Neuroscience

ScienceDaily (Mar. 19, 2012) — Researchers from Chalmers and the University of Gothenburg have shown that nanocellulose stimulates the formation of neural networks. This is the first step toward creating a three-dimensional model of the brain. Such a model could elevate brain research to totally new levels, with regard to Alzheimer’s disease and Parkinson’s disease, for example.

Nerve cells growing on a three-dimensional nanocellulose scaffold. One of the applications the research group would like to study is destruction of synapses between nerve cells, which is one of the earliest signs of Alzheimer’s disease. Synapses are the connections between nerve cells. In the image, the functioning synapses are yellow and the red spots show where synapses have been destroyed. (Credit: Illustration: Philip Krantz, Chalmers)

Over a period of two years the research group has been trying to get human nerve cells to grow on nanocellulose.

"This has been a great challenge," says Paul Gatenholm, Professor of Biopolymer Technology at Chalmers.‟Until recently the cells were dying after a while, since we weren’t able to get them to adhere to the scaffold. But after many experiments we discovered a method to get them to attach to the scaffold by making it more positively charged. Now we have a stable method for cultivating nerve cells on nanocellulose."

When the nerve cells finally attached to the scaffold they began to develop and generate contacts with one another, so-called synapses. A neural network of hundreds of cells was produced. The researchers can now use electrical impulses and chemical signal substances to generate nerve impulses, that spread through the network in much the same way as they do in the brain. They can also study how nerve cells react with other molecules, such as pharmaceuticals.

The researchers are trying to develop ‟artificial brains,” which may open entirely new possibilities in brain research and health care, and eventually may lead to the development of biocomputers. Initially the group wants to investigate destruction of synapses between nerve cells, which is one of the earliest signs of Alzheimer’s disease. For example, they would like to cultivate nerve cells and study how cells react to the patients’ spinal fluid.

In the future this method may be useful for testing various pharmaceutical candidates that could slow down the destruction of synapses. In addition, it could provide a better alternative to experiments on animals within the field of brain research in general.

The ability to cultivate nerve cells on nanocellulose is an important step ahead since there are many advantages to the material.

‟Pores can be created in nanocellulose, which allows nerve cells to grow in a three-dimensional matrix. This makes it extra comfortable for the cells and creates a realistic cultivation environment that is more like a real brain compared with a three-dimensional cell cultivation well,” says Paul Gatenholm.

Paul Gatenholm says that there are a number of new biomedical applications for nanocellulose. He is currently also leading other projects that use the material, for example a project where researchers are using nanocellulose to develop cartilage to create artificial outer ears. His research group has previously developed artificial blood vessels made of nanocellulose, which are being evaluated in pre-clinical studies.

Research on new application areas for nanocellulose is of major strategic significance for Sweden. Several projects are financed by the Knut and Alice Wallenberg Foundation and being conducted in collaboration between Chalmers and KTH within the Wallenberg Wood Science Center, WWSC.

Facts about nanocellulose: Nanocellulose is a material that consists of nanosized cellulose fibers. Typical dimensions are widths of 5 to 20 nanometers and lengths of up to 2,000 nanometers. Nanocellulose can be produced by bacteria that spin a close-meshed structure of cellulose fibers. It can also be isolated from wood pulp through processing in a high-pressure homogenizer.

Source: Science Daily

March 16, 2012 By Anne Trafton 

Alan Jasanoff. Credit: Allegra Boverman

After finishing his PhD in molecular biophysics, Alan Jasanoff decided to veer away from that field and try looking into some of the biggest questions in neuroscience: How do we perceive things? What happens in our brains when we make decisions?

After a few months, however, he realized that he didn’t have the tools he wanted to use — so he decided to start making his own.

Jasanoff, who recently earned tenure in MIT’s Department of Biological Engineering, now specializes in developing novel brain-imaging agents that can reveal information more detailed than other human brain-imaging techniques such as fMRI and PET, and more comprehensive than traditional neuroscience measurements such as microscopy and electrode recordings. With the new tools, he is also beginning to explore some of the fundamental questions that first drew him into neuroscience.

Neuroscientists commonly use fMRI, which measures blood flow in the brain, as a proxy for neural activity. In the past several years, Jasanoff has developed sensors that can be used with fMRI to image brain activity more directly, by measuring levels of neurotransmitters (the chemicals that carry messages between neurons) and calcium, which enters neurons when they fire.

Using those sensors, Jasanoff has started exploring how positive reinforcement influences behavior and decision making in animals. His work could also be applicable to fields outside of neuroscience, because intracellular signaling molecules such as calcium “are really ubiquitous — not just in neuronal signaling but signaling throughout the body, during development, immune-cell activity and so on,” says Jasanoff, who is an associate member of MIT’s McGovern Institute for Brain Research and an associate professor of biological engineering, nuclear science and engineering, and brain and cognitive sciences.

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March 16, 2012

Distinct patterns of activity— which may indicate a predisposition to care for infants — appear in the brains of adults who view an image of an infant face — even when the child is not theirs, according to a study by researchers at the National Institutes of Health and in Germany, Italy, and Japan.

Seeing images of infant faces appeared to activate in the adult’s brains circuits that reflect preparation for movement and speech as well as feelings of reward.

The findings raise the possibility that studying this activity will yield insights into care giving behavior, but also in cases of child neglect or abuse.

"These adults have no children of their own. Yet images of a baby’s face triggered what we think might be a deeply embedded response to reach out and care for that child," said senior author Marc H. Bornstein, Ph.D., head of the Child and Family Research Section of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the NIH institute that collaborated on the study.

While the researchers recorded participants’ brain activity, the participants did not speak or move. Yet their brain activity was typical of patterns preceding such actions as picking up or talking to an infant, the researchers explained. The activity pattern could represent a biological impulse that governs adults’ interactions with small children.

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March 15th, 2012

Researchers have identified the first gene mutation associated with a chronic and often fatal form of neuroblastoma that typically strikes adolescents and young adults. The finding provides the first clue about the genetic basis of the long-recognized but poorly understood link between treatment outcome and age at diagnosis.

The study involved 104 infants, children and young adults with advanced neuroblastoma, a cancer of the sympathetic nervous system. Investigators discovered the ATRX gene was mutated only in patients age 5 and older. The alterations occurred most often in patients age 12 and older. These older patients were also more likely than their younger counterparts to have a chronic form of neuroblastoma and die years after their disease is diagnosed.

The findings suggest that ATRX mutations might represent a new subtype of neuroblastoma that is more common in older children and young adults. The work is from the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project (PCGP). The study appears in the March 14 edition of the Journal of the American Medical Association.

If validated, the results may change the way doctors think about this cancer, said co-author Richard Wilson, PhD, director of The Genome Institute at Washington University School of Medicine in St. Louis.

“This suggests we may need to think about different treatment strategies for patients depending on whether or not they have the ATRX mutation,” he says.

Neuroblastoma accounts for 7 percent to 10 percent of all childhood cancers and about 15 percent of pediatric cancer deaths. In about 50 percent of patients, the disease has already spread when the cancer is discovered.

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March 15, 2012

In Batten disease, a rare but fatal neurodegenerative disorder in infants and children, proteins (shown in pink) accumulate in the brain and contribute to mental decline, paralysis and seizures. In mice with the infantile form of the disease, combination treatment with gene therapy and bone marrow transplantation reduced the buildup of proteins, dramatically increasing life span and improving motor function. Credit: Mark Sands, Ph.D

Infants with Batten disease, a rare but fatal neurological disorder, appear healthy at birth. But within a few short years, the illness takes a heavy toll, leaving children blind, speechless and paralyzed. Most die by age 5.

There are no effective treatments for the disease, which can also strike older children. And several therapeutic approaches, evaluated in mouse models and in young children, have produced disappointing results.

But now, working in mice with the infantile form of Batten disease, scientists at Washington University School of Medicine in St. Louis and Kings College London have discovered dramatic improvements in life span and motor function by treating the animals with gene therapy and bone marrow transplants.

The results are surprising, the researchers say, because the combination therapy is far more effective than either treatment alone. Gene therapy was moderately effective in the mice, and bone marrow transplants provided no benefit, but together the two treatments created a striking synergy.

The research is online in the Annals of Neurology.

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ScienceDaily (Mar. 15, 2012) — Odds are, you’re not going to make it all the way through this article without thinking about something else. In fact, studies have found that our minds are wandering half the time, drifting off to thoughts unrelated to what we’re doing — did I remember to turn off the light? What should I have for dinner?

