Neuroscience

ScienceDaily (Apr. 27, 2012) — In a new study, scientists at the University of Copenhagen show that a specific type of carbohydrate plays an important role in the intercellular signalling that controls the growth and development of the nervous system. In particular, defects in that carbohydrate may result in the uninhibited cell growth that characterizes the genetic disease neurofibromatosis and certain types of cancer.

Egghead to the right: Changes in cellular growth. (Credit: Klaus Qvortrup)

The results have just been published in the well-reputed journal PNAS.

Scientists from The Faculty of Health and Medical Sciences at the University of Copenhagen have put a special type of fruit fly under the microscope. The new research results turn the spotlight on a certain group of carbohydrates — the so-called glycolipids — and their influence on the cells’ complicated communication system. In the long term, this model study can shine new light on the disease neurofibromatosis for the benefit of patients the world over.

"The most important thing about our discovery right now is that we document a new function for carbohydrates in the communication between cells. We also show how disturbances in the signalling pathways cause changes in cellular growth. This is knowledge that cancer researchers can develop," says Ole Kjærulff, doctor and associate professor at the Department of Neuroscience and Pharmacology, who has conducted the study together with Dr. Katja Dahlgaard, and Hans Wandall, associate professor at the Copenhagen Center for Glycomics.

Sugar chains control cell growth

Glycolipids are compounds consisting of fats linked to long chains of sugar molecules. They are located in the cell membrane, where they serve various functions, such as protecting the cell or making it recognizable to the immune system.

"In the fruit fly model, if we prevent the sugar chains from lengthening, we can show that carbohydrate plays an important role in controlling the growth of normal cells. When the sugar chains are shortened, the tissue grows dramatically on account of increased cell division. In particular, it appears that the nervous system’s support cells — the glia cells — are influenced," explains Hans Wandall, associate professor.

Neurofibromatosis can cause deformity

The new results also influence our understanding of neurofibromatosis. This is a heritable disorder that results in unsightly tumours — so-called neurofibromas — in the nerves and skin. The disease affects approximately 20 people out of 100,000 and varies from mild to severe cases with decided deformities. The condition also affects the bones and often causes learning problems:

"When you get closer to an understanding of the mechanisms that result in a certain disease, naturally it is easier to influence the disease process in the form of drug development in the longer term. Neurofibromatosis is not a terminal disease, but it very much affects the life quality of the people who have it because the symptoms are so noticeable," explains Ole Kjærulff. Hans Wandall adds that the disease is also associated with certain types of cancer, particularly in the brain.

Source: Science Daily 

April 27, 2012

Aging may seem unavoidable, but that’s not necessarily so when it comes to the brain. So say researchers in the April 27th issue of the Cell Press journal Trends in Cognitive Sciences explaining that it is what you do in old age that matters more when it comes to maintaining a youthful brain not what you did earlier in life.

"Although some memory functions do tend to decline as we get older, several elderly show well preserved functioning and this is related to a well-preserved, youth-like brain," says Lars Nyberg of Umeå University in Sweden.

Education won’t save your brain — PhDs are as likely as high-school dropouts to experience memory loss with old age, the researchers say. Don’t count on your job either. Those with a complex or demanding career may enjoy a limited advantage, but those benefits quickly dwindle after retirement.

Engagement is the secret to success. Those who are socially, mentally and physically stimulated reliably show better cognitive performance with a brain that appears younger than its years.

"There is quite solid evidence that staying physically and mentally active is a way towards brain maintenance," Nyberg says.

The researchers say this new take on successful aging represents an important shift in focus for the field. Much attention in the past has gone instead to understanding ways in which the brain copes with or compensates for cognitive decline in aging. The research team now argues for the importance of avoiding those age-related brain changes in the first place. Genes play some role, but life choices and other environmental factors, especially in old age, are critical.

Elderly people generally do have more trouble remembering meetings or names, Nyberg says. But those memory losses often happen later than many often think, after the age of 60. Older people also continue to accumulate knowledge and to use what they know effectively, often to very old ages.

"Taken together, a wide range of findings provides converging evidence for marked heterogeneity in brain aging," the scientists write. "Critically, some older adults show little or no brain changes relative to younger adults, along with intact cognitive performance, which supports the notion of brain maintenance. In other words, maintaining a youthful brain, rather than responding to and compensating for changes, may be the key to successful memory aging."

Provided by Cell Press

Source: medicalxpress.com

April 27, 2012

(HealthDay) — Childhood socioeconomic status affects hippocampal volume in older adults, after adjusting for adult socioeconomic status, gender, education, and other factors, according to a study published in the May issue of the Annals of Neurology.

Childhood socioeconomic status affects hippocampal volume in older adults, after adjusting for adult socioeconomic status, gender, education, and other factors, according to a study published in the May issue of the Annals of Neurology.

Roger T. Staff, Ph.D., of the Aberdeen Royal Infirmary in the United Kingdom, and colleagues used magnetic resonance imaging of the brain to measure whole brain and hippocampal volume in 249 volunteers without dementia who were born in 1936. Childhood socioeconomic status history was recorded and mental ability at age 11 (recorded in 1947) was available for all participants.

After adjusting for mental ability at age 11 years, adult socioeconomic status, gender, and education, the researchers observed a significant association between childhood socioeconomic status and hippocampal volume.

"Early life socioeconomic conditions contribute to hippocampal volume in late adulthood independently of later life circumstances," the authors conclude. "These findings suggest that the capacity to compensate for age-related neuropathology (reserve) may well be established in early life."

More information: Abstract

Source: medicalxpress.com

ScienceDaily (Apr. 27, 2012) — Our genes control many aspects of who we are — from the colour of our hair to our vulnerability to certain diseases — but how are the genes, and consequently the proteins they make themselves controlled? Researchers have discovered a new group of molecules which control some of the fundamental processes behind memory function and may hold the key to developing new therapies for treating neurodegenerative diseases.

The mirror-miRNA (red) is expressed in hippocampal neurons, the nucleus is shown in blue. (Credit: Image courtesy of University of Bristol)

The research, led by academics from the University of Bristol’s Schools of Clinical Sciences, Biochemistry and Physiology & Pharmacology and published in the Journal of Biological Chemistry, has revealed a new group of molecules, called mirror-microRNAs.

MicroRNAs are non-coding genes that often reside within ‘junk DNA’ and regulate the levels and functions of multiple target proteins — responsible for controlling cellular processes in the brain. The study’s findings have shown that two microRNA genes with different functions can be produced from the same piece (sequence) of DNA — one is produced from the top strand and another from the bottom complementary ‘mirror’ strand.

Specifically, the research has shown that a single piece of human DNA gives rise to two fully processed microRNA genes that are expressed in the brain and have different and previously unknown functions. One microRNA is expressed in the parts of nerve cells that are known to control memory function and the other microRNA controls the processes that move protein cargos around nerve cells.

James Uney, Professor of Molecular Neuroscience in the University’s School of Clinical Sciences, said: “These findings are important as they show that very small changes in microRNA genes will have a dramatic effect on brain function and may influence our memory function or likelihood of developing neurodegenerative diseases. These findings also suggest that many more human mirror microRNAs will be found and that they could ultimately be used as treatments for human neurodegenerative diseases such as dementia.”

MicroRNAs can be seen as a novel regulatory layer within the genome, relying on the interaction between different RNA molecules. Through binding to messenger RNA (mRNA), they adjust the levels of proteins. Due to their small size, they are able to regulate many different RNAs. MicroRNAs have already been found throughout the double helix, lying in between genes or in areas of the code for a single gene that would normally be discarded. Such areas that were once considered “junk DNA” are now revealing a more complex and important role. In addition microRNAs can be produced in conjunction with their genes, within which they lie, or be controlled and produced entirely independently.

Helen Scott and Joanna Howarth, the lead authors on the study, added: “We have now found that both sides of the double helix can each produce a microRNA. These two microRNAs are almost a perfect mirror of each other, but due to slight differences in their sequence, they regulate different sets of protein producing RNAs, which will in turn affect different biological functions. Such mirror-miRNAs are likely to represent a new group of microRNAs with complex roles in coordinating gene expression, doubling the capacity of regulation.”

Source: Science Daily

ScienceDaily (Apr. 27, 2012) — Researchers at the Centre for Addiction and Mental Health (CAMH) led a study discovering a gene for a new form of intellectual disability, as well as how it likely affects cognitive development by disrupting neuron functioning.

CAMH Senior Scientist Dr. John Vincent and his team found a mutation in the gene NSUN2 among three sisters with intellectual disability, a finding to be published in the May issue of the American Journal of Human Genetics.

The discovery was made after mapping genes in a Pakistani family, in which three of seven siblings had intellectual disability as well as muscle weakness and walking difficulties, says Dr. Vincent, who heads the Molecular Neuropsychiatry and Development Laboratory in the Campbell Family Mental Health Research Institute at CAMH.

Intellectual disability is a condition in which individuals have limitations in their mental abilities and in functioning in daily life. It affects one to three per cent of the population, and is often caused by genetic mutations.

Another study in the same journal, submitted together with the CAMH-led research, also identified NSUN2 gene mutations in Iranian and Kurdish families with intellectual disability. As with the Pakistani family, first cousin marriages in these families carrying the mutations increased the likelihood of intellectual disability among their children, and enabled researchers to focus on areas to map genes.

"The combined results from these two studies mean that NSUN2 is among the most common causes of intellectual disability resulting from recessive genes," says Dr. Vincent.

As a recessive disorder, a child must inherit one defective NSUN2 gene from each parent to develop intellectual disability. This gene, located on chromosome 5p, encodes a type of protein called an RNA methyltransferase.

At the cellular level, the researchers found that the mutated protein was prevented from reaching its target area within the nucleus of a cell. As a result, it was unable to perform its normal role in cell division and/or RNA methylation.

Collaborators from the Wellcome Trust Centre for Stem Cell Research in Cambridge, U.K., showed which type of brain cells were likely to be most affected by this mutation. They are called Purkinje cells, a type of neuron that responds to the neurotransmitter GABA. Purkinje cells also control motor coordination, which were affected in the Pakistani family.

"We speculate that the muscle effects may result from the accumulation of the NSUN2 protein outside its target area in the nucleus," says Dr. Vincent.

To date, Dr. Vincent’s lab has identified five genes causing different forms of recessive intellectual disability.

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — A new University of British Columbia study finds that analytic thinking can decrease religious belief, even in devout believers.

The statue “The Thinker,” by Auguste Rodin. (Credit: © Ignatius Wooster / Fotolia)

The study, which is published in the April 27 issue of Science, finds that thinking analytically increases disbelief among believers and skeptics alike, shedding important new light on the psychology of religious belief.

“Our goal was to explore the fundamental question of why people believe in a God to different degrees,” says lead author Will Gervais, a PhD student in UBC’s Dept. of Psychology. “A combination of complex factors influence matters of personal spirituality, and these new findings suggest that the cognitive system related to analytic thoughts is one factor that can influence disbelief.”

Researchers used problem-solving tasks and subtle experimental priming – including showing participants Rodin’s sculpture The Thinker or asking participants to complete questionnaires in hard-to-read fonts – to successfully produce “analytic” thinking. The researchers, who assessed participants’ belief levels using a variety of self-reported measures, found that religious belief decreased when participants engaged in analytic tasks, compared to participants who engaged in tasks that did not involve analytic thinking.

The findings, Gervais says, are based on a longstanding human psychology model of two distinct, but related cognitive systems to process information: an “intuitive” system that relies on mental shortcuts to yield fast and efficient responses, and a more “analytic” system that yields more deliberate, reasoned responses.

“Our study builds on previous research that links religious beliefs to ‘intuitive’ thinking,” says study co-author and Associate Prof. Ara Norenzayan, UBC Dept. of Psychology. “Our findings suggest that activating the ‘analytic’ cognitive system in the brain can undermine the ‘intuitive’ support for religious belief, at least temporarily.”

The study involved more than 650 participants in the U.S. and Canada. Gervais says future studies will explore whether the increase in religious disbelief is temporary or long-lasting, and how the findings apply to non-Western cultures.

Recent figures suggest that the majority of the world’s population believes in a God, however atheists and agnostics number in the hundreds of millions, says Norenzayan, a co-director of UBC’s Centre for Human Evolution, Cognition and Culture. Religious convictions are shaped by psychological and cultural factors and fluctuate across time and situations, he says.

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — Scientists at the Gladstone Institutes have unraveled a process by which depletion of a specific protein in the brain contributes to the memory problems associated with Alzheimer’s disease. These findings provide insights into the disease’s development and may lead to new therapies that could benefit the millions of people worldwide suffering from Alzheimer’s and other devastating neurological disorders.

