were more likely to say they would adopt it if the benefit were greater:

·     79 percent of respondents said they would be willing to take a pill for an extra month of life, 90 percent would for an extra year of life and 96 percent would for an extra five years of life;

·     78 percent said they would drink a daily cup of tea for one extra month of life, 91 percent would for one extra year of life and 96 percent would drink it for an extra five years of life;

·     63 percent would be willing to exercise for an extra month of life, 84 percent would for an extra year of life and 93 percent would exercise if it meant an extra five years of life;

·     A shot was the least preferred of the options -- 68 percent would take a shot every six months if it would give them an extra month of life, 85 percent would do it for an extra year of life and 93 percent would be willing if it gave them another five years, but only about half (51 percent) would take a monthly shot for an extra month of life, 74 percent would for an extra year and 88 percent would opt for an injection every month if it gave them five extra years of life.

In addition, at least 20 percent of respondents wanted to achieve gains in life expectancy beyond what any of the individual interventions could provide.

"Our findings demonstrate that people naturally assign different weights to the pluses and minuses of interventions to improve cardiovascular health," said Erica Spatz, M.D., M.H.S., the study lead author and an assistant professor of cardiovascular medicine in the Center for Outcomes Research and Evaluation at Yale School of Medicine in New Haven, CT. "I believe we need to tap into this framework when we are talking with patients about options to manage their blood pressure. We are good about discussing side effects, but rarely do we find out if other inconveniences or burdens may be impacting a person's willingness to take a lifelong medication or to exercise regularly."

From March to June 2017, 1,284 U.S. adults recruited through Amazon MTurk and 100 patients attending an outpatient health clinic completed the survey. Most survey respondents were under 45 years old, and half were female. Roughly three-quarters of respondents were non-Hispanic white, 10 percent were African American, 7 percent were Hispanic or Latino, and 8 percent were Asian. Most had high blood pressure.

A study limitation is that most respondents were relatively young. Since cardiovascular disease is more common among older people, they may have different responses than younger people. Another limitation is that survey respondents were not told the true life-extending ability of each intervention.

High blood pressure is a leading risk factor for heart and blood vessel, or cardiovascular, disease. Yet, it is often called the silent killer because it causes no symptoms. To prevent high blood pressure, the American Heart Association recommends getting regular physical activity, in addition to other lifestyle changes. These changes include eating a healthy diet, limiting alcohol, managing stress, maintaining a healthy weight, and quitting smoking. It is also important to work with a healthcare provider and to properly take medications, if prescribed, to reduce blood pressure.

https://www.sciencedaily.com/releases/2018/04/180408190404.htm

Relaxation response may reduce blood pressure by altering expression of a set of genes

of genes

Researchers identified genes and biological pathways linked to immune regulation, metabolism, and circadian rhythm in people who reduced their hypertension after eight-week relaxation response training

April 4, 2018

Science Daily/Beth Israel Deaconess Medical Center

A new study has identified genes associated with the body's response to relaxation techniques and sheds light on the molecular mechanisms by which certain interventions may work to lower blood pressure.

High blood pressure -- or hypertension -- is a major risk factor for heart attack and stroke that affects as many as 100 million Americans and 1 billion people worldwide. Decades of research have demonstrated that the relaxation response -- the physiological and psychological opposite of the well-known fight-or-flight stress response that can be achieved through relaxation techniques like yoga or mediation -- can reduce blood pressure in people with hypertension. Exactly how these interventions act on the body to lower blood pressure remains unclear.

A new study led by investigators at Beth Israel Deaconess Medical Center (BIDMC), Massachusetts General Hospital (MGH), and the Benson-Henry Institute for Mind Body Medicine at MGH identified genes associated with the body's response to relaxation techniques and sheds light on the molecular mechanisms by which these interventions may work to lower blood pressure. The findings were published today in the Journal of Alternative and Complementary Medicine.

"Traditionally, hypertension is treated with pharmacologic therapy, but not all patients respond to drug therapy, and many experience treatment-limiting side effects," said co-senior author Randall Zusman, MD, Director of the Division of Hypertension at MGH's Corrigan Minehan Heart Center. "In these patients, alternative strategies are invaluable. In this study, we found that the relaxation response can successfully help reduce blood pressure in hypertensive patients who are not taking medication."

