Monkey plays video game – with its brain

Elon Musk’s startup devoted to meshing brains with computers was closer to its dream on Friday, having gotten a monkey to play video game Pong using only its mind.

Musk has long contended that merging minds with machines is vital if people are going to avoid being outpaced by artificial intelligence.

A video posted on YouTube by the entrepreneur’s Neuralink startup showed a macaque monkey named “Pager” playing Pong by essentially using thought to move paddles that bounce digital balls back and forth on screen.

“To control his paddle, Pager simply thinks about moving his hand up or down,” said a voice narrating the video. “As you can see, Pager is amazingly good at MindPong.”

Neuralink devices were implanted on two sides of Pager’s brain to sense neuron activity, then the monkey played the game a few minutes using a joystick to let software figure out the signals associated with hand movements.

Pager’s reward was banana smoothly served through a straw when he successfully batted the digital ball from one paddle to the other, according to the demonstration.

After a few minutes, the “decoder” program figured out what neuron signals to look for and the joystick was no longer needed for Pager to play the game.

“A monkey is literally playing a video game telepathically using a brain chip!!” Musk tweeted triumphantly.

The decoder could be calibrated to enable a person to guide a cursor on a computer screen, potentially letting them type emails, text messages, or browse the internet just by thinking, according to a blog post at

“Our first goal is to give people with paralysis their digital freedom back,” the Neuralink team said in the post.

Members of the team last year shared a “wish list” that ranged from technology returning mobility to the paralyzed and sight to the blind, to enabling telepathy and the uploading of memories for later reference—or perhaps to be downloaded into replacement bodies.

For now, Neuralink is being tested in animals with the team working on the potential for clinical trials.

With the help of a surgical robot, a piece of the skull is replaced with a Neuralink disk, and its wispy wires are strategically inserted into the brain, a previous demonstration showed.

The disk registers nerve activity, relaying the information via common Bluetooth wireless signal to a device such as a smartphone, according to Musk.

“It actually fits quite nicely in your skull. It could be under your hair and you wouldn’t know.”

Experts and academics remain cautious about his vision of symbiotically merging minds with super-powered computing.

For malnourished children, a new type of microbiome-directed food boosts growth

A new study shows that a therapeutic food designed to repair the gut microbiomes of malnourished children is better than standard therapy in supporting their growth. The research, published online April 7, 2021, in The New England Journal of Medicine, was a collaboration between Washington University School of Medicine and the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh, where the clinical trial was conducted. Pictured, a mother feeds her child one of the therapeutic foods as part of the clinical trial. Credit: International Centre for Diarrhoeal Disease Research

by Julia Evangelou Strait, Washington University School of Medicine in St. Louis

A new type of therapeutic food specifically designed to repair the gut microbiomes of malnourished children is superior to standard therapy in promoting growth, according to the results of a proof-of-concept clinical trial conducted in Bangladesh.

The study, conducted by an interdisciplinary team of researchers from Washington University School of Medicine in St. Louis and the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh (icddr,b), was designed to supplement the diet of malnourished children with a formulation that contains locally available, culturally acceptable foods selected based on the ability of the ingredients to boost key growth-promoting gut microbes. The work supports the notion that healthy growth of infants and children is closely linked to healthy development of their gut microbial communities—or microbiomes—after birth.

The results of the study are published online in The New England Journal of Medicine.

Childhood malnutrition is a major global health challenge, affecting over 150 million children under the age of 5 worldwide, with a disproportionate impact in South Asia and Sub-Saharan Africa, according to the World Health Organization. The ongoing COVID-19 pandemic is further exacerbating this problem. Numerous studies have shown that malnutrition is not due to food insecurity alone but instead reflects a combination of factors, including an important role for the gut microbiome, which fails to develop properly during the first two years of life in malnourished children.

“Malnutrition has proven extraordinary difficult to treat—standard calorie-dense therapeutic foods have been shown to prevent the deaths of malnourished children, but have been ineffective in overcoming growth stunting and other damaging effects of malnutrition, including impaired brain development, bone growth and immune function,” said senior author Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor and director of the Edison Family Center for Genome Sciences & Systems Biology at the School of Medicine. “In an attempt to address this problem, we are investigating whether repairing the poorly developed microbial communities of malnourished children will impact their growth. This is the first time that a microbiome-directed therapeutic food has been compared with a standard therapy in malnourished children; moreover, it produced a superior rate of weight gain, the key primary clinical outcome of the trial.”

An earlier, one-month long pilot clinical study conducted by the team in Bangladesh had provided evidence for the benefits of the microbiome-directed therapeutic food in a small number children who received it; however, the study was not sufficiently large or long enough to confirm the effects of the new food on growth. The current three-month long clinical trial, overseen by Tahmeed Ahmed, MBBS, Ph.D., executive director of the icddr,b, involved 118 children ages 12 to 18 months who lived in an urban slum called Mirpur in Dhaka, Bangladesh. All these children had been diagnosed with acute malnutrition, a condition in which the body consumes fat reserves and breaks down muscle, resulting in wasting, or weight loss. The immune system is also weakened, making these children more susceptible to other illnesses.