Odds are, you’re not going to make it all the way through this article without thinking about something else. In fact, studies have found that our minds are wandering half the time, drifting off to thoughts unrelated to what we’re doing — did I remember to turn off the light? What should I have for dinner? (Credit: © Yuri Arcurs / Fotolia)

A new study investigating the mental processes underlying a wandering mind reports a role for working memory, a sort of a mental workspace that allows you to juggle multiple thoughts simultaneously.

Imagine you see your neighbor upon arriving home one day and schedule a lunch date. On your way to add it to your calendar, you stop to turn off the drippy faucet, feed the cat, and add milk to your grocery list. The capacity that allows you to retain the lunch information through those unrelated tasks is working memory.

The new study, published online March 14 in the journal Psychological Science by Daniel Levinson and Richard Davidson at the University of Wisconsin-Madison and Jonathan Smallwood at the Max Planck Institute for Human Cognitive and Brain Science, reports that a person’s working memory capacity relates to the tendency of their mind to wander during a routine assignment. Lead author Levinson is a graduate student with Davidson, a professor of psychology and psychiatry, in the Center for Investigating Healthy Minds at the UW-Madison Waisman Center.

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ScienceDaily (Mar. 14, 2012) — The meal is pushed way, untouched. Loss of appetite can be a fleeting queasiness or continue to the point of emaciation. While it’s felt in the gut, more is going on inside the head.

New findings are emerging about brain and body messaging pathways that lead to loss of appetite, and the systems in place to avoid starvation.

Today, scientists report in Nature about a brain circuit that mediates the loss of appetite in mice. The researchers also discovered potential therapeutic targets within the pathway. Their experimental results may be valuable for developing new treatments for a variety of eating disorders. These include unrelenting nausea, food aversions, and anorexia nervosa, a condition in which a person no longer wants to eat enough to maintain a normal weight.

The senior author of the paper is Dr. Richard D. Palmiter, University of Washington professor of biochemistry and an investigator with the Howard Hughes Medical Institute. His co-authors are Dr. Qi Wu, formerly of the UW and now at the Eagles Diabetes Research Center and Department of Pharmacology at Carver College of Medicine, University of Iowa, and Dr. Michael S. Clark of the UW Department of Psychiatry and Behavioral Sciences. Palmiter is known for co-developing the first transgenic mice in the 1980s with Dr. Ralph Brinster at the University of Pennsylvania. His more recent studies are of chemicals that nerve cells use to communicate with each other, their roles in mouse brain development and function, and their relation to behavior.

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ScienceDaily (Mar. 14, 2012) — The difficulties that many women describe as memory problems when menopause approaches are real, according to a study published recently  in the journal Menopause, the journal of the North American Menopause Society.

The findings won’t come as a surprise to the millions of women who have had bouts of forgetfulness or who describe struggles with “brain fog” in their late 40s and 50s. But the results of the study, by scientists at the University of Rochester Medical Center and the University of Illinois at Chicago who gave women a rigorous battery of cognitive tests, validate their experiences and provide some clues to what is happening in the brain as women hit menopause.

"The most important thing to realize is that there really are some cognitive changes that occur during this phase in a woman’s life," said Miriam Weber, Ph.D., the neuropsychologist at the University of Rochester Medical Center who led the study. "If a woman approaching menopause feels she is having memory problems, no one should brush it off or attribute it to a jam-packed schedule. She can find comfort in knowing that there are new research findings that support her experience. She can view her experience as normal."

The study is one of only a handful to analyze in detail a woman’s brain function during menopause and to compare those findings to the woman’s own reports of memory or cognitive difficulties.

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ScienceDaily (Mar. 14, 2012) — People with symptoms suggesting rapid eye movement sleep behavior disorder, or RBD, have twice the risk of developing mild cognitive impairment (MCI) or Parkinson’s disease within four years of diagnosis with the sleep problem, compared with people without the disorder, a Mayo Clinic study has found.

The researchers published their findings recently in the Annals of Neurology.

One of the hallmarks of rapid eye movement (REM) sleep is a state of paralysis. In contrast, people with rapid eye movement sleep behavior disorder, appear to act out their dreams when they are in REM sleep. Researchers used the Mayo Sleep Questionnaire to diagnose probable RBD in people who were otherwise neurologically normal. Approximately 34 percent of people diagnosed with probable RBD developed MCI or Parkinson’s disease within four years of entering the study, a rate 2.2 times greater than those with normal rapid eye movement sleep.

"Understanding that certain patients are at greater risk for MCI or Parkinson’s disease will allow for early intervention, which is vital in the case of such disorders that destroy brain cells. Although we are still searching for effective treatments, our best chance of success is to identify and treat these disorders early, before cell death," says co-author Brad Boeve, M.D., a Mayo Clinic neurologist.

Previous studies of Mayo Clinic patients have shown that an estimated 45 percent of people who suffer from RBD will develop a neurodegenerative syndrome such as mild cognitive impairment or Parkinson’s disease within five years of diagnosis.

RBD, MCI and Parkinson’s Disease

"This study is the first to quantify the risk associated with probable RBD in average people, not clinical patients, and it shows that we can predict the onset of some neurodegenerative disorders simply by asking a few critical questions," says lead author Brendon P. Boot, M.D., a behavioral neurologist. Dr. Boot was at Mayo Clinic when the study was conducted. He is now at Harvard University.

• MCI is an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. It involves problems with memory, language, thinking and judgment that are greater than typical age-related changes.
• An estimated 500,000 Americans suffer from Parkinson’s disease, which is characterized by tremor or shakiness, stiffness of the limbs and trunk, slowness of movement, and impaired balance and coordination. 

Source: Science Daily

ScienceDaily (Mar. 14, 2012) — How are 100 billion cells created, each with specific duties? The human brain is evidence that nature can achieve this. Researchers at Linköping University in Sweden have now taken a step closer to solving this mystery.

The magenta-colored structures are nerve cells that use odourant receptor 47b, which senses pheromones. Expression of this receptor is controlled by the transcription factor E93. When E93 is removed, the neurons lose their ability to fulfill their task do detect pheromones, as evidenced by the deactivation of the fluorescent proteins (image to the right). The glowing, green cells, that use olfactory receptor 92a, are not affected because they are controlled by other transcription factors. (Credit: Image courtesy of Linkoeping Universitet)

"Knowledge about the mechanisms that diversify neurons and keep them diverse is necessary in order to cultivate and replace nerve cells in the future," says Mattias Alenius, Assistant Professor of Neuroscience, who has published his research breakthrough in the current issue of the journal PLoS Biology.

Alenius and his research team at the Department of Experimental and Clinical Medicine seek the answer to this pivotal question from a smaller perspective: the fruit fly’s olfactory system.

The humble fly’s olfactory system consists of 1200 olfactory neurons (humans have six million) divided into 34 groups. Each group responds to a particular set of odours, since all the neurons of the group use only one of the olfactory receptors present in the fly’s antennas. Together, the receptors provide the fly with the ability to distinguish between thousands of odours: one olfactory receptor — one neuron group, simple yet complex.

Alenius and his colleagues are the first to go through all of the fruit fly’s 753 gene regulatory genes, called transcription factors. They have identified a set of seven that, in different combinations, are required to create each of the 34 neuron groups in the antenna. A surprising finding is that most transcription factors perform two tasks simultaneously: they can activate odorant receptors’ expression; while at the same time turning off others in the same cell.

Alenius explains, “This is one of the many tricks that are useful to know for the future if you want to make and cultivate each of the many thousands of nerve cell groups that make up our brains.”

Source: Science Daily

March 14, 2012

Earlier evidence out of UCLA suggested that meditating for years thickens the brain (in a good way) and strengthens the connections between brain cells. Now a further report by UCLA researchers suggests yet another benefit.

Eileen Luders, an assistant professor at the UCLA Laboratory of Neuro Imaging, and colleagues, have found that long-term meditators have larger amounts of gyrification (“folding” of the cortex, which may allow the brain to process information faster) than people who do not meditate. Further, a direct correlation was found between the amount of gyrification and the number of meditation years, possibly providing further proof of the brain’s neuroplasticity, or ability to adapt to environmental changes.

The article appears in the online edition of the journal Frontiers in Human Neuroscience.

The cerebral cortex is the outermost layer of neural tissue. Among other functions, it plays a key role in memory, attention, thought and consciousness. Gyrification or cortical folding is the process by which the surface of the brain undergoes changes to create narrow furrows and folds called sulci and gyri. Their formation may promote and enhance neural processing. Presumably then, the more folding that occurs, the better the brain is at processing information, making decisions, forming memories and so forth.

