Neuroscience

June 5, 2012

(Medical Xpress) — Using transcranial magnetic stimulation (TMS), an international team led by French researchers from the Centre de Recherche de l’Institut du Cerveau (CNRS) has succeeded in enhancing the visual abilities of a group of healthy subjects. Following stimulation of an area of the brain’s right hemisphere involved in perceptual awareness and in orienting spatial attention, the subjects appeared more likely to perceive a target appearing on a screen. This work, published in the journal PLoS ONE, could lead to the development of novel rehabilitation techniques for certain visual disorders. In addition, it could help improve the performance of individuals whose tasks require very high precision.

TMS is a non-invasive technique that consists in sending a magnetic pulse into a given area of the brain. This results in an activation of the cortical neurons located within the range of the magnetic field, which modifies their activity in a painless and temporary manner. For several years, scientists have been looking at the possibility of using this technique to enhance certain brain functions in healthy subjects.

In this respect, the team led by Antoni Valero-Cabré has carried out research involving the stimulation of a region of the right cerebral hemisphere known as the frontal eye field. Strictly speaking, this is not a primary visual area but it participates in the planning of ocular movements and the orientation of each individual’s attention in the visual space. In a first experiment, a group of healthy subjects tried to distinguish a very low contrast target appearing on a screen for just 30 ms. In some of the tests, the subjects received a magnetic pulse lasting between 80 and 140 ms on this frontal region before the target appeared. The researchers found that the success rate was higher when using TMS. The visual sensitivity of healthy subjects was temporarily increased by around 12%. In a second experiment, the subjects were shown a fleeting visual cue indicating the spot where the target could appear. In this configuration, the enhancement of visual sensitivity, which remained of the same order, was only apparent when the cue indicated the correct location of the target.

Although cerebral functions such as conscious vision are highly optimized in healthy adults, these results show that there is a significant margin for improvement, which can be “enhanced” by TMS. This technique could be tested for the rehabilitation of patients suffering from cortical damage, due for example to a cardiovascular accident, and for that of patients with retinal disorders. The second experiment suggests that rehabilitation based on both TMS and visual cues could be more selective than the use of stimulation alone. The researchers want to further explore this possibility using repetitive TMS, which, in this case, could make it possible to obtain long-lasting modification of cerebral activity.

Furthermore, according to the researchers, TMS could be used in the near future to increase the attentional abilities of individuals performing tasks that require good visual skills.

Provided by CNRS

Source: medicalxpress.com

June 5, 2012

Researchers studying stroke patients have found a strong association between impairments in a network of the brain involved in emotional regulation and the severity of post-stroke depression. Results of the study are published online in the journal Radiology.

"A third of patients surviving a stroke experience post-stroke depression (PSD),” said lead researcher Igor Sibon, M.D., Ph.D., professor of neurology at the University of Bordeaux in Bordeaux, France. “However, studies have failed to identify a link between lesions in the brain caused by ischemia during a stroke and subsequent depression.”

Instead of looking for dysfunction in a specific area of the brain following a stroke, Dr. Sibon’s study was designed to assess a group of brain structures organized in a functional network called the default-mode network (DMN). Modifications of connectivity in the DMN, which is associated with internally generated thought processes, has been observed in depressive patients.

"The default-mode network is activated when the brain is at rest," Dr. Sibon said. "When the brain is not actively involved in a task, this area of the brain is engaged in internal thoughts involving self-related memory retrieval and processing.”

In the study, 24 patients between the ages of 18 and 80 underwent resting-state functional magnetic resonance imaging (fMRI) 10 days after having mild to moderate ischemic stroke. An fMRI imaging study measures metabolic changes in specific areas of the brain. Although many fMRI exams are designed to measure brain changes while a patient performs a specific task, during a resting-state fMRI exam, patients lie motionless.

The patients, which included 19 men and five women, were also clinically evaluated 10 days and three months post-stroke to determine the presence and severity of depression and anxiety symptoms. At three months post-stroke, patients were evaluated for depression using the DSM-IV diagnostic classification system.

Using the DSM-IV criteria, 10 patients had minor to moderate depression, and 14 patients had no depression. Results of the fMRI exams revealed an association between modifications of connectivity in the DMN 10 days after stroke and the severity of depression three months post-stroke.

"We found a strong association between early resting-state network modifications and the risk of post-stroke mood disorders," Dr. Sibon said. "These results support the theory that functional brain impairment following a stroke may be more critical than structural lesions."

According to Dr. Sibon, the widespread chemical changes that result from a stroke may lead to the modification of connectivity in brain networks such as the DMN. He said results of his study may contribute to the clinical management of stroke patients by providing an opportunity to investigate the effects of a variety of treatments on patients whose fMRI results immediately post-stroke indicate impaired connectivity in the DMN.

Provided by Radiological Society of North America

Source: medicalxpress.com

June 4, 2012

A nuzzle of the neck, a stroke of the wrist, a brush of the knee—these caresses often signal a loving touch, but can also feel highly aversive, depending on who is delivering the touch, and to whom. Interested in how the brain makes connections between touch and emotion, neuroscientists at the California Institute of Technology (Caltech) have discovered that the association begins in the brain’s primary somatosensory cortex, a region that, until now, was thought only to respond to basic touch, not to its emotional quality.

The new finding is described in this week’s issue of the Proceedings of the National Academy of Sciences (PNAS).

The team measured brain activation while self-identified heterosexual male subjects lay in a functional MRI scanner and were each caressed on the leg under two different conditions. In the first condition, they saw a video of an attractive female bending down to caress them; in the second, they saw a video of a masculine man doing the same thing. The men reported the experience as pleasurable when they thought the touch came from the woman, and aversive when they thought it came from the man. And their brains backed them up: this difference in experience was reflected in the activity measured in each man’s primary somatosensory cortex.

"We demonstrated for the first time that the primary somatosensory cortex—the brain region encoding basic touch properties such as how rough or smooth an object is—also is sensitive to the social meaning of a touch," explains Michael Spezio, a visiting associate at Caltech who is also an assistant professor of psychology at Scripps College in Claremont, California. "It was generally thought that there are separate brain pathways for how we process the physical aspects of touch on the skin and for how we interpret that touch emotionally—that is, whether we feel it as pleasant, unpleasant, desired, or repulsive. Our study shows that, to the contrary, emotion is involved at the primary stages of social touch."

Unbeknownst to the subjects, the actual touches on their leg were always exactly the same—and always from a woman. Yet, it felt different to them when they believed a man versus a woman was doing the touching.

"The primary somatosensory cortex responded more to the ‘female’ touch than to the ‘male’ touch condition, even while subjects were only viewing a video showing a person approach their leg," says Ralph Adolphs, Bren Professor of Psychology and Neuroscience at Caltech and director of the Caltech Brain Imaging Center, where the research was done. "We see responses in a part of the brain thought to process only basic touch that were elicited entirely by the emotional significance of social touch prior to the touch itself, simply in anticipation of the caress that our participants would receive."

The study was carried out in collaboration with the husband-and-wife team of Valeria Gazzola and Christian Keysers, who were visiting Caltech from the University of Groningen in the Netherlands.

"Intuitively, we all believe that when we are touched by someone, we first objectively perceive the physical properties of the touch—its speed, its gentleness, the roughness of the skin," says Gazzola. "Only thereafter, in a separable second step based on who touched us, do we believe we value this touch more or less."

The experiment showed that this two-step vision is incorrect, at least in terms of separation between brain regions, she says, and who we believe is touching us distorts even the supposedly objective representation of what the touch was like on the skin.

"Nothing in our brain is truly objective," adds Keysers. "Our perception is deeply and pervasively shaped by how we feel about the things we perceive."

One possible practical implication of the work is to help reshape social responses to touch in people with autism.

"Now that we have clear evidence that primary somatosensory cortex encodes emotional significance of touch, it may be possible to work with early sensory pathways to help children with autism respond more positively to the gentle touch of their parents and siblings," says Spezio.

The work also suggests that it may be possible to use film clips or virtual reality to reestablish positive responses to gentle touch in victims of sexual and physical abuse, and torture.

Next, the researchers hope to test whether the effect is as robust in women as in men, and in both sexes across sexual orientation. They also plan to explore how these sensory pathways might develop in infants or children.

Provided by California Institute of Technology

Source: medicalxpress.com

ScienceDaily (June 4, 2012) — Those cups of coffee that you drink every day to keep alert appear to have an extra perk — especially if you’re an older adult. A recent study monitoring the memory and thinking processes of people older than 65 found that all those with higher blood caffeine levels avoided the onset of Alzheimer’s disease in the two-to-four years of study follow-up. Moreover, coffee appeared to be the major or only source of caffeine for these individuals.

Those cups of coffee that you drink every day to keep alert appear to have an extra perk — especially if you’re an older adult. A recent study monitoring the memory and thinking processes of people older than 65 found that all those with higher blood caffeine levels avoided the onset of Alzheimer’s disease in the two-to-four years of study follow-up. (Credit: © Yuri Arcurs / Fotolia)

Researchers from the University of South Florida and the University of Miami say the case control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset. Their findings will appear in the online version of an article to be published June 5 in the Journal of Alzheimer’s Disease. The collaborative study involved 124 people, ages 65 to 88, in Tampa and Miami.

"These intriguing results suggest that older adults with mild memory impairment who drink moderate levels of coffee — about 3 cups a day — will not convert to Alzheimer’s disease — or at least will experience a substantial delay before converting to Alzheimer’s," said study lead author Dr. Chuanhai Cao, a neuroscientist at the USF College of Pharmacy and the USF Health Byrd Alzheimer’s Institute. "The results from this study, along with our earlier studies in Alzheimer’s mice, are very consistent in indicating that moderate daily caffeine/coffee intake throughout adulthood should appreciably protect against Alzheimer’s disease later in life."

The study shows this protection probably occurs even in older people with early signs of the disease, called mild cognitive impairment, or MCI. Patients with MCI already experience some short-term memory loss and initial Alzheimer’s pathology in their brains. Each year, about 15 percent of MCI patients progress to full-blown Alzheimer’s disease. The researchers focused on study participants with MCI, because many were destined to develop Alzheimer’s within a few years.

Blood caffeine levels at the study’s onset were substantially lower (51 percent less) in participants diagnosed with MCI who progressed to dementia during the two-to-four year follow-up than in those whose mild cognitive impairment remained stable over the same period.

No one with MCI who later developed Alzheimer’s had initial blood caffeine levels above a critical level of 1200 ng/ml — equivalent to drinking several cups of coffee a few hours before the blood sample was drawn. In contrast, many with stable MCI had blood caffeine levels higher than this critical level.

"We found that 100 percent of the MCI patients with plasma caffeine levels above the critical level experienced no conversion to Alzheimer’s disease during the two-to-four year follow-up period," said study co-author Dr. Gary Arendash.

The researchers believe higher blood caffeine levels indicate habitually higher caffeine intake, most probably through coffee. Caffeinated coffee appeared to be the main, if not exclusive, source of caffeine in the memory-protected MCI patients, because they had the same profile of blood immune markers as Alzheimer’s mice given caffeinated coffee. Alzheimer’s mice given caffeine alone or decaffeinated coffee had a very different immune marker profile.

Since 2006, USF’s Dr. Cao and Dr. Arendash have published several studies investigating the effects of caffeine/coffee administered to Alzheimer’s mice. Most recently, they reported that caffeine interacts with a yet unidentified component of coffee to boost blood levels of a critical growth factor that seems to fight off the Alzheimer’s disease process.