“This work is based on our studies that have shown that a derangement in the gut microbiome is responsible for malnutrition of children,” Ahmed said. “We have successfully used a food made of local ingredients to repair the deranged gut microbiome and thereby improve the growth of children receiving the food. In an era where we so sadly still have staggering numbers of children suffering and dying from malnutrition, our discovery of the microbiome-directed complementary food can be a game changer.”

Half of the children in the current study were randomly assigned to receive the microbiome-directed therapeutic food, and the other half received a standard therapeutic food that was not designed to repair the gut microbiome. The new microbiome-directed food contains a mixture of chickpeas, soy, bananas and peanuts, ingredients that the group had discovered in earlier pre-clinical models to repair the gut microbiome, among other components. The standard therapeutic food is rice- and lentil-based and contains about 20% more calories per serving than the microbiome-directed food.

The children received 25 gram

s of their assigned therapeutic foods twice daily for three months. The children’s height, weight and mid-upper arm circumference were measured at regular intervals throughout the intervention period and for one month after cessation of treatment. Blood and stool specimens were also collected at various times to assess changes in the levels of nearly 5,000 proteins in the blood, and to quantify the effects of the therapies on the representation of specific beneficial microbes in stool samples.

The researchers found that the rate of change in the children’s weight and their mid-upper arm circumferences were significantly greater in the group receiving the microbiome-directed food compared with the standard therapeutic food; this growth superiority was sustained even a month after the children had stopped receiving the nutritional intervention, which is the latest time point to be analyzed so far.

“When we look at the standard clinical measurement for assessing acute malnutrition—the weight-for-length z score—the difference between the two treatment groups was even more significant one month after we stopped the treatment,” said co-first author Robert Chen, a doctoral student in Gordon’s lab. “If this rate of growth was maintained for a year, we estimate an improvement in the weight-for-length z score of almost one full standard deviation.

“Children with acute malnutrition typically have declining or in the best case stable weight, so if this extrapolation holds up, it would be a major clinically relevant improvement in growth outcomes,” Chen added.

Said co-first author Ishita Mostafa, an assistant scientist at the International Centre for Diarrhoeal Disease Research: “We continue to monitor and collect samples from these children; this is critical in order to determine if the effects of this new treatment are indeed durable over time, or whether the intervention needs to be sustained for longer periods.”

The researchers also found that a group of 23 bacterial strains found in stool samples correlated with the increased rate of weight gain observed in the children receiving the microbiome-directed food. Twenty-one strains were positively correlated—meaning having more of these gut bacteria was linked to increased growth. And two strains were negatively correlated—meaning that having fewer of these gut bacteria was linked to increased growth. The microbiome-directed food was found to increase levels of the 21 positively correlated strains and reduce levels of the two strains that were negatively correlated.

Further, the researchers found 70 proteins in the blood samples that were positively correlated with increased weight, with greater improvements in their levels occurring after the microbiome-directed treatment compared with the standard intervention.

“These proteins are key regulators of bone biology, neurodevelopment and immune function,” Gordon said. “We discovered that this food can nurture and expand the abundance of beneficial microbes, with accompanying boosts in the levels of beneficial proteins in their human hosts that have impactful effects on growth.

“The rate of improvement in the weight of the children receiving the new therapeutic food designed with healthy gut microbes in mind was significantly greater even though its caloric density was 20% lower than the standard food,” Gordon added. “This suggests that the repair of the gut microbiome, and not just additional calories, is key to healthy growth in these children.”

The teams led by Gordon and Ahmed, funded by the Bill & Melinda Gates Foundation, plan to initiate further studies into whether therapeutic foods that nurture beneficial gut microbes can help malnourished children in other parts of the world. This involves a program of developing microbiome-directed foods that contain distinct but functionally “biosimilar” ingredients that are readily available, affordable and culturally acceptable to parents and children living in these other countries. Also, Gordon and his colleagues plan to investigate whether repairing dysfunctional gut microbial communities at younger ages and over longer timeframes could have an even greater impact.

“After the six-month period of breastfeeding recommended by the World Health Organization, we think there may be an early window to introduce these types of microbiome-directed therapeutic foods and potentially have a bigger effect,” said co-author Michael J. Barratt, Ph.D., associate professor of pathology and immunology and executive director of the Center for Gut Microbiome and Nutrition Research at Washington University.

The researchers also are planning studies to investigate the benefits of microbiome-directed therapeutic foods during pregnancy to determine whether they can not only improve the gut microbiomes of the malnourished mothers but also foster the transmission of healthy gut microbial communities to their infants and thus help break the devastating intergenerational cycle of malnutrition.

