New research identifies cells linking chronic psychological stress to inflammatory bowel disease

June 8, 2023

Science Daily/University of Pennsylvania School of Medicine

For the first time, cells involved with the communication between stress responses in the brain and inflammation in the gastrointestinal (GI) tract have been identified in animal models, according to findings from the Perelman School of Medicine at the University of Pennsylvania, published recently in Cell. Glial cells, which support neurons, communicate stress signals from the central nervous system (CNS) to the semi-autonomous nervous system within the gastrointestinal (GI) tract, called the enteric nervous system (ENS). These psychological stress signals can cause inflammation and exacerbate symptoms of inflammatory bowel disease (IBD).

An estimated 1.6 million Americans currently have IBD, which refers to two conditions -- Crohn's disease and ulcerative colitis -- characterized by inflammation of the GI tract, and can cause symptoms like persistent diarrhea, abdominal pain, and bloody stools. Prolonged inflammation can also lead to permanent damage to the GI tract. Current treatments consist of anti-inflammatory drugs, immune suppressants, dietary changes, and steroids.

"Clinicians have long observed that chronic stress can worsen IBD symptoms, but until now, no biological connection has been identified to explain how the digestive system knows when someone is stressed," said senior author Christoph Thaiss, PhD, an assistant professor of Microbiology.

In the study, researchers found that, like humans, mice with IBD developed severe symptoms when stressed. They traced the initial stress response signals to the adrenal cortex, which releases glucocorticoids -- steroid hormones that activate the physiological responses to stress throughout the body. The researchers found that neurons and glia in the ENS responded to chronically elevated glucocorticoid levels, suggesting that they are the link between stress perception by the brain and intestinal inflammation.

While glucocorticoids typically have an anti-inflammatory effect in the body, the researchers found that when glia in the ENS were exposed to the steroid hormones for a prolonged period, such as during chronic stress, they attract white blood cells to the GI tract that increase inflammation. The researchers also found that when exposed to chronic stress, the neurons in the ENS in the GI tract stop functioning as they normally do, which can lead to impaired bowel movements and exacerbated IBD symptoms.

Thaiss and collaborators verified the connection between psychological stress and IBD symptoms in humans using the UK Biobank and a patient cohort from the IBD Immunology Initiative at Penn Medicine. They found that the in patients with an IBD diagnosis, the level of reported stress correlated with an increased severity of IBD symptoms.

"This finding highlights the importance of psychological evaluations in patients being treated for IBD, as well as to inform treatment protocols," said Maayan Levy, PhD, an assistant professor of Microbiology and co-senior author of the study. "One of the most common treatments for IBD flare-ups is steroids, and our research indicates that in patients with IBD who experience chronic stress, the efficiency of this treatment could be impaired."

Researchers underscore the opportunity for more research into the biology of enteric glial cells, and the role they play in many regulatory systems within the body, including the communication between the nervous system and the immune system.

https://www.sciencedaily.com/releases/2023/06/230608195659.htm

Colorful fresh foods improve athletes' vision

Visual range is a critical asset for top athletes in almost any sport

June 8, 2023

Science Daily/University of Georgia

Nutrition is an important part of any top athlete's training program. And now, a new study by researchers from the University of Georgia proposes that supplementing the diet of athletes with colorful fruits and vegetables could improve their visual range.

The paper, which was published in Exercise and Sport Sciences Reviews, examines how a group of plant compounds that build up in the retina, known as macular pigments, work to improve eye health and functional vision.

Previous studies done by UGA researchers Billy R. Hammond and Lisa Renzi-Hammond have shown that eating foods like dark leafy greens or yellow and orange vegetables, which contain high levels of the plant compounds lutein and zeaxanthin, improves eye and brain health.

"A lot of the research into macular lutein and zeaxanthin has focused on health benefits, but from a functional perspective, higher concentrations of these plant pigments improve many aspects of visual and cognitive ability. In this paper, we discuss their ability to improve vision in the far distance or visual range," said lead author Jack Harth, a doctoral candidate in UGA's College of Public Health.

Visual range, or how well a person can see a target clearly over distance, is a critical asset for top athletes in almost any sport.

The reason why objects get harder to see and appear fuzzier the farther they are from our eyes is thanks in part to the effects of blue light.

"From a center fielder's perspective, if that ball's coming up in the air, it will be seen against a background of bright blue sky, or against a gray background if it's a cloudy day. Either way, the target is obscured by atmospheric interference coming into that path of the light," said Harth.

Many athletes already take measures to reduce the impact of blue light through eye black or blue blocker sunglasses, but eating more foods rich in lutein and zeaxanthin can improve the eye's natural ability to handle blue light exposure, said Harth.

When a person absorbs lutein and zeaxanthin, the compounds collect as yellow pigments in the retina and act as a filter to prevent blue light from entering the eye.

Previous work had been done testing the visual range ability of pilots in the 1980s, and Hammond and Renzi-Hammond have done more recent studies on how macular pigment density, or how much yellow pigment is built up in the retina, is linked to a number of measures of eye health and functional vision tests.

"In a long series of studies, we have shown that increasing amounts of lutein and zeaxanthin in the retina and brain decrease glare disability and discomfort and improve chromatic contrast and visual-motor reaction time, and supplementing these compounds facilitates executive functions like problem-solving and memory. All of these tasks are particularly important for athletes," said corresponding author Billy R. Hammond, a professor of psychology in the Behavior and Brain Sciences Program at UGA's Franklin College of Arts and Sciences.

This paper, Harth said, brings the research on these links between macular pigment and functional vision up to date and asks what the evidence suggests about optimizing athletic performance.

"We're at a point where we can say we've seen visual range differences in pilots that match the differences found in modeling, and now, we've also seen it in laboratory tests, and a future goal would be to actually bring people outside and to measure their ability to see contrast over distance through real blue haze and in outdoor environments," said Harth.

But before you start chowing down on kale in the hopes of improving your game, he cautions that everybody is different. That could mean the way our bodies absorb and use lutein and zeaxanthin varies, and it could take a while before you notice any improvements, if at all.

Still, the evidence of the overall health benefits of consuming more lutein and zeaxanthin are reason enough to add more color to your diet, say the authors.

"We have data from modeling and empirical studies showing that higher macular pigment in your retina will improve your ability to see over distance. The application for athletes is clear," said Harth.

https://www.sciencedaily.com/releases/2023/06/230608120930.htm

How chronic stress drives the brain to crave comfort food

June 8, 2023

Science Daily/Garvan Institute of Medical Research

Stress can override natural satiety cues to drive more food intake and boost cravings for sweets.

When you're stressed, a high-calorie snack may seem like a comforting go-to. But this combination has an unhealthy downside. According to Sydney scientists, stress combined with calorie-dense 'comfort' food creates changes in the brain that drive more eating, boost cravings for sweet, highly palatable food and lead to excess weight gain.

A team from the Garvan Institute of Medical Research found that stress overrode the brain's natural response to satiety, leading to non-stop reward signals that promote eating more highly palatable food. This occurred in a part of the brain called the lateral habenula, which when activated usually dampens these reward signals.

"Our findings reveal stress can override a natural brain response that diminishes the pleasure gained from eating -- meaning the brain is continuously rewarded to eat," says Professor Herzog, senior author of the study and Visiting Scientist at the Garvan Institute.

"We showed that chronic stress, combined with a high-calorie diet, can drive more and more food intake as well as a preference for sweet, highly palatable food, thereby promoting weight gain and obesity. This research highlights how crucial a healthy diet is during times of stress."

The research was published in the journal Neuron.

From stressed brain to weight gain

While some people eat less during times of stress, most will eat more than usual and choose calorie-rich options high in sugar and fat.

To understand what drives these eating habits, the team investigated in mouse models how different areas in the brain responded to chronic stress under various diets.

"We discovered that an area known as the lateral habenula, which is normally involved in switching off the brain's reward response, was active in mice on a short-term, high-fat diet to protect the animal from overeating. However, when mice were chronically stressed, this part of the brain remained silent -- allowing the reward signals to stay active and encourage feeding for pleasure, no longer responding to satiety regulatory signals," explains first author Dr Kenny Chi Kin Ip from the Garvan Institute.

"We found that stressed mice on a high-fat diet gained twice as much weight as mice on the same diet that were not stressed."

The researchers discovered that at the centre of the weight gain was the molecule NPY, which the brain produces naturally in response to stress. When the researchers blocked NPY from activating brain cells in the lateral habenula in stressed mice on a high-fat diet, the mice consumed less comfort food, resulting in less weight gain.

Driving comfort eating

The researchers next performed a 'sucralose preference test' -- allowing mice to choose to drink either water or water that had been artificially sweetened.

"Stressed mice on a high-fat diet consumed three times more sucralose than mice that were on a high-fat diet alone, suggesting that stress not only activates more reward when eating but specifically drives a craving for sweet, palatable food," says Professor Herzog.

"Crucially, we did not see this preference for sweetened water in stressed mice that were on a regular diet."

