Neuroscience

Month

May 2012

Evil Eyebrows and Pointy Chin of a Cartoon Villain Make Our ‘threat’ Instinct Kick in

ScienceDaily (May 29, 2012) — New research from the University of Warwick could explain why the evil eyebrows and pointy chin of a cartoon villain make our ‘threat’ instinct kick in.

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Triangular-shaped face. Psychologists have found that a downward pointing triangle can be perceived to carry a threat. (Credit: © Viktor Kuryan / Fotolia)

Psychologists have found that a downward pointing triangle can be perceived to carry threat just like a negative face in a crowd.

In a paper published in Emotion, a journal of the American Psychological Association, Dr Derrick Watson and Dr Elisabeth Blagrove have carried out a series of experiments with volunteers to find out if simple geometric shapes can convey positive or negative emotions.

Previous research by these scientists showed that people could pick out a negative face in a crowd more quickly than a positive or neutral face and also that it was difficult to ignore faces in general. The researchers carried out a series of experiments asking volunteers to respond to computer-generated images. They were shown positive, negative and neutral faces, and triangles facing upwards, downwards, inward and outward. This latest study shows that downward triangles are detected just as quickly as a negative face.

Dr Watson said: “We know from previous studies that simple geometric shapes are effective at capturing or guiding attention, particularly if these shapes carry the features present within negative or positive faces.”

"Our study shows that downward pointing triangles in particular convey negative emotions and we can pick up on them quickly and perceive them as a threat."

Dr Blagrove added: “If we look at cartoon characters, the classic baddie will often be drawn with the evil eyebrows that come to a downward point in the middle. This could go some way to explain why we associate the downward pointing triangle with negative faces. These shapes correspond with our own facial features and we are unconsciously making that link.”

Source: Science Daily

May 29, 201222 notes
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Researchers restore neuron function to brains damaged by Huntington's disease

May 29, 2012

Researchers from South Korea, Sweden, and the United States have collaborated on a project to restore neuron function to parts of the brain damaged by Huntington’s disease (HD) by successfully transplanting HD-induced pluripotent stem cells into animal models.

Induced pluripotent stem cells (iPSCs) can be genetically engineered from human somatic cells such as skin, and can be used to model numerous human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. In the latter case, the patient provides a sample of his or her own skin to the laboratory.

In the current study, experimental animals with damage to a deep brain structure called the striatum (an experimental model of HD) exhibited significant behavioral recovery after receiving transplanted iPS cells. The researchers hope that this approach eventually could be tested in patients for the treatment of HD.

"The unique features of the iPSC approach means that the transplanted cells will be genetically identical to the patient and therefore no medications that dampen the immune system to prevent graft rejection will be needed,” said Jihwan Song, D.Phil. Associate Professor and Director of Laboratory of Developmental & Stem Cell Biology at CHA Stem Cell Institute, CHA University, Seoul, South Korea and co-author of the study.

The study, published online this week in Stem Cells, found that transplanted iPSCs initially formed neurons producing GABA, the chief inhibitory neurotransmitter in the mammalian central nervous system, which plays a critical role in regulating neuronal excitability and acts at inhibitory synapses in the brain. GABAergic neurons, located in the striatum, are the cell type most susceptible to degeneration in HD.

Another key point in the study involves the new disease models for HD presented by this method, allowing researchers to study the underlying disease process in detail. Being able to control disease development from such an early stage, using iPS cells, may provide important clues about the very start of disease development in HD. An animal model that closely imitates the real conditions of HD also opens up new and improved opportunities for drug screening.

"Having created a model that mimics HD progression from the initial stages of the disease provides us with a unique experimental platform to study Huntington’s disease pathology" said Patrik Brundin, M.D., Ph.D., Director of the Center for Neurodegenerative Science at Van Andel Research Institute (VARI), Head of the Neuronal Survival Unit at Lund University, Sweden, and co-author of the study.

Huntington’s disease (HD) is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems. It typically becomes noticeable in mid-adult life, with symptoms beginning between 35 and 44 years of age. Life expectancy following onset of visual symptoms is about 20 years. The worldwide prevalence of HD is 5-10 cases per 100,000 persons. Key to the disease process is the formation of specific protein aggregates (essentially abnormal clumps) inside some neurons.

Provided by Van Andel Research Institute

Source: medicalxpress.com

May 29, 201213 notes
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Physical sciences illuminate neurodegenerative diseases

May 29, 2012

What do physicists, chemists, mathematicians and biologists have in common? One of the answers at Cambridge is a shared interest in unravelling the processes behind neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Motor Neurone Disease.

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Dementia. Credit: ©freshidea Fotolia

As more people live to a ripe old age, an increasing number of us will develop neurodegenerative diseases such as Alzheimer’s. Despite the escalating economic costs and human misery associated with these diseases, we still know relatively little about how they develop or how best to tackle them.

Alzheimer’s is the most common neurodegenerative disease. “It’s an enormous problem and we’re not doing very well at the moment in slowing the disease or treating its symptoms effectively,” says Professor Peter St George-Hyslop.

Neurodegenerative diseases such as Alzheimer’s are difficult to study for several reasons. “One is that it’s not easy to get pieces of living brain,” he explains. “It’s also a disease where patients become unable to speak for themselves, so unlike people with AIDS or breast cancer they aren’t demonstrating outside the houses of Parliament demanding funding.”

Although charities and campaigners are doing sterling work raising the profile of Alzheimer’s, until recently attitudes to neurodegenerative disease had much in common with the way we viewed cancer 50 years ago.

“We are, for Alzheimer’s, like where we were for cancer in the 1950s, when people didn’t like to talk about it, were frightened or ashamed of it. And therapeutically we are in the same place; although we are beginning to learn about these diseases we don’t yet have much in the way of effective therapies,” Professor St George-Hyslop says.

One crucial discovery is that proteins misfolding in the brain form clumps or aggregates and these play a major role in causing neurodegenerative diseases. When these proteins misfold they take on certain characteristics that become noxious to cells, but what we need to know now is why these proteins misfold, which aggregates do the damage, and how that damage occurs. Which is where physics, chemistry and mathematics enter the biological picture.

Professor St George-Hyslop leads a group of experts from disparate disciplines, each bringing different tools and different ways of working to the study of neurodegenerative diseases.

What began in late 2008 as a series of meetings has now developed into a 12-strong group funded by a £5.3 million Strategic Award from the Wellcome Trust and Medical Research Council. “It’s a very interesting group of people who came together because they wanted to come together. They each knew they had something to contribute but also that they needed something else – some skills, some knowledge, some point of view – from another member of the group,” he says.

“The biologists among us knew there were techniques that the physicists and chemists had that could help us. They in turn knew we had some biological knowledge that would help them apply, in a sensible way, their very good and insightful physical and chemical tools.”

Among the group is Professor David Klenerman from the Department of Chemistry. One of the inventors of rapid, high-throughput DNA sequencing, he is now applying this knowledge to protein misfolding. From the same department comes Professor Michele Vendruscolo, a theoretical physicist working on the mechanics and thermodynamics of protein misfolding. Professor Chris Dobson, who is also from the Department of Chemistry works on protein misfolding in neurodegenerative diseases, while from the Department of Chemical Engineering and Biotechnology Dr. Clemens Kaminski brings modern laser spectroscopy tools that allow you to watch these proteins misfold inside living cells in real time.

The group has applied these physical tools to study nematode worms in which a mutation produces the same protein misfolding that causes disease in humans. “That ability to see these things as they happen in a living model give us a much greater understanding compared with previous techniques, which essentially involved grinding up biological samples and examining them after these processes had occurred,” Professor St George-Hyslop explains.

“What’s important is the marriage of the physical tool with the biological question,” he says. And he hopes that by revealing where these misfolded proteins act, these new tools could help researchers develop ways of blocking the damage they cause in both Alzheimer’s and other neurodegenerative diseases.

“The primary goal is to understand what the beginning and the middle parts of the process are. We know what the end is – the cell dies and you get a disease – but if you know why the cells get sick and what the mechanisms are then you have a better chance of preventing or halting it,” says Professor St George- Hyslop. “Our goal is to provide that fundamental knowledge of cause and mechanism. Hopefully from that will come some idea of which parts of those pathways you can monitor as a diagnostic and which parts you can block or change as a treatment.”

More recently, the group has been enlarged by a £4.5 million grant from the National Institute of Health Research to support an extension of the Cambridge Biomedical Research Centre via the creation of a Biomedical Research Unit in Dementia for translational research. This has allowed the inclusion of researchers in immunology and in brain imaging from the Department of Medicine and the Wolfson Brain Imaging Centre.

Provided by University of Cambridge

Source: medicalxpress.com

May 29, 201217 notes
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New Effective Treatment for Tinnitus?

ScienceDaily (May 28, 2012) — A team of researchers from Maastricht, Leuven, Bristol and Cambridge demonstrated the effectiveness of a new tinnitus treatment approach in the journal The Lancet. Tinnitus is the perception of a noxious disabling internal sound without an external source. Roughly fifteen percent of the population suffers from this disorder in varying degrees along with the associated concentration problems, sleep disturbances, anxiety, depression and extreme fatigue.

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Tinnitus is the perception of a noxious disabling internal sound without an external source. (Credit: © BildPix.de / Fotolia)

Sometimes this disorder is so disruptive it seriously impairs their daily functioning and, unfortunately, there is no cure.

The research conducted by Rilana Cima and her colleagues, however, indicates that cognitive behavioural therapy can help improve the daily functioning of tinnitus patients.

The study, conducted at Adelante Audiology & Communication, followed 492 adult tinnitus patients for a period of twelve months. The effectiveness of an innovative tinnitus treatment protocol was compared to the standard treatment methods offered throughout the Netherlands. The ground-breaking, stepped treatment plan consists of cognitive behavioural therapy and combines elements from psychology and audiology. The therapy aims at reducing the negative thoughts and feelings surrounding tinnitus, symptoms through exposure techniques, movement and relaxation exercises, and mindfulness-based elements.

This is supplemented with elements from the so-called tinnitus retraining therapy (TRT), which examines the problems on a sound perception level. The treatment is offered by a multidisciplinary team of audiologists, psychologists, speech and movement therapists, physical therapists and social workers. The project was funded by the Netherlands Organisation for Health Research and Development (ZonMW), and directed by Johan Vlaeyen, professor behavioural medicine at KU Leuven and Maastricht University.

The results offer compelling evidence to support the effectiveness of this innovative and specialised tinnitus therapy over more traditional forms of treatment. The overall health of the tinnitus patient improves and the severity of their symptoms and perceived impairment decreases after therapy. Moreover, the new treatment is far more effective in reducing negative mood, dysfunctional beliefs and tinnitus-related fear). The specialised tinnitus treatment is effective for both milder and more severe forms of the disorder. The researchers are therefore advocating a widespread implementation of this new treatment protocol.

Source: Science Daily

May 29, 201211 notes
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Brain activity revealed when watching a feature film

May 29, 2012

Human brain functions have been studied in the past using relatively simple stimuli, such as pictures of faces and isolated sounds or words. Researchers from Aalto University Department of Biomedical Engineering and Computational Science have now taken a highly different approach: they have studied brain functions in lifelike circumstances.

In their new study, published in PLoS ONE, the group examined how the brain processes the film The Match Factory Girl by Aki Kaurismäki.

Films have been previously used to study brain activity, but the brain activity patterns have been integrated over the whole duration of the film, and thus time information is lost. This is like compressing a whole film into just one frame. In some studies, scientists have looked at dynamic brain activity, but focusing on a single brain region at a time.

The Aalto University scientists on the other hand study the full brain activity patterns with the time resolution allowed by functional magnetic resonance imaging. This way it possible to find out which events in the film cause changes in the brain activity, and which brain areas are activated at each moment.

This analysis revealed, for example, that parts of a brain network that usually respond to speech also become activated during other types of communication, such as writing. Some other areas of the network were very selective to speech.

The researchers combined two complementary approaches to disclose the brain activity. One based on dependencies of activation in different parts of the brain, and the other begins from detailed analysis of the visual and acoustic features of which the film is composed.

The results revealed brain networks in which activity follows remarkably well the complex model of the auditory and visual features of the film. For example, brain activity in the auditory cortex followed the soundtrack extremely well over the whole length of the film, and viewing the motions of characters’ hands reliably activated widespread areas of the brain.

"Our study opens new ways for studying human brain functions. Many brain areas that process sensory information reveal their principles only if sufficiently complex and naturalistic stimuli are used,” explain researcher Juha Lahnakoski and Professor Mikko Sams from Aalto University Department of Biomedical Engineering and Computational Science.

The new methods also make it possible to study brain mechanisms’ underlying behaviour in normal everyday conditions – by simulating them in films.

Provided by Aalto University

Source: medicalxpress.com

May 29, 201211 notes
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People Smile When They Are Frustrated, and the Computer Knows the Difference

ScienceDaily (May 28, 2012) — Do you smile when you’re frustrated? Most people think they don’t — but they actually do, a new study from MIT has found. What’s more, it turns out that computers programmed with the latest information from this research do a better job of differentiating smiles of delight and frustration than human observers do.

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Can you tell which of these smiles is showing happiness? Or which one is the result of frustration? A computer system developed at MIT can. The answer: The smile on the right is the sign of frustration. (Credit: Images courtesy of Hoque et al.)

The research could pave the way for computers that better assess the emotional states of their users and respond accordingly. It could also help train those who have difficulty interpreting expressions, such as people with autism, to more accurately gauge the expressions they see.

"The goal is to help people with face-to-face communication," says Ehsan Hoque, a graduate student in the Affective Computing Group of MIT’s Media Lab who is lead author of a paper just published in the IEEE Transactions on Affective Computing. Hoque’s co-authors are Rosalind Picard, a professor of media arts and sciences, and Media Lab graduate student Daniel McDuff.

In experiments conducted at the Media Lab, people were first asked to act out expressions of delight or frustration, as webcams recorded their expressions. Then, they were either asked to fill out an online form designed to cause frustration or invited to watch a video designed to elicit a delighted response — also while being recorded.

When asked to feign frustration, Hoque says, 90 percent of subjects did not smile. But when presented with a task that caused genuine frustration — filling out a detailed online form, only to then find the information deleted after pressing the “submit” button — 90 percent of them did smile, he says. Still images showed little difference between these frustrated smiles and the delighted smiles elicited by a video of a cute baby, but video analysis showed that the progression of the two kinds of smiles was quite different: Often, the happy smiles built up gradually, while frustrated smiles appeared quickly but faded fast.