Added Gordon, “We are also exploring the possibility of bringing a clinical trial of this new therapeutic food to children who would benefit from a nutritional intervention here in St. Louis. We are at the earliest stages of this process, beginning to engage with members of the local community. We can’t begin one of these trials without making sure community leaders, community members, parents and caregivers are fully engaged with the process.”

More information: Robert Y. Chen et al. A Microbiota-Directed Food Intervention for Undernourished Children, New England Journal of Medicine (2021). DOI: 10.1056/NEJMoa2023294Journal information:New England Journal of Medicine

Accelerated Cellular Aging Associated With Mortality Seen in Depressed Individuals

DNA markers in cells of patients with major depressive disorder appear to be two years older than markers in cells of people without the mental health disorder. The individuals with MDD showed no outward signs of age-related pathology, as they and the healthy controls were screened for physical health before entry into the study.

Cells from individuals with Major Depressive Disorder (MDD) were found to have higher than expected rates of methylation at specific sites on their DNA, when compared to cells from healthy individuals without MDD, according to a study by a multidisciplinary team of UC San Francisco scientists, in collaboration with others. Methylation is a process by which DNA is chemically modified at specific sites, resulting in changes in the expression of certain genes.

Methylation of particular sets of genes, called “DNA methylation clocks,” typically change in predictable ways as people age, but the rate of these changes varies between people. Methylation patterns in individuals with MDD suggested that their cellular age was, on average, accelerated relative to matched healthy controls.

In the study, published April 6, 2021 in Translational Psychiatry, blood samples from individuals with MDD were analyzed for methylation patterns using the ‘GrimAge’ clock – a mathematical algorithm designed to predict an individual’s remaining lifespan based on cellular methylation patterns. Individuals with MDD showed a significantly higher GrimAge score, suggesting increased mortality risk, compared to healthy individuals of the same chronological age – an average of approximately two years on the GrimAge clock.

The individuals with MDD showed no outward signs of age-related pathology, as they and the healthy controls were screened for physical health before entry into the study. The methylation patterns associated with mortality risk persisted even after accounting for lifestyle factors like smoking and BMI. These findings provide new insight into the increased mortality and morbidity associated with the condition, suggesting that there is an underlying biological mechanism accelerating cellular aging in some MDD sufferers.

“This is shifting the way we understand depression, from a purely mental or psychiatric disease, limited to processes in the brain, to a whole-body disease,” said Katerina Protsenko, a medical student at UCSF and lead author of the study. “This should fundamentally alter the way we approach depression and how we think about it – as a part of overall health.”

MDD is one of the most prevalent health concerns globally. According to the World health Organization, some 300 million people (4.4% of the population) suffer from some form of depression. MDD is associated with higher incidence and mortality related to increased rates of cardiovascular disease, diabetes, and Alzheimer’s disease among sufferers.

“One of the things that’s remarkable about depression is that sufferers have unexpectedly higher rates of age-related physical illnesses and early mortality, even after accounting for things like suicide and lifestyle habits,” said Owen Wolkowitz, MD, professor of psychiatry and a member of UCSF’s Weill Institute for Neurosciences, co-senior author of the study. “That’s always been a mystery, and that’s what led us to look for signs of aging at the cellular level.”

The researchers collected blood samples from 49 individuals with MDD who were unmedicated prior to the study and 60 healthy control subjects of the same chronological age. They analyzed the methylation rates of both groups using the GrimAge clock. While there are numerous methylation-based longevity algorithms, GrimAge is the only one based specifically on methylation patterns associated with mortality.

The researchers say that they don’t yet know if depression causes altered methylation in certain individuals, or if depression and methylation are both related to another underlying factor. It is possible that some individuals may have a genetic predisposition to produce specific methylation patterns in response to stressors, but this has not been well-studied. Alterations in methylation patterns have previously been observed in individuals with Post-Traumatic Stress Disorder.

Moving forward, the researchers hope to determine whether pharmacological treatments or therapy may mitigate some methylation changes related to MDD in hopes of normalizing the cellular aging process in affected individuals before it advances. Although the GrimAge methylation clock has been associated with mortality in other populations, no studies have yet determined whether this methylation pattern also predicts mortality in MDD.

“As we continue our studies, we hope to find out whether addressing the MDD with anti-depressants or other treatments alters the methylation patterns, which would give us some indication that these patterns are dynamic and can be changed,” said Synthia Mellon, PhD, professor in the Department of Ob/Gyn & Reproductive Sciences at UCSF and co-senior author of the study.

Authors: Katerina Protsenko was the study’s lead author. Owen M. Wolkowitz, MD, Synthia H. Mellon, PhD, and Victor I. Reus, MD were the study’s co-senior authors. The study was conducted in collaboration with Ruoting Yang, Rasha Hammamieh, Marti Jett, Aarti Gautam, and other scientists from the Walter Reed Army Institute of Research, Silver Spring, MD.