Stress overrides healthy energy balance

"In stressful situations it's easy to use a lot of energy and the feeling of reward can calm you down -- this is when a boost of energy through food is useful. But when experienced over long periods of time, stress appears to change the equation, driving eating that is bad for the body long term," says Professor Herzog.

The researchers say their findings identify stress as a critical regulator of eating habits that can override the brain's natural ability to balance energy needs.

"This research emphasises just how much stress can compromise a healthy energy metabolism," says Professor Herzog. "It's a reminder to avoid a stressful lifestyle, and crucially -- if you are dealing with long-term stress -- try to eat a healthy diet and lock away the junk food."

https://www.sciencedaily.com/releases/2023/06/230608120905.htm

Life before air conditioning: Curly hair kept early humans cool

Tightly curled scalp hair protected early humans from the sun's radiative heat, allowing their brains to grow to sizes comparable to those of modern humans.

June 7, 2023

Science Daily/Penn State

Curly hair does more than simply look good -- it may explain how early humans stayed cool while conserving water, according to researchers who studied the role human hair textures play in regulating body temperature. The findings can shed light on an evolutionary adaptation that enabled the human brain to grow to modern-day sizes.

"Humans evolved in equatorial Africa, where the sun is overhead for much of the day, year in and year out," said Nina Jablonski, Evan Pugh University Professor of Anthropology at Penn State. "Here the scalp and top of the head receive far more constant levels of intense solar radiation as heat. We wanted to understand how that affected the evolution of our hair. We found that tightly curled hair allowed humans to stay cool and actually conserve water."

The researchers used a thermal manikin -- a human-shaped model that uses electric power to simulate body heat and allows scientists to study heat transfer between human skin and the environment -- and human-hair wigs to examine how diverse hair textures affect heat gain from solar radiation. The scientists programmed the manikin to maintain a constant surface temperature of 95 degrees Fahrenheit (35 degrees Celsius), similar to the average surface temperature of skin, and set it in a climate-controlled wind tunnel.

The team took base measurements of body heat loss by monitoring the amount of electricity required by the manikin to maintain a constant temperature. Then they shined lamps on the manikin's head to mimic solar radiation under four scalp hair conditions -- none, straight, moderately curled and tightly curled.

The scientists calculated the difference in total heat loss between the lamp measurements and the base measurements to determine the influx of solar radiation to the head, explained George Havenith, director of the Environmental Ergonomics Research Centre at Loughborough University, U.K., who led the manikin experiments. They also calculated heat loss at different windspeeds and after wetting the scalp to simulate sweating. They ran their results through a model to study how the diverse hair textures would affect heat gain in 86-degree Fahrenheit (30 degrees Celsius) heat and 60% relative humidity, like environments in equatorial Africa.

The researchers found that all hair reduced solar radiation to the scalp, but tightly curled hair provided the best protection from the sun's radiative heat while minimizing the need to sweat to stay cool. They reported their findings yesterday (June 6) in the Proceedings of the National Academy of Sciences.

"Walking upright is the setup and brain growth is the payoff of scalp hair," said Tina Lasisi, who conducted the study as part of her doctoral dissertation at Penn State. Lasisi will start as an assistant professor of anthropology at the University of Michigan in the fall.

As early humans evolved to walk upright in equatorial Africa, the tops of their heads increasingly took the brunt of solar radiation, explained Lasisi. The brain is sensitive to heat, and it generates heat, especially the larger it grows. Too much heat can lead to dangerous conditions like heat stroke. As humans lost much of their body hair, they developed efficient sweat glands to keep cool, but sweating comes at a cost in lost water and electrolytes. Scalp hair likely evolved as a way to reduce the amount of heat gain from solar radiation, thereby keeping humans cool without the body having to expend extra resources, said Lasisi.

"Around 2 million years ago we see Homo erectus, which had the same physical build as us but a smaller brain size," she said. "And by 1 million years ago, we're basically at modern-day brain sizes, give or take. Something released a physical constraint that allowed our brains to grow. We think scalp hair provided a passive mechanism to reduce the amount of heat gained from solar radiation that our sweat glands couldn't."

The multidisciplinary research provides important preliminary results for bettering our understanding of how human hair evolved without putting humans in potentially dangerous situations, said Jablonski.

The study also shows that evolutionary anthropologists have an extra tool in the thermal manikin -- normally used for testing the functionality of protective clothing -- for quantifying human data that is otherwise very difficult to capture, added Havenith.

"The work that's been done on skin color and how melanin protects us from solar radiation can shape some of the decisions that a person makes in terms of the amount of sunscreen needed in certain environments," said Lasisi. "I imagine that similar decision making can occur with hair. When you think about the military or different athletes exercising in diverse environments, our findings give you a moment to reflect and think: is this hairstyle going to make me overheat more easily? Is this the way that I should optimally wear my hair?"

https://www.sciencedaily.com/releases/2023/06/230607215834.htm

How does dopamine regulate both learning and motivation?

June 6, 2023

Science Daily/Netherlands Institute for Neuroscience - KNAW

A new study from the Netherlands Institute for Neuroscience brings together two schools of thought on the function of the neurotransmitter dopamine: one saying that dopamine provides a learning signal, the other saying that dopamine drives motivation. 'But it is probably both', says Ingo Willuhn.

It is well-known that the dopamine system is implicated in signaling reward-related information as well as in actions that generate rewarding outcomes. This can be investigated using either Pavlovian and operant conditioning experiments. Pavlovian conditioning describes how your brain makes an association between two situations or stimuli that previously seemed unrelated. A famous example is Pavlov's experiment, where a dog heard a sound before receiving food. After several such pairings of the sound with food delivery, the sound alone began to cause the dog to salivate. Operant conditioning, or instrumental learning, differs from this in that the behavior of an individual is important to earn a food reward. Meaning that the individual after hearing a sound, has to perform a so-called operant action to receive the reward. In animal experiments, such a operant response is often the pressing of a lever.

Dopamine measurements in nucleus accumbens

In the final PhD paper of Jessica Goedhoop in collaboration with Tara Arbab and Ingo Willuhn from the Netherlands Institute for Neuroscience, they take a closer look at the role of dopamine signaling in learning and motivation. The team directly compared the two conditioning paradigms: male rats underwent either Pavlovian or operant conditioning while dopamine release was measured in the nucleus accumbens, a brain region central for processing this information. During the experiments a cue light was illuminated for a duration of 5 seconds. For the Pavlovian group, a food pellet was delivered into the reward magazine directly after the cue light turned off. For the operant conditioning group, turning off the cue light was followed by extension of the lever below the cue light into the operant box. The lever was retracted after one lever press, which immediately resulted in the delivery of one food pellet reward into the food magazine. If there was no lever press within 5 seconds after lever extension, the lever was retracted and no reward was delivered.

Sustained dopamine release in operant conditioning

Rats in both groups released the same quantity of dopamine at the onset of the reward-predictive cue. However, only the operant-conditioning group showed a subsequent, sustained plateau in dopamine concentration throughout the entire 5-second cue presentation (throughout cue presentation and before lever press). This dopamine sustainment was observed reliably and consistently throughout systematic manipulation of experimental parameters and behavioral training. Therefore, the researchers believe that sustained dopamine levels may be an intermediate between learning and action, conceptually related to the motivation to generate a reward-achieving action.

Ingo Willuhn: 'There have been a lot of studies on dopamine. We have a decent idea of when dopamine is released in the brain, but there is still lots of discussion on what the precise variables are that determine such dopamine signaling. Essentially discussion on what dopamine "means." To investigate this, scientists usually perform either Pavlovian or operant conditioning experiments. But they test slightly different things. Both have to do with learning an association between a neutral stimulus and a reward. But operant conditioning requires the motivation to perform an action in addition to that (to earn the reward). Therefore, we compared the two types of conditioning in the same experiment.'

Adding a piece to the puzzle

'Our results bring together the two camps of scientists that often battle with each other: one says that dopamine is a so-called reward-prediction error signal, meaning that dopamine is released when something better than expected happens, and is suppressed when something worse than expected happens. It is a learning (or teaching) signal. The other camp says that this is not true. They say that dopamine has something to do with motivation. Increased dopamine release will invigorate the subjects and they work harder to get the reward. There have been a few attempts in the past to bring these two camps together, but there is still need for more knowledge on the subject.'

'What we saw in our study is that only in the operant-learning task dopamine levels stayed high. It seems that the motivation is encoded in this plateau. Reward prediction is the initial dopamine peak, but how much the signal stays up, reflects motivation. Thus, our paper suggests that there is a possibility that dopamine is involved in both, learning and motivation. The next steps will be to get more details out of this. We need to replicate the experiments and make them more sophisticated. The more sophisticated you make it, the more precise our predictions have to be. We are going to build on it and see whether it still holds up.'

