How to tell if a brain is awake

EEG may not always be a reliable reflection of consciousness

December 23, 2019

Science Daily/Michigan Medicine - University of Michigan

A team was able to demonstrate, using rats, that the EEG doesn't always track with being awake. Their study raises questions about what it means to be conscious.

Remarkably, scientists are still debating just how to reliably determine whether someone is conscious. This question is of great practical importance when making medical decisions about anesthesia or treating patients in vegetative state or coma.

Currently, researchers rely on various measurements from an electroencephalogram, or EEG, to assess level of consciousness in the brain. A Michigan Medicine team was able to demonstrate, using rats, that the EEG doesn't always track with being awake.

"EEG doesn't necessarily correlate with behavior," says Dinesh Pal, Ph.D., assistant professor of anesthesiology at the U-M Medical School. "We are raising more questions and asking that people are more cautious when interpreting EEG data."

Under anesthesia, an EEG will display a sort of signature of unconsciousness: reduced brain connectivity; increased slow waves, which are also associated with deep sleep, vegetative state and coma; and less complexity or less change in brain activity over time.

Building on data from a 2018 study, Pal and his team wanted to see what happened to these measures when a brain was awakened under anesthesia. To do so, they targeted an area of the brain called the medial prefrontal cortex, which has been shown to play a role in attention, self-processing and coordinating consciousness.

Using a drug in that part of the brain that mimics the activity of neurotransmitter acetylcholine, the team was able to rouse some of the rats so that they were up and moving around despite the fact that they were receiving continuous anesthesia. Using the same drug in the back of the brain did not awaken the rats. So, both groups of rats had anesthesia in the brain but only one group "woke up."

Then, "we took the EEG data and looked at those factors that have been considered correlates of wakefulness. We figured if the animals were waking up, even while still exposed to anesthesia, then these factors should also come back up. However, despite wakeful behavior, the EEGs were the same in the moving rats and the non-moving anesthetized rats," says Pal.

What does this mean for the EEG's ability to reflect consciousness? "The study does support the possibility that certain EEG features might not always accurately capture the level of consciousness in surgical patients," says senior author George A. Mashour, M.D., Ph.D., chair of the U-M Department of Anesthesiology.

However, "EEG likely does have value in helping us understand if patients are unconscious. For example, a suppressed EEG would suggest a very high probability of unconsciousness during general anesthesia. However, using high anesthetic doses to suppress the EEG might have other consequences, like low blood pressure, that we want to avoid. So, we will have to continue to be judicious in assessing the many indices available, including pharmacologic dosing guidelines, brain activity, and cardiovascular activity."

Pal notes that there is physiological precedent for an EEG mismatching behavior; for example, the brain of someone in REM sleep is almost identical to an awake brain. "No monitor is perfect, but the current monitors we use for the brain are good and do their job most of the time. However, our data suggest there are exceptions."

Their study raises intriguing questions about how consciousness is reflected in the brain, says Pal. "These measures do have value and we have to do more studies. Maybe they are associated with awareness and what we call the content of consciousness. With rats, we don't know-we can't ask them."

https://www.sciencedaily.com/releases/2019/12/191223122837.htm

Neurons responsible for rapid eye movements/REM during sleep

December 20, 2019

Science Daily/University of Bern

Why do we move our eyes fast in the paradoxical sleep -- in that sleep phase, in which most dreams take place? The secret is not yet fully aired, but we are on his track: A team has identified the nerve cells behind this curious phenomenon.

REM -- Rapid Eye Movement -- is not only the name of a successful American rock band, but also and not least a characteristic eye movement in paradoxical sleep, so in the stage with high dream activity. This sleep phase has a peculiarity: Although the muscle tone of the sleeping person completely relaxed, the eyes suddenly move back and forth. The name "paradoxical sleep" is well deserved. Characteristic of these are signs of deep sleep (muscle atony) in connection with a brain activity, which is very similar to those in the waking state, and eye movements. This sleep phase was discovered in the 1950s by French and American researchers and consequently called rapid eye movement sleep (REM sleep), i.e. sleep with rapid eye movements. Why can this strange phenomenon be useful? For 70 years, scientists have been dreaming of getting to the bottom of the mystery. Thanks to the productive cooperation between the universities of Bern and Fribourg, this dream could now come true.

Butterfly wings arranged neurons

For several years, the team led by Franck Girard and Marco Celio at the University of Freiburg has studied neurons under the microscope, which occur in the brain stem and form a structure that is reminiscent of butterfly wings, which is why she was baptized Nucleus papilio. "These neurons are associated with multiple nerve centers, especially those responsible for eye movement, and those involved in sleep control," explains Franck Girard. "Therefore, we asked ourselves the following question: may the nucleus papilio neurons play a role in the control of eye movements during sleep?"

Stronger together

To test this hypothesis, the Freiburg researchers turned to the research group headed by Dr. C. Gutiérrez Herrera and Prof. A. Adamantidis at the Department of Neurology at the Inselspital, University Hospital Bern, and Department for BioMedical Research of the University of Bern, who are investigating sleep in mice. "To our surprise, we found that these neurons are particularly active in the phase of paradoxical sleep," reports Dr. Carolina Gutierrez. The researchers from Bern gathered the loop around the nucleus papilio neurons even more closely and were able to demonstrate with the help of optogenetic methods (combined optical and genetic techniques) that their artificial activation causes rapid eye movement, especially during this sleep phase. Conversely, the inhibition or elimination of these same neurons blocks the movement of the eyes.

After the "how" the "why"!

Now that it is clear that the nucleus papilio neurons play an important role in eye movement during REM sleep, it is important to find out what function this phenomenon has. Is it due to the visual experience of dreams? Does it matter in preserving memories? "Now that we are able to specifically activate the nucleus papilio 'on demand' in mice by optogenetic methods, we may be able to find answers to these questions," says Antoine Adamantidis. The next step, however, will be to confirm the activation of nucleus papilio neurons during REM sleep in humans. The researchers have not yet found the key to their dreams, but they've come a long way.

A better understanding of the neural circuits involved in paradoxical sleep is therefore a prerequisite for understanding for instance how these neurons are prone to degenerative changes in diseases such as Parkinson's.

https://www.sciencedaily.com/releases/2019/12/191220150557.htm

Finding your way in the dark depends on your internal clock

Surprising results show how circadian rhythm changes the way mammals can see

December 19, 2019

Science Daily/Aalto University

Surprising results show how circadian rhythm changes the way mammals can see. Mice can accomplish a vision task better at night than during day. The researchers expected the body's internal clock to alter how strong nerve signals were at night, but discovered that the animal's behavior changed depending on the time of day instead. This opens interesting lines of inqury into how circadian rhythm changes behavior.

How mammals perceive light changes between night and day. Researchers at Aalto University and the University of Helsinki discovered that mice were better at finding a dim light in pitch-darkness in experiments done at night time compared to ones done during the day time. The scientists were surprised to find that this effect had very little to do with any changes in the eye itself, and was instead controlled by how the mice actually searched for light in the dark, and how their brains processed signals at night vs. day. The results are exciting for neuroscientists interested in how animals and humans can see, and biologists interested in how the time of day alters our bodies, including sensory processing.

Many types of animals behave differently during day and night time. While the "body clock" has long been known, its effect on how different parts of the body function still aren't fully understood. For instance, researchers knew that the retina, the part of the eye that detects light, has its own circadian rhythm. The team at Aalto and Helsinki Universities were interested in seeing if the eye's internal clock affected vision, so they modified one of their previous experiments to find out.

'Our research group is able to link if a mouse can find a dim light in the dark to the mouse's underlying retinal nerve signals at the sensitivity limit of vision.' said Professor Petri Ala-Laurila, the research group leader. 'This allowed us to explore how the day/night cycle changes the mouse's visual capability, both down in the neural circuit level and all the way up to behaviour responses at the sensitivity limit of vision'

Finding your way in a pitch-dark maze

Earlier this year, Professor Ala-Laurila's group demonstrated how the eyes of mice detect faint light in near-total darkness. This allowed them to link the mammalian visually-guided behaviour to individual neural impulses, an important world-first for neuroscience. The experiment involved placing a mouse in a maze in total darkness, with a faint light next to the exit of the maze. The mouse is trained to know that the light leads to the way out. They repeated this experiment for this new study, doing some of the tests during the day, and some during the night. They observed that the behaviour change -- the mice were better at spotting the light at night than during the day. They were expecting this result, but they also observed that the nerve impulses leaving from the retina themselves did not cause the difference, which was a surprise.