New Multiple Sclerosis Subtypes Identified Using Artificial Intelligence

Combining artificial intelligence technology with brain scan data, researchers have identified three novel subtypes of multiple sclerosis.

Scientists at UCL have used artificial intelligence (AI) to identify three new multiple sclerosis (MS) subtypes. Researchers say the groundbreaking findings will help identify those people more likely to have disease progression and help target treatments more effectively.

MS affects over 2.8 million people globally and 130,000 in the UK, and is classified into four* ‘courses’ (groups), which are defined as either relapsing or progressive. Patients are categorised by a mixture of clinical observations, assisted by MRI brain images, and patients’ symptoms. These observations guide the timing and choice of treatment.

For this study, published in Nature Communications, researchers wanted to find out if there were any – as yet unidentified – patterns in brain images, which would better guide treatment choice and identify patients who would best respond to a particular therapy.

Explaining the research, lead author Dr Arman Eshaghi (UCL Queen Square Institute of Neurology) said: “Currently MS is classified broadly into progressive and relapsing groups, which are based on patient symptoms; it does not directly rely on the underlying biology of the disease, and therefore cannot assist doctors in choosing the right treatment for the right patients.

“Here, we used artificial intelligence and asked the question: can AI find MS subtypes that follow a certain pattern on brain images? Our AI has uncovered three data-driven MS subtypes that are defined by pathological abnormalities seen on brain images.”

In this study, researchers applied the UCL-developed AI tool, SuStaIn (Subtype and Stage Inference), to the MRI brain scans of 6,322 MS patients. The unsupervised SuStaIn trained itself and identified three (previously unknown) patterns.

The new MS subtypes were defined as ‘cortex-led’, ‘normal-appearing white matter-led’, and ‘lesion-led.’ These definitions relate to the earliest abnormalities seen on the MRI scans within each pattern.

Once SuStaIn had completed its analysis on the training MRI dataset, it was ‘locked’ and then used to identify the three subtypes in a separate independent cohort of 3,068 patients thereby validating its ability to detect the new MS subtypes.

Dr Eshaghi added: “We did a further retrospective analysis of patient records to see how people with the newly identified MS subtypes responded to various treatments.

While further clinical studies are needed, there was a clear difference, by subtype, in patients’ response to different treatments and in accumulation of disability over time. This is an important step towards predicting individual responses to therapies.”

NIHR Research Professor Olga Ciccarelli (UCL Queen Square Institute of Neurology), the senior author of the study, said: “The method used to classify MS is currently focused on imaging changes only; we are extending the approach to including other clinical information.

“This exciting field of research will lead to an individual definition of MS course and individual prediction of treatment response in MS using AI, which will be used to select the right treatment for the right patient at the right time.”

One of the senior authors, Professor Alan Thompson, Dean of the UCL Faculty of Brain Sciences, said: “We are aware of the limitations of the current descriptors of MS which can be less than clear when applied to prescribing treatment. Now with the help of AI and large datasets, we have made the first step towards a better understanding of the underlying disease mechanisms which may inform our current clinical classification. This is a fantastic achievement and has the potential to be a real game-changer, informing both disease evolution and selection of patients for clinical trials.”

Researchers say the findings suggest that MRI-based subtypes predict MS disability progression and response to treatment and can now be used to define groups of patients in interventional trials. Prospective research with clinical trials is required as the next step to confirm these findings.

Dr Clare Walton, Head of Research at the MS Society, said: “We’re delighted to have helped fund this study through our work with the International Progressive MS Alliance. MS is unpredictable and different for everyone, and we know one of our community’s main concerns is how their condition might develop.

Having an MRI-based model to help predict future progression and tailor your treatment plan accordingly could be hugely reassuring to those affected. These findings also provide valuable insight into what drives progression in MS, which is crucial to finding new treatments for everyone. We’re excited to see what comes next.”

MS is a neurological (nerve) condition and is one of the most common causes of disability in young people. It arises when the immune system mistakenly attacks the coating (myelin sheaths) that wrap around nerves in the brain and spinal cord. This results in the electrical signals, which pass messages along the nerves, to be disrupted, travel more slowly, or fail to get through at all.

Most people are diagnosed between the ages of 20 and 50, however the first signs of MS often start years earlier. Common early signs include tingling, numbness, a loss of balance and problems with vision, but because other conditions cause the same symptoms, it can take time to reach a definitive diagnosis.

Many patients have relapsing MS at first, a form of the disease where symptoms come and go as nerves are damaged, repaired and damaged again. But about half have a progressive form of the condition in which nerve damage steadily accumulates and causes ever worsening disability. Patients may experience tremors, speech problems and muscle stiffness or spasms, and may need walking aids or a wheelchair.