Implications

'Dopamine is not only involved in everyday life but also in disorders such as addiction, Parkinson's disease, and schizophrenia. Because of the two camps existing, there is disagreement about what happens exactly. For example, some researchers say that when addicts take drugs dopamine release increases and as a consequence all the environmental cues become more meaningful. Addicts learn that these cues are associated with the drug and they take more and more drug, because they are constantly reminded of the drug everywhere. In this view, addiction is misguided learning. Other researchers would say that motivation to take the drug intensifies with more frequent drug intake, because the drug elevates dopamine release. This study indicates that it may be both. Depending on the precise timing, both systems could be the driver, and both could be involved.'

'This is also relevant for the clinic. Prescribed drugs can influence both learning and motivation systems at the same time: and then it can get messy. If you give schizophrenic patients classic antipsychotic medication, they become slow and cannot act much because their motivation system is down. Parkinson's patients take pro-dopamine drugs essentially because they lost their dopamine, but some patients start to gamble because their dopamine system is on overdrive suddenly. We cannot influence learning and motivation components separately. As soon as you give a drug it is going to hit all of it, so it is good to keep that in mind.'

https://www.sciencedaily.com/releases/2023/06/230606111734.htm

Deep-brain stimulation during sleep strengthens memory

Researchers also report first direct evidence supporting main theory for how human memory is consolidated during sleep

June 1, 2023

Science Daily/University of California - Los Angeles Health Sciences

While it's known that sleep plays a crucial role in strengthening memory, scientists are still trying to decode how this process plays out in the brain overnight.

New research led by scientists at UCLA Health and Tel Aviv University provides the first physiological evidence from inside the human brain supporting the dominant scientific theory on how the brain consolidates memory during sleep. Further, the researchers found that targeted deep-brain stimulation during a critical time in the sleep cycle appeared to improve memory consolidation.

The research, published June 1 in Nature Neuroscience, could offer new clues for how deep-brain stimulation during sleep could one day help patients with memory disorders like Alzheimer's disease, said study co-author Itzhak Fried, MD, PhD. This was achieved by a novel "closed-loop" system that delivered electrical pulses in one brain region precisely synchronized to brain activity recorded from another region.

According to the dominant theory for how the brain converts new information into long-term memories during shuteye, there's an overnight dialogue between the hippocampus -- the brain's memory hub -- and the cerebral cortex, which is associated with higher brain functions like reasoning and planning. This occurs during a phase of deep sleep, when brain waves are especially slow and neurons across brain regions alternate between rapidly firing in sync and silence.

"This provides the first major evidence down to the level of single neurons that there is indeed this mechanism of interaction between the memory hub and the entire cortex," said Fried, the director of epilepsy surgery at UCLA Health and professor of neurosurgery, psychiatry and biobehavioral sciences at the David Geffen School of Medicine at UCLA. "It has both scientific value in terms of understanding how memory works in humans and using that knowledge to really boost memory."

The researchers had a unique opportunity to test this theory of memory consolidation via electrodes in the brains of 18 epilepsy patients at UCLA Health. The electrodes had been implanted in the patients' brains to help identify the source of their seizures during hospital stays typically lasting around 10 days.

The study was conducted across two nights and mornings. Just before bedtime, study participants were shown photo pairings of animals and 25 celebrities, including easily identifiable stars like Marilyn Monroe and Jack Nicholson. They were immediately tested on their ability to recall which celebrity was paired with which animal, and they were tested again in the morning after a night of undisturbed sleep.

On another night, they were shown 25 new animal and celebrity pairings before bedtime. This time, they received targeted electrical stimulation overnight, and their ability recall the pairings was tested in the morning. To deliver this electrical stimulation, the researchers had created a real-time closed-loop system that Fried likened to a musical conductor: The system "listened" to brain's electrical signals, and when patients fell into the period of deep sleep associated with memory consolidation, it delivered gentle electrical pulses instructing the rapidly firing neurons to "play" in sync.

Each individual tested performed better on memory tests following a night of sleep with the electrical stimulation compared to a night of undisturbed sleep. Key electrophysiological markers also indicated that information was flowing between the hippocampus and throughout the cortex, providing physical evidence supporting of memory consolidation.

"We found we basically enhanced this highway by which information flows to more permanent storage places in the brain," Fried said.

Fried in 2012 authored a New England Journal of Medicine study that for the first time showed that electrical stimulation can strengthen memory, and his work has continued to explore how deep brain stimulation could improve memory, now moving into the critical stage of sleep. He recently received a $7 million NIH grant to study whether artificial intelligence can help pinpoint and strengthen specific memories in the brain.

"In our new study, we showed we can enhance memory in general," Fried said. "Our next challenge is whether we have the ability to modulate specific memories."

https://www.sciencedaily.com/releases/2023/06/230601155923.htm

Male babies 'talk' more in the first year than female babies do

May 31, 2023

Science Daily/Cell Press

Young babies make many squeals, vowel-like sounds, growls, and short word-like sounds such as "ba" or "aga." Those precursors to speech or "protophones" are later replaced with early words and, eventually, whole phrases and sentences. While some infants are naturally more "talkative" than others, a new study reported in iScience on May 31 confirms that there are differences between males and females in the number of those sounds.

In general, they found that male infants "talk" more than female infants in the first year. While the research confirms earlier findings from a much smaller study by the same team, they still come as a surprise. That's because there's a common and long-held belief that females have a reliable advantage over males in language. They also have interesting implications for the evolutionary foundations of language, the researchers say.

"Females are believed widely to have a small but discernible advantage over males in language," says D. Kimbrough Oller of the University of Memphis, Tennessee. "But in the first year, males have proven to produce more speech-like vocalization than females."

Male infants' apparent early advantage in language development doesn't last however. "While boys showed higher rates of vocalization in the first year, the girls caught up and passed the boys by the end of the second year," Oller says.

Oller and colleagues hadn't meant to look at sex difference at all. Their primary interest is in the origins of language in infancy. If they'd had to guess, they'd have predicted female infants might make more sounds than males. But they got the same result in an earlier paper reported in Current Biologyin 2020.

In the new study, they looked to see if they could discern the same pattern in a much larger study. Oller says that the sample size in question is "enormous," including more than 450,000 hours of all-day recordings of 5,899 infants, using a device about the size of an iPod. Those recordings were analyzed automatically to count infant and adult utterances across the first 2 years of life.

"This is the biggest sample for any study ever conducted on language development, as far as we know," Oller says.

Overall, the data showed that male infants made 10% more utterances in the first year compared to females. In the second year, the difference switched directions, with female infants making about 7% more sounds than males. Those differences were observed even though the number of words spoken by adults caring for those infants was higher for female infants in both years compared to males.

The researchers say it is possible male infants are more vocal early simply because they are more active in general. But the data do not seem to support that given that the increased vocalizations in male infants go away by 16 months while their greater physical activity level does not. But the findings might fit with an evolutionary theory that infants make so many sounds early on to express their wellness and improve their own odds of surviving, Oller suggests.

Why, then, would male infants be more vocal than females in the first year and not later? "We think it may be because boys are more vulnerable to dying in the first year than girls, and given that so many male deaths occur in the first year, boys may have been under especially high selection pressure to produce vocal fitness signals," Oller says. By the second year of life, as death rates drop dramatically across the board, he added, "the pressure on special fitness signaling is lower for both boys and girls."

More study is needed to understand how caregivers react to baby sounds, according to the researchers.

"We anticipate that caregivers will show discernible reactions of interest and of being charmed by the speech-like sounds, indicators that fitness signaling by the baby elicits real feelings of fondness and willingness to invest in the well-being of infants who vocalize especially effectively," Oller says. "We wonder how caregivers will react to speech-like sounds of boys and girls. But they may have to be told which infants are which, because we don't even know if sex can be discerned in the vocalizations alone."

https://www.sciencedaily.com/releases/2023/05/230531150135.htm

Landmark study finds that the shape of the brain influences the way it works

Shape of brain, not interactions between different regions, crucial in how we think, feel and behave

May 31, 2023

Science Daily/Monash University

For over a century, researchers have thought that the patterns of brain activity that define our experiences, hopes and dreams are determined by how different brain regions communicate with each other through a complex web of trillions of cellular connections.

Now, a study led by from researchers at Monash University's Turner Institute for Brain and Mental Health has examined more than 10,000 different maps of human brain activity and found that the overall shape of a person's brain exerts a far greater influence on how we think, feel and behave than its intricate neuronal connectivity.

The study, published today in the journal, Nature draws together approaches from physics, neuroscience and psychology to overturn the century-old paradigm emphasising the importance of complex brain connectivity, instead identifying a previously unappreciated relationship between brain shape and activity.

Lead author and Research Fellow Dr James Pang, from the Turner Institute and Monash University's School of Psychological Sciences, said the findings were significant because they greatly simplified the way that we can study how the brain functions, develops and ages.

"The work opens opportunities to understand the effects of diseases like dementia and stroke by considering models of brain shape, which are far easier to deal with than models of the brain's full array of connections," Dr Pang said.

"We have long thought that specific thoughts or sensations elicit activity in specific parts of the brain, but this study reveals that structured patterns of activity are excited across nearly the entire brain, just like the way in which a musical note arises from vibrations occurring along the entire length of a violin string, and not just an isolated segment," he said.