The study, led by Gladstone Investigator Jorge J. Palop, PhD, revealed that low levels of a protein, called Nav1.1, disrupt the electrical activity between brain cells. Such activity is crucial for healthy brain function and memory. Indeed, the researchers found that restoring Nav1.1 levels in mice that were genetically modified to mimic key aspects of Alzheimer’s disease (AD-mice) improved learning and memory functions and increased their lifespan. Their findings are featured on the cover of the April 27 issue of Cell, available online April 26.

"It is estimated that more than 30 million people worldwide suffer from Alzheimer’s disease and that number is expected to rise dramatically in the near future," said Lennart Mucke, MD, who directs neurological research at Gladstone, an independent and nonprofit biomedical-research organization. "This research improves our understanding of the biological processes that underlie cognitive dysfunction in this disease and could open the door for new therapeutic interventions."

The researchers’ findings suggest that Nav1.1 levels in special regulatory nerve cells called parvalbumin cells, or PV cells, are essential to generate healthy brain-wave activity — and that problems in this process contribute to cognitive decline in AD-mice and possibly in patients with Alzheimer’s.

In the brain, neurons form highly interconnected networks, using chemical and electrical signals to communicate with each other. The researchers investigated whether this communication between neurons is disrupted in AD-mice, and if so, how this may affect the symptoms of Alzheimer’s disease.

To study this, they performed electroencephalogram (EEG) recordings — a technique that detects abnormalities in the brain’s electrical waves such as those found in patients with epilepsy. They found that similar abnormalities emerged during periods of reduced gamma-wave oscillations — a type of brain wave that is crucial to regulating learning and memory.

"Like a conductor in an orchestra, PV cells regulate brain rhythms by precisely controlling excitatory brain activity," said Laure Verret, PhD, postdoctoral fellow and lead author. "We found that PV cells in patients with Alzheimer’s and in AD-mice have low levels of the protein Nav1.1 — likely contributing to PV cell dysfunction. As a consequence, AD-mice had abnormal brain rhythms. By restoring Nav1.1 levels, we were able to re-establish normal brain function."

Indeed, the scientists found that increasing Nav1.1 levels in PV cells improves brain wave activity, learning, memory and survival rates in AD-mice.

"Enhancing Nav1.1 activity, and consequently improving PV cell function, may help in the treatment of Alzheimer’s disease and other neurological disorders associated with gamma-wave alterations and cognitive impairments such as epilepsy, autism and schizophrenia," said Dr. Palop, who is also an assistant professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "These findings may allow us to develop therapies to help patients with these devastating diseases."

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — The ability to navigate using spatial cues was impaired in mice whose brains were minus a channel that delivers potassium — a finding that may have implications for humans with damage to the hippocampus, a brain structure critical to memory and learning, according to a Baylor University researcher.

Mice missing the channel also showed diminished learning ability in an experiment dealing with fear conditioning, said Joaquin Lugo, Ph.D., the lead author in the study and an assistant professor of psychology and neuroscience in Baylor’s College of Arts & Sciences. “By targeting chemical pathways that alter those potassium channels, we may eventually be able to apply the findings to humans and reverse some of the cognitive deficits in people with epilepsy and other neurological disorders,” Lugo said.

The research was done in Baylor College of Medicine Intellectual and Developmental Disabilities Research Center Mouse Neurobehavior Core in Houston during Lugo’s time as a researcher there.

The findings are published online in the journal Learning & Memory.

The channel, called Kv4.2, delivers potassium, which aids neuron function in the brain’s hippocampus. The hippocampus forms memory for long-term storage in the brain. Potassium also helps to regulate excitability.

Individuals who have epilepsy sometimes exhibit altered or missing Kv.4.2 channels or similar types of channels.

In the experiment investigating navigation, “knockout” mice — those without the channel — were tested in a water maze four feet in diameter and 12 inches deep, with eight trials daily — each lasting about a minute — over four days, he said. Their performance was compared with that of normal mice.

Both groups responded to visual cues — colored symbols — in learning their way around the maze, but the knockout mice did not respond as well as the normal mice in terms of spatial cues — hidden platforms in the water.

"When the mice don’t have this channel, it hurts their ability to learn," Lugo said. In a separate experiment examining fear conditioning, both knockout mice and normal mice were placed in a cage, and researchers sounded a tone before giving the mice a mild electric shock. In repeated trials, both groups began to freeze upon hearing the tone as they anticipated a shock. But the normal mice also reacted to the context — being placed in the cage — while the mice who did not have the Kv4.2 channel reacted only to the tone. The research was funded by the Epilepsy Foundation and the National Institutes of Health.

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — They say you can’t teach an old dog new tricks. Fortunately, this is not always true. Researchers at the Netherlands Institute for Neuroscience (NIN-KNAW) have now discovered how the adult brain can adapt to new situations. The Dutch researchers’ findings are published on April 25 in the journal Neuron. Their study may be significant in developing treatments of neurodevelopmental disorders.

Two inhibitory synapses (yellow) disappear from the process of a nerve-cell (red) during learning. (Credit: Image courtesy of Netherlands Institute for Neuroscience)

Ability to learn

Our brain processes information in complex networks of nerve cells. The cells communicate and excite one another through special connections, called synapses. Young brains are capable of forming many new synapses, and they are consequently better at learning new things. That is why we acquire vital skills — walking, talking, hearing and seeing — early on in life. The adult brain stabilises the synapses so that we can use what we have learned in childhood for the rest of our lives.

Disappearing inhibitors

Earlier research found that approximately one fifth of the synapses in the brain inhibit rather than excite other nerve-cell activity. Neuroscientists have now shown that many of these inhibitory synapses disappear if the adult brain is forced to learn new skills. They reached this conclusion by labelling inhibitory synapses in mouse brains with fluorescent proteins and then tracking them for several weeks using a specialised microscope. They then closed one of the mice’s eyes temporarily to accustom them to seeing through just one eye. After a few days, the area of the brain that processes information from both eyes began to respond more actively to the open eye. At the same time, many of the inhibitory synapses disappeared and were later replaced by new synapses.

Regulating the information network

Inhibitory synapses are vital for the way networks function in the brain. “Think of the excitatory synapses as a road network, with traffic being guided from A to B, and the inhibitory synapses as the matrix signs that regulate the traffic,” explains research leader Christiaan Levelt. “The inhibitory synapses ensure an efficient flow of traffic in the brain. If they don’t, the system becomes overloaded, for example as in epilepsy; if they constantly indicate a speed of 20 kilometres an hour, then everything will grind to a halt, for example when an anaesthetic is administered. If you can move the signs to different locations, you can bring about major changes in traffic flows without having to entirely reroute the road network.”

Hope

Inhibitory synapses play a hugely influential role on learning in the young brain. People who have neurodevelopmental disorders — for example epilepsy, but also autism and schizophrenia — may have trouble forming inhibitory synapses. The discovery that the adult brain is still capable of pruning or forming these synapses offers hope that pharmacological or genetic intervention can be used to enhance or manage this process. This could lead to important guideposts for treating the above-mentioned neurological disorders, but also repairing damaged brain tissue.

Source: Science Daily

April 26, 2012

They say you can’t teach an old dog new tricks. Fortunately, this is not always true. Researchers at the Netherlands Institute for Neuroscience have now discovered how the adult brain can adapt to new situations. The Dutch researchers’ findings are published on Wednesday in the prestigious journal Neuron. Their study may be significant in the treatment of neurodevelopmental disorders such as epilepsy, autism and schizophrenia.

Our brain processes information in complex networks of nerve cells. The cells communicate and excite one another through special connections, called synapses. Young brains are capable of forming many new synapses, and they are consequently better at learning new things. That is why we acquire vital skills – walking, talking, hearing and seeing – early on in life. The adult brain stabilises the synapses so that we can use what we have learned in childhood for the rest of our lives.

Earlier research found that approximately one fifth of the synapses in the brain inhibit rather than excite other nerve-cell activity. Neuroscientists have now shown that many of these inhibitory synapses disappear if the adult brain is forced to learn new skills. They reached this conclusion by labelling inhibitory synapses in mouse brains with fluorescent proteins and then tracking them for several weeks using a specialised microscope. They then closed one of the mice’s eyes temporarily to accustom them to seeing through just one eye. After a few days, the area of the brain that processes information from both eyes began to respond more actively to the open eye. At the same time, many of the inhibitory synapses disappeared and were later replaced by new synapses.

Inhibitory synapses are vital for the way networks function in the brain. “Think of the excitatory synapses as a road network, with traffic being guided from A to B, and the inhibitory synapses as the matrix signs that regulate the traffic,” explains research leader Christiaan Levelt. “The inhibitory synapses ensure an efficient flow of traffic in the brain. If they don’t, the system becomes overloaded, for example as in epilepsy; if they constantly indicate a speed of 20 kilometres an hour, then everything will grind to a halt, for example when an anaesthetic is administered. If you can move the signs to different locations, you can bring about major changes in traffic flows without having to entirely reroute the road network.”

Inhibitory synapses play a hugely influential role on learning in the young brain. People who have neurodevelopmental disorders – for example epilepsy, but also autism and schizophrenia – may have trouble forming inhibitory synapses. The discovery that the adult brain is still capable of pruning or forming these synapses offers hope that pharmacological or genetic intervention can be used to enhance or manage this process. This could lead to important guideposts for treating the above-mentioned neurological disorders, but also repairing damaged brain tissue.

Provided by Royal Netherlands Academy of Arts and Sciences

Source: medicalxpress.com

April 26, 2012

What happens at the level of individual neurons while we learn? This question intrigued the neuroscientist Daniel Huber, who recently arrived at the Department of Basic Neuroscience at the University of Geneva. During his stay in the United States, he and his team tried to unravel the network mechanisms underlying learning and memory at the level of the cerebral cortex.

What’s the role of individual neurons in behavior? Do they always participate in the same functions? How do their responses evolve during learning?” asks the professor. One way to address these questions is to follow the activity of a large set of neurons while the subject learns a novel task. The goal is to link the behavioral changes with the changes in neuronal representations.

It’s currently impossible to follow the activity of a large number of individual neurons in humans, but the team of researchers quickly realized that mice are excellent subjects for such studies. “We were surprised by capacities of these small rodents. They learn novel associations quickly and are able to focus for hours on complex behavioral tasks. However, it is important to keep them motivated by rewarding them accordingly. They are very similar to us in that way.”

The behavioral task of the mice consisted in sampling the area in front of their snout with their whiskers to search for a small object. The object was presented either within reach and out of reach of their whiskers. Each time the object was detected with the whiskers, the mouse had to respond by licking to a reward spout. The correct choices were rewarded with a drop of liquid. “In this task different sensory and motor circuits have to interact in order to establish a novel association, leading to better and better performance”.

Remained the problem of how to follow the activity of the large number of neurons across many days of learning. The researchers replaced a small part of the bone overlying motor cortex with a tiny glass window. The neurons underneath the window were genetically modified to express a fluorescent marker which changes its intensity according to the activity of the neurons. This window into the brain allowed the researches around Daniel Huber to use two-photon microscopy to record the activity of the same set of 500 neurons during days of learning. 

"We then correlated the activity of the individual neurons with the different actions of the mouse, such as moving the whiskers, touching the object or licking at the right moment. It’s like synchronizing the soundtrack with the images in a movie" adds the neuroscientist. The researchers analyzed this data using a series of computational approaches to establish a link between the neuronal activity and the different sensory and motor features of the task. This allowed them to build algorithmic models that can predict different motor outputs by solely monitoring the neuronal activity. Decoding the neuronal activity allowed the researchers then to construct functional maps of the recorded neurons and quantify each neuron’s link with the different aspects of the behavior.

These functional maps revealed several fundamental findings: “Although the movements of the whiskers became more and more precise and targeted to search for the object during the learning, their relative neuronal representation remained relatively stable. In contrast, the representation of licking to respond and collect the rewards became more and more pronounced”. Taken together, only selected aspects of the learned behavior induced changes it the neuronal representation in the cortex. The scientists also found that different sensory and motor representations are spatially intermingled in the rodent brain.

Other analysis revealed that individual neurons remain stably linked to a given behavioral function, but they have a flexibility to remain silent on a given day. This functional stability despite a flexibility to join (or not) a given representation was actually suggested by different theoretical work on learning.

"If these characteristics are limited to the motor cortex or if these are more general rules that are apply across the cerebral cortex remains open" says Daniel Huber. That in fact this is one of the questions we are currently investigating in my lab in Geneva".

Provided by University of Geneva

Source: medicalxpress.com

April 26, 2012 by Stuart Mason Dambrot

(Medical Xpress) — Remarkably, cortical maps show that neurons in the primary visual cortex have specific preferences for the location and orientation of a given visual field stimulus – but how these maps develop and what function they play in visual processing remains a mystery. Evidence suggests that the retinotopic map is established by molecular gradients, but little is known about how orientation maps are wired. One hypothesis: at their inception, these orientation maps are seeded by the spatial interference of ON- and OFF-center retinal receptive field mosaics. Recently, scientists in the Departments of Neurobiology and Psychology at the University of California, Los Angeles have shown that this proposed mechanism predicts a link between the layout of orientation preferences around singularities of different signs and the cardinal axes of the retinotopic map, and have confirmed this prediction in the tree shrew primary visual cortex. The researchers say their findings support the idea that spatially structured retinal input may provide a blueprint of sorts for the early development of cortical maps and receptive fields – and that the same may hold true for other senses as well.