"We are not saying that moderate coffee consumption will completely protect people from Alzheimer’s disease," Dr. Cao cautioned. "However, we firmly believe that moderate coffee consumption can appreciably reduce your risk of Alzheimer’s or delay its onset."

Alzheimer’s pathology is a process in which plaques and tangles accumulate in the brain, killing nerve cells, destroying neural connections, and ultimately leading to progressive and irreversible memory loss. Since the neurodegenerative disease starts one or two decades before cognitive decline becomes apparent, the study authors point out, any intervention to cut the risk of Alzheimer’s should ideally begin that far in advance of symptoms.

"Moderate daily consumption of caffeinated coffee appears to be the best dietary option for long-term protection against Alzheimer’s memory loss," Dr. Arendash said. "Coffee is inexpensive, readily available, easily gets into the brain, and has few side-effects for most of us. Moreover, our studies show that caffeine and coffee appear to directly attack the Alzheimer’s disease process."

In addition to Alzheimer’s disease, moderate caffeine/coffee intake appears to reduce the risk of several other diseases of aging, including Parkinson’s disease, stroke, Type II diabetes, and breast cancer. However, supporting studies for these benefits have all been observational (uncontrolled), and controlled clinical trials are needed to definitively demonstrate therapeutic value.

A study tracking the health and coffee consumption of more than 400,000 older adults for 13 years, and published earlier this year in the New England Journal of Medicine, found that coffee drinkers reduced their risk of dying from heart disease, lung disease, pneumonia, stroke, diabetes, infections, and even injuries and accidents.

With new Alzheimer’s diagnostic guidelines encompassing the full continuum of the disease, approximately 10 million Americans now fall within one of three developmental stages of Alzheimer’s disease — Alzheimer’s disease brain pathology only, MCI, or diagnosed Alzheimer’s disease. That number is expected to climb even higher as the baby-boomer generation continues to enter older age, unless an effective and proven preventive measure is identified.

"If we could conduct a large cohort study to look into the mechanisms of how and why coffee and caffeine can delay or prevent Alzheimer’s disease, it might result in billions of dollars in savings each year in addition to improved quality of life," Dr. Cao said.

Source: Science Daily

June 4, 2012

In a new study of the effects of soy supplements for postmenopausal women, researchers at the Stanford University School of Medicine and the USC Keck School of Medicine found no significant differences — positive or negative — in overall mental abilities between those who took supplements and those who didn’t.

While questions have swirled for years around a possible link between soy consumption and changes in cognition, this research offers no evidence to support such claims. “There were no large effects on overall cognition one way or another,” said the study’s lead author, Victor Henderson, MD, professor of health research and policy and of neurology and neurological sciences at Stanford.

The findings from the 2.5-year study in middle-aged and older women, which was larger and longer than any previous trials on soy use, will appear in the June 5 issue of Neurology, the medical journal of the American Academy of Neurology. The results are in line with the largest previous study in this area: a 12-month trial of Dutch women during which daily soy intake showed “no significant effect on cognitive endpoints.” That work was published in a 2004 issue of the Journal of the American Medical Association.

Still, there are a number of randomized clinical trials on soy’s effect on cognition and memory in women that have presented conflicting takes about its benefits and harms. While improved cognition was seen in some findings, other research suggested that soy could have an adverse effect on memory.

Soy and soy-based products contain an estrogen-like compound called isoflavones, and some women choose to take soy supplements as an alternative to estrogen. It has been thought that isoflavones might be able to boost memory and perhaps overall brain function. The hippocampus, the part of the brain that controls memory, is rich in estrogen beta receptors, and isoflavones are known to activate these receptors.

Henderson’s interest in the matter is part of his broader research agenda on finding new strategies to improve cognitive function in aging.

For this work, he and his colleagues conducted the National Institutes of Health-sponsored Women’s Isoflavone Soy Health Trial, which was done between 2004 and 2008 to determine the effect of soy isoflavones on the progression of atherosclerosis and, secondarily, the effect on cognition. During this study, 350 healthy women ages 45-92 were randomized to receive daily 25 grams of isoflavone-rich soy protein (a dose comparable to that of traditional Asian diets) or a placebo. A battery of neuropsychological tests was given to the participants at the start of the study and again 2.5 years later.

Henderson and his colleagues examined changes to the composite of 14 scores and found no significant differences in global cognition — that is, overall mental abilities — from baseline to study-end between women who took the supplements and those on placebo. During a planned secondary analysis, they did identify a statistically significant difference in one of the identified cognitive factors: Women in the supplement group showed a greater improvement in visual memory (memory for faces). Henderson said this could be important, but “the finding needs to be replicated in future studies.”

According to Henderson, this research “helps provide a firm answer” about soy and overall cognition, and he and his co-authors note in the paper that postmenopausal women shouldn’t pursue a high-soy diet or take supplements for the primary goal of global cognitive benefit.

At the same time, Henderson said the work is not meant discourage women who consume soy for other purposes. “I don’t think they should be disappointed at all,” he said. “They should be pleased that there aren’t negative effects on overall cognitive function and that there are potential gains in aspects of memory. If a woman enjoys eating soy and if there may be other health benefits, she should keep doing what she’s doing.”

The researchers note that while these results are reasonably definitive — Henderson said the sample size was large enough that if there were major effects, the researchers would have likely seen them — the cognitive effects of soy isoflavones might differ for women of reproductive age and for men. More study is needed in these populations, he said. He also emphasized the need for researchers to continue studying a variety of interventions to improve cognition among older adults, including nutritional approaches, physical and mental activities, and pharmaceutical approaches.

Journal reference: Neurology

Source: medicalxpress.com

ScienceDaily (June 4, 2012) — A pair of new studies by computer scientists, biologists, and cognitive psychologists at Harvard, Northwestern, Wellesley, and Tufts suggest that collaborative touch-screen games have value beyond just play.

Multi-touch tables can recognize and accommodate several users at once, allowing students to collaborate and learn while they play an engaging game. (Credit: Michael Horn, Northwestern University)

Two games, developed with the goal of teaching important evolutionary concepts, were tested on families in a busy museum environment and on pairs of college students. In both cases, the educational games succeeded at making the process of learning difficult material engaging and collaborative.

The findings were presented at the Association for Computing Machinery (ACM) Special Interest Group on Computer-Human Interaction (SIGCHI) conference in May.

The games take advantage of the multi-touch-screen tabletop, which is essentially a desk-sized tablet computer. In a classroom or a museum, several users can gather around the table and use it simultaneously, either working on independent problems in the same space, or collaborating on a single project. The table accommodates multiple users and can also interact with physical objects like cards or blocks that are placed onto its surface.

The new research moves beyond the novelty of the system, however, and investigates the actual learning outcomes of educational games in both formal and informal settings.

"Do we know what the users are actually learning from this? That question is a step beyond the research of the past 10 years, where we’ve been seeing research publications that assess how well the system is performing, but not addressing how well it’s accomplishing what it’s really designed for," says principal investigator Chia Shen, a Senior Research Fellow in Computer Science at the Harvard School of Engineering and Applied Sciences (SEAS) and Director of the Scientists’ Discovery Room Lab.

The two collaborative games that have been developed for the system, Phylo-Genie and Build-a-Tree, are designed to help people understand phylogeny — specifically, the tree diagrams that evolutionary biologists use to indicate the evolutionary history of related species. Learners new to the discipline sometimes think of evolution as a linear progression, from the simple to the complex, with humans as the end point.

"What people are used to typically is geospatial data, like a map," explains Shen. "In phylogeny, however, the students need to understand that the relationship between species really depends on when they diverged. That’s represented by the position of the internal nodes of the tree, not by counting across the top of the tree, which is how many people intuitively do it."

The Phylo-Genie game, developed by researchers at Harvard, Wellesley, and Tufts, attempts to address the misconceptions that students hold even at the college level. Designed for a formal classroom setting, the game walks students through a scenario in which they have been bitten by an unusual species of snake and must identify its closest relatives in order to choose the correct anti-venom.

The researchers tested Phylo-Genie on pairs of undergraduate students who had not yet taken a course in evolutionary biology. Other pairs of students were given the same exercise, but in a pen-and-paper format. In comparison to the paper version, the electronic game produced statistically significantly higher scores on a post-test (an exam borrowed from a Harvard course), as well as higher participant ratings for engagement and collaboration.

Both of the phylogeny games were designed and evaluated in accordance with accepted principles of cognitive psychology and learning sciences.

The Build-a-Tree game was designed with an informal museum environment in mind. Researchers on this project, directed by lead author Michael S. Horn at Northwestern University and Shen at Harvard, observed 80 families and other social groups interacting with the Build-a-Tree game at the Harvard Museum of Natural History.

The game asks users to construct phylogenetic trees by dragging icons — for example, a bat, a bird, and a butterfly — toward one another in the correct order. As the user progresses through several levels, the problems become more challenging.

The idea, Shen says, is to encourage what museum science educators call “active prolonged engagement,” as opposed to “planned discovery.” The former allows learners to explore information independently and to interact with it in an open-ended manner; the latter approach, common in natural history museums, guides the user toward a particular set of facts.

"Natural history museums have always been a place where the exhibits are behind glass in the gallery," explains Shen. "You come here to see things that you just don’t see anywhere else — fossils millions of years old — and you come here to learn. You see school groups and parents coming in with a serious mind, and we’re breaking into that culture."

The Build-a-Tree game performed well against established measures of active prolonged engagement and social learning.

Even in the most high-tech exhibit hall, where visitors are engaged at every turn, it takes a great deal of creative thinking to demonstrate a phenomenon that is essentially imperceptible in real time.

"Evolution is a process that takes millions of years, whereas in chemistry or physics there are all sorts of phenomena that you can experiment with, like the tornado exhibit where you can go in and interrupt the air," says Shen. "This is our experiment: can we build something that is not as phenomenon-driven but can still engage them? I think we’ve succeeded in that."

Source: Science Daily

June 4, 2012

(Medical Xpress) — Ever been stuck in traffic when a feel-good song comes on the radio and suddenly your mood lightens?

Our emotions and feelings are typically associated with the right side of the brain. For example, processing the emotion in human facial expressions is done in the right hemisphere.

However, new Australian research is challenging the widely-held view that emotions and feelings are the domain of the right hemisphere only.

Dr. Sharpley Hsieh and colleagues from Neuroscience Research Australia (NeuRA) found that people with semantic dementia, a disease where parts of the left hemisphere are severely affected, have difficulty recognising emotion in music.

These findings have exciting implications for our understanding of how music, language and emotions are handled by the brain.

“It’s known that processing whether a face is happy or sad is impaired in people who lose key regions of the right hemisphere, as happens in people with Alzheimer’s and semantic dementia”, says Dr. Hsieh.

“What we have now learnt from looking at people with semantic dementia is that understanding emotions in music involves key parts of the other side of the brain as well”, she says.

“Ours is the first study from patients with dementia to show that language-based areas of the brain, primarily on the left, are important for extracting emotional meaning from music. Our findings suggest that the brain considers melodies and speech to be similar and that overlapping parts of the brain are required for both”, says Hsieh.

This paper is published in the journal Neuropsychologia.

How was this study done?

• People with Alzheimer’s disease lose episodic memory (‘What did I do yesterday?’); people with semantic dementia lose semantic memory (‘What is a zebra?’).
• Dr. Hsieh studied people with Alzheimer’s disease, semantic dementia and healthy people without either disease. Participants were played new pieces of music and had to indicate whether the song was happy, sad, peaceful or scary.
• Images were then taken of the patients’ brains using MRI so that diseased parts of the brain could be compared statistically to the answers provided in the musical test.
• Patients with Alzheimer’s and semantic dementia have problems deciding whether a human face looks happy or sad because the amygdala in the right hemisphere is diseased.
• Patients with semantic dementia have additional problems labelling whether a piece of music is happy or sad because the anterior temporal lobe in the left hemisphere is diseased.