The research team used magnetic resonance imaging (MRI) to study eigenmodes, which are the natural patterns of vibration or excitation in a system, where different parts of the system are all excited at the same frequency. Eigenmodes are normally used to study physical systems in areas such as physics and engineering and have only recently been adapted to study the brain.

This work focused on developing the best way to efficiently construct the eigenmodes of the brain.

"Just as the resonant frequencies of a violin string are determined by its length, density and tension, the eigenmodes of the brain are determined by its structural -- physical, geometric and anatomical -- properties, but which specific properties are most important has remained a mystery," said co-lead author, Dr Kevin Aquino, of BrainKey and The University of Sydney.

The team, led by the Turner Institute and School of Psychological Sciences ARC Laureate Fellow, Professor Alex Fornito, compared how well eigenmodes obtained from models of the shape of the brain could account for different patterns of activity when compared to eigenmodes obtained from models of brain connectivity.

"We found that eigenmodes defined by brain geometry -- its contours and curvature -- represented the strongest anatomical constraint on brain function, much like the shape of a drum influences the sounds that it can make," said Professor Fornito.

"Using mathematical models, we confirmed theoretical predictions that the close link between geometry and function is driven by wave-like activity propagating throughout the brain, just as the shape of a pond influences the wave ripples that are formed by a falling pebble," he said.

"These findings raise the possibility of predicting the function of the brain directly from its shape, opening new avenues for exploring how the brain contributes to individual differences in behaviour and risk for psychiatric and neurological diseases."

The research team found that, across over 10,000 MRI activity maps, obtained as people performed different tasks developed by neuroscientists to probe the human brain, activity was dominated by eigenmodes with spatial patterns that have very long wavelengths, extending over distances exceeding 40 mm.

"This result counters conventional wisdom, in which activity during different tasks is often assumed to occur in focal, isolated areas of elevated activity, and tells us that traditional approaches to brain mapping may only show the tip of the iceberg when it comes to understanding how the brain works," Dr Pang said.

https://www.sciencedaily.com/releases/2023/05/230531150131.htm

Can we learn to think further ahead?

Cognitive scientists' computational model shows how expertise improves planning depth

May 31, 2023

Science Daily/New York University

Chess grandmasters are often held up as the epitome of thinking far ahead. But can others, with a modest amount of practice, learn to think further ahead?

In addressing this question, a team of cognitive scientists has created a computational model that reveals our ability to plan for future events. The work enhances our understanding of the factors that affect decision-making and shows how we can boost our planning skills through practice.

The research, conducted by scientists in New York University's Center for Neural Science and reported in the journal Nature, centers on the role of "planning depth" -- the number of steps that an individual thinks ahead -- in decision-making.

"While artificial intelligence has made impressive progress in solving complex planning problems, much less is understood about the nature and depth of planning in people," explains Wei Ji Ma, a professor of neuroscience and psychology at NYU and the paper's senior author. "Our work adds to this body of knowledge by showing that even a relatively modest amount of practice can improve depth of planning."

It's been long established that a hallmark of human intelligence is the ability to plan multiple steps into the future. However, it's less clear whether or not skilled decision makers plan more steps ahead than do novices. This is because methods for measuring this aptitude (e.g., experiments involving board games) have notable shortcomings -- in part, because they don't reliably estimate planning depth.

The Nature paper's authors had people play a relatively simple game -- a more sophisticated version of tic-tac-toe -- that still required players to plan deeply (i.e., multiple steps ahead). Then, to understand precisely what goes on in people's minds as they are thinking of their next move in this game, the authors designed a computer model based on AI principles. The model allows them to describe and subsequently predict the moves that people make when faced with new situations in the game.

"In this computational model, players build a 'decision tree' in their heads the same way that you might plan for multiple possible scenarios for a complex travel itinerary," Ma explains.

ere, their calculations showed that human behavior can be captured using a computational cognitive model based on a heuristic search algorithm -- one that maps out a sequence of promising moves for both players.

To validate the model, the researchers conducted a series of behavioral experiments with human participants. Specifically, they tracked how players planned their moves under different scenarios while also testing their memory and their ability to learn from and reconstruct their game-playing experiences. In addition, the team conducted a Turing test experiment in which observers, who had played the game before, were asked to determine whether sequences of moves they witnessed were generated by the model or by human players. These observers were able to make the correct distinction only about half the time, suggesting that the model makes similar decisions that a human would make. Several of these experiments may be played online by going to Ma's laboratory website.

Overall, their results showed that better planning is driven by the ability to recognize patterns more accurately and in less time -- outcomes that point to the benefits of practice and experience.

"It is known that cognitive abilities can improve in adulthood through practice," observes Ma. "These findings show that even a relatively modest amount of practice can improve one's depth of planning. This opens up new avenues of research. For example, we can use these methods to study the development of planning abilities in children, or test whether planning abilities can be retained in old age. Of course, it is also crucial that we connect planning in the laboratory to planning in real life."

The paper's other authors are: Bas van Opheusden, an NYU doctoral student at the time of the study and now a research scientist at Generally Intelligent; Ionatan Kuperwajs, an NYU doctoral student; Gianni Galbiati, an NYU researcher at the time of the study and now director of research and development at Vidrovr; Zahy Bnaya, a postdoctoral researcher at NYU's Center for Neural Science; and Yunqi Li, an NYU researcher at the time of the study and now a doctoral student at Stanford University.

The research was supported by grants from the National Science Foundation (IIS-1344256, DGE1839302).

https://www.sciencedaily.com/releases/2023/05/230531150112.htm

Low sexual satisfaction linked to memory decline later in life

May 30, 2023

Science Daily/Penn State

Low sexual satisfaction in middle age may serve as an early warning sign for future cognitive decline, according to a new study led by Penn State researchers. The study, which tracked associations between erectile function, sexual satisfaction and cognition in hundreds of men aged 56 through 68, found that declines in sexual satisfaction and erectile function were correlated with future memory loss.

The study, published in the latest issue of the journal Gerontologist, is the first to longitudinally track sexual satisfaction in tandem with sexual health and cognition, the researchers state, and its findings point to a potential novel risk factor for cognitive decline.

"What was unique about our approach is that we measured memory function and sexual function at each point in the longitudinal study, so we could look at how they changed together over time," said Martin Sliwinski, professor of human development and family studies at Penn State and co-author on the study. "What we found connects to what scientists are beginning to understand about the link between life satisfaction and cognitive performance."

The study explored the relationship between physical changes like the microvascular changes relevant for erectile function, and psychological changes, such as lower sexual satisfaction, to determine how the changes relate to cognition. They examined the shifts starting in middle age because it represents a transition period where declines in erectile function, cognition and sexual satisfaction begin to emerge.

Sliwinski added that while the team discovered a strong correlation between the three health factors, they can only speculate as to the cause.

"Scientists have found that if you have low satisfaction generally, you are at a higher risk for health problems like dementia, Alzheimer's disease, cardiovascular disease and other stress-related issues that can lead to cognitive decline," he said. "Improvements in sexual satisfaction may actually spark improvement in memory function. We tell people they should get more exercise and eat better foods. We're showing that sexual satisfaction also has importance for our health and general quality of life."

For the study, the researchers used survey data from 818 men who participated in the Vietnam Era Twin Study of Aging. Through neuropsychological tests, such as tests of memory and processing speed, they examined cognitive changes of participants over the 12-year span from age 56 to 68, adjusting for participants' cognitive ability in young adulthood. Their erectile function and sexual satisfaction were measured alongside cognition, using the International Index of Erectile Function, a self-reported assessment for male sexual health. The researchers then built a statistical model to understand how the three variables changed as individuals aged.

"Research on sexual health has historically focused on quantifiable facets of sexuality like number of sexual partners or frequency of sexual activity," said Riki Slayday, a doctoral candidate at Penn State and lead author on the study. "What we were interested in is the perception of that activity, how someone feels about their sex life, and how that influences cognitive function, because multiple people could be in the same situation physically but experience completely different levels of satisfaction."

The study found that decreases in erectile function and sexual satisfaction were both associated with memory decline, which the researchers say points to a connection between psychological and physical health.

"When we mapped the relationship over time, we found increases or decreases in erectile function and sexual satisfaction were associated with concurrent increases or decreases in cognitive function," Slayday said. "These associations survived adjustment for demographic and health factors, which tells us there is a clear connection between our sex lives and our cognition."

Prior studies have found a link between microvascular changes and changes in erectile function over time. In fact, the active ingredient in Viagra (Sildenafil) was originally developed to treat cardiovascular problems, Sliwinski explained, so the connection between vascular health and erectile function is well understood. How erectile function connects to other aspects of health should be an area of focus for future research, he added.

Increasing the assessment and monitoring of erectile function as a vital sign of health may help identify those at risk of cognitive decline before their 70s, he said. The researchers note that the older adult population in the U.S. is expected to double over the next 30 years, which means twice as many people will likely enter their 60s and experience declines in erectile function and sexual satisfaction.