In such experiments, researchers usually rely on acted expressions of emotion, Hoque says, which may provide misleading results. “The acted data was much easier to classify accurately” than the real responses, he says. But when trying to interpret images of real responses, people performed no better than chance, assessing these correctly only about 50 percent of the time.

Understanding the subtleties that reveal underlying emotions is a major goal of this research, Hoque says. “People with autism are taught that a smile means someone is happy,” he says, but research shows that it’s not that simple.

While people may not know exactly what cues they are responding to, timing does have a lot to do with how people interpret expressions, he says, For example, former British prime minister Gordon Brown was widely seen as having a phony smile, largely because of the unnatural timing of his grin, Hoque says. Similarly, a campaign commercial for former presidential candidate Herman Cain featured a smile that developed so slowly — it took nine seconds to appear — that it was widely parodied, including a spoof by comedian Stephen Colbert. “Getting the timing right is very crucial if you want to be perceived as sincere and genuine with your smiles,” Hoque says.

Jeffrey Cohn, a professor of psychology at the University of Pittsburgh who was not involved in this research, says this work “breaks new ground with its focus on frustration, a fundamental human experience. While pain researchers have identified smiling in the context of expressions of pain, the MIT group may be the first to implicate smiles in expressions of negative emotion.”

Cohn adds, “This is very exciting work in computational behavioral science that integrates psychology, computer vision, speech processing and machine learning to generate new knowledge … with clinical implications.” He says this “is an important reminder that not all smiles are positive. There has been a tendency to ‘read’ enjoyment whenever smiles are found. For human-computer interaction, among other fields and applications, a more nuanced view is needed.”

In addition to providing training for people who have difficulty with expressions, the findings may be of interest to marketers, Hoque says. “Just because a customer is smiling, that doesn’t necessarily mean they’re satisfied,” he says. And knowing the difference could be important in gauging how best to respond to the customer, he says: “The underlying meaning behind the smile is crucial.”

The analysis could also be useful in creating computers that respond in ways appropriate to the moods of their users. One goal of the research of Affective Computing Group is to “make a computer that’s more intelligent and respectful,” Hoque says.

Source: Science Daily

May 28, 201232 notes
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Working with solvents tied to cognitive problems for less-educated people

May 28, 2012

Exposure to solvents at work may be associated with reduced thinking skills later in life for those who have less than a high school education, according to a study published in the May 29, 2012, print issue of Neurology, the medical journal of the American Academy of Neurology.

The thinking skills of people with more education were not affected, even if they had the same amount of exposure to solvents.

"People with more education may have a greater cognitive reserve that acts like a buffer allowing the brain to maintain its ability to function in spite of damage," said study author Lisa F. Berkman, PhD, of Harvard University in Cambridge, Mass. "This may be because education helps build up a dense network of connections among brain cells.”

The study involved 4,134 people who worked at the French national gas and electric company. The majority of the people worked at the company for their entire career. Their lifetime exposure to four types of solvents—chlorinated solvents, petroleum solvents, benzene and non-benzene aromatic solvents—was assessed. The participants took a test of thinking skills when they were an average of 59 years old and 91 percent were retired.

A total of 58 percent of the participants had less than a high school education. Of those, 32 percent had cognitive impairment, or problems with thinking skills, compared to 16 percent of those with more education. Among the less-educated, those who were highly exposed to chlorinated and petroleum solvents were 14 percent more likely to have cognitive problems than those with no exposure. People highly exposed to benzene were 24 percent more likely to have cognitive problems, and those highly exposed to non-benzene aromatic solvents were 36 percent more likely to have cognitive problems.

"These findings suggest that efforts to improve quality and quantity of education early in life could help protect people’s cognitive abilities later in life," Berkman said, who worked alongside study author Erika Sabbath, ScD. "Investment in education could serve as a broad shield against both known and unknown exposures across the lifetime. This is especially important given that some evidence shows that federal levels of permissible exposure for some solvents may be insufficient to protect workers against the health consequences of exposure.”

Provided by American Academy of Neurology

Source: medicalxpress.com

May 28, 201211 notes
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Scientists uncover deja vu mystery

May 28, 2012

In a groundbreaking study, researchers from the Czech Republic and the United Kingdom have discovered a link between the déjà vu phenomenon and structures in the human brain, effectively confirming the neurological origin of this phenomenon. Despite past studies investigating this phenomenon in healthy individuals, no concrete evidence had ever emerged … until now. The study is presented in the journal Cortex.

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Led by the Central European Institute of Technology, Masaryk University (CEITEC MU) and Masaryk University’s Faculty of Medicine in the Czech Republic, researchers discovered that specific brain structures have a direct impact on the déjà vu experience. The findings of their study showed that the size of these structures are considerably smaller in the brains of the people experiencing déjà vu, compared with individuals who had no personal experience with déjà vu.

The team from CEITEC MU, along with colleagues from other Brno research institutions as well as the University of Exeter in the United Kingdom succeeded in providing huge insight into this phenomenon that has perplexed many over the years.

The team observed how small structures in the brain’s medial temporal lobes, in which memory and recollections originate, were considerably smaller in individuals with the occurrence of déjà vu than in individuals who have not experienced déjà vu. Their findings also showed that the more often the examined individuals experience déjà vu, the smaller the brain structures are.

"One hundred and thirteen healthy subjects underwent a structural examination of their brain by means of magnetic resonance and subsequently by using a new sensitive method for an automatic analysis of brain morphology (source-based morphometry) [and] the size of individual brain regions was compared among the individuals who have never experienced déjà vu and those who have experienced it," said lead author Milan Brázdil from CEITEC.

"Except for the presence of the examined phenomenon, both groups of individuals were fully comparable. When we stimulate the hippocampus, we are able to induce déjà vu in neurological patients. By finding the structural differences in hippocampus in healthy individuals who do and do not experience déjà vu, we have unambiguously proved that déjà vu is directly linked to the function of these brain structures. We think that it is probably a certain small “error in the system” caused by higher excitability of hippocampuses. It is the consequence of changes in the most sensitive brain regions which probably occurred in the course of the development of the neural system.”

Experts say déjà vu, while fascinating, is not an uncommon experience. Between 60% and 80% of healthy individuals have reported occasional occurrences of déjà vu.

Provided by CORDIS

Source: medicalxpress.com

May 28, 2012111 notes
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Understanding how our brain perceives space

May 28, 2012

European scientists looked into the cellular properties of neurons responsible for space coordination. Insight into the neuronal network of the entorhinal cortex will help understand what determines space and movement perception, and also how it is linked to brain-related disorders.

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The ability to find one’s way is performed in a special site of the mammalian cortex known as the entorhinal cortex. Information regarding place, direction and destination is processed in specialised neurons called grid cells. These cells present with specific spatially firing fields that repeat at regular intervals and have been found to scale up progressively along the dorsal-ventral axis.

Further dissection of this neural map was the subject of the EU-funded project ‘Spatial representation in the entorhinal neural circuit’ (Entorhinal Circuits). More specifically, scientists hypothesised that the topographic expansion of grid cells paralleled changes in cellular properties and particularly in the current (Ih) which went through hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels.

Using transgenic animals with forebrain-specific knockout of the transmembrane protein HCN1, researchers found that HCN1 modulated grid cell properties, especially the size and spacing of the grid fields. This clearly indicated that HCN1 was crucial for the spatial representation in the entorhinal circuit. It also implies that during self-motion–based navigation, the current that goes through HCN1 is responsible for transforming movement signals to spatial firing fields.

Entorhinal Circuits results offered unique insights into some of the fundamental principles of neuronal assembly and microcircuit operation in the mammalian cortex. The generated knowledge will hopefully shed light into the role of the entorhinal cortex in various neuronal diseases like Alzheimer’s and schizophrenia.

Provided by CORDIS

Source: medicalxpress.com

May 28, 201225 notes
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CCR2 Involved in Removing Beta-Amyloid, Could Slow Alzheimer’s Progression

May 25th, 2012

First study to suggest that the immune system may protect against Alzheimer’s changes in humans

Recent work in mice suggested that the immune system is involved in removing beta-amyloid, the main Alzheimer’s-causing substance in the brain. Researchers have now shown for the first time that this may apply in humans.

Researchers at the Peninsula College of Medicine and Dentistry, University of Exeter with colleagues in the National Institute on Aging in the USA and in Italy screened the expression levels of thousands of genes in blood samples from nearly 700 people. The telltale marker of immune system activity against beta-amyloid, a gene called CCR2, emerged as the top marker associated with memory in people.

The team used a common clinical measure called the Mini Mental State Examination to measure memory and other cognitive functions.

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CCR2 might protect against Alzheimer’s changes, a new study claims. Image adapted from Wikimedia Commons user Pleiotrope.

The previous work in mice showed that augmenting the CCR2-activated part of the immune system in the blood stream resulted in improved memory and functioning in mice susceptible to Alzheimer’s disease.

Professor David Melzer, who led the work, commented: “This is a very exciting result. It may be that CCR2-associated immunity could be strengthened in humans to slow Alzheimer’s disease, but much more work will be needed to ensure that this approach is safe and effective”.

Dr Lorna Harries, co-author, commented: “Identification of a key player in the interface between immune function and cognitive ability may help us to gain a better understanding of the disease processes involved in Alzheimer’s disease and related disorders.”

Alzheimer’s disease is the most common form of dementia and affects around 496,000 people in the UK.

Source: Neuroscience News

May 26, 201212 notes
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Math Predicts Size of Clot-Forming Cells

ScienceDaily (May 25, 2012) — UC Davis mathematicians have helped biologists figure out why platelets, the cells that form blood clots, are the size and shape that they are. Because platelets are important both for healing wounds and in strokes and other conditions, a better understanding of how they form and behave could have wide implications.

"Platelet size has to be very specific for blood clotting," said Alex Mogilner, professor of mathematics, and neurobiology, physiology and behavior at UC Davis and a co-author of the paper, published this week in the journal Nature Communications. “It’s a longstanding puzzle in platelet formation, and this is the first quantitative solution.”

Mogilner and UC Davis postdoctoral scholars Jie Zhu and Kun-Chun Lee developed a mathematical model of the forces inside the cells that turn into platelets, accurately predicting their final size and shape.

They were collaborating with a team led by Joseph Italiano and Jonathon Thon at Harvard Medical School and Brigham and Women’s Hospital, Boston.

Platelets are made by bone marrow cells called megakaryocytes. They bud off first as large, circular pre-platelets, form into a dumbbell-shaped pro-platelet, then finally divide into a standard-sized, disc-shaped platelet. A typical person has about a trillion platelets in circulation at a time, and makes about 100 billion new platelets a day, each living for 8 to 10 days.

Inside the pre- and pro-platelets is a ring of protein microtubules, which exerts pressure to straighten and broaden the nascent cells. But overlying the ring is a rigid cortex of proteins that prevents the platelets from expanding.

By tweaking the number of microtubules in the bundles, Mogilner, Zhu and Lee found that they could correctly predict how pro-platelets would flip into a dumbbell shape, as well as the size and shape of mature platelets.

Source: Science Daily

May 26, 20127 notes
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Of mice and mental models: Neuroscientific implications of risk-optimized behavior in the mouse

May 25, 2012 by Stuart Mason Dambrot

(Medical Xpress) — Regardless of an organism’s biological complexity, every encephalized animal continuously makes under-informed behavioral choices that can have serious consequences. Despite its ubiquity, however, there’s a long-standing question about its neurological basis – namely, whether these choices are made through probabilistic world models constructed by the brain, or by reinforcement of learned associations. Recently, however, scientists in the Department of Psychology at Rutgers University found that reinforcement cannot account for the rapidity with which mice modify their behavior when the chance of a given phenomenon changes. The researchers say this indicates that mice may have primordially-evolved neural capabilities to represent likelihood and perform calculations that optimize their resulting behavior – and therefore that such genetic mechanisms can be investigated and manipulated by genetic and other procedures.

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The experimental environment. In the switch task, a trial proceeds as follows: 1: Light in the Trial-Initiation Hopper signals that the mouse may initiate a trial. 2: The mouse approaches and pokes into the trial-initiation hopper, extinguishing the light there and turning on the lights in the two feeding hoppers (trial onset). 3: The mouse goes to the short-latency hopper and pokes into it. 4: If, after 3 s have elapsed since the trial onset, poking in the short-latency hopper does not deliver a pellet, the mouse switches to the long-latency hopper, where it gets a pellet there in response to the first poke at or after 9 s since the trial onset. Lights in both feeding hoppers extinguish either at pellet delivery or when an erroneously timed poke occurs. Short trials last about 3 s and long trials about 9 s, whether reinforced or not: if the mouse is poking in the short hopper at the end of a 3-s trial, it gets a pellet and the trial ends; if it is poking in the 9-s hopper, it does not get a pellet and the trial ends at 3 s. Similarly, long trials end at 9 s: if the mouse is poking in the 9-s hopper, it gets a pellet; if in the 3-s hopper, it does not. A switch latency is the latency of the last poke in the short hopper before the mouse switches to the long hopper. Only the switch latencies from long trials are analyzed. Copyright © PNAS, doi: 10.1073/pnas.1205131109

In conducting their research, Prof. Randy Gallistel and doctoral student Aaron Kheifets had to first address a key challenge in identifying estimates of stochastic parameters versus reinforcement-driven processes as the behavior-optimizing mechanism in the laboratory mice studied (the c57bl/6j strain of Mus musculus, the common house mouse, from Jackson Labs). “Because both processes can lead to approximately optimal behavior in the long run,” Gallistel tells Medical Xpress, “one has to focus on the short run – that is, on the course of the transition in behavior. The problem in this case is that the transition is a change in the distribution of switch latencies.” A distribution of switch latencies is composed of a great many temporal discriminations on the part of the subject observed over a long sequence of trials, so this distribution can be used to prove that the process generating the distribution changed abruptly.

“Fortunately,” Gallistel continues, “it was obvious from simple inspection of the raw data that there was an abrupt change. The challenge was to develop a mathematical analysis that confirmed this. Meeting this challenge required the use of Bayesian methods, which are just now beginning to be applied to behavioral data. In addition, we had to develop analyses showing that differential reinforcement could not explain the transition.” The team therefore applied Bayesian methods of analysis to the determination of the parameters of a transition function for a 4-parameter mixture distribution.