Moiré interference of retinal mosaics predicts a link between retinotopic and orientation maps. (A) (Upper) Two hexagonal lattices representing ON- (red) and OFF-center (blue) ganglion cell receptive fields/ (Lower) A cortical cell with input dominated by a dipole has a receptive field with side-by-side subregions of opposite sign and can be tuned for orientation. (B) (Upper) The orientation of dipoles in the interference pattern, indicated by the orientation of short line segments, changes over space, generating a blueprint for an orientation map. (Lower) The organization of orientation preferences around negative (Left) and positive (Right) singularities. Image Courtesy PNAS, doi: 10.1073/pnas.1118926109

Professor of Neurobiology and Psychology Dario L. Ringach articulates the primary elements of showing that the hypothesis that orientation maps are initially seeded by the spatial interference of ON- and OFF-center retinal receptive field mosaics corresponds to a mechanism that predicts a link between the layout of orientation preferences around singularities of different signs and the cardinal axes of the retinotopic map. “The cerebral cortex of higher mammals contains diverse maps,” he tells Medical Xpress, “where information about sensory input or motor planning is laid out systematically across the surface of a given cortical area. Some scientists have postulated that these computational maps are key to cortical function. However, we still do not know exactly what role cortical maps play in normal sensory and motor processes.” Their importance, he stresses, is that understanding how cortical maps are wired during development, and what types of pathology may arise from their faulty wiring, are fundamental questions of brain function.

Ringach also notes that neurons in primary visual cortex are selective to the orientation of a stimulus in visual space, and their preference changes systematically across the cortical surface in a periodic fashion. “We know these maps are present at the earliest stages of life,” he continues, “and do not require normal sensory experience to develop – but how do they wire themselves? We’ve postulated that the initial structure of these maps is biased by the spatial organization of the periphery.” In the visual system this is represented by the signals the retina within the eye conveys to the brain.

The researchers’ model postulates that at each location in the visual field, the input from the retina constraints the range of orientation preferences that the cortex can implement at that location. “We show that, given what is known about the organization of retinal signals, that such constraints would be quasi-periodic, thereby potentially providing the blueprint for an orientation map in the cortex.” One prediction of this theory is that groups of neurons preferring the same orientation should be arranged on an approximate hexagonal lattice on the cortical surface – a prediction the researchers confirmed in a previous study¹. 

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April 26, 2012 by Larry Hardesty

In this week’s issue of the journal Neurology, researchers at MIT and two Boston hospitals provide early evidence that a simple, unobtrusive wrist sensor could gauge the severity of epileptic seizures as accurately as electroencephalograms (EEGs) do — but without the ungainly scalp electrodes and electrical leads. The device could make it possible to collect clinically useful data from epilepsy patients as they go about their daily lives, rather than requiring them to come to the hospital for observation. And if early results are borne out, it could even alert patients when their seizures are severe enough that they need to seek immediate medical attention.

Rosalind Picard, a professor of media arts and sciences at MIT, and her group originally designed the sensors to gauge the emotional states of children with autism, whose outward behavior can be at odds with what they’re feeling. The sensor measures the electrical conductance of the skin, an indicator of the state of the sympathetic nervous system, which controls the human fight-or-flight response.

In a study conducted at Children’s Hospital Boston, the research team — Picard, her student Ming-Zher Poh, neurologist Tobias Loddenkemper and four colleagues from MIT, Children’s Hospital and Brigham and Women’s Hospital — discovered that the higher a patient’s skin conductance during a seizure, the longer it took for the patient’s brain to resume the neural oscillations known as brain waves, which EEG measures.

At least one clinical study has shown a correlation between the duration of brain-wave suppression after seizures and the incidence of sudden unexplained death in epilepsy (SUDEP), a condition that claims thousands of lives each year in the United States alone. With SUDEP, death can occur hours after a seizure.

Currently, patients might use a range of criteria to determine whether a seizure is severe enough to warrant immediate medical attention. One of them is duration. But during the study at Children’s Hospital, Picard says, “what we found was that this severity measure had nothing to do with the length of the seizure.” Ultimately, data from wrist sensors could provide crucial information to patients deciding whether to roll over and go back to sleep or get to the emergency room.

Surprising signals

The realization that the wrist sensors might be of use in treating epilepsy was something of a fluke. “We’d been working with kids on the autism spectrum, and I didn’t realize, but a lot of them have seizures,” Picard says. In reviewing data from their autism studies, Picard and her group found that seizures were sometimes preceded by huge spikes in skin conductance. It seemed that their sensors might actually be able to predict the onset of seizures.

At the time, several MIT students were working in Picard’s lab through MIT’s Undergraduate Research Opportunities Program (UROP); one of them happened to be the daughter of Joseph Madsen, director of the Epilepsy Surgery Program at Children’s Hospital. “I decided it was time to meet my UROP’s dad,” Picard says.

In a project that would serve as the basis of Poh’s doctoral dissertation, Madsen agreed to let the MIT researchers test the sensors on patients with severe epilepsy, who were in the hospital for as much as a week of constant EEG monitoring. Poh and Picard considered several off-the-shelf sensors for the project, but “at the time, there was nothing we could buy that did what we needed,” Picard says. “Finally, we just built our own.”

"It’s a big challenge to make a device robust enough to withstand long hours of recording," Poh says. "We were recording days or weeks in a row." In early versions of the sensors, some fairly common gestures could produce false signals. Eliminating the sensors’ susceptibility to such sources of noise was largely a process of trial and error, Picard says.

Blending in

Additionally, Poh says, “I put a lot of thought into how to make it really comfortable and as nonintrusive as possible. So I packaged it all into typical sweatbands.” Since the patients in the study were children, “I allowed them to choose their favorite character on their wristband — for example, Superman, or Dora the Explorer, whatever they like,” Poh says. “To them, they were wearing a wristband. But there was a lot of complicated sensing going on inside the wristband.” Indeed, Picard says, the researchers actually lost five of their homemade sensors because hospital cleaning staff saw what they thought were ratty sweatbands lying around recently vacated rooms and simply threw them out.

Picard is continuing to investigate the possibility that initially intrigued her — that the devices could predict seizures. In the meantime, however, her collaborators at Children’s Hospital are conducting a study that will follow up on the one reported in Neurology, and a similar study is beginning at Brigham and Women’s Hospital. Rather than sweatbands with TV and comic-book characters, however, the new studies will use sensors produced by Affectiva, a company that Picard started in order to commercialize her lab’s work.

Provided by Massachusetts Institute of Technology 

Source: medicalxpress.com

April 26, 2012

(Medical Xpress) — The progression of the debilitating disease Multiple Sclerosis (MS) could be slowed or even halted by blocking a protein that contributes to nerve damage, according to a new study.

Professor Claude Bernard and Dr Steven Petratos

In research published today in the journal Brain, scientists from the Monash Immunology and Stem Cell Laboratories (MISCL), the University of Toronto, Yale and the University of Western Australia, have demonstrated the key role played by the collapsin response mediator protein 2 (CRMP-2) in the development of MS.

Led by MISCL’s Dr Steven Petratos, also of RMIT University, and Professor Claude Bernard, the research team found that a modified version of CRMP-2 is present in active MS lesions, which indicate damage to the nervous system, in a laboratory model of MS.

The modified CRMP-2 interacts with another protein to cause nerve fibre damage that can result in numbness, blindness, difficulties with speech and motor skills, and cognitive impairments in sufferers.

When either the modified CRMP-2 or the interaction between the two proteins was blocked, using a method already approved in both the US and Australia, the progression of the disease was halted.

Director of MISCL, Professor Richard Boyd said the discovery could lead to new treatments for MS.

“Blocking the same protein in people with MS could provide a ‘handbrake’ to the progression of the disease,” Professor Boyd said.

Dr Petratos said the method used to block the protein was approved for the treatment of other disease conditions by both the US Food and Drug Administration and Australia’s Therapeutic Goods Administration.

“This should mean that clinical trials – once they start – will be fast tracked as the form of administration has already been approved,” Dr Petratos said.

MS Australia estimates that the disease affects more than 20,000 people in Australia, and up to 2.5 million worldwide. The disease tends to strike early in adulthood, with women three times more likely than men to be diagnosed. The total cost to the Australian community of the disease is estimated at $1 billion annually.

The research received major funding from the National Multiple Sclerosis Society of the United States of America and partial funding from MS Research Australia.

Provided by Monash University

Source: medicalxpress.com

ScienceDaily (Apr. 26, 2012) — A team led by psychology professor Ian Spence at the University of Toronto reveals that playing an action videogame, even for a relatively short time, causes differences in brain activity and improvements in visual attention.

Playing an action videogame, even for a relatively short time, causes differences in brain activity and improvements in visual attention. (Credit: © j0yce / Fotolia)

Previous studies have found differences in brain activity between action videogame players and non-players, but these could have been attributed to pre-existing differences in the brains of those predisposed to playing videogames and those who avoid them. This is the first time research has attributed these differences directly to playing video games.

Twenty-five subjects — who had not previously played videogames — played a game for a total of 10 hours in one to two hour sessions. Sixteen of the subjects played a first-person shooter game and, as a control, nine subjects played a three-dimensional puzzle game.

Before and after playing the games, the subjects’ brain waves were recorded while they tried to detect a target object among other distractions over a wide visual field. Subjects who played the shooter videogame and also showed the greatest improvement on the visual attention task showed significant changes in their brain waves. The remaining subjects — including those who had played the puzzle game — did not.

"After playing the shooter game, the changes in electrical activity were consistent with brain processes that enhance visual attention and suppress distracting information," said Sijing Wu, a PhD student in Spence’s lab in U of T’s Department of Psychology and lead author of the study.

"Studies in different labs, including here at the University of Toronto, have shown that action videogames can improve selective visual attention, such as the ability to quickly detect and identify a target in a cluttered background," said Spence. "But nobody has previously demonstrated that there are differences in brain activity which are a direct result of playing the videogame."

"Superior visual attention is crucial in many important everyday activities," added Spence. "It’s necessary for things such as driving a car, monitoring changes on a computer display, or even avoiding tripping while walking through a room with children’s toys scattered on the floor."

Source: Science Daily

April 25th, 2012

National Institutes of Health researchers have reversed behaviors in mice resembling two of the three core symptoms of autism spectrum disorders (ASD). An experimental compound, called GRN-529, increased social interactions and lessened repetitive self-grooming behavior in a strain of mice that normally display such autism-like behaviors, the researchers say.

GRN-529 is a member of a class of agents that inhibit activity of a subtype of receptor protein on brain cells for the chemical messenger glutamate, which are being tested in patients with an autism-related syndrome. Although mouse brain findings often don’t translate to humans, the fact that these compounds are already in clinical trials for an overlapping condition strengthens the case for relevance, according to the researchers.

“Our findings suggest a strategy for developing a single treatment that could target multiple diagnostic symptoms,” explained Jacqueline Crawley, Ph.D., of the NIH’s National Institute of Mental Health (NIMH). “Many cases of autism are caused by mutations in genes that control an ongoing process – the formation and maturation of synapses, the connections between neurons. If defects in these connections are not hard-wired, the core symptoms of autism may be treatable with medications.”

Crawley, Jill Silverman, Ph.D., and colleagues at NIMH and Pfizer Worldwide Research and Development, Groton, CT, report on their discovery April 25th, 2012 in the journal Science Translational Medicine.

“These new results in mice support NIMH-funded research in humans to create treatments for the core symptoms of autism,” said NIMH director Thomas R. Insel, M.D. “While autism has been often considered only as a disability in need of rehabilitation, we can now address autism as a disorder responding to biomedical treatments.”

(Video: Agent Reduces Repetitive Behavior in Mice)
Autism-like behaviors in mice have been reduced, using an experimental agent being tested in patients for a related disorder. Here, a mouse is absorbed in repetitive self-grooming. The experimental agent reduced this repetitive behavior in a strain of mice that is prone to it, and almost stopped repetitive vertical jumping in another strain of mice. Credit: MuYang, Ph.D., Adam Katz, and Jacqueline Crawley, Ph.D., NIMH Laboratory of Behavioral Neuroscience. 

Crawley’s team followed-up on clues from earlier findings hinting that inhibitors of the receptor, called mGluR5, might reduce ASD symptoms. This class of agents – compounds similar to GRN-529, used in the mouse study – are in clinical trials for patients with the most common form of inherited intellectual and developmental disabilities, Fragile X syndrome, about one third of whom also meet criteria for ASDs.

