Monday, April 1, 2024

Novel AI model explains retinal sex difference

reposted from Novel AI model explains retinal sex difference Stories Mar 20, 2024 3 minutes The approach could lead to further biomarker discoveries to assist in disease diagnostics and early treatment interventions. Artificial intelligence (AI) applications are revolutionizing health diagnostics and precision medicine, yet how they identify patterns of disease in layers of data has largely remained a mystery. Research led by Vancouver Coastal Health Research Institute researcher Dr. Ipek Oruç revealed for the first time AI behaviours that differentiated between female and male retinal images, paving the way for other novel biomarkers of disease to aid in precision care. Dr. Ipek Oruc is an associate professor in the Department of Ophthalmology and Visual Sciences; associate member of the School of Biomedical Engineering; investigator with the Data Science Institute; and director of the NOVA Lab at the University of British Columbia. She is also a principal investigator with ICORD. An expert in visual neuroscience and artificial intelligence applications of retinal image analysis, Oruç’s PNAS Nexus study charts a path for other research teams to peek under the hood of AI algorithms to understand how the algorithm was developed in order to improve patient diagnostics and outcomes using medical imaging. “Our research opens the black box of AI, setting the stage for future research to apply this methodology to leverage its potential and identify previously unseen characteristics of various conditions.” Oruç and her team’s proof-of-concept study examined a convolutional neural network (CNN) model trained to classify patient sex in retinal images. CNNs are a type of deep neural network AI that can mimic human cognition in image processing and classification at superhuman speeds, processing thousands of images in a matter of seconds. The technology is already applied to a number of different AI algorithms using medical imaging for the detection and classification of conditions such as cancers and heart disease. The CNN used in Oruç’s study was trained to detect male and female retinal scans taken using a specialized fundus camera, a mainstay tool of optometry and ophthalmology used to capture images of the retina and other eye features. Ophthalmologists and nonexperts better able to detect retinal sex difference The research team developed and applied a novel methodology to discover for the first time retinal features that differentiate between male and female eyes. They tested 14 exploratory research questions that were derived from the behaviours and decisions of the CNN in what investigators termed the “Inspiration” phase of the model. Nine of the hypotheses revealed significant findings, five of which were verified. These biomarkers of sex difference in retinal images included greater retinal vascularization and a darker ring around the optic disk region in male retinas as compared to female retinas. These two images show subtle differences between male and female retinal images. The male image has a darker area around the optic disk, which appears as a bright spot in the images here, as well as more vasculature and nodes. Researchers then shared these distinguishing features with 26 expert ophthalmologists and 31 nonexperts. Prior to receiving this information, both groups’ ability to detect sex difference in retinal images averaged 50 per cent. After receiving training on the distinguishing characteristics between female and male retinal images discovered through Oruç’s novel methodology, both groups were able to identify the sex of the retinal images with approximately 66 per cent accuracy in the post-training block. This significant improvement is still a ways away from a 100 per cent detection rate, which indicates that additional differences have yet to be discovered to enable greater accuracy, Oruç says. "Our findings showcase an opportunity for biomarker discovery through CNN applications, with the added benefit of equipping medical practitioners with new diagnostic options that can be added to their clinical toolkit.” “We are now investigating other biomarkers present in fundus images that can be identified from CNNs, such as whether changes in the eye might signal a risk of stroke or dementia.” Oruç is also currently working on a study to apply this novel methodology to identify biomarkers in women that could lead to improvements in disease detection and treatment.

