Posts tagged neuroscience

ScienceDaily (May 20, 2012) — To learn its signature melody, the male songbird uses a trial-and-error process to mimic the song of its father, singing the tune over and over again, hundreds of times a day, making subtle changes in the pitch of the notes. For the male Bengalese finch, this rigorous training process begins around the age of 40 days and is completed about day 90, just as he becomes sexually mature and ready to use his song to woo females.

To learn its signature melody, the male songbird uses a trial-and-error process to mimic the song of its father, singing the tune over and over again, hundreds of times a day, making subtle changes in the pitch of the notes. (Credit: © fasphotographic / Fotolia)

To accomplish this feat, the finch’s brain must receive and process large quantities of information about its performance and use that data to precisely control the complex vocal actions that allow it to modify the pitch and pattern of its song.

Now, scientists at UCSF have shown that a key brain structure acts as a learning hub, receiving information from other regions of the brain and figuring out how to use that information to improve its song, even when it’s not directly controlling the action. These insights may help scientists figure out new ways to treat neurological disorders that impair movement such as Huntington’s disease and Parkinson’s disease.

The research is reported as an advanced online publication on May 20, 2012 by the journal Nature, and will appear at a later date in the journal’s print edition.

Years of research conducted in the lab of Michael Brainard, PhD, an associate professor of physiology at UCSF, has shown that adult finches can keep track of slight differences in the individual “syllables,” or notes, they play and hear, and make mental computations that allow them to alter the pitch.

For previous experiments, Brainard and his colleagues developed a training process that induced adult finches to calibrate their song. They created a computer program that could recognize the pitch of every syllable the bird sang. The computer also delivered a sound the birds didn’t like — a kind of white noise — at the very moment they uttered a specific note. Within a few hours, the finches learned to alter the pitch of that syllable to avoid hearing the unpleasant sound.

In the new research, the UCSF neuroscientists used their technology to investigate how the learning process is controlled by the brain. A prevailing theory suggests that new learning is controlled by a “smart” brain structure called the basal ganglia, a cluster of interconnected brain regions involved in motor control and learning.

"It’s the first place where the brain is putting two and two together," said Jonathan Charlesworth, a recent graduate of UCSF’s neuroscience PhD program and the first author of the new paper. "If you remove the basal ganglia in a bird that hasn’t yet learned to sing, it will never learn to do so."

Once a basic, frequently repeated skill such as typing, singing the same song or shooting a basketball from the free-throw line is learned, the theory suggests, control of that activity is carried out by the motor pathway, the part of the nervous system that transmits signals from the brain to muscles. But for the basic routine to change — for a player to shoot from another spot on the basketball court or a bird to sing at a different pitch — the basal ganglia must again get involved, providing feedback that allows learning based on trial and error, the theory suggests.

What remained unclear is what makes the basal ganglia so “smart” and enables them to support such detailed trial-and-error learning. Was it something to do with their structure? Or were they getting information from elsewhere?

The scientists sought to answer this question by blocking the output of a key basal ganglia circuit while training male finches to alter their song using the white-noise blasts. As long as the basal ganglia were kept from sending signals to the motor pathway, the finches didn’t change their tune or show signs of learning. But when Brainard’s team stopped blocking the basal ganglia, something surprising happened: the finches immediately changed the pitch of their song, with no additional practice.

"It’s as if a golfer went to the driving range and was terrible, hitting the ball into the trees all day and not getting any better," said Charlesworth. "Then, at the end of the day, you throw a switch and all of a sudden you’re hitting the fairway like you’re Tiger Woods."

Normally, you’d expect improvement in skill performance like this to take time as the basal ganglia evaluates information, makes changes and gets new feedback, Brainard said.

"The surprise here is that the basal ganglia can pay attention, observe what other motor structures are doing and get information even when they aren’t involved in motor control," Brainard said. "They covertly learned how to improve skill performance and this explains how they did it."

These findings suggest that the basal ganglia’s “smartness” is due in large part to the steady flow of information they receive about the commands of other motor structures. It also portrays the basal ganglia as far more versatile than previously understood, able to learn how to calibrate fine-motor skills by acting as a specialized hub that receives information from various parts of the brain and responds to that information with new directives.