Research reveals why redheads may have different pain thresholds

by Noah Brown, Massachusetts General Hospital

New research led by investigators at Massachusetts General Hospital (MGH) provides insights on why people with red hair exhibit altered sensitivity to certain kinds of pain. The findings are published in Science Advances.

In people with red hair (as in numerous other species of animals with red fur), the pigment-producing cells of the skin—called melanocytes—contain a variant form of the melanocortin 1 receptor. This receptor sits on the cell surface, and if it becomes activated by circulating hormones called melanocortins, it causes the melanocyte to switch from generating yellow/red melanin pigment to producing brown/black melanin pigment. Earlier work by David E. Fisher, MD, Ph.D., director of the Mass General Cancer Center’s Melanoma Program and director of MGH’s Cutaneous Biology Research Center, demonstrated that the inability of red-haired individuals to tan or darken their skin pigment is traced to inactive variants of this receptor.

To investigate the mechanisms behind different pain thresholds in red-haired individuals, Fisher and his colleagues studied a strain of red-haired mice that (as in humans) contains a variant that lacks melanocortin 1 receptor function and also exhibits higher pain thresholds.

The team found that loss of melanocortin 1 receptor function in the red-haired mice caused the animals’ melanocytes to secrete lower levels of a molecule called POMC (proopiomelanocortin) that is subsequently cut into different hormones including one that sensitizes to pain and one that blocks pain. The presence of these hormones maintains a balance between opioid receptors that inhibit pain and melanocortin 4 receptors that enhance perception of pain.

In red-haired mice (and therefore, possibly humans), having both hormones at low levels would seemingly cancel each other out. However, the body also produces additional, non-melanocyte-related factors that activate opioid receptors involved in blocking pain. Therefore, the net effect of lower levels of the melanocyte-related hormones is more opioid signals, which elevates the threshold for pain.

“These findings describe the mechanistic basis behind earlier evidence suggesting varied pain thresholds in different pigmentation backgrounds,” says Fisher. “Understanding this mechanism provides validation of this earlier evidence and a valuable recognition for medical personnel when caring for patients whose pain sensitivities may vary.”

Fisher adds that the results suggest new ways to manipulate the body’s natural processes that control pain perception—for example, by designing new medications that inhibit melanocortin 4 receptors involved in sensing pain.

“Our ongoing work is focused on elucidating how additional skin-derived signals regulate pain and opioid signaling,” adds co-lead author Lajos V. Kemény, MD, Ph.D., a research fellow in Dermatology at MGH. “Understanding these pathways in depth may lead to the identification of novel pain-modulating strategies.”

Brisk Walking Is Good for the Aging Brain

Older people with mild cognitive impairment showed improvements in brain blood flow and memory after a yearlong aerobic exercise program.

By Gretchen Reynolds

Brisk walking improves brain health and thinking in aging people with memory impairments, according to a new, yearlong study of mild cognitive impairment and exercise. In the study, middle-aged and older people with early signs of memory loss raised their cognitive scores after they started walking frequently. Regular exercise also amplified the healthy flow of blood to their brains. The changes in their brains and minds were subtle but consequential, the study concludes, and could have implications not just for those with serious memory problems, but for any of us whose memories are starting to fade with age.

Most of us, as we get older, will find that our ability to remember and think dulls a bit. This is considered normal, if annoying. But if the memory loss intensifies, it may become mild cognitive impairment, a medical condition in which the loss of thinking skills grows obvious enough that it becomes worrisome to you and others around you. Mild cognitive impairment is not dementia, but people with the condition are at heightened risk of developing Alzheimer’s disease later.

Scientists have not yet pinpointed the underlying causes of mild cognitive impairment, but there is some evidence that changes in blood flow to the brain can contribute. Blood carries oxygen and nutrients to brain cells and if that stream sputters, so can the vitality of neurons.

Unfortunately, many people experience declines in the flow of blood to their brains with age, when their arteries stiffen and hearts weaken.

But the good news is that exercise can increase brain blood flow, even when exercisers are not moving. In a 2013 neurological study, the brains of physically active older men showed much better blood saturation than those of sedentary men, even when everyone was quietly resting. The greater brain blood flow in people who exercise also is associated with better scores on tests of memory and thinking than among sedentary people.

But these studies generally focused on people whose brains and cognition were relatively normal. Exercise bulked up, for them, what already was reasonably sound. Far less is known about whether physical activity similarly benefits the blood flow, brains and thinking of people who are starting to experience more serious memory loss.

So, for the new study, which was published this month in the Journal of Alzheimer’s Disease, researchers at the University of Texas Southwestern Medical Center in Dallas and other institutions asked a group of 70 sedentary men and women, aged 55 or older and diagnosed with mild cognitive impairment, to start moving more.

