Day: July 28, 2023

A Curious Mindset Helps Memory More than an Urgent One

Photo by Mari Lezhava on Unsplash

New research from Duke University found that shifting to a curious mindset helps memory – such as video game players who imagined being a thief scouting a virtual art museum in preparation for a heist. This mindset resulted in better recalling the paintings there. Adopting a high-pressure mindset, such as players trying to execute the heist, resulted in fewer paintings being recalled.

These subtle differences in motivation – urgent, immediate goal-seeking versus curious exploration for a future goal – have big potential for framing real-world challenges such encouraging vaccination. The findings appeared in PNAS.

Alyssa Sinclair, PhD ’23, a postdoctoral researcher working in the lab of Duke Institute for Brain Sciences director Alison Adcock, PhD, MD, recruited 420 adults to pretend to be art thieves for a day. The participants were then randomly assigned to one of two groups and received different backstories.

“For the urgent group, we told them, ‘You’re a master thief, you’re doing the heist right now. Steal as much as you can!’,” Sinclair said. “Whereas for the curious group, we told them they were a thief who’s scouting the museum to plan a future heist.”

After getting these different backstories, however, participants in the two groups played the exact same computer game, scored the exact same way. They explored an art museum with four coloured doors, representing different rooms, and clicked on a door to reveal a painting from the room and its value. Some rooms held more valuable collections of art. No matter which scenario they were pretending to be in, everyone earned real bonus money by finding more valuable paintings.

The impact of this difference in mindset was most apparent the following day. When participants logged back in, they were met with a pop quiz about whether they could recognise 175 different paintings (100 from the day before, and 75 new ones). If participants flagged a painting as familiar, they also had to recall how much it was worth.

Sinclair and her co-author, fellow Duke psychology & neuroscience graduate student Candice Yuxi Wang, were gratified after they graded the tests to see their predictions had played out.

“The curious group participants who imagined planning a heist had better memory the next day,” Sinclair said. “They correctly recognized more paintings. They remembered how much each painting was worth. And reward boosted memory, so valuable paintings were more likely to be remembered. But we didn’t see that in the urgent group participants who imagined executing the heist.”

Urgent group participants, however, had a different advantage. They were better at figuring out which doors hid more expensive pieces, and as a result snagged more high value paintings. Their stash was appraised at about $230 more than the curious participants’ collection.

The difference in strategies (curious versus urgent) and their outcomes (better memory versus higher-valued paintings) doesn’t mean one is better than the other, though.

“It’s valuable to learn which mode is adaptive in a given moment and use it strategically,” Dr Adcock said.

For example, being in an urgent, high-pressure mode might be the best option for a short-term problem.

“If you’re on a hike and there’s a bear, you don’t want to be thinking about long-term planning,” Sinclair said. “You need to focus on getting out of there right now.”

Opting for an urgent mindset might also be useful in less grisly scenarios that require short-term focus, Sinclair explained, like prompting people to get a COVID vaccine.

For encouraging long-term memory or action, stressing people out is less effective.

“Sometimes you want to motivate people to seek information and remember it in the future, which might have longer term consequences for lifestyle changes,” Sinclair said. “Maybe for that, you need to put them in a curious mode so that they can actually retain that information.”

Sinclair and Wang are now following up on these findings to see how urgency and curiosity activate different parts of the brain. Early evidence suggests that, by engaging the amygdala, an almond-shaped brain region best known for its role in fear memory, “urgent mode” helps form focused, efficient memories. Curious exploration, however, seems to shuttle the learning-enhancing neurochemical dopamine to the hippocampus, a brain region crucial for forming detailed long-term memories.

With these brain results in mind, Dr Adcock is exploring how her lab’s research might also benefit the patients she sees as a psychiatrist.

“Most of adult psychotherapy is about how we encourage flexibility, like with curious mode” Dr Adcock said. “But it’s much harder for people to do since we spend a lot of our adult lives in an urgency mode.”

These thought exercises may give people the ability to manipulate their own neurochemical spigots and develop “psychological manoeuvres,” or cues that act similar to pharmaceuticals, Dr Adcock explained.

“For me, the ultimate goal would be to teach people to do this for themselves,” Dr Adcock said. “That’s empowering.”

Source: Duke University

Nasal Swabs, not Snot Colour, are The Best Way to Determine if Kids’ Sinusitis is Bacterial

Photo by Andrea Piacquadio on Unsplash

In children with suspected sinusitis, a nasal swab to test for three types of bacteria can tell whether antibiotics are likely to be effective or not, according to a new JAMA study by researchers at the University of Pittsburgh and UPMC. They also found that nasal discharge colour was no help in differentiating a viral or bacterial infection.

“Sinusitis is one of the most common diseases we see in children, but it’s difficult to diagnose because it’s based on the duration of symptoms: If the child has a runny nose or congestion for more than 10 days, we suspect sinusitis,” said said lead author Nader Shaikh, MD. “For an ear infection, we can look inside the ear; for pneumonia, we listen to the lungs. But for sinusitis, we have nothing to go on from a physical exam. That was very unsatisfying to me.”