Thursday, February 1, 2024

Gut microbes can boost the motivation to exercise

source Gut microbes can boost the motivation to exercise Study in mice uncovers gut-to-brain pathway that increases exercise performance Date: December 14, 2022 Source: University of Pennsylvania School of Medicine Summary: Some species of gut-dwelling bacteria activate nerves in the gut to promote the desire to exercise, according to a study in mice. The study reveals the gut-to-brain pathway that explains why some bacteria boost exercise performance. Share: FULL STORY Some species of gut-dwelling bacteria activate nerves in the gut to promote the desire to exercise, according to a study in mice that was led by researchers at the Perelman School of Medicine at the University of Pennsylvania. The study was published today in Nature, and reveals the gut-to-brain pathway that explains why some bacteria boost exercise performance. In the study, the researchers found that differences in running performance within a large group of lab mice were largely attributable to the presence of certain gut bacterial species in the higher-performing animals. The researchers traced this effect to small molecules called metabolites that the bacteria produce -- metabolites that stimulate sensory nerves in the gut to enhance activity in a motivation-controlling brain region during exercise. "If we can confirm the presence of a similar pathway in humans, it could offer an effective way to boost people's levels of exercise to improve public health generally," said study senior author Christoph Thaiss, PhD, an assistant professor of Microbiology at Penn Medicine. Thaiss and colleagues set up the study to search broadly for factors that determine exercise performance. They recorded the genome sequences, gut bacterial species, bloodstream metabolites, and other data for genetically diverse mice. They then measured the amount of daily voluntary wheel running the animals did, as well as their endurance. The researchers analyzed these data using machine learning, seeking attributes of the mice that could best explain the animals' sizeable inter-individual differences in running performance. They were surprised to find that genetics seemed to account for only a small portion of these performance differences -- whereas differences in gut bacterial populations appeared to be substantially more important. In fact, they observed that giving mice broad-spectrum antibiotics to get rid of their gut bacteria reduced the mice's running performance by about half. Ultimately, in a years-long process of scientific detective work involving more than a dozen separate laboratories at Penn and elsewhere, the researchers found that two bacterial species closely tied to better performance, Eubacterium rectale and Coprococcus eutactus, produce metabolites known as fatty acid amides (FAAs). The latter stimulate receptors called CB1 endocannabinoid receptors on gut-embedded sensory nerves, which connect to the brain via the spine. The stimulation of these CB1 receptor-studded nerves causes an increase in levels of the neurotransmitter dopamine during exercise, in a brain region called the ventral striatum. The striatum is a critical node in the brain's reward and motivation network. The researchers concluded that the extra dopamine in this region during exercise boosts performance by reinforcing the desire to exercise. "This gut-to-brain motivation pathway might have evolved to connect nutrient availability and the state of the gut bacterial population to the readiness to engage in prolonged physical activity," said study co-author, J. Nicholas Betley, PhD, an associate professor of Biology at the University of Pennsylvania's School of Arts and Sciences. "This line of research could develop into a whole new branch of exercise physiology." The findings open up many new avenues of scientific investigation. For example, there was evidence from the experiments that the better-performing mice experienced a more intense "runner's high" -- measured in this case by a reduction in pain sensitivity -- hinting that this well-known phenomenon is also at least partly controlled by gut bacteria. The team now plans further studies to confirm the existence of this gut-to-brain pathway in humans. Apart from possibly offering cheap, safe, diet-based ways of getting ordinary people running and optimizing elite athletes' performance, he added, the exploration of this pathway might also yield easier methods for modifying motivation and mood in settings such as addiction and depression. The study was led by Penn Medicine scientist Lenka Dohnalová. Other Penn Medicine authors include: Patrick Lundgren, Jamie Carty, Nitsan Goldstein, Lev Litichevskiy, Hélène Descamps, Karthikeyani Chellappa, Ana Glassman, Susanne Kessler, Jihee Kim, Timothy Cox, Oxana Dmitrieva-Posocco, Andrea Wong, Erik Allman, Soumita Ghosh, Nitika Sharma, Kasturi Sengupta, Mark Sellmyer, Garret FitzGerald, Andrew Patterson, Joseph Baur, Amber Alhadeff, and Maayan Levy. The study was supported in part by the National Institutes of Health (S10-OD021750, DP2AG067492, R01-DK-129691, , P01-DK119130 and R01-DK115578), the Pew Charitable Trust, the Edward Mallinckrodt, Jr. Foundation, the Agilent Early Career Professor Award, the Global Probiotics Council, the IDSA Foundation, the Thyssen Foundation, the Human Frontier Science Program, and Penn Medicine, including the Dean's Innovation Fund. RELATED TOPICS Health & Medicine Fitness Ulcers Gastrointestinal Problems Colitis Plants & Animals Mice Bacteria Veterinary Medicine Biology RELATED TERMS Anaerobic exercise Aerobic exercise Histamine Gastrointestinal tract Swimming Bacteria Physical exercise Gymnastics Story Source: Materials provided by University of Pennsylvania School of Medicine. Note: Content may be edited for style and length. Journal Reference: Dohnalová, L., Lundgren, P., Carty, J.R.E. et al. A microbiome-dependent gut–brain pathway regulates motivation for exercise. Nature, 2022 DOI: 10.1038/s41586-022-05525-z Cite This Page: MLA APA Chicago University of Pennsylvania School of Medicine. "Gut microbes can boost the motivation to exercise." ScienceDaily. ScienceDaily, 14 December 2022. .

Friday, February 3, 2023

Can We Put the Brakes on Parkinson’s Progression?