Provided by Neuroscience Research Australia

Source: medicalxpress.com

June 3, 2012

Unlike their visual cousins, the neurons that control movement are not a predictable bunch. Scientists working to decode how such neurons convey information to muscles have been stymied when trying to establish a one-to-one relationship between a neuron’s behavior and external factors such as muscle activity or movement velocity.

The 19th century mathematician Joseph Fourier showed that two rhythms could be summed to produce a third rhythm. Researchers at Stanford have shown that this principle is behind the brain activity that produces arm movements. Credit: Mark Churchland, Stanford School of Engineering

In an article published online June 3rd by the journal Nature, a team of electrical engineers and neuroscientists working at Stanford University propose a new theory of the brain activity behind arm movements. Their theory is a significant departure from existing understanding and helps to explain, in relatively simple and elegant terms, some of the more perplexing aspects of the activity of neurons in motor cortex.

In their paper, electrical engineering Associate Professor Krishna Shenoy and post-doctoral researchers Mark Churchland, now a professor at Columbia, and John Cunningham of Cambridge University, now a professor at Washington University in Saint Louis, have shown that the brain activity controlling arm movement does not encode external spatial information—such as direction, distance and speed—but is instead rhythmic in nature.

Understanding the brain

Neuroscientists have long known that the neurons responsible for vision encode specific, external-world information—the parameters of sight. It had been theorized and widely suggested that motor cortex neurons function similarly, conveying specifics of movement such as direction, distance and speed, in the same way the visual cortex records color, intensity and form.

"Visual neurons encode things in the world. They are a map, a representation," said Churchland, who is first author of the paper. "It’s not a leap to imagine that neurons in the motor cortex should behave like neurons in the visual cortex, relating in a faithful way to external parameters, but things aren’t so concrete for movement."

Scientists have disagreed about which movement parameters are being represented by individual neurons. They could not look at a particular neuron firing in the motor cortex and determine with confidence what information it was encoding.

"Many experiments have sought such lawfulness and yet none have found it. Our findings indicate an alternative principle is at play," said co-first author Cunningham.

Read More →

ScienceDaily (June 1, 2012) — Neuroscientists at Cold Spring Harbor Laboratory (CSHL) just reached an important milestone, publicly releasing the first installment of data from the 500 terabytes so far collected in their pathbreaking project to construct the first whole-brain wiring diagram of a vertebrate brain, that of the mouse.

Composite image generated with Mouse Brain Architecture project data. Injections of two fluorescently marked (red and green) adeno-associated viral (AAV) tracers indicate neural pathways, superimposed upon a whole-brain image stained to reveal the protective sheathing around myelinated axons. Axonal paths leaving the injection site are seen, including horizontal ones crossing over to the other side of the brain along the Corpus Callosum. (Credit: Image courtesy of Cold Spring Harbor Laboratory)

The data consist of gigapixel images (each close to 1 billion pixels) of whole-brain sections that can be zoomed to show individual neurons and their processes, providing a “virtual microscope.” The images are integrated with other data sources from the web, and are being made fully accessible to neuroscientists as well as interested members of the general public (http://mouse.brainarchitecture.org). The data are being released pre-publication in the spirit of open science initiatives that have become familiar in digital astronomy (e.g., Sloan Digital Sky Survey) but are not yet as widespread in neurobiology.

Each sampled brain is represented in about 500 images, each image showing an optical section through a 20 micron-thick slice of brain tissue. A multi-resolution viewer permits users to journey through each brain from “front” to “back,” and thus enables them to follow the pathways taken through three-dimensional brain space by tracer-labeled neuronal pathways. The tracers were picked to follow neuronal inputs and outputs of given brain regions.

"We’re executing a grid-based "shotgun" strategy for neuronal tract tracing that we first proposed a few years ago, and which I am pleased to note has gained acceptance elsewhere within the neuroscience community," says Partha P. Mitra, Ph.D., the Crick-Clay Professor of Biomathematics at CSHL and director of the Mouse Brain Architecture (MBA) Project. After the initial June 1 release, project data will be made public continuously on a monthly basis, Mitra says.

Project addresses a large gap in knowledge

"Our project seeks to address a remarkable gap in our knowledge of the brain," Mitra explains. "Our knowledge of how the brain is wired remains piecemeal and partial after a century of intense activity. Francis Crick and Ted Jones emphasized this in an article published in Nature nearly 20 years ago. Yet to understand how the brain works (or fails to work in neurological or neuropsychiatric disease), it is critical that we understand this wiring diagram more fully. Further, there remain fundamental questions about brain evolution that cannot be addressed without obtaining such wiring diagrams for the brains of different species.”

The MBA Project, which has received critical funding from the Keck Foundation and from the National Institutes of Health, is distinguished by the approach advocated by Mitra and colleagues in a position paper published in 2009. Mitra there proposed mapping vertebrate brains at what he calls the “mesoscopic” scale, a middle-range amenable to light microscopy, providing far more detail than, for instance, MRI-based methods, and yet considerably less detail than is achievable via electron microscopy (EM). The latter approach, while useful for mapping synaptic connections between individual neurons, is feasible on a whole-brain basis only for very small brains (e.g. that of the fruitfly) or very small portions of the mouse brain.

The pragmatic approach Mitra advocated and which is realized in this first data release, is to image whole mouse brains in a semi-automated, quality-controlled process using light microscopy and injected neural tracers (both viruses and classically used tracer substances). While the basic methodology has been available for some time, systematically applying it to a grid of locations spanning the entire brain, and digitizing and re-assembling the resulting collection of brains, is a new approach made feasible by the rapidly falling costs of computer storage. A single mouse brain at light-microscope resolution produces about a terabyte (1 trillion bytes, or 1000 GB) of data; thus, generating and storing the data set currently being gathered would have been prohibitively expensive a decade or so ago.

Assembling the circuit diagram at a mesoscopic scale using ‘shotgun approach’

A key point is that at the mesoscopic scale, the team expects to assemble a picture of connections that are stereotypical — that is, essentially the same in different individuals, and probably genetically determined in a species-specific manner. By dividing the volume of a hemisphere of the mouse brain into 250 equidistant, predefined grid-points, and administering four different kinds of tracer injections at each grid point — in different animals of the same sex and age — the eight-member team at CSHL assisted by collaborating scientists at Boston University, MIT and the University of California, San Diego seeks to assemble a complete wiring diagram that will be stitched together from the full dataset.

The project in this sense is analogous to the Human Genome Project’s “shotgun” approach, in that its final product — a comprehensive wiring diagram — will be the product of many individually obtained data components, woven together thanks to the power of advanced computing and informatics. Indeed, Mitra says one of the genome project’s early advocates, Dr. James D. Watson (now CSHL Chancellor Emeritus), provided him with motivation and encouragement to pursue the project.

"We will never understand how the brain works until we have the wiring diagram," Dr. Watson comments today. "Mitra is on the right track and I’m impressed he’s gone from conception to putting out data in a couple of years on a quite modest budget. His approach deserves strong funding support."

The MBA Project was also inspired by early efforts of the Allen Institute, funded by Microsoft co-founder and philanthropist Paul Allen, which resulted in assembly of a comprehensive map of gene expression across the mouse brain. That effort was the product of standard molecular biology procedures iterated in a quasi-industrialized process. The resulting whole-brain gene-expression map, while a triumph, was not designed to shed light on connections in the brain, which became a point of departure for Mitra.

Since the 2009 publication of Mitra and colleagues’ proposal for meso-scale circuit-mapping projects for whole vertebrate brains, the approach has not only spawned Mitra’s CSHL project, but also other meso-scale circuit-mapping projects for the mouse at the Allen Institute and at UCLA. Each differs in aim and technical detail.

A number of features distinguish the “meso-scale” circuit project at CSHL. The 20-micron spacing between brain “slices” gives the CSHL results a particularly rich sense of three-dimensional depth and detail. The team’s use of four tracers including both classical tracer substances as well as neurotropic viruses (attenuated or disabled viruses that infect nerve cells), provides redundancy and helps control for differing efficacies of the different tracer substances. The images one sees on the MBA Project website begininng today provide hard data on actual neuronal processes — the “ground truth” of neuroanatomy, in Mitra’s words — and do not rely on inferential methodologies such as functional MRI scans and diffusion tensor imaging to suggest areas in which connections occur. Finally, it is noteworthy that the slides generated by the project are being physically stored, to permit re-examination at a later date, using more refined imaging methods if necessary or as new methods become available.

"Our project is what I’d call a necessary first step in a much larger enterprise, that of understanding both structure and dynamics of the vertebrate, and ultimately, the human brain," says Mitra. "While facile comparisons with Genome projects should be avoided, the data sets generated by the MBA and similar projects will provide a useful framework — not unlike a reference genome — on which we can ‘hang’ all kinds of neuroscience knowledge, the body of which has always been notably fragmentary."

Source: Science Daily

ScienceDaily (June 1, 2012) — Exercise helps to alleviate pain related to nerve damage (neuropathic pain) by reducing levels of certain inflammation-promoting factors, suggests an experimental study in the June issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

The results support exercise as a potentially useful nondrug treatment for neuropathic pain, and suggest that it may work by reducing inflammation-promoting substances called cytokines. The lead author was Yu-Wen Chen, PhD, of China Medical University, Taichung, Taiwan.

Exercise Reduces Nerve Pain and Cytokine Expression in Rats Neuropathic pain is a common and difficult-to-treat type of pain caused by nerve damage, seen in patients with trauma, diabetes, and other conditions. Phantom limb pain after amputation is an example of neuropathic pain.

Dr Chen and colleagues examined the effects of exercise on neuropathic pain induced by sciatic nerve injury in rats. After nerve injury, some animals performed progressive exercise — either swimming or treadmill running — over a few weeks. The researchers assessed the effects of exercise on neuropathic pain severity by monitoring observable pain behaviors.

The results suggested significant reductions in neuropathic pain in rats assigned to swimming or treadmill running. Exercise reduced abnormal responses to temperature and pressure — both characteristic of neuropathic pain.

Exercise also led to reduced expression of inflammation-promoting cytokines in sciatic nerve tissue — specifically, tumor necrosis factor-alpha and interleukin-1-beta. That was consistent with previous studies suggesting that inflammation and pro-inflammatory cytokines play a role in the development of neuropathic pain in response to nerve injury.

Exercise also led to increased expression of a protein, called heat shock protein-27, which may have contributed to the reductions in cytokine expression.

Neuropathic pain causes burning pain and numbness that is not controlled by conventional pain medications. Antidepressant and antiepileptic drugs may be helpful, but have significant side effects. Exercise is commonly recommended for patients with various types of chronic pain, but there are conflicting data as to whether it is helpful in neuropathic pain.

The new results support the benefits of exercise in reducing neuropathic pain, though not eliminating it completely. In the experiments, exercise reduced abnormal pain responses by 30 to 50 percent.

The study also adds new evidence that inflammation contributes to the development of neuropathic pain, including the possible roles of pro-inflammatory cytokines. The results provide support for exercise as a helpful, nondrug therapy for neuropathic pain — potentially reducing the need for medications and resulting side effects.

Source: Science Daily

ScienceDaily (June 1, 2012) — Too often, communication barriers exist between those who can hear and those who cannot. Sign language has helped bridge such gaps, but many people are still not fluent in its motions and hand shapes.