The findings also support the notion that problems in the basal ganglia circuit’s ability to receive information and learn from it may help trigger the movement disorders that are symptoms of Huntington’s and Parkinson’s, Brainard said.

Source: Science Daily

ScienceDaily (May 19, 2012) — Preliminary results from an ongoing, large-scale study by Yale School of Medicine researchers shows that oxytocin — a naturally occurring substance produced in the brain and throughout the body — increased brain function in regions that are known to process social information in children and adolescents with autism spectrum disorders (ASD).

Preliminary results from an ongoing, large-scale study by Yale School of Medicine researchers shows that oxytocin — a naturally occurring substance produced in the brain and throughout the body— increased brain function in regions that are known to process social information in children and adolescents with autism spectrum disorders (ASD). (Credit: Image courtesy of Yale University)

A Yale Child Study Center research team that includes postdoctoral fellow Ilanit Gordon and Kevin Pelphrey, the Harris Associate Professor of Child Psychiatry and Psychology, will present the results on May 19 at the International Meeting for Autism Research.

"Our findings provide the first, critical steps toward devising more effective treatments for the core social deficits in autism, which may involve a combination of clinical interventions with an administration of oxytocin," said Gordon. "Such a treatment approach will fundamentally improve our understanding of autism and its treatment."

Social-communicative dysfunctions are a core characteristic of autism, a neurodevelopmental disorder that can have an enormous emotional and financial burden on the affected individual, their families, and society.

Gordon said that while a great deal of progress has been made in the field of autism research, there remain few effective treatments and none that directly target the core social dysfunction. Oxytocin has recently received attention for its involvement in regulating social abilities because of its role in many aspects of social behavior and social cognition in humans and other species.

To assess the impact of oxytocin on the brain function, Gordon and her team conducted a first-of-its-kind, double-blind, placebo-controlled study on children and adolescents aged 7 to 18 with ASD. The team members gave the children a single dose of oxytocin in a nasal spray and used functional magnetic resonance brain imaging to observe its effect.

The team found that oxytocin increased activations in brain regions known to process social information. Gordon said these brain activations were linked to tasks involving multiple social information processing routes, such as seeing, hearing, and processing information relevant to understanding other people.

Source: Science Daily

ScienceDaily (May 18, 2012) — Exercise clears the mind. It gets the blood pumping and more oxygen is delivered to the brain. This is familiar territory, but Dartmouth’s David Bucci thinks there is much more going on.

Exercise clears the mind. It gets the blood pumping and more oxygen is delivered to the brain. This is familiar territory, but Dartmouth’s David Bucci thinks there is much more going on. (Credit: © Galina Barskaya / Fotolia)

"In the last several years there have been data suggesting that neurobiological changes are happening — [there are] very brain-specific mechanisms at work here," says Bucci, an associate professor in the Department of Psychological and Brain Sciences.

From his studies, Bucci and his collaborators have revealed important new findings:

• The effects of exercise are different on memory as well as on the brain, depending on whether the exerciser is an adolescent or an adult.
• A gene has been identified which seems to mediate the degree to which exercise has a beneficial effect. This has implications for the potential use of exercise as an intervention for mental illness.

Bucci began his pursuit of the link between exercise and memory with attention deficit hyperactivity disorder (ADHD), one of the most common childhood psychological disorders. Bucci is concerned that the treatment of choice seems to be medication.

"The notion of pumping children full of psycho-stimulants at an early age is troublesome," Bucci cautions. "We frankly don’t know the long-term effects of administering drugs at an early age — drugs that affect the brain — so looking for alternative therapies is clearly important."

Anecdotal evidence from colleagues at the University of Vermont started Bucci down the track of ADHD. Based on observations of ADHD children in Vermont summer camps, athletes or team sports players were found to respond better to behavioral interventions than more sedentary children. While systematic empirical data is lacking, this association of exercise with a reduction of characteristic ADHD behaviors was persuasive enough for Bucci.