"Rather than just comparing meditators and non-meditators, we wanted to see if there is a link between the amount of meditation practice and the extent of brain alteration," said Luders. "That is, correlating the number of years of meditation with the degree of folding."

The researchers took MRI scans of 50 meditators, 28 men and 22 women, and compared them to 50 control subjects matched for age, handedness and sex. The scans for the controls were obtained from an existing MRI database, while the meditators were recruited from various meditation venues. The meditators had practiced their craft on average for 20 years using a variety of meditation types — Samatha, Vipassana, Zen and more. The researchers applied a well-established and automated whole-brain approach to measure cortical gyrification at thousands of points across the surface of the brain.

They found pronounced group differences (heightened levels of gyrification in active meditation practitioners) across a wide swatch of the cortex, including the left precentral gyrus, the left and right anterior dorsal insula, the right fusiform gyrus and the right cuneus.

Perhaps most interesting, though, was the positive correlation between the number of meditation years and the amount of insular gyrification.

"The insula has been suggested to function as a hub for autonomic, affective and cognitive integration," said Luders. "Meditators are known to be masters in introspection and awareness as well as emotional control and self-regulation, so the findings make sense that the longer someone has meditated, the higher the degree of folding in the insula."

While Luders cautions that genetic and other environmental factors could have contributed to the effects the researchers observed, still, “The positive correlation between gyrification and the number of practice years supports the idea that meditation enhances regional gyrification.”

Provided by University of California - Los Angeles

Source: medicalxpress.com

March 14, 2012 By Bill Hathaway

The aging brain loses its ability to recognize when it is time to move on to a new task, explaining why the elderly have difficulty multi-tasking, Yale University researchers report.

“The aged brain seems to get lost in transition,” said Mark Laubach, associate professor at the John B. Pierce Laboratory and the Yale School of Medicine, and senior author of a study that appears in the March 14 issue of The Journal of Neuroscience.

Laubach’s team was studying the impact of aging on working memory, the type of memory that allows you to recall that dinner is in the oven when you are talking on the phone. The researchers examined brain activity in the medial prefrontal cortex of young and older rats that is related to spatial working memory — the type of memory that allows you to recall, for example, that mashed potatoes are on the stove and the turkey is in the oven

Based on previous studies, they expected that it would be spatial memory most affected by aging. Instead, the Yale team found that the aged brain seems to lose its ability to respond to cues that indicate when it is time to move on to a new task.

This ability to transition between tasks is critical for many daily activities, such as cooking dinner or handling situations that can arise in the workplace. The brain’s failure to monitor the timing of actions leads people to forget to turn off a burner on the stove while setting the table.

The research team found that neurons in the medial prefrontal cortex of older rats reacted more slowly to signals indicating that reward was available. Conversely, these signals immediately triggered a response in younger rats.

“Neurons in older rats fired fewer spikes in response to reward-predictive cues. The animals failed to respond immediately to the cues. They seemed to be stuck in time,” Laubach said.

Researchers hope that by understanding the mechanisms of working memory, scientists might one day be able to slow or perhaps eliminate deterioration of these brain functions over a lifespan, Laubach said.

Provided by Yale University

Source: medicalxpress.com

March 14, 2012 by Catherine Zandonella

(Medical Xpress) — Princeton University researchers have used a novel virtual reality and brain imaging system to detect a form of neural activity underlying how the brain forms short-term memories that are used in making decisions.

Using a virtual reality maze and brain imaging system, Princeton researchers have detected a form of neural activity the formation of short-term memories used in decision-making. These panels show the view of the virtual reality maze as seen by the mouse. The top panel shows a cue or sign that indicates to the mouse to turn right to receive a water reward. The middle panel shows a cue telling the mouse to turn left. The bottom panel shows the view at the T-intersection of the maze. (Image courtesy of Nature, Christopher Harvey and David Tank)

By following the brain activity of mice as they navigated a virtual reality maze, the researchers found that populations of neurons fire in distinctive sequences when the brain is holding a memory. Previous research centered on the idea that populations of neurons fire together with similar patterns to each other during the memory period.

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March 13, 2012

The next time you set a trap for that rat running around in your basement, here’s something to consider: you are going up against an opponent whose ability to assess the situation and make decisions is statistically just as good as yours.

A Cold Spring Harbor Laboratory (CSHL) study that compared the ability of humans and rodents to make perceptual decisions based on combining different modes of sensory stimuli—visual and auditory cues, for instance—has found that just like humans, rodents also combine multisensory information and exploit it in a “statistically optimal” way — or the most efficient and unbiased way possible.

"Statistically optimal combination of multiple sensory stimuli has been well documented in humans, but many have been skeptical about this behavior occurring in other species," explains Assistant Professor Anne Churchland, Ph.D., a neuroscientist who led the new study. "Our work is the first demonstration of its occurrence in rodents." The study appears in the March 14 issue of the Journal of Neuroscience.

This discovery is exciting, according to Churchland, because it suggests that the same evolutionarily conserved neural circuits underlie this behavior in both humans and rodents. “By observing this behavior in rodents, we have a chance to explore its neural basis – something that is not feasible to do in people,” Churchland says.

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ScienceDaily (Mar. 13, 2012) — A team of neuroscientists led by a Wayne State University School of Medicine professor has discovered stark developmental differences in brain network function in children of parents with schizophrenia when compared to those with no family history of mental illness.

The study, led by Vaibhav Diwadkar, Ph.D., assistant professor of psychiatry and behavioral neurosciences and co-director of the Division of Brain Research and Imaging Neuroscience, was published in the March 2012 issue of the American Medical Association journal Archives of General Psychiatry and is titled, “Disordered Corticolimbic Interactions During Affective Processing in Children and Adolescents at Risk for Schizophrenia Revealed by Functional Magnetic Resonance Imaging and Dynamic Causal Modeling.”

The results provide significant insight into plausible origins of schizophrenia in terms of dysfunctional brain networks in adolescence, demonstrate sophisticated analyses of functional magnetic resonance imaging (fMRI) data and clarify the understanding of developmental mechanisms in normal versus vulnerable brains. The resulting information can provide unique information to psychiatrists.

The study took place over three years, using MRI equipment at Harper University Hospital in Detroit. Using fMRI the researchers studied brain function in young individuals (8 to 20 years of age) as they observed pictures of human faces depicting positive, negative and neutral emotional expressions. Participants were recruited from the metropolitan Detroit area. Because children of patients are at highly increased risk for psychiatric illnesses such as schizophrenia, the team was interested in studying brain network function associated with emotional processing and the relevance of impaired network function as a potential predictor for schizophrenia.

To investigate brain networks, the researchers applied advanced analyses techniques to the fMRI data to investigate how brain regions dynamically communicate with each other. The study demonstrated that children at risk for the illness are characterized by reduced network communication and disordered network responses to emotional faces. This suggests that brain developmental processes are going awry in children whose parents have schizophrenia, suggesting this is a subgroup of interest to watch in future longitudinal studies.

"Brain network dysfunction associated with emotional processing is a potential predictor for the onset of emotional problems that may occur later in life and that are in turn associated with illnesses like schizophrenia," Diwadkar said. "If you clearly demonstrate there is something amiss in how the brain functions in children, there is something you can do about it. And that’s what we’re interested in."

The results don’t show whether schizophrenia will eventually develop in the subjects. “It doesn’t mean that they have it, or that they will have it,” he said.

"The kids we studied were perfectly normal if you looked at them," he said. "By using functional brain imaging we are trying to get underneath behavior."

"We are able to do this because we can investigate dynamic changes in brain network function by assessing changes in the fMRI signal. This allowed us to capture dramatic differences in how regions in the brain network are interacting with each other," he said.

According to the National Alliance on Mental Illness, schizophrenia affects men and women with equal frequency, but generally manifests in men in their late teens or early 20s, and in women in their late 20s or early 30s.

Source: Science Daily

ScienceDaily (Mar. 13, 2012) — A compound that previously progressed to Phase II clinical trials for cancer treatment slows neurological damage and improves brain function in an animal model of Alzheimer’s disease, according to a new study. The study published the week of March 13 in the Journal of Neuroscience shows that the compound epothilone D (EpoD) is effective in preventing further neurological damage and improving cognitive performance in a mouse model of Alzheimer’s disease (AD). The results establish how the drug might be used in early-stage AD patients.

This is an electron micrographic picture of a cross section of a nerve from an Alzheimer’s model mouse. Structural abnormalities in the nerve are indicated by the arrows. Alzheimer model mice that received the drug epothilone D had a significant reduction in the number of these abnormalities. (Credit: Zhang, et al. The Journal of Neuroscience 2012.)