So, if the nerve signals from the eyes aren't changing, how could the mice be seeing better at night? The researchers were able to answer this using their new laboratory set up. A big part of the technique invented by the group at Aalto involves using high-tech night vision cameras and their own deep-learning based software to accurately track how the animals moved, and what they could see. The team observed that during the night time experiments, the mice searched for the light more effectively by scanning the environment for example by turning around more. Once the night group learned this behavioural strategy after searching at night, they were then also able to use it during the day, solving the maze puzzles quicker in day experiments than identical mice who'd never attempted it at night.

'Previously, it had not been possible to measure behaviour as accurately as our group now can, so researchers had to treat mice as having a predefined set of behavioural rules in experiments like this. It's exciting to now show that even in the simplest of tasks -- finding a light in the dark -- animals can use vastly different behavioural strategies and, what's more, we are able to quantify day/night differences in them.' said Sanna Koskela, a PhD student at Helsinki University and the first author of the paper in Current Biology which published the results.

Internal Clock effects on the eye

The team now hope to further investigate the effects the circadian rhythm has on the eye. Although this specific test doesn't appear to show any signal effects from time of day, it is just one of many visual tasks the eye can perform at low light level, and others may yet still show circadian influence.

'We now have a remarkable opportunity to study sensory performance from the retina to behaviour in dim light, including things like how circadian rhythm controls it. Our next set of experiments will explore how the brain processes weak signals originating from increasing and decreasing light intensities in the retina at different times of day and night. This will help us understand more deeply how mammals see at low light levels.' said Professor Ala-Laurila

https://www.sciencedaily.com/releases/2019/12/191219142813.htm

Light pollution can suppress melatonin production in humans and animals

December 19, 2019

Science Daily/Forschungsverbund Berlin

Melatonin sets the internal clock. Researchers from Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB) in an international team have analyzed data on the impact of light pollution on melatonin formation in humans and vertebrates. They found that even the low light intensities of urban skyglow can suppress melatonin production.

Melatonin synchronizes the day-night-rhythm in animals and humans. It adjusts the circadian clocks of cells, tissues and organs, and regulates other seasonal processes like reproduction. In vertebrates, differences in light levels are detected by photoreceptors for example in the retina. At high light levels, melatonin production is suppressed. In darkness, melatonin is produced.

The sensitivity threshold for humans is 6 lux -- street lighting is typically higher

Artificial light at night can disturb the nocturnal melatonin production. Within a literature review of 1900 studies, the researchers identified 72 relevant works that fulfilled their criteria for light pollution. Based on the data, they showed that even very low illuminance levels can suppress melatonin production for some vertebrate classes: in fish the threshold is 0.01 lux, in rodents 0.03 lux and in sensitive humans 6 lux; pure blue light showed much lower thresholds.

For comparison, the illuminance levels at night: On a starry night, the illuminance is 0.001 lux. On a full-moon night it reaches a maximum of 0.3 lux. The skyglow of a city, a form of light pollution, can reach illuminances of up to 0.1 lux, and outdoor lighting on the order of 150 lux.

"Surprisingly, the low light levels of skyglow are sufficient to suppress melatonin production in several vertebrate classes," says first author Dr. Maja Grubisic from IGB Berlin. "Skyglow affects large areas on a world-wide scale, as we know from satellite data," adds her colleague Dr. Andreas Jechow. The light from artificial lighting shines into the night sky, brighter with rain and snow, and is reflected by clouds and particles, which is called skyglow. The scientists unraveled several knowledge gaps: "There are no studies on melatonin and light pollution in reptiles and amphibians and no long term-studies at all. Particularly, the impacts on human health are not fully understood," says IGB researcher Dr. Franz Hoelker, head of the study.

https://www.sciencedaily.com/releases/2019/12/191219111431.htm

Can good sleep patterns offset genetic susceptibility to heart disease and stroke?

December 18, 2019

Science Daily/Tulane University

Getting a good night's sleep could be beneficial for long-term health. A pioneering new study led by Dr. Lu Qi, director of the Tulane University Obesity Research Center, found that even if people had a high genetic risk of heart disease or stroke, healthy sleep patterns could help offset that risk. The study is published in the European Heart Journal.

The researchers looked at genetic variations known as SNPs (single nucleotide polymorphisms) that were already known to be linked to the development of heart disease and stroke. They analysed the SNPs from blood samples taken from more than 385,000 healthy participants in the UK Biobank project and used them to create a genetic risk score to determine whether the participants were at high, intermediate or low risk of cardiovascular problems.

The researchers followed the participants for an average of 8.5 years, during which time there were 7,280 cases of heart disease or stroke.

"We found that compared to those with an unhealthy sleep pattern, participants with good sleeping habits had a 35% reduced risk of cardiovascular disease and a 34% reduced risk of both heart disease and stroke," Qi says. Researchers say those with the healthiest sleep patterns slept 7 to 8 hours a night, without insomnia, snoring or daytime drowsiness.

When the researchers looked at the combined effect of sleep habits and genetic susceptibility on cardiovascular disease, they found that participants with both a high genetic risk and a poor sleep pattern had a more than 2.5-fold greater risk of heart disease and a 1.5-fold greater risk of stroke compared to those with a low genetic risk and a healthy sleep pattern. This meant that there were 11 more cases of heart disease and five more cases of stroke per 1000 people a year among poor sleepers with a high genetic risk compared to good sleepers with a low genetic risk. However, a healthy sleep pattern compensated slightly for a high genetic risk, with just over a two-fold increased risk for these people.

A person with a high genetic risk but a healthy sleep pattern had a 2.1-fold greater risk of heart disease and a 1.3-fold greater risk of stroke compared to someone with a low genetic risk and a good sleep pattern. While someone with a low genetic risk, but an unhealthy sleep pattern had 1.7-fold greater risk of heart disease and a 1.6-fold greater risk of stroke.

"As with other findings from observational studies, our results indicate an association, not a causal relation," Qi says. "However, these findings may motivate other investigations and, at least, suggest that it is essential to consider overall sleep behaviors when considering a person's risk of heart disease or stroke."

https://www.sciencedaily.com/releases/2019/12/191218153412.htm

A new way to optimize sleep and light exposure can reduce jet lag and improve alertness

Wearable technology can be used to calculate optimal personalized sleep and light schedule

December 18, 2019

Science Daily/Rensselaer Polytechnic Institute

Researchers explain how they have developed and demonstrated a series of algorithms that can analyze biometric information recorded by a smart device and then recommend the best combination of sleep and light to help a person readjust their circadian rhythm.

Whether you're traveling for work or for fun, nothing ruins the start of a trip quite like jet lag. Engineers affiliated with the Lighting Enabled Systems & Applications (LESA) Center at Rensselaer Polytechnic Institute have developed a way to deliver personalized advice using smart wearable technology that would help travelers adjust more quickly.

In a series of articles, including one published today in PLOS ONE, the researchers explain how they have developed and demonstrated a series of algorithms that can analyze biometric information recorded by a smart device and then recommend the best combination of sleep and light to help a person readjust their circadian rhythm.

"Using these algorithms and a mathematical model of a person's circadian rhythm, we have the ability to compute the best light to adjust your circadian rhythm and foster your well-being. This opens the opportunity to create a smart and healthy environment," said Agung Julius, an associate professor of electrical, computer, and systems engineering at Rensselaer and one of the authors on this paper.

The same, he said, goes for determining the sleep -- both how much and when it should be received -- a person needs.

Circadian rhythms are master internal clocks that help regulate many of our physiological processes, including sleep, metabolism, hormone secretion, and even how our brain functions. Energy, alertness, and other biological processes can suffer when that rhythm doesn't align with the clock one is actually trying to follow.

The Department of Defense is funding this research because of the benefits the researchers' findings could bring to the alertness of service members.

"The circadian and sleep processes are also very tightly related to your mental state and how alert you are," Julius said. "If you try to do something in the wrong time of day, your alertness is not going to be as effective as if you do it in the right time of day as defined by your circadian clock."

Julius explained that a person's circadian rhythm variation is typically determined using information gathered from a blood or saliva test that measures levels of the hormone melatonin. The problem with that traditional approach is that obtaining the results takes time and doesn't allow for instant analysis.