"We already have a pill for treating erectile dysfunction. What we don't have is an effective treatment for memory loss," Sliwinski said. "Instead of the conversation being about treating ED, we should see that as a leading indicator for other health problems and also focus on improving sexual satisfaction and overall well-being, not just treating the symptom."

https://www.sciencedaily.com/releases/2023/05/230530125414.htm

Obesity increases risk of mental disorders throughout life

May 30, 2023

Science Daily/Complexity Science Hub Vienna

Being obese significantly increases the chances of also developing mental disorders. This applies to all age groups, with women at higher risk than men for most diseases, as a recent study of the Complexity Science Hub and the Medical University of Vienna shows. The results were published in the specialist journal Translational Psychiatry.

"We analyzed a population-wide national registry of inpatient hospitalizations in Austria from 1997 to 2014 in order to determine the relative risks of comorbidities in obesity and identify statistically significant sex differences," explains Elma Dervic of the Complexity Science Hub. Consequently, it became evident that an obesity diagnosis significantly enhances the likelihood of a wide range of mental disorders across all age groups -- including depression, nicotine addiction, psychosis, anxiety, eating and personality disorders. "From a clinical point of view, these results emphasise the need to raise awareness of psychiatric diagnoses in obese patients and, if necessary, to consult specialists at an early stage of diagnosis," says Michael Leutner of the Medical University of Vienna.

FIRST DIAGNOSIS: OBESITY

"In order to find out which illness typically appeared prior and subsequently to the obesity diagnosis, we had to develop a new method," explains Dervic. This allowed the researchers to determine if there were trends and typical patterns in disease occurrence.

In case of all co-diagnoses, with the exception of the psychosis spectrum, obesity was in all likelihood the first diagnosis made prior to the manifestation of a psychiatric diagnosis. "Until now, physicians often considered psychopharmacological medications to cause the association between mental disorders and obesity as well as diabetes. This may be true for schizophrenia, where we see the opposite time order, but our data does not support this for depression or other psychiatric diagnoses," explains Alexander Kautzky from Department of Psychiatry and Psychotherapy of the Medical University Vienna. However, whether obesity directly affects mental health or whether early stages of psychiatric disorders are inadequately recognised is not yet known.

GREATER IMPACT IN WOMEN

Surprisingly, the researchers found significant gender differences for most disorders -- with women showing an increased risk for all disorders except schizophrenia and nicotine addiction.

While 16.66% of obese men also suffer from nicotine abuse disorder, this is only the case in up to 8.58% of obese women. The opposite is true for depression. The rate of diagnosed depressive episodes was almost three times higher in obese women (13.3% obese; 4.8% non-obese). Obese men were twice as likely to be affected (6.61% obese; 3.21% non-obese).

COUNTERACT AT A YOUNG AGE

At present, obesity is a highly prevalent disease worldwide and affects more than 670 million people. The fact that the disease promotes metabolic disorders and serious cardio-metabolic complications (diabetes mellitus, arterial hypertension, and dyslipidaemia) has already been extensively researched.

Since this study now also shows that obesity often precedes severe mental disorders, the findings underscore its importance as a pleiotropic risk factor for health problems of all kinds. This is primarily true for young age groups, where the risk is most pronounced. For this reason, thorough screening for mental health problems in obese patients is urgently needed to facilitate prevention or ensure that appropriate treatment can be given, so the researchers conclude.

https://www.sciencedaily.com/releases/2023/05/230530125412.htm

Junk food may impair our deep sleep

May 30, 2023

Science Daily/Uppsala University

In a new study, researchers at Uppsala University have investigated how junk food affects sleep. Healthy participants consumed an unhealthier as well as a healthier diet in a randomised order. After the unhealthier diet, the quality of the participants' deep sleep had deteriorated, compared with those who had followed the healthier diet. The results have been published in the journal Obesity.

Several epidemiological studies have shown that what we eat is associated with changes in our sleep. However, few studies have investigated how diet itself directly affects sleep. One way to do that is to have the same participant consume different diets in a randomised order.

"Both poor diet and poor sleep increase the risk of several public health conditions. As what we eat is so important for our health, we thought it would be interesting to investigate whether some of the health effects of different diets could involve changes to our sleep. In this context, so-called intervention studies have so far been lacking; studies designed to allow the mechanistic effect of different diets on sleep to be isolated," says Jonathan Cedernaes, Physician and Associate Professor in Medical Cell Biology at Uppsala University.

Previous epidemiological studies have shown that diets with greater sugar content, for example, are linked to poorer sleep. Yet sleep is an interplay of different physiological states, as Cedernaes explains:

"For example, deep sleep can be affected by what we eat. But no study had previously investigated what happens if we consume an unhealthy diet and then compared it to quality of sleep after that same person follows a healthy diet. What is exciting in this context is that sleep is very dynamic. Our sleep consists of different stages with different functions, such as deep sleep which regulates hormonal release, for example. Furthermore, each sleep stage is hallmarked by different types of electrical activity in the brain. This regulates aspects such as how restorative sleep is, and differs across different brain regions. But the depth or integrity of the sleep stages can also be negatively affected by factors such as insomnia and ageing. Previously, it has not been investigated whether similar changes in our sleep stages can occur after exposure to different diets."

Each study session involved several days of monitoring in a sleep laboratory. Therefore, only 15 individuals were included in the study. A total of 15 healthy normal-weight young men participated in two sessions. Participants were first screened for aspects such as their sleep habits, which had to be normal and within the recommended range (an average of seven to nine hours of sleep per night).

In random order, the participants were given both a healthier diet and an unhealthier diet. The two diets contained the same number of calories, adjusted to each individual's daily requirements. Among other things, the unhealthier diet contained a higher content of sugar and saturated fat and more processed food items. The meals of each diet had to be consumed at individually adjusted times, which were matched across the two dietary conditions. Each diet was consumed for a week, while the participants' sleep, activity and meal schedules were monitored at an individual level.

After each diet, the participants were examined in a sleep laboratory. There, they were first allowed to sleep a normal night, while their brain activity was measured to monitor their sleep. The participants were then kept awake in the sleep laboratory, before being allowed to catch up on sleep. Their sleep was recorded in this case, too.

"What we saw was that the participants slept for the same amount of time when they consumed the two diets. This was the case both while they were following the diets, as well as after they had switched to another, identical diet. In addition, across the two diets, the participants spent the same amount of time in the different sleep stages. But we were particularly interested in investigating the properties of their deep sleep. Specifically, we looked at slow-wave activity, a measure that can reflect how restorative deep sleep is. Intriguingly, we saw that deep sleep exhibited less slow-wave activity when the participants had eaten junk food, compared with consumption of healthier food. This effect also lasted into a second night, once we had switched the participants to an identical diet. Essentially, the unhealthy diet resulted in shallower deep sleep. Of note, similar changes in sleep occur with ageing and in conditions such as insomnia. It can be hypothesised, from a sleep perspective, that greater importance should potentially be attached to diet in such conditions," explains Cedernaes.

The researchers do not currently know how long-lasting the sleep effects of the unhealthier diet may be. The study did not investigate whether the shallower deep sleep may alter functions that are regulated by deep sleep, for example.

"It would also be interesting to conduct functional tests, for example to see whether memory function can be affected. This is regulated to a large extent by sleep. And it would be equally interesting to understand how long-lasting the observed effects may be. Currently, we do not know which substances in the unhealthier diet worsened the depth of deep sleep. As in our case, unhealthy diets often contain both higher proportions of saturated fat and sugar and a lower proportion of dietary fibre. It would be interesting to investigate whether there is a particular molecular factor that plays a greater role. Our dietary intervention was also quite short, and both the sugar and fat content could have been higher. It is possible that an even unhealthier diet would have had more pronounced effects on sleep," notes Cedernaes.

https://www.sciencedaily.com/releases/2023/05/230530125400.htm

Low-flavanol diet drives age-related memory loss

May 29, 2023

Science Daily/Columbia University Irving Medical Center

Age-related memory loss is likely caused, in part, by lack of flavanols -- nutrients found in certain fruits and vegetables -- according to a large study in older adults.

A large-scale study led by researchers at Columbia and Brigham and Women's Hospital/Harvard is the first to establish that a diet low in flavanols -- nutrients found in certain fruits and vegetables -- drives age-related memory loss.

The study found that flavanol intake among older adults tracks with scores on tests designed to detect memory loss due to normal aging and that replenishing these bioactive dietary components in mildly flavanol-deficient adults over age 60 improves performance on these tests.

"The improvement among study participants with low-flavanol diets was substantial and raises the possibility of using flavanol-rich diets or supplements to improve cognitive function in older adults," says Adam Brickman, PhD, professor of neuropsychology at Columbia University Vagelos College of Physicians and Surgeons and co-leader of the study.

The finding also supports the emerging idea that the aging brain requires specific nutrients for optimal health, just as the developing brain requires specific nutrients for proper development.