To test their hunch, the researchers examined effects of GRN-529 in a naturally occurring inbred strain of mice that normally display autism-relevant behaviors. Like children with ASDs, these BTBR mice interact and communicate relatively less with each other and engage in repetitive behaviors – most typically, spending an inordinate amount of time grooming themselves.

Crawley’s team found that BTBR mice injected with GRN-529 showed reduced levels of repetitive self-grooming and spent more time around – and sniffing nose-to-nose with – a strange mouse.

(Video: Agent Boosts Sociability in Mice)
Autism-like behaviors in mice have been reduced, using an experimental agent being tested in patients for a related disorder. Here, a mouse pays a social visit to a strange animal. The experimental agent increased such sociability, which is impaired in autism. Credit: MuYang, Ph.D., and Jacqueline Crawley, Ph.D., NIMH Laboratory of Behavioral Neuroscience.

Moreover, GRN-529 almost completely stopped repetitive jumping in another strain of mice.

“These inbred strains of mice are similar, behaviorally, to individuals with autism for whom the responsible genetic factors are unknown, which accounts for about three fourths of people with the disorders,” noted Crawley. “Given the high costs – monetary and emotional – to families, schools, and health care systems, we are hopeful that this line of studies may help meet the need for medications that treat core symptoms.” 

Source: Neuroscience News  

ScienceDaily (Apr. 25, 2012) — New research from UC Davis and Washington State University shows that PCBs, or polychlorinated biphenyls, launch a cellular chain of events that leads to an overabundance of dendrites — the filament-like projections that conduct electrochemical signals between neurons — and disrupts normal patterns of neuronal connections in the brain.

New findings underscore the developing brain’s vulnerability to environmental exposures and demonstrate how PCBs could add to autism risk. (Credit: © yalayama / Fotolia)

"Dendrite growth and branching during early development is a finely orchestrated process, and the presence of certain PCBs confuses the conductor of that process," said Pamela Lein, a developmental neurobiologist and professor of molecular biosciences in the UC Davis School of Veterinary Medicine. "Impaired neuronal connectivity is a common feature of a number of conditions, including autism spectrum disorders."

Reported April 24 in two related studies in the journal Environmental Health Perspectives, the findings underscore the developing brain’s vulnerability to environmental exposures and demonstrate how PCBs could add to autism risk.

"We don’t think PCB exposure causes autism," Lein said, "but it may increase the likelihood of autism in children whose genetic makeup already compromises the processes by which neurons form connections."

The senior authors of the studies were Lein and Isaac Pessah, chair of molecular biosciences in the School of Veterinary Medicine and director of the Center for Children’s Environmental Health at UC Davis. Both are researchers with the UC Davis MIND Institute, which is dedicated to finding answers to autism and other neurodevelopmental disorders. The lead author was Gary Wayman of Washington State University’s Program in Neuroscience, who first described the molecular pathway that controls the calcium signaling in the brain that guides normal dendrite growth.

Wayman found that key cellular players, called calcium and calmodulin kinases, are activated by increased calcium levels. Activated calmodulin kinase then turns on the protein known as CREB that regulates genes that produce Wnt2, a potent molecule and the final arbiter of whether and how dendrites grow. Wnt2 directs structural proteins to construct scaffolding that supports dendrite growth and branching.

"Orderly choreography of the calmodulin kinase-to-Wnt2 pathway translates normal increases in calcium levels into normal levels of dendrite production," said Wayman. "The wiring of billions of neurons is dependent on the health of this cellular process and is crucial to proper development of virtually all complex behaviors, learning, memories and language."

For the current studies, the team set out to determine if that pathway was altered by exposure to PCBs, focusing on neurons of the hippocampus — the brain region linked with learning and memory and known to suffer impaired connectivity in many neurodevelopmental disorders.

The scientists also focused on the effects of an understudied PCB subset known as non-dioxin-like PCBs, which have been shown to increase calcium levels in neurons. Both non-dioxin-like PCBs and the more familiar dioxin-like subset were widely used in electrical equipment in the 1950s and 1960s. Banned in the 1970s because of the potential for dioxin-like PCBs to cause cancer, all PCBs are stable compounds that persist throughout the environment today.

One of the current UC Davis studies examined dendrite growth in rat pups born to and nursed by PCB-exposed mothers. Another study analyzed how PCBs affect rat neurons in cell cultures at developmental stages similar to those in the third trimester of pregnancy in humans. In both studies, PCB exposure levels were similar to those found in the human diet and in human tissues, including the placenta and breast milk.

Evaluation of the brains of the rats exposed to PCBs early in life showed significant overproduction of dendrites. The cellular studies showed that PCBs triggered the calcium pathway that led to the aberrant brain architecture, and that dendrite production was normal when that cellular pathway was blocked.

"We are the first to show that non-dioxin-like PCBs alter how the developing brain gets wired by hijacking the calcium signaling pathway and greatly expanding dendrite growth," said Lein.

The experiments also helped identify for the first time the specific trigger for this cellular chain of events as the ryanodine receptor (RyR) calcium channel. Pessah, a recognized leader in calcium-channel dysfunction and neurodevelopment, previously showed that RyR is selectively activated by non-dioxin-like PCBs. The new studies prove that RyR is a necessary component in the pathway that controls dendritic growth.

"These same calcium pathways are implicated in some forms of autism and, while environmental exposures alone do not cause autism, these new findings provide good evidence that PCBs could add to autism risk in genetically predisposed children," said Pessah. "Understanding the fundamental mechanisms by which PCBs alter neural networks sets the stage for research on environmental contaminants that are structurally related to PCBs, including flame retardants, and their risks to susceptible populations."

Source: Science Daily

April 25th, 2012

Second U-M stem cell line now publicly available to help researchers find treatments for nerve condition.
Charcot-Marie-Tooth disease line made from a never-frozen donated embryo.

The University of Michigan’s second human embryonic stem cell line has just been placed on the U.S. National Institutes of Health’s registry, making the cells available for federally-funded research. It is the second of the stem cell lines derived at U-M to be placed on the registry.

The line, known as UM11-1PGD, was derived from a cluster of about 30 cells removed from a donated five-day-old embryo roughly the size of the period at the end of this sentence. That embryo was created for reproductive purposes, tested and found to be affected with a genetic disorder, deemed not suitable for implantation, and would therefore have otherwise been discarded when it was donated in 2011.

It carries the gene defect responsible for Charcot-Marie-Tooth disease, a hereditary neurological disorder characterized by a slowly progressive degeneration of the muscles in the foot, lower leg and hand. CMT, as it is known, is one of the most common inherited neurological disorders, affecting one in 2,500 people in the United States. People with CMT usually begin to experience symptoms in adolescence or early adulthood.

The embryo used to create the cell line was never frozen, but rather was transported from another IVF laboratory in the state of Michigan to the U-M in a special container. This may mean that these stem cells will have unique characteristics and utilities in understanding CMT disease progression or screening therapies in comparison to other human embryonic stem cells.

“We are proud to provide this cell line to the scientific community, in hopes that it may aid the search for new treatments and even a cure for CMT,” says Gary Smith, Ph.D., who derived the line and also is co-director of the U-M Consortium for Stem Cell Therapies, part of the A. Alfred Taubman Medical Research Institute. “Once again, the acceptance of these cells to the registry demonstrates our attention to details of proper oversight, consenting, and following of NIH guidelines.”

U-M is one of only four institutions – including two other universities and one private company – to have disease-specific stem cell lines listed in the national registry. U-M has several other disease-specific hESC lines submitted to NIH and awaiting approval, says Smith, who is a professor in the Department of Obstetrics and Gynecology at the University of Michigan Medical School. The first line, a genetically normal one, was accepted to the registry in February.

“Stem cell lines that carry genetic traits linked to specific diseases are a model system to investigate what causes these diseases and come up with treatments,” says Sue O’Shea, Ph.D., professor of Cell and Developmental Biology at the U-M Medical School, and co-director of the Consortium for Stem Cell Therapies.

Each line is the culmination of years of preparation and cooperation between U-M and Genesis Genetics, a Michigan-based genetic diagnostic company. This work was made possible by Michigan voters’ November 2008 approval of a state constitutional amendment permitting scientists to derive embryonic stem cell lines using surplus embryos from fertility clinics or embryos with genetic abnormalities and not suitable for implantation.

The amendment also made possible an unusual collaboration that has blossomed between the University of Michigan and molecular research scientists at Genesis Genetics, a company that has grown in only eight years to become the leading global provider of pre-implantation genetic diagnosis (PGD) testing. PGD is a testing method used to identify days-old embryos carrying the genetic mutations responsible for serious inherited diseases. During a PGD test, a single cell is removed from an eight-celled embryo. The other seven cells continue to multiply and on the fifth day form a cluster of roughly 100 cells known as a blastocyst.

Genesis Genetics performs nearly 7,500 PGD tests annually. Under the arrangement between the company and U-M, patients with embryos that test positive for a genetic disease now have the option of donating those embryos to U-M if they have decided not to use them for reproductive purposes and the embryos would otherwise be discarded.

The agreement was worked out between U-M’s Smith and Mark Hughes, M.D., Ph.D., founder and president of Genesis Genetics and a pioneer in the field of pre-implantation genetic diagnosis. “These are very precious cells, and it would be unconscionable not to take advantage of such an opportunity for medical science and the cure of disease,” Hughes says.

“This is another major step forward for medical science in Michigan. It opens up another avenue for researchers to really begin exploring the causes and progression of those diseases, with the ultimate goal of finding new therapies for patients,” says Eva Feldman, M.D., Ph.D., F.A.A.N., director of the A. Alfred Taubman Medical Research Institute and the Russell N. DeJong professor of neurology at the U-M Medical School. Feldman sees patients with CMT as part of her clinical practice.

Contributors to the A. Alfred Taubman Medical Research Institute’s Consortium for Stem Cell Therapies include the Taubman Institute; the Office of the Executive Vice President for Medical Affairs; the Office of the Medical School Dean; the Comprehensive Cancer Center; the Department of Pediatrics and Communicable Diseases; the Office of the Vice President for Research; the School of Dentistry; the Department of Pathology; the Department of Cell and Developmental Biology; the College of Engineering; the Life Sciences Institute; the Department of Neurology; and U-M’s Michigan Institute for Clinical and Health Research.

A. Alfred Taubman, founder and chair of U-M’s Taubman Institute, called the second registry placement a tremendous step for stem cell research. “I consider stem cells to be a modern medical miracle – the most exciting advance in medicine since antibiotics. The progress we have made throughout the state in stem cell research has been nothing short of remarkable,” he says.

“This new milestone means much to the University and the state of Michigan, but also to the world. It offers another route for researchers to move ahead in studying these horrible diseases. We hope it is the first of many lines that we can contribute to the global efforts to improve human health.”

Written by Kara Gavin

Source: Neuroscience News

ScienceDaily (Apr. 25, 2012) — University of California, San Diego scientists have used powerful computational tools and laboratory tests to discover new support for a once-marginalized theory about the underlying cause of Parkinson’s disease.

This image shows a construction of a possible ring oligomer position in the cell membrane after four nanoseconds of molecular dynamics simulations. Image courtesy of Igor Tsigelny, San Diego Supercomputer Center and Department of Neurosciences, UC San Diego. (Credit: Image courtesy of University of California, San Diego)

The new results conflict with an older theory that insoluble intracellular fibrils called amyloids cause Parkinson’s disease and other neurodegenerative diseases. Instead, the new findings provide a step-by-step explanation of how a “protein-run-amok” aggregates within the membranes of neurons and punctures holes in them to cause the symptoms of Parkinson’s disease.

The discovery, published in the March 2012 issue of the FEBS Journal, describes how α-synuclein (a-syn), can turn against us, particularly as we age. Modeling results explain how α-syn monomers penetrate cell membranes, become coiled and aggregate in a matter of nanoseconds into dangerous ring structures that spell trouble for neurons.

"The main point is that we think we can create drugs to give us an anti-Parkinson’s effect by slowing the formation and growth of these ring structures," said Igor Tsigelny, lead author of the study and a research scientist at the San Diego Supercomputer Center and Department of Neurosciences, both at UC San Diego.

Familial Parkinson’s disease is caused in many cases by a limited number of protein mutations. One of the most toxic is A53T. Tsigelny’s team showed that the mutant form of α-syn not only penetrates neuronal membranes faster than normal α-syn, but the mutant protein also accelerates ring formation.

"The most dangerous assault on the neurons of Parkinson’s patients appears to be the relatively small α-syn ring structures themselves," said Tsigelny. "It was once heretical to suggest that these ring structures, rather than long fibrils found in neurons of people having Parkinson’s disease, were responsible for the symptoms of the disease; however, the ring theory is becoming more and more accepted for this neurodegenerative disease and others such as Alzheimer’s disease. Our results support this shift in thinking."

The modeling results also are consistent with the electron microscopy images of neurons in Parkinson’s disease patients; the damaged neurons are riddled with ring structures.