They first brought everyone into the lab and tested their current health, cognitive function and aerobic fitness. Then, using advanced ultrasounds and other techniques, they measured the stiffness of their carotid artery, which carries blood to the brain, and the amount of blood flowing to and through their brains.

Finally, they divided the volunteers into two groups. One began a program of light stretching and toning exercises, to serve as an active control group. The others started to exercise aerobically, mostly by walking on treadmills at the lab, and then, after a few weeks, outside on their own. The exercisers were asked to keep their exertions brisk, so that their heart rates and breathing rose noticeably. (They could swim, ride bikes or do ballroom dancing if they chose, but almost everyone walked.) The control group kept their heart rates low.

Everyone in both groups worked out three times a week at first, for about half an hour and under supervision. They then added sessions on their own, until after six months, they were completing about five workouts most weeks. This program continued for a year, in total. About 20 volunteers dropped out over that time, mostly from the walking group.

Then the volunteers returned to the lab for a repeat of the original tests, and the researchers compared results. To no one’s surprise, the exercise group was more fit, with higher aerobic capacity, while the stretchers’ endurance had not budged. The aerobic exercise group also showed much less stiffness in their carotid arteries and, in consequence, greater blood flow to and throughout their brains.

Perhaps most important, they also performed better now than the stretch-and-tone group on some of the tests of executive function, which are thinking skills involved in planning and decision-making. These tend to be among the abilities that decline earliest in dementia.

Interestingly, though, both groups had raised their scores slightly on most tests of memory and thinking, and to about the same extent. In effect, getting up and moving in any way — and perhaps also interacting socially with people at the lab — appeared to have burnished thinking skills and helped to stave off accelerating declines.

Still, the researchers believe that over a longer period of time, brisk walking would result in greater cognitive gains and less memory decline than gentle stretching, says Rong Zhang, a neurology professor at UT Southwestern Medical Center, who oversaw the new study.

“It probably takes more time” than a year for the improved brain blood flow to translate into improved cognition, he says. He and other researchers are planning larger, longer-lasting studies to test that idea, he says. They hope, too, to investigate how more — or fewer — sessions of exercise each week might aid the brain, and whether there might be ways to motivate more of the volunteers to stick with an exercise program.

For now, though, he believes the group’s findings serve as a useful reminder that moving changes minds. “Park farther away” when you shop or commute, he says. “Take the stairs,” and try to get your heart rate up when you exercise. Doing so, he says, may help to protect your lifelong ability to remember and think.

Common Alzheimer’s Treatment Linked to Slower Cognitive Decline

Summary: Cholinesterase inhibitors such as galantamine, donepezil, and rivastigmine, appear to generate persistent cognitive benefits, and increased life span for up to five years in Alzheimer’s patients.

Source: Karolinska Institute

Cholinesterase inhibitors are a group of drugs recommended for the treatment of Alzheimer’s disease, but their effects on cognition have been debated and few studies have investigated their long-term effects.

A new study involving researchers from Karolinska Institutet in Sweden and published in the journal Neurology shows persisting cognitive benefits and reduced mortality for up to five years after diagnosis.

Alzheimer’s disease is a cognitive brain disease that affects millions of patients around the world. Some 100,000 people in Sweden live with the diagnosis, which has a profound impact on the lives of both them and their families. Most of those who receive a diagnosis are over 65, but there are some patients who are diagnosed in their 50s.

The current cost of care and treatment for people with dementia is approximately SEK 60 billion a year in Sweden. This is on a par with the cost of care and treatment of cardiovascular diseases and is twice as high as cancer care.

In Alzheimer’s disease changes to several chemical neurotransmitters in the brain are found, and thus to the ability of the neurons to communicate with each other. Acetylcholine is one such substance and plays a key role in cognitive functions such as memory, attention and concentration.

There are three drugs that work as cholinesterase inhibitors and that are used in the treatment of Alzheimer’s disease: galantamine, donepezil and rivastigmine.

The effects of cholinesterase inhibitors have, however, been debated, partly because there are relatively few longitudinal clinical studies. Researchers at Karolinska Institutet and Umeå University have now conducted a registry study of patients with Alzheimer’s disease over a period of five years from point of diagnosis.’

The study is based on data from SveDem (the Swedish Dementia Registry) on 11,652 patients treated with cholinesterase inhibitors and a matched control group of 5,826 untreated patients.

The results showed that treatment with cholinesterase inhibitors was associated with slower cognitive decline over five years, and 27 per cent lower mortality in patients with Alzheimer’s disease compared with the controls.

“Of all three drugs, galantamine had the strongest effect on cognition, which may bedue to its effect on nicotine receptors and its inhibiting effect on the enzyme acetylcholinesterase, which breaks down the neurotransmitter acetylcholine,” says the study’s first author Hong Xu, postdoctoral researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.