"The identification of nutrients critical for the proper development of an infant's nervous system was a crowning achievement of 20th century nutrition science," says the study's senior author, Scott Small, MD, the Boris and Rose Katz Professor of Neurology at Columbia University Vagelos College of Physicians and Surgeons.

"In this century, as we are living longer research is starting to reveal that different nutrients are needed to fortify our aging minds. Our study, which relies on biomarkers of flavanol consumption, can be used as a template by other researchers to identify additional, necessary nutrients."

Age-related memory loss linked to changes in hippocampus

The current study builds on over 15 years of research in Small's lab linking age-related memory loss to changes in the dentate gyrus, a specific area within the brain's hippocampus -- a region that is vital for learning new memories -- and showing that flavanols improved function in this brain region.

Additional research, in mice, found that flavanols -- particularly a bioactive substance in flavanols called epicatechin -- improved memory by enhancing the growth of neurons and blood vessels and in the hippocampus.

Next, Small's team tested flavanol supplements in people. One small study confirmed that the dentate gyrus is linked to cognitive aging. A second, larger trial showed that flavanols improved memory by acting selectively on this brain region and had the most impact on those starting out with a poor-quality diet.

In the new study, the Columbia team collaborated with researchers at Brigham and Women's Hospital studying the effects of flavanols and multivitamins in COSMOS (COcoa Supplements and Multivitamin Outcomes Study). The current study, COSMOS-Web, was designed to test the impact of flavanols in a much larger group and explore whether flavanol deficiency drives cognitive aging in this area of the brain.

Study methods

More than 3,500 healthy older adults were randomly assigned to receive a daily flavanol supplement (in pill form) or placebo pill for three years. The active supplement contained 500 mg of flavanols, including 80 mg epicatechins, an amount that adults are advised to get from food.

At the beginning of the study, all participants completed a survey that assessed the quality of their diet, including foods known to be high in flavanols. Participants then performed a series of web-based activities in their own homes, designed and validated by Brickman, to assess the types of short-term memory governed by the hippocampus. The tests were repeated after years one, two, and three. Most of the participants identified themselves as non-Hispanic and white.

More than a third of the participants also supplied urine samples that allowed researchers to measure a biomarker for dietary flavanol levels, developed by co-study authors at Reading University in the UK, before and during the study. The biomarker gave the researchers a more precise way to determine if flavanol levels corresponded to performance on the cognitive tests and ensure that participants were sticking to their assigned regimen (compliance was high throughout the study). Flavanol levels varied moderately, though no participants were severely flavanol-deficient.

People with mild flavanol deficiency benefited from flavanol supplement

Memory scores improved only slightly for the entire group taking the daily flavanol supplement, most of whom were already eating a healthy diet with plenty of flavanols.

But at the end of the first year of taking the flavanol supplement, participants who reported consuming a poorer diet and had lower baseline levels of flavanols saw their memory scores increase by an average of 10.5% compared to placebo and 16% compared to their memory at baseline. Annual cognitive testing showed the improvement observed at one year was sustained for at least two more years.

The results strongly suggest that flavanol deficiency is a driver of age-related memory loss, the researchers say, because flavanol consumption correlated with memory scores and flavanol supplements improved memory in flavanol-deficient adults.

The findings of the new study are consistent with those of a recent study, which found that flavanol supplements did not improve memory in a group of people with a range of baseline flavanol levels. The previous study did not look at the effects of flavanol supplements on people with low and high flavanol levels separately.

"What both studies show is that flavanols have no effect on people who don't have a flavanol deficiency," Small says.

It's also possible that the memory tests used in the previous study did not assess memory processes in the area of the hippocampus affected by flavanols. In the new study, flavanols only improved memory processes governed by the hippocampus and did not improve memory mediated by other areas of the brain.

Next steps

"We cannot yet definitively conclude that low dietary intake of flavanols alone causes poor memory performance, because we did not conduct the opposite experiment: depleting flavanol in people who are not deficient," Small says, adding that such an experiment might be considered unethical.

The next step needed to confirm flavanols' effect on the brain, Small says, is a clinical trial to restore flavanol levels in adults with severe flavanol deficiency.

"Age-related memory decline is thought to occur sooner or later in nearly everyone, though there is a great amount of variability," says Small. "If some of this variance is partly due to differences in dietary consumption of flavanols, then we would see an even more dramatic improvement in memory in people who replenish dietary flavanols when they're in their 40s and 50s."

https://www.sciencedaily.com/releases/2023/05/230529171757.htm

Improvement in older adults' cognitive function and manual dexterity due to repetitive training

May 26, 2023

Science Daily/University of Tsukuba

Among the many harmful effects of aging, a decline in hand dexterity can lead to difficulties in the performance of daily activities, such as writing, cooking, gardening, craftwork, and the ability to open bottles and jars. These detrimental, aging-associated changes are observed in both men and women, especially in those older than 65 years of age.

Preserving hand dexterity is therefore essential for day-to-day living among older adults. In this study, we hypothesize that home-based repetitive manual dexterity training is capable to selectively improve cognitive function. In addition, we examined brain activation (cognitive load) patterns during the performance of manual dexterity training.

In total, 57 elderly adults (mean age: 73.6 ± 6.1 years; male: 31.6%, female: 68.4%) residing in Ibaraki Prefecture were randomly divided into 28 intervention groups (mean age: 72.9 ± 5.6 years; male: 32.1%, female: 67.9%) and 29 control groups (mean age: 74.4 ± 6.5 years; male: 31%, female: 69%). The intervention group performed manual dexterity training daily for 12 weeks.

It was found that the intensity of the level of training undertaken positively correlated with the amount of active blood hemoglobin that could be measured in the prefrontal cortex. Among the cognitive functions, executive function was observed to considerably improve in the intervention group compared with the control group. Other cognitive functions did not considerably improve; however, the effect size of these functions was higher in the intervention group than in the control group.

Therefore, the findings of this study suggest that home-based manual dexterity training can improve hand dexterity and cognitive functioning in older adults.

https://www.sciencedaily.com/releases/2023/05/230526121047.htm

Keeping time: Understanding the master clock in the brain

Researchers find a molecular pathway that controls sleep rhythms and homeostasis

May 25, 2023

Science Daily/University of Tsukuba

Researchers found that, in neurons that produced the neuropeptide NMS, the interaction between molecules SIK3 and HDAC4 has a critical role in sleep regulation through both the length of the circadian period and sleep homoeostasis. Given the similarities among different mammals, new information about how the circadian system works in mice could lead to new treatments for sleep and circadian rhythm disorders in humans.

Most living creatures exhibit a circadian rhythm, an internal clock that repeats around every 24 hours. Now, researchers from Japan have found new details about the molecular processes that govern sleep/wake rhythms in mice.

In a recently published study, researchers from the University of Tsukuba have revealed that a key molecule involved in sleep homeostasis (called SIK3 or salt-inducible kinase 3) also plays a critical role in circadian behavior.

Animals are able to adapt to the 24-hour cycle of light and dark in terms of both behavior and physiology via changes in the suprachiasmatic nucleus (SCN), which is the brain's master clock that synchronizes the various rhythms in the body. However, the biological activities within the SCN that induce time-specific wakefulness have not been fully characterized; the research team aimed to address this.

"Most animals show a peak in activity at a specific point in the circadian cycle," explains lead author of the study Professor Masashi Yanagisawa. "Because the SCN has been found to regulate sleep and wakefulness at certain times of the day, we wanted to investigate the distinct neurons that control this process."

To do this, the research team genetically manipulated levels of SIK3 in specific neuron groups in the SCN of mice. Then, they examined sleep and circadian behaviors in the mice, such as when and for how long the mice exhibited activity with respect to the light-dark cycle.

"We found that SIK3 in the SCN can influence circadian cycle length and the timing of peak arousal activity, without changing the daily sleep amount," says Professor Yanagisawa.

The research team previously reported that SIK3 interacts with LKB1 (an upstream molecule of SIK3) and HDAC4 (an important target of SIK3) in glutamatergic neurons to regulate the amount and depth of sleep. Now, they have found that the SIK3-HDAC4 pathway modulates the length of the circadian period through NMS-producing neurons, and contributes to the sleep/wake rhythm.

The length of the behavioral period and the timing of peak activity are important components of the circadian rhythm. Given the similarities between the circadian systems of different mammals, new information about how this system works in mice could lead to new treatments for sleep and circadian rhythm disorders in humans.

https://www.sciencedaily.com/releases/2023/05/230525141332.htm

Your thoughts can harm your neck and back during lifting tasks

In lab, contradictory feedback linked to increased spine loading

May 25, 2023

Science Daily/Ohio State University

The mental distress of cognitive dissonance -- encountering information that conflicts with how we act or what we believe -- can lead to added pressure on the neck and low back during lifting and lowering tasks, new research suggests.

When study participants were told they were performing poorly in a precision lowering experiment in the lab, after initially being told they were doing well, their movements were linked to increased loads on vertebrae in their neck and low back.