Investigators from the Perelman School of Medicine at the University of Pennsylvania, led by first author Bin Zhang, MD, PhD, senior research investigator, and senior author Kurt R. Brunden, PhD, Director of Drug Discovery at the Center for Neurodegenerative Disease Research (CNDR), administered EpoD to aged mice that had memory deficits and inclusions within their brains that resemble the tangles formed by misfolded tau protein, a hallmark of AD. In nerve cells, tau normally stabilizes structures called microtubules, the molecular railroad tracks upon which cellular cargo is transported. Tangles may compromise microtubule stability, with resulting damage to nerve cells. A drug that could increase microtubule stability might improve nerve-cell function in AD and other diseases where tangles form in the brain.

EpoD acts by the same microtubule-stabilizing mechanism as the FDA-approved cancer drug paclitaxel (Taxol™). These drugs prevent cancer cell proliferation by over-stabilizing specialized microtubules involved in the separation of chromosomes during the process of cell division. However, the Penn researchers previously demonstrated that EpoD, unlike paclitaxel, readily enters the brain and so may be useful for treating AD and related disorders.

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March 13, 2012

Warm weather may hinder cognitive performance in people with multiple sclerosis (MS), according to results of a Kessler Foundation study e-published online ahead of print by Neurology. An accompanying editorial by Meier & Christodoulou, MS and heat: The smoke and the fire, details the study’s unique aspects, ie, longitudinal followup in a cohort with apparently quiescent disease.

Victoria M. Leavitt, Ph.D., research scientist at Kessler Foundation, is principal investigator for the study, which for the first time, shows a link between warm weather and cognition in people with MS. With more research, this information might help guide people with MS in making life decisions and assist their clinicians in choosing clinical treatment. Scientists may also want to consider the effect of warmer weather on cognition when designing and conducting clinical trials.

Kessler Foundation co-investigators are James F. Sumowski, Ph.D., Research Scientist, Nancy Chiaravalloti, Ph.D., Director of Neuropsychology & Neuroscience Research, and John DeLuca, Ph.D., Vice President for Research. All also have faculty appointments at UMDNJ-New Jersey Medical School.

Memory and processing speed were measured in 40 individuals with MS and 40 healthy people without MS. The study was conducted throughout the calendar year, and the daily temperature at the time of testing was recorded. The results showed that people with MS scored 70 percent higher on the tests on cooler days. There was no connection between daily temperature and cognitive performance for individuals without MS.

To confirm the effect of outdoor temperature, the group examined a separate sample of 45 persons with MS for whom cognitive tests were given at two sessions separated by a 6-month interval. For each person, cognitive performance was worse for testing during the warmer temperature. This finding is particularly important for researchers planning clinical trials with cognitive outcomes, especially since such trials frequently span a 6-month period. If baseline measurements of cognitive function are taken during warm months, the effect of the treatment may be inflated by the temperature effect. Cognitive performance may be a more sensitive indicator of subclinical disease activity than traditional assessments based on sensorimotor or EDSS (Expanded Disability Status score).

Provided by Kessler Foundation

Source: medicalxpress.com

Article Date: 13 Mar 2012 - 1:00 PDT

More than two-thirds of human genes have counterparts in the well-studied fruit fly, Drosophila melanogaster, so although it may seem that humans don’t have much in common with flies, the correspondence of our genetic instructions is astonishing. In fact, there are hundreds of inherited diseases in humans that have Drosophila counterparts.

At the Genetics Society of America’s 53rd Annual Drosophila Research Conference in Chicago, several scientific investigators shared their knowledge of some of these diseases, including ataxia-telangiectasia (A-T), a neurodegenerative disorder; Rett Syndrome, a neurodevelopmental disorder; and kidney stones, a common health ailment. All are the subject on ongoing research using the Drosophila model system.

Andrew Petersen, a graduate student in Dr. David Wassarman’s laboratory at the University of Wisconsin-Madison, discussed his experiments with a fly model of the rare childhood disease ataxia-telangiectasia. A-T causes cell death within the brain, poor coordination, characteristic spidery blood vessels that show through the skin, and susceptibility to leukemias and lymphomas. A-T generally results in a life expectancy of only 25 years.

A-T is normally lethal in flies, but Mr. Petersen induced a mutant that develops symptoms only when the environmental temperature rises above a certain level, allowing Mr. Petersen to control the lethality by varying the fly’s environment. The mutant flies lose their ability to climb up the sides of their vial habitats - a sign of neurodegeneration - and die prematurely. Their glial cells are primarily affected, rather than the neurons that the glia support. In addition, an innate immune response is activated in the compromised glia, a scenario reminiscent of Alzheimer’s and Parkinson’s diseases. “We are one step closer to knowing how these diseases occur and possibly how we can treat them,” Mr. Petersen concluded.

Sarah Certel, Ph.D., assistant professor of biological sciences at the University of Montana-Missoula, works with flies that have been altered to include the human gene MeCP2. This gene controls how neurons use many other genes, and the amount of the protein that it encodes must be within a specific range for the brain to develop normally. Too little of the protein and Rett syndrome results, a disorder on the X chromosome, which exclusively affects females in childhood. (Males with this mutation are generally miscarried or are stillborn.) It causes a constellation of symptoms including characteristic hand-wringing, autism, seizures, cognitive impairment, and loss of mobility. Yet too much of the protein causes similar problems.

In flies, altered levels of the MeCP2 protein affect sleep and aggression. For flies and most model organisms, sleep is inferred as the absence of activity during the day and night. To study sleep, Dr. Certel conducted “actograms” for individual flies. “The actogram records the activities of individually housed flies when they cross an infrared beam,” she explained. The flies’ sleep became fragmented, delayed, and shortened. “We’re studying the link between the cellular changes and behaviors,” she added.

Switching from the brain to the urinary system, it was noted that “Drosophila get kidney stones too” began Julian Dow, Ph.D., professor of molecular and integrative physiology at the University of Glasgow, United Kingdom. The fly version of a kidney is much simpler in design, a quartet of Malpighian tubules that are conveniently transparent.

Dr. Dow discussed a fly mutant called “rosy,” discovered a century ago, that corresponds to the rare human inborn error of metabolism called xanthinuria type 1, as well as a diet-induced blockage that corresponds to the more common human condition of calcium oxalate kidney stones. In time-lapse video, Dr. Dow showed stones appearing and growing in the Malpighian tubule.

“This was the first time in history that we saw kidney stones form - something that you cannot ethically do in humans,” he said. His research group, in collaboration with Dr. Michael Romero at the Mayo Institute, is now searching for chemical compounds that interfere with the formation of stones and their tendency to accrete into painful obstructions. They’ve already found a way to block a gene responsible for transporting the oxalate, slowing stone formation. With time, this work could help reduce the 250,000 emergency room admissions for kidney stones in the USA annually and the more than $2 billion in health care costs for treating them.

These were only three of several human diseases discussed at the Drosophila Conference. Others included oxidative stress, cancer linked to diabetes, amyloid build-up in Alzheimer’s disease, epilepsy, and muscular dystrophy. There are so many human diseases that have Drosophila counterparts that they are listed in a database called Homophila. Given the number that exist, we are certain to be learning more about our health from the fly in the years ahead.  

Source: Medical News Today

ScienceDaily (Mar. 13, 2012) — One of the trickiest parts of treating brain conditions is the blood brain barrier, a blockade of cells that prevent both harmful toxins and helpful pharmaceuticals from getting to the body’s control center. But, a technique published in JoVE, uses an MRI machine to guide the use of microbubbles and focused ultrasound to help drugs enter the brain, which may open new treatment avenues for devastating conditions like Alzheimer’s and brain cancers.

"It’s getting close to the point where this could be done safely in humans," said paper-author Meaghan O’Reilly, "there is a push towards applications."

The current method of disrupting the blood-brain barrier (BBB) is by using osmotic agents such as mannitol, which suck the water out of the cells that form the barrier, causing the gaps between them to get bigger. Unfortunately, this method opens large areas of the barrier, leaving the brain exposed to toxins.

The benefit of the microbubble technique is that it can be used on a very small area of the BBB. The microbubbles, made of lipids (fats) and gas, are injected into the blood stream. When focused ultrasound is applied, the bubbles expand and contract. It is thought that the force of the movement in the bubbles causes the cells that form the BBB to temporarily separate, which allows drugs to reach the brain.

"Microbubble technology has been around for years, though its applications have mostly been as contrast agents for diagnostic ultrasound," said JoVE Editorial Director, Dr. Beth Hovey. "This newer approach, using ultrasound to help the bubbles permeablize the blood brain barrier, will hopefully allow for better treatment of diseases within the brain."