During the past semester, students in UH’s engineering technology and industrial design programs teamed up to develop the concept and prototype for MyVoice, a device that reads sign language and translates its motions into audible words. (Credit: Image courtesy of University of Houston)

Thanks to a group of University of Houston students, the hearing impaired may soon have an easier time communicating with those who do not understand sign language. During the past semester, students in UH’s engineering technology and industrial design programs teamed up to develop the concept and prototype for MyVoice, a device that reads sign language and translates its motions into audible words. Recently, MyVoice earned first place among student projects at the American Society of Engineering Education (ASEE) — Gulf Southwest Annual Conference.

The development of MyVoice was through a collaborative senior capstone project for engineering technology students (Anthony Tran, Jeffrey Seto, Omar Gonzalez and Alan Tran) and industrial design students (Rick Salinas, Sergio Aleman and Ya-Han Chen). Overseeing the student teams were Farrokh Attarzadeh, associate professor of engineering technology, and EunSook Kwon, director of UH’s industrial design program.

MyVoice’s concept focuses on a handheld tool with a built-in microphone, speaker, soundboard, video camera and monitor. It would be placed on a hard surface where it reads a user’s sign language movements. Once MyVoice processes the motions, it then translates sign language into space through an electronic voice. Likewise, it would capture a person’s voice and can translate words into sign language, which is projected on its monitor.

The industrial designers researched the application of MyVoice by reaching out to the deaf community to understand the challenges associated with others not understanding sign language. They then designed MyVoice, while the engineering technology students had the arduous task of programming the device to translate motion into sound.

"The biggest difficulty was sampling together a databases of images of the sign languages. It involved 200-300 images per sign," Seto said. "The team was ecstatic when the prototype came together."

From its conceptual stage, MyVoice evolved into a prototype that could translate a single phrase: “A good job, Cougars.”

"This wasn’t just a project we did for a grade," said Aleman, who just graduated from UH. "While designing and developing it, it turned into something very personal. When we got to know members of the deaf community and really understood their challenges, it made this MyVoice very important to all of us."

Since MyVoice’s creation and first place prize at the ASEE conference, all of the team members have graduated. Still, Aleman said that the project is not history.

"We got it to work, but we hope to work with someone to implement this as a product," Aleman said. "We want to prove to the community that this will work for the hearing impaired."

"We are proud of such a contribution to society through MyVoice, which breaks the barrier between deaf community and common society," added Attarzadeh.

Source: Science Daily

June 1, 2012

In a step towards improving rehabilitation for patients with walking impairments, researchers from the Kennedy Krieger Institute found that non-invasive stimulation of the cerebellum, an area of the brain known to be essential in adaptive learning, helped healthy individuals learn a new walking pattern more rapidly. The findings suggest that cerebellar transcranial direct current stimulation (tDCS) may be a valuable therapy tool to aid people relearning how to walk following a stroke or other brain injury.

Previous studies in the lab of Amy Bastian, PhD, PT, director of the Motion Analysis Laboratory at Kennedy Krieger Institute, have shown that the cerebellum, a part of the brain involved in movement coordination, is essential for walking adaptation. In this new study, Dr. Bastian and her colleagues explored the impact of stimulation over the cerebellum on adaptive learning of a new walking pattern. Specifically, her team tested how anode (positive), cathode (negative) or sham (none) stimulation affected this learning process.

"We’ve known that the cerebellum is essential to adaptive learning mechanisms like reaching, walking, balance and eye movements,” says Dr. Bastian. “In this study, we wanted to examine the effects of direct stimulation of the cerebellum on locomotor learning utilizing a split-belt treadmill that separately controls the legs.”

The study, published today in the Journal of Neurophysiology, found that by placing electrodes on the scalp over the cerebellum and applying very low levels of current, the rate of walking adaptation could be increased or decreased. Dr. Bastian’s team studied 53 healthy adults in a series of split-belt treadmill walking tests. Rather than a single belt, a split-belt treadmill consists of two belts that can move at different speeds. During split-belt walking, one leg is set to move faster than the other. This initially disrupts coordination between the legs so the user is not walking symmetrically, however over time the user learns to adapt to the disturbance.

The main experiment consisted of a two-minute baseline period of walking with both belts at the same slow speed, followed by a 15-minute period with the belts at two separate speeds. While people were on the treadmill, researchers stimulated one side of the cerebellum to assess the impact on the rate of re-adjustment to a symmetric walking pattern.

Dr. Bastian’s team found not only that cerebellar tDCS can change the rate of cerebellum-dependent locomotor learning, but specifically that the anode speeds up learning and the cathode slows it down. It was also surprising that the side of the cerebellum that was stimulated mattered; only stimulation of the side that controls the leg walking on the faster treadmill belt changed adaptation rate.

"It is important to demonstrate that we can make learning faster or slower, as it suggests that we are not merely interfering with brain function," says Dr. Bastian. "Our findings also suggest that tDCS can be selectively used to assess and understand motor learning."

The results from this study present an exciting opportunity to test cerebellar tDCS as a rehabilitation tool. Dr. Bastian says, “If anodal tDCS prompts faster learning, this may help reduce the amount of time needed for stroke patients to relearn to walk evenly. It may also be possible to use tDCS to help sustain gains made in therapy, so patients can retain and practice improved walking patterns for a longer period of time. We are currently testing these ideas in individuals who have had a stroke.”

Provided by Kennedy Krieger Institute

Source: medicalxpress.com

ScienceDaily (May 31, 2012) — When flies are made to lose a gene with links to Restless Legs Syndrome (RLS), they suffer the same sleep disturbances and restlessness that human patients do. The findings reported online on May 31 in Current Biology, a Cell Press publication, strongly suggest a genetic basis for RLS, a condition in which patients complain of an irresistible urge to move that gets worse as they try to rest.

"Although widely prevalent, RLS is a disorder whose pathophysiological basis remains very poorly understood," said Subhabrata Sanyal of Emory University School of Medicine. "The major significance of our study is to highlight the fact that there might be a genetic basis for RLS. Understanding the function of these genes also helps to understand and diagnose the disease and may offer more focused therapeutic options that are currently limited to very general approaches."

Sanyal’s team recognized that a number of genome-wide association studies in humans had suggested connections between RLS and variation in a single gene (BTBD9).

"BTBD9 function or its relationship to RLS and sleep were a complete mystery," Sanyal said.

His team realized that there might be a way to shed some light on that mystery in fruit flies. Flies have a single, highly conserved version of the human BTBD9. They decided to test whether the gene that had turned up in those human studies would have any effect on sleep in the insects. In fact, flies need sleep just like humans do, and their sleep patterns are influenced by the same kinds of brain chemistry.

The researchers now report that flies lacking their version of the RLS-associated gene do lose sleep as they move more. When those flies were treated with a drug used for RLS, they showed improvements in their sleep.

The studies also yielded evidence about how the RLS gene works by controlling dopamine levels in the brain as well as iron balance in cells. Sanyal said his team will continue to explore other RLS-related genes that have been identified in human studies in search of more details of their interaction and function.

"Our results support the idea that genetic regulation of dopamine and iron metabolism constitute the core pathophysiology of at least some forms of RLS," the researchers write.

More broadly, they say, the study emphasizes the utility of simple animals such as fruit flies in unraveling the genetics of sleep and sleep disorders.

Source: Science Daily

ScienceDaily (May 31, 2012) — Rats with spinal cord injuries and severe paralysis are now walking (and running) thanks to researchers at EPFL. Published in the June 1, 2012 issue of Science, the results show that a severed section of the spinal cord can make a comeback when its own innate intelligence and regenerative capacity is awakened. The study, begun five years ago at the University of Zurich, points to a profound change in our understanding of the central nervous system. According to lead author Grégoire Courtine, it is yet unclear if similar rehabilitation techniques could work for humans, but the observed nerve growth hints at new methods for treating paralysis.

Test subject takes first steps up stairs after neurorehabilitation with a combination of robotic harness and electrical-chemical stimulation. (Credit: EPFL/Grégoire Courtine)

"After a couple of weeks of neurorehabilitation with a combination of a robotic harness and electrical-chemical stimulation, our rats are not only voluntarily initiating a walking gait, but they are soon sprinting, climbing up stairs and avoiding obstacles when stimulated," explains Courtine, who holds the International Paraplegic Foundation (IRP) Chair in Spinal Cord Repair at EPFL.

Waking up the spinal cord

It is well known that the brain and spinal cord can adapt and recover from moderate injury, a quality known as neuroplasticity. But until now the spinal cord expressed so little plasticity after severe injury that recovery was impossible. Courtine’s research proves that, under certain conditions, plasticity and recovery can take place in these severe cases — but only if the dormant spinal column is first woken up.

To do this, Courtine and his team injected a chemical solution of monoamine agonists into the rats. These chemicals trigger cell responses by binding to specific dopamine, adrenaline, and serotonin receptors located on the spinal neurons. This cocktail replaces neurotransmitters released by brainstem pathways in healthy subjects and acts to excite neurons and ready them to coordinate lower body movement when the time is right.

Five to 10 minutes after the injection, the scientists electrically stimulated the spinal cord with electrodes implanted in the outermost layer of the spinal canal, called the epidural space. “This localized epidural stimulation sends continuous electrical signals through nerve fibers to the chemically excited neurons that control leg movement. All that is left was to initiate that movement,” explains Rubia van den Brand, contributing author to the study.

The innate intelligence of the spinal column

In 2009, Courtine already reported on restoring movement, albeit involuntary. He discovered that a stimulated rat spinal column — physically isolated from the brain from the lesion down — developed in a surprising way: It started taking over the task of modulating leg movement, allowing previously paralyzed animals to walk over treadmills. These experiments revealed that the movement of the treadmill created sensory feedback that initiated walking — the innate intelligence of the spinal column took over, and walking essentially occurred without any input from the rat’s actual brain. This surprised the researchers and led them to believe that only a very weak signal from the brain was needed for the animals to initiate movement of their own volition.

To test this theory, Courtine replaced the treadmill with a device that vertically supported the subjects, a mechanical harness did not facilitate forward movement and only came into play when they lost balance, giving them the impression of having a healthy and working spinal column. This encouraged the rats to will themselves toward a chocolate reward on the other end of the platform. “What they deemed willpower-based training translated into a fourfold increase in nerve fibers throughout the brain and spine — a regrowth that proves the tremendous potential for neuroplasticity even after severe central nervous system injury,” says Janine Heutschi, co-author in the study.

First human rehabilitation on the horizon

Courtine calls this regrowth “new ontogeny,” a sort of duplication of an infant’s growth phase. The researchers found that the newly formed fibers bypassed the original spinal lesion and allowed signals from the brain to reach the electrochemically-awakened spine. And the signal was sufficiently strong to initiate movement over ground — without the treadmill — meaning the rats began to walk voluntarily towards the reward, entirely supporting their own weight with their hind legs.

"This is the world-cup of neurorehabilitation," exclaims Courtine. "Our rats have become athletes when just weeks before they were completely paralyzed. I am talking about 100% recuperation of voluntary movement."

In principle, the radical reaction of the rat spinal cord to treatment offers reason to believe that people with spinal cord injury will soon have some options on the horizon. Courtine is optimistic that human, phase-two trials will begin in a year or two at Balgrist University Hospital Spinal Cord Injury Centre in Zurich, Switzerland. Meanwhile, researchers at EPFL are coordinating a nine million Euro project called NeuWalk that aims at designing a fully operative spinal neuroprosthetic system, much like the one used here with rats, for implanting into humans.

Source: Science Daily

ScienceDaily (May 31, 2012) — The molecular structure of a protein involved in Alzheimer’s disease — and the surprising discovery that it binds cholesterol — could lead to new therapeutics for the disease, Vanderbilt University investigators report in the June 1 issue of the journal Science.