Towia Libermann, PhD, Director of the Genomics, Proteomics, Bioinformatics, and Systems Biology Center at BIDMC said, "To our knowledge, this is the first study to test such a mind-body intervention for a population of unmedicated adults with carefully documented, persistent hypertension, and this is the first study to identify gene expression changes specifically associated with the impact of a mind-body intervention on hypertension. Our results provide new insights into how integrative medicine -- especially mind-body approaches -- influences blood pressure control at the molecular level."

First described more than four decades ago by Herbert Benson, MD, Director Emeritus of the Benson Henry Institute and a co-author of the current study, the relaxation response is characterized by a set of measurable changes to the body, including decreased respiration rate and heart rate, all of which can be induced by mind-body techniques including meditation and yoga. Long-term relaxation response practice has been associated with increased brain cortical thickness and specific changes in gene expression.

In this study, Libermann, Zusman and colleagues enrolled 58 people with Stage 1 essential hypertension -- defined as having a systolic (top number) blood pressure between 140-159mm Hg and diastolic (bottom number) between 90-104mm Hg. Participants were either not taking medications to control their blood pressure or had tapered off them for five weeks prior to the outset of the study. Participants also filled out standardized questionnaires about stress, depression and anxiety.

Over the next eight weeks, participants attended eight weekly training sessions at which they were guided through mind-body interventions designed to elicit the relaxation response -- including diaphragmatic breathing, mantra repetition and mindfulness meditation -while passively ignoring intrusive thoughts. Participants were also given an audio CD that guided them through the same sequence for use at home once a day.

After the eight weeks of training, patients filled out the same stress, depression and anxiety questionnaires and had blood drawn for gene expression testing along with blood pressure measurement. Overall, 13 of the 24 participants who completed the eight-week intervention experienced a clinically relevant drop in blood pressure -- that is, specific reductions in both systolic and diastolic blood pressure readings that moved participants below 140/90 mm Hg, the clinical definition of stage 1 hypertension.

Patients who demonstrated significant reductions in both systolic and diastolic blood pressure -- enough so that their blood pressure was below the definition of Stage I essential hypertension -- were classified as "responders." Those whose blood pressure still fell within the definition of Stage I hypertension -- and those who did not see reduction in both numbers -- were classified as "non-responders."

When Libermann and colleagues ran gene expression analyses comparing blood samples from the two groups, they found that specific gene expression changes had occurred in the responders over the course of the eight-week relaxation response intervention that were not observed in the non-responders. Specifically, among responders the expression of 1,771 genes differed between the baseline blood tests and those taken after the eight weeks of relaxation response practice. Further, Libermann and colleagues determined that the reduction in blood pressure was correlated with genes linked to immune regulatory pathways, metabolism and glucose metabolism, cardiovascular system development and circadian rhythm.

"Interactive network analysis of the gene signature identified several molecules, particularly immune system-linked genes, as critical molecules for blood pressure reduction," said first author Manoj Bhasin, PhD, Co-Director of the Genomics, Proteomics, Bioinformatics, and Systems Biology Center at BIDMC.

"Our results suggest that the relaxation response reduced blood pressure -- at least in part -- by altering expression of genes in a select set of biological pathways," co-first author John Denninger, MD, PhD, Director of Research at the Benson-Henry Institute, noted. "Importantly, the changes in gene expression associated with this drop in blood pressure are consistent with the physical changes in blood pressure and inflammatory markers that one would anticipate and hope to observe in patients successfully treated for hypertension."

In addition to Zusman and Libermann, investigators included co-first author Manoj Bhasin and Marie Joseph of Beth Israel Deaconess Medical Center; co-first author John Denninger, Jeffrey Huffman, Halsey Niles, Emma Chad-Friedman, Roberta Goldman, Beverly Buczynski Kelley, Barbara Mahoney, Gregory Fricchione and Herbert Benson of Massachusetts General Hospital and Benson-Henry Institute for Mind Body Medicine at MGH; and Jeffery Dusek of Abbott Northwestern Hospital, Institute for Health and Healing.

https://www.sciencedaily.com/releases/2018/04/180404093929.htm

Human daily rhythms: Clocks vs light/dark cycle

April 3, 2018

Science Daily/University of Seville

A new study analyses daily primary activities of European laborers and the sources of social synchronization.