Wasting no time, the modeling discoveries have spawned an intense hunt at UC San Diego for drug candidates that block ring formation in neuron membranes. The sophisticated modeling required involves a complex realm of science at the intersection of chemistry, physics, and statistical probabilities. A kaleidoscope of interacting forces in this realm makes α-syn proteins bump and tremble like they’re in an earthquake, coil and uncoil, and join together in pairs or larger groups of inventive ballroom dancers.

The modeling is creating a much better understanding of the mysterious a-syn protein itself, according to Tsigelny. A few years ago it was shown to accumulate in the central nervous system of patients with Parkinson’s disease and a related disorder called dementia with Lewy bodies.

The new modeling study has revealed precisely how two α-syn proteins insert their molecular toes into the membrane of a neuron, wiggle into it in only a few nanoseconds and immediately join together as a pair. The pair isn’t itself toxic; however, when more α-syn proteins join the dance, a key threshold is eventually crossed; polymerization accelerates into a ring structure that perforates the membrane, damaging the cell.

Tsigelny said many ring structures may be required to actually kill neurons, which are known for their durability. The nerve cells may be able to repair dozens of ring-induced perforations, keeping pace with a-syn assault. But at some point, the rate of perforations surpasses the ability of neurons to repair them. As a result, symptoms of Parkinson’s disease gradually appear and worsen.

"We think we can create a drug that stops the α-syn polymerization at the point of non-propagating dimers," Tsigelny said. "By interrupting the polymerization at this crucial step, we may be able to slow the disease significantly."

Tsigelny’s research team included Yuriy Sharikov, with SDSC and UC San Diego’s Department of Neurosciences; Wolfgang Wrasidlo, with the university’s Moores Cancer Center; and Tania Gonzalez, Paula A. Desplats, Leslie Crews, and Brian Spencer, all with UC San Diego’s Department of Neurosciences. The experimental validation studies were performed by Eliezer Masliah, a professor in the UC San Diego departments of Neurosciences and Pathology, and his associates. They relied on 3-D models of proteins, plus molecular dynamics simulations of the proteins, other modeling techniques and cell-culture experiments.

Given their deeper understanding of α-syn polymerization in neurons, they are now focused on understanding how monomers of α-syn stick to one another. Their search for drug candidates will include molecules that induce different conformations of α-syn proteins that are less inclined to stick together. Tsigelny said this effect, even if small, could reduce symptoms.

This computationally intensive approach includes an examination of the many possible three-dimensional arrangements of α-syn dimers, trimmers and tetramers. Pharmaceutical companies have used versions of the approach to develop drug candidates designed to bind to ‘anchor residues’ or ‘hot spots’ within target proteins. Algorithms assess in virtual experiments the theoretical ability of thousands of candidate drugs to bind to human proteins in the ever-expanding database of known 3-D structures of those proteins.

However, attempts to find drugs this way have generated promising candidates that fail in clinical trials with expensive regularity.

"Out of these failures we’ve come to appreciate that proteins change their shapes so often that what would appear to be a primary drug target may be present one nanosecond, gone the next, or it wasn’t relevant in the first place," said Tsigelny, a physicist-turned-drug-designer.

Tsigelny’s approach takes advantage of classical drug-discovery algorithms, but adds additional analytical techniques to expand the search to include how a target protein’s conformations change in response to the forces operating on the scale of molecules.

"Sometimes, the drug-discovery models, despite being ‘nice looking,’ can be completely wrong," Tsigelny said. "Scientists involved in drug discovery need to know when and to what extent to trust them. Even a slight shift in a cell’s environment can profoundly change the interactions of proteins with neighboring molecules. We think it’s realistically possible to design a drug to treat neurodegenerative diseases such as Parkinson’s disease and other diseases like diabetes with a more fundamental understanding of the proteins involved in those diseases."

Source: Science Daily

ScienceDaily (Apr. 25, 2012) — Advertisers and public health officials may be able to access hidden wisdom in the brain to more effectively sell their products and promote health and safety, UCLA neuroscientists report in the first study to use brain data to predict how large populations will respond to advertisements.

The brain, with the medial prefrontal cortex highlighted in green. (Credit: Image courtesy of University of California - Los Angeles)

Thirty smokers who were trying to quit watched television commercials from three advertising campaigns, which all ended by showing the phone number of the National Cancer Institute’s smoking-cessation hotline. They were asked which commercials they thought would be most effective; they responded that advertising campaigns “A” and “B” would be the best and “C” would be the worst.

The UCLA researchers also consulted experts who work in the anti-smoking field and who have been involved in creating anti-smoking advertisements. These experts agreed that campaigns “A” and “B” were the best and “C” was the worst.

While the smokers watched the advertisements, they underwent functional magnetic resonance imaging (fMRI) brain scans at UCLA’s Ahmanson-Lovelace Brain Mapping Center, and the neuroscientists focused on part of the medial prefrontal cortex — located in the front of the brain, between the eyebrows — a region that they have found to be especially important in previous persuasion studies.

The researchers found that activity in the medial prefrontal cortex increased much more during advertising campaign “C” than it did during campaign “A,” and somewhat more than it did during campaign “B.”

"The medial prefrontal cortex predicted ‘C’ would be the best, ‘B’ would be second best and ‘A’ would be the worst — essentially the opposite of what the experts and the participants told us they thought would happen," said the study’s senior author, Matthew Lieberman, a UCLA professor of psychology and of psychiatry and biobehavioral sciences.

"We didn’t expect how radically different people’s predictions would be from the predictions we made based on their brain activity," said Lieberman, one of the founders of social cognitive neuroscience. "We had people telling us one thing and this brain region telling us something diametrically opposed."

Initially, Lieberman and first author Emily Falk, an assistant professor of communication studies and psychology at the University of Michigan-Ann Arbor, were concerned when they saw the results from the medial prefrontal cortex.

"We were hoping the brain data would add something to the self-reports of our participants," Lieberman said. "Given how different they were from one another, we were afraid our brain data might not end up predicting the real-world outcomes at all."

A few months later, after the advertisements had been broadcast, the authors received the call-volume data from the National Cancer Institute’s 1-800-QUIT-NOW hotline. They compared the number of people who called the hotline the month before and the month after each of the advertising campaigns was run. All three advertising campaigns were successful in increasing the number of phone calls to the hotline. Campaign “A” more than doubled the number of calls, “B” increased the number of calls more than ten-fold and “C” boosted the number of calls a remarkable thirty-fold. (The advertisements were shown in Michigan, Massachusetts and Louisiana.)

Activity in the medial prefrontal cortex predicted which ads persuaded more people to call the hotline significantly better than the smokers’ own thoughts about how successful the ads would be.

The research is published this month in the online edition of the journal Psychological Science.

What are the implications for the advertising industry, which often relies, at least partly, on unscientific focus groups?

"If people are making decisions based on what focus groups tell them, here’s an important brain region saying, ‘No, spend your money a different way,’" Lieberman said. "If I were deciding on an advertising campaign, I would want to know which ads are activating this region the most — that is where I would want to spend my money."

This new research represents “the first thing you could call a neural focus group,” Lieberman said.

One reason focus groups can be misleading, he said, is that people often do not know what motivates their own behavior.

"Our brain is built to generate reasons for our actions," Lieberman said, "and we think the reasons we come up with must be true. We believe our own reasons with an intensity that is out of proportion to their accuracy. In this study, we are bypassing people’s self-reports and getting at a form of hidden wisdom in the brain.

"We wanted to determine what kind of brain activity serves as the catalyst between people seeing a message and whether they actually change their behavior," he said. "This is the region we identified. We have tested it multiple times, and each time, it has been successful."

John Wanamaker, a 19th-century U.S. department store pioneer, famously said he wasted half the money he spent on advertising, but “the trouble is I don’t know which half.” Many people since Wanamaker have hoped to predict which advertising campaigns will succeed or fail before committing their advertising dollars.

"We’re too late for Wanamaker, but now we have a method for figuring out which ads will succeed," Lieberman said.

The 30 smokers in the study were between the ages of 28 and 69; half were female.

Brain regions associated with thinking analytically have not been consistently associated with whether people change their behavior in these studies, Lieberman said. The medial prefrontal cortex is associated not with analytical thinking but with self-reflection — thinking about our own identity as well as what we like and do not like.

"Persuasive advertising seems to be about getting to people’s hearts and their identity," Lieberman said. "We are just at the beginning of this line of research. There are many more questions than answers, but the initial results have been promising."

In research Lieberman and Falk published in the Journal of Neuroscience in 2010, greater activity in the same medial prefrontal region was predictive of who would increase their sunscreen usage after seeing persuasive messages about daily sunscreen use.

"We knew from prior studies that this brain region predicted people’s behavior change in response to a persuasive message," Lieberman said.

With the new study, Lieberman and his colleagues wanted to know whether they could predict not only people’s own behavior but use these brain responses to predict how effective advertisements would be throughout the country.

Source: Science Daily

April 25, 2012

Can one feel too attached? Does one need to let go to mature? Neural stem cells have this problem, too.

As immature cells, neural stem cells must stick together in a protected environment called a niche in order to divide so they can make all of the cells that populate the nervous system. But when it’s time to mature, or differentiate, the neural stem cells must stop dividing, detach from their neighbors and migrate to where they are needed to form the circuits necessary for humans to think, feel and interact with the world.

Now, stem cell researchers at UCLA have identified new components of the genetic pathway that controls the adhesive properties and proliferation of neural stem cells and the formation of neurons in early development.

The finding by scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA could be important because errors in this pathway can lead to a variety of birth defects that affect the structure of the nervous system, as well as more subtle changes that impair cognitive and motor functions associated with disorders such as autism.

The results of the four-year study are published April 26, 2012 in the peer-reviewed journal Neuron.

The UCLA team found that a delicate balance of gene expression enables the pool of neural stem and progenitor cells in early development to initially increase and then quickly stop dividing to form neurons at defined times.

"One of the greatest mysteries in developmental biology is what constitutes the switch between stem cell proliferation and differentiation. In our studies of the formation of motor neurons, the cells that are essential for movement, we were able to uncover what controls the early expansion of neural stem and progenitor cells, and more importantly what stops their proliferation when there are enough precursors built up," said Bennett G. Novitch, an assistant professor of neurobiology, a Broad Stem Cell Research Center scientist and senior author of the study. "If the neurons don’t form at the proper time, it could lead to deficits in their numbers and to catastrophic, potentially fatal neurological defects." 

During the first trimester of development, the neural stem and progenitor cells form a niche, or safe zone, within the nervous system. The neural stem and precursor cells adhere to each other in a way that allows them to expand their numbers and keep from differentiating. A protein called N-cadherin facilitates this adhesion, Novitch said.

When it is time for the neural precursors to become motor neurons, two proteins that repress gene expression, called Foxp2 and Foxp4, become elevated and then silence N-cadherin expression, causing the clustered neural stem and precursor cells to break apart and begin differentiating.

"We have these cells in a dividing state, making more of themselves, and to make neurons that process has to be stopped and those contacts between the cells disassembled," Novitch said. "Until now, it has not been clear how the cells are pulled apart."

Novitch and his team showed that if you eliminate Foxp protein function, motor neurons and other mature cells in the nervous system are not properly formed because the N-cadherin gene is not silenced, confirming the delicate balancing act that must be achieved for normal development of both the stem and precursor cells and their neuronal progeny.

"It’s a fundamental discovery. Most studies have focused on defining what promotes the adhesiveness and self-renewal of neural stem cells, rather than what breaks these contacts," Novitch said. "We were also surprised to see how small changes in the degree of cell adhesion can markedly alter the development and structure of the nervous system. It’s all about balance, if you have too many or too few stem and precursor cells, the result could be disastrous."

Going forward, Novitch and his team will examine whether the functions of Foxp2 and Foxp4 in regulating cell adhesion may be important for the maintenance and differentiation of neural stem cells in the adult brain, and whether the loss of their activity may contribute to the formation and growth of brain tumors. In addition, Novitch’s group plans to examine whether their findings are relevant for investigating the function of Foxp2 and Foxp4 in other aspects of neural development, as mutations in Foxp proteins have previously been associated with a range of intellectual disabilities and speech-language disorders.

"It is tempting to speculate that these loss-of-function phenotypes might result from abnormal cell adhesion associated with dysregulated N-cadherin expression or function," the study states. "If true, these findings could provide a molecular explanation for the association of Foxp mutations with developmental human language and motor disorders, including autism."

Provided by University of California - Los Angeles Health Sciences

Source: medicalxpress.com

April 25, 2012 By Allison Flynn

McGill physiology research team sheds light on how the brain processes what we sense.