“Also,” Gallistel adds, “a graphical means of displaying the raw data in such a way as to make the basic phenomenon visually apparent was required. To this end, we devised a figure with a huge number of bits per square centimeter – that is, it shows an enormous amount of readily graspable information in a small space.”

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May 26, 20126 notes
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Synchronized Brains: Feeling Strong Emotions Makes People's Brains 'Tick Together'

ScienceDaily (May 24, 2012) — Experiencing strong emotions synchronizes brain activity across individuals, a research team at Aalto University and Turku PET Centre in Finland has revealed.

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Experiencing strong emotions synchronizes brain activity across individuals. (Credit: Image courtesy of Aalto University)

Human emotions are highly contagious. Seeing others’ emotional expressions such as smiles triggers often the corresponding emotional response in the observer. Such synchronization of emotional states across individuals may support social interaction: When all group members share a common emotional state, their brains and bodies process the environment in a similar fashion.

Researchers at Aalto University and Turku PET Centre have now found that feeling strong emotions makes different individuals’ brain activity literally synchronous.

The results revealed that especially feeling strong unpleasant emotions synchronized brain’s emotion processing networks in the frontal and midline regions. On the contrary, experiencing highly arousing events synchronized activity in the networks supporting vision, attention and sense of touch.

"Sharing others’ emotional states provides the observers a somatosensory and neural framework that facilitates understanding others’ intentions and actions and allows to ‘tune in’ or ‘sync’ with them. Such automatic tuning facilitates social interaction and group processes," says Adjunct Professor Lauri Nummenmaa from the Aalto University, Finland.

"The results have major implications for current neural models of human emotions and group behavior. It also deepens our understanding of mental disorders involving abnormal socioemotional processing," Nummenmaa says.

Participants’ brain activity was measured with functional magnetic resonance imaging while they were viewing short pleasant, neutral and unpleasant movies.

Source: Science Daily

May 25, 2012668 notes
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Protein Necessary for Behavioral Flexibility Discovered

ScienceDaily (May 24, 2012) — Researchers have identified a protein necessary to maintain behavioral flexibility, which allows us to modify our behaviors to adjust to circumstances that are similar, but not identical, to previous experiences. Their findings, which appear in the journal Cell Reports, may offer new insights into addressing autism and schizophrenia — afflictions marked by impaired behavioral flexibility.

Our stored memories from previous experiences allow us to repeat certain tasks. For instance, after driving to a particular location, we recall the route the next time we make that trip. However, sometimes circumstances change — one road on the route is temporarily closed — and we need to make adjustments to reach our destination. Our behavioral flexibility allows us to make such changes and, then, successfully complete our task. It is driven, in part, by protein synthesis, which produces experience-dependent changes in neural function and behavior.

However, this process is impaired for many, preventing an adjustment in behavior when faced with different circumstances. In the Cell Reports study, the researchers sought to understand how protein synthesis is regulated during behavioral flexibility.

To do so, they focused on the kinase PERK, an enzyme that regulates protein synthesis. PERK is known to modify eIF2α, a factor that is required for proper protein synthesis. Their experiments involved comparing normal lab mice, which possessed the enzyme, with those that lacked it.

In their study, the mice were asked to navigate a water maze, which included elevating themselves onto a platform to get out of the water. Normal mice and those lacking PERK learned to complete this task.

However, in a second step, the researchers tested the mice’s behavioral flexibility by moving the maze’s platform to another location, thereby requiring them to respond to a change in the terrain. Here, the normal mice located the platform, but those lacking PERK were unable to do so or took significantly more time to complete the task.

A second experiment offered a different test of the role of PERK in aiding behavioral flexibility. In this measure, both normal and mutant mice heard an audible tone that was followed by a mild foot shock. At this stage, all of the mice developed a normal fear response — freezing at the tone in anticipation of the foot shock. However, the researchers subsequently removed the foot shock from the procedure and the mice heard only the tone. Eventually, the normal mice adjusted their responses so they did not freeze after hearing the tone. However, the mutant mice continued to respond as if they expected a foot shock to follow.

The researchers sought additional support for their conclusion that the absence of PERK may contribute to impaired behavioral flexibility in human neurological disorders. To do so, they conducted postmortem analyses of human frontal cortex samples from patients afflicted with schizophrenia, who often exhibit behavioral inflexibility, and unaffected individuals. The samples from the control group showed normal levels of PERK while those from the schizophrenic patients had significantly reduced levels of the protein.

"A rapidly expanding list of neurological disorders and neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Fragile X syndrome, have already been linked to aberrant protein synthesis," explained Eric Klann, a professor in NYU’s Center for Neural Science and one of the study’s co-authors. "Our results show the significance of PERK in maintaining behavioral flexibility and how its absence might be associated with schizophrenia. Further studies clarifying the specific role of PERK-regulated protein synthesis in the brain may provide new avenues to tackle such widespread and often debilitating neurological disorders."

Source: Science Daily

May 25, 201219 notes
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Boundary stops molecule right where it needs to be

May 24, 2012

A molecule responsible for the proper formation of a key portion of the nervous system finds its way to the proper place not because it is actively recruited, but instead because it can’t go anywhere else.

Researchers at Baylor College of Medicine have identified a distal axonal cytoskeleton as the boundary that makes sure AnkyrinG clusters where it needs to so it can perform properly.

The findings appear in the current edition of Cell.

"It has been known that AnkyrinG is needed for the axon initial segment to form. Without the axon initial segment there would be no output of information within the nervous system,” said Dr. Matthew Rasband, associate professor of neuroscience at BCM. “Every known protein found at the axon initial segment depends on AnkyrinG, so if it is eliminated then the axon initial segment doesn’t form and the neuron doesn’t fire.”

To answer the question of how AnkyrinG gets to where it needs to be for proper function, Rasband, along with first author Dr. Mauricio Galiano, postdoctoral associate in neuroscience at BCM, and colleagues, began by analyzing how the axon initial segment forms. They found that AnkyrinG always appeared in exactly the same spot during development.

"It would start to enter into the axon and then it was almost as if it hit a wall and couldn’t go any further," Rasband said. "We would see it stop very close to the cell body and then it would backfill. This showed us that there was some type of boundary or barrier marking that area."

To further study the properties of the boundary they began to look at ways they could disrupt or move it to test the effects of AnkyrinG clustering in different areas.

In cell cultures mouse models they were able to move the boundary to different distances along the axon. Doing this allowed researchers to change the length of the axon initial segment. If the boundary was farther away from the cell body than the length of the segment was longer. If it was closer to the cell body, then the length was shorter.

When researchers removed the boundary all together, AnkyrinG would not cluster in the appropriate area and the axon initial segment would not form.

"We had anticipated there was a kind of molecule that recruited AnkyrinG but instead we found a barrier that excludes it," Rasband said. "These results have important implications because they imply a similar exclusion mechanism might be in play or functioning not only at the axon initial segment, but all of the places where AnkyrinG is found."

Rasband said within many disorders like autism or epilepsy proteins that AnkyrinG is responsible for forming are disrupted. So understanding how this molecule functions properly could one day play a role in finding treatment targets for diseases.

Provided by Baylor College of Medicine

Source: medicalxpress.com

May 24, 20127 notes
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Locating ground zero: How the brain's emergency workers find the disaster area

May 24, 2012

Like emergency workers rushing to a disaster scene, cells called microglia speed to places where the brain has been injured, to contain the damage by ‘eating up’ any cellular debris and dead or dying neurons. Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have now discovered exactly how microglia detect the site of injury, thanks to a relay of molecular signals. Their work, published today in Developmental Cell, paves the way for new medical approaches to conditions where microglia’s ability to locate hazardous cells and material within the brain is compromised.

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Microglia (green) move to the site of injury (arrow) to clear up debris. Credit: Copyright EMBL/Peri

"Considering that they help keep our brain healthy, we know surprisingly little about microglia," says Francesca Peri, who led the work. "Now, for the first time, we’ve identified the mechanism that allows microglia to detect brain injury, and how that emergency call is transmitted from neuron to neuron.”

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When microglia (green) cannot detect ATP (bottom), they don’t move to the injury site as they usually would (top). Credit: Copyright EMBL/Peri

When an emergency occurs, cries can alert bystanders, who will dial the emergency number. A call will go out over the radio, and ambulances, police or fire engines in the area will respond as needed. In the brain, Peri and colleagues found, injured neurons send out their own distress cry: they release a molecule called glutamate. Neighbouring neurons sense that glutamate and respond by taking up calcium. As glutamate spreads out from the injury site, this creates a wave of calcium swallowing. Along that wave, as neurons take up calcium they release a third molecule, called ATP. When the wave comes within reach, a microglial cell detects that ATP and takes it as a call to action, moving in that direction – essentially tracing the wave backwards until it reaches the injury.

Scientists knew already that microglia can detect ATP, but this molecule doesn’t last long outside of cells, so there were doubts about how ATP alone could be a signal that carried far enough to reach microglia located far from the site of injury. The trick, as Peri and colleagues discovered, is the long-lasting glutamate-driven calcium wave that can travel the length of the brain. Thanks to this wave, the ATP signal is not just emitted by the injured cells, but is repeatedly sent out by the neurons along the way, until it reaches microglia.

Dirk Sieger and Christian Moritz in Peri’s lab took advantage of the fact that zebrafish have transparent heads, which allow scientists to peer down a microscope straight into the fish’s brain. They used a laser to injure a few of the fish’s brain cells, and watched fluorescently-labelled microglia move in on the injury. When they genetically engineered zebrafish to make neurons’ calcium levels traceable under the microscope, too, the scientists were able to confirm that when the calcium wave reached microglia, these cells immediately started moving toward the injury.

Knowing all the steps in this process, and how they feed into each other, could help to design treatments to improve microglia’s detection ability, which go awry in conditions such as Alzheimer’s and Parkinson’s diseases.

Provided by European Molecular Biology Laboratory

Source: medicalxpress.com

May 24, 201212 notes
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Persistent sensory experience is good for aging brain

May 24, 2012

Despite a long-held scientific belief that much of the wiring of the brain is fixed by the time of adolescence, a new study shows that changes in sensory experience can cause massive rewiring of the brain, even as one ages. In addition, the study found that this rewiring involves fibers that supply the primary input to the cerebral cortex, the part of the brain that is responsible for sensory perception, motor control and cognition. These findings promise to open new avenues of research on brain remodeling and aging.

Published in the May 24, 2012 issue of Neuron, the study was conducted by researchers at the Max Planck Florida Institute (MPFI) and at Columbia University in New York.

"This study overturns decades-old beliefs that most of the brain is hard-wired before a critical period that ends when one is a young adult," said MPFI neuroscientist Marcel Oberlaender, PhD, first author on the paper. "By changing the nature of sensory experience, we were able to demonstrate that the brain can rewire, even at an advanced age. This may suggest that if one stops learning and experiencing new things as one ages, a substantial amount of connections within the brain may be lost."

The researchers conducted their study by examining the brains of older rats, focusing on an area of the brain known as the thalamus, which processes and delivers information obtained from sensory organs to the cerebral cortex. Connections between the thalamus and the cortex have been thought to stop changing by early adulthood, but this was not found to be the case in the rodents studied.

Being nocturnal animals, rats mainly rely on their whiskers as active sensory organs to explore and navigate their environment. For this reason, the whisker system is an ideal model for studying whether the brain can be remodeled by changing sensory experience. By simply trimming the whiskers, and preventing the rats from receiving this important and frequent form of sensory input, the scientists sought to determine whether extensive rewiring of the connections between the thalamus and cortex would occur.

On examination, they found that the animals with trimmed whiskers had altered axons, nerve fibers along which information is conveyed from one neuron (nerve cell) to many others; those whose whiskers were not trimmed had no axonal changes. Their findings were particularly striking as the rats were considered relatively old – meaning that this rewiring can still take place at an age not previously thought possible. Also notable was that the rewiring happened rapidly – in as little as a few days.

"We’ve shown that the structure of the rodent brain is in constant flux, and that this rewiring is shaped by sensory experience and interaction with the environment," said Dr. Oberlaender. "These changes seem to be life-long and may pertain to other sensory systems and species, including people. Our findings open the possibility of new avenues of research on development of the aging brain using quantitative anatomical studies combined with noninvasive imaging technologies suitable for humans, such as functional MRI (fMRI)."

The study was possible due to recent advances in high-resolution imaging and reconstruction techniques, developed in part by Dr. Oberlaender at MPFI. These novel methods enable researchers to automatically and reliably trace the fine and complex branching patterns of individual axons, with typical diameters less than a thousandth of a millimeter, throughout the entire brain.

Provided by Tartaglia Communications

Source: medicalxpress.com

May 24, 201216 notes
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The auditory cortex adapts agilely with concentration

May 24, 2012

The birth of sensory perception on the human cerebral cortex is yet to be fully explained. The different areas on the cortex function in cooperation, and no perception is the outcome of only one area working alone. In his doctoral dissertation for the Department of Biomedical Engineering and Computational Science in Aalto University Jaakko Kauramäki shows that the auditory cortex is not left to its own devices.

Kauramäki’s dissertation in the field of cognitive neuroscience studied neural top-down processes, that is, the ways the brain as a system handles sounds arriving onto the auditory cortex in the frontal lobes.

Moving from parts towards a whole, bottom-up processes analyse a sound by dissecting it in hierarchical chain reactions from small and sophisticated bits towards a concise auditory sensation.

"The operation of the system as a whole can be affected by focusing on a specific task or sound. In my research I focused precisely on how the top-down effects manifest themselves on the auditory cortex," explains Kauramäki his study.

Right kind of noise promotes concentration and reinforces perception?

Kauramäki studied the auditory cortex in two separate tasks: reactions caused by selective attention during sound recognition and by lipreading. Kauramäki recorded the electrical and magnetic activity on the cortex using electroencephalography (EEG) and magnetoencephalography (MEG) respectively.

"40 years ago a so-called ‘gain effect’ was formulated: focusing attention enhances responses on the auditory cortex, which means that attention helps to better perceive audio stimuli," tells Kauramäki.

In the attention tests Kauramäki masked the sounds played for the test subjects with different frequencies of noise – and made a discovery. During periods of selective attention, the enhanced responses on the auditory cortex depended on the type of noise used. The frequency content of the noise affected the prominence of the responses. The responses are not only enhanced, but they are feature and task-specific.