Vanderbilt Center for Structural Biology investigators determined the structure of the C99 protein (shown in green and blue), which participates in triggering Alzheimer’s disease. Their discovery that C99 binds to cholesterol (shown in black, white and red) suggests a mechanism for cholesterol’s recognized role in promoting the memory-robbing disease and may lead to new therapeutics. (Credit: Charles Sanders and colleagues/Vanderbilt University)

Charles Sanders, Ph.D., professor of Biochemistry, and colleagues in the Center for Structural Biology determined the structure of part of the amyloid precursor protein (APP) — the source of amyloid-beta, which is believed to trigger Alzheimer’s disease. Amyloid-beta clumps together into oligomers that kill neurons, causing dementia and memory loss. The amyloid-beta oligomers eventually form plaques in the brain — one of the hallmarks of the disease.

"Anything that lowers amyloid-beta production should help prevent, or possibly treat, Alzheimer’s disease," Sanders said.

Amyloid-beta production requires two “cuts” of the APP protein. The first cut, by the enzyme beta-secretase, generates the C99 protein, which is then cut by gamma-secretase to release amyloid-beta. The Vanderbilt researchers used nuclear magnetic resonance and electron paragmagnetic resonance spectroscopy to determine the structure of C99, which has one membrane-spanning region.

They were surprised to discover what appeared to be a “binding” domain in the protein. Based on previously reported evidence that cholesterol promotes Alzheimer’s disease, they suspected that cholesterol might be the binding partner. The researchers used a model membrane system called “bicelles” (that Sanders developed as a postdoctoral fellow) to demonstrate that C99 binds cholesterol.

"It has long been thought that cholesterol somehow promotes Alzheimer’s disease, but the mechanisms haven’t been clear," Sanders said. "Cholesterol binding to APP and its C99 fragment is probably one of the ways it makes the disease more likely."

Sanders and his team propose that cholesterol binding moves APP to special regions of the cell membrane called “lipid rafts,” which contain “cliques of molecules that like to hang out together,” he said.

Beta- and gamma-secretase are part of the lipid raft clique.

"We think that when APP doesn’t have cholesterol around, it doesn’t care what part of the membrane it’s in," Sanders said. "But when it binds cholesterol, that drives it to lipid rafts, where these ‘bad’ secretases are waiting to clip it and produce amyloid-beta."

The findings suggest a new therapeutic strategy to reduce amyloid-beta production, he said.

"If you could develop a drug that blocks cholesterol from binding to APP, then you would keep the protein from going to lipid rafts. Instead it would be cleaved by alpha-secretase — a ‘good’ secretase that isn’t in rafts and doesn’t generate amyloid-beta."

Drugs that inhibit beta- or gamma-secretase — to directly limit amyloid-beta production — have been developed and tested, but they have toxic side effects. A drug that blocks cholesterol binding to APP may be more specific and effective in reducing amyloid-beta levels and in preventing, or treating, Alzheimer’s disease.

The C99 structure had some other interesting details, Sanders said.

The membrane domain of C99 is curved, which was unexpected but fits perfectly into the predicted active site of gamma-secretase. Also, a certain sequence of amino acids (GXXXG) that usually promotes membrane protein dimerization (two of the same proteins interacting with each other) turned out to be central to the cholesterol-binding domain. This is a completely new function for GXXXG motifs, Sanders said.

"This revealing new information on the structure of the amyloid precursor protein and its interaction with cholesterol is a perfect example of the power of team science," said Janna Wehrle, Ph.D., who oversees grants focused on the biophysical properties of proteins at the National Institutes of Health’s National Institute of General Medical Sciences (NIGMS), which partially funded the work. "The researchers at Vanderbilt brought together biological and medical insight, cutting-edge physical techniques and powerful instruments, each providing a valuable tool for piecing together the puzzle."

"When we were developing bicelles 20 years ago, no one was saying, ‘someday these things are going to lead to discoveries in Alzheimer’s disease,’" he said. "It was interesting basic science research that is now paying off."

Source: Science Daily

ScienceDaily (May 31, 2012) — Working memory training is unlikely to be an effective treatment for children suffering from disorders such as attention-deficit/hyperactivity or dyslexia, according to a research analysis published by the American Psychological Association. In addition, memory training tasks appear to have limited effect on healthy adults and children looking to do better in school or improve their cognitive skills.

"The success of working memory training programs is often based on the idea that you can train your brain to perform better, using repetitive memory trials, much like lifting weights builds muscle mass," said the study’s lead author, Monica Melby-Lervåg, PhD, of the University of Oslo. "However, this analysis shows that simply loading up the brain with training exercises will not lead to better performance outside of the tasks presented within these tests." The article was published online in Developmental Psychology.

Working memory enables people to complete tasks at hand by allowing the brain to retain pertinent information temporarily. Working memory enhancing tasks usually involve trying to get people to remember information presented to them while they are performing distracting activities. For example, participants may be presented with a series of numbers one at a time on a computer screen. The computer presents a new digit and then prompts participants to recall the number immediately preceding. More difficult versions might ask participants to recall what number appeared two, three or four digits ago.

In this meta-analysis, researchers from the University of Oslo and University College London examined 23 peer-reviewed studies with 30 different comparisons of groups that met their criteria. The studies were randomized controlled trials or experiments, had some sort of working memory treatment and a control group. The studies comprised a wide range of participants, including young children, children with cognitive impairments, such as ADHD, and healthy adults. Most of the studies had been published within the last 10 years.

Overall, working memory training improved performance on tasks related to the training itself but did not have an impact on more general cognitive performance such as verbal skills, attention, reading or arithmetic. “In other words, the training may help you improve your short-term memory when it’s related to the task implemented in training but it won’t improve reading difficulties or help you pay more attention in school,” said Melby-Lervåg.

In recent years, several commercial, computer-based working memory training programs have been developed and purport to benefit students suffering from ADHD, dyslexia, language disorders, poor academic performance or other issues. Some even claim to boost people’s IQs. These programs are widely used around the world in schools and clinics, and most involve tasks in which participants are given many memory tests that are designed to be challenging, the study said.

"In the light of such evidence, it seems very difficult to justify the use of working memory training programs in relation to the treatment of reading and language disorders," said Melby-Lervåg. "Our findings also cast strong doubt on claims that working memory training is effective in improving cognitive ability and scholastic attainment."

Source: Science Daily

ScienceDaily (May 31, 2012) — Summer vacation time is upon us. If you have been saving up for your dream vacation for years, you may want to make sure your dream spot is still the best place to go. A new study has found that when we fantasize about such trips before they are possible, we tend to overlook the negatives — thus influencing our decision-making down the line.

Summer vacation time is upon us. If you have been saving up for your dream vacation for years, you may want to make sure your dream spot is still the best place to go. A new study has found that when we fantasize about such trips before they are possible, we tend to overlook the negatives — thus influencing our decision-making down the line. (Credit: © XtravaganT / Fotolia)

"We were interested in the effects of positive fantasies — what happens when people imagine an idealized, best-case-scenario version of the future, compared to when they imagine a less idealized version," says Heather Barry Kappes of New York University, co-author of the study published online this week in Personality and Social Psychology Bulletin. “This is one of the first papers to examine selective information acquisition at this early stage, before people are seriously considering a possibility.”

Say, for example, that you would like to take a trip to Australia this year but think you are very unlikely to do so — you have no more vacation time left, cannot afford it, or would rather save up for a new car. But you still daydream about how nice it would be to see the Australian Outback and lie on the white sand beaches, perhaps without thinking about the long plane ride there or the poisonous animals. Those daydreams, Kappes says, have powerful effects.

To test those effects, Kappes and co-author Gabriele Oettingen asked people to imagine a particular future about one of three topics: wearing glamorous high-heeled shoes, making money in the stock market, or taking a vacation. To induce positive fantasies for each topic, the study participants were prompted to think about how great it would be to do each activity. In the control condition, participants also imagined experiencing the future, but were prompted to think about the negatives as well, with questions like “Would it really be so great?” In both conditions, participants wrote down what they were thinking, for the researchers to ensure they were engaged in the imagery.

After that exercise, the researchers offered the participants a choice of different types of information. For example, participants could browse a website describing the positive and negative health consequences of wearing high heels, and researchers noted how much more time they spent reading about positive versus negative consequences. Or, they could choose which of five (fictitious) tripadvisor.com reviews they wanted to read, and researchers recorded whether they chose one that was more pro-trip (i.e., five stars) or con-trip (i.e., one star).

Kappes’ team found that for each topic, imagining the idealized version made people prefer to learn about the pros rather than the cons of the future event. “These effects are pronounced when people are not seriously considering pursuing a given future,” Kappes says.

The work has important implications for even the most deliberate of decision-makers. “When people are seriously considering implementing a decision like taking a trip, they often engage in careful deliberations about the pros versus cons,” Kappes says. “Our work suggests that before getting to this point, positive fantasies might lead people to acquire biased information — to learn more about the pros rather than the cons. Thus, even if people deliberate very carefully on the information they’ve acquired, they could still make poor decisions.”

People need to be aware of these effects to ensure that they acquire balanced information before it is time to make a decision, she says. The study also contributes to a larger body of research about the powerful consequences of mental imagery — and shows that positive thinking may not always be best. “Although there are benefits to imagining a positive future, there are also drawbacks, and it’s important to recognize them in order to most effectively pursue our goals.”

Source: Science Daily

ScienceDaily (May 30, 2012) — New findings from the Monell Center reveal that humans can identify the age of other humans based on differences in body odor. Much of this ability is based on the capacity to identify odors of elderly individuals, and contrary to popular supposition, the so-called ‘old-person smell’ is rated as less intense and less unpleasant than body odors of middle-aged and young individuals.

Baby-smell. Humans can identify the age of other humans based on differences in body odor. (Credit: © S.Kobold / Fotolia)

"Similar to other animals, humans can extract signals from body odors that allow us to identify biological age, avoid sick individuals, pick a suitable partner, and distinguish kin from non-kin," said senior author Johan Lundström, a sensory neuroscientist at Monell.

Like non-human animals, human body odors contain a rich array of chemical components that can transmit various types of social information. The perceptual characteristics of these odors are reported to change across the lifespan, as are concentrations of the underlying chemicals.

Scientists theorize that age-related odors may help animals select suitable mates: older males might be desirable because they contribute genes that enable offspring to live longer, while older females might be avoided because their reproductive systems are more fragile.

In humans, a unique ‘old person smell’ is recognized across cultures. This phenomenon is so acknowledged in Japan that there is a special word to describe this odor, kareishū.

Because studies with non-human animals at Monell and other institutions have demonstrated the ability to identify age via body odor, Lundström’s team examined whether humans are able to do the same.

In the study, published in the journal PLoS ONE, body odors were collected from three age groups, with 12-16 individuals in each group: Young (20-30 years old), Middle-age (45-55), and Old-age (75-95). Each donor slept for five nights in unscented t-shirts containing underarm pads, which were then cut into quadrants and placed in glass jars.

Odors were assessed by 41 young (20-30 years old) evaluators, who were given two body odor glass jars in nine combinations and asked to identify which came from the older donors. Evaluators also rated the intensity and pleasantness of each odor. Finally evaluators were asked to estimate the donor’s age for each odor sample.

Evaluators were able to discriminate the three donor age categories based on odor cues. Statistical analyses revealed that odors from the old-age group were driving the ability to differentiate age. Interestingly, evaluators rated body odors from the old-age group as less intense and less unpleasant than odors from the other two age groups.