Results showed that the higher the cognitive dissonance score, the greater the extent of loading on the upper and lower parts of the spine.

The finding suggests cognitive dissonance may be a previously unidentified risk factor for neck and low back pain, which could have implications for risk prevention in the workplace, according to researchers.

"This increased spine loading occurred under just one condition with a fairly light load -- you can imagine what this would be like with more complex tasks or higher loads," said senior author William Marras, executive director of the Spine Research Institute at The Ohio State University. "Basically, the study scratched the surface of showing there's something to this."

The research was published recently in the journal Ergonomics.

Marras' lab has been studying daily living and occupational forces on the spine for decades. About 20 years ago, he found that psychological stress could influence spine biomechanics, using a study design that involved having a fake argument with a graduate student in front of research participants.

"We found that in certain personality types, the loads in the spine increased by up to 35%," Marras said. "We ended up finding that when you're under that kind of psychosocial stress, what you tend to do is what we call co-activate muscles in your torso. It creates this tug of war in the muscles because you're always tense.

"In this study, to get at that mind-body connection, we decided to look at the way people think and, with cognitive dissonance, when people are disturbed by their thoughts."

Seventeen research participants -- nine men and eight women aged 19-44 -- completed three phases of an experiment in which they placed a light-weight box within a square on a surface that was moved left and right, up and down. After a short practice run, researchers gave almost exclusively positive feedback during the first of two 45-minute trial blocks. During the second, the feedback increasingly suggested participants were performing in an unsatisfactory way.

To arrive at a cognitive dissonance score for each participant, changes during the experiment to blood pressure and heart rate variability were combined with responses to two questionnaires assessing discomfort levels as well as positive and negative affect -- feeling strong and inspired versus distressed and ashamed.

Wearable sensors and motion-capture technology were used to detect peak spinal loads in the neck and low back: both compression of vertebrae and vertebral movement, or shear, from side to side (lateral) and forward and back (A/P).

Statistical modeling showed that, on average, peak spinal loads on cervical vertebrae in the neck were 11.1% higher in compression, 9.4% higher in A/P shear and 19.3% higher in lateral shear during the negative-feedback trial block compared to the baseline measures from the practice run. Peak loading in the lumbar region of the low back -- an area that bears the brunt of any spinal loading -- increased by 1.7% in compression and 2.2% in shear during the final trial block.

"Part of the motivation here was to see whether cognitive dissonance can manifest itself not only in the low back -- we thought we'd find it there, but we didn't know what we'd find in the neck. We did find a pretty strong response in the neck," said Marras, a professor of integrated systems engineering with College of Medicine academic appointments in neurosurgery, orthopaedics and physical medicine and rehabilitation.

"Our tolerance to shear is much, much lower than it is to compression, so that's why that's important," he said. "A small percentage of load is no big deal for one time. But think about when you're working day in and day out, and you're in a job where you're doing this 40 hours a week -- that could be significant, and be the difference between a disorder and not having a disorder."

Marras is also principal investigator on a federally funded multi-institution clinical trial assessing different treatments for low back pain that range from medication to exercise to cognitive behavioral therapy.

"We're trying to unravel this onion and understand all the different things that affect spine disorders because it's really, really complex," he said. "Just like the whole system has got to be right for a car to run correctly, we're learning that that's the way it is with the spine. You could be in physically great shape, but if you're not thinking correctly or appropriately, or you have all these mental irregularities, like cognitive dissonance, that will affect the system. And until you get that right, you're not going to be right.

"We're looking for causal pathways. And now we can say cognitive dissonance plays a role and here's how it works."

https://www.sciencedaily.com/releases/2023/05/230525141244.htm

Running throughout middle age keeps 'old' adult-born neurons 'wired'

'Mice on the run:' study reveals how exercise helps maintain memory function during aging

May 25, 2023

Science Daily/Florida Atlantic University

A new study provides novel insight into the benefits of exercise, which should motivate adults to keep moving throughout their lifetime, especially during middle age. Long-term exercise profoundly benefits the aging brain and may prevent aging-related memory function decline by increasing the survival and modifying the network of the adult-born neurons born during early adulthood, and thereby facilitating their participation in cognitive processes.

Aging often is accompanied by cognitive decline. Among the first structures of the brain affected are the hippocampus and adjacent cortices, areas essential for learning and memory. Deficits in cognitive ability are associated with reduced hippocampal volume and degradation of synaptic connectivity between the hippocampus and the (peri)-entorhinal cortex.

Increasing evidence indicates that physical activity can delay or prevent these structural and functional reductions in older adults. A new study by Florida Atlantic University and CINVESTAV, Mexico City, Mexico, provides novel insight into the benefits of exercise, which should motivate adults to keep moving throughout their lifetime, especially during middle age.

For the study, researchers focused on the effects of long-term running on a network of new hippocampal neurons that were generated in young adult mice, at middle age. These "mice on the run" demonstrate that running throughout middle age keeps old adult-born neurons wired, which may prevent or delay aging-related memory loss and neurodegeneration.

Adult-born neurons are thought to contribute to hippocampus-dependent memory function and are believed to be temporarily important, during the so-called 'critical period' at about three to six weeks of cell age, when they can fleetingly display increased synaptic plasticity. However, these new neurons do remain present for many months, but it was unclear whether those born in early adulthood remain integrated into neural networks and whether their circuitry is modifiable by physical activity in middle age.

To address these questions, researchers used a unique rabies virus-based circuit tracing approach with a long-time interval between the initial labeling of new neurons and subsequent analysis of their neural circuitry in rodents. More than six months after tagging of the adult-born neurons with a fluorescent reporter vector, they identified and quantified the direct afferent inputs to these adult-born neurons within the hippocampus and (sub)cortical areas, when the mice were middle-aged.

Results of the study, published in the journal eNeuro, show long-term running wires 'old' new neurons, born during early adulthood, into a network that is relevant to the maintenance of episodic memory encoding during aging.

"Long-term exercise profoundly benefits the aging brain and may prevent aging-related memory function decline by increasing the survival and modifying the network of the adult-born neurons born during early adulthood, and thereby facilitating their participation in cognitive processes," said Henriette van Praag, Ph.D., corresponding author, an associate professor of biomedical science in FAU's Schmidt College of Medicine and a member of the FAU Stiles-Nicholson Brain Institute.

Findings from the study showed long-term running significantly increased the number of adult-born neurons and enhanced the recruitment of presynaptic (sub)-cortical cells to their network.

"Long-term running may enhance pattern separation ability, our ability to distinguish between highly similar events and stimuli, a behavior closely linked to adult neurogenesis, which is among the first to display deficits indicative of age-related memory decline," said Carmen Vivar, Ph.D., corresponding author, Department of Physiology, Biophysics and Neuroscience, Centro de Investigacion y de Estudios Avanzados del IPN in Mexico.

Aging-related memory function decline is associated with the degradation of synaptic inputs from the perirhinal and entorhinal cortex onto the hippocampus, brain areas that are essential for pattern separation, and contextual and spatial memory.

"We show that running also substantially increases the back-projection from the dorsal subiculum onto old adult-born granule cells," said van Praag. "This connectivity may provide navigation-associated information and mediate the long-term running-induced improvement in spatial memory function."

Results from the study show that running not only rescued perirhinal connectivity but also increased and altered the contribution of the entorhinal cortices to the network of old adult-born neurons.

"Our study provides insight as to how chronic exercise, beginning in young adulthood and continuing throughout middle age, helps maintain memory function during aging, emphasizing the relevance of including exercise in our daily lives," said Vivar.

https://www.sciencedaily.com/releases/2023/05/230525140336.htm

Brain connectivity, memory improves in older adults after walking

May 25, 2023

Science Daily/University of Maryland

Regular walks strengthen connections in and between brain networks, according to new research, adding to growing evidence linking exercise with slowing the onset of Alzheimer's disease. The study examined the brains and story recollection abilities of older adults with normal brain function and those diagnosed with mild cognitive impairment, which is a slight decline in mental abilities like memory, reasoning and judgment and a risk factor for Alzheimer's.

A new University of Maryland School of Public Health study reveals how walking strengthens connections within and between three of the brain's networks, including one associated with Alzheimer's disease, adding to the growing evidence that exercise improves brain health.

Published this month in the Journal for Alzheimer's Disease Reports, the study examined the brains and story recollection abilities of older adults with normal brain function and those diagnosed with mild cognitive impairment, which is a slight decline in mental abilities like memory, reasoning and judgment and a risk factor for Alzheimer's.

"Historically, the brain networks we studied in this research show deterioration over time in people with mild cognitive impairment and Alzheimer's disease," said J. Carson Smith, a kinesiology professor with the School of Public Health and principal investigator of the study. "They become disconnected, and as a result, people lose their ability to think clearly and remember things. We're demonstrating that exercise training strengthens these connections."

The study builds upon Smith's previous research, which showed how walking may decrease cerebral blood flow and improve brain function in older adults with mild cognitive impairment.