"Similar results have not been obtained earlier because the stimuli used in the experiments have been too simple. The noise mask added a combinatory effect that brought the specificity and selectivity of the responses to the fore."

"Focusing attention may then be easier in a rich sound environment. Complete silence is of course an extreme case, but in total silence the auditory cortex begins to create connections out of thin air, to make up sensory perceptions."

"Then again, the more stimuli there are in the environment, the harder it becomes to focus. In attention disorders such as ADHD, precisely the top-down ability to filter sounds may be lacking," suspects Kauramäki.

In the lipreading tasks Kauramäki did not encounter such a dependency on frequency. Instead, lipreading suppressed the auditory cortex’s ability to react. The reason for this is the neural response of the speech production system.

"The suppressing effect is caused by the adaptation of the areas on the auditory cortex that specialise in speech. Suppressing occurs even when the speech is inaudible – the articulatory gestures of the mouth alone activate parts of the auditory cortex."

For Kauramäki the result suggests that the neural responses of the speech production system can reach the auditory cortex and thus reinforce perception.

"In noisy meetings, for example, it pays off to concentrate on the face of whoever is speaking: lipreading helps in the processing. It may suppress the reaction of the auditory cortex, but the big picture becomes clearer."

Provided by Aalto University

Source: medicalxpress.com

May 24, 201210 notes
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World's biggest stroke clot-buster trial reveals patient benefits

May 24, 2012

(Medical Xpress) — Patients given a clot-busting drug within six hours of a stroke are more likely to make a better recovery than those who do not receive the treatment, new research has found.

The trial was set up in 2000 by the University of Sydney’s Professor Richard Lindley, while he was employed at the University of Edinburgh.

The study of more than 3000 patients is the world’s largest trial of the drug rt-PA and was coordinated at the University of Edinburgh. Since coming to Sydney Medical School in 2003, Professor Lindley has continued as the co-principal investigator of the research.

The findings of the study are published today in The Lancet, alongside an analysis of all other trials of the drug carried out in the past 20 years.

The trial found that following treatment with the drug rt-PA, which is given intravenously to patients who have suffered an acute ischaemic stroke, more patients were able to look after themselves.

"The trial results, together with the updated review, mean that rt-PA can now be offered to a much wider group of patients presenting with stroke", Professor Lindley said.

A patient’s chances of making a complete recovery within six months of a stroke were also increased.

An ischaemic stroke happens when the brain’s blood supply is interrupted by a blood clot. The damage caused can be permanent or fatal.

Researchers now know that for every 1000 patients given rt-PA within three hours of stroke, 80 more will survive and live without help from others than if they had not been given the drug.

The benefits of using rt-PA do come at a price, say researchers. Patients are at risk of death within seven days of treatment because the drug can cause a secondary bleed in the brain. The research team concluded that the benefits were seen in a wide variety of patients, despite the risks.

Stroke experts stress that these mortality figures need to be viewed in the context of deaths from stroke. Without treatment, one third of people who suffer a stroke die, with another third left permanently dependent and disabled.

Researchers say the threat of death and disability means many stroke patients are prepared to take the early risks of being treated with rt-PA to avoid being disabled.

The authors conclude that for those who do not experience bleeding, the drug improves patients’ longer term recovery.

About half of those who took part in the trial were over 80.

"The trial underlines the benefits of treating patients with the drug as soon as possible and provides the first reliable evidence that treatment is effective for those aged 80 and over," Professor Lindley said.

The study also found no reason to restrict use of rt-PA - also known as alteplase - on the basis of how severe a patient’s stroke has been.

Chief investigator Professor Peter Sandercock of the University of Edinburgh’s Centre for Clinical Brain Sciences said: “Our trial shows that it is crucial that treatment is given as fast as possible to all suitable patients.”

Provided by University of Sydney

Source: medicalxpress.com

May 24, 20127 notes
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Genetic 'reset switch' enables signaling pathway to induce multiple developmental outcomes for olfactory neurons

May 24, 2012

Within the nervous system, a handful of signaling pathways modulate development of a cornucopia of different neuronal subtypes. “Even small alterations in neuron differentiation pathways can disrupt subsequent circuit organization and catalyze the genesis of neurological disorders,” explains Adrian Moore of the RIKEN Brain Science Institute in Wako.

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Figure 1: Interplay between Notch signaling and Hamlet activity gives rise to diverse olfactory receptor neurons (ORNs), each with distinct structures and subsets of olfactory receptors (left). The precursor cell (right) divides to yield two daughter cells, one of which undergoes Notch (N)-mediated gene activation. Hamlet (Ham) subsequently resets Notch’s genetic effects, and the absence or subsequent restoration of Notch signaling determines which type of ORN (Naa or Nab) will result from differentiation. Credit: 2012 Adrian Moore, RIKEN Brain Science Institute

Recent work from Moore’s team, which includes Keita Endo of the University of Tokyo, has revealed mechanisms governing this complexity in the fruit fly olfactory system. Within the antennae—the fly equivalent of the nose—it was known that cells called neuronal precursors undergo multiple rounds of ‘asymmetric division’, wherein each resulting daughter cell follows a distinct developmental path, yielding different combinations of olfactory receptor neurons (ORNs). Moore’s team showed specifically that ORN precursors undergo two rounds of division, yielding four different cellular subtypes, three of which will typically mature into ORNs.

Earlier work from Endo showed that the activation or suppression of signaling by the Notch protein helps differentiate these cellular fates, but other factors were clearly involved. Their joint research demonstrated that a second protein, Hamlet, modulates the effects of Notch. 

“This [process] provides an important foundation for all future studies of odorant receptor expression and axon targeting control on the olfactory system,” says Moore. The researchers found that presence or absence of Notch and Hamlet activity plays a central role in establishing the identity of these subtypes, and this in turn determines both the connections formed by the resulting ORNs as well as the subset of olfactory receptor proteins that will be expressed (Fig. 1). 

Moore and Endo’s study also revealed a surprising mode of action for Hamlet. Chromosomal DNA is wrapped around clusters of protein, and chemical changes to those proteins profoundly alter local gene activity—a mechanism called ‘epigenetic regulation’. They found that Hamlet selectively deactivates genes activated by Notch by triggering such changes. This means that immature ORNs produced by division of a Notch-activated cell can essentially be ‘reset’ by Hamlet. The ultimate developmental fate of those cells is then determined, in part, by whether or not they subsequently undergo a new round of Notch activation. 

Moore and colleagues also observed that, beyond simply switching off active Notch genes, Hamlet may define subsets of target genes that can subsequently be reactivated by Notch signaling. “The modifications induced by Hamlet may help establish cell fate by marking gene promoters for use later during differentiation,” says Moore. “This could prove fundamental to understanding the process of neuronal diversification.”

Provided by RIKEN

Source: medicalxpress.com

May 24, 20124 notes
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No new neurons in the human olfactory bulb

May 24, 2012

(Medical Xpress) — Research from Karolinska Institutet shows that the human olfactory bulb - a structure in the brain that processes sensory input from the nose - differs from that of other mammals in that no new neurons are formed in this area after birth. The discovery, which is published in the scientific journal Neuron, is based on the age-determination of the cells using the carbon-14 method, and might explain why the human sense of smell is normally much worse than that of other animals.

"I’ve never been so astonished by a scientific discovery," says lead investigator Jonas Frisén, Tobias Foundation Professor of stem cell research at Karolinska Institutet. "What you would normally expect is for humans to be like other animals, particularly apes, in this respect."

It was long thought that all brain neurons were formed up to the time of birth, after which production stopped. A paradigm shift occurred when scientists found that nerve cells were being continually formed from stem cells in the mammalian brain, which changed scientific views on the plasticity of the brain and raised hopes of being able to replace neurons lost during some types of neurological disease.

In the adult mammal, new nerve cells are formed in two regions of the brain: the hippocampus and the olfactory bulb. While the former has an important part to play in memory, the latter is essential to the interpretation of smells. However, owing to the difficulty of studying the formation of new neurons in humans, the extent to which this phenomenon also occurs in the human brain has remained unclear. In this present study, researchers at Karolinska Institutet and their Austrian and French colleagues made use of the sharp rise in atmospheric carbon-14 caused by Cold War nuclear tests to find an answer to this question.

Carbon-14 is incorporated in DNA, making it possible to gauge the age of the cells by measuring how much of the isotope they contain. Doing this, the team found that the olfactory bulb neurons in their adult human subjects had carbon-14 levels that matched those at the atmosphere at the time of their birth. This is a strong indication that there is no significant generation of new neurons in this part of the brain, something that sets humans apart from all other mammals.

"Humans are less dependent on their sense of smell for their survival than many other animals, which may be related to the loss of new cell generation in the olfactory bulb, but this is just speculation,” says Professor Frisén.

Professor Frisén and his team now plan to study the extent of neuron generation in the hippocampus, a part of the brain that is important for higher cerebral functions in humans.

Provided by Karolinska Institutet

Source: medicalxpress.com

May 24, 201212 notes
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'Obesity Genes' May Influence Food Choices, Eating Patterns

ScienceDaily (May 23, 2012) — Blame it on your genes? Researchers from The Miriam Hospital’s Weight Control and Diabetes Research Center say individuals with variations in certain “obesity genes” tend to eat more meals and snacks, consume more calories per day and often choose the same types of high fat, sugary foods.

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Blame it on your genes? Researchers say individuals with variations in certain “obesity genes” tend to eat more meals and snacks and consume more calories per day. (Credit: © Gennadiy Poznyakov / Fotolia)

Their study, published online by the American Journal of Clinical Nutrition and appearing in the June issue, reveals certain variations within the FTO and BDNF genes — which have been previously linked to obesity — may play a role in eating habits that can cause obesity.

The findings suggest it may be possible to minimize genetic risk by changing one’s eating patterns and being vigilant about food choices, in addition to adopting other healthy lifestyle habits, like regular physical activity.

"Understanding how our genes influence obesity is critical in trying to understand the current obesity epidemic, yet it’s important to remember that genetic traits alone do not mean obesity is inevitable," said lead author Jeanne M. McCaffery, Ph.D., of The Miriam Hospital’s Weight Control and Diabetes Research Center.

"Our lifestyle choices are critical when it comes to determining how thin or heavy we are, regardless of your genetic traits," she added. "However, uncovering genetic markers can possibly pinpoint future interventions to control obesity in those who are genetically predisposed."

Previous research has shown individuals who carry a variant of the fast mass and obesity-associated gene FTO and BDNF (or brain-derived neurotrophic factor gene) are at increased risk for obesity. The genes have also been linked with overeating in children and this is one of the first studies to extend this finding to adults. Both FTO and BDNF are expressed in the part of the brain that controls eating and appetite, although the mechanisms by which these gene variations influence obesity is still unknown.

As part of the Look AHEAD (Action in Health and Diabetes) trial, more than 2,000 participants completed a questionnaire about their eating habits over the past six months and also underwent geneotyping. Researchers focused on nearly a dozen genes that have been previously associated with obesity. They then examined whether these genetic markers influenced the pattern or content of the participants’ diet.

Variations in the FTO gene specifically were significantly associated with a greater number of meals and snacks per day, greater percentage of energy from fat and more servings of fats, oils and sweets. The findings are largely consistent with previous research in children.

Researchers also discovered that individuals with BDNF variations consumed more servings from the dairy and the meat, eggs, nuts and beans food groups. They also consumed approximately 100 more calories per day, which McCaffery notes could have a substantial influence on one’s weight.

"We show that at least some of the genetic influence on obesity may occur through patterns of dietary intake," she said. "The good news is that eating habits can be modified, so we may be able to reduce one’s genetic risk for obesity by changing these eating patterns."

McCaffery says that while this research greatly expands their knowledge on how genetics may influence obesity, the data must be replicated before the findings can be translated into possible clinical measures.

Source: Science Daily

May 24, 20127 notes
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Antioxidant Urate Could Protect Against Parkinson’s Disease

May 23rd, 2012

Study supports urate protection against Parkinson’s disease, hints at novel mechanism

In vitro study indicates urate protection extends beyond antioxidant effect

Use of the antioxidant urate to protect against the neurodegeneration caused by Parkinson’s disease appears to rely on more than urate’s ability to protect against oxidative damage. In the May issue of the open-access journal PLoS One, researchers from the MassGeneral Institute for Neurodegenerative Diseases (MGH-MIND) describe experiments suggesting the involvement of a novel mechanism in urate’s protection of cultured brain cells against Parkinson’s-like damage.

“Our experiments showed, unexpectedly, that urate’s ability to protect neurons requires the presence of neighboring cells called astrocytes,” says Michael Schwarzschild, MD, PhD, of MGH-MIND, the study’s senior author. “The results suggest there may be multiple ways that raising urate could help protect against neurodegeneration in diseases like Parkinson’s and further support the development of treatments designed to elevate urate in the brain.” Schwarzschild and colleagues in the Parkinson’s Study Group currently are conducting a clinical trial investigating one approach to that strategy.

Characterized by tremors, rigidity, difficulty walking and other symptoms, Parkinson’s disease is caused by destruction of brain cells that produce the neurotransmitter dopamine. Several epidemiological studies suggested that healthy people with elevated levels of urate, a normal component of the blood, may have a reduced risk of developing Parkinson’s disease, and investigations by Schwarzschild’s team found that Parkinson’s patients with higher naturally occuring urate levels had slower progression of their symptoms.

The current study was designed to investigate whether both added urate and urate already present within the cells protect cultured dopamine-producing neurons against Parkinson-like degeneration. In addition, since previous studies suggested that urate’s protective effects depended on the presence of astrocytes,  star-shaped cells of the central nervous system that provide both structural and metabolic support to neurons,  the MGH-MIND team explored how the presence of astrocytes affects the ability of urate to protect against damage induced by MPP+, a toxic molecule that produces the same kind of neurodegeneration seen in Parkinson’s and is widely used in research studies.

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Raising urate levels could help to protect against neurodegenerative diseases like Parkinsons. Image adapted from Flickr user Niels_Olson.