"Elderly people have a discernible underarm odor that younger people consider to be fairly neutral and not very unpleasant," said Lundström. "This was surprising given the popular conception of old age odor as disagreeable. However, it is possible that other sources of body odors, such as skin or breath, may have different qualities."

Future studies will both attempt to identify the underlying biomarkers that evaluators use to identify age-related odors and also determine how the brain is able to identify and evaluate this information.

Source: Science Daily

ScienceDaily (May 30, 2012) — Children today may be busier than ever, but Case Western Reserve University psychologists have found that their imagination hasn’t suffered — in fact, it appears to have increased.

Children today may be busier than ever, but Case Western Reserve University psychologists have found that their imagination hasn’t suffered — in fact, it appears to have increased. (Credit: © BeTa-Artworks / Fotolia)

Psychologists Jessica Dillon and Sandra Russ expected the opposite outcome when they analyzed 14 play studies that Russ conducted between 1985 and 2008.

But as they report in “Changes in Children’s Play Over Two Decades,” an article in the Creativity Research Journal, the data told a story contrary to common assumptions. First, children’s use of imagination in play and their overall comfort and engagement with play activities actually increased over time. In addition, the results suggested that children today expressed less negative feelings in play. Finally, their capacity to express a wide range of positive emotions, to tell stories and to organize thoughts stayed consistent.

Dillon, a fifth-year doctoral student, and Russ, a professor in psychological sciences at Case Western Reserve, decided to revisit the play data after a 2007 report from the American Academy of Pediatrics showed children played less.

They set out to see if having less time for unstructured play affected the processes in play that influence cognition and emotional development, a focus of the play research.

The pretend play studies focused on children between the ages of 6 and 10. The children’s play was measured for comfort, imagination, the range and amount of positive to negative emotions used and expressed, and the quality of storytelling by using Russ’ Affect in Play Scale (APS).

The APS is a five-minute, unstructured play session. Children are asked to play freely with three wooden blocks and two human hand puppets. The play is videotaped, and later reviewed and scored for imagination, expression of emotions, actions and storytelling.

Russ explains that children who exhibit good play skills with imaginative and emotional play situations have shown better skills at coping, creativity and problem solving. She stresses there is no link between being a good player and intelligence.

The APS data provided a consistent measurement and research structure over the 23-year period. Russ said the consistency of having the same tool to measure play provided this unique opportunity to track changes in play.

"We were surprised that outside of imagination and comfort, play was consistent over time," said Dillon.

Russ did voice concern about the decrease in displayed negative emotions and actions. “Past studies have linked negative emotions in play with creativity,” she said.

But even with the lack of time to play, Russ said, children, like some other forms of higher mammals, have a drive to play and always will find ways to do it.

As new stimuli, like video games and the Internet, have crept into everyday life, Russ explains that children might gain cognitive skills from using technology where they once got it from acting out situations in play. Skills might also develop from daydreaming.

Russ said future research will need to focus on whether acting out emotions and creating stories in play is as important as it once was in helping children to be creative.

Even though children have less time these days for play, Russ still advises giving children time for it, adding that it helps children develop emotional and cognitive abilities.

Video: Studying imagination in children’s play

Source: Science Daily

ScienceDaily (May 30, 2012) — In a new paper, the researchers describe a mathematical model they created that helps predict pragmatic reasoning and may eventually lead to the manufacture of machines that can better understand inference, context and social rules.

Noah Goodman, right, and Michael Frank, both assistant professors of psychology, discuss their research at the white board that covers the wall in Goodman’s office. (Credit: L.A. Cicero)

Language is so much more than a string of words. To understand what someone means, you need context.

Consider the phrase, “Man on first.” It doesn’t make much sense unless you’re at a baseball game. Or imagine a sign outside a children’s boutique that reads, “Baby sale — One week only!” You easily infer from the situation that the store isn’t selling babies but advertising bargains on gear for them.

Present these widely quoted scenarios to a computer, however, and there would likely be a communication breakdown. Computers aren’t very good at pragmatics — how language is used in social situations.

But a pair of Stanford psychologists has taken the first steps toward changing that.

In a new paper published recently in the journal Science, Assistant Professors Michael Frank and Noah Goodman describe a quantitative theory of pragmatics that promises to help open the door to more human-like computer systems, ones that use language as flexibly as we do.

The mathematical model they created helps predict pragmatic reasoning and may eventually lead to the manufacture of machines that can better understand inference, context and social rules. The work could help researchers understand language better and treat people with language disorders.

It also could make speaking to a computerized customer service attendant a little less frustrating.

"If you’ve ever called an airline, you know the computer voice recognizes words but it doesn’t necessarily understand what you mean," Frank said. "That’s the key feature of human language. In some sense it’s all about what the other person is trying to tell you, not what they’re actually saying."

Frank and Goodman’s work is part of a broader trend to try to understand language using mathematical tools. That trend has led to technologies like Siri, the iPhone’s speech recognition personal assistant.

But turning speech and language into numbers has its obstacles, mainly the difficulty of formalizing notions such as “common knowledge” or “informativeness.”

That is what Frank and Goodman sought to address.

The researchers enlisted 745 participants to take part in an online experiment. The participants saw a set of objects and were asked to bet which one was being referred to by a particular word.

For example, one group of participants saw a blue square, a blue circle and a red square. The question for that group was: Imagine you are talking to someone and you want to refer to the middle object. Which word would you use, “blue” or “circle”?

The other group was asked: Imagine someone is talking to you and uses the word “blue” to refer to one of these objects. Which object are they talking about?

"We modeled how a listener understands a speaker and how a speaker decides what to say," Goodman explained.

The results allowed Frank and Goodman to create a mathematical equation to predict human behavior and determine the likelihood of referring to a particular object.

"Before, you couldn’t take these informal theories of linguistics and put them into a computer. Now we’re starting to be able to do that," Goodman said.

The researchers are already applying the model to studies on hyperbole, sarcasm and other aspects of language.

"It will take years of work but the dream is of a computer that really is thinking about what you want and what you mean rather than just what you said," Frank said.

Source: Science Daily

ScienceDaily (May 30, 2012) — The same gene variations that make it difficult to stop smoking also increase the likelihood that heavy smokers will respond to nicotine-replacement therapy and drugs that thwart cravings, a new study shows.

High-risk genetic variations can increase the risk for nicotine dependence, but the same gene variants predict a more robust response to anti-smoking medications. (Credit: Li-Shiun Chen)

The research, led by investigators at Washington University School of Medicine in St. Louis, will appear online May 30 in the American Journal of Psychiatry.

The study suggests it may one day be possible to predict which patients are most likely to benefit from drug treatments for nicotine addiction.

"Smokers whose genetic makeup puts them at the greatest risk for heavy smoking, nicotine addiction and problems kicking the habit also appear to be the same people who respond most robustly to pharmacologic therapy for smoking cessation," says senior investigator Laura Jean Bierut, MD, professor of psychiatry. "Our research suggests that a person’s genetic makeup can help us better predict who is most likely to respond to drug therapy so we can make sure those individuals are treated with medication in addition to counseling or other interventions."

For the new study, the researchers analyzed data from more than 5,000 smokers who participated in community-based studies and more than 1,000 smokers in a clinical treatment study. The scientists focused on the relationship between their ability to quit smoking successfully and genetic variations that have been associated with risk for heavy smoking and nicotine dependence.

"People with the high-risk genetic markers smoked an average of two years longer than those without these high-risk genes, and they were less likely to quit smoking without medication," says first author Li-Shiun Chen, MD, assistant professor of psychiatry at Washington University. "The same gene variants can predict a person’s response to smoking-cessation medication, and those with the high-risk genes are more likely to respond to the medication."

In the clinical treatment trial, individuals with the high-risk variants were three times more likely to respond to drug therapy, such as nicotine gum, nicotine patches, the antidepressant buproprion and other drugs used to help people quit.

Tobacco use is the leading cause of preventable illness and death in the United States and a major public health problem worldwide. Cigarette smoking contributes to the deaths of an estimated 443,000 Americans each year. Although lung cancer is the leading cause of smoking-related cancer death among both men and women, tobacco also contributes to other lung problems, many other cancers and heart attacks.

Bierut and Chen say that the gene variations they studied are not the only ones involved in whether a person smokes, becomes addicted to nicotine or has difficulty quitting. But they contend that because the same genes can predict both heavy smoking and enhanced response to drug treatment, the genetic variants are important to the addiction puzzle.

"It’s almost like we have a ‘corner piece’ here," Bierut says. "It’s a key piece of the puzzle, and now we can build on it. Clearly these genes aren’t the entire story — other genes play a role, and environmental factors also are important. But we’ve identified a group that’s responding to pharmacologic treatment and a group that’s not responding, and that’s a key step in improving, and eventually tailoring, treatments to help people quit smoking."

Since people without the risky genetic variants aren’t as likely to respond to drugs, Bierut says they should get counseling or other non-drug therapies.

"This is an actionable genetic finding," Chen says. "Scientific journals publish genetic findings every day, but this one is actionable because treatment could be based on a person’s genetic makeup. I think this study is moving us closer to personalized medicine, which is where we want to go."

And Bierut says that although earlier studies suggested the genes had only a modest influence on smoking and addiction, the new clinical findings indicate the genetic variations are having a big effect on treatment response.

"These variants make a very modest contribution to the development of nicotine addiction, but they have a much greater effect on the response to treatment. That’s a huge finding," she says.

Source: Science Daily

ScienceDaily (May 30, 2012) — Changes to just three genetic letters among billions contributed to the evolution and development of the mammalian motor sensory circuits and laid the groundwork for the defining characteristics of the human brain, Yale University researchers report.

Illustration of neurons. Changes to just three genetic letters among billions contributed to the evolution and development of the mammalian motor sensory circuits and laid the groundwork for the defining characteristics of the human brain. (Credit: © nobeastsofierce / Fotolia)

In a study published in the May 31 issue of the journal Nature, Yale researchers found that a small, simple change in the mammalian genome was critical to the evolution of the corticospinal neural circuits. This circuitry directly connects the cerebral cortex, the conscious part of the human brain, with the brainstem and the spinal cord to make possible the fine, skilled movements necessary for functions such as tool use and speech. The evolutionary mechanisms that drive the formation of the corticospinal circuit, which is a mammalian-specific advance, had remained largely mysterious.

"What we found is a small genetic element that is part of the gene regulatory network directing neurons in the cerebral cortex to form the motor sensory circuits," said Nenad Sestan, professor of neurobiology, researcher for the Kavli Institute for Neuroscience, and senior author of the paper.

Most mammalian genomes contain approximately 22,000 protein-encoding genes. The critical drivers of evolution and development, however, are thought to reside in the non-coding portions of the genome that regulate when and where genes are active. These so-called cis-regulatory elements control the activation of genes that carry out the formation of basic body plans in all organisms.

Sungbo Shim, the first author, and other members of Sestan’s lab identified one such regulatory DNA region they named E4, which specifically drives the development of the corticospinal system by controlling the dynamic activity of a gene called Fezf2 — which, in turn, directs the formation of the corticospinal circuits. E4 is conserved in all mammals but divergent in other craniates, suggesting that it is important to both the emergence and survival of mammalian species. The species differences within E4 are tiny, but crucially drive the regulation of E4 activity by a group of regulatory proteins, or transcription factors, that include SOX4, SOX11, and SOX5. In cooperation, they control the dynamic activation and repression of E4 to shape the development of the corticospinal circuits in the developing embryo.

Source: Science Daily

ScienceDaily (May 30, 2012) — A new method for rapidly solving the three-dimensional structures of a special group of proteins, known as integral membrane proteins, may speed drug discovery by providing scientists with precise targets for new therapies, according to a paper published May 20 in Nature Methods.

