Arquivo da tag: neurociências

Small advances: understanding the micro biome (ABC RN)

Tuesday 1 September 2015 4:27PM

Amanda Smith



What is it that makes you, you? While you’re made up of 10 trillion human cells, 100 trillion microbial cells also live on you and in you. This vast array of microscopic bugs may be your defining feature, and scientists around the world are racing to find out more. Amanda Smith reports.


Microbes, it seems, are the next big thing. Around the world, scientists are researching the human microbiome—the genes of our microbes—in the hope of unlocking quite a different way to understand sickness and health.

At the Microbiome Initiative at the University of California, San Diego, Rob Knight runs the American Gut Project, a citizen science initiative where you can get your microbiome sequenced.

Breast milk is meant to present the baby with a manageable dose of everything in the environment. It samples the entire environment—everything the mother eats, breathes, touches.


‘What we can do right now is put you on this microbial map, where we can compare your microbes to the microbes of thousands of other people we’ve already looked at,’ he says. ‘But what we need to do is develop more of a microbial GPS that doesn’t just tell you where you are, but tells you where you want to go and what you need to do, step by step, in order to get there.’

The Australian Centre for Ecogenomics is also setting up a service where you can get your gut microbes analysed. The centre’s director, Phillip Hugenholtz, predicts that in years to come such a process will be a diagnostic procedure when you go to the doctor, much like getting a blood test.

‘I definitely think that’s going to become a standard part of your personalised medicine’, he says. ‘Micro-organisms are sometimes a very good early indicator of things occurring in your body and so it will become something that you’d go and get done maybe once or twice a year to see what’s going on.’

While this level of interest in the microbiome is new, the first person to realise we’re all teeming with micro-organisms was Dutchman Anton Leeuwenhoek, way back in 1676. Leeuwenhoek was interested in making lenses, and constructed himself a microscope.

‘He was looking at the scum from his teeth, and was amazed to see in this scraped-off plaque from inside his own mouth what he called hundreds of different “animalcules swimming a-prettily”,’ says Tim Spector, professor of genetic epidemiology at Kings College London.

‘He was the first to describe this, and it took hundreds of years before people actually believed that we were completely full of these microbes and we’d co-evolved with them.’

Microbes have come a long way over the last century. Until recent advances in DNA sequencing, all tummy bugs were considered bad.

‘We used to think that there was no such thing as a good microbe in our guts, that they were all out to do us no good, and we’ve basically spent the last 100 years trying to eliminate them with disinfectants and then the last 50 years with antibiotics,’ says Spector.

This has given rise to the ‘hygiene hypothesis’, which contends that by keeping ourselves too clean, we’re denying ourselves the microbes necessary to keep our immune system balanced, resulting in all sorts of chronic diseases.

‘Over the last half-century, as infectious diseases like polio and measles and hepatitis and so-on have plummeted in their frequency, chronic diseases—everything from obesity to diabetes to inflammatory bowel disease—have been skyrocketing,’ says the Microbiome Initiative’s Rob Knight.

‘So the idea is that potentially without exposure to a diverse range of healthy microbes our immune systems might be going into overdrive and attacking our own cells, or overreacting to harmless things we find in the environment.’

Antonie van Leeuwenhoek


In terms of human DNA, we’re all 99.99 per cent identical. However our microbial profiles can differ enormously. We might share just 10 per cent of our dominant microbial species with others.

According to Knight, some of the differences are explained by method of birth.

‘If you come out the regular way you get coated with microbes as you’re passing through your mother’s birth canal,’ he says.

Babies delivered by Caesarian section, on the other hand, have microbes that are mostly found on adult skin, from being touched by different doctors and nurses.

‘One thing that’s potentially interesting about that is differences between C-section and vaginally delivered babies have been reported: higher rates in C-section babies of asthma, allergies, atopic disease, even obesity. All of those have been linked to the microbiome now.’

Also important to the development of healthy microbiota in babies is breastfeeding, according to Maureen Minchin, the author of Milk Matters.

‘We’ve known for over 100 years that breast milk and formula result in very, very different gut flora in babies, but it’s only very recently that anyone has thought to look and see what breast milk does contain, and at last count there were well over 700 species of bacteria in breast milk,’ she says.

According to Minchin, breastfeeding is the bridge between the womb and the world for babies.

‘Breast milk is meant to present the baby with a manageable dose of everything in the environment. It samples the entire environment—everything the mother eats, breathes, touches. Her microbiome is present in that breast milk and will help create the appropriate microbiome in the baby.’

Minchin is an advocate of the World Health Organisation’s recommendation to breastfeed exclusively to six months and then continue breastfeeding while introducing other foods through the first and second year.

Related: Why the digestive system and its bacteria are a ‘second brain’

So if what babies are fed is important for their microbiome, what about adults? Tim Spector says research into microbes is yielding new information about healthy eating.

‘It’s going to soon revolutionise how we look at food and diet. This is one of the most exciting things in science at the moment, because it’s obviously much easier to change your microbes than it is to change your genes.’

‘Most processed foods only contain about five ingredients, and in a way our epidemic of the last 30 years of obesity and allergy is that our diets have become less and less diverse.’

According to Spector, studies of people with various chronic diseases, obesity and diabetes show a common feature, which is that their gut microbes have a much-reduced diversity compared to healthy people.

He likes to use the analogy of a garden: ‘A neglected garden has very few species, not much fertilised soil, and this allows weeds to take over in great numbers,’ he says.

‘I think this is a nice concept because we’re very good gardeners, humans, and I think we need to start using those principles—fertilising, adding soil, experimenting and avoiding adding nasty toxins to our own bodies as we would our gardens.’

May your gut flora bloom!

What Concepts and Emotions Are (and Aren’t) (Knowledge Ecology)

August 1, 2015

Adam Robbert

Lisa Feldman Barrett has an interesting piece up in yesterday’s New York Times that I think is worth some attention here. Barrett is the director of the The Interdisciplinary Affective Science Laboratory, where she studies the nature of emotional experience. Here is the key part of the article, describing her latest findings:

The Interdisciplinary Affective Science Laboratory (which I direct) collectively analyzed brain-imaging studies published from 1990 to 2011 that examined fear, sadness, anger, disgust and happiness. We divided the human brain virtually into tiny cubes, like 3-D pixels, and computed the probability that studies of each emotion found an increase in activation in each cube.

Overall, we found that no brain region was dedicated to any single emotion. We also found that every alleged “emotion” region of the brain increased its activity during nonemotional thoughts and perceptions as well . . .

Emotion words like “anger,” “happiness” and “fear” each name a population of diverse biological states that vary depending on the context. When you’re angry with your co-worker, sometimes your heart rate will increase, other times it will decrease and still other times it will stay the same. You might scowl, or you might smile as you plot your revenge. You might shout or be silent. Variation is the norm.

This highly distributed, variable, and contextual description of emotions matches up quite well with what scientists have found to be true of conceptualization—namely, that it is a situated process drawn from a plurality of bodily forces. For instance, compare Barrett’s findings above to what I wrote about concepts in my paper on concepts and capacities from June (footnote references are in the paper):

In short, concepts are flexible and distributed modes of bodily organization grounded in modality-specific regions of the brain;[1] they comprise semantic knowledge embodied in perception and action;[2] and they underwrite the organization of sensory experience and guide action within an environment.[3] Concepts are tools for constructing in the mind new pathways of relationship and discrimination, for shaping the body, and for attuning it to contrast. Such pathways are recruited in an ecologically specific way as part of the dynamic bringing-to-apprehension of phenomena.

I think the parallel is clear enough, and we would do well to adopt this more ecological view of emotions and concepts into our thinking. The empirical data is giving us a strong argument for talking about the ecological basis of emotion and conceptuality, a basis that continues to grow stronger by the day.

Can the Bacteria in Your Gut Explain Your Mood? (New York Times)

Eighteen vials were rocking back and forth on a squeaky mechanical device the shape of a butcher scale, and Mark Lyte was beside himself with excitement. ‘‘We actually got some fresh yesterday — freshly frozen,’’ Lyte said to a lab technician. Each vial contained a tiny nugget of monkey feces that were collected at the Harlow primate lab near Madison, Wis., the day before and shipped to Lyte’s lab on the Texas Tech University Health Sciences Center campus in Abilene, Tex.

Lyte’s interest was not in the feces per se but in the hidden form of life they harbor. The digestive tube of a monkey, like that of all vertebrates, contains vast quantities of what biologists call gut microbiota. The genetic material of these trillions of microbes, as well as others living elsewhere in and on the body, is collectively known as the microbiome. Taken together, these bacteria can weigh as much as six pounds, and they make up a sort of organ whose functions have only begun to reveal themselves to science. Lyte has spent his career trying to prove that gut microbes communicate with the nervous system using some of the same neurochemicals that relay messages in the brain.

Inside a closet-size room at his lab that afternoon, Lyte hunched over to inspect the vials, whose samples had been spun down in a centrifuge to a radiant, golden broth. Lyte, 60, spoke fast and emphatically. ‘‘You wouldn’t believe what we’re extracting out of poop,’’ he told me. ‘‘We found that the guys here in the gut make neurochemicals. We didn’t know that. Now, if they make this stuff here, does it have an influence there? Guess what? We make the same stuff. Maybe all this communication has an influence on our behavior.’’

Since 2007, when scientists announced plans for a Human Microbiome Project to catalog the micro-organisms living in our body, the profound appreciation for the influence of such organisms has grown rapidly with each passing year. Bacteria in the gut produce vitamins and break down our food; their presence or absence has been linked to obesity, inflammatory bowel disease and the toxic side effects of prescription drugs. Biologists now believe that much of what makes us human depends on microbial activity. The two million unique bacterial genes found in each human microbiome can make the 23,000 genes in our cells seem paltry, almost negligible, by comparison. ‘‘It has enormous implications for the sense of self,’’ Tom Insel, the director of the National Institute of Mental Health, told me. ‘‘We are, at least from the standpoint of DNA, more microbial than human. That’s a phenomenal insight and one that we have to take seriously when we think about human development.’’

Given the extent to which bacteria are now understood to influence human physiology, it is hardly surprising that scientists have turned their attention to how bacteria might affect the brain. Micro-organisms in our gut secrete a profound number of chemicals, and researchers like Lyte have found that among those chemicals are the same substances used by our neurons to communicate and regulate mood, like dopamine, serotonin and gamma-aminobutyric acid (GABA). These, in turn, appear to play a function in intestinal disorders, which coincide with high levels of major depression and anxiety. Last year, for example, a group in Norway examined feces from 55 people and found certain bacteria were more likely to be associated with depressive patients.

At the time of my visit to Lyte’s lab, he was nearly six months into an experiment that he hoped would better establish how certain gut microbes influenced the brain, functioning, in effect, as psychiatric drugs. He was currently compiling a list of the psychoactive compounds found in the feces of infant monkeys. Once that was established, he planned to transfer the microbes found in one newborn monkey’s feces into another’s intestine, so that the recipient would end up with a completely new set of microbes — and, if all went as predicted, change their neurodevelopment. The experiment reflected an intriguing hypothesis. Anxiety, depression and several pediatric disorders, including autism and hyperactivity, have been linked with gastrointestinal abnormalities. Microbial transplants were not invasive brain surgery, and that was the point: Changing a patient’s bacteria might be difficult but it still seemed more straightforward than altering his genes.

When Lyte began his work on the link between microbes and the brain three decades ago, it was dismissed as a curiosity. By contrast, last September, the National Institute of Mental Health awarded four grants worth up to $1 million each to spur new research on the gut microbiome’s role in mental disorders, affirming the legitimacy of a field that had long struggled to attract serious scientific credibility. Lyte and one of his longtime colleagues, Christopher Coe, at the Harlow primate lab, received one of the four. ‘‘What Mark proposed going back almost 25 years now has come to fruition,’’ Coe told me. ‘‘Now what we’re struggling to do is to figure out the logic of it.’’ It seems plausible, if not yet proved, that we might one day use microbes to diagnose neurodevelopmental disorders, treat mental illnesses and perhaps even fix them in the brain.

In 2011, a team of researchers at University College Cork, in Ireland, and McMaster University, in Ontario, published a study in Proceedings of the National Academy of Science that has become one of the best-known experiments linking bacteria in the gut to the brain. Laboratory mice were dropped into tall, cylindrical columns of water in what is known as a forced-swim test, which measures over six minutes how long the mice swim before they realize that they can neither touch the bottom nor climb out, and instead collapse into a forlorn float. Researchers use the amount of time a mouse floats as a way to measure what they call ‘‘behavioral despair.’’ (Antidepressant drugs, like Zoloft and Prozac, were initially tested using this forced-swim test.)

For several weeks, the team, led by John Cryan, the neuroscientist who designed the study, fed a small group of healthy rodents a broth infused with Lactobacillus rhamnosus, a common bacterium that is found in humans and also used to ferment milk into probiotic yogurt. Lactobacilli are one of the dominant organisms babies ingest as they pass through the birth canal. Recent studies have shown that mice stressed during pregnancy pass on lowered levels of the bacterium to their pups. This type of bacteria is known to release immense quantities of GABA; as an inhibitory neurotransmitter, GABA calms nervous activity, which explains why the most common anti-anxiety drugs, like Valium and Xanax, work by targeting GABA receptors.

Cryan found that the mice that had been fed the bacteria-laden broth kept swimming longer and spent less time in a state of immobilized woe. ‘‘They behaved as if they were on Prozac,’’ he said. ‘‘They were more chilled out and more relaxed.’’ The results suggested that the bacteria were somehow altering the neural chemistry of mice.