The LESA team, which includes John Wen, head of the Department of Electrical, Computer, and Systems Engineering at Rensselaer and co-author on this paper, has been working on algorithms that process data -- like heart rate and body temperature -- that can be collected from wearable smart technology and converted into an estimate of a person's circadian rhythm variation.

"The question is whether that kind of data can give you as accurate an estimation as the clinical standard," Julius said.

What the team has found and demonstrated is that the estimates their algorithms generated are in line with clinical hormone measurement techniques. Julius said these findings are indicative that the team's approach works.

"This work is important, because it characterizes the fundamental processes the human body uses to synchronize circadian and sleep processes. By developing biosensing analytics to characterize circadian phase, it is now possible to optimize the efficient use of light with appropriate spectral properties to help optimize and maintain human health and performance," said Robert Karlicek, the director of the LESA Center. "This will be important to other work related to lighting and health in LESA's clinical research test beds at Thomas Jefferson University and the University of New Mexico."

https://www.sciencedaily.com/releases/2019/12/191218153325.htm

Blue light may not be as disruptive to our sleep patterns as originally thought

December 16, 2019

Science Daily/University of Manchester

Contrary to common belief, blue light may not be as disruptive to our sleep patterns as originally thought -- according to scientists. According to the team, using dim, cooler, lights in the evening and bright warmer lights in the day may be more beneficial to our health.

According to the team, using dim, cooler, lights in the evening and bright warmer lights in the day may be more beneficial to our health.

Twilight is both dimmer and bluer than daylight, they say, and the body clock uses both of those features to determine the appropriate times to be asleep and awake.

Current technologies designed to limit our evening exposure to blue light, for example by changing the screen colour on mobile devices, may therefore send us mixed messages, they argue.

This is because the small changes in brightness they produce are accompanied by colours that more resemble day.

The research, which was carried out on mice, used specially designed lighting that allowed the team to adjust colour without changing brightness.

That showed blue colours produced weaker effects on the mouse body clock than equally bright yellow colours.

The findings, say the team, have important implications for the design of lighting and visual displays intended to ensure healthy patterns of sleep and alertness.

The study is published in Current Biology and funded by the Biotechnology and Biological Sciences Research Council.

The body clock uses a specialised light sensitive protein in the eye to measure brightness, called melanopsin, which is better at detecting shorter wavelength photons.

This is why, say the team, researchers originally suggested blue light might have a stronger effect.

However, our perception of colour comes from the retinal cone cells and the new research shows that the blue colour signals they supply reduce the impact on light on the clock.

Dr Tim Brown, from The University of Manchester, said: "We show the common view that blue light has the strongest effect on the clock is misguided; in fact, the blue colours that are associated with twilight have a weaker effect than white or yellow light of equivalent brightness.

"There is lots of interest in altering the impact of light on the clock by adjusting the brightness signals detected by melanopsin but current approaches usually do this by changing the ratio of short and long wavelength light; this provides a small difference in brightness at the expense of perceptible changes in colour."

He added: "We argue that this is not the best approach, since the changes in colour may oppose any benefits obtained from reducing the brightness signals detected by melanopsin.

"Our findings suggest that using dim, cooler, lights in the evening and bright warmer lights in the day may be more beneficial.

"Research has already provided evidence that aligning our body clocks with our social and work schedules can be good for our health. Using colour appropriately could be a way to help us better achieve that."

https://www.sciencedaily.com/releases/2019/12/191216173654.htm

Have you found meaning in life? Answer determines health and well-being

Study examines meaning in life and relationship with physical, mental and cognitive functioning

December 10, 2019

Science Daily/University of California - San Diego

Over the last three decades, meaning in life has emerged as an important question in medical research, especially in the context of an aging population. A recent study by researchers at University of California San Diego School of Medicine found that the presence of and search for meaning in life are important for health and well-being, though the relationships differ in adults younger and older than age 60.

"Many think about the meaning and purpose in life from a philosophical perspective, but meaning in life is associated with better health, wellness and perhaps longevity," said senior author Dilip V. Jeste, MD, senior associate dean for the Center of Healthy Aging and Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine. "Those with meaning in life are happier and healthier than those without it."

The study, publishing online in the December 10, 2019 edition of the Journal of Clinical Psychiatry, found the presence of meaning in life is associated with better physical and mental well-being, while the search for meaning in life may be associated with worse mental well-being and cognitive functioning. "When you find more meaning in life, you become more contented, whereas if you don't have purpose in life and are searching for it unsuccessfully, you will feel much more stressed out," said Jeste.

The results also showed that the presence of meaning in life exhibited an inverted U-shaped relationship, while the search for meaning in life showed a U-shaped relationship with age. The researchers found that age 60 is when the presence of meaning in life peaks and the search for meaning of life was at its lowest point.

"When you are young, like in your twenties, you are unsure about your career, a life partner and who you are as a person. You are searching for meaning in life," said Jeste. "As you start to get into your thirties, forties and fifties, you have more established relationships, maybe you are married and have a family and you're settled in a career. The search decreases and the meaning in life increases."

"After age 60, things begin to change. People retire from their job and start to lose their identity. They start to develop health issues and some of their friends and family begin to pass away. They start searching for the meaning in life again because the meaning they once had has changed."

The three-year, cross-sectional study examined data from 1,042 adults, ages 21 to 100-plus, who were part of the Successful Aging Evaluation (SAGE) -- a multi-cohort study of senior residents living in San Diego County. The presence and search for meaning in life were assessed with interviews, including a meaning in life questionnaire where participants were asked to rate items, such as, "I am seeking a purpose or mission for my life" and "I have discovered a satisfying life purpose."

"The medical field is beginning to recognize that meaning in life is a clinically relevant and potentially modifiable factor, which can be targeted to enhance the well-being and functioning of patients," said Awais Aftab, MD, first author of the paper and a former fellow in the Department of Psychiatry at UC San Diego. "We anticipate that our findings will serve as building blocks for the development of new interventions for patients searching for purpose."

Jeste said next research steps include looking at other areas, such as wisdom, loneliness and compassion, and how these impact meaning in life. "We also want to examine if some biomarkers of stress and aging are associated with searching and finding the meaning in life. It's an exciting time in this field as we are seeking to discover evidence-based answers to some of life's most profound questions."

https://www.sciencedaily.com/releases/2019/12/191210131935.htm

Want to avoid the holiday blues? New report suggests skipping the sweet treats

December 12, 2019

Science Daily/University of Kansas

A new study from a team of clinical psychologists suggests eating added sugars -- common in so many holiday foods -- can trigger metabolic, inflammatory and neurobiological processes tied to depressive illness.

If you're prone to depression, this holiday season you might want to say "bah humbug" to offers of sugar plum pudding, caramel corn and chocolate babka.

A new study from a team of clinical psychologists at the University of Kansas suggests eating added sugars -- common in so many holiday foods -- can trigger metabolic, inflammatory and neurobiological processes tied to depressive illness. The work is published in the journal Medical Hypotheses.

Coupled with dwindling light in wintertime and corresponding changes in sleep patterns, high sugar consumption could result in a "perfect storm" that adversely affects mental health, according to the researchers.

"For many people, reduced sunlight exposure during the winter will throw off circadian rhythms, disrupting healthy sleep and pushing five to 10% of the population into a full-blown episode of clinical depression," said Stephen Ilardi, KU associate professor of clinical psychology.

Ilardi, who coauthored the study with KU graduate students Daniel Reis (lead author), Michael Namekata, Erik Wing and Carina Fowler (now of Duke University), said these symptoms of "winter-onset depression" could prompt people to consume more sweets.

"One common characteristic of winter-onset depression is craving sugar," he said. "So, we've got up to 30% of the population suffering from at least some symptoms of winter-onset depression, causing them to crave carbs -- and now they're constantly confronted with holiday sweets."

Ilardi said avoidance of added dietary sugar might be especially challenging because sugar offers an initial mood boost, leading some with depressive illness to seek its temporary emotional lift.

"When we consume sweets, they act like a drug," said the KU researcher, who also is author of "The Depression Cure" (First De Capo Press, 2009). "They have an immediate mood-elevating effect, but in high doses they can also have a paradoxical, pernicious longer-term consequence of making mood worse, reducing well-being, elevating inflammation and causing weight gain."