reposted from Can We Put the Brakes on Parkinson’s Progression? May 05, 2022 put breaks pd progression blog Researchers are lasered in on slowing and someday stopping Parkinson's disease (PD) in its tracks. Explore what they've discovered, see what the future might hold and learn how some of the strongest weapons in the fight against Parkinson's progression are practices you can put in place today. This article is based on Can We Put the Brakes on PD Progression, a Parkinson’s Foundation Expert Briefing webinar presented by Joash Lazarus, MD, Multiple Sclerosis Center of Atlanta. PD symptoms stem from a protein, called alpha-synuclein, that clumps and accumulates in certain areas of the brain. This process depletes dopamine, which is critical to many body processes, including smooth, coordinated movements. Though dopamine declines for everyone who lives with Parkinson's, each person experiences disease symptoms differently. Parkinson's symptoms can impact your life in numerous ways. Using a range of therapies and supports as needed can make all the difference. Personalized medicines, social support groups, mental health care and participation in clinical trials have all shown benefit to people with Parkinson's. But is there a way to slow Parkinson's progression? While scientists are evaluating everything from medications to mindfulness practice for clues, they've discovered some of the biggest benefits start at home. Healthy Eating and Regular Exercise: A Powerful Combo Making nutritious food the mainstay of your meals and enjoying regular exercise has countless proven benefits. Studies show targeted nutrition may slow Parkinson's advancement. Eating a whole-food, plant-based, Mediterranean-style diet — including fresh vegetables, fruit and berries, nuts, seeds, fish, olive and coconut oils and more — may be linked to slower PD progression. When you live with PD, exercise is also critical to optimal health. In fact, the Parkinson’s Outcomes Project shows at least 2.5 hours a week of physical activity can slow PD symptom progression. Research reveals regular exercise also shows neuroprotective effects in animal models with Parkinson's. Exercise benefits people of all ages. As people get older, their risk for falls increase. For people with PD, the chance of falls is two to three times higher. Up to half of these falls can result in major injury. Exercise is the only thing to notably minimize a person’s risk of falling. Regular physical activity can also boost balance, improve heart and lung function, increase memory, thinking and problem solving, minimize depression and more. Here's how to make exercise work for you: Maximize benefits by exercising moderately to vigorously 150 minutes a week. Plan a weekly routine that includes aerobic activity, strength training, balance and stretching exercises. Visit a physical therapist with Parkinson’s expertise for a functional evaluation and exercise recommendations. Reference this Parkinson’s Exercise Recommendations PDF in English or Spanish to help guide your physical activity plan. Specialized Parkinson's movement and speech therapies, such as the Lee Silverman Voice Treatment (LSVT) BIG and LOUD programs, have also shown potential to lessen symptoms and slow PD progression. Exploring Therapy Advances People with Parkinson's take a variety of medications to manage symptoms. PD researchers have spent decades working to discover therapies powerful enough to slow or stop Parkinson's. Some of these include: Rasagiline The 2009 ADAGIO study looked at whether rasagiline — a monoamine oxidase-B (MAO-B) inhibitor (these can minimize the enzyme MAO-B's breakdown of dopamine and ease movement symptoms) — could put the brakes on disease progression for people in early-stage Parkinson's. The results suggested the possibility that a 1 mg daily dose of rasagiline might hold disease-modifying potential, but a 2mg daily dose did not. Despite the study's uncertainties, it still showed ample evidence that rasagiline better controlled symptoms for people with PD, which is why it's used in concert with levodopa, currently the most powerful medication for Parkinson's and a treatment mainstay since its discovery in the 1960s. Levodopa Levodopa is a proven effective therapy throughout the Parkinson's journey. In the past, people often delayed starting levodopa therapy based on the myth that it would stop working after a few years. A 2019 study looked at whether starting levodopa earlier or later could change the course of Parkinson's. While research showed levodopa didn't slow PD, it proved starting the medication early on in Parkinson's is safe. Deep Brain Stimulation When people who live with PD begin to experience severe motor fluctuations, tremors and dyskinesia, involuntary muscle movements that can't be controlled by optimal medication doses, a surgically implanted deep brain stimulation (DBS) device can deliver electrical pulses to the brain, easing symptoms and boosting quality