Coupled with his interest in learning and memory and their underlying brain functions, Bucci and teams of graduate and undergraduate students embarked upon a project of scientific inquiry, investigating the potential connection between exercise and brain function. They published papers documenting their results, with the most recent now available in the online version of the journal Neuroscience.

Bucci is quick to point out that “the teams of both graduate and undergraduates are responsible for all this work, certainly not just me.” Michael Hopkins, a graduate student at the time, is first author on the papers.

Early on, laboratory rats that exhibit ADHD-like behavior demonstrated that exercise was able to reduce the extent of these behaviors. The researchers also found that exercise was more beneficial for female rats than males, similar to how it differentially affects male and female children with ADHD.

Moving forward, they investigated a mechanism through which exercise seems to improve learning and memory. This is “brain derived neurotrophic factor” (BDNF) and it is involved in growth of the developing brain. The degree of BDNF expression in exercising rats correlated positively with improved memory, and exercising as an adolescent had longer lasting effects compared to the same duration of exercise, but done as an adult.

"The implication is that exercising during development, as your brain is growing, is changing the brain in concert with normal developmental changes, resulting in your having more permanent wiring of the brain in support of things like learning and memory," says Bucci. "It seems important to [exercise] early in life."

Bucci’s latest paper was a move to take the studies of exercise and memory in rats and apply them to humans. The subjects in this new study were Dartmouth undergraduates and individuals recruited from the Hanover community.

Bucci says that, “the really interesting finding was that, depending on the person’s genotype for that trophic factor [BDNF], they either did or did not reap the benefits of exercise on learning and memory. This could mean that you may be able to predict which ADHD child, if we genotype them and look at their DNA, would respond to exercise as a treatment and which ones wouldn’t.”

Bucci concludes that the notion that exercise is good for health including mental health is not a huge surprise. “The interesting question in terms of mental health and cognitive function is how exercise affects mental function and the brain.” This is the question Bucci, his colleagues, and students continue to pursue.

Source: Science Daily

May 18, 2012

University of Iowa neuroscientist John Wemmie, M.D., Ph.D., is interested in the effect of acid in the brain. His studies suggest that increased acidity or low pH, in the brain is linked to panic disorders, anxiety, and depression. But his work also suggests that changes in acidity are important for normal brain activity too.

University of Iowa researchers have developed an MRI-based method to detect and monitor pH changes in living brains. The image shows MRI brain scans of human subject breathing air (left) or air containing 7.5 percent carbon dioxide (middle). The difference between the two scans (shown right) shows increased brain acidity in red caused by carbon dioxide inhalation as measured by the new MRI-based strategy. Credit: Vincent Magnotta, University of Iowa

"We are interested in the idea that pH might be changing in the functional brain because we’ve been hot on the trail of receptors that are activated by low pH,” says Wemmie, a UI associate professor of psychiatry. “The presence of these receptors implies the possibility that low pH might be playing a signaling role in normal brain function.”

Wemmie’s studies have shown that these acid-sensing proteins are required for normal fear responses and for learning and memory in mice. However, while you can buy a kit to measure the pH (acidity) of your garden soil, there currently is no easy way to measure pH changes in the brain.

Wemmie teamed up with Vincent Magnotta, Ph.D., UI associate professor of radiology, psychiatry, and biomedical engineering, and using Magnotta’s expertise in developing MRI (magnetic resonance imaging)-based brain imaging techniques, the researchers developed and tested a new, non-invasive method to detect and monitor pH changes in living brains.

According to Wemmie, the new imaging technique provides the best evidence so far that pH changes do occur with normal function in the intact human brain. The findings were published May 7 in the Proceedings of the National Academy of Sciences (PNAS) Early Edition.

Specifically, the study showed the MRI-based method was able to detect global changes in brain pH in mice. Breathing carbon dioxide, which lowers pH (makes the brain more acidic), increased the signal, while bicarbonate injections, which increases brain pH, decreased the MRI signal. The relationship between the signal and the pH was linear over the range that was tested.