Using their new rapid technique, Choe’s team generated the structure of a hIMP known as TMEM14A, shown here in multiple three-dimensional conformations. (Credit: Courtesy of the Salk Institute for Biological Studies)

The technique, developed by scientists at the Salk Institute for Biological Studies, provides a shortcut for determining the structure of human integral membrane proteins (hIMPs), molecules found on the surface of cells that serve as the targets for about half of all current drugs.

Knowing the exact three-dimensional shape of hIMPs allows drug developers to understand the precise biochemical mechanisms by which current drugs work and to develop new drugs that target the proteins.

"Our cells contain around 8,000 of these proteins, but structural biologists have known the three-dimensional structure of only 30 hIMPs reported by the entire field over many years," says Senyon Choe, a professor in Salk’s Structural Biology Laboratory and lead author on the paper. "We solved six more in a matter of months using this new technique. The very limited information on the shape of human membrane proteins hampers structure-driven drug design, but our method should help address this by dramatically increasing the library of known hIMP structures."

Integral membrane proteins are attached to the membrane surrounding each cell, serving as gateways for absorbing nutrients, hormones and drugs, removing waste products, and allowing cells to communicate with their environment. Many diseases, including Alzheimer’s, heart disease and cancer have been linked to malfunctioning hIMPs, and many drugs, ranging from aspirin to schizophrenia medications, target these proteins.

Most of the existing drugs were discovered through brute force methods that required screening thousands of potential molecules in laboratory studies to determine if they had a therapeutic effect. Given a blueprint of the 3D structure of a hIMP involved in a specific disease, however, drug developers could focus only on molecules that are most likely to interact with the target hIMP, saving time and expense.

In the past, it was extremely difficult to solve the structure of hIMPs, due to the difficulty of harvesting them from cells and the difficulty of labeling the amino acids that compose the proteins, a key step in determining their three-dimensional configuration.

"One problem was that hIMPs serve many functions in a cell, so if you tried to engineer cells with many copies of the proteins on their membrane, they would die before you could harvest the hIMPs," says Christian Klammt, a postdoctoral researcher in Choe’s lab and a first author on the paper.

To get around this, the scientists created an outside-the-cell environment, called cell-free expression system, to synthesize the proteins. They used a plexiglass chamber that contained all the biochemical elements necessary to manufacture hIMPs as if they were inside the cell. This system provided the researchers with enough of the proteins to conduct structural analysis.

The cell-free method also allowed them to easily add labeled amino acids into the biochemical stew, which were then incorporated into the proteins. These amino acids gave off telltale structural clues when analyzed with nuclear magnetic resonance spectroscopy, a method for using the magnetic properties of atoms to determine a molecule’s physical and chemical properties.

"It was very difficult and inefficient to introduce labeled amino acids selectively into the protein produced in live cells," says Innokentiy Maslennikov, a Salk staff scientist and co-first author on the paper. "With a cell-free system, we can precisely control what amino acids are available for protein production, giving us isotope-labeled hIMPs in large quantities. Using a proprietary labeling strategy we devised a means to minimize the number of samples to prepare."

Prior methods might take up to a year to determine a single protein structure, but using their new method, the Salk scientists determined the structure of six hIMPs within just 18 months. They have already identified 38 more hIMPs that are suitable for analysis with their technique, and expect it will be used to solve the structure for many more.

Source: Science Daily

May 30, 2012

(Medical Xpress) — A protein produced by the central nervous system’s support cells seems to play two opposing roles in protecting nerve cells from damage, an animal study by Johns Hopkins researchers suggests: Decreasing its activity seems to trigger support cells to gear up their protective powers, but increasing its activity appears to be key to actually use those powers to defend cells from harm.

Seth Blackshaw, Ph.D., an associate professor in the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine, explains that researchers have long suspected that central nervous system cells called glia play an important role in saving nerve cells from almost certain death after either an acute injury, such as a blow to the head, or chronic damage, such as that caused by Alzheimer’s or Parkinson’s disease. Glia — named after the Greek word for glue, since decades ago they were thought to play a very passive role in holding the central nervous system together — respond to an assault on nearby neurons in a dramatic way, puffing up to a larger size and turning off several genes involved in routine maintenance functions.

Previous research in cell cultures containing both neurons and glia showed that when the entire group was exposed to an assault, the reaction of the glia seemed to drive a response that protects cells from subsequent damage. However, Blackshaw says, it’s been unclear exactly what glia are doing when they change in size and gene expression. Even whether this response is actually important for protection was uncertain, he adds, since it’s been impossible to study this so-called glial reactivity without treating whole tissues that include neurons and other types of cells that may exert their own protective effects.

Hoping to find a way to trigger glial reactivity without assaulting entire tissues, Blackshaw and his colleagues searched for proteins that could play an important role in this response. The team used Mueller glia as their model system. These glia are the most abundant type in the retina, and are highly likely to behave like other glia throughout the central nervous system, Blackshaw says.

The researchers’ investigation eventually zeroed in on a protein called Lhx2. When they bred mutant mice that selectively lacked Lhx2 in the glia of the eye, these cells displayed the physical and genetic characteristics of being reactive all the time, even without any damaging stimulus. However, to the researchers’ surprise, hitting the mutant animals’ eyes with extraordinarily bright light caused considerably more damage to their retinas compared to the same stimulus in normal mice.

To understand why these reactive glia didn’t produce the expected protective response, the researchers looked for other pro-survival proteins that glia produce under assault. In the mutant animals, these other proteins were conspicuously missing, Blackshaw says, suggesting that Lhx2 is necessary for glia to produce other protective proteins.

“Lhx2 seems to be a master regulator of glial reactivity, and we’ve shown here that it has two faces,” Blackshaw says of these results, reported in the March 20 issue of the Proceedings of the National Academy of Sciences. While the protein’s absence seems to be critical for triggering the physical and genetic changes glia use to bring their protective proteins to bear to help neurons survive, its presence is vital to produce these proteins in the first place. Levels of Lhx2 activity likely dip and then increase in glia exposed to an attack, he says, explaining both the initial glial reactivity researchers see under a microscope as well as the resulting neural protection.

Once researchers understand this mechanism better, Blackshaw adds, they may be able to craft drugs that stimulate glia to pump out more pro-survival proteins, making novel therapies for neurodegenerative diseases.

Provided by Johns Hopkins University

Source: medicalxpress.com

May 30, 2012

Patients who are blind in one side of their visual field benefit from presentation of sounds on the affected side. After passively hearing sounds for an hour, their visual detection of light stimuli in the blind half of their visual field improved significantly. Neural pathways that simultaneously process information from different senses are responsible for this effect.

"We have embarked on a whole new therapy approach" says PD Dr. Jörg Lewald from the RUB’s Cognitive Psychology Unit. Together with colleagues from the Neurological University Clinic at Bergmannsheil (Prof. Dr. Martin Tegenthoff) and Durham University (PD Dr. Markus Hausmann), he describes the results in PLoS ONE.

To investigate the effectiveness of the auditory stimulation, the research team carried out a visual test before and after the acoustic stimulation. Patients were asked to determine the position of light flashes in the healthy and in the blind field of vision. While performance was stable in the intact half of their field of vision, the number of correct answers in the blind half increased after the auditory stimulation. This effect lasted for 1.5 hours. “In other treatments, the patients undergo arduous and time-consuming visual training” explains Lewald. “The therapeutic results are moderate and vary greatly from patient to patient. Our result suggests that passive hearing alone can improve vision temporarily.”

If strokes or injuries cause damage to the area of the brain that processes the information of the visual sense, this results in a visual field defect. The area most commonly affected is the primary visual cortex, the first processing point for visual input to the cerebral cortex. The more neurons die in this brain area, the bigger the visual deficit. Usually the entire half of the visual field is affected, a condition known as hemianopia. “Hemianopia restricts patients immensely in their everyday life” says Lewald. “When objects or people are missed on the blind side, this can quickly lead to accidents.”

"There is increasing evidence that processing of incoming sensory information is not strictly separated in the brain", says Lewald. "At various stages there are connections between the sensory systems." In particular the nerve cells in the so-termed superior colliculus, part of the midbrain, process auditory and visual information simultaneously. This area is not usually affected by visual field defects, and thus continues to analyse visual stimuli. Therefore, remaining visual functions are retained in the blind half, which the patients, however, are not aware of. “Since the same nerve cells also receive auditory information, we had the idea to use acoustic stimuli to increase their sensitivity to light stimuli” says Lewald.

The team of researchers now aims to further refine their therapy approach in order to reveal sustained improvement in visual functioning. They will also investigate whether the stimulation of the sense of hearing also has an effect on more complex visual functions. Finally, they aim to explore the mechanisms that underlie the effect observed.

Provided by Ruhr-Universitaet-Bochum

Source: medicalxpress.com

May 30, 2012

(Medical Xpress) — Scientists have unlocked the secrets of the zebra fish’s ability to heal its spinal cord after injury, in research that could deliver therapy for paraplegics and quadriplegics in the future.

Scientists discovered the role of a protein in the remarkable self-healing ability of the fish

A team from Monash University’s Australian Regenerative Medicine Institute (ARMI), led by Dr Yona Goldshmit and Professor Peter Currie, discovered the role of a protein in the remarkable self-healing ability of the fish.

The findings, detailed in The Journal of Neuroscience, could eventually lead to ways to stimulate spinal cord regeneration in humans.

When the spinal cord is severed in humans and other mammals, the immune system kicks in, activating specialised cells called glia to prevent bleeding into it, Professor Currie said.

“Glia are the workmen of nervous system. The glia proliferate, forming bigger cells that span the wound site in order to prevent bleeding into it. They come in and try to sort out problems. A glial scar forms,” Professor Currie said.

However, the scar prevents axons, threadlike structures of nerve cells that carry impulses to the brain, of neighbouring nerve cells from penetrating the wound. The result is paralysis.

“The axons upstream and downstream of the lesion sites are never able to penetrate the glial scar to reform. This is a major barrier in mammalian spinal cord regeneration,” Professor Currie said.

In contrast, the zebra fish glia form a bridge that spans the injury site but allow the penetration of axons into it.

The fish can fully regenerate its spinal cord within two months of injury. “You can’t tell there’s been any wound at all,” Professor Currie said.

Scientists discovered the protein, called fibroblast growth factor (fgf), controlled the shape of the glia, and accounted for the difference in the response to spinal cord injury between humans and zebra fish.

The scientists showed the protein could be manipulated in the zebra fish to speed up tissue repair even more.

“The hope is that fgf could eventually be used to promote better results in spinal cord repair in people,” Professor Currie said.

Provided by Monash University

Source: medicalxpress.com

ScienceDaily (May 30, 2012) — Bipolar disorder is a serious and debilitating condition where individuals experience severe swings in mood between mania and depression. The episodes of low or elevated mood can last days or months, and the risk of suicide is high.

Antidepressants are commonly prescribed to treat or prevent the depressive episodes, but they are not universally effective. Many patients still continue to experience periods of depression even while being treated, and many patients must try several different types of antidepressants before finding one that works for them. In addition, it may take several weeks of treatment before a patient begins to feel relief from the drug’s effects.

For these reasons, better treatments for depression are desperately needed. A new study in Biological Psychiatry this week confirms that scientists may have found one in a drug called ketamine.

A group of researchers at the National Institute of Mental Health, led by Dr. Carlos Zarate, previously found that a single dose of ketamine produced rapid antidepressant effects in depressed patients with bipolar disorder. They have now replicated that finding in an independent group of depressed patients, also with bipolar disorder. Replication is an important component of the scientific method, as it helps ensure that the initial finding wasn’t accidental and can be repeated.