Until he joined his colleagues at Cork 10 years ago, Cryan thought about microbiology in terms of pathology: the neurological damage created by diseases like syphilis or H.I.V. ‘‘There are certain fields that just don’t seem to interact well,’’ he said. ‘‘Microbiology and neuroscience, as whole disciplines, don’t tend to have had much interaction, largely because the brain is somewhat protected.’’ He was referring to the fact that the brain is anatomically isolated, guarded by a blood-brain barrier that allows nutrients in but keeps out pathogens and inflammation, the immune system’s typical response to germs. Cryan’s study added to the growing evidence that signals from beneficial bacteria nonetheless find a way through the barrier. Somehow — though his 2011 paper could not pinpoint exactly how — micro-organisms in the gut tickle a sensory nerve ending in the fingerlike protrusion lining the intestine and carry that electrical impulse up the vagus nerve and into the deep-brain structures thought to be responsible for elemental emotions like anxiety. Soon after that, Cryan and a co-author, Ted Dinan, published a theory paper in Biological Psychiatry calling these potentially mind-altering microbes ‘‘psychobiotics.’’

It has long been known that much of our supply of neurochemicals — an estimated 50 percent of the dopamine, for example, and a vast majority of the serotonin — originate in the intestine, where these chemical signals regulate appetite, feelings of fullness and digestion. But only in recent years has mainstream psychiatric research given serious consideration to the role microbes might play in creating those chemicals. Lyte’s own interest in the question dates back to his time as a postdoctoral fellow at the University of Pittsburgh in 1985, when he found himself immersed in an emerging field with an unwieldy name: psychoneuroimmunology, or PNI, for short. The central theory, quite controversial at the time, suggested that stress worsened disease by suppressing our immune system.

By 1990, at a lab in Mankato, Minn., Lyte distilled the theory into three words, which he wrote on a chalkboard in his office: Stress->Immune->Disease. In the course of several experiments, he homed in on a paradox. When he dropped an intruder mouse in the cage of an animal that lived alone, the intruder ramped up its immune system — a boost, he suspected, intended to fight off germ-ridden bites or scratches. Surprisingly, though, this did not stop infections. It instead had the opposite effect: Stressed animals got sick. Lyte walked up to the board and scratched a line through the word ‘‘Immune.’’ Stress, he suspected, directly affected the bacterial bugs that caused infections.

To test how micro-organisms reacted to stress, he filled petri plates with a bovine-serum-based medium and laced the dishes with a strain of bacterium. In some, he dropped norepinephrine, a neurochemical that mammals produce when stressed. The next day, he snapped a Polaroid. The results were visible and obvious: The control plates were nearly barren, but those with the norepinephrine bloomed with bacteria that filigreed in frostlike patterns. Bacteria clearly responded to stress.

Then, to see if bacteria could induce stress, Lyte fed white mice a liquid solution of Campylobacter jejuni, a bacterium that can cause food poisoning in humans but generally doesn’t prompt an immune response in mice. To the trained eye, his treated mice were as healthy as the controls. But when he ran them through a plexiglass maze raised several feet above the lab floor, the bacteria-fed mice were less likely to venture out on the high, unprotected ledges of the maze. In human terms, they seemed anxious. Without the bacteria, they walked the narrow, elevated planks.

Credit: Illustration by Andrew Rae 

Each of these results was fascinating, but Lyte had a difficult time finding microbiology journals that would publish either. ‘‘It was so anathema to them,’’ he told me. When the mouse study finally appeared in the journal Physiology & Behavior in 1998, it garnered little attention. And yet as Stephen Collins, a gastroenterologist at McMaster University, told me, those first papers contained the seeds of an entire new field of research. ‘‘Mark showed, quite clearly, in elegant studies that are not often cited, that introducing a pathological bacterium into the gut will cause a change in behavior.’’

Lyte went on to show how stressful conditions for newborn cattle worsened deadly E. coli infections. In another experiment, he fed mice lean ground hamburger that appeared to improve memory and learning — a conceptual proof that by changing diet, he could change gut microbes and change behavior. After accumulating nearly a decade’s worth of evidence, in July 2008, he flew to Washington to present his research. He was a finalist for the National Institutes of Health’s Pioneer Award, a $2.5 million grant for so-called blue-sky biomedical research. Finally, it seemed, his time had come. When he got up to speak, Lyte described a dialogue between the bacterial organ and our central nervous system. At the two-minute mark, a prominent scientist in the audience did a spit take.

‘‘Dr. Lyte,’’ he later asked at a question-and-answer session, ‘‘if what you’re saying is right, then why is it when we give antibiotics to patients to kill bacteria, they are not running around crazy on the wards?’’

Lyte knew it was a dismissive question. And when he lost out on the grant, it confirmed to him that the scientific community was still unwilling to imagine that any part of our neural circuitry could be influenced by single-celled organisms. Lyte published his theory in Medical Hypotheses, a low-ranking journal that served as a forum for unconventional ideas. The response, predictably, was underwhelming. ‘‘I had people call me crazy,’’ he said.

But by 2011 — when he published a second theory paper in Bioessays, proposing that probiotic bacteria could be tailored to treat specific psychological diseases — the scientific community had become much more receptive to the idea. A Canadian team, led by Stephen Collins, had demonstrated that antibiotics could be linked to less cautious behavior in mice, and only a few months before Lyte, Sven Pettersson, a microbiologist at the Karolinska Institute in Stockholm, published a landmark paper in Proceedings of the National Academy of Science that showed that mice raised without microbes spent far more time running around outside than healthy mice in a control group; without the microbes, the mice showed less apparent anxiety and were more daring. In Ireland, Cryan published his forced-swim-test study on psychobiotics. There was now a groundswell of new research. In short order, an implausible idea had become a hypothesis in need of serious validation.

Late last year, Sarkis Mazmanian, a microbiologist at the California Institute of Technology, gave a presentation at the Society for Neuroscience, ‘‘Gut Microbes and the Brain: Paradigm Shift in Neuroscience.’’ Someone had inadvertently dropped a question mark from the end, so the speculation appeared to be a definitive statement of fact. But if anyone has a chance of delivering on that promise, it’s Mazmanian, whose research has moved beyond the basic neurochemicals to focus on a broader class of molecules called metabolites: small, equally druglike chemicals that are produced by micro-organisms. Using high-powered computational tools, he also hopes to move beyond the suggestive correlations that have typified psychobiotic research to date, and instead make decisive discoveries about the mechanisms by which microbes affect brain function.

Two years ago, Mazmanian published a study in the journal Cell with Elaine Hsiao, then a graduate student at his lab and now a neuroscientist at Caltech, that made a provocative link between a single molecule and behavior. Their research found that mice exhibiting abnormal communication and repetitive behaviors, like obsessively burying marbles, were mollified when they were given one of two strains of the bacterium Bacteroides fragilis.

The study added to a working hypothesis in the field that microbes don’t just affect the permeability of the barrier around the brain but also influence the intestinal lining, which normally prevents certain bacteria from leaking out and others from getting in. When the intestinal barrier was compromised in his model, normally ‘‘beneficial’’ bacteria and the toxins they produce seeped into the bloodstream and raised the possibility they could slip past the blood-brain barrier. As one of his colleagues, Michael Fischbach, a microbiologist at the University of California, San Francisco, said: ‘‘The scientific community has a way of remaining skeptical until every last arrow has been drawn, until the entire picture is colored in. Other scientists drew the pencil outlines, and Sarkis is filling in a lot of the color.’’

Mazmanian knew the results offered only a provisional explanation for why restrictive diets and antibacterial treatments seemed to help some children with autism: Altering the microbial composition might be changing the permeability of the intestine. ‘‘The larger concept is, and this is pure speculation: Is a disease like autism really a disease of the brain or maybe a disease of the gut or some other aspect of physiology?’’ Mazmanian said. For any disease in which such a link could be proved, he saw a future in drugs derived from these small molecules found inside microbes. (A company he co-founded, Symbiotix Biotherapies, is developing a complex sugar called PSA, which is associated with Bacteroides fragilis, into treatments for intestinal disease and multiple sclerosis.) In his view, the prescriptive solutions probably involve more than increasing our exposure to environmental microbes in soil, dogs or even fermented foods; he believed there were wholesale failures in the way we shared our microbes and inoculated children with these bacteria. So far, though, the only conclusion he could draw was that disorders once thought to be conditions of the brain might be symptoms of microbial disruptions, and it was the careful defining of these disruptions that promised to be helpful in the coming decades.

The list of potential treatments incubating in labs around the world is startling. Several international groups have found that psychobiotics had subtle yet perceptible effects in healthy volunteers in a battery of brain-scanning and psychological tests. Another team in Arizona recently finished an open trial on fecal transplants in children with autism. (Simultaneously, at least two offshore clinics, in Australia and England, began offering fecal microbiota treatments to treat neurological disorders, like multiple sclerosis.) Mazmanian, however, cautions that this research is still in its infancy. ‘‘We’ve reached the stage where there’s a lot of, you know, ‘The microbiome is the cure for everything,’ ’’ he said. ‘‘I have a vested interest if it does. But I’d be shocked if it did.’’

Lyte issues the same caveat. ‘‘People are obviously desperate for solutions,’’ Lyte said when I visited him in Abilene. (He has since moved to Iowa State’s College of Veterinary Medicine.) ‘‘My main fear is the hype is running ahead of the science.’’ He knew that parents emailing him for answers meant they had exhausted every option offered by modern medicine. ‘‘It’s the Wild West out there,’’ he said. ‘‘You can go online and buy any amount of probiotics for any number of conditions now, and my paper is one of those cited. I never said go out and take probiotics.’’ He added, ‘‘We really need a lot more research done before we actually have people trying therapies out.’’

If the idea of psychobiotics had now, in some ways, eclipsed him, it was nevertheless a curious kind of affirmation, even redemption: an old-school microbiologist thrust into the midst of one of the most promising aspects of neuroscience. At the moment, he had a rough map in his head and a freezer full of monkey fecals that might translate, somehow, into telling differences between gregarious or shy monkeys later in life. I asked him if what amounted to a personality transplant still sounded a bit far-fetched. He seemed no closer to unlocking exactly what brain functions could be traced to the same organ that produced feces. ‘‘If you transfer the microbiota from one animal to another, you can transfer the behavior,’’ Lyte said. ‘‘What we’re trying to understand are the mechanisms by which the microbiota can influence the brain and development. If you believe that, are you now out on the precipice? The answer is yes. Do I think it’s the future? I think it’s a long way away.’’

Brain Cells Break Their Own DNA to Allow Memories to Form (IFL Science)

June 22, 2015 | by Justine Alford

photo credit: Courtesy of MIT Researchers 

Given the fundamental importance of our DNA, it is logical to assume that damage to it is undesirable and spells bad news; after all, we know that cancer can be caused by mutations that arise from such injury. But a surprising new study is turning that idea on its head, with the discovery that brain cells actually break their own DNA to enable us to learn and form memories.

While that may sound counterintuitive, it turns out that the damage is necessary to allow the expression of a set of genes, called early-response genes, which regulate various processes that are critical in the creation of long-lasting memories. These lesions are rectified pronto by repair systems, but interestingly, it seems that this ability deteriorates during aging, leading to a buildup of damage that could ultimately result in the degeneration of our brain cells.

This idea is supported by earlier work conducted by the same group, headed by Li-Huei Tsai, at the Massachusetts Institute of Technology (MIT) that discovered that the brains of mice engineered to develop a model of Alzheimer’s disease possessed a significant amount of DNA breaks, even before symptoms appeared. These lesions, which affected both strands of DNA, were observed in a region critical to learning and memory: the hippocampus.

To find out more about the possible consequences of such damage, the team grew neurons in a dish and exposed them to an agent that causes these so-called double strand breaks (DSBs), and then they monitored the gene expression levels. As described in Cellthey found that while the vast majority of genes that were affected by these breaks showed decreased expression, a small subset actually displayed increased expression levels. Importantly, these genes were involved in the regulation of neuronal activity, and included the early-response genes.

Since the early-response genes are known to be rapidly expressed following neuronal activity, the team was keen to find out whether normal neuronal stimulation could also be inducing DNA breaks. The scientists therefore applied a substance to the cells that is known to strengthen the tiny gap between neurons across which information flows – the synapse – mimicking what happens when an organism is exposed to a new experience.

“Sure enough, we found that the treatment very rapidly increased the expression of those early response genes, but it also caused DNA double strand breaks,” Tsai said in a statement.

So what is the connection between these breaks and the apparent boost in early-response gene expression? After using computers to scrutinize the DNA sequences neighboring these genes, the researchers found that they were enriched with a pattern targeted by an architectural protein that, upon binding, distorts the DNA strands by introducing kinks. By preventing crucial interactions between distant DNA regions, these bends therefore act as a barrier to gene expression. The breaks, however, resolve these constraints, allowing expression to ensue.

These findings could have important implications because earlier work has demonstrated that aging is associated with a decline in the expression of genes involved in the processes of learning and memory formation. It therefore seems likely that the DNA repair system deteriorates with age, but at this stage it is unclear how these changes occur, so the researchers plan to design further studies to find out more.