Importantly, the method also seems able to detect localized brain activity. When human volunteers viewed a flashing checkerboard — a classic experiment that activates a particular brain region involved in vision — the MRI method detected a drop in pH in that region. The team also confirmed the pH drop using other methods.

"Our study tells us, first, we have a technique that we believe can measure pH changes in the brain, and second, this MRI-based technique suggests that pH changes do occur with brain function,” Magnotta says.

"The results support our original idea that brain activity can change local pH in human brains during normal activity, meaning that pH change in conjunction with the pH-sensitive receptors could be part of a signaling system that affects brain activity and cognitive function," Wemmie adds

A new way to view brain activity

Importantly, this technique may also provide a new way to image the brain

Currently, functional MRI (fMRI) measures brain activity by detecting a signal that’s due to oxygen levels in the blood flowing to active brain regions. The UI team showed that their method responds to pH changes but is not influenced by changes in blood oxygenation. Conversely, fMRI does not respond to changes in pH.

"What we show is our method of detecting brain activity probably depends on pH changes and, more than that, it is distinct from the signal that fMRI measures," says Wemmie. "This gives us another tool to study brain activity."

pH and brain function

Wemmie’s previous studies have suggested a role for pH changes in certain psychiatric diseases, including anxiety and depression. With the new method, he and his colleagues hope to explore how pH is involved in these conditions.

“Brain activity is likely different in people with brain disorders, such as bipolar or depression and that might be reflected in this measure,” Wemmie says. “And perhaps most important, at the end of the day; could this signal be abnormal or perturbed in human psychiatric disease? And if so, it might be a target for manipulation and treatment?”

Provided by University of Iowa

Source: medicalxpress.com

May 18, 2012

It has been known for years that eating too many foods containing “bad” fats, such as saturated fats or trans fats, isn’t healthy for your heart. However, according to new research from Brigham and Women’s Hospital (BWH), one “bad” fat—saturated fat—was found to be associated with worse overall cognitive function and memory in women over time. By contrast, a “good” fat—mono-unsaturated fat was associated with better overall cognitive function and memory.

This study is published online by Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society, on May 18, 2012.

The research team analyzed data from the Women’s Health Study—originally a cohort of nearly 40,000 women, 45 years and older. The researchers focused on data from a subset of 6,000 women, all over the age of 65. The women participated in three cognitive function tests, which were spaced out every two years for an average testing span of four years. These women filled out very detailed food frequency surveys at the start of the Women’s Health Study, prior to the cognitive testing.

"When looking at changes in cognitive function, what we found is that the total amount of fat intake did not really matter, but the type of fat did,” explained Olivia Okereke, MD, MS, BWH Department of Psychiatry.

Women who consumed the highest amounts of saturated fat, which can come from animal fats such as red meat and butter, compared to those who consumed the lowest amounts, had worse overall cognition and memory over the four years of testing. Women who ate the most of the monounsaturated fats, which can be found in olive oil, had better patterns of cognitive scores over time.

"Our findings have significant public health implications," said Okereke. "Substituting in the good fat in place of the bad fat is a fairly simple dietary modification that could help prevent decline in memory."

Okereke notes that strategies to prevent cognitive decline in older people are particularly important. Even subtle declines in cognitive functioning can lead to higher risk of developing more serious problems, like dementia and Alzheimer disease.

Provided by Brigham and Women’s Hospital

Source: medicalxpress.com

May 17, 2012

Around 1 in 50 people in the general population and 1 in 6 of those aged over 40 years experience neuropathy (damage to the nerves of the peripheral nervous system), which can cause numbness, tingling, pain, or weakness. The most common cause of neuropathy is diabetes, and up to half of diabetes patients can be affected. Currently, among the only treatments for neuropathy are glucose control (which often only delays it) and pain management. Yet less than half of patients are treated for pain, despite the availability of many effective therapies . Growing evidence suggests that various metabolic risk factors, including prediabetes, could be linked with neuropathy and thus be targets for new disease-modifying drugs. The issues are discussed in a Review in the June issue of The Lancet Neurology, by Dr Brian C Callaghan and colleagues, all of the University of Michigan, Ann Arbor, MI, USA.