of life. Results of a 2020 study proved people with Parkinson's disease can also get long-term symptom relief with DBS. The research shows people who have DBS therapy early on — coupled with optimal medication — generally do better with dyskinesia control. Despite the profound benefits of DBS, it's not proven to delay disease progression. As researchers work to solve the Parkinson's puzzle, empower yourself by prioritizing your well-being. Wholesome food paired with regular exercise habits and comprehensive team-based treatment are the building blocks of a better life with PD. Additional Information The Parkinson’s Foundation Exercise Guidelines for People with Parkinson’s offers tips to stay in top shape. Learn more about PD therapies in Medications: A Treatment Guide to Parkinson’s Disease. Get moving with Fitness Fridays — Parkinson's Foundation PD-tailored at home workouts. Dig in to why what and how you eat matters with Mindfulness: Nutrition and Mindful Eating, part of our Mindfulness Mondays series.

Pineapple Pesticide Linked to Parkinson's Disease

reposted from Pineapple Pesticide Linked to Parkinson's Disease The pineapple pesticide made its way into milk in Hawaii and then into men's brains. A study is the latest to link pesticides to Parkinson's. Image: Pineapples lay in the middle of a large plantation Pineapples lay in the middle of a large plantation in January 2014.Kaveh Kazemi / Getty Images, file Link copied Dec. 9, 2015, 6:55 PM EST / Updated Dec. 9, 2015, 6:55 PM EST By Maggie Fox A pineapple pesticide that made its way into milk in Hawaii also made its way into men’s brains, and those men were more likely to develop Parkinson’s disease, a new study finds. It’s the latest in a very long series of studies linking various pesticides to Parkinson’s, which is caused by the loss of certain brain cells. And the study also seems to support a mystifying observation: smokers seem to be protected against Parkinson’s. For the study, Dr. Robert Abbott of the Shiga University of Medical Science in Otsu, Japan, and colleagues studied 449 Japanese-American men living in Hawaii who were taking part in a larger study of aging. They gave details of how much milk they drank as part of a larger survey, and they donated their brains for study after they died. “For people living with Parkinson's, understanding the impact of environmental factors is crucial." The men who drank more than 16 ounces of milk a day had the fewest brain cells in a part of the brain called the substantia nigra, which is damaged in Parkinson’s, they reported in the journal Neurology. The researchers also looked for the pesticide heptachlor, which was taken off the market for most uses in the U.S. in 1988. "Among those who drank the most milk, residues of heptachlor epoxide were found in nine of 10 brains as compared to 63.4 percent for those who consumed no milk," the researchers wrote. It’s known the milk in Hawaii was contaminated, probably from the feed given to the cattle. "The researchers could not test whether the milk the men drank was contaminated with pesticides (heptachlor, in this case), and no one knows how long or how widespread the contamination was before being detected," the Parkinson’s Disease Foundation said in a statement on its website. Recommended OUT NEWS Trans physician uses life savings to keep clinic open after insurers deny reimbursements HEALTH NEWS As weight loss drugs soar in popularity, many who could benefit can't get them "The potential link between drinking milk, pesticides and development of Parkinson’s disease needs further investigation," the foundation said. The men who smoked and who also drank milk showed none of the brain cell loss. "This study is unique because it brings together two critical but different pieces of information — environmental exposure and physical changes in the brain — to understand potential contributors of Parkinson’s disease," James Beck, vice president of scientific affairs at the Parkinson's Disease Foundation, said in a statement. “The potential link between drinking milk, pesticides and development of Parkinson’s disease needs further investigation.” "For people living with Parkinson's, understanding the impact of environmental factors is crucial as nearly 85 percent have no idea why they developed Parkinson’s. There is no clear genetic link," Beck said. The Parkinson's Disease Foundation estimates that 1 million Americans have the condition, marked by tremor, rigid muscles and problems with movement. There is no cure, although early treatment can delay the worst symptoms. "For scientists, the opportunity to study brains generously donated by the participants of this study was crucial to establishing a potential link between different environmental exposures and Parkinson’s, and will be crucial to solving the disease overall," Beck said. Maggie Fox Maggie Fox is a senior writer for NBC News and TODAY, covering health policy, science, medical treatments and disease.