Thirty-three participants, who ranged between 71 and 85 years old, walked while supervised on a treadmill four days a week for 12 weeks. Before and after this exercise regimen, researchers asked participants to read a short story and then repeat it out loud with as many details as possible.

Participants also underwent functional magnetic resonance imaging (fMRI) so researchers could measure changes in communication within and between the three brain networks that control cognitive function:

• Default mode network - Activates when a person isn't doing a specific task (think daydreaming about the grocery list) and is connected to the hippocampus -- one of the first brain regions affected by Alzheimer's disease. It's also where Alzheimer's and amyloid plaques, a prime suspect for Alzheimer's disease found around nerve cells, show up in tests.

• Frontoparietal network -- Regulates decisions made when a person is completing a task. It also involves memory.

• Salience network -- Monitors the external world and stimuli and then decides what deserves attention. It also facilitates switching between networks to optimize performance.

After 12 weeks of exercise, researchers repeated the tests and saw significant improvements in participants' story recall abilities.

"The brain activity was stronger and more synchronized, demonstrating exercise actually can induce the brain's ability to change and adapt," Smith said. "These results provide even more hope that exercise may be useful as a way to prevent or help stabilize people with mild cognitive impairment and maybe, over the long term, delay their conversion to Alzheimer's dementia."

Researchers also observed stronger activity within the default mode network, within the salience network and in the connections between the three networks.

https://www.sciencedaily.com/releases/2023/05/230525135932.htm

Living in an almshouse boosts life expectancy

Living in an almshouse can boost the longevity of its residents by as much as two-and-a-half years compared to their counterparts in the general population

May 25, 2023

Science Daily/City University London

Analysing up to 100 years' worth of residents' records from various almshouses in England, new research suggests that living in these communities can reduce the negative impact on health and social wellbeing which is commonly experienced by the older population in lower socioeconomic groups, particularly those individuals who are living in isolation.

Living in an almshouse can boost the longevity of its residents by as much as two-and-a-half years compared to their counterparts in the general population, according to a new Bayes Business School report.

Almshouses provide affordable community housing for local people in housing need. They are generally designed around a courtyard to provide a 'community spirit', that is synonymous with the almshouse movement. They offer independent living but provide friendship and support when needed.

Analysing up to 100 years' worth of residents' records from various almshouses in England, the research suggests that living in these communities can reduce the negative impact on health and social wellbeing which is commonly experienced by the older population in lower socioeconomic groups, particularly those individuals who are living in isolation.

The results are very encouraging. They show that, for several of the almshouses included in the study, residents can expect to live as long as wealthier members of the general population despite coming from the most deprived quintile. This shows that the disparity in longevity and health outcomes could be mitigated even after reaching retirement age, provided a suitable social infrastructure can be put in place.

The report, authored by Professor Ben Rickayzen, Dr David Smith, Dr Anastasia Vikhanova and Alison Benzimra, concludes that almshouses could help the Government's aims to reduce inequalities in mortality, which are observed between socioeconomic groups, by reducing the social isolation experienced by many in the older population.

Titled 'Almshouse Longevity Study -- Can living in an almshouse lead to a longer life?', the report's key findings are:

• Residents in almshouses in England receive a longevity boost relative to people of the same socioeconomic group from the wider population.

• The best-performing almshouses in the study so far have shown a longevity boost which increases life expectancy to that of a life in the second-highest socioeconomic quintile -- a remarkable outcome.

• As an example, the authors estimate that a 73-year-old male entering an almshouse such as The Charterhouse today would receive a longevity boost of 2.4 years (an extra 15% of future lifetime at the point of joining) compared to his peers from the same socioeconomic group, and 0.7 years when compared to an average 73-year-old from the general population.

• This longevity boost could be due to both the strong sense of community and social belonging within almshouses which lead to better physical and mental health. Enhanced wellbeing helps to mitigate loneliness which is endemic in older age groups.

Professor Ben Rickayzen, Professor of Actuarial Science at Bayes Business School, said:

"It is well known that, on average, the lower a person's socioeconomic status, the lower their life expectancy. However, intriguingly, our research has found that this doesn't have to be the case. We discovered that many almshouse residents receive a longevity boost when compared to their peers of the same socioeconomic status from the wider population.

"More research is needed to ascertain exactly what factors cause almshouse residents to have a longer life; however, we postulate that it is the sense of the community that is the most powerful ingredient. For example, a common theme within the almshouses included in the study is that they encourage residents to undertake social activities and responsibilities on behalf of their fellow residents. This is likely to increase their sense of belonging and give them a greater sense of purpose in their everyday lives while mitigating against social isolation.

"We would encourage the Government to invest in retirement communities, such as almshouses, which would be in keeping with their overarching levelling up agenda. While this agenda is commonly associated with enhancing equality on a regional basis, it is important that levelling up should also aim to combat health inequalities experienced by people from lower socioeconomic groups across the country. There is an opportunity to improve the Government's levelling up agenda by incorporating the best features of communal living into their social housing policy. This should make a significant difference to the quality of life experienced by the older population across the UK.

"The findings from this research are important as they could offer solutions to the social care problems currently being experienced in the UK."

Alison Benzimra, a co-author of the report and Head of Research at United St Saviour's Charity, said:

"Many almshouse trustees and staff members anecdotally believe that almshouse living is beneficial for residents. The results from this study demonstrate that the community spirit provided by almshouses does in fact result in longer life expectancy. These findings are encouraging to those living and working in the almshouse community and provide the motivation to continue to explore what it is about almshouses' physical design and support services that result in positive outcomes for older residents. This study strengthens the case that this historic form of housing is addressing the evolving needs of older people living in our modern-day society."

Nick Phillips, CEO, The Almshouse Association, said:

"We are delighted to read this report. It is further evidence that the almshouse model -- 1,000 years after its inception -- seems to be adding something special to the lives of residents. There is a growing body of research that is suggesting this model of community housing seems to be right for the future. This must now beg the question, where are the philanthropists to lead this robust charity housing model into the next century?"

https://www.sciencedaily.com/releases/2023/05/230525141438.htm

People who live to be 90+ with superior thinking skills are resilient to Alzheimer's pathology in their brains

These oldest-old are also less susceptible to other types of neurodegenerative changes

May 24, 2023

Science Daily/University of California - Irvine

Researchers have discovered that the oldest-old, those who live to be 90+ and have superior cognitive skills, have similar levels of brain pathology as Alzheimer's patients, however, they also have less brain pathology of other neurodegenerative diseases that cause memory and thinking problems.

A University of California, Irvine-led team of researchers have discovered that the oldest-old, those who live to be 90+ and have superior cognitive skills, have similar levels of brain pathology as Alzheimer's patients, however, they also have less brain pathology of other neurodegenerative diseases that cause memory and thinking problems.

The study, "Superior Global Cognition in Oldest-Old is Associated with Resistance to Neurodegenerative Pathologies: Results from the 90+ Study," was published in the Journal of Alzheimer's Disease.

"People who are 90+ and still have good memory and thinking abilities tend to have similar levels of Alzheimer's pathology in their brains," Roshni Biswas, post-doctoral scholar with The 90+ Study. "Our findings indicate that while Alzheimer's Disease neuropathological changes and vascular changes are common in their brains, these individuals are less susceptible to other types of neurodegenerative changes such as Lewy body disease."

Age is the primary risk factor for cognitive issues, such as Alzheimer's, Lewy body disease and other related dementias. Over the past 30 years, the number of people aged 90 and older in the U.S. has nearly tripled, and this number is projected to quadruple in the next four decades.

With this rise in age, many people see increased problems with memory and brain function. However, little data is available on the changes in the brains of 90+ people who maintain superior cognitive abilities, despite their age.

The objective of the study was to examine the brain features of people without cognitive impairment and their relation to superior cognitive skills and reasoning in those that are 90+.

"There are some individuals who can maintain high levels of cognitive function well into advanced ages," said María M. Corrada, ScD, co-principal investigator of the study and professor in the Department of Neurology at UCI School of Medicine. "Further research into the factors that enable these individuals to maintain their cognitive function could provide insights into how to preserve cognitive health despite advanced age."

The study results were derived by analyzing autopsy data from 102 cognitively normal individuals who died at a mean age of 97.6 years. They also used cognitive test scores from people taken between two to twelve months before death. The average age of study participants at the time of their last visit was 97.1 years of age.

"In our future research, we will examine how lifestyle habits and health conditions are associated with superior cognition in individuals who are 90+ and the factors that contribute to maintaining stable cognitive function over time," said Biswas.

The 90+ Study is a longitudinal study on aging and dementia that was initiated in 2003 to study the oldest-old population, which is the fastest growing age group in the United States.

With more than 2000 participants enrolled, it is now one of the largest studies of its kind in the world. The project has produced several significant findings regarding cognitive function, health and lifestyle habits in the oldest-old population information obtained during life.

This work was supported by the National Institutes of Health.

https://www.sciencedaily.com/releases/2023/05/230524182040.htm