New Vessels Found In The Human Body That Connect Immune System And Brain (IFLScience)

June 3, 2015 | by Stephen Luntz

photo credit: Topic / Shutterstock. It used to be thought that the lymphatic system stopped at the neck, but it has now been found to reach into the brain

In contradiction to decades of medical education, a direct connection has been reported between the brain and the immune system. Claims this radical always require plenty of testing, even after winning publication, but this could be big news for research into diseases like multiple sclerosis (MS) and Alzheimer’s.

It seems astonishing that, after centuries of dissection, a system of lymphatic vessels could have survived undetected. That, however, is exactly what Professor Jonathan Kipnis of the University of Virginia claims in Nature.

Old and new representations of the lymphatic system that carries immune cells around the body. CreditUniversity of Virginia Health System

“It changes entirely the way we perceive the neuro-immune interaction,” says Kipnis. “We always perceived it before as something esoteric that can’t be studied. But now we can ask mechanistic questions.”

MS is known to be an example of the immune system attacking the brain, although the reasons are poorly understood. The opportunity to study lymphatic vessels that link the brain to the immune system could transform our understanding of how these attacks occur, and what could stop them. The causes of Alzheimer’s disease are even more controversial, but may also have immune system origins, and the authors suggest protein accumulation is a result of the vessels failing to do their job.

Indeed, Kipnis claims, “We believe that for every neurological disease that has an immune component to it, these vessels may play a major role.”

The discovery originated when Dr. Antoine Louveau, a researcher in Kipnis’ lab, mounted the membranes that cover mouse brains, known as meninges, on a slide. In the dural sinuses, which drain blood from the brain, he noticed linear patterns in the arrangement of immune T-cells. “I called Jony [Kipnis] to the microscope and I said, ‘I think we have something,'” Louveau recalls.

Kipnis was skeptical, and now says, “I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not.” Extensive further research convinced him and a group of co-authors from some of Virginia’s most prestigious neuroscience institutes that the vessels are real, they carry white blood cells and they also exist in humans. The network, they report, “appears to start from both eyes and track above the olfactory bulb before aligning adjacent to the sinuses.”

Kipnis pays particular credit to colleague Dr. Tajie Harris who enabled the team to image the vessels in action on live animals, confirming their function. Louveau also credits the discovery to fixing the meninges to a skullcap before dissecting, rather than the other way around. This, along with the closeness of the network to a blood vessel, is presumably why no one has observed it before.

The authors say the vessels, “Express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes.”

The authors add that the network bears many resemblances to the peripheral lymphatic system, but it “displays certain unique features,” including being “less complex [and] composed of narrower vessels.”

The discovery reinforces findings that immune cells are present even within healthy brains, a notion that was doubted until recently.

Meningial lymphatic vessels in mice. Credit: Louveau et al, Nature.

An evolutionary approach reveals new clues toward understanding the roots of schizophrenia (AAAS)



Is mental illness simply the evolutionary toll humans have to pay in return for our unique and superior cognitive abilities when compared to all other species? But if so, why have often debilitating illnesses like schizophrenia persisted throughout human evolutionary history when the affects can be quite negative on an individual’s chances of survival or reproductive success?

In a new study appearing in Molecular Biology and Evolution, Mount Sinai researcher Joel Dudley has led a new study that suggests that the very changes specific to human evolution may have come at a cost, contributing to the genetic architecture underlying schizophrenia traits in modern humans.

“We were intrigued by the fact that unlike many other mental traits, schizophrenia traits have not been observed in species other than humans, and schizophrenia has interesting and complex relationships with human intelligence,” said Dr. Joel Dudley, who led the study along with Dr. Panos Roussos. “The rapid increase in genomic data sequenced from large schizophrenia patient cohorts enabled us to investigate the molecular evolutionary history of schizophrenia in sophisticated new ways.”

The team examined a link between these regions, and human-specific evolution, in genomic segments called human accelerated regions, or HARs. HARs are short signposts in the genome that are conserved among non-human species but experienced faster mutation rates in humans. Thus, these regions, which are thought to control the level of gene expression, but not mutate the gene itself, may be an underexplored area of mental illness research.

The team’s research is the first study to sift through the human genome and identify a shared pattern between the location of HARs and recently identified schizophrenia gene loci. To perform their work, they utilized a recently completed, largest schizophrenia study of its kind, the Psychiatric Genomics Consortium (PGC), which included 36,989 schizophrenia cases and 113,075 controls. It is the largest genome-wide association study ever performed on any psychiatric disease.

They found that the schizophrenic loci were most strongly associated in genomic regions near the HARs that are conserved in non-human primates, and these HAR-associated schizophrenic loci are found to be under stronger evolutionary selective pressure when compared with other schizophrenic loci. Furthermore, these regions controlled genes that were expressed only in the prefrontal cortex of the brain, indicating that HARs may play an important role in regulating genes found to be linked to schizophrenia. They specifically found the greatest correlation between HAR-associated schizophrenic loci and genes controlling the expression of the neurotransmitter GABA, brain development, synaptic formations, adhesion and signaling molecules.

Their new evolutionary approach provides new insights into schizophrenia, and genomic targets to prioritize future studies and drug development targets. In addition, there are important new avenues to explore the roles of HARs in other mental diseases such as autism or bipolar disorder.

Common anticholinergic drugs like Benadryl linked to increased dementia risk (Harvard Health Blog)

POSTED JANUARY 28, 2015, 8:55 PM

Beverly Merz, Harvard Women’s Health Watch

One long-ago summer, I joined the legion of teens helping harvest our valley’s peach crop in western Colorado. My job was to select the best peaches from a bin, wrap each one in tissue, and pack it into a shipping crate. The peach fuzz that coated every surface of the packing shed made my nose stream and my eyelids swell. When I came home after my first day on the job, my mother was so alarmed she called the family doctor. Soon the druggist was at the door with a vial of Benadryl (diphenhydramine) tablets. The next morning I was back to normal and back on the job. Weeks later, when I collected my pay (including the ½-cent-per-crate bonus for staying until the end of the harvest), I thanked Benadryl.

Today, I’m thankful my need for that drug lasted only a few weeks. A report published online this week in JAMA Internal Medicine offers compelling evidence of a link between long-term use of anticholinergic medications like Benadryl and dementia.

Anticholinergic drugs block the action of acetylcholine. This substance transmits messages in the nervous system. In the brain, acetylcholine is involved in learning and memory. In the rest of the body, it stimulates muscle contractions. Anticholinergic drugs include some antihistamines, tricyclic antidepressants, medications to control overactive bladder, and drugs to relieve the symptoms of Parkinson’s disease.

What the study found

A team led by Shelley Gray, a pharmacist at the University of Washington’s School of Pharmacy, tracked nearly 3,500 men and women ages 65 and older who took part in Adult Changes in Thought (ACT), a long-term study conducted by the University of Washington and Group Health, a Seattle healthcare system. They used Group Health’s pharmacy records to determine all the drugs, both prescription and over-the-counter, that each participant took the 10 years before starting the study. Participants’ health was tracked for an average of seven years. During that time, 800 of the volunteers developed dementia. When the researchers examined the use of anticholinergic drugs, they found that people who used these drugs were more likely to have developed dementia as those who didn’t use them. Moreover, dementia risk increased along with the cumulative dose. Taking an anticholinergic for the equivalent of three years or more was associated with a 54% higher dementia risk than taking the same dose for three months or less.

The ACT results add to mounting evidence that anticholinergics aren’t drugs to take long-term if you want to keep a clear head, and keep your head clear into old age. The body’s production of acetylcholine diminishes with age, so blocking its effects can deliver a double whammy to older people. It’s not surprising that problems with short-term memory, reasoning, and confusion lead the list of anticholinergic side effects, which also include drowsiness, dry mouth, urine retention, and constipation.

The University of Washington study is the first to include nonprescription drugs. It is also the first to eliminate the possibility that people were taking a tricyclic antidepressant to alleviate early symptoms of undiagnosed dementia; the risk associated with bladder medications was just as high.

“This study is another reminder to periodically evaluate all of the drugs you’re taking. Look at each one to determine if it’s really helping,” says Dr. Sarah Berry, a geriatrician and assistant professor of medicine at Harvard Medical School. “For instance, I’ve seen people who have been on anticholinergic medications for bladder control for years and they are completely incontinent. These drugs obviously aren’t helping.”

Many drugs have a stronger effect on older people than younger people. With age, the kidneys and liver clear drugs more slowly, so drug levels in the blood remain higher for a longer time. People also gain fat and lose muscle mass with age, both of which change the way that drugs are distributed to and broken down in body tissues. In addition, older people tend to take more prescription and over-the-counter medications, each of which has the potential to suppress or enhance the effectiveness of the others.

What should you do?

In 2008, Indiana University School of Medicine geriatrician Malaz Boustani developed the anticholinergic cognitive burden scale, which ranks these drugs according to the severity of their effects on the mind. It’s a good idea to steer clear of the drugs with high ACB scores, meaning those with scores of 3. “There are so many alternatives to these drugs,” says Dr. Berry. For example, selective serotonin re-uptake inhibitors (SSRIs) like citalopram (Celexa) or fluoxetine (Prozac) are good alternatives to tricyclic antidepressants. Newer antihistamines such as loratadine (Claritin) can replace diphenhydramine or chlorpheniramine (Chlor-Trimeton). Botox injections and cognitive behavioral training can alleviate urge incontinence.

One of the best ways to make sure you’re taking the most effective drugs is to dump all your medications — prescription and nonprescription — into a bag and bring them to your next appointment with your primary care doctor.

Protein in coffee with effects like morphine discovered in Brazil (EFE)

Published January 25, 2015

Research done by the state University of Brasilia, or UnB, and Brazil’s state-owned agriculture and livestock research company Embrapa have discovered a protein in coffee with effects similar to morphine, scientists said on Saturday.

A communique from Embrapa said that its Genetics and Biotechnology Resources Division and the UnB successfully “identified previously unknown fragments of protein – peptides – in coffee that have an effect similar to morphine, in other words they have an analgesic and sedative activity.”

Those peptides, the note said, “have a positive differential: their effects last longer in experiments with laboratory mice.”

The two institutions applied for patents to Brazilian regulators for the seven “opioid peptides” identified in the study.

The discovery of the molecules came about through the doctorate research work of Felipe Vinecky of the Molecular Biology Department at UnB, who with the consultation of Embrapa was looking to combine coffee genes to improve the quality of the grain.

The studies also have the support of France’s Center for International Cooperation on Agricultural Research and Development, or CIRAD.

Another Weird Story: Intentional, Post-Intentional, and Unintentional Philosophy (The Cracked Egg)

JANUARY 18, 2015

I was a “2e” kid: gifted with ADHD but cursed with the power to ace standardized tests. I did so well on tests they enrolled me in a Hopkins study, but I couldn’t remember to brush my hair. As if that wasn’t enough, there were a lot of other unusual things going on, far too many to get into here. My brain constantly defied people’s expectations. It was never the same brain from day to day. I am, apparently, a real neuropsychiatric mystery, in both good and bad ways. I’m a walking, breathing challenge to people’s assumptions and perceptions. Just a few examples: the assumption that intelligence is a unitary phenomenon, and the perception that people who think like you are smarter than those who think differently. Even my reasons for defying expectations were misinterpreted. I hated the way people idolized individuality, because being different brought me only pain. People mistook me for trying to be different. Being different is a tragedy!

And it got weirder: I inherited the same sociocognitive tools as everyone else, so I made the same assumptions. Consequently, I defied even my own expectations. So I learned to mistrust my own perceptions, always looking over my shoulder, predicting my own behavior as if I were an outside observer. I literally had to re-engineer myself in order to function in society, and that was impossible to do without getting into some major philosophical questions. I freely admit that this process has taken me my entire life and only recently have I had any success. I am just now learning to function in society–I’m a cracked egg. Cracked once from outside, and once from inside. And just now growing up, a decade late.

So it’s no surprise that I’m so stuck on the question of what people’s brains are actually doing when they theorize.

I stumbled onto R. Scott Bakker’s theories after reading his philosophical thriller, Neuropath. Then I found his blog, and I was blown away that someone besides me was obsessed with the role of ingroup/outgroup dynamics in intellectual circles. As someone with no ingroup (at least not yet), it’s very refreshing. But what really blew my mind was that he had a theory of cognitive science that could explain many of my frustrating experiences: the Blind Brain Theory, or BBT.

The purpose of this post is not to explain BBT, so you’ll have to click the link if you want that. I’ll go more into depth on the specifics of BBT later, but for a ridiculously short summary: it’s a form of eliminativism. Eliminativism is the philosophical view that neuroscience reveals our traditional conceptions of the human being, like free will, mind, and meaning, to be radically mistaken. But BBT is unique among eliminativisms in its emphasis of neglect: the way in which blindness, or lack of information, actually *enables* our brains to solve problems, especially the problem of what we are. And from my perspective, that makes perfect sense.

BBT is a profoundly counterintuitive theory that cautions us against intuition itself. And ironically, it substantiates my skeptical intuitions.  In short, it shows I’m not the only one who has no clue what she’s doing. If BBT is correct, non-neurotypical individuals aren’t really “impaired.” They simply fit differently with other people. Fewer intersecting lines, that’s all. Bakker has developed his theory further since he published this paper, building on his notion of post-intentional theory (see here for a more general introduction). BBT has stirred up quite a lot of drama.

While we all argue over BBT, absorbed in defending our positions, I feel like an outsider, even among people who understand ingroups. Why? Because most of the people in the debate seem to be discussing something hypothetical, something academic. For me, as I’ve explained, the question of intentionality is a question of everyday life. So I can’t shirk my habit of wondering about biology: what’s going on in the brains of intentionalists? What’s going on in the brains of post-intentionalists? And what’s going on inside my own brain? Bakker would say this is precisely the sort of question a post-intentionalist would ask.