“Our results provide strong support for current recommendations to treat people with Alzheimer’s disease with cholinesterase inhibitors, but also shows that the therapeutic effect lasts for a long time,” says the study’s last author and initiator Maria Eriksdotter, professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.

Funding: The study was supported by grants from the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare (FORTE), the ALF scheme, the Swedish Order of St John, the Swedish Society for Medical Research, and the Strategic Research Area in Neuroscience (StratNeuro), Karolinska Institutet.

Long Term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality” by Hong Xu et al. Neurology

‘Game of thrones’ study reveals the power of fiction on the mind

by Dennis Thompson

It’s not unusual for a fictional character to ring such a chord that their story shapes your life.

Think of educators inspired by Robin Williams’ character in “Dead Poets Society,” lawyers drawn to the profession by Perry Mason or Atticus Finch, or health professionals motivated by the doctors on “ER” or “Grey’s Anatomy.”

Now researchers think they’ve figured out why fiction can so strongly affect a person’s reality, thanks to a brain study using the fantasy TV show “Game of Thrones.”

It turns out that when you strongly identify with a fictional character, you’re activating the same region of the brain that you use to think about yourself and those closest to you, researchers report.

“People really do internalize those experiences and draw on them, almost as if they’ve had those experiences themselves,” said lead researcher Timothy Broom, a doctoral student in psychology at Ohio State University. “They’re using the same neural mechanism by which they access autobiographical information.”

For this study, Broom and colleagues scanned the brains of 19 self-described fans of “Game of Thrones” while they thought about themselves, nine of their friends and nine characters from the HBO series.

Participants also reported which character from the series they felt closest to and liked most. (For “GOT” fans: The characters were Bronn, Catelyn Stark, Cersei Lannister, Davos Seaworth, Jaime Lannister, Jon Snow, Petyr “Littlefinger” Baelish, Sandor “The Hound” Clegane and Ygritte.)

The research team was investigating a phenomenon called “trait identification,” Broom said.

“That is where you become really immersed in the story and the narrative, but it’s not just that you become immersed in it. You become immersed specifically in the psychological perspective of a character or characters within the story,” Broom said.

“You tend to think what the character is thinking,” he continued. “You feel what they’re feeling. You really want them to achieve the goal they’re trying to achieve. It really is in a sense almost as if you become the character. You really inhabit their perspective.”

‘Internalizing experiences’

Researchers scanned a part of the brain called the ventral medial prefrontal cortex, or vMPFC, which is strongly linked to self-reflection.

“If you have a task where you’re thinking about yourself or you’re thinking about other people, this brain region reliably shows up in study after study,” Broom said. For example, people with damage in this part of the brain are not able to fully access autobiographical information.

Overall, study participants experienced more response in this brain region when they thought about themselves than when they thought either about friends or fictional characters from the TV show.

But some participants were better than others in their ability to identify with fictional characters, and activity in the vMPFC region was especially active for those folks when they evaluated the “Game of Thrones” character they most admired or to whom they felt closest, researchers said.

“They’re really internalizing the experiences of those characters, because they are experiencing the story from that perspective,” Broom said. “They really internalize that and incorporate that character into their self-concept.”

These results show the power fiction has over people’s attitudes, beliefs and behaviors, said Nancy Mramor, a media psychologist and author of the book “Get Reel: Produce Your Own Life.” She was not involved with the study.

“I caution viewers to view mindfully so that they are aware of their biological and emotional responses to anything or any hero they view, whether it is in the news or a crime show,” Mramor said.

“Know when to engage and when to step back and watch from a distance, especially if your favorite character is on an emotional roller coaster and is taking you with them,” she continued. “Decide what and who you want to influence you and make choices.”

Using fiction to plot real life

Even compelling dramas are not healthy if the content is too disturbing. “And everyone has to make that choice for themselves,” Mramor said

Public health campaigns could benefit from skilled writers who create compelling characters with which readers or viewers can identify, Broom said.

“If people really identify with the characters in those narratives that are targeted in these health interventions, people will go on to engage in more healthy behaviors,” he said.

You might even be able to help steer your own emotional growth through your choice of fiction, although that would depend on your ability to identify with characters, Broom added.

“It is probably possible to, in theory, trot out your own path for your own goals for self-growth, by finding characters that meet that criteria you’re trying to achieve,” Broom said.

“I think it would be something that would not necessarily happen right away,” he said. “It would happen over a longer period of time, and would probably be easier for people who are already in the practice of engaging with fictional characters in this way.”

The new study was published online recently in the journal Social Cognitive and Affective Neuroscience.