The investigators reached their conclusions by analyzing a wide range of research on the physiological and psychological effects of consuming added sugar, including the Women's Health Initiative Observational Study, the NIH-AARP Diet and Health Study, a study of Spanish university graduates, and studies of Australian and Chinese soda-drinkers.

Ilardi cautioned it might be appropriate to view added sugar, at high enough levels, as physically and psychologically harmful, akin to drinking a little too much liquor.

"We have pretty good evidence that one alcoholic drink a day is safe, and it might have beneficial effect for some people," he said. "Alcohol is basically pure calories, pure energy, non-nutritive and super toxic at high doses. Sugars are very similar. We're learning when it comes to depression, people who optimize their diet should provide all the nutrients the brain needs and mostly avoid these potential toxins."

The researchers found inflammation is the most important physiological effect of dietary sugar related to mental health and depressive disorder.

"A large subset of people with depression have high levels of systemic inflammation," said Ilardi. "When we think about inflammatory disease we think about things like diabetes and rheumatoid arthritis -- diseases with a high level of systemic inflammation. We don't normally think about depression being in that category, but it turns out that it really is -- not for everyone who's depressed, but for about half. We also know that inflammatory hormones can directly push the brain into a state of severe depression. So, an inflamed brain is typically a depressed brain. And added sugars have a pro-inflammatory effect on the body and brain."

Ilardi and his collaborators also identify sugar's impact on the microbiome as a potential contributor to depression.

"Our bodies host over 10 trillion microbes and many of them know how to hack into the brain," Ilardi said. "The symbiotic microbial species, the beneficial microbes, basically hack the brain to enhance our well-being. They want us to thrive so they can thrive. But there are also some opportunistic species that can be thought of as more purely parasitic -- they don't have our best interest in mind at all. Many of those parasitic microbes thrive on added sugars, and they can produce chemicals that push the brain in a state of anxiety and stress and depression. They're also highly inflammatory."

Ilardi recommended a minimally processed diet rich in plant-based foods and Omega-3 fatty acids for optimal psychological benefit. As for sugar, the KU researcher recommended caution -- not just during the holidays, but year-round.

"There's no one-size-fits-all approach to predicting exactly how any person's body will react to any given food at any given dose," Ilardi stated. "As a conservative guideline, based on our current state of knowledge, there could be some risk associated with high-dose sugar intake -- probably anything above the American Heart Association guideline, which is 25 grams of added sugars per day."

https://www.sciencedaily.com/releases/2019/12/191212122532.htm

Skipping one night of sleep may leave insomniacs twice as impaired

December 11, 2019

Science Daily/Washington State University

Poor daytime functioning is a frequent complaint among those suffering from insomnia. Previous studies have found that their daytime cognitive performance is not significantly degraded, seemingly suggesting it is a perceived issue that does not reflect a real impairment. A new study of individuals with sleep-onset insomnia revealed that the impairment may be real but hidden during the normal day -- yet exposed after pulling an all-nighter, which impacted them much more than age-matched control subjects.

A new study conducted by researchers at Washington State University shows that individuals with chronic sleep-onset insomnia who pulled an all-nighter performed up to twice as bad on a reaction time task as healthy normal sleepers. Their findings were published today in the online journal Nature and Science of Sleep.

Poor daytime functioning is a frequent complaint among those suffering from insomnia, said lead author Devon Hansen, an assistant professor in the Elson S. Floyd College of Medicine and a researcher in the WSU Sleep and Performance Research Center. However, previous studies have found that their daytime cognitive performance is not significantly degraded, seemingly suggesting that it is a perceived issue that does not reflect a real impairment. The WSU study of individuals with sleep-onset insomnia revealed that the impairment may in fact be real but hidden during the normal day -- yet exposed after pulling an all-nighter, which impacted them much more than age-matched control subjects.

The finding caught the WSU research team by surprise.

"There has been a theory about what perpetuates insomnia that focuses on hyperarousal, an activation in their system that keeps those with insomnia from being able to wind down when they go to bed," Hansen said. "We thought that this hyperarousal would protect them to some extent and had hypothesized that their performance after a night of total sleep deprivation would be better than normal healthy sleepers. Instead, we found the exact opposite."

Hansen, who in a previous career worked as a therapist in a sleep clinic, said the study adds credibility to insomnia patients' experiences. She also said it serves as a warning to poor sleepers that they should try to maintain a regular sleep schedule and avoid pushing their limits by staying up all night.

The research team studied 14 volunteer participants. Half of the group consisted of individuals who had chronic sleep-onset insomnia, the inability to fall asleep within 30 minutes for at least three nights a week for more than three months. The other half were healthy normal sleepers who served as controls. The two groups of participants were matched in age, with all participants aged between 22 and 40 and an average age of 29 for both groups.

Participants spent a total of five days and four nights in the sleep laboratory. They were allowed to sleep normally during the first two nights. They were kept awake the next night and following day -- totaling 38 hours of total sleep deprivation -- followed by a night of recovery sleep.

During their time awake, participants completed a series of performance tasks every three hours. This included a widely used alertness test known as the psychomotor vigilance test (PVT), which measures participants' response times to visual stimuli that appear on a screen at random intervals. The researchers analyzed PVT data for lapses of attention (i.e., slow reaction times) and false starts (i.e., responses that occur before the stimulus appears), comparing the findings between the two groups both before and during sleep deprivation.

Before sleep deprivation, the insomnia group's performance on the PVT looked very similar to that of the control group. However, as soon as sleep deprivation started the researchers began to see a dramatic increase in lapses of attention and false starts in the insomnia group. At one point during the night, their performance was twice as bad as that of the healthy normal sleepers.

"Our study suggests that even with a few hours of sleep deprivation -- which people routinely experience for work or family reasons -- those with sleep-onset insomnia may be much more impaired than those who normally sleep well at night," Hansen said. "This may increase their risk of errors and accidents whenever time-sensitive performance is required, such as while driving or when focused on a safety-critical task."

Hansen cautioned that since their study looked specifically at individuals with sleep-onset insomnia, their findings may not hold up in other insomnia subtypes, such as sleep-maintenance insomnia -- which is characterized by difficulty staying asleep -- and terminal insomnia -- which involves early-morning awakenings. She plans to repeat the study in those groups to find out.

https://www.sciencedaily.com/releases/2019/12/191211100243.htm

Take long naps? Sleep more than nine hours a night? Your stroke risk may be higher

Science Daily/December 11, 2019

American Academy of Neurology

People who take long naps during the day or sleep nine or more hours at night may have an increased risk of stroke, according to a study published in the December 11, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.

People who took a regular midday nap lasting more than 90 minutes were 25 percent more likely to later have a stroke than people who took a regular nap lasting from one to 30 minutes. People who took no naps or took naps lasting from 31 minutes to one hour were no more likely to have a stroke than people who took naps lasting from one to 30 minutes.

"More research is needed to understand how taking long naps and sleeping longer hours at night may be tied to an increased risk of stroke, but previous studies have shown that long nappers and sleepers have unfavorable changes in their cholesterol levels and increased waist circumferences, both of which are risk factors for stroke," said study author Xiaomin Zhang, MD, PhD, of Huazhong University of Science and Technology in Wuhan, China. "In addition, long napping and sleeping may suggest an overall inactive lifestyle, which is also related to increased risk of stroke."

The study involved 31,750 people in China with an average age of 62. The people did not have any history of stroke or other major health problems at the start of the study. They were followed for an average of six years. During that time, there were 1,557 stroke cases.

The people were asked questions about their sleep and napping habits. Midday napping is common in China, Zhang said. Eight percent of the people took naps lasting more than 90 minutes. And 24 percent said they slept nine or more hours per night.

The study found that people who sleep nine or more hours per night are 23 percent more likely to later have a stroke than people who sleep seven to less than eight hours per night. People who sleep less than seven hours per night or between eight and less than nine hours per night were no more likely to have a stroke than those who slept from seven to less than eight hours per night.

The results were all adjusted for other factors that could affect the risk of stroke. These include high blood pressure, diabetes and smoking.

People who were both long nappers and long sleepers were 85 percent more likely to later have a stroke than people who were moderate sleepers and nappers.

The researchers also asked people about how well they slept. People who said their sleep quality was poor were 29 percent more likely to later have a stroke than people who said their sleep quality was good.