But what happens if the post-intentionalist has never done intentional philosophy? Allow me to explain, with a fictionalized example from my own experience. I use the term “intentional” in both an everyday and philosophical sense, interchangeably:

Intentional, Post-Intentional, and Unintentional Philosophy

Imagine you’re an ordinary person. You just want to get on with your life, but you have a terminal illness. It’s an extremely rare neuropsychiatric syndrome: in order to recover, you must solve an ancient philosophical question. You can’t just come up with any old answer. You actually have to prove you solved it, and convince everyone alive you at least have to convince yourself that you could convince anyone whose counterargument could possibly sway you. You’re skeptical to the marrow, and very good at Googling.

Remember, this is a terminal illness, so you have limited time to solve the problem.

In college, philosophy professors said you were a brilliant student. Plus, you have a great imagination from always being forced to do bizarre things. So naturally, you think you can solve it.

But it takes more time than you thought it would. Years more time. Enough time that you turn into a mad hermit. Your life collapses around you and you’re left with no friends, family, or work. But your genes are really damn virulent, and they simply don’t contain the stop codons for self-termination, so you persist.

And finally, after many failed attempts, you cough up something that sticks. An intellectual hairball.

But then the unimaginable happens: you come across a horrifying argument. The argument goes that when it comes to philosophy, intention matters. If your “philosophy” is just a means to survive, it is not philosophy at all; only that which is meant as philosophy can be called philosophical. So therefore, your solution is not valid. It is not even wrong.

So, it’s back to the drawing board for you. You have to find a new solution that makes your intention irrelevant. A solution that satisfies both the intentional philosophers, who do philosophy because they want to, and the unintentional philosophers who do it because they are forced to.

And then you run across something called post-intentional philosophy. It seems like a solution, but…

But post-intentional philosophy, as you see, requires a history: namely, a history of pre-post-intentional philosophy. Or, to oversimplify, intentional philosophy! The kind people do on purpose, not with a gun to their head.

You know that problems cannot be solved from the same level of consciousness that created them, so you try to escape what intentional and post-intentional philosophy share: theory. You think you can tackle your problem by finding a way out of theory altogether. A way that allows for the existence of all sorts of brains generating all sorts of things, intentional, post-intentional, and unintentional. A nonphilosophy, not a Laruellian non-philosophy. That way must exist, otherwise your philosophy will leave your very existence a mystery!

What do you do?

Are Theory and Practice Separate? Separable? Or something completely different?

Philosophy is generally a debate, but as an unintentional thinker I can’t help but remain neutral on everything except responsiveness to reality (more on that coming later). In this section I am attempting neither to support nor to attack it, but to explore it.

Bakker’s heuristic brand of eliminativism appears to bank on the ability to distinguish between the general and the specific, the practical and the theoretical. Correct me if I am wrong.

As the case of the “unintentional philosopher” suggests, philosophers themselves are counterexamples to the robustness of this distinction, just like people with impaired intentional cognition offer counterexamples that question folk psychology. If BBT is empirically testable, the practice-vs-theory distinction must remain empirically testable. We should be able to study everyday cognition (“Square One”) independently of theoretical cognition (“Square Two”) and characterize the neurobiological relationship of the two as either completely modular, somewhat modular, or somewhere in between. We should also be able to predict whether someone is an intentionalist or a post-intentionalist by observing their brains.

From a sociobiological perspective, one possibility is that Bakker is literally trying to hack philosophers’ brains: to separate the neural circuitry that connects philosophical cognition with daily functionality.

If that were the case, their disagreement would come as no surprise.

But my real point here, going back to my struggles with my unusual neurobiology, is that I am personally, neurologically, as close to “non-intentional” as people get. And that presents a problem for my ability to understand any of these philosophical distinctions regarding intentionality, post-intentionality, etc. But just as a person with Aspergers syndrome is forced to intellectually explore the social, my relative deficit of intentionality has simultaneously made it unavoidable–necessary for me to explore intentionality.  My point about theory and practice is to ask whether this state of affairs is “just my problem,” or whether it says something about the entire project of theory.

If nothing else, it certainly questions the assumption that the doctor is never the patient, that the post-intentional theorist is always, necessarily some sort of detached intellectual observer with no deviation from the intentional norm in his own neurobiology.

Come back later for a completely different view…

Do viruses make us smarter? (Science Daily)

Date: January 12, 2015

Source: Lund University

Summary: Inherited viruses that are millions of years old play an important role in building up the complex networks that characterize the human brain, researchers say. They have found that retroviruses seem to play a central role in the basic functions of the brain, more specifically in the regulation of which genes are to be expressed, and when.

Retroviruses seem to play a central role in the basic functions of the brain, more specifically in the regulation of which genes are to be expressed, and when, researchers say. Credit: © Sergey Bogdanov / Fotolia

A new study from Lund University in Sweden indicates that inherited viruses that are millions of years old play an important role in building up the complex networks that characterise the human brain.

Researchers have long been aware that endogenous retroviruses constitute around five per cent of our DNA. For many years, they were considered junk DNA of no real use, a side-effect of our evolutionary journey.

In the current study, Johan Jakobsson and his colleagues show that retroviruses seem to play a central role in the basic functions of the brain, more specifically in the regulation of which genes are to be expressed, and when. The findings indicate that, over the course of evolution, the viruses took an increasingly firm hold on the steering wheel in our cellular machinery. The reason the viruses are activated specifically in the brain is probably due to the fact that tumours cannot form in nerve cells, unlike in other tissues.

“We have been able to observe that these viruses are activated specifically in the brain cells and have an important regulatory role. We believe that the role of retroviruses can contribute to explaining why brain cells in particular are so dynamic and multifaceted in their function. It may also be the case that the viruses’ more or less complex functions in various species can help us to understand why we are so different,” says Johan Jakobsson, head of the research team for molecular neurogenetics at Lund University.

The article, based on studies of neural stem cells, shows that these cells use a particular molecular mechanism to control the activation processes of the retroviruses. The findings provide us with a complex insight into the innermost workings of the most basal functions of the nerve cells. At the same time, the results open up potential for new research paths concerning brain diseases linked to genetic factors.

“I believe that this can lead to new, exciting studies on the diseases of the brain. Currently, when we look for genetic factors linked to various diseases, we usually look for the genes we are familiar with, which make up a mere two per cent of the genome. Now we are opening up the possibility of looking at a much larger part of the genetic material which was previously considered unimportant. The image of the brain becomes more complex, but the area in which to search for errors linked to diseases with a genetic component, such as neurodegenerative diseases, psychiatric illness and brain tumours, also increases.”

Journal Reference:

  1. Liana Fasching, Adamandia Kapopoulou, Rohit Sachdeva, Rebecca Petri, Marie E. Jönsson, Christian Männe, Priscilla Turelli, Patric Jern, Florence Cammas, Didier Trono, Johan Jakobsson. TRIM28 Represses Transcription of Endogenous Retroviruses in Neural Progenitor CellsCell Reports, 2015; 10 (1): 20 DOI: 10.1016/j.celrep.2014.12.004

The Surprising Link Between Gut Bacteria And Anxiety (Huff Post)

 |  By

Posted: 01/04/2015 10:05 am EST 


In recent years, neuroscientists have become increasingly interested in the idea that there may be a powerful link between the human brain and gut bacteria. And while a growing body of research has provided evidence of the brain-gut connection, most of these studies so far have been conducted on animals.

Now, promising new research from neurobiologists at Oxford University offers some preliminary evidence of a connection between gut bacteria and mental health in humans. The researchers found that supplements designed to boost healthy bacteria in the gastrointestinal tract (“prebiotics”) may have an anti-anxiety effect insofar as they alter the way that people process emotional information.

While probiotics consist of strains of good bacteria, prebiotics are carbohydrates that act as nourishment for those bacteria. With increasing evidence that gut bacteria may exert some influence on brain function and mental health, probiotics and prebiotics are being increasingly studied for the potential alleviation of anxiety and depression symptoms.

“Prebiotics are dietary fibers (short chains of sugar molecules) that good bacteria break down, and use to multiply,” the study’s lead author, Oxford psychiatrist and neurobiologist Dr. Philip Burnet, told The Huffington Post. “Prebiotics are ‘food’ for good bacteria already present in the gut. Taking prebiotics therefore increases the numbers of all species of good bacteria in the gut, which will theoretically have greater beneficial effects than [introducing] a single species.”

To test the efficacy of prebiotics in reducing anxiety, the researchers asked 45 healthy adults between the ages of 18 and 45 to take either a prebiotic or a placebo every day for three weeks. After the three weeks had passed, the researchers completed several computer tests assessing how they processed emotional information, such as positive and negatively-charged words.

The results of one of the tests revealed that subjects who had taken the prebiotic paid less attention to negative information and more attention to positive information, compared to the placebo group, suggesting that the prebiotic group had less anxiety when confronted with negative stimuli. This effect is similar to that which has been observed among individuals who have taken antidepressants or anti-anxiety medication.

The researchers also found that the subjects who took the prebiotics had lower levels of cortisol — a stress hormone which has been linked with anxiety and depression — in their saliva when they woke up in the morning.

While previous research has documented that altering gut bacteria has a similarly anxiety-reducing effect in mice, the new study is one of the first to examine this phenomenon in humans. As of now, research on humans is in its early stages. A study conducted last year at UCLA found that women who consumed probiotics through regularly eating yogurt exhibited altered brain function in both a resting state and when performing an emotion-recognition task.

“Time and time again, we hear from patients that they never felt depressed or anxious until they started experiencing problems with their gut,” Dr. Kirsten Tillisch, the study’s lead author, said in a statement. “Our study shows that the gut–brain connection is a two-way street.”

So are we moving towards a future in which mental illness may be able to be treated (or at least managed) using targeted probiotic cocktails? Burnet says it’s possible, although they’re unlikely to replace conventional treatment.

“I think pre/probiotics will only be used as ‘adjuncts’ to conventional treatments, and never as mono-therapies,” Burnet tells HuffPost. “It is likely that these compounds will help to manage mental illness… they may also be used when there are metabolic and/or nutritional complications in mental illness, which may be caused by long-term use of current drugs.”

The findings were published in the journal Psychopharmacology.

Gut microbiota influences blood-brain barrier permeability (Science Daily)

Date: November 19, 2014

Source: Karolinska Institutet

Summary: Our natural gut-residing microbes can influence the integrity of the blood-brain barrier, which protects the brain from harmful substances in the blood, a new study in mice shows. The blood-brain barrier is a highly selective barrier that prevents unwanted molecules and cells from entering the brain from the bloodstream.

Uptake of the substance Raclopride in the brain of germ-free versus conventional mice. Credit: Miklos Toth

A new study in mice, conducted by researchers at Sweden’s Karolinska Institutet together with colleagues in Singapore and the United States, shows that our natural gut-residing microbes can influence the integrity of the blood-brain barrier, which protects the brain from harmful substances in the blood. According to the authors, the findings provide experimental evidence that our indigenous microbes contribute to the mechanism that closes the blood-brain barrier before birth. The results also support previous observations that gut microbiota can impact brain development and function.

The blood-brain barrier is a highly selective barrier that prevents unwanted molecules and cells from entering the brain from the bloodstream. In the current study, being published in the journal Science Translational Medicine, the international interdisciplinary research team demonstrates that the transport of molecules across the blood-brain barrier can be modulated by gut microbes — which therefore play an important role in the protection of the brain.

The investigators reached this conclusion by comparing the integrity and development of the blood-brain barrier between two groups of mice: the first group was raised in an environment where they were exposed to normal bacteria, and the second (called germ-free mice) was kept in a sterile environment without any bacteria.

“We showed that the presence of the maternal gut microbiota during late pregnancy blocked the passage of labeled antibodies from the circulation into the brain parenchyma of the growing fetus,” says first author Dr. Viorica Braniste at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. “In contrast, in age-matched fetuses from germ-free mothers, these labeled antibodies easily crossed the blood-brain barrier and was detected within the brain parenchyma.”

The team also showed that the increased ‘leakiness’ of the blood-brain barrier, observed in germ-free mice from early life, was maintained into adulthood. Interestingly, this ‘leakiness’ could be abrogated if the mice were exposed to fecal transplantation of normal gut microbes. The precise molecular mechanisms remain to be identified. However, the team was able to show that so-called tight junction proteins, which are known to be important for the blood-brain barrier permeability, did undergo structural changes and had altered levels of expression in the absence of bacteria.

According to the researchers, the findings provide experimental evidence that alterations of our indigenous microbiota may have far-reaching consequences for the blood-brain barrier function throughout life.

“These findings further underscore the importance of the maternal microbes during early life and that our bacteria are an integrated component of our body physiology,” says Professor Sven Pettersson, the principal investigator at the Department of Microbiology, Tumor and Cell Biology. “Given that the microbiome composition and diversity change over time, it is tempting to speculate that the blood-brain barrier integrity also may fluctuate depending on the microbiome. This knowledge may be used to develop new ways for opening the blood-brain-barrier to increase the efficacy of the brain cancer drugs and for the design of treatment regimes that strengthens the integrity of the blood-brain barrier.”