Tuesday, January 31, 2023

Mitochondrial Metabolism Dictates Neurons’ Growth Rate

reposted from Mitochondrial Metabolism Dictates Neurons’ Growth Rate Altering the rate of respiration in mitochondria changes how fast neurons grow, making mouse neurons grow more like human ones and vice versa, a study finds. a human neuron illuminated in bright green on a black background. A black and white headshot of Katherine Irving Katherine Irving Jan 30, 2023 | 4 min read PDF VERSION ABOVE: A human cortical neuron RYOHEI IWATA Human brains grow extraordinarily slowly—a trait many neuroscientists speculate is related to our distinctive intellect. But how and why a human neuron takes years to grow when a mouse neuron grows for mere weeks has remained unclear. Now, scientists have uncovered one piece of the puzzle: Neuron growth is mediated by its mitochondria’s metabolism, according to a January 26 study in Science. The finding could not only help answer fundamental questions about brain development, the study authors say it could widen treatment options for developmental disorders. “This is the most exciting study I’ve read in a while,” says Suzana Herculano-Houzel, a biologist and neuroscientist at Vanderbilt University who wasn’t involved in the research. “It opens a path for finding answers to, what is to me, one of the biggest questions we have: What makes different brains different?” For senior study author and developmental biologist Pierre Vanderhaeghen, the underlying cause of human neurons’ prolonged growth had long lay tantalizingly out of reach. Nearly a decade ago, he and colleagues at the Free University of Brussels in Belgium put human cortical neurons inside mouse brains, expecting them to grow faster. But to their surprise, the human neurons still grew slowly when transplanted. This suggested to Vanderhaeghen, who also works at the Flanders Institute for Biotechnology and the Catholic University of Leuven, that the cause of a neuron’s glacial growth was intrinsic to the neuron itself and not the consequence of signals from the surrounding brain, he explains. Moreover, he and his colleagues at the time noted that every single aspect of the neuron, from its dendrites to its synapses to its axon, grows in synchrony, indicating that the growth is regulated by a ubiquitous, basal component of the cell. Other research had posited that mitochondria may somehow play important roles in the development of cells. So he and his team set out to investigate whether mitochondria are involved in regulating neuron growth. A purple human neuron with white mitochondria dotting the surface A human neuron with mitochondria stained in white RYOHEI IWATA First, though, they needed to ensure they could accurately pinpoint the age of any given neuron. Knowing a neuron’s age is vital for gauging its growth over time, but getting an exact birthdate for each neuron had been next to impossible, Vanderhaeghen explains, as neurons don’t develop at the same rate as one another, even when their original stem cells are created at the same time. However, stem cells can only become neurons after promoter NeuroD1 is activated. So Vanderhaeghen and colleagues came up with a genetic tool that uses an engineered recombinase enzyme called CreER that identifies when NeuroD1 is turned on and immediately tags the neuron—essentially flagging its “birth.” With the ability to date the neurons, Vanderhaeghen and his team could start testing the effect mitochondria have on neuron growth rates. Initially, Vanderhaeghen says, the team examined mitochondrial morphology and genetics. But on a whim, they also decided to look at the organelles’ respiration rates—basically, how much oxygen they consume, which is also a measure of how much cellular fuel they produce. They used oxygraphy to monitor the oxygen intake of mouse neurons for the first 20 days after their birth—and were stunned to find that after two weeks, the oxygen consumption rate of neurons had grown to nearly ten times that of human neurons. From there, Vanderhaeghen says everything fell into place. The team knew they could manipulate mitochondrial respiration pharmacologically, so they sped up metabolism in human cortical neurons in vitro. Vanderhaeghen recalls a moment in the lab looking at the neurons; at only a few weeks old, the accelerated cortical neurons were considerably more mature than a normal human neuron. “To us, this was a big eureka moment,” he says. “There we thought, ‘this is it.’” The scientists tested the same principle in vivo, speeding up the mitochondrial metabolism of human neurons and implanting them into mice, as well as slowing down the mitochondrial metabolism of mouse neurons both in culture and inside the mice’s brains. The results from both in and out of the brain aligned: Human neurons with increased metabolic rates grew faster than normal, and mouse neurons with decreased mitochondrial metabolic rates displayed slower growth. Many scientists theorize that the human brain’s slow growth is part of what allows for our unique mental capacities. Knowing that a metabolism regulator can slow or speed up that growth will allow for further studies into what makes us human, Vanderhaeghen posits. He adds that targeting mitochondrial metabolism could one day be considered in the treatment of some developmental disorders, which can arise from brain development that is either too fast or too slow. However, he emphasizes that this study is only the beginning. “I would be very naive to think that mitochondria are the [only] solution” to resolving issues related to developmental timing, he says. “Mitochondria are just one mechanism, and there are probably going to be many others.” Nonetheless, Herculano-Houzel is excited to see where this research will go. “That is the definition of good science: You answer one question, and that brings up ten new questions you didn’t know you had,” she says. “What happens if you play with energy transfer in a developing brain? Do you directly affect the size of the brain? Do you affect how many neurons are generated? These are all fundamental questions, and they can all be asked now.” Keywords: brain developmentbrain plasticitycell biologycortical neurondevelopmental biologydevelopmental delaygrowthhuman cognitionmetabolismmicrobiologymitochondriamouse brainneural developmentneuronal plasticityneuronsNewsNews Brief