In this new study, they administered a single dose of ketamine and a single dose of placebo to a group of patients on two different days, two weeks apart. The patients were then carefully monitored and repeatedly completed ratings to ‘score’ their depressive symptoms and suicidal thoughts.

When the patients received ketamine, their depression symptoms significantly improved within 40 minutes, and remained improved over 3 days. Overall, 79% of the patients improved with ketamine, but 0% reported improvement when they received placebo.

Importantly, and for the first time in a group of patients with bipolar depression, they also found that ketamine significantly reduced suicidal thoughts. These antisuicidal effects also occurred within one hour. Considering that bipolar disorder is one of the most lethal of all psychiatric disorders, these study findings could have a major impact on public health.

"Our finding that a single infusion of ketamine produces rapid antidepressant and antisuicidal effects within one hour and that is fairly sustained is truly exciting," Dr. Zarate commented. "We think that these findings are of true importance given that we only have a few treatments approved for acute bipolar depression, and none of them have this rapid onset of action; they usually take weeks or longer to have comparable antidepressant effects as ketamine does."

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist, which means that it works by blocking the actions of NMDA. Dr. Zarate added, “Importantly, confirmation that blocking the NMDA receptor complex is involved in generating rapid antidepressant and antisuicidal effects offers an avenue for developing the next generation of treatments for depression that are radically different than existing ones.”

Source: Science Daily

May 30, 2012

(Medical Xpress) — The first large non-commercial study to investigate whether the main active constituent of cannabis (tetrahydrocannabinol or THC) is effective in slowing the course of progressive multiple sclerosis (MS) shows that there is no evidence to suggest this; although benefits were noted for those at the lower end of the disability scale.

The CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study was carried out by researchers from the Peninsula College of Medicine and Dentistry (PCMD), Plymouth University. The study was funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership, the Multiple Sclerosis Society and the Multiple Sclerosis Trust.

The preliminary results of CUPID were presented by lead researcher Professor John Zajicek at the Association of British Neurologists’ Annual Meeting in Brighton on Tuesday 29th May.

CUPID enrolled nearly 500 people with MS from 27 centres around the UK, and has taken eight years to complete. People with progressive MS were randomised to receive either THC capsules or identical placebo capsules for three years, and were carefully followed to see how their MS changed over this period. The two main outcomes of the trial were a disability scale administered by neurologists (the Expanded Disability Status Scale), and a patient report scale of the impact of MS on people with the condition (the Multiple Sclerosis Impact Scale 29).

Overall the study found no evidence to support an effect of THC on MS progression in either of the main outcomes. However, there was some evidence to suggest a beneficial effect in participants who were at the lower end of the disability scale at the time of enrolment but, as the benefit was only found in a small group of people rather than the whole population, further studies will be needed to assess the robustness of this finding. One of the other findings of the trial was that MS in the study population as a whole progressed slowly, more slowly than expected. This makes it more challenging to find a treatment effect when the aim of the treatment is that of slow progression.

As well as evaluating the potential neuroprotective effects and safety of THC over the long-term, one of the aims of the CUPID study was to improve the way that clinical trial research is done by exploring newer methods of measuring MS and using the latest statistical methods to make the most of every piece of information collected. This analysis will continue for several months. The CUPID study will therefore provide important information about conducting further large scale clinical trials in MS.

Professor John Zajicek, Professor of Clinical Neuroscience at PCMD, Plymouth University, said: “To put this study into context: current treatments for MS are limited, either being targeted at the immune system in the early stages of the disease or aimed at easing specific symptoms such as muscle spasms, fatigue or bladder problems. At present there is no treatment available to slow MS when it becomes progressive. Progression of MS is thought to be due to death of nerve cells, and researchers around the world are desperately searching for treatments that may be ‘neuroprotective’. Laboratory experiments have suggested that certain cannabis derivatives may be neuroprotective.”

He added: “Overall our research has not supported laboratory based findings and shown that, although there is a suggestion of benefit to those at the lower end of the disability scale when they joined CUPID, there is little evidence to suggest that THC has a long term impact on the slowing of progressive MS.”

Dr. Doug Brown, Head of Biomedical Research at the MS Society, said: “There are currently no treatments for people with progressive MS to slow or stop the worsening of disability. The MS Society is committed to supporting research in this area and this was an important study for us to fund. While this study sadly suggests THC is ineffective at slowing the course of progressive MS, we will not stop our search for effective treatments. We are encouraged by the possibility shown by this study that THC may have potential benefits for some people with MS and we welcome further investigation in this area.”

Provided by University of Plymouth

Source: medicalxpress.com

ScienceDaily (May 29, 2012) — A specific antioxidant supplement may be an effective therapy for some features of autism, according to a pilot trial from the Stanford University School of Medicine and Lucile Packard Children’s Hospital that involved 31 children with the disorder.

The antioxidant, called N-Acetylcysteine, or NAC, lowered irritability in children with autism as well as reducing the children’s repetitive behaviors. The researchers emphasized that the findings must be confirmed in a larger trial before NAC can be recommended for children with autism.

Irritability affects 60 to 70 percent of children with autism. “We’re not talking about mild things: This is throwing, kicking, hitting, the child needing to be restrained,” said Antonio Hardan, MD, the primary author of the new study. “It can affect learning, vocational activities and the child’s ability to participate in autism therapies.”

The study appears in the June 1 issue of Biological Psychiatry. Hardan is an associate professor of psychiatry and behavioral sciences at Stanford and director of the Autism and Developmental Disabilities Clinic at Packard Children’s. Stanfordis filing a patent for the use of NAC in autism, and one of the study authors has a financial stake in a company that makes and sells the NAC used in the trial.

Finding new medications to treat autism and its symptoms is a high priority for researchers. Currently, irritability, mood swings and aggression, all of which are considered associated features of autism, are treated with second-generation antipsychotics. But these drugs cause significant side effects, including weight gain, involuntary motor movements and metabolic syndrome, which increases diabetes risk. By contrast, side effects of NAC are generally mild, with gastrointestinal problems such as constipation, nausea, diarrhea and decreased appetite being the most common.

The state of drug treatments for autism’s core features, such as social deficits, language impairment and repetitive behaviors, is also a major problem. “Today, in 2012, we have no effective medication to treat repetitive behavior such as hand flapping or any other core features of autism,” Hardan said. NAC could be the first medication available to treat repetitive behavior in autism — if the findings hold up when scrutinized further.

The study tested children with autism ages 3 to 12. They were physically healthy and were not planning any changes in their established autism treatments during the trial. In a double-blind study design, children received NAC or a placebo for 12 weeks. The NAC used was a pharmaceutical-grade preparation donated by the drug manufacturer Bioadvantex Inc. Subjects were evaluated before the trial began and every four weeks during the study using several standardized surveys that measure problem behaviors, social behaviors, autistic preoccupations and drug side effects.

During the 12-week trial, NAC treatment decreased irritability scores from 13.1 to 7.2 on the Aberrant Behavior Checklist, a widely used clinical scale for assessing irritability. The change is not as large as that seen in children taking antipsychotics. “But this is still a potentially valuable tool to have before jumping on these big guns,” Hardan said.

In addition, according to two standardized measures of autism mannerisms and stereotypic behavior, children taking NAC showed a decrease in repetitive and stereotyped behaviors.

"One of the reasons I wanted to do this trial was that NAC is being used by community practitioners who focus on alternative, non-traditional therapies," Hardan said. "But there is no strong scientific evidence to support these interventions. Somebody needs to look at them."

Hardan cautioned that the NAC for sale as a dietary supplement at drugstores and grocery stores differs in some important respects from the individually packaged doses of pharmaceutical-grade NAC used in the study, and that the over-the-counter version may not produce the same results. “When you open the bottle from the drugstore and expose the pills to air and sunlight, it gets oxidized and becomes less effective,” he said.

Although the study did not test how NAC works, the researchers speculated on two possible mechanisms of action. NAC increases the capacity of the body’s main antioxidant network, which some previous studies have suggested is deficient in autism. In addition, other research has suggested that autism is related to an imbalance in excitatory and inhibitory neurotransmitters in the brain. NAC can modulate the glutamatergic family of excitatory neurotransmitters, which might be useful in autism.

The scientists are now applying for funding to conduct a large, multicenter trial in which they hope to replicate their findings.

"This was a pilot study," Hardan said. "Final conclusions cannot be made before we do a larger trial."

Source: Science Daily

ScienceDaily (May 29, 2012) — TAU research finds that existing diabetes medication may ease damage caused by brain-addling explosions.

Although the death toll is relatively low for people who suffer from traumatic brain injury (TBI), it can have severe, life-long consequences for brain function. TBI can impair a patient’s mental abilities, impact memory and behavior, and lead to dramatic personality changes. And long-term medical treatment carries a high economic cost.

Now, in research commissioned by the United States Air Force, Prof. Chaim Pick of Tel Aviv University’s Sackler Faculty of Medicine and Dr. Nigel Greig of the National Institute of Aging in the US have discovered that Exendin-4, an FDA-approved diabetes drug, significantly minimizes damage in TBI animal models when administered shortly after the initial incident. Originally designed to control sugar levels in the body, the drug has recently been found effective in protecting neurons in disorders such as Alzheimer’s disease.

Prof. Pick’s collaborators include his TAU colleagues Dr. Vardit Rubovitch, Lital Rachmany-Raber, and Prof. Shaul Schreiber, and Dr. David Tweedie of the National Institute of Aging in the US. Detailed in the journal Experimental Neurology, this breakthrough is the first step towards developing a cocktail of medications to prevent as much brain damage as possible following injury.

Diabetes medication to halt trauma

Prof. Pick has been researching TBI for many years, beginning with the effects of everyday injuries such as hitting the windshield in a car accident. As a result of his work for the Air Force, he has expanded his research to include trauma sustained when a person is exposed to an explosion, such as during a terrorist attack.

TBI causes long-term damage by changing the chemistry of the brain. During an explosion, increased pressure followed by an intense vacuum shakes the fluid inside the brain and damages the brain’s structure. This damage cannot be reversed, but mapping the injury through behavioral and physical tests is crucial to understanding and quantifying the damage and forming a treatment plan through therapy or medication.

Prof. Pick and his colleagues designed a pre-clinical experiment that exposed mice to controlled explosions from 23 and 33 feet away, and then analyzed the resulting injuries. They also studied the effect of Exendin-4 as an additional parameter in minimizing brain damage.

The researchers divided their mice into four groups: a control group; a second group that was exposed to the blast without medication; a third group that received the medication but was not exposed to the blast; and a fourth group, exposed to the explosion but given the medication within an hour after the blast and continuing for seven days afterwards. The mice were placed under anesthesia before the explosion.

Behavioral and physical tests showed that the mice that had been exposed to the blast had severely impaired brain function compared to the control group. However, the mice that had also received the Exendin-4 treatment were almost on a par with the control group in terms of brain function, proving that Exendin-4 significantly reduced the long-term damage done by an explosion. In separate experiments, the drug was also associated with an improved outcome in mice who sustained TBI by blunt force.

Finding the ideal drug cocktail

Prof. Pick says this promising discovery can help researchers find the ideal combination of medications to minimize the lasting impact of TBI. “We are moving in the right direction. Now we need to find the right dosage and delivery system, then build a cocktail of drugs that will increase the therapeutic value of this concept,” he explains. He adds that in treating such traumatic injuries, one drug is unlikely to be sufficient.

Source: Science Daily

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.

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, 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

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.

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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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.

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

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 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, 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.

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.”

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, 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, 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, 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