Of the long nappers, 1 percent of cases per person-years later had a stroke, compared to 0.7 percent of cases per person-years of the moderate nappers. The numbers were the same for the long and moderate sleepers, with 1 percent of cases per person-years compared to 0.7 percent of cases per person-years having a stroke.

"These results highlight the importance of moderate napping and sleeping duration and maintaining good sleep quality, especially in middle-age and older adults," Zhang said.

Zhang noted that the study does not prove cause and effect between long napping and sleeping and stroke. It only shows an association.

Limitations of the study include that information on sleep and napping was taken from questionnaires, not from recording people's actual sleep and information was not collected on sleep disorders such as snoring and sleep apnea. Also, the study involved older, healthy Chinese adults, so the results may not apply to other groups.

The study was supported by the National Natural Science Foundation of China and the National Key Research and Development Program of China.

https://www.sciencedaily.com/releases/2019/12/191211171146.htm

Migraine headaches? Consider aspirin for treatment and prevention

December 3, 2019

Science Daily/Florida Atlantic University

Evidence from 13 randomized trials of the treatment of migraine in 4,222 patients and tens of thousands of patients in prevention of recurrent attacks supports the use of high dose aspirin from 900 to 1,300 milligrams to treat acute migraine as well as low dose daily aspirin from 81 to 325 milligrams to prevent recurrent attacks. Aspirin is available without a prescription, is inexpensive, and has a relatively favorable side-effect profile compared to alternative more expensive medications.

Migraine headache is the third most common disease in the world affecting about 1 in 7 people. More prevalent than diabetes, epilepsy and asthma combined, migraine headaches are among the most common and potentially debilitating disorders encountered by primary health care providers. Migraines also are associated with an increased risk of stroke.

There are effective prescription medications available to treat acute migraine headaches as well as to prevent recurrent attacks. Nonetheless, in the United States many patients are not adequately treated for reasons that include limited access to health care providers and lack of health insurance or high co-pays, which make expensive medications of proven benefit unaffordable. The rates of uninsured or underinsured individuals have been estimated to be 8.5 percent nationwide and 13 percent in Florida. Furthermore, for all patients, the prescription drugs may be poorly tolerated or contraindicated.

Researchers from Florida Atlantic University's Schmidt College of Medicine have proposed aspirin as a possible option for consideration by primary care providers who treat the majority of patients with migraine. Their review includes evidence from 13 randomized trials of the treatment of migraine in 4,222 patients and tens of thousands of patients in prevention of recurrent attacks.

Their findings, published in the American Journal of Medicine, suggest that high-dose aspirin, in doses from 900 to 1,300 milligrams given at the onset of symptoms, is an effective and safe treatment option for acute migraine headaches. In addition, some but not all randomized trials suggest the possibility that daily aspirin in doses from 81 to 325 milligrams may be an effective and safe treatment option for the prevention of recurrent migraine headaches.

"Our review supports the use of high dose aspirin to treat acute migraine as well as low dose daily aspirin to prevent recurrent attacks," said Charles H. Hennekens, M.D., Dr.PH, corresponding author, first Sir Richard Doll Professor and senior academic advisor in FAU's Schmidt College of Medicine. "Moreover, the relatively favorable side effect profile of aspirin and extremely low costs compared with other prescription drug therapies may provide additional clinical options for primary health care providers treating acute as well as recurrent migraine headaches."

Common symptoms of migraine include a headache that often begins as a dull pain and then grows into a throbbing pain, which can be incapacitating and often occurs with nausea and vomiting, and sensitivity to sound, light and smell. Migraines can last anywhere from four to 72 hours and may occur as many times as several times a week to only once a year.

"Migraine headaches are among the most common and potentially debilitating disorders encountered by primary health care providers," said Bianca Biglione, first author and a second-year medical student in FAU's Schmidt College of Medicine. "In fact, about 1 in 10 primary care patients present with headache and three out of four are migraines. Aspirin is readily available without a prescription, is inexpensive, and based on our review, was shown to be effective in many migraine patients when compared with alternative more expensive therapies."

Approximately 36 million Americans suffer from migraine headaches and the cause of this disabling disorder is not well understood. There is a higher prevalence in women (18 percent) than men (9 percent). In women, the prevalence is highest during childbearing age.

Approximately 90 percent of migraine sufferers report moderate to severe pain, with more than 50 percent reporting severe impairment or the need for bed rest as well as reduced work or school productivity.

https://www.sciencedaily.com/releases/2019/12/191203091010.htm

Feeling loved in everyday life linked with improved well-being

November 25, 2019

Science Daily/Penn State

Researchers find that people who experience higher 'felt love' -- brief experiences of love and connection in everyday life -- also have significantly higher levels of psychological well-being, which includes feelings of purpose and optimism, compared to those who had lower felt love scores.

Poets and songwriters may tend to focus their artistry on passion and romance, but it may be those unsung, brief feelings of love throughout the day that are connected with psychological well-being, according to a team of researchers led by two Penn State Institute for Computational and Data Sciences (ICDS) researchers. They added that the findings could one day lead to interventions aimed at boosting well-being.

In two studies, the researchers found that people who experienced higher "felt love" -- brief experiences of love and connection in everyday life -- also had significantly higher levels of psychological well-being, which includes feelings of purpose and optimism, compared to those who had lower felt love scores. They also found that people with higher felt love tended to have higher extraversion personality scores, while people with lower felt love scores were more likely to show signs of neuroticism.

"We took a very broad approach when we looked at love," said Zita Oravecz, assistant professor of human development and family studies and ICDS faculty co-hire. "Everyday felt love is conceptually much broader than romantic love. It's those micro-moments in your life when you experience resonance with someone. For example, if you're talking to a neighbor and they express concern for your well-being, then you might resonate with that and experience it as a feeling of love, and that might improve your well-being."

According to the researchers, the baseline of the subjects' felt love experiences, in general, rose throughout the study, suggesting that the nudges to recognize examples of love and connection during the study may also have gradually increased the subjects' overall sense of being loved. Stronger experiences of felt love, in turn, are associated with improvements in psychological well-being.

"It's something that we've seen in the literature on mindfulness, when people are reminded to focus attention on positive things, their overall awareness of those positive things begins to rise," said Oravecz. "Similarly, just by paying attention to those everyday moments of felt love, we may also increase our awareness of the overall positive aspects of love in our daily lives. This effect replicates in both studies, implying that raising awareness of felt love in day-to-day life may itself be an intervention that raises levels of felt love over a longer period of time."

The researchers, who report their findings in the current issue of Personality and Individual Differences, added that because the studies have only shown a correlation between felt love and well-being, more research would be needed to establish a causal relationship. If a firmer connection is established, the researchers said possible interventions could be designed, such as sending regular reminders to a person's smartphone to draw attention to the felt love that they may be experiencing in that moment to raise psychological well-being. Similar interventions have been designed for mindfulness and gratitude.

The team relied on smartphone technology to gather data from participants throughout their everyday lives. In the first study, they recruited 52 people of various ages. The second study consisted of 160 undergraduate students. Participants received six random prompts throughout the day over a four-week period to assess felt love and well-being, according to Timothy Brick, assistant professor of human development and family studies and ICDS co-hire. He added that sending these messages randomly throughout the day was critical to manage the possible effects of expectation bias.

"It's important from a research point-of-view," said Brick. "If the participants expect a call or a text at a certain time of day, they are no longer reacting to what's going on in their daily life, but are expecting the prompt and reacting to that expectation."

Gathering data multiple times throughout the day from more than 200 subjects over a month can produce a lot of data, said Brick. Also, these everyday experiences of love tend to fluctuate during the study, which can result in what the researchers termed "noisy" data.

"It's often very difficult to measure psychological quantities because we don't always have a great idea about what's going on in our own heads," said Brick.

Oravecz added, "But with the right statistical methods, we can start to get at questions about difficult constructs like love or compassion, and hopefully build interventions to promote them."

To analyze this large amount of noisy data, the researchers used nuanced statistical tools. According to Oravecz, the researchers specifically used a Bayesian latent stochastic differential equations model to cut through the noise in the data and identify processes happening underneath. This method is especially suited to help scientists investigate intricate social systems, which often involve relationships that generate complex, highly variable data, she said.

According to the researchers, this statistical method may be used more as social scientists begin to gather large amounts of real-world data from sensors on wearable devices. The researchers used computational resources of ICDS's advanced computer infrastructure for their analysis.

https://www.sciencedaily.com/releases/2019/11/191125121005.htm

Science underestimated dangerous effects of sleep deprivation

November 21, 2019

Science Daily/Michigan State University

One of the largest sleep studies dubunks theory that suggests attention is the only cognitive function affected by sleep deprivation.