Tuesday, December 20, 2022

Mice With a Healthy Gut Microbiome Are More Motivated to Exercise

reposted from Mice With a Healthy Gut Microbiome Are More Motivated to Exercise A neural pathway between the gut and the brain led to the release of dopamine when the mice ran on a wheel or treadmill, but only in the presence of a robust microbiome. a white mouse sits on a blue exercise wheel, looking out onto the shavings below A black and white headshot of Katherine Irving Katherine Irving Dec 16, 2022 | 4 min read PDF VERSION ABOVE: © ISTOCK.COM, MARY SWIFT The gut is a jungle teeming with microorganisms that are instrumental to the process of digesting food, regulating metabolism, and defending against infection. However, research now suggests yet another way that the gut microbiome’s influence extends far past the bounds of its abdominal home. In mice, gut bacteria stimulate the production of dopamine during exercise, without which the mice lack the motivation to continue running, scientists at the University of Pennsylvania reported December 14 in Nature. “This is the most comprehensive study I have ever seen,” says Theodore Garland Jr., an evolutionary physiologist studying the gut-brain axis in mice at the University of California, Riverside, who wasn’t involved in the research. “[It’s] pulling together lots of different pieces that we knew before in different contexts or in isolation of other parts in a way that hasn’t been done before.” Exercise is “the single most effective lifestyle intervention that we have that protects us from a very large range of diseases,” says study coauthor Christoph Thaiss, a microbiologist at the University of Pennsylvania Perelman School of Medicine. Yet despite being a very physical activity, he says the success of an individual’s attempts to exercise often depends on their mental state. “If you look at what elite athletes say, many of them will say that they are not necessarily physically better than their competitors, but their mind is very well prepared,” he says. “But when it comes to preparing athletes, mentally or motivationally, for their competitions, there’s very little scientific evidence of how these methods might work.” Previous research had already found that the gut microbiome can influence muscle tissue and cardiovascular fitness as well as brain chemistry. But Thaiss aimed to bring such findings together and examine the broader role of the gut microbiome in exercise performance. So, he and his colleagues set up an experiment using 199 outcrossed mice from eight different genetic backgrounds to ensure that any findings weren’t limited to one strain. Using multiple antibiotics, the researchers altered the mice’s microbiome communities: some mice had fully functioning microbiomes, while the others had their gut microbiomes either partially or entirely removed. See “Tinkering with Gut Microbes Boosts Brain Plasticity in Mice” They then tested each mouse’s performance while running in two different settings: a treadmill, on which the mice were forced to run for an extended period to test their endurance, and a wheel, on which the mice were allowed to run as often and for as long as they wanted. Although all the mice were equally capable of moving around their cages, the mice with reduced microbiomes tired more quickly when exercising on the treadmill than mice with robust microbiomes. They also spent less time on the wheel, which the researchers attributed to reduced motivation to exercise. Thaiss then searched for a neural explanation for the behavioral differences among the groups of mice. He and his team used RNA sequencing to analyze the mice’s striatal spiny neurons, which are involved in producing the behavior-reinforcing neurotransmitter dopamine both before and after exercise, and found that many of the genes normally expressed during exercise were dampened without the microbiome. When he performed an experiment limiting dopamine production during exercise by inhibiting these neurons, it had the same effect that limiting or entirely removing the microbiome had in the previous experiment. From these experiments, Thaiss inferred that the production of dopamine was a significant factor in a mouse’s propensity to exercise, and that a mouse’s gut microbiome composition played some role in the regulation of dopamine in its brain. That led him to conclude that the mice lacking gut bacteria didn’t experience the dopamine rush animals usually get through exercise, known as the “runner’s high.” “If we can remote[ly] control the brain from the perspective of the GI tract, then this becomes a much more accessible problem.” —Christoph Thaiss, University of Pennsylvania Perelman School of Medicine The question then became how microbes in the gut influence dopamine in the brain. To find out, the team inhibited a set of neurons that connects the gastrointestinal tract to the brain using formulated drugs. In the same wheel and treadmill experiments as before, mice with healthy microbiomes but inhibited gut-brain neurons exhibited reduced exercise rates on par with the mice with limited microbiomes, suggesting that it was the stimulation of these neurons that controlled the amount the mice exercised. Finally, the researchers treated mice with specific antibiotics to determine what kinds of microbes were triggering the neurons. They performed a metabolomics analysis to determine which bacterial metabolites triggered the neural response. They found that metabolites known as fatty acid amides (FAAs) made by some microbes found in a healthy mouse gut were the most active during exercise. These FAAs generate neurotransmitters known as endocannabinoids. The scientists performed more experiments using ingestible inhibitors to determine that the endocannabinoids produced by the bacteria’s FAAs were stimulating receptors in the GI tract neurons during exercise, thereby triggering the neurons that subsequently stimulated dopamine production in the brain. “It was really elegant the way they structured the entire story,” says Francesca Ronchi, an immunologist at the Institute of Microbiology, Infectious Diseases and Immunology in Berlin, Germany who wasn’t involved in the study. She adds that she was very impressed by the thoroughness of the paper. “You couldn’t do it better.” Thaiss says that the next step will be to take this research from mice to humans and determine whether the same pathway exists in us. Garland explains that analyzing motivation in humans is more complicated than it is in mice: a person’s incentive to exercise is based on many more factors, including external ones such as their social environment and influence from family or friends, than is a mouse’s. “We don’t go and give our mice pep talks when they run a lot on the wheel,” he observes. In humans, by contrast, those that are naturally talented at some form of exercise may receive more praise, fueling them to exercise more. See “Regular Exercise Helps Patients Combat Cancer” Nonetheless, Ronchi says findings like these could one day reveal ways to stimulate exercise in those who need it, including cancer, Parkinson’s, or Alzheimer’s patients, for whom exercise is a valuable tool in mitigating symptoms. After all, if such a pathway does exist in people, gut microbes may be easier to manipulate or influence than neurons in the brain, Thaiss suggests: Unlike neurons, which are finicky and often inaccessible, gut bacteria could be influenced by an ingestible treatment. “If we can remote[ly] control the brain from the perspective of the GI tract, then this becomes a much more accessible problem,” he says. “But that’s still science fiction for now.” Keywords: bacteriaexercisefitnessgut bacteriagut microbiotaimmunologymicrobiologymicrobiomemicrobiotamouse studyneural activationneuronneurotransmittersNewspathwaysignaling pathwaysstudy story