In this method, O’Reilly and her colleagues use the MRI machine to ensure that the barrier opens, and they can also time how long it takes for it to close, which will be important for when the technique is used on patients.

"The ability of focused ultrasound combined with microbubbles to disrupt the blood brain barrier has been known for over a decade. However, because the actual technique can be challenging — there are critical steps involved — the video article fills a gap in the literature that is a major hindrance to people getting into the field," she said.

Source: Science Daily

ScienceDaily (Mar. 13, 2012) — People often wonder if computers make children smarter. Scientists at the University of California, Berkeley, are asking the reverse question: Can children make computers smarter? And the answer appears to be ‘yes.’

Research indicates that babies and toddlers do most of their learning as they “play.” (Credit: © matka_Wariatka / Fotolia)

UC Berkeley researchers are tapping the cognitive smarts of babies, toddlers and preschoolers to program computers to think more like humans.

If replicated in machines, the computational models based on baby brainpower could give a major boost to artificial intelligence, which historically has had difficulty handling nuances and uncertainty, researchers said

"Children are the greatest learning machines in the universe. Imagine if computers could learn as much and as quickly as they do," said Alison Gopnik a developmental psychologist at UC Berkeley and author of "The Scientist in the Crib" and "The Philosophical Baby."

In a wide range of experiments involving lollipops, flashing and spinning toys, and music makers, among other props, UC Berkeley researchers are finding that children — at younger and younger ages — are testing hypotheses, detecting statistical patterns and drawing conclusions while constantly adapting to changes.

"Young children are capable of solving problems that still pose a challenge for computers, such as learning languages and figuring out causal relationships," said Tom Griffiths, director of UC Berkeley’s Computational Cognitive Science Lab. "We are hoping to make computers smarter by making them a little more like children."

For example, researchers said, computers programmed with kids’ cognitive smarts could interact more intelligently and responsively with humans in applications such as computer tutoring programs and phone-answering robots.

And that’s not all.

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March 12th, 2012

Regular use of cholesterol-lowering statin drugs may be associated with a modest reduction in risk for developing Parkinson disease, particularly among younger patients, according to a study in the March issue of Archives of Neurology, one of the JAMA Archives journals.

Statins are one of the most prescribed classes of drugs in the United States and some researchers have hypothesized that the anti-inflammatory and immunomodulating effects of these medications may be neuroprotective. However, statins also may have unfavorable effects on lowering the level of plasma coenzyme Q10, which may be neuroprotective in patients with Parkinson disease (PD), the researchers write in their study background.

Xiang Gao, M.D., Ph.D., of Brigham and Women’s Hospital and Harvard School of Public Health, Boston, and colleagues conducted a prospective study that included 38,192 men and 90,874 women participating in the Health Professional Follow-up study and the Nurses’ Health study.

During 12 years of follow-up from 1994 to 2006, researchers documented 644 incident PD cases (338 in women and 306 in men).

“In summary, we observed an association between regular use of statins and lower risk of developing PD, particularly among younger patients,” the researchers comment. “However, our results should be interpreted with caution because only approximately 70 percent of users of cholesterol-lowering drugs at baseline were actual statin users. Further, the results were only marginally significant and could be due to chance.”

Researchers note that because they classified the use of any cholesterol-lowering drugs before 2000 as statin use, misclassification was inevitably introduced. They also did not collect information on the use of specific statins, which could have different effects on the central nervous system.

When researchers did observe a significant interaction between statin use and age in relation to PD risk it was among study participants younger than 60 years at the start of follow-up, not among those participants who were older.

The authors note that not only have epidemiologic studies produced mixed results on statin use and PD risk, but statins also may have unfavorable effects on the central nervous system.

“In contrast with use of ibuprofen, which has been consistently found to be inversely associated with PD risk in these cohorts as well as in other longitudinal studies, the overall epidemiological evidence relating stain use to PD risk remains unconvincing,” the authors conclude. “Given the potential adverse effects of statins, further prospective observational studies are needed to explore the potential effects of different subtypes of statin on risk of PD and other neurodegenerative diseases.”
(Arch Neurol. 2012;69[3]:380-384).

Source: Neuroscience News

March 12th, 2012

Scientists from the Monell Center report that seven of 12 related mammalian species have lost the sense of sweet taste. As each of the sweet-blind species eats only meat, the findings demonstrate that a liking for sweets is frequently lost during the evolution of diet specialization.

Previous research from the Monell team had revealed the remarkable finding that both domestic and wild cats are unable to taste sweet compounds due to defects in a gene that controls structure of the sweet taste receptor.

Cats are obligate carnivores, meaning that they subsist only on meat. In the current study, published online in Proceedings of the National Academy of Sciences USA, the Monell scientists next asked whether other strict carnivores have also lost the sweet taste receptor.

To do this, they examined sweet taste receptor genes from 12 related mammalian species with varying dietary habits. They once again found taste loss and to their surprise, it was widespread in the meat-eating species.

Senior author Gary Beauchamp, Ph.D., a behavioral biologist at Monell, comments, “Sweet taste was thought to be nearly a universal trait in animals. That evolution has independently led to its loss in so many different species was quite unexpected.”

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ScienceDaily (Mar. 8, 2012) — A new study in Science suggests that thrill-seeking is not limited to humans and other vertebrates. Some honey bees, too, are more likely than others to seek adventure. The brains of these novelty-seeking bees exhibit distinct patterns of gene activity in molecular pathways known to be associated with thrill-seeking in humans, researchers report.

A new study in Science suggests that thrill-seeking is not limited to humans and other vertebrates. Some honey bees, too, are more likely than others to seek adventure. (Credit: L. Brian Stauffer)

The findings offer a new window on the inner life of the honey bee hive, which once was viewed as a highly regimented colony of seemingly interchangeable workers taking on a few specific roles (nurse or forager, for example) to serve their queen. Now it appears that individual honey bees actually differ in their desire or willingness to perform particular tasks, said University of Illinois entomology professor and Institute for Genomic Biology director

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ScienceDaily (Mar. 8, 2012) — How do neurons in the brain communicate with each other? One common theory suggests that individual cells do not exchange signals among each other, but rather that exchange takes place between groups of cells. Researchers from Japan, the United States and Germany have now developed a mathematical model that can be used to test this assumption. Their results have been published in the current issue of the journal “PLoS Computational Biology.”

A neuron in the neocortex, the part of the brain that deals with higher brain functions, contacts thousands of other neurons and receives as many inputs from other neurons. Previously, it has been very difficult to use measured signals to interpret the way the cells work together. Scientists at the RIKEN Brain Science Institute (BSI) in Japan have now joined forces with researchers at the Forschungszentrum Jülich, Germany, and MIT in Boston, USA, to develop a mathematical model that can clarify the way neurons collaborate.

"From the many signals measured in parallel, the novel method filters the information on whether the neurons communicate individually or as a group," explains Dr. Hideaki Shimazaki from BSI. "Furthermore it takes into account that these groups of cells are not fixed but, instead, can organize themselves flexibly within milliseconds into groups of different composition, depending on the current requirements of the brain."

Prof. Sonja Grün from Forschungszentrum Jülich hopes that the method can help researchers to prove the existence of dynamic cell assemblies and clearly assign their activities to certain behaviors. The scientists already demonstrated that neurons work together when an animal anticipates a signal, which may allow it to have a more rapid or more sensitive response.

In future, the scientists hope to learn how to use their methods on the signals recorded from hundreds of neurons simultaneously. This would raise the probability of observing cell assemblies involved in planning and controlling behavior.

Source: Science Daily

ScienceDaily (Mar. 8, 2012) — UT Southwestern Medical Center investigators have identified a genetic manipulation that increases the development of neurons in the brain during aging and enhances the effect of antidepressant drugs.

UT Southwestern Medical Center investigators have identified a genetic manipulation that increases the development of neurons in the brain during aging and enhances the effect of antidepressant drugs. (Credit: © rolffimages / Fotolia)

The research finds that deleting the Nf1 gene in mice results in long-lasting improvements in neurogenesis, which in turn makes those in the test group more sensitive to the effects of antidepressants.

"The significant implication of this work is that enhancing neurogenesis sensitizes mice to antidepressants — meaning they needed lower doses of the drugs to affect ‘mood’ — and also appears to have anti-depressive and anti-anxiety effects of its own that continue over time," said Dr. Luis Parada, director of the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration and senior author of the study published in The Journal of Neuroscience.