Michigan State University's Sleep and Learning Lab has conducted one of the largest sleep studies to date, revealing that sleep deprivation affects us much more than prior theories have suggested.

Published in the Journal of Experimental Psychology: General, the research is not only one of the largest studies, but also the first to assess how sleep deprivation impacts placekeeping -- or, the ability to complete a series of steps without losing one's place, despite potential interruptions. This study builds on prior research from MSU's sleep scientists to quantify the effect lack of sleep has on a person's ability to follow a procedure and maintain attention.

"Our research showed that sleep deprivation doubles the odds of making placekeeping errors and triples the number of lapses in attention, which is startling," Fenn said. "Sleep-deprived individuals need to exercise caution in absolutely everything that they do, and simply can't trust that they won't make costly errors. Oftentimes -- like when behind the wheel of a car -- these errors can have tragic consequences."

By sharing their findings on the separate effects sleep deprivation has on cognitive function, Fenn -- and co-authors Michelle Stepan, MSU doctoral candidate and Erik Altmann, professor of psychology -- hope that people will acknowledge how significantly their abilities are hindered because of a lack of sleep.

"Our findings debunk a common theory that suggests that attention is the only cognitive function affected by sleep deprivation," Stepan said. "Some sleep-deprived people might be able to hold it together under routine tasks, like a doctor taking a patient's vitals. But our results suggest that completing an activity that requires following multiple steps, such as a doctor completing a medical procedure, is much riskier under conditions of sleep deprivation."

The researchers recruited 138 people to participate in the overnight sleep assessment; 77 stayed awake all night and 61 went home to sleep. All participants took two separate cognitive tasks in the evening: one that measured reaction time to a stimulus; the other measured a participant's ability to maintain their place in a series of steps without omitting or repeating a step -- even after sporadic interruptions. The participants then repeated both tasks in the morning to see how sleep-deprivation affected their performance.

"After being interrupted there was a 15% error rate in the evening and we saw that the error rate spiked to about 30% for the sleep-deprived group the following morning," Stepan said. "The rested participants' morning scores were similar to the night before.

"There are some tasks people can do on auto-pilot that may not be affected by a lack of sleep," Fenn said. "However, sleep deprivation causes widespread deficits across all facets of life."

https://www.sciencedaily.com/releases/2019/11/191121183923.htm

Dissecting connections between chronic stress, inflammation and depression

November 21, 2019

Science Daily/Medical College of Georgia at Augusta University

Chronic stress can inflame our brain, destroy the connections between our neurons and result in depression, scientists say.

Now they are working to better understand how the destructive cycle happens and how best to intervene.

Even powerful, prescription anti-inflammatory drugs that should help break the connectivity between chronic stress and inflammation don't help many patients with depression, says Dr. Anilkumar Pillai, neuroscientist in the Department of Psychiatry and Health Behavior at the Medical College of Georgia at Augusta University.

Two new grants totaling about $2.4 million from the National Institute of Mental Health are helping Pillai further explore his increasing evidence that the problem may start with the impact stress has on our bodies and the body's fundamental, frontline and nonspecific immune response called innate immunity.

The complement system, named because it was first found to help the immune system fight invaders, is part of this innate immune response, and Pillai has found elevated levels of C3 -- which he calls the hub of all complement activation pathways -- in both the brains of people with depression and animal models.

The complement system also has the important job during development of removing bad connections between neurons, and there is good evidence the same thing happens in a developed brain in problems like major depressive disorder and Alzheimer's, when losing these important connections, called synapses, is problematic rather than helpful.

"You have to have a functioning complement system during development," says Pillai. But he and his research colleagues have put together some of the first evidence that in depression, the complement also is active, causing inflammation and synaptic loss in the prefrontal cortex, an area of the brain important to working memory, personality and executive function. "Under chronic stress you are losing your synapses," he says.

C3 is known to play a key role in inflammation in the brain, and microglia, the resident immune cells in the brain, are known to use C3 during brain development to eliminate synapses.

"We expect that chronic stress increases C3," Pillai says as he continues to put the complex puzzle together. Now he and his colleagues want to know where the high C3 is coming from, whether it's the immune cells called monocytes, circulating in the body in response to stress, or the microglia. It may turn out that microglia are the direct source but changes chronic stress makes to the body are the instigators in this vicious, destructive circle.

Studies have shown that chronic stress is a major factor in depression, says Pillai. In fact, people with physical health problems like cancer or heart disease where inflammation also is a major factor, often develop depression, and at least one reason is that high levels of inflammation that are impacting the body also may be affecting the brain, Pillai says.

"They are basically bidirectionally fueling each other," he says. "It's not everyone; it's a subset of individuals with these conditions."

In a paper published in March 2018 in the journal Brain, Behavior and Immunity, Pillai's lab reported significant increases in C3 expression in the prefrontal cortex of depressed individuals who had committed suicide. They also found increased C3 expression in the prefrontal cortex of mice in response to chronic stress but that mice lacking C3 did not get depressive-like behavior in response. In fact, just causing overexpression of C3 in certain areas of the prefrontal cortex caused depression-like behavior, even without the stress.

Their early findings indicate that when NF-kappa B, a transcription factor that regulates both innate and adaptive immunity and is implicated as a key regulator of inflammation in depression, is inhibited, stress-induced increases of C3 in a mouse's prefrontal cortex are reduced. Depleting microglia appears to do essentially the same thing.

This time they are bringing down both levels of C3 and its receptors in microglia as well as peripheral monocytes to further parse the role of the complement system and the source of C3.

Pillai's collaborators include Dr. Stephen Tomlinson, an expert in the complement system and central nervous system inflammation, who is interim chair of the Department of Microbiology and Immunology at the Medical University of South Carolina College of Medicine. One of the many things Tomlinson's lab does is generate complement inhibitors, including drugs that block C3's activation through different pathways, which Pillai is using for these studies and will give additional insight into how activation is happening.

If the complement inhibitors work in animal models, some iteration of these research drugs may also one day help people with depression based on their level of inflammation, Pillai says.

The second NIMH grant is enabling additional studies of how microglia get activated and Pillai suspects it's interferon alpha circulating in the body that get the microglia and C3 going.

Interferon alpha is a drug used to treat maladies like cancer and hepatitis, but it's also a natural protein that stimulates the immune system to kill things like melanoma and viral infections.

High levels of interferon alpha have been found in the blood of people with depression, and long-term interferon alpha treatment for problems like cancer or chronic hepatitis B can trigger depression or other mental health problems. Even healthy lab animals injected with interferon alpha exhibit depressive symptoms.

The MCG scientists have seen treatment with an interferon receptor antibody reduce social-deficient and depression-like behavior in mice exposed to chronic stress.

The new studies will enable further exploration of their hypothesis that increased interferon alpha activation in the body by stress activates microglia and their C3 production in the brain, which leads to loss of neuron connections and depressed behavior. These studies include use of an interferon receptor antibody to block its action. The fact that interferon alpha goes up in the face of chronic stress is another indicator the body doesn't like stress, Pillai notes.

Immune cells in the brain are typically not as reactive as those circulating in the rest of the body, but stress definitely gets their attention, Pillai says. The major immune function of C3 is mediated through microglia in the brain and monocytes throughout the body, another reason he wants to knock out C3 in both cell types to see the effect.

Current anti-inflammatory therapies have focused on inflammation generated by adaptive immunity, an immune response specific to some invader like a bacterium, rather than less specific innate immunity. But innate immunity is becoming a target in other conditions like cancer and cardiovascular disease, and its role in both inflammation and synapse regulation peaked Pillai's interest in its role in depression.

https://www.sciencedaily.com/releases/2019/11/191121163326.htm

A new link between migraines, opioid overuse may be key to treating pain

November 20, 2019

Science Daily/University of Illinois at Chicago

Researchers have discovered that a peptide links together migraine pain and pain induced by opioid overuse.

About 10% of the world population suffers from migraine headaches, according to the National Institute of Neurological Disorders and Stroke. To alleviate migraine pain, people are commonly treated with opioids. But, while opioid treatment can provide temporary pain relief for episodic migraines, prolonged use can increase the frequency and severity of painful migraines.