We rely on our senses in all aspects of our lives. Unfortunately, many people suffer from some kind of impaired sensory function. In Canada alone, 600,000 people are visually impaired while almost three million suffer from partial or total hearing loss. In a paper published this week in The Journal of Neuroscience, researchers from McGill University have demonstrated for the first time that there are specific neurons that respond selectively to first and second order sensory attributes. In the visual system, for example, luminance is a first-order attribute, whereas contrast is second-order. These findings could pave the way to the development of novel therapies and improved prosthetics for those with sensory deficiencies.

The research team, led by physiology student Patrick McGillivray, recorded the responses to stimuli of midbrain electro-sensory neurons in the weakly electric fish. Based on these responses, the researchers were able to demonstrate that there are specific neurons that respond selectively to different attributes at the same time. Moreover, they uncovered the simple and generic neural circuits that enable this selectivity. These findings provide important clues about how the brain processes first and second order sensory attributes in audition (like pitch and timbre) and vision (like luminance and contrast).

"Uncovering these clues relies on identifying the attributes that we use to perceive stimuli, the computations performed by the brain, and the actual neural networks that implement these," explained Dr. Maurice Chacron, lead author and principal investigator at McGill’s Computational Systems Neuroscience Lab. "Stimuli like speech and music are characterized by multiple attributes. For example, when listening to music, we can perceive both frequency (how low or high an instrument is playing), as well as timbre (the type of instrument playing)."

Provided by McGill University

Source: medicalxpress.com

April 24th, 2012

Researchers at the University of Sydney have thrown new light on the tricks the brain plays as it struggles to make sense of the visual and other sensory signals it constantly receives.

In this tilt illusion, the lines in the centre of the image appear tilted counterclockwise, but they are actually vertical. Image adapted from University of Sydney image.

The research has implications for understanding how the brain interprets the world visually and how the brain itself works.

People rely on their eyes for most tasks – yet the information provided by our visual sensing system is often distorted, unreliable and subject to illusion.

In a just published article in Proceedings of the National Academy of Science, Dr Isabelle Mareschal and Professor Colin Clifford, from the University’s School of Psychology and The Vision Centre, report a series of groundbreaking experiments tracing the origins of the tilt illusion to the cells of the primary visual cortex. This is where the first stage of vision processing takes place before the conscious mind takes over.

“We tend to regard what we see as the real world,” said Dr Mareschal.

“In fact a lot of it is distortion, and it is occurring in the early processing of the brain, before consciousness takes over. Our work shows that the cells of the primary visual cortex create small distortions, which then pass on to the higher levels of the brain, to interpret as best it can.”

A common example of this that is often exploited by artists and designers is known as the tilt illusion where perfectly vertical lines appear tilted because they are placed on an oriented background.

“We wanted to test at what level the illusion occurs in the brain, unconscious or conscious – and also to see if the higher brain is aware of the illusions it is receiving and how it tries to correct for them,” she explains.

“The answer is that the brain seeks more contextual information from the background to try to work out the alignment of the object it is seeing.”

The team subjected volunteers to a complex test in which they indicated the orientation of a vertical line, perceived as constantly tilting from side to side, against a fuzzy background that was also changing.

“These illusions happen very fast, perhaps in milliseconds,” Dr Mareschal says. “And we found that even the higher brain cannot always correct for them, as it doesn’t in fact know they are illusions.”

This is one reason why people’s eyes sometimes mislead them when looking at objects in their visual landscape.

Normally, Dr Mareschal explains, it doesn’t matter all that much – but in the case of a person driving a car fast in traffic, an athlete performing complex acrobatic feats, a pilot landing an aircraft or other high-speed uses of sight, the illusion may be of vital importance by causing them to misinterpret the objects they ‘see’.

The brain uses context, or background, to interpret a host of other visual signals besides the orientation of objects. For example, it uses context to tell colour, motion, texture and contrast. The research will help study how the brain understands these visual cues adding to our overall understanding of brain function.

Source: Neuroscience News

By Brian Alexander

Good news for all those who ever had a teacher or a parent say “If you would just apply yourself you could learn anything! You’re only using 10 percent of your brain!”

All those people were wrong. If we did use only 10 percent of our brains we’d be close to dead, according to Eric Chudler, director of the Center for Sensorimotor Neural Engineering at the University of Washington, who maintains an entertaining brain science website for kids. “When recordings are made from brain EEGs, or PET scans, or any type of brain scan, there’s no part of the brain just sitting there unused,” he said. 

Larry Squire, a research neuroscientist with the Veterans Administration hospital in San Diego, and at the University of California San Diego, pointed out that “any place the brain is damaged there is a consequence.”

Damaged brains may have been where this myth originated. During the first half of the last century, a pioneering neuroscientist named Karl Lashley experimented on rodents by excising portions of their brains to see what happened. When he put these rodents in mazes they’d been trained to navigate, he found that animals with missing bits of brain often successfully navigated the mazes.

This wound up being transmuted into the idea humans must be wasting vast brain potential. With the rise of the human potential movement in the 1960s, some preached that all sorts of powers, including bending spoons and psychic abilities, were laying dormant in our heads and that all we had to do was get off our duffs and activate them.

“That’s a case of something one often sees, of taking something from the world of psychology and in trying to make the idea concrete, bringing in the mechanisms of biology,” Squire explained. “It’s fair to say we can all do better, and we have room for improvement through practice and developing skills, but that has nothing to do with the idea that we use only 10 percent of our brains.”

The brain, Chudler said, isn’t like a disc drive with some set amount of capacity. It’s a dynamic maze of wiring where new connections can be created in response to new stimuli, or lost with disuse. And much of it is constantly occupied not with intellectual thinking, but running our systems.

“That’s why the brain is such an expensive organ,” he explained. “It requires 20 percent of our blood supply, and it’s a real energy hog.” If we used only 10 percent of it, the brain wouldn’t require such high maintenance.

“Besides,” he pointed out, “why would our brains have gotten bigger through evolution if so much of it were going unused?”

Source: The Body Odd

April 24, 2012

Older animals show cellular changes in the brain “clock” that sets sleep and wakeful periods, according to new research in the April 25 issue of The Journal of Neuroscience. The findings may help explain why elderly people often experience trouble sleeping at night and are drowsy during the day.

Like humans, mice experience shifts in daily activities and sleep patterns as they age. To find out why, researchers directed by Johanna Meijer, PhD, at the Leiden University Medical Center in the Netherlands studied the electrical activity of cells in the suprachiasmatic nucleus (SCN), an area of the brain responsible for setting sleep-wake cycles.

Consistent with previous studies, the researchers found aged mice showed disrupted sleep behavior and weakened brain network activity in the SCN. But Meijer and colleagues also found changes occurring in individual SCN cells, not just in their networks.

"In fact, the changes at the single-cell level were more severe than the changes at the network level," said Meijer. This represents a shift in understanding of aging’s effects on the brain.

The researchers made electrophysiological recordings from isolated SCN neurons, a difficult experiment given the advanced age of the animals and the small size of this type of neuron. They found aged SCN neurons lack day-night rhythms in some membrane properties. In addition, the team identified age-related reductions of certain potassium currents that are important to the neurons’ rhythmic firing.

Because potassium and other ion channels can be manipulated with drugs, “This work provides a new target for potential therapeutic interventions that can mitigate the age-related decline in the sleep-wake cycle,” said Christopher Colwell, PhD, an expert in circadian clock function at the University of California, Los Angeles, who was not involved in the study.

Provided by Society for Neuroscience

Source: medicalxpress.com

April 24, 2012

A history of binge eating — consuming large amounts of food in a short period of time — may make an individual more likely to show other addiction-like behaviors, including substance abuse, according to Penn State College of Medicine researchers. In the short term, this finding may shed light on the factors that promote substance abuse, addiction, and relapse. In the long term, may help clinicians treat individuals suffering from this devastating disease.

"Drug addiction persists as a major problem in the United States," said Patricia Sue Grigson, Ph.D., professor, Department of Neural and Behavioral Sciences. "Likewise, excessive food intake, like binge eating, has become problematic. Substance-abuse and binge eating are both characterized by a loss of control over consumption. Given the common characteristics of these two types of disorders, it is not surprising that the co-occurrence of eating disorders and substance abuse disorders is high. It is unknown, however, whether loss of control in one disorder predisposes an individual to loss of control in another."

Grigson and her colleagues found a link between bingeing on fat and the development of cocaine-seeking and -taking behaviors in rats, suggesting that conditions promoting excessive behavior toward one substance can increase the probability of excessive behavior toward another. They report their results in Behavioral Neuroscience.

The researchers used rats to test whether a history of binge eating on fat would augment addiction-like behavior toward cocaine by giving four groups of rats four different diets: normal rat chow; continuous ad lib access to an optional source of dietary fat; one hour of access to optional dietary fat daily; and one hour of access to dietary fat on Mondays, Wednesdays, and Fridays. All four groups also had unrestricted access to nutritionally complete chow and water. The researchers then assessed the cocaine-seeking and -taking behaviors.

"Fat bingeing behaviors developed in the rats with access to dietary fat on Mondays, Wednesdays, and Fridays — the group with the most restricted access to the optional fat," Grigson said. 

This group tended to take more cocaine late in training, continued to try to get cocaine when signaled it was not available, and worked harder for cocaine as work requirements increased.

"While the underlying mechanisms are not known, one point is clear from behavioral data: A history of bingeing on fat changed the brain, physiology, or both in a manner that made these rats more likely to seek and take a drug when tested more than a month later," Grigson said. "We must identify these predisposing neurophysiological changes."

While the consumption of fat in and of itself did not increase the likelihood of subsequent addiction-like behavior for cocaine, the irregular binge-type manner in which the fat was eaten proved critical. Rats that had continuous access to fat consumed more fat than any other group, but were three times less likely to exhibit addiction-like behavior for cocaine than the group with access only on Mondays, Wednesdays and Fridays.

"Indeed, while about 20 percent of those rats and humans exposed to cocaine will develop addiction-like behavior for the drug under normal circumstances, in our study, the probability of addiction to cocaine increased to approximately 50 (percent) for subjects with a history of having binged on fat," Grigson said.

Future studies will look more closely at how bingeing can lead to addiction-like behaviors — whether bingeing on sugar or a mixture of sugar and fat also promotes cocaine or heroin addiction, for example, and whether bingeing on a drug, in turn, increases the likelihood of bingeing on fat.

Provided by Pennsylvania State University

Source: medicalxpress.com

ScienceDaily (Apr. 24, 2012) — Scientists at The Scripps Research Institute have found clinical evidence that the drug gabapentin, currently on the market to treat neuropathic pain and epilepsy, helps people to quit smoking marijuana (cannabis). Unlike traditional addiction treatments, gabapentin targets stress systems in the brain that are activated by drug withdrawal.

In a 12-week trial of 50 treatment-seeking cannabis users, those who took gabapentin used less cannabis, experienced fewer withdrawal symptoms such as sleeplessness, and scored higher on tests of attention, impulse-control, and other cognitive skills, compared to patients who received a placebo. If these results are confirmed by ongoing larger trials, gabapentin could become the first FDA-approved pharmaceutical treatment for cannabis dependence.

"A lot of other drugs have been tested for their ability to decrease cannabis use and withdrawal, but this is the first to show these key effects in a controlled treatment study," said Barbara J. Mason, the Pearson Family Chair and Co-Director of the Pearson Center for Alcoholism and Addiction Research at Scripps Research. "The other nice thing about gabapentin is that it is already widely prescribed, so its safety is less likely to be an issue."

Mason led the new gabapentin study, recently published online ahead of print by the journal Neuropsychopharmacology.

Stress Circuits

Addiction researchers have long known that recreational drugs hook users by disrupting the normal tuning of their brains’ reward and motivation circuitry. But as scientists at Scripps Research and other institutions have shown in animal studies, cannabis withdrawal after prolonged heavy use also leads to the long-term activation of basic stress circuits. “In human cannabis users who try to quit, this stress response is reflected in reports of drug craving, sleep disturbances, anxiety, irritability, and dysphoria, any one of which can motivate a person to return to using, because cannabis will quiet these symptoms,” said Mason.

A 2008 study by Pearson Center Co-Director George Koob and his colleagues found that gabapentin, an FDA-approved anticonvulsant drug that resembles the neurotransmitter GABA, can quiet this withdrawal-related activation in stress circuitry in alcohol-dependent rats. That finding motivated Mason to set up a pilot trial of gabapentin in cannabis-dependent individuals, whose withdrawal syndrome features a similar over-activation of stress circuits.

She and her colleagues recruited cannabis users with local newspaper and web ads headlined: “Smoking too much pot? We want to help you stop.” "We needed only 50 subjects, but we quickly got more than 700 queries from cannabis users who were eager to quit," Mason said. "Some people deny that cannabis can be addictive, but surveys show that between 16 and 25 percent of substance use treatment admissions around the world every year involve people with primary cannabis dependence."