Just as in people, mice produce new neurons throughout adulthood, although the rate declines with age and stress, said Dr. Parada, chairman of developmental biology at UT Southwestern. Studies have shown that learning, exercise, electroconvulsive therapy and some antidepressants can increase neurogenesis. The steps in the process are well known but the cellular mechanisms behind those steps are not.

"In neurogenesis, stem cells in the brain’s hippocampus give rise to neuronal precursor cells that eventually become young neurons, which continue on to become full-fledged neurons that integrate into the brain’s synapses," said Dr. Parada, an elected member of the National Academy of Sciences, its Institute of Medicine, and the American Academy of Arts and Sciences.

The researchers used a sophisticated process to delete the gene that codes for the Nf1 protein only in the brains of mice, while production in other tissues continued normally. After showing that mice lacking Nf1 protein in the brain had greater neurogenesis than controls, the researchers administered behavioral tests designed to mimic situations that would spark a subdued mood or anxiety, such as observing grooming behavior in response to a small splash of sugar water.

The researchers found that the test group mice formed more neurons over time compared to controls, and that young mice lacking the Nf1 protein required much lower amounts of anti-depressants to counteract the effects of stress. Behavioral differences between the groups persisted at three months, six months and nine months. “Older mice lacking the protein responded as if they had been taking antidepressants all their lives,” said Dr. Parada.

"In summary, this work suggests that activating neural precursor cells could directly improve depression- and anxiety-like behaviors, and it provides a proof-of-principle regarding the feasibility of regulating behavior via direct manipulation of adult neurogenesis," Dr. Parada said.

Dr. Parada’s laboratory has published a series of studies that link the Nf1 gene — best known for mutations that cause tumors to grow around nerves — to wide-ranging effects in several major tissues. For instance, in one study researchers identified ways that the body’s immune system promotes the growth of tumors, and in another study, they described how loss of the Nf1 protein in the circulatory system leads to hypertension and congenital heart disease.

Source: Science Daily

March 9, 2012

(Medical Xpress) — Despite a century of research, memory encoding in the brain has remained mysterious. Neuronal synaptic connection strengths are involved, but synaptic components are short-lived while memories last lifetimes. This suggests synaptic information is encoded and hard-wired at a deeper, finer-grained molecular scale.

In an article in the March 8 issue of the journal PLoS Computational Biology, physicists Travis Craddock and Jack Tuszynski of the University of Alberta, and anesthesiologist Stuart Hameroff of the University of Arizona demonstrate a plausible mechanism for encoding synaptic memory in microtubules, major components of the structural cytoskeleton within neurons.

Microtubules are cylindrical hexagonal lattice polymers of the protein tubulin, comprising 15 percent of total brain protein. Microtubules define neuronal architecture, regulate synapses, and are suggested to process information via interactive bit-like states of tubulin. But any semblance of a common code connecting microtubules to synaptic activity has been missing. Until now.

The standard experimental model for neuronal memory is long term potentiation (LTP) in which brief pre-synaptic excitation results in prolonged post-synaptic sensitivity. An essential player in LTP is the hexagonal enzyme calcium/calmodulin-dependent protein kinase II (CaMKII). Upon pre-synaptic excitation, calcium ions entering post-synaptic neurons cause the snowflake-shaped CaMKII to transform, extending sets of 6 leg-like kinase domains above and below a central domain, the activated CaMKII resembling a double-sided insect. Each kinase domain can phosphorylate a substrate, and thus encode one bit of synaptic information. Ordered arrays of bits are termed bytes, and 6 kinase domains on one side of each CaMKII can thus phosphorylate and encode calcium-mediated synaptic inputs as 6-bit bytes. But where is the intra-neuronal substrate for memory encoding by CaMKII phosphorylation? Enter microtubules.

Using molecular modeling, Craddock et al reveal a perfect match among spatial dimensions, geometry and electrostatic binding of the insect-like CaMKII, and hexagonal lattices of tubulin proteins in microtubules. They show how CaMKII kinase domains can collectively bind and phosphorylate 6-bit bytes, resulting in hexagonally-based patterns of phosphorylated tubulins in microtubules. Craddock et al calculate enormous information capacity at low energy cost, demonstrate microtubule-associated protein logic gates, and show how patterns of phosphorylated tubulins in microtubules can control neuronal functions by triggering axonal firings, regulating synapses, and traversing scale.

Microtubules and CaMKII are ubiquitous in eukaryotic biology, extremely rich in brain neurons, and capable of connecting membrane and cytoskeletal levels of information processing. Decoding and stimulating microtubules could enable therapeutic intervention in a host of pathological processes, for example Alzheimer’s disease in which microtubule disruption plays a key role, and brain injury in which microtubule activities can repair neurons and synapses.

Hameroff, senior author on the study, said: “Many neuroscience papers conclude by claiming their findings may help understand how the brain works, and treat Alzheimer’s, brain injury and various neurological and psychiatric disorders. This study may actually do that. We may have a glimpse of the brain’s biomolecular code for memory.”

Provided by University of Arizona

Source: medicalxpress.com

ScienceDaily (Mar. 8, 2012) — The hair cells of the inner ear have a previously unknown “root” extension that may allow them to communicate with nerve cells and the brain to regulate sensitivity to sound vibrations and head position, researchers at the University of Illinois at Chicago College of Medicine have discovered.

Type 2 hair cell with hair cell rootlets ending as expected in the cuticular plate. (Credit: Copyright University of Illinois Board of Trustees/Artist, Anna Lysakowski)

Their finding is reported online in advance of print in the Proceedings of the National Academy of Sciences.

The hair-like structures, called stereocilia, are fairly rigid and are interlinked at their tops by structures called tip-links.

When you move your head, or when a sound vibration enters your ear, motion of fluid in the ear causes the tip-links to get displaced and stretched, opening up ion channels and exciting the cell, which can then relay information to the brain, says Anna Lysakowski, professor of anatomy and cell biology at the UIC College of Medicine and principal investigator on the study.

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ScienceDaily (Mar. 8, 2012) — In both animals and humans, vocal signals used for communication contain a wide array of different sounds that are determined by the vibrational frequencies of vocal cords. For example, the pitch of someone’s voice, and how it changes as they are speaking, depends on a complex series of varying frequencies. Knowing how the brain sorts out these different frequencies — which are called frequency-modulated (FM) sweeps — is believed to be essential to understanding many hearing-related behaviors, like speech. Now, a pair of biologists at the California Institute of Technology (Caltech) has identified how and where the brain processes this type of sound signal.

This diagram shows areas in the midbrain region where direction- selective neurons were found. (Credit: Guangying Wu/Caltech)

Their findings are outlined in a paper published in the March 8 issue of the journal Neuron.

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ScienceDaily (Mar. 8, 2012) — A new study led by the Neuroscience Institute of Alicante reveals how manipulating the endocannabinoid system can modulate high levels of impulsivity. This is the main problem in psychiatric illnesses such a schizophrenia, bipolar disorder and substance abuse.

Spanish researchers have for the first time demonstrated that the CB2 receptor, which has modulating functions in the nervous system, is involved in regulating impulsive behaviour.

"Such a result proves the relevance that manipulation of the endocannabinoid system can have in modulating high levels of impulsivity present in a wide range of psychiatric and neurological illness," explains Jorge Manzanares Robles, a scientist at the Alicante Neuroscience Institute and director of the study.

Carried out on mice, the study suggests the possibility of undertaking future clinical trials using drugs that selectively act on the CB2 and thus avoid the psychoactive effects deriving from receptor CB1 manipulation, whose role in impulsivity has already been proven.

However, the authors of the study published in the British Journal of Pharmacology remain cautious. Francisco Navarrete, lead author of the study, states that “it is still very early to be able to put forward a reliable therapeutic tool.”

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March 8, 2012

New research from the University of Calgary’s Hotchkiss Brain Institute shows that by using a CT scan (computerized tomography), doctors can predict which patients are at risk of continued bleeding in the brain after a stroke. This vital information will allow doctors to utilize the most powerful blood clotting medications for those with the highest risk.

One in three individuals will continue to accumulate blood in the brain from a leak in a small artery. Pooling blood in the brain has serious consequences, and could lead to disability or even death. Previously, doctors in emergency stroke situations could not discern whether or not a patient’s brain bleeding had stopped. Using CT scan images, researchers can now identify “spot signs” that are seen as a small area of contrast on the CT scan. This spot sign is the actual location of bleeding within an artery in the brain.

"Technology that has emerged has allowed us to see the brain’s blood flow system in exquisite detail to precisely identify the source of the problem," explains Dr. Andrew Demchuk, Professor in the departments of clinical neurosciences and radiology, and lead author of this study. "We are now at a point where we can harness this technology to develop better treatments for patients with a blockage or breakage in a brain artery. Ultimately this research will confirm when immediate treatment is necessary – essentially, as soon as you see the spot sign."