Journal Reference:

  1. V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, N. Bakocevic, N. L. Guan, P. Kundu, B. Gulyas, C. Halldin, K. Hultenby, H. Nilsson, H. Hebert, B. T. Volpe, B. Diamond, S. Pettersson. The gut microbiota influences blood-brain barrier permeability in miceScience Translational Medicine, 2014; 6 (263): 263ra158 DOI: 10.1126/scitranslmed.3009759

Brain researchers pinpoint gateway to human memory (Science Daily)


November 26, 2014


DZNE – German Center for Neurodegenerative Diseases


An international team of researchers has successfully determined the location, where memories are generated with a level of precision never achieved before. To this end the scientists used a particularly accurate type of magnetic resonance imaging technology.


Magnetic resonance imaging provides insights into the brain. Credit: DZNE/Guido Hennes

The human brain continuously collects information. However, we have only basic knowledge of how new experiences are converted into lasting memories. Now, an international team led by researchers of the University of Magdeburg and the German Center for Neurodegenerative Diseases (DZNE) has successfully determined the location, where memories are generated with a level of precision never achieved before. The team was able to pinpoint this location down to specific circuits of the human brain. To this end the scientists used a particularly accurate type of magnetic resonance imaging (MRI) technology. The researchers hope that the results and method of their study might be able to assist in acquiring a better understanding of the effects Alzheimer’s disease has on the brain.

The findings are reported in Nature Communications.

For the recall of experiences and facts, various parts of the brain have to work together. Much of this interdependence is still undetermined, however, it is known that memories are stored primarily in the cerebral cortex and that the control center that generates memory content and also retrieves it, is located in the brain’s interior. This happens in the hippocampus and in the adjacent entorhinal cortex.

“It is been known for quite some time that these areas of the brain participate in the generation of memories. This is where information is collected and processed. Our study has refined our view of this situation,” explains Professor Emrah Düzel, site speaker of the DZNE in Magdeburg and director of the Institute of Cognitive Neurology and Dementia Research at the University of Magdeburg. “We have been able to locate the generation of human memories to certain neuronal layers within the hippocampus and the entorhinal cortex. We were able to determine which neuronal layer was active. This revealed if information was directed into the hippocampus or whether it traveled from the hippocampus into the cerebral cortex. Previously used MRI techniques were not precise enough to capture this directional information. Hence, this is the first time we have been able to show where in the brain the doorway to memory is located.”

For this study, the scientists examined the brains of persons who had volunteered to participate in a memory test. The researchers used a special type of magnetic resonance imaging technology called “7 Tesla ultra-high field MRI.” This enabled them to determine the activity of individual brain regions with unprecedented accuracy.

A Precision method for research on Alzheimer’s

“This measuring technique allows us to track the flow of information inside the brain and examine the areas that are involved in the processing of memories in great detail,” comments Düzel. “As a result, we hope to gain new insights into how memory impairments arise that are typical for Alzheimer’s. Concerning dementia, is the information still intact at the gateway to memory? Do troubles arise later on, when memories are processed? We hope to answer such questions.”

Story Source:

The above story is based on materials provided by DZNE – German Center for Neurodegenerative Diseases. Note: Materials may be edited for content and length.

Journal Reference:

  1. Anne Maass, Hartmut Schütze, Oliver Speck, Andrew Yonelinas, Claus Tempelmann, Hans-Jochen Heinze, David Berron, Arturo Cardenas-Blanco, Kay H. Brodersen, Klaas Enno Stephan, Emrah Düzel. Laminar activity in the hippocampus and entorhinal cortex related to novelty and episodic encoding. Nature Communications, 2014; 5: 5547 DOI: 10.1038/ncomms6547

How the bacteria in our gut affect our cravings for food (Conversation)

November 6 2014, 10.00pm EST

Vincent Ho

Gut bacteria can manufacture special proteins that are very similar to hunger-regulating hormones. Lighthunter/Shutterstock

We’ve long known that that the gut is responsible for digesting food and expelling the waste. More recently, we realised the gut has many more important functions and acts a type of mini-brain, affecting our mood and appetite. Now, new research suggests it might also play a role in our cravings for certain types of food.

How does the mini-brain work?

The gut mini-brain produces a wide range of hormones and contains many of the same neurotransmitters as the brain. The gut also contains neurons that are located in the walls of the gut in a distributed network known as the enteric nervous system. In fact, there are more of these neurons in the gut than in the entire spinal cord.

The enteric nervous system communicates to the brain via the brain-gut axis and signals flow in both directions. The brain-gut axis is thought to be involved in many regular functions and systems within the healthy body, including the regulation of eating.

Let’s consider what happens to the brain-gut axis when we eat a meal. When food arrives in the stomach, certain gut hormones are secreted. These activate signalling pathways from the gut to the brainstem and the hypothalamus to stop food consumption. Such hormones include the appetite-suppressing hormones peptide YY and cholecystokinin.

Gut hormones can bind and activate receptor targets in the brain directly but there is strong evidence that the vagus nerve plays a major role in brain-gut signalling. The vagus nerve acts as a major highway in the brain-gut axis, connecting the over 100 million neurons in the enteric nervous system to the medulla (located at the base of the brain).

Research has shown that vagus nerve blockade can lead to marked weight loss, while vagus nerve stimulation is known to trigger excessive eating in rats.

This brings us to the topic of food cravings. Scientists have largely debunked the myth that food cravings are our bodies’ way of letting us know that we need a specific type of nutrient. Instead, an emerging body of research suggests that our food cravings may actually be significantly shaped by the bacteria that we have inside our gut. In order to explore this further we will cover the role of gut microbes.

Gut microbiota

As many as 90% of our cells are bacterial. In fact, bacterial genes outnumber human genes by a factor of 100 to one.

The gut is an immensely complex microbial ecosystem with many different species of bacteria, some of which can live in an oxygen-free environment. An average person has approximately 1.5 kilograms of gut bacteria. The term “gut microbiota” is used to describe the bacterial collective.

We each have around 1.5kg of bacteria in our guts. Christopher PooleyCC BY

Gut microbiota send signals to the brain via the brain-gut axis and can have dramatic effects on animal behaviour and health.

In one study, for example, mice that were genetically predisposed to obesity remained lean when they were raised in a sterile environment without gut microbiota. These germ-free mice were, however, transformed into obese mice when fed a faecal pellet that came from an obese mouse raised conventionally.

The role of gut microbiota in food cravings

There is growing evidence to support the role of gut microbiota in influencing why we crave certain foods.

We know that mice that are bred in germ-free environments prefer more sweets and have greater number of sweet taste receptors in their gut compared to normal mice. Research has also found that persons who are “chocolate desiring” have microbial breakdown products in their urine that are different from those of “chocolate indifferent individuals” despite eating identical diets.

Many gut bacteria can manufacture special proteins (called peptides) that are very similar to hormones such as peptide YY and ghrelin that regulate hunger. Humans and other animals have produced antibodies against these peptides. This raises the distinct possibility that microbes might be able to directly influence human eating behaviour through their peptides that mimic hunger-regulating hormones or indirectly through antibodies that can interfere with appetite regulation.

Practical implications

There are substantial challenges to overcome before we can apply this knowledge about gut microbiota in a practical sense.

First, there is the challenge of collecting the gut microbes. Traditionally this is collected from stools but gut microbiota is known to vary between different regions of the gut, such as the small intestine and colon. Obtaining bacterial tissue through endoscopy or another invasive collection technique in addition to stool samples may lead to more accurate representation of the gut microbiome.

Second, the type of sequencing that is currently used for gut microbiota screening is expensive and time-consuming. Advances will need to be made before this technology is in routine use.

Probably the greatest challenge in gut microbiota research is the establishment of a strong correlation between gut microbiota patterns and human disease. The science of gut microbiota is in its infancy and there needs to be much more research mapping out disease relationships.

Probiotics contain live microorganisms. Quanthem/Shutterstock

But there is reason to be hopeful. There is now strong interest in utilising both prebiotics and probiotics to alter our gut micro biome. Prebiotics are non-digestible carbohydrates that trigger the growth of beneficial gut bacteria, while probiotics are beneficial live microorganisms contained in foods and supplements.

Faecal transplantation is also now an accepted treatment for those patients that have a severe form of gut bacterial infection called Clostridium difficile, which has been unresponsive to antibiotics.

The use of such targeted strategies is likely to become increasingly common as we better understand how gut microbiota influence our bodily functions, including food cravings.

Ghost illusion created in the lab (Science Daily)

Date: November 6, 2014

Source: Ecole Polytechnique Fédérale de Lausanne

Summary: Patients suffering from neurological or psychiatric conditions have often reported ‘feeling a presence’ watching over them. Now, researchers have succeeded in recreating these ghostly illusions in the lab.

This image depicts a person experiencing the ghost illusion in the lab. Credit: Alain Herzog/EPFL

Ghosts exist only in the mind, and scientists know just where to find them, an EPFL study suggests. Patients suffering from neurological or psychiatric conditions have often reported feeling a strange “presence.” Now, EPFL researchers in Switzerland have succeeded in recreating this so-called ghost illusion in the laboratory.

On June 29, 1970, mountaineer Reinhold Messner had an unusual experience. Recounting his descent down the virgin summit of Nanga Parbat with his brother, freezing, exhausted, and oxygen-starved in the vast barren landscape, he recalls, “Suddenly there was a third climber with us… a little to my right, a few steps behind me, just outside my field of vision.”

It was invisible, but there. Stories like this have been reported countless times by mountaineers, explorers, and survivors, as well as by people who have been widowed, but also by patients suffering from neurological or psychiatric disorders. They commonly describe a presence that is felt but unseen, akin to a guardian angel or a demon. Inexplicable, illusory, and persistent.

Olaf Blanke’s research team at EPFL has now unveiled this ghost. The team was able to recreate the illusion of a similar presence in the laboratory and provide a simple explanation. They showed that the “feeling of a presence” actually results from an alteration of sensorimotor brain signals, which are involved in generating self-awareness by integrating information from our movements and our body’s position in space.

In their experiment, Blanke’s team interfered with the sensorimotor input of participants in such a way that their brains no longer identified such signals as belonging to their own body, but instead interpreted them as those of someone else. The work is published in Current Biology.

Generating a “Ghost”

The researchers first analyzed the brains of 12 patients with neurological disorders — mostly epilepsy — who have experienced this kind of “apparition.” MRI analysis of the patients’s brains revealed interference with three cortical regions: the insular cortex, parietal-frontal cortex, and the temporo-parietal cortex. These three areas are involved in self-awareness, movement, and the sense of position in space (proprioception). Together, they contribute to multisensory signal processing, which is important for the perception of one’s own body.

The scientists then carried out a “dissonance” experiment in which blindfolded participants performed movements with their hand in front of their body. Behind them, a robotic device reproduced their movements, touching them on the back in real time. The result was a kind of spatial discrepancy, but because of the synchronized movement of the robot, the participant’s brain was able to adapt and correct for it.

Next, the neuroscientists introduced a temporal delay between the participant’s movement and the robot’s touch. Under these asynchronous conditions, distorting temporal and spatial perception, the researchers were able to recreate the ghost illusion.

An “Unbearable” Experience

The participants were unaware of the experiment’s purpose. After about three minutes of the delayed touching, the researchers asked them what they felt. Instinctively, several subjects reported a strong “feeling of a presence,” even counting up to four “ghosts” where none existed. “For some, the feeling was even so strong that they asked to stop the experiment,” said Giulio Rognini, who led the study.

“Our experiment induced the sensation of a foreign presence in the laboratory for the first time. It shows that it can arise under normal conditions, simply through conflicting sensory-motor signals,” explained Blanke. “The robotic system mimics the sensations of some patients with mental disorders or of healthy individuals under extreme circumstances. This confirms that it is caused by an altered perception of their own bodies in the brain.”

A Deeper Understanding of Schizophrenia

In addition to explaining a phenomenon that is common to many cultures, the aim of this research is to better understand some of the symptoms of patients suffering from schizophrenia. Such patients often suffer from hallucinations or delusions associated with the presence of an alien entity whose voice they may hear or whose actions they may feel. Many scientists attribute these perceptions to a malfunction of brain circuits that integrate sensory information in relation to our body’s movements.

“Our brain possesses several representations of our body in space,” added Giulio Rognini. “Under normal conditions, it is able to assemble a unified self-perception of the self from these representations. But when the system malfunctions because of disease — or, in this case, a robot — this can sometimes create a second representation of one’s own body, which is no longer perceived as ‘me’ but as someone else, a ‘presence’.”

It is unlikely that these findings will stop anyone from believing in ghosts. However, for scientists, it’s still more evidence that they only exist in our minds.

Watch the video:

Journal Reference:

  1. Olaf Blanke, Polona Pozeg, Masayuki Hara, Lukas Heydrich, Andrea Serino, Akio Yamamoto, Toshiro Higuchi, Roy Salomon, Margitta Seeck, Theodor Landis, Shahar Arzy, Bruno Herbelin, Hannes Bleuler, Giulio Rognini. Neurological and Robot-Controlled Induction of an Apparition. Current Biology, 2014; DOI:10.1016/j.cub.2014.09.049

Direct brain interface between humans (Science Daily)

Date: November 5, 2014

Source: University of Washington

Summary: Researchers have successfully replicated a direct brain-to-brain connection between pairs of people as part of a scientific study following the team’s initial demonstration a year ago. In the newly published study, which involved six people, researchers were able to transmit the signals from one person’s brain over the Internet and use these signals to control the hand motions of another person within a split second of sending that signal.