Twice as Many Abstinent from Cannabis Use

The trial was based at Mason’s laboratory at The Scripps Research Institute. Half of the 50 recruits were randomly assigned to take 1,200 mg/day of gabapentin; the rest were given identical-looking placebo capsules. Over 12 weeks, Mason and her colleagues, including a medical team from the nearby Scripps Clinic, monitored the subjects with tests. Using standard behavioral therapy techniques, they also counseled the patients to stay off cannabis.

The subjects’ self-reports and more objective urine tests revealed that gabapentin, compared to placebo, significantly reduced their continuing cannabis use. “Urine metabolite readings indicate about twice as many of the gabapentin subjects had no new cannabis use during the entire study, and, in the last four weeks of the study, all of the gabapentin subjects who completed the study stayed abstinent,” Mason said.

Gabapentin also clearly reduced the reported symptoms of withdrawal such as sleep disturbances, drug cravings, and dysphoria. And even though gabapentin normally is thought of as a brain-quieting drug that can cause sleepiness as a side effect, there was some evidence that it sharpened cognition among the cannabis users. Seven gabapentin and ten placebo patients sat for tests of attention, impulse-control, and other executive functions just before the start of the trial and at week four. While the placebo patients tended to score lower after four weeks of attempted abstinence, the gabapentin patients generally scored higher.

Help Resisting Cravings

Addiction researchers now recognize that one of the effects of repeated drug use is the weakening of executive functions — which can happen through the over-activation of reward circuitry as well as by withdrawal-related stress. “That weakening of self-control-related circuits makes it even harder for people to resist drug cravings when they’re trying to quit, but gabapentin may help restore those circuits, by reducing stress and enabling patients to sleep better, so that they function better while awake,” Mason said.

She is now conducting a larger, confirmatory study of gabapentin in cannabis users, as well as a new study of a novel drug that targets the same stress circuitry.

"People in the treatment community have told me that they’re eager for these trial results to come out, because until now nothing has been shown to work against both relapse and withdrawal symptoms," Mason said.

Source: Science Daily

ScienceDaily (Apr. 24, 2012) — Stanford University School of Medicine neuroscientists have demonstrated, in a study published online April 24 in Stroke, that a compound mimicking a key activity of a hefty, brain-based protein is capable of increasing the generation of new nerve cells, or neurons, in the brains of mice that have had strokes. The mice also exhibited a speedier recovery of their athletic ability.

These results are promising, because the compound wasn’t administered to the animals until a full three days after they had suffered strokes, said the study’s senior author, Marion Buckwalter, MD, PhD, an assistant professor of neurology and neurological sciences. This means that the compound works not by limiting a stroke’s initial damage to the brain, but by enhancing recovery.

This is of critical significance, said Buckwalter, a practicing clinical neurologist who often treats recently arrived stroke patients in Stanford Hospital’s intensive care unit.

"No existing therapeutic agents today enhance recovery from stroke," Buckwalter said. "The only approved stroke drug, tissue plasminogen activator, can bust up clots that initially caused the stroke but does nothing to stimulate the restoration of brain function later." Furthermore, to be effective, tPA has to be given within four and a half hours after a stroke has occurred, she added. "In real life, many people don’t get to the hospital that quickly. They may live alone or have their stroke while sleeping, or they and the people close to them didn’t recognize the stroke’s symptoms well enough to realize they’d just had one."

Looking for an alternative, Buckwalter chose to focus on a compound called LM22A-4, which had shown promise in previous research. LM22A-4 is a small molecule whose bulk is less than one-seventieth that of the brain protein it mimics: brain-derived neurotrophic factor, a powerful and long-studied nerve growth factor. BDNF is critical during the development of the nervous system and known to be involved in important brain functions including memory and learning.

Stem-cell therapy, while an exciting prospect, is a relatively invasive and expensive way to replace lost or damaged tissue. A drug that could achieve similar results in such a delicate and complex organ as the brain would be a welcome development.

Read More →

ScienceDaily (Apr. 24, 2012) — In an important test of one of the first drugs to target core symptoms of autism, researchers at Mount Sinai School of Medicine are undertaking a pilot clinical trial to evaluate insulin-like growth factor (IGF-1) in children who have SHANK3 deficiency (also known as 22q13 Deletion Syndrome or Phelan-McDermid Syndrome), a known cause of autism spectrum disorder (ASD).

This study builds on findings announced by the researchers in 2010, which showed that after two weeks of treatment with IGF-1 in a mouse model, deficits in nerve cell communication were reversed and deficiencies in adaptation of nerve cells to stimulation, a key part of learning and memory, were restored.

"This clinical trial is part of a paradigm shift to develop medications specifically to treat the core symptoms of autism, as opposed to medications that were developed for other purposes but were found to be beneficial for autism patients as well," said Joseph Buxbaum, PhD, Director of the Seaver Autism Center at Mount Sinai. "Our study will evaluate the impact of IGF-1 vs. placebo on autism-specific impairments in socialization and associated symptoms of language and motor disability."

The seven-month study, which begins this month, will be conducted under the leadership of the Seaver Autism Center Clinical Director Alex Kolevzon, MD, and will utilize a double-blind, placebo-controlled crossover design in children ages 5 to 17 years old with SHANK3 deletions or mutations. Patients will receive three months of treatment with active medication or placebo, separated by a four-week washout period. Future trials are planned to explore the utility of IGF-1 in ASD without SHANK3 deficiency.

The primary aim of the study is to target core features of ASD, including social withdrawal and language impairment, which will be measured using both behavioral and objective assessments. If preliminary results are promising, the goal is to expand the studies into larger, multi-centered efforts to include as many children as possible affected by this disorder.

IGF-1 is a US Food and Drug Administration-approved, commercially available compound that is known to promote neuronal cell survival as well as synaptic maturation and plasticity. Side effects of IGF-1 administration include low blood sugar, liver function abnormalities, and increased cholesterol and triglyceride levels. Study subjects will undergo rigorous safety screening before they are enrolled in the trial, and will be carefully monitored every two to four weeks with safety and efficacy assessments.

"We are excited that the researchers at the Seaver Autism Center are undertaking this pilot study to evaluate a possible treatment for SHANK3 deficiency, which may also help everyone with ASD," said Geraldine Bliss, Research Support Chair of the Phelan-McDermid Foundation. "This will be the first clinical trial in Phelan-McDermid Syndrome to emerge from convincing preclinical evidence in a model system."

The cause of autism has been debated for many years. Currently the best scientific evidence indicates that genetic mutations are the most likely culprits, acting either directly or indirectly, in upwards of 80 to 90 percent of individuals with ASDs. In the past few years, gene mutations and gene copy number variations have been identified that cause approximately 15 percent of cases of ASD. However, it is thought that hundreds of genes may be involved in causing autism.

One copy of the q13 portion of chromosome 22 is either missing or otherwise mutated in SHANK3 deficiency, also known as Phelan-McDermid Syndrome or 22q13 Deletion Syndrome (22q13DS). The area in question contains the gene SHANK3, and there is overwhelming evidence that it is the loss of one copy of SHANK3 that produces the neurological and behavioral aspects of the syndrome. The SHANK3 gene is key to the development of the human nervous system, and loss of SHANK3 can impair the ability of neurons to communicate with one another.

Source: Science Daily

ScienceDaily (Apr. 24, 2012) — Chronic fatigue syndrome, a medical disorder characterized by extreme and ongoing fatigue with no other diagnosed cause, remains poorly understood despite decades of scientific study. Although researchers estimate that more than 1 million Americans are affected by this condition, the cause for chronic fatigue syndrome, a definitive way to diagnose it, and even its very existence remain in question. In a new study, researchers have found differing brain responses in people with this condition compared to healthy controls, suggesting an association between a biologic functional response and chronic fatigue syndrome.

The findings show that patients with chronic fatigue syndrome have decreased activation of an area of the brain known as the basal ganglia in response to reward. Additionally, the extent of this lowered activation was associated with each patient’s measured level of fatigue. The basal ganglia are at the base of the brain and are associated with a variety of functions, including motor activity and motivation. Diseases affecting basal ganglia are often associated with fatigue. These results shed more light on this mysterious condition, information that researchers hope may eventually lead to better treatments for chronic fatigue syndrome.

The study was conducted by Elizabeth R. Unger, James F. Jones, and Hao Tian of the Centers for Disease Control and Prevention (CDC), Andrew H. Miller and Daniel F. Drake of Emory University School of Medicine, and Giuseppe Pagnoni of the University of Modena and Reggio Emilia. An abstract of their study entitled, “Decreased Basal Ganglia Activation in Chronic Fatigue Syndrome Subjects is Associated with Increased Fatigue,” will be discussed at the meeting Experimental Biology 2012, being held April 21-25 at the San Diego Convention Center. The abstract is sponsored by the American Society for Investigative Pathology (ASIP), one of six scientific societies sponsoring the conference which last year attracted some 14,000 attendees.

More Fatigue, Less Activation

Dr. Unger says that she and her colleagues became curious about the role of the basal ganglia after previous studies by collaborators at Emory University showed that patients treated with interferon alpha, a common treatment for chronic hepatitis C and several other conditions, often experienced extreme fatigue. Further investigation into this phenomenon showed that basal ganglia activity decreased in patients who received this immune therapy. Since the fatigue induced by interferon alpha shares many characteristics with chronic fatigue syndrome, Unger and her colleagues decided to investigate whether the basal ganglia were also affected in this disorder.

The researchers recruited 18 patients with chronic fatigue syndrome, as well as 41 healthy volunteers with no symptoms of CFS. Each study participant underwent functional magnetic resonance imaging, a brain scan technique that measures activity in various parts of the brain by blood flow, while they played a simple card game meant to stimulate feelings of reward. The participants were each told that they’d win a small amount of money if they correctly guessed whether a preselected card was red or black. After making their choice, they were presented with the card while researchers measured blood flow to the basal ganglia during winning and losing hands.

The researchers showed that patients with chronic fatigue syndrome experienced significantly less change in basal ganglia blood flow between winning and losing than the healthy volunteers. When the researchers looked at scores for the Multidimensional Fatigue Inventory, a survey often used to document fatigue for chronic fatigue syndrome and various other conditions, they also found that the extent of a patient’s fatigue was tightly tied with the change in brain activity between winning and losing. Those with the most fatigue had the smallest change.

Results Suggest Role of Inflammation

Unger notes that the findings add to our understanding of biological factors that may play a role in chronic fatigue syndrome. “Many patients with chronic fatigue syndrome encounter a lot of skepticism about their illness,” she says. “They have difficulty getting their friends, colleagues, coworkers, and even some physicians to understand their illness. These results provide another clue into the biology of chronic fatigue syndrome.”

The study also suggests some areas of further research that could help scientists develop treatments for this condition in the future, she adds. Since the basal ganglia use the chemical dopamine as their major neurotransmitter, dopamine metabolism may play an important role in understanding and changing the course of this illness. Similarly, the difference in basal ganglia activation between the patients and healthy volunteers may be caused by inflammation, a factor now recognized as pivotal in a variety of conditions, ranging from heart disease to cancer.

Estimates from the CDC suggest that annual medical costs associated with chronic fatigue syndrome total about $14 billion in the United States. Annual losses to productivity because of lost work time range between $9 and $37 billion, with costs to individual households ranging between $8,000 and $20,000 per year.

Source: Science Daily

ScienceDaily (Apr. 24, 2012) — Toxic prions in the brain can be detected with self-illuminating polymers. The originators, at Linköping University in Sweden, has now shown that the same molecules can also render the prions harmless, and potentially cure fatal nerve-destroying illnesses.

Linköping researchers and their colleagues at the University Hospital in Zürich tested the luminescent conjugated polymers, or LCPs, on tissue sections from the brains of mice that had been infected with prions. The results show that the number of prions, as well as their toxicity and infectibility, decreased drastically. This is the first time anyone has been able to demonstrate the possibility of treating illnesses such as mad cow disease and Creutzfeldt-Jacobs with LCP molecules.

"When we see this effect on prion infections, we believe the same approach could work on Alzheimer’s disease as well," says Peter Nilsson, researcher in Bioorganic Chemistry funded by ERC, the European Research Council.

Along with professors Per Hammarström and Adriano Aguzzi and others, he is now publishing the results in The Journal of Biological Chemistry.

Prions are diseased forms of normally occurring proteins in the brain. When they clump together in large aggregates, nerve cells in the surrounding area are affected, which leads to serious brain damage and a quick death. Prion illnesses can be inherited, occur spontaneously or through infection, for example through infected meat — as was the case with mad cow disease.

The course of the illness is relentless when the prions fall to pieces and replicate at an exponential rate. When researchers inserted the LCP molecules into their model system, the replication was arrested, possible through stabilizing the prion aggregates.

The variable components in an LCP are various chemical subgroups attached onto the polymer. In the published study, eight different substances were tested, and all of them had significant effect on the toxicity of the prions.

"Based on these results, we can now customise entirely new molecules with potentially even better effect. These are now being tested on animal models," Nilsson says.