This research provides validation of a new imaging marker to identify patients that may need to be treated with clotting medications versus those that don’t. “We must be very careful when and to whom these drugs are administered because they are so powerful at forming clots. These drugs can cause clots not only where there are holes and leaks – but also in intact arteries –potentially causing stroke and heart attacks,” says Demchuk. “Therefore this CT scan selection is critical for targeting only those patients at highest risk of continued bleeding.”

Clinical trials have now begun to test powerful clotting drugs in these patients.

This University of Calgary-led “PREDICT” study was coordinated with researchers at the Universities of Ottawa and Toronto, along with collaboration amongst nine other centres around the world. Their results were published in the March 8th online edition of the prestigious journal Lancet Neurology.

Provided by University of Calgary

Source: medicalxpress.com

March 8, 2012

The left image shows GABA inhibitory neurons (labeled green) in the brain’s reward pathway. The right panel shows electrical activity of GABA inhibitory neuron in a saline-injected or methamphetamine (METH)-injected mouse. Activation of the GABA type B receptor normally silences electrical activity, but has no effect in a mouse 24 hours after a single injection of methamphetamine Credit: Courtesy of Kelly Tan and Claire Padgett, Salk Institute for Biological Studies

A single injection of cocaine or methamphetamine in mice caused their brains to put the brakes on neurons that generate sensations of pleasure, and these cellular changes lasted for at least a week, according to research by scientists at the Salk Institute for Biological Studies.

Their findings, reported March 7 in Neuron, suggest this powerful reaction to the drug assault may be a protective, anti-addiction response. The scientists theorize that it might be possible to mimic this response to treat addiction to these drugs and perhaps others, although more experiments are required to explore this possibility.

"It was stunning to discover that one exposure to these drugs could promote such a strong response that lasts well after the drug has left the body," says Paul Slesinger, an associate professor in the Clayton Foundation Laboratories for Peptide Biology. "We believe this could be the brain’s immediate response to counteract the stimulation of these drugs."

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ScienceDaily (Mar. 7, 2012) — While the thought of any type of surgery can be disconcerting, the thought of brain surgery can be downright frightening. But for people with a particular form of epilepsy, surgical intervention can literally be life-restoring.

A PET scan of a brain from a patient with epiepsy, between seizures. The red indicates healthy tissue. On the right side of the image, there is less red in the mesial temporal area. This is hypometabolism, reflecting decreased brain function in the area where seizures begin. (Credit: Image courtesy of University of California - Los Angeles)

Yet among people who suffer from what’s known as medically intractable epilepsy, in which seizures are resistant to drugs, only a small fraction will seek surgery, seeing it only as a last resort. As a result, they continue to suffer seizures year after year. They can’t drive, they can’t work and they lose cognitive function as the years pass. Premature death is not uncommon.

But a multi-center study led by researchers at UCLA shows that for people suffering from intractable temporal lobe epilepsy, the most common form of intractable epilepsy, early surgical intervention followed by antiepileptic drugs stopped their seizures, improved their quality of life and helped them avoid decades of disability.

The report appears in the March 7 edition of the Journal of the American Medical Association.

"In short, they got their lives back," said Dr. Jerome Engel, the study’s principal investigator and director of the UCLA Seizure Disorder Center.

But the frustration of Engel and his colleagues is this: Few patients are referred to them for surgical evaluation, and those who are have had epilepsy for an average of 22 years.

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ScienceDaily (Mar. 7, 2012) — Stimulating the brain with a weak electrical current is a safe and effective treatment for depression and could have other surprise benefits for the body and mind, a major Australian study of transcranial Direct Current Stimulation (tDCS) has found.

Medical researchers from the University of New South Wales (UNSW) and the Black Dog Institute have carried out the largest and most definitive study of tDCS and found up to half of depressed participants experienced substantial improvements after receiving the treatment.

A non-invasive form of brain stimulation, tDCS passes a weak depolarising electrical current into the front of the brain through electrodes on the scalp. Patients remain awake and alert during the procedure.

"We are excited about these results. This is the largest randomised controlled trial of transcranial direct current stimulation ever undertaken and, while the results need to be replicated, they confirm previous reports of significant antidepressant effects," said trial leader, Professor Colleen Loo, from UNSW’s School of Psychiatry.

The trial saw 64 depressed participants who had not benefited from at least two other depression treatments receive active or sham tDCS for 20 minutes every day for up to six weeks.

"Most of the people who went into this trial had tried at least two other antidepressant treatments and got nowhere. So the results are far more significant than they might initially appear — we weren’t dealing with people who were easy to treat," Professor Loo said.

Significantly, results after six weeks were better than at three weeks, suggesting the treatment is best applied over an extended period. Participants who improved during the trial were offered follow up weekly ‘booster’ treatments, with about 85 percent showing no relapse after three months.

"These results demonstrate that multiple tDCS sessions are safe and not associated with any adverse cognitive outcomes over time," Professor Loo said, adding tDCS is simple and cost effective to deliver, requiring a short visit to a clinic.

The study also turned up additional unexpected physical and mental benefits, including improved attention and information processing.

"One participant with a long-standing reading problem said his reading had improved after the trial and others commented that they were able to think more clearly.

"Another participant with chronic neck pain reported that the pain had disappeared during the trial. We think that is because tDCS actually changes the brain’s perception of pain. We believe these cognitive benefits are another positive aspect of the treatment worthy of investigation," Professor Loo said.

The researchers are now looking at an additional trial to include people with bipolar disorder, with early results from overseas suggesting tDCS is just as effective in this group.

Source: Science Daily

March 8, 2012 By Katie Neith

(Medical Xpress) — In both animals and humans, vocal signals used for communication contain a wide array of different sounds that are determined by the vibrational frequencies of vocal cords. For example, the pitch of someone’s voice, and how it changes as they are speaking, depends on a complex series of varying frequencies. Knowing how the brain sorts out these different frequencies—which are called frequency-modulated (FM) sweeps—is believed to be essential to understanding many hearing-related behaviors, like speech. Now, a pair of biologists at the California Institute of Technology (Caltech) has identified how and where the brain processes this type of sound signal.

Their findings are outlined in a paper published in the March 8 issue of the journal Neuron.

Knowing the direction of an FM sweep—if it is rising or falling, for example—and decoding its meaning, is important in every language. The significance of the direction of an FM sweep is most evident in tone languages such as Mandarin Chinese, in which rising or dipping frequencies within a single syllable can change the meaning of a word.

In their paper, the researchers pinpointed the brain region in rats where the task of sorting FM sweeps begins.

"This type of processing is very important for understanding language and speech in humans," says Guangying Wu, principal investigator of the study and a Broad Senior Research Fellow in Brain Circuitry at Caltech. "There are some people who have deficits in processing this kind of changing frequency; they experience difficulty in reading and learning language, and in perceiving the emotional states of speakers. Our research might help us understand these types of disorders, and may give some clues for future therapeutic designs or designs for prostheses like hearing implants."

This diagram shows areas in the midbrain region where direction- selective neurons were found.Credit: Guangying Wu/Caltech

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March 7, 2012

Neurons (nerve cells) are labeled with green fluorescent protein, and other neurons in the brain are labeled in the background with either red or blue tracers. The small bulbs (i.e., dendritic spines) on the spidery dendrites show places where nerve cells connect and communicate, called synapses, and when these spines shrank over time, this predicted vocal degradation in the songbirds. Credit: Katie Tschida, Duke Department of Neurobiology

Portions of a songbird’s brain that control how it sings have been shown to decay within 24 hours of the animal losing its hearing.

The findings, by researchers at Duke University Medical Center, show that deafness penetrates much more rapidly and deeply into the brain than previously thought. As the size and strength of nerve cell connections visibly changed under a microscope, researchers could even predict which songbirds would have worse songs in coming days.

"When hearing was lost, we saw rapid changes in motor areas in that control song, the bird’s equivalent of speech," said senior author Richard Mooney, Ph.D., professor of neurobiology at Duke. "This study provided a laser-like focus on what happens in the living songbird brain, narrowed down to the particular cell type involved."

The study was published in Neuron journal online on March 7, 2012.

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ScienceDaily (Mar. 6, 2012) — A team of academic researchers has identified the intracellular mechanisms regulated by vitamin D3 that may help the body clear the brain of amyloid beta, the main component of plaques associated with Alzheimer’s disease.