Researchers have tried to understand how opioids cause this paradoxical increase in pain for a decade, but the mechanism remained elusive -- until now.

Researchers at the University of Illinois at Chicago and colleagues discovered that a peptide -- small chains of amino acids that can regulate many behaviors and brain signaling pathways -- links together migraine pain and pain induced by opioid overuse.

Their findings are published in the journal Molecular and Cellular Proteomics.

Amynah Pradhan, senior author and UIC associate professor of psychiatry at the College of Medicine said, "Endorphin is an example of a peptide that signals the brain to give a 'runner's high.' However, not all peptides signal for pleasant outcomes. Pituitary adenylate cyclase-activating peptide, or PACAP, is a peptide that can induce migraines in migraine-prone individuals. Because the overuse of opioids can lead to worse migraines, we wanted to determine whether opioid-induced pain changed the amounts of peptides in the brain and understand if pain from migraines and opioid overuse shared any peptides in common."

To study these peptides, Pradhan and her colleagues, including researchers at the University of Illinois at Urbana-Champaign, developed two animal models: migraine pain and opioid overuse pain, both in mouse models. Using mass spectrometry to identify peptides and their quantities in the animal samples, they found only a few peptides were altered in both models. PACAP was one of them.

"We were amazed to find PACAP in both models," Pradhan said. "This study validates prior work on PACAP's role in migraine pain and, more importantly, is the first to identify PACAP as a factor in opioid-induced pain. It is also significant that the PACAP increase was seen in major pain processing sites of the brain, in both models.

"These findings provide strong evidence that PACAP is involved in both migraine and opioid-overuse pain. We finally understand a mechanism through which opioids may exacerbate migraines -- through PACAP."

Pradhan said these findings can inform the development of real-world treatments.

"Companies are developing therapies for migraine pain right now," Pradhan said. "There are clinical trials underway to test antibodies targeting PACAP and a PACAP-binding receptor. Based on our data, these therapies may be extremely effective for people that have used opioids to treat their migraines."

This research may benefit people suffering from non-migraine pain as well, she said, as people with chronic pain also experience opioid-induced pain after overuse.

https://www.sciencedaily.com/releases/2019/11/191120131307.htm

Earthquake-like brain-wave bursts found to be essential for healthy sleep

Findings link healthy sleep to brain-wave bursts that mathematically mimic earthquakes

November 14, 2019

Science Daily/PLOS

New research in rats shows that cortical arousals and brief awakenings during sleep exhibit non-equilibrium dynamics and complex organization across time scales necessary for spontaneous sleep-stage transitions and for maintaining healthy sleep. Prof. Plamen Ch. Ivanov of Boston University and colleagues present these findings in PLOS Computational Biology.

Sleep is traditionally considered to be a homeostatic process that resists deviation from equilibrium. In that regard, brief episodes of waking are viewed as perturbations that lead to sleep fragmentation and related sleep disorders. While addressing aspects of sleep regulation related to consolidated sleep and wake and the sleep-wake cycle, the homeostatic paradigm does not account for the dozens of abrupt sleep-stage transitions and micro-states within sleep stages throughout the night. Ivanov and colleagues hypothesized that, while sleep is indeed homeostatic at time scales of hours and days, non-equilibrium dynamics and criticality underlie sleep micro-architecture at shorter time scales.

To test this hypothesis, the researchers collected electroencephalogram (EEG) recordings of brain activity over multiple days in normal rats and in rats with injuries to the parafacial zone, a brain region that helps regulate sleep. They analyzed the bursting dynamics of brain activity patterns known as theta waves and delta waves, which are seen in both sleeping rats and humans.

Their empirical findings and modeling indicate that arousals from sleep are a manifestation of an intrinsic non-equilibrium sleep regulatory mechanism related to self-organization of neuronal assemblies. This mechanism acts at time scales of seconds and minutes and stays on track via continuous bursts in brain wave rhythms.

The study also suggests that maintaining a non-equilibrium critical state is essential for the sleep-regulation system's flexibility to spontaneously activate multiple transitions between different sleep stages and between sleep and brief wakefulness throughout the sleep period. Such critical state is also necessary for the complex sleep micro-architecture that is increasingly recognized to be characteristic of healthy sleep. The observed critical behavior in sleep draws parallels to other non-equilibrium systems at criticality, such as earthquakes.

"Paradoxically, we find that the 'resting' state of healthy sleep is maintained through bursts in cortical rhythm activity that obey similar temporal organization, statistics, and mathematical laws as earthquakes," Ivanov says. "Our findings serve as building blocks to better understand sleep, and could help improve detection and treatment of sleep disorders."

https://www.sciencedaily.com/releases/2019/11/191114141237.htm

Gut instincts: Researchers discover first clues on how gut health influences brain health

October 23, 2019

Science Daily/Weill Cornell Medicine

New cellular and molecular processes underlying communication between gut microbes and brain cells have been described for the first time by scientists at Weill Cornell Medicine and Cornell's Ithaca campus.

Over the last two decades, scientists have observed a clear link between autoimmune disorders and a variety of psychiatric conditions. For example, people with autoimmune disorders such as inflammatory bowel disease (IBD), psoriasis and multiple sclerosis may also have depleted gut microbiota and experience anxiety, depression and mood disorders. Genetic risks for autoimmune disorders and psychiatric disorders also appear to be closely related. But precisely how gut health affects brain health has been unknown.

"Our study provides new insight into the mechanisms of how the gut and brain communicate at the molecular level," said co-senior author Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease, director of the Friedman Center for Nutrition and Inflammation and the Michael Kors Professor of Immunology at Weill Cornell Medicine. "No one yet has understood how IBD and other chronic gastrointestinal conditions influence behavior and mental health. Our study is the beginning of a new way to understand the whole picture."

For the study, published Oct. 23 in Nature, the researchers used mouse models to learn about the changes that occur in brain cells when gut microbiota are depleted. First author Dr. Coco Chu, a postdoctoral associate in the Jill Roberts Institute for Research in Inflammatory Bowel Disease, led a multidisciplinary team of investigators from several departments across Weill Cornell Medicine, Cornell's Ithaca campus, Boyce Thompson Institute, Broad Institute at MIT and Harvard, and Northwell Health with specialized expertise in behavior, advanced gene sequencing techniques and the analysis of small molecules within cells.

Mice treated with antibiotics to reduce their microbial populations, or that were bred to be germ-free, showed a significantly reduced ability to learn that a threatening danger was no longer present. To understand the molecular basis of this result, the scientists sequenced RNA in immune cells called microglia that reside in the brain and discovered that altered gene expression in these cells plays a role in remodeling how brain cells connect during learning processes. These changes were not found in microglia of healthy mice.

"Changes in gene expression in microglia could disrupt the pruning of synapses, the connections between brain cells, interfering with the normal formation of new connections that should occur through learning," said co-principal investigator Dr. Conor Liston, an associate professor of neuroscience in the Feil Family Brain & Mind Research Institute and an associate professor of psychiatry at Weill Cornell Medicine.

The team also looked into chemical changes in the brain of germ-free mice and found that concentrations of several metabolites associated with human neuropsychiatric disorders such as schizophrenia and autism were changed. "Brain chemistry essentially determines how we feel and respond to our environment, and evidence is building that chemicals derived from gut microbes play a major role," said Dr. Frank Schroeder, a professor at the Boyce Thompson Institute and in the Chemistry and Chemical Biology Department at Cornell Ithaca.

Next, the researchers tried to reverse the learning problems in the mice by restoring their gut microbiota at various ages from birth. "We were surprised that we could rescue learning deficits in germ-free mice, but only if we intervened right after birth, suggesting that gut microbiota signals are required very early in life," said Dr. Liston. "This was an interesting finding, given that many psychiatric conditions that are associated with autoimmune disease are associated with problems during early brain development."

"The gut-brain axis impacts every single human being, every day of their lives," said Dr. Artis. "We are beginning to understand more about how the gut influences diseases as diverse as autism, Parkinson's disease, post-traumatic stress disorder and depression. Our study provides a new piece of understanding of how the mechanisms operate."