Diabetes can cause various patterns of so-called diabetic neuropathy, but the most common presentation is a distal symmetrical polyneuropathy (DSP), in which symptoms begin in the feet and spread up the limbs. Patients experience decreased quality of life, both physically and mentally. DSP can cause balance problems, which may lead to falls. Neuropathy is one of three main risk factors for falls in patients with diabetes, along with retinopathy and vestibular dysfunction. Patients with diabetic DSP are two to three times more likely to fall than those with diabetes and no neuropathy. Additionally, patients with severe DSP are at risk of ulcerations and lower-extremity amputations, with 15% developing an ulcer during the course of their disease. Diabetes is the leading cause of lower-extremity amputations, roughly 80 000 of which are undertaken in the USA every year in patients with the disorder. Indeed, patients with diabetes are 15 times more likely than people without diabetes to have this life-changing complication.

Overall, costs associated with diabetic neuropathy in the USA are estimated to be between 4•6 and 13•7 billion dollars, with most of the expense attributed to those with type 2 diabetes. Therefore, neuropathy is associated with a quarter of the total costs of diabetes care in the USA.

Since the data linking prediabetes (a condition with higher than normal blood sugar levels, but not yet high enough for a diabetes diagnosis) with neuropathy are conflicting, a comprehensive study is needed to establish whether or not it is one of the metabolic drivers that underlie the onset and progression of neuropathy. The answer has direct implications for potential therapies for many patients with neuropathy. Currently one third of adult Americans meet criteria for prediabetes, but less than 5% of these people have received a formal diagnosis of prediabetes from their health-care providers and only a small percentage are being treated .Establishing a causal relation between prediabetes and neuropathy would change the clinical management of a substantial number of patients.

Research suggests that various metabolic factors (components of ‘metabolic syndrome’) other than blood glucose control—such as levels of LDL (bad) cholesterol and high blood pressure—might have a role in the development of neuropathy. The authors say that there are promising lines of investigation that could lead to improved prevention and treatment of the disorder. The magnitude of the effect of glucose control on neuropathy is much smaller in patients with type 2 diabetes than in those with type 1 diabetes. In view of this small effect size and the fact that many patients with type 2 diabetes continue to develop neuropathy despite adequate glucose control, discovery of modifiable risk factors for neuropathy is essential. Callaghan and colleagues are currently conducting such a study.

The authors conclude: “Components of the metabolic syndrome, including prediabetes, are potential risk factors for neuropathy, and studies are needed to establish whether they are causally related to neuropathy. These lines of enquiry will have direct implications for the development of new treatments for diabetic neuropathy.”

Provided by Lancet

Source: medicalxpress.com

ScienceDaily (May 17, 2012) — Training the brain to reduce pain could be a promising approach for treating phantom limb pain and complex regional pain syndrome, according to an internationally known neuroscience researcher speaking May 17 at the American Pain Society’s Annual Scientific Meeting.

G. Lorimer Moseley, PhD, professor of clinical neurosciences at University of South Australia and Neuroscience Research Australia, and head of the Body in Mind research team, told the plenary session audience that the brain stores maps of the body that are integrated with neurological systems that survey, regulate, and protect the integrity of the body physically and psychologically. These cortical maps govern movement, sensation and perception, and there is growing evidence, according to Moseley, showing that disruptions of brain maps occur in people with chronic pain. The best evidence is from those with phantom limb pain and complex regional pain syndrome, but there is also data from chronic back pain.

Moseley’s research is focused on the role of the brain and mind in chronic and complex pain disorders. Through collaborations with clinicians, scientists and patients, the Body in Mind team is exploring how the brain and its representation of the body change when pain persists, how the mind influences physiological regulation of the body, how the changes in the brain and mind can be normalized with treatment.