The experiments showed that, while added urate reduced MPP+-induced cell death by about 50 percent in cultured dopamine-producing mouse neurons, urate treatment virtually eliminated neuronal death in cultures containing both neurons and astrocytes. They also showed that reducing intracellular urate levels by induced expression of the enzyme that breaks it down increased neuronal vulnerability to MPP+ toxicity significantly in cultures that included astrocytes but only slightly in neuron-rich cultures. The fact that the presence of astrocytes greatly increases the protection of both externally applied urate and urate produced within cells indicates that the effect depends on more than urate’s ability to directly protect neurons against oxidative stress.

“A valuable next step will be determining whether endogenous urate is protective in live animal models of Parkinson’s disease,” says Schwarzschild. “It also will be important to determine whether we can selectively increase urate levels in brain cells by targeting urate transporter molecules. The approach now in early clinical trials examines whether treatment with the urate precursor inosine, which increases urate levels throughout the body, can slow the progression of the disease. If we could raise urate levels in brain cells without changing them in the rest of the body, we could avoid the risks of of excessive urate, which when accumulated in joints can cause gout.”

Source: Neuroscience News

May 24, 201210 notes
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Study shows how immune cells change wiring of the developing mouse brain

May 23, 2012

Researchers have shown in mice how immune cells in the brain target and remove unused connections between brain cells during normal development. This research, supported by the National Institutes of Health, sheds light on how brain activity influences brain development, and highlights the newly found importance of the immune system in how the brain is wired, as well as how the brain forms new connections throughout life in response to change.

Disease-fighting cells in the brain, known as microglia, can prune the billions of tiny connections (or synapses) between neurons, the brain cells that transmit information through electric and chemical signals. This new research demonstrates that microglia respond to neuronal activity to select synapses to prune, and shows how this pruning relies on an immune response pathway – the complement system – to eliminate synapses in the way that bacterial cells or other pathogenic debris are eliminated. The study was led by Beth Stevens, Ph.D., assistant professor of neurology at Boston Children’s Hospital and Harvard Medical School.

The brain is created with many more synapses than it retains into adulthood. As the brain develops, it goes through dynamic changes to refine its circuitry, trimming away the synaptic connections that do not have a lot of activity, and preserving the stronger, more active synapses. This period, known as synaptic pruning, is a key part of normal brain development.

Scientists do not have a clear understanding of how these synapses are selected, targeted and then pruned. However, precise elimination of unused synapses and strengthening those that are most needed is essential for normal brain function. Many childhood disorders, such as amblyopia (a loss of vision in one eye that can occur when the eyes are misaligned), various forms of mental retardation, epilepsy and autism are thought to be due to abnormal brain development.

Microglia originate in the bone marrow and transform into an activated state to defend the body against infections. Activated microglia are also found in other disease states, ranging from stroke to Alzheimer’s disease. It is not always clear, however, if these cells cause degeneration of brain cells, or if they are part of the brain’s recovery process. In more recent years, several research groups reported that activated microglia are also present in the normal brain. Additionally, during the most robust synaptic pruning periods there is an increased number of activated microglia present and clustered around synapses.

As reported in the May 24 issue of Neuron, scientists in Dr. Stevens’s lab used the visual system in mice to study synaptic pruning, a model that undergoes robust change and remodeling during development and which has circuitry that is well-defined and easy to manipulate. Researchers labeled neurons that project from the eye into an area of the brain called the lateral geniculate nucleus, or LGN, and found that reactive microglia contained portions of the synapses from the labeled neurons. They also saw that these labeled pieces of synaptic material were specifically found inside the microglia’s lysosomes – compartments responsible for digesting foreign particles.

The researchers then investigated if the amount of neuronal activity at a synapse determines whether microglia target it for removal. They used a drug to increase activity in the neurons projecting from one eye and saw less pruning of synapses in the corresponding brain region, as compared to the untreated eye. When they used a drug to reduce activity, this resulted in more pruning compared to the untreated eye. The researchers think microglia select a synapse for removal based on the synapse’s level of activity. This may be directly relevant to amblyopia, a loss of vision in one eye that can occur when the eyes are misaligned. Children with amblyopia will preferentially use one eye and vision in the less used eye deteriorates due loss of synapses and cells in the LGN.

Earlier research revealed that proteins involved in the complement system are found near synapses during development and are necessary for pruning. To see if these same proteins are used by microglia to shape neuronal connections, the researchers disrupted complement pathway proteins that are found only in the brain’s immune cells. Their results indicate that these complement proteins signal the microglia to trim away synapses, and suggest that immune system pathways are key to proper synaptic pruning.

"The concept that microglia prune synapses using immune system pathways has been difficult to prove,” said Edmund Talley, Ph.D., program director at the National Institute of Neurological Disorders and Stroke, “This exquisitely careful and meticulous research confirms the role of microglia in brain development, plasticity and learning.”

Dr. Stevens said the study sheds light on the role of microglia in the normal brain, and supports further investigations into the role of microglia in brain disease. “Almost every neurodegenerative brain disease involves several interesting common denominators,” she said. “It’s becoming increasingly recognized that early synapse loss is a hallmark of many neurodegenerative diseases.”

Provided by NIH/National Institute of Neurological Disorders and Stroke

Source: medicalxpress.com

May 24, 20127 notes
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Brain research shows visual perception system unconsciously affects our preferences

May 23, 2012

When grabbing a coffee mug out of a cluttered cabinet or choosing a pen to quickly sign a document, what brain processes guide your choices?

New research from Carnegie Mellon University’s Center for the Neural Basis of Cognition (CNBC) shows that the brain’s visual perception system automatically and unconsciously guides decision-making through valence perception. Published in the journal Frontiers in Psychology, the review hypothesizes that valence, which can be defined as the positive or negative information automatically perceived in the majority of visual information, integrates visual features and associations from experience with similar objects or features. In other words, it is the process that allows our brains to rapidly make choices between similar objects.

The findings offer important insights into consumer behavior in ways that traditional consumer marketing focus groups cannot address. For example, asking individuals to react to package designs, ads or logos is simply ineffective. Instead, companies can use this type of brain science to more effectively assess how unconscious visual valence perception contributes to consumer behavior.

To transfer the research’s scientific application to the online video market, the CMU research team is in the process of founding the start-up company neonlabs through the support of the National Science Foundation (NSF) Innovation Corps (I-Corps).

"This basic research into how visual object recognition interacts with and is influenced by affect paints a much richer picture of how we see objects," said Michael J. Tarr, the George A. and Helen Dunham Cowan Professor of Cognitive Neuroscience and co-director of the CNBC. “What we now know is that common, household objects carry subtle positive or negative valences and that these valences have an impact on our day-to-day behavior.”

Tarr added that the NSF I-Corps program has been instrumental in helping the neonlabs’ team take this basic idea and teaching them how to turn it into a viable company. “The I-Corps program gave us unprecedented access to highly successful, experienced entrepreneurs and venture capitalists who provided incredibly valuable feedback throughout the development process,” he said.

NSF established I-Corps for the sole purpose of assessing the readiness of transitioning new scientific opportunities into valuable products through a public-private partnership. The CMU team of Tarr, Sophie Lebrecht, a CNBC and Tepper School of Business postdoctoral fellow, Babs Carryer, an embedded entrepreneur at CMU’s Project Olympus, and Thomas Kubilius, president of Pittsburgh-based Bright Innovation and adjunct professor of design at CMU, were awarded a $50,000, six-month grant to investigate how understanding valence perception could be used to make better consumer marketing decisions. They are launching neonlabs to apply their model of visual preference to increase click rates on online videos, by identifying the most visually appealing thumbnail from a stream of video. The web-based software product selects a thumbnail based on neuroimaging data on object perception and valence, crowd sourced behavioral data and proprietary computational analyses of large amounts of video streams.

"Everything you see, you automatically dislike or like, prefer or don’t prefer, in part, because of valence perception," said Lebrecht, lead author of the study and the entrepreneurial lead for the I-Corps grant. "Valence links what we see in the world to how we make decisions."

Lebrecht continued, “Talking with companies such as YouTube and Hulu, we realized that they are looking for ways to keep users on their sites longer by clicking to watch more videos. Thumbnails are a huge problem for any online video publisher, and our research fits perfectly with this problem. Our approach streamlines the process and chooses the screenshot that is the most visually appealing based on science, which will in the end result in more user clicks.”

Today (May 23), Lebrecht will join the other 23 I-Corps project teams in Palo Alto, Calif., for the final presentation of each team’s I-Corps journey from basic science idea to real-world business application. She will present neonlabs’ solution, outlining the customer landscape, competition and business model.

Carnegie Mellon is well known for its entrepreneurial culture. The university’s Greenlighting Startups initiative, a portfolio of five business incubators, is designed to speed company creation at CMU. In the past 15 years, Carnegie Mellon faculty and students have helped to create more than 300 companies and 9,000 jobs; the university averages 15 to 20 new startups each year.

"CMU has been an amazing place to build neonlabs," Lebrecht said. "There’s a great intellectual community and facilities here as well as people unbelievably experienced in tech transfer and startups who have been so incredibly generous with their time."

Provided by Carnegie Mellon University

Source: medicalxpress.com

May 24, 201219 notes
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Robust White Matter Helps Keep Us Smart As We Age

May 23rd, 2012

Well-connected brains make you smarter in older age
Brains that maintain healthy nerve connections as we age help keep us sharp in later life, new research funded by the charity Age UK has found

Brains that maintain healthy nerve connections as we age help keep us sharp in later life, new research funded by the charity Age UK has found.

Older people with robust brain ‘wiring’, that is, the nerve fibres that connect different, distant brain areas, can process information quickly and that this makes them generally smarter, the study suggests.

According to the findings, joining distant parts of the brain together with better wiring improves mental performance, suggesting that intelligence is not found in a single part of the brain.

However a loss of condition of this wiring or ‘white matter’, the billions of nerve fibres that transmit signals around the brain, can negatively affect our intelligence by altering these networks and slowing down our processing speed.

The research by the University of Edinburgh shows for the first time that the deterioration of white matter with age is likely to be a significant cause of age-related cognitive decline.

The research team used three different brain imaging techniques in compiling the results, including two that have never been used before in the study of intelligence.

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Healthy nerve connections in the brain help to reduce mental decline and dementia in older people. Image by Flickr user Brian Auer. See below for attribution.

These techniques measure the amount of water in brain tissue, indicate structural loss in the brain, and show how well the nerve fibres are insulated.

The researchers examined scans and results of thinking and reaction time tests from 420 people in the Lothian Birth Cohort of 1936, a group of nearly 1100 people whose intelligence & general health have been tracked since they were 11

The research was part of the Disconnected Mind Project, a large study of the causes of people’s differences in cognitive ageing, led by Professor Ian Deary.

Study author Doctor Lars Penke said “Our results suggest a first plausible way how brain structure differences lead to higher intelligence. The results are exciting for our understanding of human intelligence differences at all ages.”

“They also suggest a clear target for seeking treatment for mental difficulties, be they pathological or age-related. That the brain’s nerve connections tend to stay the same throughout the brain means we can now look at factors that affect the overall condition of the brain, like its bloody supply.”

Professor Deary said that uncovering the secrets of good thinking skills in old age is a high priority. “The research team is now looking at what keeps the brain’s connections healthy. We value our thinking skills, and research should address how we might retain them or slow their decline with age.”

Doctor Mark Bastin, who co-authored the study, said “These findings are exciting as they show how quantitative brain imaging can provide novel insights into the links between brain structure and cognitive ability. This is a key research area given the importance of identifying strategies for retaining good mental ability into older age.”

Professor James Goodwin, Head of Research at Age UK, said: “This research is very exciting as it could have a real impact on tackling mental decline in later life, including dementia. With new understanding on how the brain functions we can work out why mental faculties decline with age in some people and not others and look at what can be done to improve our minds’ chances of ageing better.”

Source: Neuroscience News

May 24, 20129 notes
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Researchers uncover new ways sleep-wake patterns are like clockwork

May 23, 2012

Researchers at New York University and Albert Einstein College of Medicine of Yeshiva University have discovered new ways neurons work together to ease the transition between sleep and wakefulness. Their findings, which appear in the journal Neuron, provide additional insights into sleep-wake patterns and offer methods to explore what may disrupt them.

Their study explored the biological, or circadian, clocks of Drosophila fruit flies, which are commonly used for research in this area. This is because it is relatively easy to find mutants with malfunctioning biological clocks and then to identify the genes underlying the altered behavior. Such studies in fruit flies have allowed the identification of similar “clock genes" in mammals, which function in largely the same manner as they do in a fly’s clock.

In the Neuron study, the researchers moved up a level to study how pacemaker clock neurons—which express clock genes—interact with each other. Specifically, they looked at the relationship between master pacemaker neurons, which control the overall pace of the circadian system, and non-master pacemaker neurons, whose role in circadian rhythms has been less clear.

To do so, they examined flies with normally functioning master and non-master clock neurons and compared them with mutant flies in which the signaling of these neurons was either increased or decreased. These comparisons allowed the researchers to isolate the individual roles of these neurons and, in particular, to understand how master and non-master pacemaker neurons work together to control circadian rhythms.

Their results revealed a previously unknown role for non-master pacemaker neurons. Specifically, these neurons employ a neurotransmitter, glutamate, which suppresses signaling of the master pacemaker neurons during the evening. Artificially increasing this suppression by the non-master clock neurons in the morning made it much harder for flies to wake up. So in normal flies, these non-master pacemaker neurons have to stand aside at dawn, allowing the master pacemaker neurons to fire to wake up the fly. The authors concluded that the balance between signaling of these two groups of clock neurons helps to set the precise time of the transition between sleep and wakefulness.

"Our work shifts the emphasis away from clock genes and starts to address how clock neurons function in a neural network to regulate behavior," explained Justin Blau, an associate professor in NYU’s Department of Biology and one of the study’s co-authors. "And it shows the importance of studying individual groups of clock neurons, since different subsets can have opposite effects on animal behavior.”

"This work helps to elucidate the neurotransmitters and receptors that facilitate communication between specific groups of nerve cells that regulate circadian rhythm," said co-author Myles Akabas, professor of Physiology & Biophysics and of Neuroscience at Albert Einstein College of Medicine. "It demonstrates the power of collaborative interdisciplinary research to address the molecular and cellular basis for behavior."

Provided by New York University

Source: medicalxpress.com

May 23, 201216 notes
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Reverse engineering epilepsy's 'miracle' diet

May 23, 2012 by R. Alan Leo

For decades, neurologists have known that a diet high in fat and extremely low in carbohydrates can reduce epileptic seizures that resist drug therapy. But how the diet worked, and why, was a mystery—so much so that in 2010, The New York Times Magazine called it “Epilepsy’s Big, Fat Miracle.”