In this photo, UW students Darby Losey, left, and Jose Ceballos are positioned in two different buildings on campus as they would be during a brain-to-brain interface demonstration. The sender, left, thinks about firing a cannon at various points throughout a computer game. That signal is sent over the Web directly to the brain of the receiver, right, whose hand hits a touchpad to fire the cannon.Mary Levin, U of Wash. Credit: Image courtesy of University of Washington

Sometimes, words just complicate things. What if our brains could communicate directly with each other, bypassing the need for language?

University of Washington researchers have successfully replicated a direct brain-to-brain connection between pairs of people as part of a scientific study following the team’s initial demonstration a year ago. In the newly published study, which involved six people, researchers were able to transmit the signals from one person’s brain over the Internet and use these signals to control the hand motions of another person within a split second of sending that signal.

At the time of the first experiment in August 2013, the UW team was the first to demonstrate two human brains communicating in this way. The researchers then tested their brain-to-brain interface in a more comprehensive study, published Nov. 5 in the journal PLOS ONE.

“The new study brings our brain-to-brain interfacing paradigm from an initial demonstration to something that is closer to a deliverable technology,” said co-author Andrea Stocco, a research assistant professor of psychology and a researcher at UW’s Institute for Learning & Brain Sciences. “Now we have replicated our methods and know that they can work reliably with walk-in participants.”

Collaborator Rajesh Rao, a UW associate professor of computer science and engineering, is the lead author on this work.

The research team combined two kinds of noninvasive instruments and fine-tuned software to connect two human brains in real time. The process is fairly straightforward. One participant is hooked to an electroencephalography machine that reads brain activity and sends electrical pulses via the Web to the second participant, who is wearing a swim cap with a transcranial magnetic stimulation coil placed near the part of the brain that controls hand movements.

Using this setup, one person can send a command to move the hand of the other by simply thinking about that hand movement.

The UW study involved three pairs of participants. Each pair included a sender and a receiver with different roles and constraints. They sat in separate buildings on campus about a half mile apart and were unable to interact with each other in any way — except for the link between their brains.

Each sender was in front of a computer game in which he or she had to defend a city by firing a cannon and intercepting rockets launched by a pirate ship. But because the senders could not physically interact with the game, the only way they could defend the city was by thinking about moving their hand to fire the cannon.

Across campus, each receiver sat wearing headphones in a dark room — with no ability to see the computer game — with the right hand positioned over the only touchpad that could actually fire the cannon. If the brain-to-brain interface was successful, the receiver’s hand would twitch, pressing the touchpad and firing the cannon that was displayed on the sender’s computer screen across campus.

Researchers found that accuracy varied among the pairs, ranging from 25 to 83 percent. Misses mostly were due to a sender failing to accurately execute the thought to send the “fire” command. The researchers also were able to quantify the exact amount of information that was transferred between the two brains.

Another research team from the company Starlab in Barcelona, Spain, recently published results in the same journal showing direct communication between two human brains, but that study only tested one sender brain instead of different pairs of study participants and was conducted offline instead of in real time over the Web.

Now, with a new $1 million grant from the W.M. Keck Foundation, the UW research team is taking the work a step further in an attempt to decode and transmit more complex brain processes.

With the new funding, the research team will expand the types of information that can be transferred from brain to brain, including more complex visual and psychological phenomena such as concepts, thoughts and rules.

They’re also exploring how to influence brain waves that correspond with alertness or sleepiness. Eventually, for example, the brain of a sleepy airplane pilot dozing off at the controls could stimulate the copilot’s brain to become more alert.

The project could also eventually lead to “brain tutoring,” in which knowledge is transferred directly from the brain of a teacher to a student.

“Imagine someone who’s a brilliant scientist but not a brilliant teacher. Complex knowledge is hard to explain — we’re limited by language,” said co-author Chantel Prat, a faculty member at the Institute for Learning & Brain Sciences and a UW assistant professor of psychology.

Other UW co-authors are Joseph Wu of computer science and engineering; Devapratim Sarma and Tiffany Youngquist of bioengineering; and Matthew Bryan, formerly of the UW.

The research published in PLOS ONE was initially funded by the U.S. Army Research Office and the UW, with additional support from the Keck Foundation.

Journal Reference:

  1. Rajesh P. N. Rao, Andrea Stocco, Matthew Bryan, Devapratim Sarma, Tiffany M. Youngquist, Joseph Wu, Chantel S. Prat. A Direct Brain-to-Brain Interface in Humans. PLoS ONE, 2014; 9 (11): e111332 DOI: 10.1371/journal.pone.0111332

How the brain leads us to believe we have sharp vision (Science Daily)

Date: October 17, 2014

Source: Bielefeld University

Summary: We assume that we can see the world around us in sharp detail. In fact, our eyes can only process a fraction of our surroundings precisely. In a series of experiments, psychologists have been investigating how the brain fools us into believing that we see in sharp detail.

The thumbnail at the end of an outstretched arm: This is the area that the eye actually can see in sharp detail. Researchers have investigated why the rest of the world also appears to be uniformly detailed. Credit: Bielefeld University

We assume that we can see the world around us in sharp detail. In fact, our eyes can only process a fraction of our surroundings precisely. In a series of experiments, psychologists at Bielefeld University have been investigating how the brain fools us into believing that we see in sharp detail. The results have been published in the scientific magazine Journal of Experimental Psychology: General. Its central finding is that our nervous system uses past visual experiences to predict how blurred objects would look in sharp detail.

“In our study we are dealing with the question of why we believe that we see the world uniformly detailed,” says Dr. Arvid Herwig from the Neuro-Cognitive Psychology research group of the Faculty of Psychology and Sports Science. The group is also affiliated to the Cluster of Excellence Cognitive Interaction Technology (CITEC) of Bielefeld University and is led by Professor Dr. Werner X. Schneider.

Only the fovea, the central area of the retina, can process objects precisely. We should therefore only be able to see a small area of our environment in sharp detail. This area is about the size of a thumb nail at the end of an outstretched arm. In contrast, all visual impressions which occur outside the fovea on the retina become progressively coarse. Nevertheless, we commonly have the impression that we see large parts of our environment in sharp detail.

Herwig and Schneider have been getting to the bottom of this phenomenon with a series of experiments. Their approach presumes that people learn through countless eye movements over a lifetime to connect the coarse impressions of objects outside the fovea to the detailed visual impressions after the eye has moved to the object of interest. For example, the coarse visual impression of a football (blurred image of a football) is connected to the detailed visual impression after the eye has moved. If a person sees a football out of the corner of her eye, her brain will compare this current blurred picture with memorised images of blurred objects. If the brain finds an image that fits, it will replace the coarse image with a precise image from memory. This blurred visual impression is replaced before the eye moves. The person thus thinks that she already sees the ball clearly, although this is not the case.

The psychologists have been using eye-tracking experiments to test their approach. Using the eye-tracking technique, eye movements are measured accurately with a specific camera which records 1000 images per second. In their experiments, the scientists have recorded fast balistic eye movements (saccades) of test persons. Though most of the participants did not realise it, certain objects were changed during eye movement. The aim was that the test persons learn new connections between visual stimuli from inside and outside the fovea, in other words from detailed and coarse impressions. Afterwards, the participants were asked to judge visual characteristics of objects outside the area of the fovea. The result showed that the connection between a coarse and detailed visual impression occurred after just a few minutes. The coarse visual impressions became similar to the newly learnt detailed visual impressions.

“The experiments show that our perception depends in large measure on stored visual experiences in our memory,” says Arvid Herwig. According to Herwig and Schneider, these experiences serve to predict the effect of future actions (“What would the world look like after a further eye movement”). In other words: “We do not see the actual world, but our predictions.”

Journal Reference:

  1. Arvid Herwig, Werner X. Schneider. Predicting object features across saccades: Evidence from object recognition and visual search. Journal of Experimental Psychology: General, 2014; 143 (5): 1903 DOI: 10.1037/a0036781

Scientists find ‘hidden brain signatures’ of consciousness in vegetative state patients (Science Daily)

Date: October 16, 2014

Source: University of Cambridge

Summary: Scientists in Cambridge have found hidden signatures in the brains of people in a vegetative state, which point to networks that could support consciousness even when a patient appears to be unconscious and unresponsive. The study could help doctors identify patients who are aware despite being unable to communicate.

These images show brain networks in two behaviorally similar vegetative patients (left and middle), but one of whom imagined playing tennis (middle panel), alongside a healthy adult (right panel). Credit: Srivas Chennu

Scientists in Cambridge have found hidden signatures in the brains of people in a vegetative state, which point to networks that could support consciousness even when a patient appears to be unconscious and unresponsive. The study could help doctors identify patients who are aware despite being unable to communicate.

There has been a great deal of interest recently in how much patients in a vegetative state following severe brain injury are aware of their surroundings. Although unable to move and respond, some of these patients are able to carry out tasks such as imagining playing a game of tennis. Using a functional magnetic resonance imaging (fMRI) scanner, which measures brain activity, researchers have previously been able to record activity in the pre-motor cortex, the part of the brain which deals with movement, in apparently unconscious patients asked to imagine playing tennis.

Now, a team of researchers led by scientists at the University of Cambridge and the MRC Cognition and Brain Sciences Unit, Cambridge, have used high-density electroencephalographs (EEG) and a branch of mathematics known as ‘graph theory’ to study networks of activity in the brains of 32 patients diagnosed as vegetative and minimally conscious and compare them to healthy adults. The findings of the research are published today in the journal PLOS Computational Biology. The study was funded mainly by the Wellcome Trust, the National Institute of Health Research Cambridge Biomedical Research Centre and the Medical Research Council (MRC).

The researchers showed that the rich and diversely connected networks that support awareness in the healthy brain are typically — but importantly, not always — impaired in patients in a vegetative state. Some vegetative patients had well-preserved brain networks that look similar to those of healthy adults — these patients were those who had shown signs of hidden awareness by following commands such as imagining playing tennis.

Dr Srivas Chennu from the Department of Clinical Neurosciences at the University of Cambridge says: “Understanding how consciousness arises from the interactions between networks of brain regions is an elusive but fascinating scientific question. But for patients diagnosed as vegetative and minimally conscious, and their families, this is far more than just an academic question — it takes on a very real significance. Our research could improve clinical assessment and help identify patients who might be covertly aware despite being uncommunicative.”

The findings could help researchers develop a relatively simple way of identifying which patients might be aware whilst in a vegetative state. Unlike the ‘tennis test’, which can be a difficult task for patients and requires expensive and often unavailable fMRI scanners, this new technique uses EEG and could therefore be administered at a patient’s bedside. However, the tennis test is stronger evidence that the patient is indeed conscious, to the extent that they can follow commands using their thoughts. The researchers believe that a combination of such tests could help improve accuracy in the prognosis for a patient.

Dr Tristan Bekinschtein from the MRC Cognition and Brain Sciences Unit and the Department of Psychology, University of Cambridge, adds: “Although there are limitations to how predictive our test would be used in isolation, combined with other tests it could help in the clinical assessment of patients. If a patient’s ‘awareness’ networks are intact, then we know that they are likely to be aware of what is going on around them. But unfortunately, they also suggest that vegetative patients with severely impaired networks at rest are unlikely to show any signs of consciousness.”

Journal Reference:

  1. Chennu S, Finoia P, Kamau E, Allanson J, Williams GB, et al. Spectral Signatures of Reorganised Brain Networks in Disorders of Consciousness. PLOS Computational Biology, 2014; 10 (10): e1003887 DOI:10.1371/journal.pcbi.1003887

Amputees discern familiar sensations across prosthetic hand (Science Daily)

Date: October 8, 2014

Source: Case Western Reserve University

Summary: Patients connected to a new prosthetic system said they ‘felt’ their hands for the first time since they lost them in accidents. In the ensuing months, they began feeling sensations that were familiar and were able to control their prosthetic hands with more — well — dexterity.

Medical researchers are helping restore the sense of touch in amputees. Credit: Image courtesy of Case Western Reserve University

Even before he lost his right hand to an industrial accident 4 years ago, Igor Spetic had family open his medicine bottles. Cotton balls give him goose bumps.

Now, blindfolded during an experiment, he feels his arm hairs rise when a researcher brushes the back of his prosthetic hand with a cotton ball.

Spetic, of course, can’t feel the ball. But patterns of electric signals are sent by a computer into nerves in his arm and to his brain, which tells him different. “I knew immediately it was cotton,” he said.

That’s one of several types of sensation Spetic, of Madison, Ohio, can feel with the prosthetic system being developed by Case Western Reserve University and the Louis Stokes Cleveland Veterans Affairs Medical Center.

Spetic was excited just to “feel” again, and quickly received an unexpected benefit. The phantom pain he’d suffered, which he’s described as a vice crushing his closed fist, subsided almost completely. A second patient, who had less phantom pain after losing his right hand and much of his forearm in an accident, said his, too, is nearly gone.

Despite having phantom pain, both men said that the first time they were connected to the system and received the electrical stimulation, was the first time they’d felt their hands since their accidents. In the ensuing months, they began feeling sensations that were familiar and were able to control their prosthetic hands with more — well — dexterity.

To watch a video of the research, click here:

“The sense of touch is one of the ways we interact with objects around us,” said Dustin Tyler, an associate professor of biomedical engineering at Case Western Reserve and director of the research. “Our goal is not just to restore function, but to build a reconnection to the world. This is long-lasting, chronic restoration of sensation over multiple points across the hand.”