"We’re learning that chronic pain is associated with disruption of brain maps of the body and of the space around the body. When the brain determines the location of a sensory event, it integrates the location of the event in the body with a map of space. Disruption of these processes might be contributing to the problem," said Moseley. He added that it is possible for the body to be unharmed but the brain will respond by causing pain because it misinterpreted a benign stimulus as an attack. "We want to gradually train the brain to stop trying to protect body tissue that doesn’t need protecting."

Moseley said the brain can “rewire” itself, a process called neuroplasticity. Often painful stimuli triggered by a broken bone or other trauma cause the brain to rewire and, as a result, the damage signal is never switched off after the initial body trauma is resolved. The result: Chronic pain. So if the brain is capable of changing to cause persistent pain, can it be changed back to normal to alleviate pain?

"The brain is the focal point of the pain experience, but the plasticity phenomena can be harnessed to help alleviate pain," Moseley said.

He further stated that disrupted cortical body maps may contribute to the development or maintenance of chronic pain and, therefore, could be viable targets for treatment. One treatment approach involves targeting motor systems through a process Moseley calls graded motor imagery. It relies on using visual images to help the brain change its perceptions of the body after prolonged pain stimuli. “For someone with phantom limb pain, the brain’s body map still includes the severed arm or leg, and without any real stimuli from the region, it continues to produce pain,” Moseley explained.

He reported that studies with graded motor imagery have shown encouraging results in complex regional pain syndrome and in phantom limb pain.

"Our work shows that the complex neural connections in the brain not only are associated with chronic pain, they can be reconnected or manipulated through therapy that alters brain perceptions and produce pain relief," said Moseley.

Source: Science Daily

ScienceDaily (May 17, 2012) — Mental distractions make pain easier to take, and those pain-relieving effects aren’t just in your head, according to a report published online on May 17 in Current Biology, a Cell Press publication.

The findings based on high-resolution spinal fMRI (functional magnetic resonance imaging) as people experienced painful levels of heat show that mental distractions actually inhibit the response to incoming pain signals at the earliest stage of central pain processing.

"The results demonstrate that this phenomenon is not just a psychological phenomenon, but an active neuronal mechanism reducing the amount of pain signals ascending from the spinal cord to higher-order brain regions," said Christian Sprenger of the University Medical Center Hamburg-Eppendorf.

Those effects involve endogenous opioids, which are naturally produced by the brain and play a key role in the relief of pain, the new evidence shows.

The research group asked participants to complete either a hard or an easy memory task, both requiring them to remember letters, while they simultaneously applied a painful level of heat to their arms.

When study participants were more distracted by the harder of the two memory tasks, they did indeed perceive less pain. What’s more, their less painful experience was reflected by lower activity in the spinal cord as observed by fMRI scans. (fMRI is often used to measure changes in brain activity, Sprenger explained, and recent advances have made it possible to extend this tool for use in the spinal cord.)

Sprenger and colleagues then repeated the study again, this time giving participants either a drug called naloxone, which blocks the effects of opioids, or a simple saline infusion. The pain-relieving effects of distraction dropped by 40 percent during the application of the opioid antagonist compared to saline, evidence that endogenous opioids play an essential role.

The findings show just how deeply mental processes can go in altering the experience of pain, and that may have clinical importance.

"Our findings strengthen the role of cognitive-behavioral therapeutic approaches in the treatment of pain diseases, as it could be extrapolated that these approaches might also have the potential to alter the underlying neurobiological mechanisms as early as in the spinal cord," the researchers say.

Source: Science Daily

May 17, 2012

Fool me once, shame on you. Fool me twice, shame on my parahippocampal gyrus.

Read Montague, Ph.D., and colleagues at the Virginia Tech Carilion Research Institute discovered two distinct sites for suspicion in the brain: the amygdala, which correlates strongly with a baseline distrustfulness, and the parahippocampal gyrus, which acts like a cerebral lie detector. Credit: Virginia Tech

Scientists at the Virginia Tech Carilion Research Institute have found that suspicion resides in two distinct regions of the brain: the amygdala, which plays a central role in processing fear and emotional memories, and the parahippocampal gyrus, which is associated with declarative memory and the recognition of scenes.