With the goal of developing a better tool to diagnose bacterial sinusitis, Shaikh and his team enrolled about 500 children with sinusitis symptoms from six centres across the US and randomly assigned them to receive either a course of antibiotics or placebo. The researchers also took nasal swabs from each child and tested for the three main types of bacteria involved in sinusitis.

Children who tested positive for the bacteria had better resolution of symptoms with antibiotic treatment compared to those who did not have bacteria. These findings suggest that testing for bacteria could be a simple and effective way to detect children who are likely to benefit from antibiotics and avoid prescribing antibiotics to those who wouldn’t.

“If antibiotics aren’t necessary, then why use them?” said Shaikh. “These medications can have side effects, such as diarrhoea, and alter the microbiome, which we still don’t understand the long-term implications of. Overuse of antibiotics can also encourage antibiotic resistance, which is an important public health threat.”

According to Shaikh, a common belief among parents and doctors is that yellow or green snot signals a bacterial infection. Although several small studies have suggested that nasal discharge colour is not meaningful, Shaikh and his team formally tested this idea by asking parents to identify the hue of their child’s snot on a colour card.

“If kids with green or yellow discharge benefitted more from antibiotics than those with clear-coloured discharge, we would know that colour is relevant for bacterial infection,” explained Shaikh. “But we found no difference, which means that colour should not be used to guide medical decisions.”

The researchers are now looking at how to best roll out nasal testing in the clinic. A major challenge is that bacterial culture-based tests used in the study are not easy for most family doctors to order and can take several days to get results. A more practical approach could be commercially available molecular testing, which could return results overnight, said Shaikh.

Another possibility could be development of rapid antigen tests that work like COVID-19 at-home testing kits. The researchers also plan to delve deeper into the data from this study to see whether there could be another type of biomarker in nasal discharge indicating the presence of bacteria that would be easier to test for.

Source: University of Pittsburgh

Metformin Also Seems to Protect Against Muscle Atrophy and Fibrosis

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Diabetes and muscle function might seem like they don’t have much to do with each other. But University of Utah Health researchers have discovered that metformin can also prevent muscle atrophy and muscular fibrosis – which can help the elderly bounce back faster from injury or illness. Their findings were published in the journal Aging Cell.

Metformin, the researchers found, actually has surprising applications on a cellular level. It can target senescent cells which impact muscle function. Senescent cells secrete factors associated with inflammation that may underlie fibrotic tissue, a hardening or scarring of tissues. They also discovered that metformin also reduces muscle atrophy.

“We’re interested in clinical application of this research,” says Micah Drummond, PhD, senior author of the study and professor of physical therapy and athletic training at the College of Health. “For example, knee surgeries in the elderly are notoriously hard to recover from. If we give a metformin-type agent during the recovery period, could we help the muscles get back to normal faster?”

Reinvigorating muscle recovery

Ageing comes with the risks of falls, hospitalisation, or developing chronic disease, which are more likely with muscle disuse. The research team wanted to find a therapeutic solution that could properly target both disuse atrophy and muscle recovery.

There’s an optimal level of senescent cells that are beneficial, no matter your age. In younger, healthier people, short-term senescence is required for a proper recovery from injury, and completely blocking the senescent effect impedes the body’s efforts to heal. Typically, a younger person can bounce back more easily after muscle disuse without the use of an intervention such as Metformin.

“In the case of aging, we know that there’s immune dysfunction,” says Drummond. “As you get older, it becomes harder for your body to clear senescent cells and they accumulate. That’s one reason recovery is much slower for the elderly after periods of disuse.”

Metformin’s anti-senescent properties have been demonstrated through pre-clinical studies. To test the intervention in humans, the team recruited 20 healthy male and female older adults for a multi-week study. They had participants undergo a muscle biopsy and MRI before the intervention, which involved five days of bed rest. One group of 10 received metformin and the other 10 received placebo pills during a two-week run-in period, then each group continued the placebo or metformin treatment during bed rest.

After the bed rest, participants received another muscle biopsy and MRI, then ceased treatments. All patients completed a seven-day re-ambulation period followed by a final muscle biopsy.

“We saw two things in our study,” Drummond says. “When participants took Metformin during a bed rest, they had less muscle atrophy. During the recovery period, their muscles also had less fibrosis or excessive collagen. That build-up can make it harder for the muscle to properly function.”

Tying these results to senescence, the research team examined muscle biopsies from study participants. They found that the participants who took Metformin had fewer markers of cellular senescence.

“This is the first paper that has made the direct connection between a therapy targeting cellular senescence and improved muscle recovery following disuse in aging,” says lead author Jonathan Petrocelli, PhD He explains that metformin helps muscle cells better remodel and repair tissue during periods of recovery after inactivity.

“Our real goal is to have patients maintain their muscle mass and function as they age, because atrophy and weakness are some of the strongest predictors of disease development and death,” he says.