Should people living along a meridian be doing their basic activities (sleep/wake, working, eating, leaving home/coming home) at the same time? A 'yes' is an intuitive answer since solar noon happens simultaneously along the meridian. This phenomenon helps setting clock time. Therefore, a 'yes' is also pointing to clock synchronization, irrespective of latitude.

On a second thought we may understand that nobody gets to work at, say, 8am because it is four hours before noon, the bare meaning of clock ticking 8am. Instead the decision making process (whether 8am is fine, late or early) is driven by light conditions: did the Sun already rise? The answer to this question varies with latitude and season following the natural cycle of light and dark. Therefore, if this question influences human behaviour then people living along a meridian would not be doing their basic activities at the same time.

José María Martín Olalla, professor at University of Seville, addresses this issue in a paper entitled "Latitudinal trends in human primary activities: characterizing the winter day as a synchronizer" published in Scientific Reports, the Springer Nature open access megajournal. From time use surveys in 17 European countries and 2 American countries (located from 35º to 61º latitude) he characterizes laborer's primary activities and get them positioned along the daily and yearly cycle of light and dark.

Results show up latitudinal patterns tied to the light/dark cycle with the winter terminator as a source of synchronization for daily activities of laborers. Societies memorize the shortest photoperiod (daytime) of the year, the most challenging condition in one year. Winter photoperiod decreases by two hours from 40 to 54 degree latitude.

Winter sunrise (the later sunrise of the year and increasingly later with increasing latitude) triggers human activity in the morning year round and dominates morning trends. Its fingerprint can be traced on rising times, leaving home and working start times, all of them occur earlier with decreasing latitude. From 40 to 54 degree latitude, winter sunrise delays by one whole hour, the size of a standard time zone.

Winter sunset (the earliest sunset of the year, increasingly earlier with increasing latitude, it delays another whole hour from 54 to 40 degree latitude) triggers the reverse, shutdown process and dominates evening activities like stop working, coming home or dinning.

Two overturning sequences can also be identified. The first one occur at noon where lunch times exhibit both a meridional behaviour (tied to noon) and a latitudinal trend tied to the winter sunset. In this case people advance lunch times as latitude increases foreseeing the incoming dusk while people delay lunch times with decreasing latitude as light conditions do not worsen comparatively too much.

The second overturning sequence occurs at night and indoors: TV prime time marks and bedtimes are not tied to the winter sunset. Instead, they exhibit meridional behavior or trends weakly coupled to the winter sunrise. Societies are foreseeing the uprise in the following day.

The magnitude of the latitudinal gradient which dominates human activity can be comparatively traced out by observing how the terminator sweeps Europe in winter, when morning times are relatively similar as the sunrise terminator efficiently sweeps the continent, while evening times goes step by step following the sunset terminator.

Indirectly this study also inspects the role of time zone and time advance in human behaviour. The case of France, Belgium and Spain illustrates this issue. There, clocks are set one hour ahead of their physical time zone: that is an advanced clock, not an uncommon option for local time on Earth. Despite this time marks make perfect sense when properly tested against the LD cycle. That means people offset clock advancing by delaying time schedules apparently. In so doing they kept in phase with the LD cycle. This poses no harm to population. It only jeopardizes time comparisons, most notably in Spain due to its Southwestern most location. A rule of thumb valid for comparisons (both academic and non-academic) is subtracting one whole hour. That would convert "advanced clock" reading into standard time values.

https://www.sciencedaily.com/releases/2018/04/180403090052.htm

Frequency of alpha brain waves could be used to assess a person’s predisposition to pain

March 28, 2018

Science Daily/University of Birmingham

The frequency of alpha brain waves can be used as a measure of an individual’s vulnerability to developing and experiencing pain, researchers have discovered.

The personal experience of pain is highly variable among individuals, even in instances where the underlying injury is assessed to be identical.