Published in the March 6 issue of the Journal of Alzheimer’s Disease, the early findings show that vitamin D3 may activate key genes and cellular signaling networks to help stimulate the immune system to clear the amyloid-beta protein.

Previous laboratory work by the team demonstrated that specific types of immune cells in Alzheimer’s patients may respond to therapy with vitamin D3 and curcumin, a chemical found in turmeric spice, by stimulating the innate immune system to clear amyloid beta. But the researchers didn’t know how it worked.

"This new study helped clarify the key mechanisms involved, which will help us better understand the usefulness of vitamin D3 and curcumin as possible therapies for Alzheimer’s disease," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System.

For the study, scientists drew blood samples from Alzheimer’s patients and healthy controls and then isolated critical immune cells from the blood called macrophages, which are responsible for gobbling up amyloid beta and other waste products in the brain and body.

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ScienceDaily (Mar. 6, 2012) — Antibodies that block the process of synapse disintegration in Alzheimer’s disease have been identified, raising hopes for a treatment to combat early cognitive decline in the disease.

Amyloid beta (cyan blue) binds to nerve cells of the hippocampus (red) and attacks synapses resulting in the loss of memories in Alzheimer’s disease. New research has led to important insights into the mechanisms that induce synapse loss. The discovery brings hope for the development of new therapies that protect synapses and therefore prevent memory loss in Alzheimer’s disease. (Credit: Silvia Purro/Patricia Salinas/UCL)

Alzheimer’s disease is characterized by abnormal deposits in the brain of the protein Amyloid-ß, which induces the loss of connections between neurons, called synapses.

Now, scientists at UCL have discovered that specific antibodies that block the function of a related protein, called Dkk1, are able to completely suppress the toxic effect of Amyloid-ß on synapses. The findings are published March 6 in the Journal of Neuroscience.

Professor Patricia Salinas (UCL Department of Cell & Developmental Biology) who led the study, said: “These novel findings raise the possibility that targeting this secreted Dkk1 protein could offer an effective treatment to protect synapses against the toxic effect of Amyloid-ß.

"Importantly, these results raise the hope for a treatment and perhaps the prevention of cognitive decline early in Alzheimer’s disease."

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March 6, 2012

Schematic diagrams of a normal brain (left) and an autistic brain (right) highlight the white matter alterations in autism. Credit: Carnegie Mellon University

New research from Carnegie Mellon University’s Marcel Just provides an explanation for some of autism’s mysteries — from social and communication disorders to restricted interests — and gives scientists clear targets for developing intervention and treatment therapies.

Autism has long been a scientific enigma, mainly due to its diverse and seemingly unrelated symptoms until now.

Published in the journal Neuroscience and Biobehavioral Reviews, Just and his team used brain imaging and computer modeling to show how the brain’s white matter tracts — the cabling that connects separated brain areas — are altered in autism and how these alterations can affect brain function and behavior. The deficiencies affect the tracts’ bandwidth — the speed and rate at which information can travel along the pathways.

"White matter is the unsung hero of the human brain," said Just, the D.O. Hebb Professor of Psychology within CMU’s Dietrich College of Humanities and Social Sciences and director of the university’s Center for Cognitive Brain Imaging. "In autistic individuals, we can measure the quality of the white matter, and our computer model can predict how coordinated their brain activity will be. This gives us a precise account of the underlying alterations affecting autistic thought."

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March 6, 2012

Thromboembolic stroke, caused by a blood clot in the brain, results in damage to the parts of the brain starved of oxygen. Breaking up the clot with tissue plasminogen activator (tPA) reduces the amount of damage, however, there is a very short time window when the value of the treatment outweighs the side effects. New research published in BioMed Central’s open access journal Experimental & Translational Stroke Medicine shows that, during the first 24 hours after a stroke, mild hypothermia (34C) can reduce the side effects of tPA and potentially increase the window of opportunity for tPA treatment.

When a blood clot blocks off blood flow in the brain (ischemic stroke) the part starved of oxygen quickly begins to die. In order to prevent significant damage tPA must be given to the patient as early as possible after the onset of symptoms - doctors recommend that it must be administered within the first four and a half hours. Delayed treatment also increases the patient’s risk of intracerebral hemorrhage and brain swelling (edema).

Mild hyperthermia is known to be neuroprotective and to reduce damage caused by the return of blood flow to an area of the brain starved of oxygen by a clot. Researchers from the University of Erlangen, led by Dr Rainer Kollmar, tested whether mild hyperthermia could also prevent damage to the brain due to tPA treatment in rats. After 24 hours they found that, while hypothermia reduced the amount of swelling and damaged tissue in the brain after a stroke, tPA (administered 90 minutes after the onset of stroke) increased it. However, they also discovered that hypothermia therapy was able to offset the damage due to tPA.

This seemed to be true for all the measurements they looked at. Dr Kollmar explained, “Patients often loose brain function such as control over parts of their body, speech or memory after stroke. We looked at ‘neuroscore’, to examine how much control of the body had been affected, and at markers for inflammation (TIMP-1 and sICAM) or evidence of damage to the blood brain barrier. In all cases hypothermia was able to offset the side effects of tPA.”

While these results are still experimental, new techniques which prevent shivering mean that this technique is easier to administer in conscious patients. Preliminary clinical trials are also beginning to show that it is possible to treat patients, who have had a stroke, with tPA plus hypothermia. Our results suggest that hypothermia can offset the side effects of tPA and further studies will show if it is also able to increase the window of opportunity of tPA treatment in patients.

Provided by BioMed Central

Source: medicalxpress.com

March 6, 2012

Getting rid of a protein increases the birth of new nerve cells and shortens the time it takes for antidepressants to take effect, according to an animal study in the March 7 issue of The Journal of Neuroscience. The protein, neurofibromin 1, normally helps prevent uncontrolled cell growth. The findings suggest therapeutic strategies aimed at stimulating new nerve cell birth may help treat depression better than current antidepressants that commonly take several weeks to reach full efficacy.

Throughout life, a section of the hippocampus — the brain’s learning and memory center — produces new nerve cells. This process, called neurogenesis, is made possible by specialized cells called neural progenitor cells (NPCs). While previous studies show adult neurogenesis declines with age and stress, therapies known to alleviate symptoms of depression, such as exercise and antidepressants, increase neurogenesis.

In the new study, a team of scientists directed by Luis Parada, PhD, of the University of Texas Southwestern, examined neurogenesis after deleting the neurofibromin 1 (Nf1) gene from NPCs in adult mice. Removal of Nf1 increased the number and maturation of newborn nerve cells in the adult hippocampus. Nf1 mutant mice showed reductions in depressive- and anxiety-like behaviors following 7 days of antidepressant treatment, whereas mice without the mutation took longer to show improvements.

"Our findings establish an important role for Nf1 in controlling neurogenesis in the hippocampus and demonstrate that activation of adult NPCs is enough to regulate depression- and anxiety-like behaviors," said study co-author Renee McKay, PhD, of the University of Texas Southwestern. "Our work is among the first to demonstrate the feasibility of altering mood via direct manipulation of adult neurogenesis," McKay added.

To determine if deleting Nf1 in adult NPCs leads to long-term behavioral changes in mice, the scientists ran 8-month-old mice through a battery of tests designed to measure anxiety- and depressive-like behaviors. Compared with other mice, the mutant mice showed less signs of anxiety and demonstrated resistance to the effects of chronic mild, unpredictable stress. The finding shows even without antidepressants, the deletion of Nf1 from NPCs in adult mice decreases symptoms of depression and anxiety.

"This study demonstrates that inducing neurogenesis is sufficient to produce antidepressant behavioral actions, and provides novel targets for therapeutic interventions," said Ronald Duman, PhD, a neurogenesis expert from Yale University.

Provided by Society for Neuroscience

Source: medicalxpress.com

ScienceDaily (Mar. 5, 2012) — A new marker of Alzheimer’s disease can predict how rapidly a patient’s memory and other mental abilities will decline after the disorder is diagnosed, researchers at Washington University School of Medicine in St. Louis have found.

In 60 patients with early Alzheimer’s disease, higher levels of the marker, visinin-like protein 1 (VILIP-1), in the spinal fluid were linked to a more rapid mental decline in the years that followed.

Scientists need to confirm the results in larger studies, but the new data suggest that VILIP-1 potentially may be a better predictor of Alzheimer’s progression than other markers.

“VILIP-1 appears to be a strong indicator of ongoing injury to brain cells as a result of Alzheimer’s disease,” says lead author Rawan Tarawneh, MD, now an assistant professor of neurology at the University of Jordan. “That could be very useful in predicting the course of the disease and in evaluating new treatments in clinical trials.”

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