Posts tagged neuroscience

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, 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.

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

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.

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, 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

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.

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, 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, 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.

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, 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.

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 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.

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

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