Previous research has found some genetic factors influence pain susceptibility, but methods to accurately predict pain level consequent to medical intervention such as chemotherapy or surgery are lacking.

The objective of this study was to see if, from the resting brain activity of a healthy individual, it was possible to predict how much pain they would report once prolonged pain had been induced.

The researchers induced the pain using a capsaicin paste -- an ingredient found in hot chili peppers -- to study participants' left forearm and then heated it. Topical capsaicin exposure induces 'robust thermal hyperalgesia' -- a common symptom in chronic pain. All 21 participants in the study were induced in a state of prolonged pain for around an hour.

Using an electroencephalogram (EEG) -- a non-invasive test used to find problems related to the electrical activity of the brain -- the researchers found that across all 21 study participants, those who had a slower frequency of alpha brain waves recorded before the pain, reported being in much more pain than those who had a fast frequency of alpha brain waves.

The researchers also recorded the activity of alpha brain waves during the experience of pain, and if alpha frequency increased (relative to the no-pain condition) the individuals reported to be in less pain than when alpha pain decreased.

Co-senior author Dr Ali Mazaheri, of the University of Birmingham's Center for Human Brain Health, said: "Here we observe that an individual's alpha frequency can be used as a measure of an individual's predisposition to developing pain.

"This has a direct relevance to understanding what makes an individual prone to chronic pain after a medical intervention, such as surgery or chemotherapy.

"Potentially this means we could be able to identify which individuals are more likely to develop pain as a result of a medical procedure and take steps early on in formulating treatment strategies in patients likely to be predisposed to developing chronic pain."

Dr David Seminowicz and Andrew Furman, of the University of Maryland in the US, were also authors of the report.

Andrew Furman said: "Alpha frequency has been found to be slower in individuals who have experienced chronic pain. So the fact we observed that the slowing down of alpha activity as a result of pain correlated with the intensity of an individual's pain report was not that unexpected.

"What was very surprising though, was that prior to the pain -- that is pain-free alpha frequency -- could predict how much pain individuals would experience.

"This would suggest that it could be that the slowing of alpha activity in the chronic pain patients, isn't because of the pain, but rather these individuals had slow alpha frequency to begin with, and as such were more prone or vulnerable to developing pain."

The research, published in Neuroimage, was also carried out in collaboration with the Maryland Exercise and Robotics Center of Excellence in the US.

https://www.sciencedaily.com/releases/2018/03/180328092417.htm

Vagus nerve stimulation boosts post-stroke motor skill recovery

March 27, 2018

Science Daily/University of Texas at Dallas

Researchers have demonstrated a method to accelerate motor skill recovery after a stroke by helping the brain reorganize itself more quickly. In a preclinical study, the scientists paired vagus nerve stimulation with a physical therapy task aimed at improving the function of an upper limb in rodents. The results showed a doubled long-term recovery rate relative to current therapy methods.

In a preclinical study, the scientists paired vagus nerve stimulation (VNS) with a physical therapy task aimed at improving the function of an upper limb in rodents. The results showed a doubled long-term recovery rate relative to current therapy methods, not only in the targeted task but also in similar muscle movements that were not specifically rehabbed. Their work was recently published in the journal Stroke.

A clinical trial to test the technique in humans is underway in Dallas and 15 other sites across the country.

Dr. Michael Kilgard, associate director of the Texas Biomedical Device Center (TxBDC) and Margaret Forde Jonsson Professor of Neuroscience in the School of Behavioral and Brain Sciences, led the research team with Dr. Seth Hays, the TxBDC director of preclinical research and assistant professor of bioengineering in the Erik Jonsson School of Engineering and Computer Science, and postdoctoral researcher Eric Meyers PhD'17.

"Our experiment was designed to ask this new question: After a stroke, do you have to rehabilitate every single action?" Kilgard said. "If VNS helps you, is it only helping with the exact motion or function you paired with stimulation? What we found was that it also improves similar motor skills as well, and that those results were sustained months beyond the completion of VNS-paired therapy."

Kilgard said the results provide an important step toward creating guidelines for standardized usage of VNS for post-stroke therapy.