“The work reactivates areas of the brain that produce the sense of touch, said Tyler, who is also associate director of the Advanced Platform Technology Center at the Cleveland VA. “When the hand is lost, the inputs that switched on these areas were lost.”

How the system works and the results will be published online in the journal Science Translational Medicine Oct. 8.

“The sense of touch actually gets better,” said Keith Vonderhuevel, of Sidney, Ohio, who lost his hand in 2005 and had the system implanted in January 2013. “They change things on the computer to change the sensation.

“One time,” he said, “it felt like water running across the back of my hand.”

The system, which is limited to the lab at this point, uses electrical stimulation to give the sense of feeling. But there are key differences from other reported efforts.

First, the nerves that used to relay the sense of touch to the brain are stimulated by contact points on cuffs that encircle major nerve bundles in the arm, not by electrodes inserted through the protective nerve membranes.

Surgeons Michael W Keith, MD and J. Robert Anderson, MD, from Case Western Reserve School of Medicine and Cleveland VA, implanted three electrode cuffs in Spetic’s forearm, enabling him to feel 19 distinct points; and two cuffs in Vonderhuevel’s upper arm, enabling him to feel 16 distinct locations.

Second, when they began the study, the sensation Spetic felt when a sensor was touched was a tingle. To provide more natural sensations, the research team has developed algorithms that convert the input from sensors taped to a patient’s hand into varying patterns and intensities of electrical signals. The sensors themselves aren’t sophisticated enough to discern textures, they detect only pressure.

The different signal patterns, passed through the cuffs, are read as different stimuli by the brain. The scientists continue to fine-tune the patterns, and Spetic and Vonderhuevel appear to be becoming more attuned to them.

Third, the system has worked for 2 ½ years in Spetic and 1½ in Vonderhueval. Other research has reported sensation lasting one month and, in some cases, the ability to feel began to fade over weeks.

A blindfolded Vonderhuevel has held grapes or cherries in his prosthetic hand — the signals enabling him to gauge how tightly he’s squeezing — and pulled out the stems.

“When the sensation’s on, it’s not too hard,” he said. “When it’s off, you make a lot of grape juice.”

Different signal patterns interpreted as sandpaper, a smooth surface and a ridged surface enabled a blindfolded Spetic to discern each as they were applied to his hand. And when researchers touched two different locations with two different textures at the same time, he could discern the type and location of each.

Tyler believes that everyone creates a map of sensations from their life history that enables them to correlate an input to a given sensation.

“I don’t presume the stimuli we’re giving is hitting the spots on the map exactly, but they’re familiar enough that the brain identifies what it is,” he said.

Because of Vonderheuval’s and Spetic’s continuing progress, Tyler is hopeful the method can lead to a lifetime of use. He’s optimistic his team can develop a system a patient could use at home, within five years.

In addition to hand prosthetics, Tyler believes the technology can be used to help those using prosthetic legs receive input from the ground and adjust to gravel or uneven surfaces. Beyond that, the neural interfacing and new stimulation techniques may be useful in controlling tremors, deep brain stimulation and more.

Journal Reference:

  1. D. W. Tan, M. A. Schiefer, M. W. Keith, J. R. Anderson, J. Tyler, D. J. Tyler. A neural interface provides long-term stable natural touch perception. Science Translational Medicine, 2014; 6 (257): 257ra138 DOI:10.1126/scitranslmed.3008669

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Mind-controlled prosthetic arms that work in daily life are now a reality (Science Daily)

Date: October 8, 2014

Source: Chalmers University of Technology

Summary: For the first time, robotic prostheses controlled via implanted neuromuscular interfaces have become a clinical reality. A novel osseointegrated (bone-anchored) implant system gives patients new opportunities in their daily life and professional activities.

For the first time, robotic prostheses controlled via implanted neuromuscular interfaces have become a clinical reality. Credit: Image courtesy of Chalmers University of Technology

For the first time, robotic prostheses controlled via implanted neuromuscular interfaces have become a clinical reality. A novel osseointegrated (bone-anchored) implant system gives patients new opportunities in their daily life and professional activities.

In January 2013 a Swedish arm amputee was the first person in the world to receive a prosthesis with a direct connection to bone, nerves and muscles. An article about this achievement and its long-term stability will now be published in the Science Translational Medicine journal.

“Going beyond the lab to allow the patient to face real-world challenges is the main contribution of this work,” says Max Ortiz Catalan, research scientist at Chalmers University of Technology and leading author of the publication.

“We have used osseointegration to create a long-term stable fusion between man and machine, where we have integrated them at different levels. The artificial arm is directly attached to the skeleton, thus providing mechanical stability. Then the human’s biological control system, that is nerves and muscles, is also interfaced to the machine’s control system via neuromuscular electrodes. This creates an intimate union between the body and the machine; between biology and mechatronics.”

The direct skeletal attachment is created by what is known as osseointegration, a technology in limb prostheses pioneered by associate professor Rickard Brånemark and his colleagues at Sahlgrenska University Hospital. Rickard Brånemark led the surgical implantation and collaborated closely with Max Ortiz Catalan and Professor Bo Håkansson at Chalmers University of Technology on this project.

The patient’s arm was amputated over ten years ago. Before the surgery, his prosthesis was controlled via electrodes placed over the skin. Robotic prostheses can be very advanced, but such a control system makes them unreliable and limits their functionality, and patients commonly reject them as a result.

Now, the patient has been given a control system that is directly connected to his own. He has a physically challenging job as a truck driver in northern Sweden, and since the surgery he has experienced that he can cope with all the situations he faces; everything from clamping his trailer load and operating machinery, to unpacking eggs and tying his children’s skates, regardless of the environmental conditions (read more about the benefits of the new technology below).

The patient is also one of the first in the world to take part in an effort to achieve long-term sensation via the prosthesis. Because the implant is a bidirectional interface, it can also be used to send signals in the opposite direction — from the prosthetic arm to the brain. This is the researchers’ next step, to clinically implement their findings on sensory feedback.

“Reliable communication between the prosthesis and the body has been the missing link for the clinical implementation of neural control and sensory feedback, and this is now in place,” says Max Ortiz Catalan. “So far we have shown that the patient has a long-term stable ability to perceive touch in different locations in the missing hand. Intuitive sensory feedback and control are crucial for interacting with the environment, for example to reliably hold an object despite disturbances or uncertainty. Today, no patient walks around with a prosthesis that provides such information, but we are working towards changing that in the very short term.”

The researchers plan to treat more patients with the novel technology later this year.

“We see this technology as an important step towards more natural control of artificial limbs,” says Max Ortiz Catalan. “It is the missing link for allowing sophisticated neural interfaces to control sophisticated prostheses. So far, this has only been possible in short experiments within controlled environments.”

More about: How the technology works

The new technology is based on the OPRA treatment (osseointegrated prosthesis for the rehabilitation of amputees), where a titanium implant is surgically inserted into the bone and becomes fixated to it by a process known as osseointegration (Osseo = bone). A percutaneous component (abutment) is then attached to the titanium implant to serve as a metallic bone extension, where the prosthesis is then fixated. Electrodes are implanted in nerves and muscles as the interfaces to the biological control system. These electrodes record signals which are transmitted via the osseointegrated implant to the prostheses, where the signals are finally decoded and translated into motions.

More about: Benefits of the new technology, compared to socket prostheses

Direct skeletal attachment by osseointegration means:

  • Increased range of motion since there are no physical limitations by the socket — the patient can move the remaining joints freely
  • Elimination of sores and pain caused by the constant pressure from the socket
  • Stable and easy attachment/detachment
  • Increased sensory feedback due to the direct transmission of forces and vibrations to the bone (osseoperception)
  • The prosthesis can be worn all day, every day
  • No socket adjustments required (there is no socket)

Implanting electrodes in nerves and muscles means that:

  • Due to the intimate connection, the patients can control the prosthesis with less effort and more precisely, and can thus handle smaller and more delicate items.
  • The close proximity between source and electrode also prevents activity from other muscles from interfering (cross-talk), so that the patient can move the arm to any position and still maintain control of the prosthesis.
  • More motor signals can be obtained from muscles and nerves, so that more movements can be intuitively controlled in the prosthesis.
  • After the first fitting of the controller, little or no recalibration is required because there is no need to reposition the electrodes on every occasion the prosthesis is worn (as opposed to superficial electrodes).
  • Since the electrodes are implanted rather than placed over the skin, control is not affected by environmental conditions (cold and heat) that change the skin state, or by limb motions that displace the skin over the muscles. The control is also resilient to electromagnetic interference (noise from other electric devices or power lines) as the electrodes are shielded by the body itself.
  • Electrodes in the nerves can be used to send signals to the brain as sensations coming from the prostheses.

Journal Reference:

  1. M. Ortiz-Catalan, B. Hakansson, R. Branemark. An osseointegrated human-machine gateway for long-term sensory feedback and motor control of artificial limbs. Science Translational Medicine, 2014; 6 (257): 257re6 DOI:10.1126/scitranslmed.3008933

Consciência pode permanecer por até três minutos após a morte, diz estudo (O Globo)

Cientistas entrevistaram pacientes que chegaram a ter morte clínica, mas voltaram à vida


Cena da novela "Amor Eterno Amor" da Rede Globo retrata a experiência de quase morte estudadas pelos cientistas da Universidade de Southampton Foto: ReproduçãoCena da novela “Amor Eterno Amor” da Rede Globo retrata a experiência de quase morte estudadas pelos cientistas da Universidade de Southampton – Reprodução

RIO – Aquele túnel com uma luz brilhante no fundo e uma sensação de paz descritos por filmes e outras pessoas que alegaram ter passado por experiência de quase morte podem ser reais. No maior estudo já feito sobre o tema, cientistas da Universidade de Southampton disseram ter comprovado que a consciência humana permanece por ao menos três minutos após o óbito biológico. Durante esse meio tempo, pacientes conseguiriam testemunhar e lembrar depois de eventos como a saída do corpo e os movimentos ao redor do quarto do hospital.

Ao longo de quatro anos, os especialistas examinaram mais de duas mil pessoas que sofreram paradas cardíacas em 15 hospitais no Reino Unido, Estados Unidos e Áustria. Cerca de 16% sobreviveram. E destes, mais de 40% descreveram algum tipo de “consciência” durante o tempo em que eles estavam clinicamente mortos, antes de seus corações voltarem a bater.

O caso mais emblemático foi de um homem ainda lembrou ter deixado seu corpo totalmente e assistindo sua reanimação do canto da sala. Apesar de ser inconsciente e “morto” por três minutos, o paciente narrou com detalhes as ações da equipe de enfermagem e descreveu o som das máquinas.

– Sabemos que o cérebro não pode funcionar quando o coração parou de bater. Mas neste caso, a percepção consciente parece ter continuado por até três minutos no período em que o coração não estava batendo, mesmo que o cérebro normalmente encerre as atividades dentro de 20 a 30 segundos após o coração – explicou ao jornal inglês The Telegraph o pesquisador Sam Parnia.

Dos 2.060 pacientes com parada cardíaca estudados, 330 sobreviveram e 140 disseram ter experimentado algum tipo de consciência ao ser ressuscitado. Embora muitos não se lembrassem de detalhes específicos, alguns relatos coincidiram. Um em cada cinco disseram que tinha sentido uma sensação incomum de tranquilidade, enquanto quase um terço disse que o tempo tinha se abrandado ou se acelerado.

Alguns lembraram de ter visto uma luz brilhante, um flash de ouro ou o sol brilhando. Outros relataram sentimentos de medo, afogamento ou sendo arrastado pelas águas profundas. Cerca de 13% disseram que se sentiam separados de seus corpos.

De acordo com Parnia, muito mais pessoas podem ter experiências quando estão perto da morte, mas as drogas ou sedativos utilizados no processo de ressuscitação podem afetar a memória:

– As estimativas sugerem que milhões de pessoas tiveram experiências vivas em relação à morte. Muitas assumiram que eram alucinações ou ilusões, mas os relatos parecem corresponder a eventos reais. E uma proporção maior de pessoas pode ter experiências vivas de morte, mas não se lembrarem delas devido aos efeitos da lesão cerebral ou sedativos em circuitos de memória.


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Near-death experiences? Results of the world’s largest medical study of the human mind and consciousness at time of death (Science Daily)

Date: October 7, 2014

Source: University of Southampton

Summary: The results of a four-year international study of 2060 cardiac arrest cases across 15 hospitals concludes the following. The themes relating to the experience of death appear far broader than what has been understood so far, or what has been described as so called near-death experiences. In some cases of cardiac arrest, memories of visual awareness compatible with so called out-of-body experiences may correspond with actual events. A higher proportion of people may have vivid death experiences, but do not recall them due to the effects of brain injury or sedative drugs on memory circuits. Widely used yet scientifically imprecise terms such as near-death and out-of-body experiences may not be sufficient to describe the actual experience of death. The recalled experience surrounding death merits a genuine investigation without prejudice.

The results of a four-year international study of 2060 cardiac arrest cases across 15 hospitals are in. Among those who reported a perception of awareness and completed further interviews, 46 per cent experienced a broad range of mental recollections in relation to death that were not compatible with the commonly used term of near death experiences. Credit: © sudok1 / Fotolia

The results of a four-year international study of 2060 cardiac arrest cases across 15 hospitals concludes the following. The themes relating to the experience of death appear far broader than what has been understood so far, or what has been described as so called near-death experiences. In some cases of cardiac arrest, memories of visual awareness compatible with so called out-of-body experiences may correspond with actual events. A higher proportion of people may have vivid death experiences, but do not recall them due to the effects of brain injury or sedative drugs on memory circuits. Widely used yet scientifically imprecise terms such as near-death and out-of-body experiences may not be sufficient to describe the actual experience of death.