Wednesday, August 17, 2022

Nurtured by nature Psychological research is advancing our understanding of how time in nature can improve our mental health and sharpen our cognition

reposted from FEATURE Nurtured by nature Psychological research is advancing our understanding of how time in nature can improve our mental health and sharpen our cognition By Kirsten Weir Date created: April 1, 2020 12 min read Vol. 51, No. 3 Print version: page 50 Cognition and the Brain Environment and Population 91 Girl and mother walking through a park Be honest: How much time do you spend staring at a screen each day? For most Americans, that number clocks in at more than 10 hours, according to a 2016 Nielsen Total Audience Report. Our increasing reliance on technology, combined with a global trend toward urban living, means many of us are spending ever less time outdoors—even as scientists compile evidence of the value of getting out into the natural world. From a stroll through a city park to a day spent hiking in the wilderness, exposure to nature has been linked to a host of benefits, including improved attention, lower stress, better mood, reduced risk of psychiatric disorders and even upticks in empathy and cooperation. Most research so far has focused on green spaces such as parks and forests, and researchers are now also beginning to study the benefits of blue spaces, places with river and ocean views. But nature comes in all shapes and sizes, and psychological research is still fine-tuning our understanding of its potential benefits. In the process, scientists are charting a course for policymakers and the public to better tap into the healing powers of Mother Nature. “There is mounting evidence, from dozens and dozens of researchers, that nature has benefits for both physical and psychological human well­being,” says Lisa Nisbet, PhD, a psychologist at Trent University in Ontario, Canada, who studies connectedness to nature. “You can boost your mood just by walking in nature, even in urban nature. And the sense of connection you have with the natural world seems to contribute to happiness even when you’re not physically immersed in nature.” Cognitive benefits Spending time in nature can act as a balm for our busy brains. Both correlational and experimental research have shown that interacting with nature has cognitive benefits—a topic University of Chicago psychologist Marc Berman, PhD, and his student Kathryn Schertz explored in a 2019 review. They reported, for instance, that green spaces near schools promote cognitive development in children and green views near children’s homes promote self-control behaviors. Adults assigned to public housing units in neighborhoods with more green space showed better attentional functioning than those assigned to units with less access to natural environments. And experiments have found that being exposed to natural environments improves working memory, cognitive flexibility and attentional control, while exposure to urban environments is linked to attention deficits (Current Directions in Psychological Science, Vol. 28, No. 5, 2019). Researchers have proposed a number of ideas to explain such findings, as Nisbet and colleagues described in a review of the benefits of connection with nature (Capaldi, C.A., et al., International Journal of Wellbeing, Vol. 5, No. 4, 2015). The biophilia hypothesis argues that since our ancestors evolved in wild settings and relied on the environment for survival, we have an innate drive to connect with nature. The stress reduction hypothesis posits that spending time in nature triggers a physiological response that lowers stress levels. A third idea, attention restoration theory, holds that nature replenishes one’s cognitive resources, restoring the ability to concentrate and pay attention. The truth may be a combination of factors. “Stress reduction and attention restoration are related,” Nisbet points out. “And because of the societal problems we’re dealing with in terms of stress, both of these theories have gotten a lot of attention from researchers.” Experimental findings show how impressive nature’s healing powers can be—just a few moments of green can perk up a tired brain. In one example, Australian researchers asked students to engage in a dull, attention-draining task in which they pressed a computer key when certain numbers flashed on a screen. Students who looked out at a flowering green roof for 40 seconds midway through the task made significantly fewer mistakes than students who paused for 40 seconds to gaze at a concrete rooftop (Lee, K.E., et al., Journal of Environmental Psychology, Vol. 42, No. 1, 2015). Even the sounds of nature may be recuperative. Berman and colleagues found that study participants who listened to nature sounds like crickets chirping and waves crashing performed better on demanding cognitive tests than those who listened to urban sounds like traffic and the clatter of a busy café (Van Hedger, S.C., et. al., Psychonomic Bulletin & Review, Vol. 26, No. 2, 2019). grinning boy standing on his head Nature and happiness While such laboratory experiments are intriguing, they don’t fully capture the diverse benefits that go hand in hand with time spent in the outdoor world, says Cynthia Frantz, PhD, a professor of psychology and environmental studies at Oberlin College in Ohio. “Spending time in nature has cognitive benefits, but it also has emotional and existential benefits that go beyond just being able to solve arithmetic problems more quickly,” she notes. In a review of the research, Gregory Bratman, PhD, an assistant professor at the University of Washington, and colleagues shared evidence that contact with nature is associated with increases in happiness, subjective well-being, positive affect, positive social interactions and a sense of meaning and purpose in life, as well as decreases in mental distress (Science Advances, Vol. 5, No. 7, 2019). Other work suggests that when children get outside, it leaves a lasting impression. In a study of residents of Denmark, researchers used satellite data to assess people’s exposure to green space from birth to age 10, which they compared with longitudinal data on individual mental health outcomes. The researchers examined data from more than 900,000 residents born between 1985 and 2003. They found that children who lived in neighborhoods with more green space had a reduced risk of many psychiatric disorders later in life, including depression, mood disorders, schizophrenia, eating disorders and substance use disorder. For those with the lowest levels of green space exposure during childhood, the risk of developing mental illness was 55% higher than for those who grew up with abundant green space (Engemann, K., et al., PNAS, Vol. 116, No. 11, 2019). There is even evidence that images of nature can be beneficial. Frantz and colleagues compared outcomes of people who walked outside in either natural or urban settings with those of people who watched videos of those settings. They found that any exposure to nature—in person or via video—led to improvements in attention, positive emotions and the ability to reflect on a life problem. But the effects were stronger among those who actually spent time outside (Mayer, F.S., et al., Environment and Behavior, Vol. 41, No. 5, 2009). More recently, scientists have begun exploring whether virtual reality nature experiences are beneficial. In a review of this work, Mathew White, PhD, an environmental psychologist at the University of Exeter in England, and colleagues concluded that while the real deal is best, virtual reality can be a worthwhile substitute for people who are unable to get outdoors, such as those with mobility problems or illness (Neuro­psychiatric Disease and Treatment, Vol. 14, 2018). Nature might also make us nicer—to other people as well as to the planet. John Zelenski, PhD, a professor of psychology at Carleton University in Ontario, Canada, and colleagues showed undergraduates either nature documentaries or videos about architectural landmarks. Then the participants played a fishing game in which they made decisions about how many fish