"We don't know yet, but down the road, there is a potential for identifying promising targets that might be used as treatments for humans in the future," Dr. Liston said. "That's something we will need to test going forward."

https://www.sciencedaily.com/releases/2019/10/191023172106.htm

In Alzheimer's research, scientists reveal brain rhythm role

October 23, 2019

Science Daily/Picower Institute at MIT

In the years since her lab discovered that exposing Alzheimer's disease model mice to light flickering at the frequency of a key brain rhythm could stem the disorder's pathology, MIT neuroscientist Li-Huei Tsai and her team at The Picower Institute for Learning and Memory have been working to understand what the phenomenon may mean both for fighting the disease and understanding of how the brain works.

Two papers earlier this year in Cell and in Neuron replicated and substantially extended the initial findings reported in Nature in 2016 and clinical trials with human volunteers recently began. In a special lecture at the Society for Neuroscience Annual Meeting in Chicago Oct. 22, Tsai will share the latest research updates on what she's found -- and the new questions she is asking -- about using light and sound to strengthen the brain' s 40Hz "gamma" rhythm, a technique she calls "GENUS," for Gamma Entrainment Using Sensory stimuli.

"We are eager to learn as much as we can about GENUS for two main reasons," said Tsai, Picower Professor of Neuroscience in the Department of Brain and Cognitive Sciences and a founder of MIT's Aging Brain Initiative. "We hope our findings in mice will translate to helping people with Alzheimer's disease, though it's certainly too soon to tell and many things that have worked in mice have not worked in people. But there also may be exciting implications for fundamental neuroscience in understanding why stimulating a specific rhythm via light or sound can cause profound changes in multiple types of cells in the brain."

Gamma and Alzheimer's disease

In 2016, Tsai and colleagues showed that Alzheimer's disease model mice exposed to a light flickering at 40 Hz for an hour a day for a week had significantly less buildup of amyloid and tau proteins in the visual cortex, the brain region that processes sight, than experimental control mice did. Amyloid plaques and tangles of phosphorylated tau are both considered telltale hallmarks of Alzheimer's disease.

But the study raised new questions: Could GENUS prevent memory loss? Could it prevent the loss of neurons? Does it reach other areas of the brain? And could other senses be stimulated for beneficial effect?

The new studies addressed those questions. In March, the team reported that sound stimulation reduced amyloid and tau not only in the auditory cortex, but also in the hippocampus, a crucial region for learning and memory. GENUS-exposed mice also performed significantly better on memory tests than unstimulated controls. Simultaneous light and sound, meanwhile, reduced amyloid across the cortex, including the prefrontal cortex, a locus of cognition.

In May, another study reported similar advances from exposing Alzheimer's model mice to light for 3 or 6 weeks. Coordinated increases in gamma rhythm power were evident across the brains of GENUS-exposed mice. Memory improved compared to controls. More neurons survived and they maintained more circuit connections, called synapses. In her talk, Tsai will share data showing that longer-term GENUS light exposure also reduced amyloid and tau across the cortex.

Encouraged by the results, the lab has begun human trials. At SfN Tsai will present some initial data, indicating that GENUS safely increases gamma rhythm power and synchrony across the brain in healthy people.

Gamma "signatures" in the brain

Tsai's team has also been working to understand the mechanisms underlying the changes they see. The research has revealed that brain rhythms appear to exert a great deal of influence over the activity of multiple cell types in the brain.

Neuroscientists have known about rhythms for more than a century, but they have only recently begun to acknowledge that they might affect how the brain works. Gamma is associated with brain functions like sensory processing, working memory and spatial navigation, but scientists have long debated whether they are consequential or mere byproducts.

But Tsai will describe how her studies show that increasing gamma power and synchrony with sensory stimulation causes changes in neurons, brain immune cells called microglia, and the brain's vasculature. These changes may be "signatures" of gamma's significance, she says.

Increasing gamma power causes neurons to reduce processing of amyloid precursor protein and changes endosomal physiology as well, the team has found. In Alzheimer's model mice, neuronal gene expression related to synaptic function and biochemical transport within cells is reduced, but with GENUS exposure, gene expression related to those functions improves.

Microglia similarly experience major changes after GENUS exposure, all three studies have found. Gene expression becomes less inflammatory and more consistent with capturing and disposing of amyloid. Indeed, they hunt amyloid more effectively, the data show, and they secrete less of an inflammatory marker.

The March study with audio stimulation showed that amid GENUS exposure, blood vessels in the brain expand and more amyloid co-locates with a protein that draws amyloid to the vessels. The results suggest increased gamma power may help drive a mechanism for clearing amyloid out of the brain.

In several new experiments, Tsai says, the lab is continuing to study these underlying mechanistic changes. Related conference posters from her lab at the conference describe some of that work. The results of these new experiments may both help improve the possibility of translating GENUS for clinical use and further demonstrate the importance of rhythms in affecting brain function.

https://www.sciencedaily.com/releases/2019/10/191023093435.htm

Coping with Chronic Pain

Contributed by Jackie Waters

Living with chronic pain can drain you physically and emotionally. It’s normal to experience frustration when you’re unable to do the things you used to do. Aching muscles, sore joints, and fatigue are just a few of the symptoms chronic pain sufferers deal with on a daily basis. Whether you have fibromyalgia, osteoarthritis, or any other disease that causes pain, you know that such a condition transforms your life into a day-to-day battle. If you’ve recently been diagnosed with a chronic pain condition, read these tips to help you cope.

What Is Chronic Pain?

 Chronic pain is any pain that lasts more than six months. People can experience chronic pain for a number of reasons. It may be triggered by an injury or even a sickness. Often, there is no apparent cause for the pain. In the past, doctors thought pain was always the result of a disease or undiagnosed injury. As a result, doctors concentrated on treating the cause of the pain. They believed curing the cause would automatically eliminate the problem. If the patient wasn’t cured, doctors sometimes told patients that they were imagining their pain. Fortunately, today’s medical professionals realize that chronic pain is a disease and not some phantom pain inside a patient’s head.

Over-the-Counter and Prescription Painkillers

 In the past, traditional methods of treating chronic pain typically included over-the-counter and prescription painkillers. But the negatives far outweigh the positives. Using prescription painkillers can lead to liver failure and stomach ulcers. And it’s easy to become addicted to painkillers as well. Doctors now recognize that alternative treatments help reduce the symptoms associated with chronic pain. Even better, these alternative treatments don’t lead to addiction or other negative effects.

Give Your Body a Rest at Home

 It’s okay to take breaks to help relieve chronic pain. While you rest, let others help you get things done. Ask a friend or family member to run an errand for you. Another option to consider is calling a professional on occasion to take care of a home project, like doing yard work or cleaning the house. You can find a service within your budget by searching online. If you absolutely need to do your own cleaning, look for a vacuum that’s lightweight and easily maneuvered so you don’t strain yourself.

Exercise

 If you want to treat chronic pain using natural methods, incorporate exercise into your daily life. When you are physically active, the body releases natural hormones called endorphins that work as natural painkillers. Endorphins affect brain receptors, changing the way we perceive pain.

Before you begin an exercise regimen, discuss your plans with your physician. As long as your doctor says it’s okay, start a gradual exercise routine. Do easy stretches each day. If you find your joints are sore and tight, try taking a warm bath or shower before beginning your workout. Yoga, tai chi and Pilates are all gentle forms of exercise that help some chronic pain sufferers. And, of course, you can’t go wrong with good, old-fashioned walking!

Combine a Balanced Diet with Natural Supplements

 Incorporating more vegetables and whole, clean foods into your diet makes you healthier. A healthy diet can help reduce inflammation in your body, which is linked to chronic pain. Additionally, probiotic foods and supplements can help your body and mind become healthier by boosting the immune system, aiding in digestion, and increasing emotional health. Probiotics contain good strains of microbes that work in your gut, and since around 95 percent of all your microbes are in your gut, it’s especially important to take care of it. 

Acupuncture and Other Natural Therapies

Some people with chronic pain experience relief through acupuncture. It’s an ancient Chinese healing method where tiny, thin needles are inserted into specific parts of the body to relieve pain and stimulate healing. Other natural therapies may include massage or relaxation therapy. Some pain sufferers benefit from guided imagery, when a trained professional teaches you to focus your mind on specific images so you’re not concentrating on the pain you feel.

Just because you’ve recently been diagnosed with a chronic pain condition doesn’t mean you need to give up on an active lifestyle. Talk with your physician and devise a strategy to combat your chronic pain. As you incorporate lifestyle changes and investigate various therapies and treatments, you just might find the right combination that will help you alleviate your pain triggers and place you on the road to a happier, pain-free life.