"This study tells us that if we use this approach on complicated motor skills, those improvements can filter down to improve simpler movements," he said.

Building Stronger Cell Connections

When a stroke occurs, nerve cells in the brain can die due to lack of blood flow. An arm's or a leg's motor skills fail because, though the nerve cells in the limb are fine, there's no longer a connection between them and the brain. Established rehab methods bypass the brain's damaged area and enlist other brain cells to handle the lost functions. However, there aren't many neurons to spare, so the patient has a long-lasting movement deficit.

The vagus nerve controls the parasympathetic nervous system, which oversees elements of many unconscious body functions, including digestion and circulation. Electrical stimulation of the nerve is achieved via an implanted device in the neck. Already used in humans to treat depression and epilepsy, VNS is a well-documented technique for fine-tuning brain function.

The UT Dallas study's application of VNS strengthens the communication path to the neurons that are taking over for those damaged by stroke. The experiments showed a threefold-to-fivefold increase in engaged neurons when adding VNS to rehab.

"We have long hypothesized that VNS is making new connections in the brain, but nothing was known for sure," Hays said. "This is the first evidence that we are driving changes in the brain in animals after brain injury. It's a big step forward in understanding how the therapy works -- this reorganization that we predicted would underlie the benefits of VNS."

In anticipation of the technique's eventual use in humans, the team is working on an at-home rehab system targeting the upper limbs.

"We've designed a tablet app outlining hand and arm tasks for patients to interact with, delivering VNS as needed," Meyers said. "We can very precisely assess their performance and monitor recovery remotely. This is all doable at home."

Expanding the Possibilities for Therapy

The researchers are motivated in part by an understanding of the practical limitations of current therapeutic options for patients.

"If you have a stroke, you may have a limited time with a therapist," Hays said. "So when we create guidelines for a therapist, we now know to advise doing one complex activity as many times as possible, as opposed to a variety of activities. That was an important finding -- it was exciting that not only do we improve the task that we trained on, but also relatively similar tasks. You are getting generalization to related things, and you're getting sustained improvement months down the line."

For stroke patients, the opportunity to benefit from this technology may not be far off.

"A clinical trial that started here at UTD is now running nationwide, including at UT Southwestern," Kilgard said. "They are recruiting patients. People in Dallas can enroll now -- which is only fitting, because this work developed here, down to publishing this in a journal of the American Heart Association, which is based here in Dallas. This is a homegrown effort.

"The ongoing clinical trial is the last step in getting approved as an established therapy," Kilgard said. "We're hopefully within a year of having this be standard practice for chronic stroke."

https://www.sciencedaily.com/releases/2018/03/180327162606.htm

From lullabies to live concerts: How music and rhythm shape our social brains

March 27, 2018

Science Daily/Cognitive Neuroscience Society

A universal sign of motherhood is the lullaby. The world over, mothers sing to their babies, whether Twinkle Twinkle Little Star, their favorite song from the radio, or even random notes. This universality makes the simple lullaby a great window into the human mind. In a new study, cognitive neuroscientists found that lullabies soothe both moms and babies simultaneously, while playsongs increase babies' attention and displays of positive emotion toward their mothers.

The behavioral implications of music are vast, says Laura Cirelli of the University of Toronto Mississauga, who is presenting the new work on maternal singing at the 25th meeting of the Cognitive Neuroscience Society (CNS) in Boston today. "Infant brains must be able to track auditory events in a predictive manner to make sense of music," she explains, and many complex things are going on in their brains to make that possible.

From infancy to old age, music demands much from the human brain. Learning more about how we process music is helping scientists better understand perception, multisensory integration, and social coordination across the lifespan. Technological advancements -- for example, more portable electroencephalography (EEG) and electrophysiology set-ups and- are allowing cognitive neuroscientists to study music in a variety of situations, from mother-child interactions to live concert halls.

"Music and rhythm are human universals but do not appear to be shared by most other species," says Jessica Grahn of the University of Western Ontario who is chairing the CNS session on musical rhythm and who co-authored a new study of live music and brain rhythms. "Rhythm in particular is mysterious: We are sensitive to the 'beat' -- that steady, underlying pulse that we tap our foot or bob our head to -- from early in life. But, even after decades of trying, 'beat-tracking' algorithms can't approach anything like the automaticity and flexibility that humans show to feel the beat across different speeds, genres, and instruments."