to harvest across multiple seasons. Those who had watched the nature video were more likely to cooperate with other players, and also more likely to make choices that would sustain the fish population (Journal of Environmental Psychology, Vol. 42, No. 1, 2015). In another experiment, Zelenski and his colleagues found that elementary school children acted more prosocially to classmates and strangers after a field trip to a nature school than they did after a visit to an aviation museum (Dopko, R.L., et al., Journal of Environmental Psychology, Vol. 63, No. 1, 2019). Those generous behaviors weren’t attributed to students’ moods, Zelenski and his colleagues found, so it wasn’t simply that spending time in nature made them happier and therefore more giving. Another plausible (though unproven) explanation is the emotion of awe. “There are some hints that awe is associated with generosity, and nature can be a way to induce awe,” he says. “One of the things that may come from awe is the feeling that the individual is part of a much bigger whole.” Experience vs. connection With so many benefits linked to nature, people naturally wonder: How much time outside is enough? White and colleagues took a stab at answering that question by studying a representative sample of nearly 20,000 adults across the United Kingdom. They found people who had spent at least two recreational hours in nature during the previous week reported significantly greater health and well-being. That pattern held true across subgroups including older adults and people with chronic health problems, and the effects were the same whether they got their dose of nature in a single 120-minute session or spread out over the course of the week (Scientific Reports, Vol. 9, No. 1, 2019). “We’re not saying we’ve cracked this nut yet, but this is a first step toward making specific recommendations about how much time in nature is enough,” White says. The amount of time one spends in nature isn’t the only element to consider—it’s also beneficial to feel connected to the natural world even when you’re stuck at a desk. Researchers call this feeling by a variety of names, including nature relatedness, connectedness to nature and inclusion of nature in self, and they’ve developed a number of scales to measure the trait. Whatever you call it, connectedness to nature seems to benefit mood and mental health. In a meta-analysis, Alison Pritchard, PhD, ABPP, at the University of Derby in England, and colleagues found that people who feel more connected to nature have greater eudaimonic well-being—a type of contentment that goes beyond just feeling good and includes having meaningful purpose in life (Journal of Happiness Studies, online first publication, 2019). Zelenski and Nisbet studied whether connection itself is the magic ingredient. They assessed the overlap between connectedness with nature and a general sense of connectedness, such as feeling in tune with one’s friends or community. They found that feeling connected to nature was a significant predictor of happiness even after controlling for the effects of general connectedness (Environment and Behavior, Vol. 46, No. 1, 2014). “People who feel that their self-concept is intertwined with nature report being a bit happier,” says Zelenski. “Nature connectedness isn’t the biggest predictor of happiness, but [the association between the two] is quite consistent.” In fact, nature might help to buffer the effects of loneliness or social isolation. White and his colleagues surveyed 359 U.K. residents about their social connectedness and proximity to nature over the previous week. Social isolation is typically associated with worse subjective well-being. But the researchers found that when people with low social connectedness had high levels of nearby nature, they reported high levels of well­being (Cartwright, B.D.S., et al., International Journal of Environmental Research and Public Health, Vol. 15, No. 6, 2018). “There are people who don’t necessarily want to spend their time with others, but they feel connected to the natural environment, and that can enhance their well-being,” White says. Green and blue spaces It’s clear that getting outside is good for us. Now, scientists are working to determine what types of environments are best. Much attention has gone to green spaces, but White has studied a variety of marine and freshwater environments and found these blue spaces are also good for well-being (Gascon, M., et al., International Journal of Hygiene and Environmental Health, Vol. 220, No. 8, 2017.) In fact, he says, they may even be slightly more restorative than green spaces. There may also be value in trekking to remote locations. In a survey of 4,515 U.K. residents, White found that people reported more connection to nature and felt more restored after visiting rural and coastal locations than they did after spending time in urban green spaces. Areas deemed to be “high environmental quality”—such as nature reserves and protected habitats—were also more beneficial than areas with low biodiversity (Wyles, K.J., et al., Environment and Behavior, Vol. 51, No. 2, 2019). In other work, White and his colleagues found that people who watched nature videos with a diverse mix of flora and fauna reported lower anxiety, more vitality and better mood than those who watched videos featuring less biodiverse landscapes (Wolf, L.J., et al., PLOS ONE, Vol. 12, No. 1, 2017). woman admiring body of water and beautiful hills But there’s an important caveat, White adds: “If you have a break from work and you’ve only got half an hour, then a wild remote place is no use to you at all.” Urban parks and trees also produce positive outcomes. Just like a little exercise is better than none, we should take­ advantage of green and blue spaces wherever and whenever we can. That’s easier said than done, though, especially for people at a socioeconomic disadvantage. Poorer neighborhoods, White notes, are seldom the ones with leafy groves and ocean views. Yet policymakers, city planners, environmental organizations and government agencies are coming around to the importance of natural spaces, and psychologists are offering them their expertise, says White, who has presented his research to groups such as the U.K.’s Department for Environment, Food and Rural Affairs. Organizations and cities are expressing interest in this research, Zelenski says, though many policymakers are waiting to see the results of intervention studies before investing in green infrastructure. One of the United Nations’ sustainable development goals includes the target of providing universal access to safe, inclusive and accessible green and public spaces by 2030. There is urgency in fostering these connections, says Nisbet. Because while people benefit from their connection with the natural world, the environment also benefits when people feel connected and committed to caring for the Earth—and between climate change and habitat loss, the planet is in serious need of some care. “When people are disconnected from nature, they aren’t motivated to work on wicked problems like climate change. We’re losing the environments that contribute to our flourishing,” she says. “The key question is, How do we help people feel connected to nature so we’re motivated to protect the places that will help us thrive?” Key points Spending time in nature is linked to both cognitive benefits and improvements in mood, mental health and emotional well-being.Feeling connected to nature can produce similar benefits to well-being, regardless of how much time one spends outdoors.Both green spaces and blue spaces (aquatic environments) produce well-being benefits. More remote and biodiverse spaces may be particularly helpful, though even urban parks and trees can lead to positive outcomes. Related article Bringing nature into treatment Further reading Environmental Neuroscience Berman, M.G., et al., American Psychologist, 2019 Nature and Mental Health: An Ecosystem Service Perspective Bratman, G.N., et al., Science Advances, 2019 Ecotherapy: Theory, Research and Practice Jordan, M., & Hinds, J. (Eds.), Red Globe Press, 2016