Drummond’s team is following up on these findings by examining combining the drug with leucine, an amino acid that promotes growth and could accelerate recovery even further. They’ve already demonstrated the potency of this combination in preclinical animal studies.

“Metformin is cheap, effective and quite safe, so it’s exciting to see that we can use it to accelerate recovery for older individuals,” adds Drummond.

Source: University of Utah Health

Study Reveals How The Brain Detects and Regulates Inflammation

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A study published in the journal Neuron has revealed the existence of a circuit in the brain that senses and regulates the anti-inflammatory response, including the triggering of behaviours associated with sickness and releasing cortisone, a potent negative regulator of immune responses. This circuit embodies a two-way connection between the brain and immune system.

Whenever infections or injuries occur, the immune system is triggered to control the infection and repair damaged tissue. This process involves the release of pro-inflammatory mediators that inform the brain of the body’s immune status and coordinate the immune response. In response to this signal, the brain sets off a complex reaction known as ‘sickness behaviour’ whose purpose is to reassign energy to the body’s different systems. This state is associated with behavioural changes including social avoidance and lethargy, metabolic adjustments such as fever and loss of appetite, and the release of hormones such as cortisone, to increase resistance to infection while also regulating immune responses.

In this study, a multidisciplinary group consisting of neurobiologists and immunologists from the Institut Pasteur, Inserm and the CNRS discovered a novel circuit used by the brain to measure inflammation levels in the blood and, in response to this, regulate inflammation. A region of the brainstem known as the vagal complex directly detects levels and types of inflammatory hormones in the bloodstream. This information is then relayed to neurons in another region of the brainstem called the parabrachial nucleus, which also receives information related to pain and certain aversive or traumatic memories. In turn, these neurons activate neurons in the hypothalamus leading to a rapid increase in cortisone in the blood.

The scientists used state-of-the-art neuroscience approaches to identify this circuit, which enabled them to individually observe the neurons involved during inflammation. The experts observed how the activity of specific neurons in the parabrachial nucleus could regulate the production of white blood cells involved in the immune response. “This research demonstrates that neural activity in the brain alone can have a powerful effect on the development of immune responses during infection or injury. It therefore provides a clear example of the powerful two-way connection between the body and brain. It also fuels our ambition to discover the impact of our brain on the way we interact with microbes, fight off pathogens and heal wounds,” explains Gérard Eberl, Head of the Institut Pasteur’s Microenvironment and Immunity Unit.

The discovery of this circuit opens up new opportunities for research that will jointly contribute to the fields of neurobiology and immunology: “This study gives us additional tools to better understand the impact of systemic inflammation on our brain, mood and on certain neurodegenerative processes,” adds Gabriel Lepousez, a neurobiologist in the Perception and Memory Unit (Institut Pasteur/CNRS).

Given the established role of the parabrachial nucleus in aversive memory processes, potential infectious threats could be averted if this circuit is reactivated by the memory of past inflammatory or aversive experiences. Drawing on this neuro-immune communication, the immune system could therefore benefit from the brain’s ability to predict and anticipate threats in our environment.

Source: Institut Pasteur

Food Allergy in Infancy Linked to Childhood Asthma and Reduced Lung Function

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Infants that have a food allergy have an increased risk of asthma and reduced lung function later in childhood, according to a world first study published in the Lancet Child & Adolescent Health.

Food allergy affects 10% of babies and 5% of children and adolescents. The research, led by Murdoch Children’s Research Institute, found that early life food allergy was associated with an increased risk of both asthma and reduced lung growth at six years of age.

Murdoch Children’s Associate Professor Rachel Peters said this was the first study to examine the relationship between challenge-confirmed food allergy in infancy and asthma and poorer lung health later in childhood.

The Melbourne research involved 5276 infants from the HealthNuts study, who underwent skin prick testing to common food allergens, such as peanut and egg, and oral food challenges. At six years, children were followed up with further food allergy and lung function tests.

The study found by six years of age, 13.7% reported a diagnosis of asthma. Babies with a food allergy were almost four times more likely to develop asthma at six years of age, compared to children without a food allergy. The impact was greatest in children whose food allergy persisted to age six as opposed to those who had outgrown their allergy. Children with a food allergy were also more likely to have reduced lung function.

Associate Professor Peters said food allergy in infancy, whether it resolved or not, was linked to poorer respiratory outcomes in children.

“This association is concerning given reduced lung growth in childhood is associated with health problems in adulthood including respiratory and heart conditions,” she said.

“Lung development is related to a child’s height and weight and children with a food allergy can be shorter and lighter compared to their peers without an allergy. This could explain the link between food allergy and lung function. There are also similar immune responses involved in the development of both food allergy and asthma.

“The growth of infants with food allergy should be monitored. We encourage children who are avoiding foods because of their allergy to be under the care of a dietician so that nutrition can be catered for to ensure healthy growth.”

Source: Murdoch Childrens Research Institute