"We wondered how individuals assess the credibility of other people in simple social interactions," said Read Montague, director of the Human Neuroimaging Laboratory and the Computational Psychiatry Unit at the Virginia Tech Carilion Research Institute, who led the study. "We found a strong correlation between the amygdala and a baseline level of distrust, which may be based on a person’s beliefs about the trustworthiness of other people in general, his or her emotional state, and the situation at hand. What surprised us, though, is that when other people’s behavior aroused suspicion, the parahippocampal gyrus lit up, acting like an inborn lie detector.”

The scientists used functional magnetic resonance imaging, or fMRI, to study the neural basis of suspicion. Seventy-six pairs of players, each with a buyer and a seller, competed in 60 rounds of a simple bargaining game while having their brains scanned. At the beginning of each round, the buyer would learn the value of a hypothetical widget and suggest a price to the seller. The seller would then set the price. If the seller’s price fell below the widget’s given value, the trade would go through, with the seller receiving the selling price and the buyer receiving any difference between the selling price and the actual value. If the seller’s price exceeded the value, though, the trade would not execute, and neither party would receive cash.

The authors found, as detailed in a previous paper, that buyers fell into three strategic categories: 42 percent were incrementalists, who were relatively honest about the widget’s value; 37 percent were conservatives, who adopted the strategy of withholding information; and 21 percent were strategists, who were actively deceptive, mimicking incrementalist behavior by sending high suggestions during low-value trials and then reaping greater benefits by sending low suggestions during high-value trials.

The sellers had a monetary incentive to read the buyers’ strategic profiles correctly, yet they received no feedback about the accuracy of the information they were receiving, so they could not confirm any suspicions about patterns of behavior. Without feedback, the sellers were forced to decide whether they should trust the buyers based on the pricing suggestions alone. “The more uncertain a seller was about a buyer’s credibility,” Montague said, “the more active his or her parahippocampal gyrus became.”

The authors believe a person’s baseline suspicion may have important consequences for his or her financial success. “People with a high baseline suspicion were often interacting with fairly trustworthy buyers, so in ignoring the information those buyers provided, they were giving up potential profits,” said Meghana Bhatt, the first author on the research paper. “The ability to recognize credible information in a competitive environment can be just as important as detecting untrustworthy behavior.”

The findings may also have implications for such psychiatric conditions as paranoia and anxiety disorders, said Montague. “The fact that increased amygdala activation corresponds to an inability to detect trustworthy behavior may provide insight into the social interactions of people with anxiety disorders, who often have increased activity in this area of the brain,” he said.

Provided by Virginia Tech

Source: medicalxpress.com

ScienceDaily (May 16, 2012) — A well-known genetic risk factor for Alzheimer’s disease triggers a cascade of signaling that ultimately results in leaky blood vessels in the brain, allowing toxic substances to pour into brain tissue in large amounts, scientists report May 16 in the journal Nature.

The left photo shows destructive proteins (green) lining blood vessels in living brain tissue of mice with the human ApoE4 gene; after the drug cyclosporine A is added, the harmful proteins are nearly gone (right). (Credit: Image courtesy of University of Rochester Medical Center)

The results come from a team of scientists investigating why a gene called ApoE4 makes people more prone to developing Alzheimer’s. People who carry two copies of the gene have roughly eight to 10 times the risk of getting Alzheimer’s disease than people who do not.

A team of scientists from the University of Rochester, the University of Southern California, and other institutions found that ApoE4 works through cyclophilin A, a well-known bad actor in the cardiovascular system, causing inflammation in atherosclerosis and other conditions. The team found that cyclophilin A opens the gates to the brain assault seen in Alzheimer’s.

"We are beginning to understand much more about how ApoE4 may be contributing to Alzheimer’s disease," said Robert Bell, Ph.D., the post-doctoral associate at Rochester who is first author of the paper. "In the presence of ApoE4, increased cyclophilin A causes a breakdown of the cells lining the blood vessels in Alzheimer’s disease in the same way it does in cardiovascular disease or abdominal aneurysm. This establishes a new vascular target to fight Alzheimer’s disease."