This Is Exactly What Alcohol Does To Your Brain as You Age, According to a Neuroscientist

by Kara Jillian Brown

The impact of alcohol on your body changes as you age. While some differences are immediately recognizable (a terrible hangovers after one drink the night before, for example), others are a bit more subtle. “The effects of alcohol on the brain are dependent on age and daily consumption habits,” says Dr. Willeumier. “With aging, specific structural and functional changes happen in the brain, including thinning of the cerebral cortex, neuronal shrinkage, decreased spine density, decreased white-matter connectivity, and diminished neurotransmitter production.” Alcohol consumption only exacerbates symptoms of brain aging.

Dr. Willeumier cites an August 2020 neuroimaging study, published in the journal Nature Scientific Reports. Researchers looked at 353 participants age 39 to 45 who underwent an MRI and used neurological and neuropsychiatric assessments to find that moderate alcohol consumption (fewer than three drinks per day for females, four drinks per day or less for males) was associated with a smaller brain volume. An October 2008 neuroimaging study, published in JAMA Neurology, looked at 1,839 participants age 33 to 88 and found that higher levels of alcohol consumption were associated with smaller brain volume.

“The prefrontal cortex and hippocampus are vulnerable to the aging process, and a decline in brain volume in these regions can contribute significantly to memory impairments,” says Dr. Willeumier. “Alcohol consumption has an added impact on the aging brain, particularly in these regions essential to cognitive function.”

How much you drink impacts the extent to which alcohol affects your brain. While the potential benefits of having one-to-two drinks per on cognitive health have been reported, Dr. Whilleumier says moderate alcohol consumption has been demonstrated to reduce hippocampal volume, the area of the brain essential to learning and memory, and decrease total brain volume.

“Moderate-to-heavy alcohol consumption, four or more drinks per day, is detrimental to brain function,” she says. “Ethanol can have a neurotoxic effect on the brain, leading to structural and functional brain damage. Heavy drinking can impact vascular function due to the inflammatory response and oxidative stress, increasing the risk of hypertension, coronary heart disease, stroke, and peripheral artery disease, which can adversely affect cognitive health.”

Heavy alcohol use is associated with an increased risk of dementia. A June 2018 study, published in The Lancet Public Health, “found in a cohort of 1,109,343 dementia cases that there was an association of alcohol use disorders with all types of dementia,” says Dr. Whilleumier. “The authors note that the burden of dementia is much larger than previously thought, with alcohol use disorders linked to a threefold increase risk of all types of dementia. Therefore, early detection and intervention in heavy alcohol users are essential in the prevention of dementia.”

While short-term impacts of alcohol like decreased attention, mood, and memory changes can be undone by abstaining from alcohol consumption, be mindful that long-term impacts are often irreversible.

Simple Spit Test Could Diagnose Concussions

by Asher Jones

As many as 3.8 million people sustain sports- and recreation-related concussions each year in the US, but diagnoses of these brain injuries remain challenging. In a study published this week in the British Journal of Sports Medicine, researchers describe a saliva-based test that accurately detected concussions in male rugby players.

“What’s exciting about this is we not only found a very accurate way of identifying brain trauma, but also we found it in saliva, which is not invasive,” Antonio Belli, a trauma neurosurgery researcher at the University of Birmingham in the UK and a coauthor of the study, tells The Washington Post. “Everybody, including myself, has been looking at blood for many years. We’ve never really seen anything so exciting for mild traumatic brain injury.”

The test measures expression levels of 14 small noncoding RNAs in saliva, including microRNAs. “MicroRNAs are messages the cells transmit in response to an event, like a brain injury,” Belli tells The Guardian.“The place where you find microRNAs most abundantly is saliva. Salivary glands are connected directly to the brain by nerves. We’re seeing this response within minutes of injury.”

The researchers compared saliva samples in male rugby players that experienced head injuries, uninjured players, and those with injuries to another part of the body. More than 1,000 people participated in the study. On the basis of these RNA saliva biomarkers, they detected concussions with 94 percent accuracy, the Post reports.

Concussion diagnoses are often made based on symptoms such as behavior or, in hospital settings, with brain imaging. “The diagnosis of concussions is really based on clinical findings. A lot of that is based on what a person reports,” William Barr, the director of neuropsychology at New York University who wasn’t involved with the research, tells the Post. “What we’ve always been looking for is: Is there something objective? Because, in a lot of cases, they’ll deny [feeling symptoms]. That’s what this really adds.” 

The saliva-based test described in the study relies on PCR and must be sent to a lab for analysis. But, according to The Guardian, the researchers are in the process of developing an over-the-counter version that could provide instant results to injured athletes, victims of traffic accidents, soldiers, and others who experience head injuries.

There is currently an FDA-approved blood test for concussion that measures the abundance of two proteins. Penn State researchers have also developed a test that measures saliva noncoding RNAs as biomarkers of concussion. According to Fox43, these researchers are also planning to develop a handheld tool that could deliver results within 30 minutes. 

Notably, the UK-based study only tested male rugby players. Research suggests that there are gender- and sex-related differences in concussions, meaning that further study would be needed before the test could be applied to women.