Now, researchers at Dana-Farber Cancer Institute and Harvard Medical School have proposed an answer, linking resistance to seizures to a protein that modifies cellular metabolism in the brain. The research, to be published in the May 24th issue of the journal Neuron, may lead to the development of new treatments for epilepsy.

The research was led jointly by Nika Danial, HMS assistant professor of cell biology at Dana-Farber Cancer Institute, and Gary Yellen, professor of neurobiology at Harvard Medical School. The first author was Alfredo Giménez-Cassina, a research fellow in Danial’s lab.

Epilepsy is a neurological disorder characterized by repeated seizures, an electrical storm in the brain that can manifest as convulsions, loss of motor control, or loss of consciousness. Some cases of epilepsy can be improved by a diet that drastically reduces sugar intake, triggering neurons to switch from their customary fuel of glucose to fat byproducts called ketone bodies. The so-called ketogenic diet, which mimics effects of starvation, was described more than 80 years ago and received renewed interest in the 1990s. Recent studies corroborate that it works, but shed little light on how.

"The connection between metabolism and epilepsy has been such a puzzle," said Yellen, who was introduced to the ketogenic diet through his wife, Elizabeth Thiele, HMS professor of neurology, who directs the Pediatric Epilepsy Program at MassGeneral Hospital for Children, but was not directly involved in the study. "I’ve met a lot of kids whose lives are completely changed by this diet," Yellen said. "It’s amazingly effective, and it works for many kids for whom drugs don’t work."

"We knew we needed to come at this link between metabolism and epilepsy from a new angle," said Danial, who had previously discovered a surprising double duty for a protein known for its role in apoptosis: The protein, BCL-2-associated Agonist of Cell Death, or BAD, also regulated glucose metabolism.

Giménez-Cassina further discovered that certain modifications in BAD switched metabolism in brain cells from glucose to ketone bodies. “It was then that we realized we had come upon a metabolic switch to do what the ketogenic diet does to the brain without any actual dietary therapy,” said Gimenez-Cassina, who went on to show that these same BAD modifications protect against seizures in experimental models of epilepsy. Still, it wasn’t clear exactly how.

Yellen suspected the solution involved potassium ion channels. While sodium and calcium ion channels tend to excite cells, including neurons, potassium channels tend to suppress cell electrical activity. His lab had previously linked ketone bodies to the activation of ATP-sensitive potassium (KATP) channels in neurons. Yellen had hypothesized that the ketogenic diet worked because ketone bodies provide neurons enough fuel for normal function, but when the electrical and energy storm of an epileptic seizure threatens, the activated KATP channels can shut the storm down. But the effects of diets are broad and complex, so it was impossible to say for sure.

The effects that Danial’s lab had discovered—BAD’s ability to alter metabolism and seizures—offered a new avenue for studying the therapeutic effects of altered metabolism. Together, the researchers decided to investigate whether Danial’s switch governed Yellen’s pathway, and whether they could reverse engineer the seizure protection of a ketogenic diet.

They could. Working in genetically altered mice, the researchers modified the BAD protein to reduce glucose metabolism and increase ketone body metabolism in the brain. Seizures decreased, but the benefit was erased when they knocked out the KATP channel—strong evidence that a BAD-KATP pathway conferred resistance to epileptic seizures. Further experiments suggested that it was indeed BAD’s role in metabolism, not cell death that mattered. The findings make the BAD protein a promising target for new epilepsy drugs.

"Diet sounds like this wholesome way to treat seizures, but it’s very hard. I mean, diets in general are hard, and this diet is really hard," said Yellen, whose wife’s Center for Dietary Therapy in Epilepsy hosts a candy-free Halloween party for its many patients on the ketogenic diet. “So finding a pharmacological substitute for this would make lots of people really happy.”

Provided by Harvard Medical School

Source: medicalxpress.com

May 23, 201210 notes
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Treating pain with transplants

May 23, 2012

A new study finds that transplanting embryonic cells into adult mouse spinal cord can alleviate persistent pain. The research, published by Cell Press in the May 24th issue of the journal Neuron, suggests that reduced pain results from successful integration of the embryonic cells into the host spinal cord. The findings open avenues for clinical strategies aimed not just at treating the symptoms of chronic debilitating pain, but correcting the underlying disease pathology.

There are two major classes of chronic pain: inflammatory pain that results from injury to tissue, such as muscle and bone, and neuropathic pain from injury to nerves, for example, in the limbs or face. Damage to nerves can occur after physical trauma and from chemotherapy drugs. With neuropathic pain, the pain occurs in the absence of stimulation, and there is hypersensitivity and exacerbated pain to stimuli that would not normally cause pain. Neuropathic pain is thought to involve the loss of inhibitory neurons that release the chemical GABA, which is an inhibitory neurotransmitter that controls the excitability of neurons, including neurons that transmit pain information.

"Pharmacological approaches to managing neuropathic pain enhance GABA-mediated inhibition. However, some patients do not respond to these therapies and there are significant adverse side effects," explains senior study author, Dr. Allan Basbaum from the University of California, San Francisco. "Therefore, new therapeutic approaches for neuropathic pain are essential." Dr. Basbaum and colleagues explored whether replacement of the damaged inhibitory neurons might be useful for reducing neuropathic pain.

The researchers transplanted immature GABA neurons from mouse fetal brain into the spinal cord of mice with nerve injury-induced pain, a model for human neuropathic pain. The transplanted cells not only survived, but made connections with appropriate targets and integrated into the host spinal cord circuitry. This resulted in an almost complete reversal of the mechanical hypersensitivity generated in a nerve injury model of neuropathic pain. In contrast, the transplant procedure was not effective at reducing pain in a mouse model of inflammatory pain, which is induced by tissue injury.

Taken together, the findings have exciting implications for a cell-based treatment of neuropathic pain in humans. “Our strategy not only ameliorates the symptoms of neuropathic pain but, importantly, is also potentially disease modifying,” concludes Dr. Basbaum. “It is worth considering whether transplants such as these might have clinical utility in humans, a great advantage being that the adverse side effects associated with drug administration can be avoided.”

Provided by Cell Press

Source: medicalxpress.com

May 23, 20124 notes
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Dementia patients reveal how we construct a picture of the future

May 23, 2012

(Medical Xpress) — Our ability to imagine and plan our future depends on brain regions that store general knowledge, new research shows.

Dr. Muireann Irish from Neuroscience Research Australia (NeuRA) found that dementia patients who can no longer recall general knowledge – for example, the names of famous people or popular songs – are also unable to imagine themselves in the future.

"We already know that if memory of past events is compromised, as is the case in Alzheimer’s disease, then the ability to imagine future scenarios is also impaired,” says Dr. Irish.

"We have now discovered that damage to parts of the brain that store knowledge of facts and meanings can also produce the same effect," she says.

Thinking about the future is an important ability because it helps us to plan and anticipate the consequences of our actions.

"For example, a person with dementia who may leave the oven on, partly because they forget the appropriate action, but also because they cannot project forward in time to anticipate the dangerous consequences this might have," says Dr. Irish.

Dr. Irish and colleagues used MRI to study people with Alzheimer’s disease (memories of past experiences are lost) as well as patients with semantic dementia who have lost the ability to remember facts (semantic memory) but have little problem remembering past experiences.

Surprisingly, she found that the semantic dementia group was as impaired as the Alzheimer’s group when imagining future events, even though their memory of past experiences was relatively intact.

"This is an important finding, as it points to multiple regions in the brain that are responsible for our ability to imagine and plan for the future,” she says.

Provided by Neuroscience Research Australia

Source: medicalxpress.com

May 23, 201210 notes
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Discoveries Into Perception Via Popular Magic Tricks

ScienceDaily (May 22, 2012) — Researchers at Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center have unveiled how and why the public perceives some magic tricks in recent studies that could have real-world implications in military tactics, marketing and sports.

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A professional magician believed that if he moved his hand in a straight line while performing a trick the audience would focus on the beginning and end points of the motion, but not in between. In contrast, he believed if he moved his hand in a curved motion the audience would follow his hand’s trajectory from beginning to end. (Credit: © luzitanija / Fotolia)

Susana Martinez-Conde, PhD, of Barrow’s Laboratory of Visual Neuroscience, and Stephen Macknik, PhD, of Barrow’s Laboratory of Behavioral Neurophysiology are well known for their research into magic and illusions. Their most recent original research projects, published in Frontiers in Human Neuroscience, offer additional insight into perception and cognition.

One of the studies was initiated by professional magician Apollo Robbins, who believed that audience members directed their attention differently depending on the type of hand motion used. Robbins believed that if he moved his hand in a straight line while performing a trick the audience would focus on the beginning and end points of the motion, but not in between. In contrast, he believed if he moved his hand in a curved motion the audience would follow his hand’s trajectory from beginning to end.

By studying the eye movements of individuals as they watched Robbins perform, Barrow researchers confirmed Robbins’ theory. Perhaps more importantly, they also found that the different types of hand motion triggered two different types of eye movement. The researchers discovered that curved motion engaged smooth pursuit eye movements (in which the eye follows a moving object smoothly), whereas straight motion led to saccadic eye movements (in which the eye jumps from one point of interest to another).

"Not only is this discovery important for magicians, but the knowledge that curved motion attracts attention differently from straight motion could have wide-reaching implications — for example, in predator-prey evasion techniques in the natural world, military tactics, sports strategies and marketing," says Martinez-Conde. This finding is believed to be the first discovery in the neuroscientific literature initiated by a magician, rather than a scientist.

In another study, the researchers worked with professional magician Mac King to investigate magicians’ use of social cues — like the position of their gaze — to misdirect observers.

They studied a popular coin-vanishing trick, in which King tosses a coin up and down in his right hand before “tossing” it to his left hand, where it subsequently disappears. In reality, the magician only simulates tossing the coin to the left hand, an implied motion that essentially tricks the neurons into responding as they would have if the coin had actually been thrown.

The Barrow researchers discovered that social misdirection does not always help magic. By presenting two different videos of King — one in which the audience could see his face and another in which his face was hidden — they found that social misdirection did not play a role in this particular trick.

"We wondered if the observer’s perception of magic was going to be different if they could see the magician’s head and eye position. To our surprise, it didn’t matter," says Martinez-Conde. "This indicates that social misdirection in magic is more complicated than previously believed, and not necessary for the perception of all magic tricks."

Source: Science Daily

May 23, 20124 notes
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Neuron-Nourishing Cells Appear to Retaliate in Alzheimer's

ScienceDaily (May 22, 2012) — When brain cells start oozing too much of the amyloid protein that is the hallmark of Alzheimer’s disease, the astrocytes that normally nourish and protect them deliver a suicide package instead, researchers report.

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Drs. Michael Dinkins (from left), Guanghu Wang and Erhard Bieberich. (Credit: Image courtesy of Georgia Health Sciences University)

Amyloid is excreted by all neurons, but rates increase with aging and dramatically accelerate in Alzheimer’s. Astrocytes, which deliver blood, oxygen and nutrients to neurons in addition to hauling off some of their garbage, get activated and inflamed by excessive amyloid.

Now researchers have shown another way astrocytes respond is by packaging the lipid ceramide with the protein PAR-4, which independently can do damage but together are a more “deadly duo,” said Dr. Erhard Bieberich, biochemist at the Medical College of Georgia at Georgia Health Sciences University.

"If the neuron makes something toxic and dumps it at your door, what would you do?" said Bieberich, corresponding author of the study published in the Journal of Biological Chemistry. “You would probably do something to defend yourself.”

The researchers hypothesize that this lipid-coated package ultimately kills them both, which could help explain the brain-cell death and shrinkage that occurs in Alzheimer’s. “If the astrocytes die, the neurons die,” Bieberich said, noting studies suggest that excess amyloid alone does not kill brain cells. “There must be a secondary process toxifying the amyloid; otherwise the neuron would self-intoxicate before it made a big plaque,” he said. “The neuron would die first.”

One of many avenues for future pursuit include whether a ceramide antibody could be a viable Alzheimer’s treatment. In the researchers’ studies of brain cells of humans with Alzheimer’s as well as an animal model of the disease, antibodies to ceramide and Par-4 prevented astrocytes’ amyloid-induced death.

Ceramide and Par-4 get packaged in lipid-coated vesicles called exosomes; all cells secrete thousands of these vesicles but scientists are only beginning to understand their normal function. When exosomes become deadly, they are called apoxosomes.

Ceramide and Par-4 are typically not in a vesicle, rather in two distinct parts of a cell. Ceramide appears to take the lead in bringing the two together when confronted with amyloid. Bieberich and colleagues at the University of Georgia reported in 2003 that the deadly duo helps eliminate duplicate brain cells that occur early in brain development when their survival could result in a malformed brain. They suspected then that the duo might also have a role in Alzheimer’s.

Risk factors for Alzheimer’s include aging, family history and genetics, according to the Alzheimer’s Association. Increasing evidence suggests that Alzheimer’s also shares many of the same risk factors for cardiovascular disease, such as high cholesterol, high blood pressure and inactivity.

Source: Science Daily

May 22, 20125 notes
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Learning and memory: The role of neo-neurons revealed

May 22, 2012

(Medical Xpress) — Researchers at the Institut Pasteur and the CNRS have recently identified in mice the role played by neo-neurons formed in the adult brain. By using selective stimulation the researchers were able to show that these neo-neurons increase the ability to learn and memorize difficult cognitive tasks. This newly discovered characteristic of neo-neurons to assimilate complex information could open up new avenues in the treatment of some neurodegenerative diseases. This publication is available online on the Nature Neuroscience journal’s website.

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Section of a mouse brain observed using a fluorescence microscope. The green filaments represent neo-neurons in an organized network. Credit: Institut Pasteur

The discovery that new neurons could be formed in the adult brain created quite a stir in 2003 by debunking the age-old belief that a person is born with a set number of neurons and that any loss of neurons is irreversible. This discovery was all the more incredible considering that the function of these new neurons remained undetermined. That is, until today.