Music for mom and baby

While working at a daycare one summer as an undergraduate student, Cirelli was at a playground when a 2-year-old girl asked her for help down the slide. The rest of the toddlers saw this, looked at each other, and excitedly ran over to line up and wait their turn. "I was amazed at the complexity of their social understanding at an age where they can't even tell us what they are thinking," she explains. This sent her down the path of exploring how sociality develops at a young age, and as a piano player and ballerina, the natural fit was to use music as a way to understand the social brain.

In her new study on lullabies, Cirelli and colleagues investigated how mothers adjust their infant-directed singing depending on their goal, to be soothing or to be playful. The participating mothers repeatedly sang Twinkle Twinkle to their babies who were sitting in a highchair facing them. The mothers alternated between singing in a playful way or a soothing manner. At the same time, researchers were tracking the mothers' and babies' arousal responses, measured through skin conductance and behavior. "When we are excited or stressed, arousal levels increase," Cirelli explains. "When we are calm, they decrease."

The researchers found that the moms' arousal levels were higher during playful compared to soothing song. And they found coordinated decreases in arousal for both the moms and babies as the soothing songs progressed. In the playful conditions, the babies' arousal levels remained stable and their attention to mother and displays of positive emotion increased. "The findings show the physiological and behavioral changes by mom and baby to different song styles."

This study builds on a growing body of work about the social implications of musical engagement with others. Cirelli points to past studies showing that when people move together in synchrony, they feel socially connected and are later more likely to help and cooperate with one another. And in a study of toddlers, she and colleagues had similar findings: 14-month-olds who bounced synchronously with unfamiliar adults helped those adults substantially more by retrieving dropped objects than those who bounced with them asynchronously. "Music is a tool that we can use to bring people together, and this starts in infancy."

Music for a live audience

Despite being able to listen to music from virtually anywhere in modern times, people will still pay hundreds of dollars for the opportunity attend a live musical performance. Why? This question helps drive forward the work of Grahn and Molly Henry, both of the University of Ontario.

In new work she will be presenting at the CNS meeting today, Henry used the LIVELab at McMaster University to test how the presence of live performers and an audience changes the experience of concert-goers at a neural level, Specifically, she and colleagues looked at brain rhythm synchronization.

A live band played in front of 80 people, 20 of whom were having their brain activity recorded with EEG. They then compared those EEG measurements to those in two other conditions: one, in which 20 audience members were watching a recording of the first concert on a large movie screen with audio identical to the live concert; and another in which 20 participants in small groups of 2 were seated apart while they observed the recorded musical performance. "Thus, we manipulated the presence of the performers while keeping audience context fixed," the authors explain.

They found that audience members' brain waves were more synchronized with each other when the performers were present. Moreover, individuals whose brain rhythms were more synched up with other audience members enjoyed the concert more and felt more connected to the performers.

"I was extremely excited to see that across the live audience, brain rhythms were synchronized in exactly the frequency range that corresponds to the 'beat' of the music, so it looks as if the beat is driving audience brain rhythms," Henry says. "That may seem common sense, but it's really something. These are novel findings in the context of live music listening that are providing insights into the more social side of music listening."

Music for the future

Moving forward, Henry says that the biggest challenge for studying musical rhythm is that "there's so much other stuff tied up in the experience of music and rhythm listening or performing. Music makes us want to move, it elicits emotions, it triggers memories." Teasing apart these influences will require creative stimulus and experimental design combined with integration of converging evidence across lots of different studies.

In the meantime, Grahn says: "We are seeing relationships between rhythm and language abilities, attention, development, hearing acuity, and even social interactions. Every sensation we have or action we make on the world unfolds over time, and we are now beginning to understand why humans are sensitive to certain types of patterns in time, but not others." Understanding these patterns will inform not only basic science, she says, but also potential music-driven therapies for patients suffering from neurodegenerative diseases.

https://www.sciencedaily.com/releases/2018/03/180327102835.htm