Recollections in relation to death, so-called out-of-body experiences (OBEs) or near-death experiences (NDEs), are an often spoken about phenomenon which have frequently been considered hallucinatory or illusory in nature; however, objective studies on these experiences are limited.

In 2008, a large-scale study involving 2060 patients from 15 hospitals in the United Kingdom, United States and Austria was launched. The AWARE (AWAreness during REsuscitation) study, sponsored by the University of Southampton in the UK, examined the broad range of mental experiences in relation to death. Researchers also tested the validity of conscious experiences using objective markers for the first time in a large study to determine whether claims of awareness compatible with out-of-body experiences correspond with real or hallucinatory events.

Results of the study have been published in the journal Resuscitation.

Dr Sam Parnia, Assistant Professor of Critical Care Medicine and Director of Resuscitation Research at The State University of New York at Stony Brook, USA, and the study’s lead author, explained: “Contrary to perception, death is not a specific moment but a potentially reversible process that occurs after any severe illness or accident causes the heart, lungs and brain to cease functioning. If attempts are made to reverse this process, it is referred to as ‘cardiac arrest’; however, if these attempts do not succeed it is called ‘death’. In this study we wanted to go beyond the emotionally charged yet poorly defined term of NDEs to explore objectively what happens when we die.”

Thirty-nine per cent of patients who survived cardiac arrest and were able to undergo structured interviews described a perception of awareness, but interestingly did not have any explicit recall of events.

“This suggests more people may have mental activity initially but then lose their memories after recovery, either due to the effects of brain injury or sedative drugs on memory recall,” explained Dr Parnia, who was an Honorary Research Fellow at the University of Southampton when he started the AWARE study.

Among those who reported a perception of awareness and completed further interviews, 46 per cent experienced a broad range of mental recollections in relation to death that were not compatible with the commonly used term of NDE’s. These included fearful and persecutory experiences. Only 9 per cent had experiences compatible with NDEs and 2 per cent exhibited full awareness compatible with OBE’s with explicit recall of ‘seeing’ and ‘hearing’ events.

One case was validated and timed using auditory stimuli during cardiac arrest. Dr Parnia concluded: “This is significant, since it has often been assumed that experiences in relation to death are likely hallucinations or illusions, occurring either before the heart stops or after the heart has been successfully restarted, but not an experience corresponding with ‘real’ events when the heart isn’t beating. In this case, consciousness and awareness appeared to occur during a three-minute period when there was no heartbeat. This is paradoxical, since the brain typically ceases functioning within 20-30 seconds of the heart stopping and doesn’t resume again until the heart has been restarted. Furthermore, the detailed recollections of visual awareness in this case were consistent with verified events.

“Thus, while it was not possible to absolutely prove the reality or meaning of patients’ experiences and claims of awareness, (due to the very low incidence (2 per cent) of explicit recall of visual awareness or so called OBE’s), it was impossible to disclaim them either and more work is needed in this area. Clearly, the recalled experience surrounding death now merits further genuine investigation without prejudice.”

Further studies are also needed to explore whether awareness (explicit or implicit) may lead to long term adverse psychological outcomes including post-traumatic stress disorder.

Dr Jerry Nolan, Editor-in-Chief of Resuscitation, stated: “The AWARE study researchers are to be congratulated on the completion of a fascinating study that will open the door to more extensive research into what happens when we die.”

Journal Reference:

  1. Parnia S, et al. AWARE—AWAreness during REsuscitation—A prospective study. Resuscitation, 2014 DOI: 10.1016/j.resuscitation.2014.09.004

How learning to talk is in the genes (Science Daily)

Date: September 16, 2014

Source: University of Bristol

Summary: Researchers have found evidence that genetic factors may contribute to the development of language during infancy. Scientists discovered a significant link between genetic changes near the ROBO2 gene and the number of words spoken by children in the early stages of language development.

Researchers have found evidence that genetic factors may contribute to the development of language during infancy. Credit: © witthaya / Fotolia

Researchers have found evidence that genetic factors may contribute to the development of language during infancy.

Scientists from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol worked with colleagues around the world to discover a significant link between genetic changes near the ROBO2 gene and the number of words spoken by children in the early stages of language development.

Children produce words at about 10 to 15 months of age and our range of vocabulary expands as we grow — from around 50 words at 15 to 18 months, 200 words at 18 to 30 months, 14,000 words at six-years-old and then over 50,000 words by the time we leave secondary school.

The researchers found the genetic link during the ages of 15 to 18 months when toddlers typically communicate with single words only before their linguistic skills advance to two-word combinations and more complex grammatical structures.

The results, published in Nature Communications today [16 Sept], shed further light on a specific genetic region on chromosome 3, which has been previously implicated in dyslexia and speech-related disorders.

The ROBO2 gene contains the instructions for making the ROBO2 protein. This protein directs chemicals in brain cells and other neuronal cell formations that may help infants to develop language but also to produce sounds.

The ROBO2 protein also closely interacts with other ROBO proteins that have previously been linked to problems with reading and the storage of speech sounds.

Dr Beate St Pourcain, who jointly led the research with Professor Davey Smith at the MRC Integrative Epidemiology Unit, said: “This research helps us to better understand the genetic factors which may be involved in the early language development in healthy children, particularly at a time when children speak with single words only, and strengthens the link between ROBO proteins and a variety of linguistic skills in humans.”

Dr Claire Haworth, one of the lead authors, based at the University of Warwick, commented: “In this study we found that results using DNA confirm those we get from twin studies about the importance of genetic influences for language development. This is good news as it means that current DNA-based investigations can be used to detect most of the genetic factors that contribute to these early language skills.”

The study was carried out by an international team of scientists from the EArly Genetics and Lifecourse Epidemiology Consortium (EAGLE) and involved data from over 10,000 children.

Journal Reference:
  1. Beate St Pourcain, Rolieke A.M. Cents, Andrew J.O. Whitehouse, Claire M.A. Haworth, Oliver S.P. Davis, Paul F. O’Reilly, Susan Roulstone, Yvonne Wren, Qi W. Ang, Fleur P. Velders, David M. Evans, John P. Kemp, Nicole M. Warrington, Laura Miller, Nicholas J. Timpson, Susan M. Ring, Frank C. Verhulst, Albert Hofman, Fernando Rivadeneira, Emma L. Meaburn, Thomas S. Price, Philip S. Dale, Demetris Pillas, Anneli Yliherva, Alina Rodriguez, Jean Golding, Vincent W.V. Jaddoe, Marjo-Riitta Jarvelin, Robert Plomin, Craig E. Pennell, Henning Tiemeier, George Davey Smith. Common variation near ROBO2 is associated with expressive vocabulary in infancy. Nature Communications, 2014; 5: 4831 DOI:10.1038/ncomms5831

Nudge: The gentle science of good governance (New Scientist)

25 June 2013

Magazine issue 2922

NOT long before David Cameron became UK prime minister, he famously prescribed some holiday reading for his colleagues: a book modestly entitled Nudge.

Cameron wasn’t the only world leader to find it compelling. US president Barack Obama soon appointed one of its authors, Cass Sunstein, a social scientist at the University of Chicago, to a powerful position in the White House. And thus the nudge bandwagon began rolling. It has been picking up speed ever since (see “Nudge power: Big government’s little pushes“).

So what’s the big idea? We don’t always do what’s best for ourselves, thanks to cognitive biases and errors that make us deviate from rational self-interest. The premise of Nudge is that subtly offsetting or exploiting these biases can help people to make better choices.

If you live in the US or UK, you’re likely to have been nudged towards a certain decision at some point. You probably didn’t notice. That’s deliberate: nudging is widely assumed to work best when people aren’t aware of it. But that stealth breeds suspicion: people recoil from the idea that they are being stealthily manipulated.

There are other grounds for suspicion. It sounds glib: a neat term for a slippery concept. You could argue that it is a way for governments to avoid taking decisive action. Or you might be concerned that it lets them push us towards a convenient choice, regardless of what we really want.

These don’t really hold up. Our distaste for being nudged is understandable, but is arguably just another cognitive bias, given that our behaviour is constantly being discreetly influenced by others. What’s more, interventions only qualify as nudges if they don’t create concrete incentives in any particular direction. So the choice ultimately remains a free one.

Nudging is a less blunt instrument than regulation or tax. It should supplement rather than supplant these, and nudgers must be held accountable. But broadly speaking, anyone who believes in evidence-based policy should try to overcome their distaste and welcome governance based on behavioural insights and controlled trials, rather than carrot-and-stick wishful thinking. Perhaps we just need a nudge in the right direction.

Brain circuit differences reflect divisions in social status (Science Daily)

Date: September 2, 2014

Source: University of Oxford

Summary: Life at opposite ends of primate social hierarchies is linked to specific brain networks, research has shown. The more dominant you are, the bigger some brain regions are. If your social position is more subordinate, other brain regions are bigger.


Group of young barbary macaques (stock image). The research determined the position of 25 macaque monkeys in their social hierarchy and then analyzed non-invasive scans of their brains that had been collected as part of other ongoing University research programs. The findings show that brain regions in one neural circuit are larger in more dominant animals. The regions composing this circuit are the amygdala, raphe nucleus and hypothalamus. Credit: © scphoto48 / Fotolia

Life at opposite ends of primate social hierarchies is linked to specific brain networks, a new Oxford University study has shown.

The importance of social rank is something we all learn at an early age. In non-human primates, social dominance influences access to food and mates. In humans, social hierarchies influence our performance everywhere from school to the workplace and have a direct influence on our well-being and mental health. Life on the lowest rung can be stressful, but life at the top also requires careful acts of balancing and coalition forming. However, we know very little about the relationship between these social ranks and brain function.

The new research, conducted at the University of Oxford, reveals differences between individual primate’s brains which depend on the their social status. The more dominant you are, the bigger some brain regions are. If your social position is more subordinate, other brain regions are bigger. Additionally, the way the brain regions interact with each other is also associated with social status. The pattern of results suggests that successful behaviour at each end of the social scale makes specialised demands of the brain.

The research, led by Dr MaryAnn Noonan of the Decision and Action Laboratory at the University of Oxford, determined the position of 25 macaque monkeys in their social hierarchy and then analysed non-invasive scans of their brains that had been collected as part of other ongoing University research programs. The findings, publishing September 2 in the open access journal PLOS Biology, show that brain regions in one neural circuit are larger in more dominant animals. The regions composing this circuit are the amygdala, raphe nucleus and hypothalamus. Previous research has shown that the amygdala is involved in learning, and processing social and emotional information. The raphe nucleus and hypothalamus are involved in controlling neurotransmitters and neurohormones, such as serotonin and oxytocin. The MRI scans also revealed that another circuit of brain regions, which collectively can be called the striatum, were found to be larger in more subordinate animals. The striatum is known to play a complex but important role in learning the value of our choices and actions.

The study also reports that the brain’s activity, not just its structure, varies with position in the social hierarchy. The researchers found that the strength with which activity in some of these areas was coupled together was also related to social status. Collectively, these results mean that social status is not only reflected in the brain’s hardware, it is also related to differences in the brain’s software, or communication patterns.

Finally, the size of another set of brain regions correlated not only with social status but also with the size of the animal’s social group. The macaque groups ranged in size between one and seven. The research showed that grey matter in regions involved in social cognition, such as the mid-superior temporal sulcus and rostral prefrontal cortex, correlated with both group size and social status. Previous research has shown that these regions are important for a variety of social behaviours, such as interpreting facial expressions or physical gestures, understanding the intentions of others and predicting their behaviour.

“This finding may reflect the fact that social status in macaques depends not only on the outcome of competitive social interactions but on social bonds formed that promote coalitions,” says Matthew Rushworth, the head of the Decision and Action Laboratory in Oxford. “The correlation with social group size and social status suggests this set of brain regions may coordinate behaviour that bridges these two social variables.”

The results suggest that just as animals assign value to environmental stimuli they may also assign values to themselves — ‘self-values’. Social rank is likely to be an important determinant of such self-values. We already know that some of the brain regions identified in the current study track the value of objects in our environment and so may also play a key role in monitoring longer-term values associated with an individual’s status.

The reasons behind the identified brain differences remain unclear, particularly whether they are present at birth or result from social differences. Dr Noonan said: “One possibility is that the demands of a life in a particular social position use certain brain regions more frequently and as a result those areas expand to step up to the task. Alternatively, it is possible that people born with brains organised in a particular way tend towards certain social positions. In all likelihood, both of these mechanisms will work together to produce behaviour appropriate for the social context.”

Social status also changes over time and in different contexts. Dr Noonan added: “While we might be top-dog in one circle of friends, at work we might be more of a social climber. The fluidity of our social position and how our brains adapt our behavior to succeed in each context is the next exciting direction for this area of research.”


Journal Reference:

  1. MaryAnn P. Noonan, Jerome Sallet, Rogier B. Mars, Franz X. Neubert, Jill X. O’Reilly, Jesper L. Andersson, Anna S. Mitchell, Andrew H. Bell, Karla L. Miller, Matthew F. S. Rushworth. A Neural Circuit Covarying with Social Hierarchy in Macaques. PLoS Biology, 2014; 12 (9): e1001940 DOI:10.1371/journal.pbio.1001940