Using mice models the team working under Pierre-Marie Lledo, head of the Laboratory for Perception and Memory (Institut Pasteur/CNRS) recently revealed the role of these neo-neurons formed in the adult brain with respect to learning and memory. With the help of an experimental approach using optogenetics, developed by this very same team and published in December 2010, the researchers were able to show that when stimulated by a brief flash of light these neo-neurons facilitate both learning and the memorization of complex tasks. This resulted in mice models that were able to memorize information given during the learning activity more quickly and remember exercises even 50 days after experimentation had ended. The study also shows that neo-neurons generated just after birth hold no added advantages as relates to either learning or memory. In this respect it is only the neurons produced by the adult brain that have any considerable significance.

“This study shows that the activity of just a few neurons produced in the adult brain can still have considerable effects on cognitive processes and behavior. Moreover, this work helps to illustrate how the brain assimilates new stimulations seeing as normally electrical activity (which we mimic using flashes of light) is produced within the brain’s attention centers”, explains the study’s director Pierre-Marie Lledo.

Beyond simply discovering the functional contribution of these neo-neurons, the study has also reaffirmed the clear link between “mood” (defined here by a specific pattern of stimulation) and cerebral activity. It has been shown that curiosity, attentiveness and pleasure all promote the formation of neo-neurons and consequently the acquisition of new cognitive abilities. Conversely, a state of depression is detrimental to the production of new neurons and triggers a vicious cycle which prolongs this state of despondency. These results, and the optogenetics technologies that enabled this study, may prove very useful for devising therapeutic protocols which aim to counter the development of neurologic or psychiatric diseases.

Provided by CNRS

Source: medicalxpress.com

May 22, 201219 notes
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GPS for the brain: Researchers develop new brain map

May 22, 2012

University of Georgia researchers have developed a map of the human brain that shows great promise as a new guide to the inner workings of the body’s most complex and critical organ.

With this map, researchers hope to create a next-generation brain atlas that will be an alternative option to the atlas created by German anatomist Korbinian Brodmann more than 100 years ago, which is still commonly used in clinical and research settings.

Tianming Liu, assistant professor of computer science in the UGA Franklin College of Arts and Sciences, and his students Dajiang Zhu and Kaiming Li identified 358 landmarks throughout the brain related to memory, vision, language, arousal regulation and many other fundamental bodily operations. Their findings were published in the April issue of Cerebral Cortex.

The landmarks were discovered using diffusion tensor imaging, a sophisticated neuroimaging technique that allows scientists to visualize nerve fiber connections throughout the brain. Unlike many other neuroimaging studies, their map does not focus only on one section of the brain but rather the whole cerebral cortex.

"Previously, researchers would examine at most three or four small brain networks," Liu said. "We want to examine the whole brain connection, and this is the so-called connectome."

The new map provides a clearer picture of how different areas of the brain are physically connected and how these connections relate to basic brain function. Liu and his team examined hundreds of healthy young adults to establish the landmarks, which they call dense individualized and common connectivity-based cortical landmarks, or DICCCOL.

After extensive testing and comparison, the team determined that these nodes are present in every normal brain, meaning they can be used as a basis of comparison for those with damaged brain tissue or altered brain function.

"DICCCOL is very similar to a GPS system," Zhu said, "only it’s a GPS map of the human brain."

Now, thanks in part to a five-year, $1.6 million grant from the National Institutes of Health, Liu and collaborators Xiaoping Hu and Claire Coles at Emory University are preparing to test their brain map by comparing healthy brains with those of children whose brains were damaged by exposure to cocaine while in the womb.

Prenatal cocaine exposure, or PCE, can cause serious damage to brain networks. Because of this, analysis of the damage provides Liu and his team with an excellent opportunity to evaluate the usefulness of their map.

After comparing the PCE brains to those of healthy individuals, they hope to determine the segments of the brain responsible for physical or mental disabilities observed in children exposed to cocaine.

"The PCE brain is disrupted in a systematic way; the whole brain is wrongly wired," Liu said. "We want to test our map in one of the worst cases, and then we will know if it will work in other cases."

Once the robustness of their map is established, Liu and his team hope that it may prove useful in the evaluation of many other brain disorders, such as Alzheimer’s disease, Parkinson’s disease or stroke.

"This really is a fundamental technology," Liu said. "When we establish these DICCCOLS, we can very easily extend this project to other populations, to other brain diseases."

More information: Liu’s team published their DICCCOL data sets, which includes the source code and diffusion tensor images, at http://dicccol.cs.uga.edu so other researchers may use the findings in their own experiments.

The article, “DICCCOL: Dense Individualized and Common Connectivity-Based Cortical Landmarks,” is available at http://cercor.oxfordjournals.org/content/early/2012/04/05/cercor.bhs072.short

Provided by University of Georgia

Source: medicalxpress.com

May 22, 20129 notes
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Seventy-Two Percent of Teenagers Experienced Reduced Hearing Ability After Attending Concert

ScienceDaily (May 21, 2012) — Seventy-two percent of teenagers participating in a study experienced reduced hearing ability following exposure to a pop rock performance by a popular female singer.

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Seventy-two percent of teenagers participating in a study experienced reduced hearing ability following exposure to a pop rock performance by a popular female singer. (Credit: © DWP / Fotolia)

M. Jennifer Derebery, MD, House Clinic physician, along with the House Research Institute tested teens’ hearing before and after a concert and presented the study findings at the American Otologic Society meeting on April 21, 2012. The study has been accepted for publication in an upcoming issue of Otology & Neurotology.

The hearing loss that may be experienced after a pop rock concert is not generally believed to be permanent. It is called a temporary threshold shift and usually disappears within 16-48 hours, after which a person’s hearing returns to previous levels.

“Teenagers need to understand a single exposure to loud noise either from a concert or personal listening device can lead to hearing loss,” said M. Jennifer Derebery, MD, lead author and physician at the House Clinic. “With multiple exposures to noise over 85 decibels, the tiny hair cells may stop functioning and the hearing loss may be permanent.”

In the study, twenty-nine teenagers were given free tickets to a rock concert. To ensure a similar level of noise exposure for the teens, there were two blocks of seats within close range of each other. The seats were located in front of the stage at the far end of the venue approximately 15-18 rows up from the floor.

Parental consent was obtained for all of the underage study participants. The importance of using hearing protection was explained to the teenagers. Researchers then offered hearing protection to the subjects and encouraged them to use the foam ear plugs. However, only three teenagers chose to do so.

Three adult researchers sat with the teenagers. Using a calibrated sound pressure meter, 1,645 measurements of sound decibel (dBA) levels were recorded during the 26 songs played during the three hour concert. The sound levels ranged from 82-110 dBA, with an average of 98.5 dBA. The mean level was greater than 100 dBA for 10 of the 26 songs.

The decibel levels experienced at the concert exceeded what is allowable in the workplace, according to Occupational Safety and Health Administration (OSHA). OSHA safe listening guidelines set time limits for exposures to sound levels of 85 dB and greater in the workplace. The volumes recorded during the concert would have violated OSHA standards in less than 30 minutes. In fact, one third of the teen listeners showed a temporary threshold shift that would not be acceptable in adult workplace environments.

Following the concert, the majority of the study participants also were found to have a significant reduction in the Distortion Product Otoacoustic Emissions (OAE) test. This test checks the function of the tiny outer hair cells in the inner ear that are believed to be the most vulnerable to damage from prolonged noise exposure, and are crucial to normal hearing, the ability to hear soft (or low level sounds), and the ability to understand speech, especially in noisy environments. With exposure to loud noise, the outer hair cells show a reduction in their ability to function, which may later recover. However, it is known that with repeated exposure to loud noise, the tiny hair cells may become permanently damaged. Recent animal research suggests that a single exposure to loud noise may result in permanent damage to the hearing nerve connections themselves that are necessary to hear sound.

Following the concert, 53.6 percent of the teens said they did not think they were hearing as well after the concert. Twenty-five percent reported they were experiencing tinnitus or ringing in their ears, which they did not have before the concert.

Researchers are especially concerned, because in the most recent government survey on health in the United States National Health and Nutrition Examination Survey (NHANES) 2005-2006, 20% of adolescents were found to have at least slight hearing loss, a 31% increase from a similar survey done from 1988-1994.

The findings of the study clearly indicate more research is necessary to determine if the guidelines for noise exposure need to be revised for teenagers. More research is also needed to determine if teenager’s ears are more sensitive to noise than adults.

“It also means we definitely need to be doing more to ensure the sound levels at concerts are not so loud as to cause hearing loss and neurological damage in teenagers, as well as adults,” said Derebery. “Only 3 of our 29 teens chose to use ear protection, even when it was given to them and they were encouraged to do so. We have to assume this is typical behavior for most teen listeners, so we have the responsibility to get the sound levels down to safer levels.”

Researchers recommend teenagers and young adults take an active role in protecting their hearing by utilizing a variety of sound meter ‘apps’ available for smart phones. The sound meters will give a rough estimate of the noise level allowing someone to take the necessary steps to protect their hearing such as wearing ear plugs at a concert.

In addition, Derebery and the study co-authors would like to see concert promoters and the musicians themselves take steps to lower sound levels as well as encourage young concert goers to use hearing protection.

Source: Science Daily

May 22, 20126 notes
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What Baboons Can Teach Us About Social Status

ScienceDaily (May 21, 2012) — Turns out it’s not bad being top dog, or in this case, top baboon.

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Wounded baboon. (Credit: Image courtesy of University of Notre Dame)

A new study by University of Notre Dame biologist Beth Archie and colleagues from Princeton and Duke Universities finds that high-ranking male baboons recover more quickly from injuries and are less likely to become ill than other males.

Archie, Jeanne Altmann of Princeton and Susan Alberts of Duke examined health records from the Amboseli Baboon Research Project in Kenya. They found that high rank is associated with faster wound healing. The finding is somewhat surprising, given that top-ranked males also experience high stress, which should suppress immune responses. They also found that social status is a better predictor of wound healing than age.

"In humans and animals, it has always been a big debate whether the stress of being on top is better or worse than the stress of being on the bottom," said Archie, lead researcher on the study. "Our results suggest that, while animals in both positions experience stress, several factors that go along with high rank might serve to protect males from the negative effects of stress."

"The power of this study is in identifying the biological mechanisms that may confer health benefits to high-ranking members of society," said George Gilchrist, program director in the National Science Foundation (NSF)’s Division of Biology, which funded the research. "We know that humans have such benefits, but it took meticulous long-term research on baboon society to tease out the specific mechanisms. The question remains of causation: Is one a society leader because of stronger immune function or vice versa?"

The researchers examined 27 years of data on naturally occurring illness and injuries in wild male baboons, which is a notably large data set. Although research of health and disease in animals in laboratory settings has been quite extensive, this study is one of most comprehensive ever conducted on animals in a natural setting.

The research team investigated how differences in age, physical condition, stress, reproductive effort and testosterone levels contribute to status-related differences in immune functions. Previous research found that high testosterone levels and intense reproductive efforts can suppress immune function and are highest among high-ranking males.

However, Archie and her colleagues found that high-ranking males were less likely to become ill and recovered faster from injuries and illnesses than low-ranking males. The authors suggest that chronic stress, old age and poor physical condition associated with low rank may suppress immune function in low-ranking males.

"The complex interplay among social context, physiology and immune system-mediated health costs and benefits illustrates the power of interdisciplinary research," said Carolyn Ehardt, NSF program director for biological anthropology, which co-funded the research. "This research begins to tease apart the trade-offs in both high and low status in primates, including ourselves, which may lead to understanding the effects of social status on death and disease — not inconsequential for society as a whole."

Source: Science Daily

May 22, 20127 notes
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Newly Discovered Protein Makes Sure Brain Development Isn't 'Botched'

ScienceDaily (May 21, 2012) — Johns Hopkins scientists have discovered a protein that appears to play an important regulatory role in deciding whether stem cells differentiate into the cells that make up the brain, as well as countless other tissues. This finding, published in the April Developmental Cell, could eventually shed light on developmental disorders as well as a variety of conditions that involve the generation of new neurons into adulthood, including depression, stroke, and posttraumatic stress disorder.

Researchers have long known that a small group of proteins called Notch plays a pivotal role in helping the immature cells present in embryos to develop into the variety of cells present throughout the body, including those that make up the brain, blood, kidneys and muscles.

"Notch signaling is involved in almost all aspects of tissue development," explains study leader Valina Dawson, Ph.D., a professor in the departments of Neurology, Neuroscience, and Physiology and co-director of the Stem Cell and Neuroregeneration Programs at the Institute for Cell Engineering at the Johns Hopkins University School of Medicine.

However, she says, even for researchers who have been studying Notch for decades, how this small group of proteins manages the development of such a diverse array of tissues and organs in the body remains unknown. It’s a pivotal mystery to solve, Dawson adds, since problems in Notch signaling seem to be involved in various cancers, Alzheimer’s disease, juvenile stroke and many other health problems.

In their new study, Dawson and her colleagues shed light on one way Notch proteins might be regulated, through a protein they recently discovered in the lab. This protein seemed to be involved in development, but at first, the researchers didn’t know its function.

To determine what purpose this protein serves in cells, Dawson, postdoctoral fellow Zhikai Chi, M.D., Ph.D., and their colleagues started by trying to determine what other proteins it’s able to bind to. By adding the mystery protein to cell cultures that expressed a variety of other proteins, they determined that the unknown protein altered cellular activity in those expressing Notch.

Since Notch is involved intimately in determining the fate of brain precursor cells, driving neural stem cells to proliferate and determining whether they become neurons or supporting cells known as glia, the researchers next examined how this mystery protein affected brain development in mouse embryos. They found that by increasing expression of the unknown protein, more neurons developed in certain parts of the developing brain, including the intermediate zone and cortical plate. In contrast, decreasing expression led to fewer neurons. Taken together, Dawson says, these experiments provided even more evidence that their unknown protein was somehow influencing Notch.

To determine exactly how the mystery protein was affecting Notch, the researchers examined the effect of the protein on neural stem cells in the process of differentiating into mature cell types. Increasing the amount of the unknown protein swayed development as if Notch wasn’t working. Since the unknown protein appeared to prevent Notch from acting on cells, the researchers named it Botch for “blocks Notch.”

With Botch’s role now clear, the researchers turned next to the mechanism behind how this protein exerts its influence. A series of experiments suggests that Botch interacts with Notch in the Golgi body, a cellular organelle involved in modifying proteins. For Notch to act in development, an immature version of this protein needs to be cleaved in order for the protein to be rearranged. Botch appears to prevent this pivotal modification from taking place, reducing the amount of mature Notch available to do its job.