The team found that ApoE4 makes it more likely that cyclophilin A will accumulate in large amounts in cells that help maintain the blood-brain barrier, a network of tightly bound cells that line the insides of blood vessels in the brain and carefully regulates what substances are allowed to enter and exit brain tissue.

ApoE4 creates a cascade of molecular signaling that weakens the barrier, causing blood vessels to become leaky. This makes it more likely that toxic substances will leak from the vessels into the brain, damaging cells like neurons and reducing blood flow dramatically by choking off blood vessels.

Doctors have long known that the changes in the brain seen in Alzheimer’s patients — the death of crucial brain cells called neurons — begins happening years or even decades before symptoms appear. The steps described in Nature discuss events much earlier in the disease process.

The idea that vascular problems are at the heart of Alzheimer’s disease is one championed for more than two decades by Berislav Zlokovic, M.D., Ph.D., the leader of the team and a neuroscientist formerly with the University of Rochester Medical Center and now at USC. For 20 years, Zlokovic has investigated how blood flow in the brain is affected in people with the disease, and how the blood-brain barrier allows nutrients to pass into the brain, and harmful substances to exit the brain.

At Rochester, Zlokovic struck up a collaboration with Bradford Berk, M.D., Ph.D.,a cardiologist and CEO of the Medical Center. For more than two decades Berk has studied cyclophilin A, showing how it promotes destructive forces in blood vessels and how it’s central to the forces that contribute to cardiovascular diseases like atherosclerosis and heart attack.

"As a cardiologist, I’ve been interested in understanding the role of cyclophilin A in patients who suffer from cardiovascular illness," said Berk, a professor at the Aab Cardiovascular Research Institute. "Now our collaboration in Rochester has resulted in the discovery that it also has an important role in Alzheimer’s disease. The finding reinforces the basic research enterprise — you never know when knowledge gained in one area will turn out to be crucial in another."

In studies of mice, the team found that mice carrying the ApoE4 gene had five times as much cyclophilin A compared to other mice in cells known as pericytes, which are crucial to maintaining the integrity of the blood-brain barrier. Blood vessels died, blood did not flow as completely through the brain as it did in other mice, and harmful substances like thrombin, fibrin, and hemosiderin, entered the brain tissue.

When the team blocked the action of cyclophilin A, either by knocking out its gene or by using the drug cyclosporine A to inhibit it, the damage in the mice was reversed. Blood flow resumed to normal, and unhealthy leakage of toxic substances from the blood vessels into the brain was slashed by 80 percent.

The team outlined the chain of events involved. Briefly:

• When ApoE4 is present, cyclophilin A is much more plentiful;
• Cyclophilin A causes an increase in a the inflammatory molecule NF Kappa B;
• NF Kappa B boosts levels of certain types of molecules known as MMPs or matrix metalloproteinases that are known to damage blood vessels, reducing blood flow.

Altogether, the activity results in a dramatic boost in the amount of toxic substances in brain tissue. And when the cascade is interrupted at any of several points — when ApoE4 is not present, when cyclophilin A is blocked or shut off, or when NF Kappa B or the MMPs are inhibited — the blood-brain barrier is restored, blood flow returns to normal, and toxic substances do not leak into brain tissue.

For many years, researchers studying Alzheimer’s disease have been focused largely on amyloid beta, a protein structure that accumulates in the brains of patients with Alzheimer’s disease. The latest works points up the importance of other approaches, said Zlokovic, an adjunct professor at Rochester. At USC, Zlokovic is also deputy director of the Zilkha Neurogenetic Institute, director of the Center for Neurodegeneration and Regeneration, and professor and chair of the Department of Physiology and Biophysics.

"Our study has shown major neuronal injury resulting from vascular defects that are not related to amyloid beta," said Zlokovic. "This damage results from a breakdown of the blood-brain barrier and a reduction in blood flow.

"Amyloid beta definitely has an important role in Alzheimer’s disease," added Zlokovic. "But it’s very important to investigate other leads, perhaps where amyloid beta isn’t as centrally involved."

Source: Science Daily