Because Botch appears to play such an important role in regulating Notch, Dawson says, it could be involved in a number of diseases in which the generation of new neurons is misregulated. She and her colleagues are already performing some preliminary experiments to determine whether Botch expression might vary from the norm in diseases such as depression, which has been linked to a decrease in neurogenesis in the brain’s hippocampus. Eventually, researchers might be able to develop drugs that act on Botch to restart stalled neurogenesis, potentially treating depression and other diseases in which a lack of neurogenesis is thought to play a role.

"There are potentially some very large neurological problems that could be addressed through changing Botch activity," Dawson says.

Source: Science Daily

May 22, 20126 notes
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Weight struggles? Blame new neurons in your hypothalamus

May 21, 2012

New nerve cells formed in a select part of the brain could hold considerable sway over how much you eat and consequently weigh, new animal research by Johns Hopkins scientists suggests in a study published in the May issue of Nature Neuroscience.

The idea that the brain is still forming new nerve cells, or neurons, into adulthood has become well-established over the past several decades, says study leader Seth Blackshaw, Ph.D., an associate professor in the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine. However, he adds, researchers had previously thought that this process, called neurogenesis, only occurs in two brain areas: the hippocampus, involved in memory, and the olfactory bulb, involved in smell.

More recent research suggests that a third area, the hypothalamus — associated with a variety of bodily functions, including sleep, body temperature, hunger and thirst — also produces new neurons. However, the precise source of this neurogenesis and the function of these newborn neurons remained a mystery.

To answer these questions, Blackshaw and his colleagues used mice as a model system. The researchers started by investigating whether any particular part of the hypothalamus had a high level of cell growth, suggesting that neurogenesis was occurring. They injected the animals with a compound called bromodeoxyuridine (BrdU), which selectively incorporates itself into newly replicating DNA of dividing cells, where it’s readily detectable. Within a few days, the researchers found high levels of BrdU in an area of the hypothalamus called the median eminence, which lies on the base of the brain’s fluid-filled third ventricle.

Further tests showed that these rapidly proliferating cells were tanycytes, a good candidate for producing new neurons since they have many characteristics in common with cells involved in neurogenesis during early development. To confirm that tanycytes were indeed producing new neurons and not other types of cells, Blackshaw and his colleagues selectively bred mice that produced a fluorescent protein only in their tanycytes. Within a few weeks, they found neurons that also fluoresced, proof that these cells came from tanycyte progenitors.

With the source of hypothalamic neurogenesis settled, the researchers turned to the question of function. Knowing that many previous studies have suggested that animals raised on a high-fat diet are at significantly greater risk of obesity and metabolic syndrome as adults, Blackshaw’s team wondered whether hypothalamic neurogenesis might play a role in this phenomenon.

The researchers fed mice a diet of high-fat chow starting at weaning and looked for evidence of neurogenesis at several different time points. While very young animals showed no difference compared with mice fed normal chow, neurogenesis quadrupled in adults that had consistently eaten the high-fat chow since weaning. These animals gained more weight and had higher fat mass than animals raised on normal chow.

When Blackshaw and his colleagues killed off new neurons in the high-fat eaters by irradiating just their median eminences with precise X-ray beams, the mice gained significantly less weight and fat than animals who had eaten the same diet and were considerably more active, suggesting that these new neurons play a critical role in regulating weight, fat storage and energy expenditure.

"People typically think growing new neurons in the brain is a good thing — but it’s really just another way for the brain to modify behavior," Blackshaw explains. He adds that hypothalamic neurogenesis is probably a mechanism that evolved to help wild animals survive and helped our ancestors do the same in the past. Wild animals that encounter a rich and abundant food source would be well-served to eat as much as possible, since such a resource is typically scarce in nature.

Being exposed to such a resource during youth, and consequently encouraging the growth of neurons that would promote more food intake and energy storage in the future, would be advantageous. However, Blackshaw explains, for lab animals as well as people in developed countries, who have nearly unlimited access to abundant food, such neurogenesis isn’t necessarily beneficial — it could encourage excessive weight gain and fat storage when they’re not necessary.

If the team’s work is confirmed in future studies, he adds, researchers might eventually use these findings as a basis to treat obesity by inhibiting hypothalamic neurogenesis, either by irradiating the median eminence or developing drugs that inhibit this process.

Provided by Johns Hopkins University School of Medicine

Source: medicalxpress.com

May 22, 201212 notes
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Growth factor in stem cells may spur recovery from multiple sclerosis

May 21, 2012

A substance in human mesenchymal stem cells that promotes growth appears to spur restoration of nerves and their function in rodent models of multiple sclerosis (MS), researchers at Case Western Reserve University School of Medicine have found.

Their study appeared in the online version of Nature Neuroscience on Sunday, May 20.

In animals injected with hepatocyte growth factor, inflammation declined and neural cells grew. Perhaps most important, the myelin sheath, which protects nerves and their ability to gather and send information, regrew, covering lesions caused by the disease.

"The importance of this work is we think we’ve identified the driver of the recovery," said Robert H. Miller, professor of neurosciences at the School of Medicine and vice president for research at Case Western Reserve University.

Miller, neurosciences instructor Lianhua Bai and biology professor Arnold I. Caplan, designed the study. They worked with Project Manager Anne DeChant, and research assistants Jordan Hecker, Janet Kranso and Anita Zaremba, from the School of Medicine; and Donald P. Lennon, a research assistant from the university’s Skeletal Research Center.

In MS, the immune system attacks myelin, risking injury to exposed nerves’ intricate wiring. When damaged, nerve signals can be interrupted, causing loss of balance and coordination, cognitive ability and other functions. Over time, intermittent losses may become permanent.

Miller and Caplan reported in 2009 that when they injected human mesenchymal stem cells into rodent models of MS, the animals recovered from the damage wrought by the disease. Based on their work, a clinical trial is underway in which MS patients are injected with their own stem cells.

In this study, the researchers first wanted to test whether the presence of stem cells or something cells produce promotes recovery. They injected mice with the medium in which mesenchymal stem cells, culled from bone marrow, grew.

All 11 animals, which have a version of MS, showed a rapid reduction in functional deficits.

Analysis showed that the disease remained on course unless the molecules injected were of a certain size; that is, the molecular weight ranged between 50 and 100 kiloDaltons.

Research by others and results of their own work indicated hepatocyte growth factor, which is secreted by mesenchymal stem cells, was a likely instigator.

The scientists injected animals with 50 or 100 nanograms of the growth factor every other day for five days. The level of signaling molecules that promote inflammation decreased while the level of signaling molecules that counter inflammation increased. Neural cells grew and nerves laid bare by MS were rewrapped with myelin. The 100-nanogram injections appeared to provide slightly better recovery.

To test the system further, researchers tied up cell-surface receptors, in this case cMet receptors that are known to work with the growth factor.

When they jammed the receptors with a function-blocking cMet antibody, neither the mesenchymal stem cell medium nor the hepatocyte growth factor injections had any effect on the disease. In another test, injections of an anti-hepatocyte growth factor also blocked recovery.

The researchers will continue their studies, to determine if they can screen mesenchymal stem cells for those that produce the higher amounts of hepatocyte growth factor needed for effective treatment. That could lead to a more precise cell therapy.

"Could we now take away the mesenchymal stem cells and treat only with hepatocyte growth factor?” Miller asked. “We’ve shown we can do that in an animal but it’s not clear if we can do that in a patient.”

They also plan to test whether other factors may be used to stimulate the cMet receptors and induce recovery.

Provided by Case Western Reserve University

Source: medicalxpress.com

May 21, 20124 notes
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Rare neurons discovered in monkey brains

May 21, 2012

Max Planck scientists discover brain cells in monkeys that may be linked to self-awareness and empathy in humans.

The anterior insular cortex is a small brain region that plays a crucial role in human self-awareness and in related neuropsychiatric disorders. A unique cell type – the von Economo neuron (VEN) – is located there. For a long time, the VEN was assumed to be unique to humans, great apes, whales and elephants. Henry Evrard, neuroanatomist at the Max Planck Institute for Biological Cybernetics in Tübingen, Germany, now discovered that the VEN occurs also in the insula of macaque monkeys. The morphology, size and distribution of the monkey VEN suggest that it is at least a primal anatomical homolog of the human VEN. This finding offers new and much-needed opportunities to examine in detail the connections and functions of a cell and brain region that could have a key role in human self-awareness and in mental disorders including autism and specific forms of dementia.

The insular cortex, or simply insula, is a hidden cortical region folded and tucked away deep in the brain – an island within the cortex. Within the last decade, the insula has emerged from darkness as having a key role in diverse functions usually linked to our internal bodily states, to our emotions, to our self-awareness, and to our social interactions. The very anterior part of the insula in particular is where humans consciously sense subjective emotions, such as love, hate, resentment, self-confidence or embarrassment. In relation to these feelings, the anterior insula is involved in various psychopathologies. Damage of the insula leads to apathy, and to the inability to tell what feelings we or our conversational partner experience. These inabilities and alteration of the insula are also encountered in autism and other highly detrimental neuropsychiatric disorders including the behavioural variant of frontotemporal dementia (bvFTD).

The von Economo neuron (VEN) occurs almost exclusively in the anterior insula and anterior cingulate cortex. Until recently it was believed that the VEN is only present in humans, great apes and some large-brained mammals with complex social behaviour such as whales and elephants. In contrast to the typical neighbouring pyramidal neuron that is present in all mammals and all brain regions, the VEN has a peculiar spindle shape and is about three times as large. Their numeral density is selectively altered in autism and bvFTD. Henry Evrard and his team, at the Max Planck Institute for Biological Cybernetics in Tübingen now discovered VENs in the anterior insula in macaque monkeys. His present work provides compelling evidence that monkeys possess at least a primitive form of the human VEN although they do not have the ability to recognize themselves in a mirror, a behavioural hallmark of self-awareness.

"This means, other than previously believed, that highly concentrated VEN populations are not an exclusivity of hominids, but also occurs in other primate species", explains Henry Evrard. "The VEN phylogeny needs to be reexamined. Most importantly, the very much-needed analysis of the connections and physiology of these specific neurons is now possible.” Knowing the functions of the VEN and its connections to other regions of the brain in monkeys could give us clues on the evolution of the anatomical substrate of self-awareness in humans and may help us in better understanding serious neuropsychiatric disabilities including autism, or even addictions such as to drugs or smoking.

Provided by Max Planck Society

Source: medicalxpress.com

May 21, 201220 notes
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Research holds out hope for stroke patients

May 21, 2012

(Medical Xpress) — People with a curious condition that causes them to apply make-up on only one side of their face, or ignore food on half of their plate, are playing a new role in understanding stroke recovery.

Researchers from the Queensland Brain Institute (QBI) at The University of Queensland have found the condition, a subset of the stroke called ‘unilateral spatial neglect’, tend to have the worst recovery outcomes in regaining lost functioning in their bodies, leading them to believe attention may have an important impact on recovering successfully.

Unilateral spatial neglect is typically caused by strokes on the right hand side of the brain and manifests in patients ignoring the left side of their body.

People with the condition may ignore food on the left hand side of their plate or, if asked to draw a clock, squash all 12 numbers into the right side of the clock face, leaving the other side blank.

They may also fail to shave, or to put make-up on the left side of their faces and. In severe cases, they behave as though the left side of their world does not exist.

“We know that brain plasticity plays a critical role in recovering from stroke,” says Professor Jason Mattingley, who holds the Foundation Chair in Cognitive Neuroscience at The University of Queensland.

“The fact that people with spatial neglect tend to have poorer recovery of motor function suggested to us that attention may be important for guiding plasticity following stroke.”

Current research being undertaken by the Mattingley laboratory is exploring this link.

“What we’re trying to do is explore what effect attention has on brain plasticity, and how attention might be used in neurorehabilitation” says Professor Mattingley.

Volunteers first undergo a magnetic resonance imaging (MRI) scan, which provides researchers with a three-dimensional picture of the brain.

“In terms of their structure, brains are like fingerprints – no two are exactly the same, even though superficially they seem very similar,” Professor Mattingley explains.

The MRI scan allows researchers to guide a transcranial magnetic stimulation (TMS) coil into position upon a volunteer’s scalp.

The device induces a small electrical current in the underlying brain tissue, causing it to become more active.

The researchers specifically target a part of the motor cortex that controls the thumb muscle in the left hand.

“It’s well established that the more often neurons activate at the same time, the more likely they are to communicate efficiently in the future. This is how the brain learns,” says Professor Mattingley.

“We’re exploiting that general principle in this research.”

Dr Marc Kamke, Research Fellow at QBI explains: “By adjusting the type of brain stimulation delivered we can artificially induce short-term changes that resemble naturally-occurring plasticity.”

But what the researchers have found is that the effects of stimulation upon a brain’s plasticity are dependent on attention.

“When we ask people to undertake a visual task that is irrelevant to the brain stimulation, but that demands a great deal of their attention, we observe a reduction in plasticity,” Dr Marc Kamke explains.

“When the task does not require much attention, however, the brain’s plastic response is apparent.”

“These results show that attention plays an important role in guiding brain plasticity,” says Professor Mattingley.

He adds, “while practical applications remain several steps away, this knowledge may ultimately help us develop more effective strategies for physical therapy after stroke.”

The results of the research, which was funded by the National Health and Medical Research Council of Australia, are published this week in The Journal of Neuroscience.

Provided by University of Queensland 

Source: medicalxpress.com

May 21, 2012
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Songbirds' Learning Hub in Brain Offers Insight Into Motor Control

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.

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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

May 21, 20128 notes
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Oxytocin Improves Brain Function in Children With Autism

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).

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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

May 20, 201221 notes
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How Exercise Affects the Brain: Age and Genetics Play a Role

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.

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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 19, 201215 notes
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Acid in the brain: Team develops new way to look at brain function

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.

image

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 19, 201213 notes
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With fat: What's good or bad for the heart, may be the same for the brain

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 18, 201211 notes
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Various metabolic risk factors could be linked to diabetes-related pain with major implications for treatment

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

May 18, 20121 note
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Training the Brain Could Help Reduce Pain

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

May 18, 20128 notes
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Pain Relief Through Distraction: It's Not All in Your Head

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, 20125 notes
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Suspicion resides in two regions of the brain

May 17, 2012

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

image

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

May 17, 201216 notes
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