Researchers want to go even further and test whether the molecules will function on fruit flies with an Alzheimer’s-like nerve disorder. Alzheimer’s is caused by what is known as amyloid plaque, which has a similar but slower course than prion diseases.

Source: Science Daily

April 23rd, 2012

A team of scientists from Johns Hopkins and elsewhere have developed nano-devices that successfully cross the brain-blood barrier and deliver a drug that tames brain-damaging inflammation in rabbits with cerebral palsy.

Schematic picture of a dendrimer with multiple branches that are tagged with drug molecules and imaging agents. Image adapted from press release image from Johns Hopkins.

A report on the experiments, conducted at Wayne State University in collaboration with the Perinatology Research Branch of the National Institute of Child Health and Human Development, before the lead and senior investigators moved to Johns Hopkins, is published in the April 18 issue of Science Translational Medicine.

For the study, researchers used tiny, manmade molecules laced with N-acetyl-L-cysteine (NAC), an anti-inflammatory drug used as antidote in acetaminophen poisoning. The researchers precision-targeted brain cells gone awry to halt brain injury. In doing so they improved the animals’ neurologic function and motor skills.

The new approach holds therapeutic potential for a wide variety of neurologic disorders in humans that stem from neuro-inflammation, including Alzheimer’s disease, stroke, autism and multiple sclerosis, the investigators say.

The scientists caution that the findings are a long way from human application, but that the simplicity and versatility of the drug-delivery system make it an ideal candidate for translation into clinical use.

“In crossing the blood-brain barrier and targeting the cells responsible for inflammation and brain injury, we believe we may have opened the door to new therapies for a wide-variety of neurologic disorders that stem from an inflammatory response gone haywire,” says lead investigator Sujatha Kannan, M.D., now a pediatric critical-care specialist at Johns Hopkins Children’s Center.

Cerebral palsy (CP), estimated to occur in three out of 1,000 newborns, is a lifelong, often devastating disorder caused by infection or reduced oxygen to the brain before, during or immediately after birth. Current therapies focus on assuaging symptoms and improving quality of life, but can neither reduce nor reverse neurologic damage and loss of motor function.

Neuro-inflammatory damage occurs when two types of brain cells called microglia and astrocytes — normally deployed to protect the brain during infection and inflammation — actually damage it by going into overdrive and destroying healthy brain cells along with damaged ones.

Directly treating cells in the brain has long proven difficult because of the biological and physiological systems that have evolved to protect the brain from blood-borne infections. The quest to deliver the drug to the brain also involved developing a technique to get past the brain-blood barrier, spare healthy brain cells and deliver the anti-inflammatory drug exclusively inside the rogue cells.

To do all this, the scientists used a globular, tree-like synthetic molecule, known as a dendrimer. Its size — 2,000 times smaller than a red blood cell — renders it fit for travel across the blood-brain barrier. Moreover, the dendrimer’s tree-like structure allowed scientists to attach to it molecules of an anti-inflammatory NAC. The researchers tagged the drug-laced dendrimers with fluorescent tracers to monitor their journey to the brain and injected them into rabbits with cerebral palsy six hours after birth. Another group of newborn rabbits received an injection of NAC only.

Not only did the drug-loaded dendrimers make their way inside the brain but, once there, were rapidly swallowed by the overactive astrocytes and microglia.

“These rampant inflammatory cells, in effect, gobbled up their own poison,” Kannan says.

“The dendrimers not only successfully crossed the blood-brain barrier but, perhaps more importantly, zeroed in on the very cells responsible for neuro-inflammation, releasing the therapeutic drug directly into them,” says senior investigator Rangaramanujam Kannan, Ph.D., of the Center for Nanomedicine at the Johns Hopkins Wilmer Eye Institute.

Animals treated with dendrimer-borne NAC showed marked improvement in motor control and coordination within five days after birth, nearly reaching the motor skill of healthy rabbits. By comparison, rabbits treated with dendrimer-free NAC showed minimal, if any, improvement, even at doses 10 times higher than the dendrimer-borne version. Animals treated with the dendrimer-delivered drug also showed better muscle tone and less stiffness in the hind leg muscles, both hallmarks of CP.

Brain tissue analysis revealed that rabbits treated with dendrimer-borne NAC had notably fewer “bad” microglia — the inflammatory cells responsible for brain damage — as well as markedly lower levels of other inflammation markers. They also had better preserved myelin, the protein that sheaths nerves and is stripped or damaged in CP and other neurologic disorders. And even though CP is marked by neuron death in certain brain centers, animals who received dendrimer-borne NAC had higher number of neurons in the brain regions responsible for coordination and motor control, compared with untreated animals and those treated with NAC only.

The findings suggest that the treatment not only reduces inflammation in the cells, but may also prevent cell damage and cell death, the researchers said. The Kannans, who are married, say they plan to follow some treated animals into adulthood to ensure the improvements are not temporary.

Source: Neuroscience News

April 23, 2012

St. Jude Children’s Research Hospital scientists have rewritten the job description of the protein TopBP1 after demonstrating that it guards early brain cells from DNA damage. Such damage might foreshadow later problems, including cancer.

Researchers showed that cells in the developing brain require TopBP1 to prevent DNA strands from breaking as the molecule is copied prior to cell division. Investigators also reported that stem cells and immature cells known as progenitor cells involved at the beginning of brain development are more sensitive to unrepaired DNA damage than progenitor cells later in the process. Although more developmentally advanced than stem cells, progenitor cells retain the ability to become one of a variety of more specialized neurons.

"Such DNA strand breaks have great potential for creating mutations that push a normal cell toward malignancy," said Peter McKinnon, Ph.D., a St. Jude Department of Genetics member and the paper’s senior author. "When we selectively knocked out TopBP1 in mice, the amount of DNA damage we saw suggests that TopBP1 is likely to be a tumor suppressor. We are exploring that question now."

The work appeared in the April 22 online edition of the scientific journal Nature Neuroscience. The research builds on McKinnon’s interest in DNA repair systems, including the enzymes ATM and ATR, which are associated with a devastating cancer-prone neurodegenerative disease in children called ataxia telangiectasia, and a neurodevelopmental disorder called Seckel syndrome.

TopBP1 was known to activate ATR. Previous laboratory research by other investigators also suggested that activation made TopBP1 indispensable for DNA replication and cell proliferation. This study, however, showed that was not the case. Most progenitor cells in the embryonic mouse brain kept dividing after investigators switched off the TopBP1 gene. 

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April 23, 2012

A cellular protein called HDAC6, newly characterized as a gatekeeper of steroid biology in the brain, may provide a novel target for treating and preventing stress-linked disorders, such as depression and post-traumatic stress disorder (PTSD), according to research from the Perelman School of Medicine at the University of Pennsylvania.

Glucocorticoids are natural steroids secreted by the body during stress. A small amount of these hormones helps with normal brain function, but their excess is a precipitating factor for stress-related disorders.

Glucocorticoids exert their effects on mood by acting on receptors in the nucleus of emotion–regulating neurons, such as those producing the neurotransmitter serotonin. For years, researchers have searched for ways to prevent deleterious effects of stress by blocking glucocorticoids in neurons. However, this has proved difficult to do without simultaneously interfering with other functions of these hormones, such as the regulation of immune function and energy metabolism.

In a recent Journal of Neuroscience paper, the lab of Olivier Berton, PhD, assistant professor of Psychiatry, shows how a regulator of glucocorticoid receptors may provide a path towards resilience to stress by modulating glucocorticoid signaling in the brain. The protein HDAC6, which is particularly enriched in serotonin pathways, as well as in other mood-regulatory regions in both mice and humans, is ideally distributed in the brain to mediate the effect of glucocorticoids on mood and emotions. HDAC6 likely does this by controlling the interactions between glucocorticoid receptors and hormones in these serotonin circuits.

Experiments that first alerted Berton and colleagues to a peculiar role of HDAC6 in stress adaptation came from an approach that reproduces certain clinical features of traumatic stress and depression in mice. The animals are exposed to brief bouts of aggression from trained “bully” mice. In most aggression-exposed mice this experience leads to the development of a lasting form of social aversion that can be treated by chronic administration of antidepressants. 

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April 23, 2012

Ten years ago, a landmark clinical trial in Canada demonstrated the unequivocal effectiveness of brain surgeries for treating uncontrolled epilepsy, but since then the procedure has not been widely adopted—in fact, it is dramatically underutilized according to a new study from the University of California, San Francisco (UCSF).

The study, published this month in the journal Neurology, showed that the number of Americans having the surgery has not changed in the decade since release of the effectiveness study, though surgical treatment is now uniformly encouraged by neurology and neurosurgery professional societies.

The U.S. Centers for Disease Control and Prevention estimates that 2 million Americans have epilepsy. Hundreds of thousands of these men, women and children suffer from uncontrolled seizures, but nationally only a few hundred are treated surgically each year with UCSF performing about 50 of the operations.

Among people who do have the operation, the study found, there are significant disparities by race and insurance status. White patients were more likely to have surgery than racial minorities, and privately insured patients were more likely to undergo surgery than those with Medicaid or Medicare.

"As a medical community, we are not practicing evidence-based medicine with regard to the treatment of patients who have epilepsy," said Edward Chang, MD, chief of adult epilepsy surgery in the UCSF Department of Neurological Surgery and the UCSF Epilepsy Center. "There are a lot of people who are taking medications and continuing to have seizures even though they can potentially be seizure-free."

A MODERN SURGERY FOR AN ANCIENT DISEASE

Epilepsy has been recognized as an important neurological condition since ancient times and its name means “seizures” in Greek. It can be inherited or it can be caused by anything that injures or irritates the brain. Hippocrates, the father of western medicine, described it in detail in his writings some 2,500 years ago, and it is believed to have afflicted many famous people throughout history, including Julius Caesar.

UCSF is one of the world’s leading institutions involved in epilepsy research, with one of the few medical centers that has top-ranking departments in relevant areas: neurology, biomedical imaging, and neurosurgery.

Paul Garcia, MD, director of the clinical epilepsy program and a study co-author, said that most patients referred to UCSF for surgical evaluation have had uncontrolled seizures for many years despite trying several medications. Research has shown that after the first two medicines fail, it is uncommon for patients to gain complete seizure control with medical treatment alone. Without control over their seizures, patients are at risk for physical injuries or even dying. Furthermore, the seizures often interfere with normal life activities such as driving, studying and working.

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April 23, 2012

Omega-3 fatty acid supplements were not associated with beneficial effects on disease activity in patients with relapsing-remitting multiple sclerosis, according to a report of a randomized controlled trial published Online First by Archives of Neurology.

Multiple sclerosis is a chronic, incurable disease of the central nervous system that affects about 2.5 million people worldwide. Some patients use, or have tried, omega-3 fatty acids supplementation to control the disease because the essential fatty acids could theoretically have anti-inflammatory and neuroprotective effects in multiple sclerosis, the authors write in their study background.

Øivind Torkildsen, M.D., Ph.D., of Haukeland University Hospital, Bergen, Norway, and colleagues included 92 patients with multiple sclerosis in their double-blind, placebo-controlled trial to examine whether omega-3 fatty acid supplementation as a monotherapy (single therapy) or in combination with subcutaneous (under the skin) interferon beta-1a could reduce disease activity.

Half of the patients (46) were given omega-3 fatty acids – 1350 mg of eicosapentaenoic acid and 850 mg of docosahexaenoic acid daily - and the other half (46) were administered placebo. After six months, all patients received interferon beta-1a three times a week for another 18 months. Researchers used magnetic resonance imaging (MRI) to measure disease activity by the number of new T1-weighted gadolinium-enhancing lesions in the brain.

"The results from this study did not show any beneficial effects of ω-3 [omega-3] fatty acid supplementation on disease activity in multiple sclerosis as a monotherapy or in combination with interferon beta," the authors comment. They note their results were in contrast with two other studies reporting a possible positive effect.

The median number of new T1-weighted gadolinium-enhancing lesions was three in the omega-3 fatty acids group and two in the placebo group during the first six months, according to the study results. The results indicate no difference between the two groups in the number of relapses during the first six months of treatment or after 24 months. No differences were detected either in fatigue or quality-of-life scores.

However, the authors comment their data do not suggest that omega-3 fatty acid supplementation was harmful or that it interfered with interferon beta treatment, which they note can reduce disease activity in the relapsing-remitting course of the disease.

"The design of this study allowed us to compare the effect of ω-3 fatty acid supplementation both against placebo alone and in combination with interferon beta. As expected, the MRI disease activity was significantly reduced when interferon beta-1a was introduced," they conclude.

Provided by JAMA and Archives Journals

Source: medicalxpress.com

April 23, 2012

According to a new study, the neuron-killing pathology of Alzheimer’s disease (AD), which begins before clinical symptoms appear, requires the presence of both amyloid-beta (a-beta) plaque deposits and elevated levels of an altered protein called p-tau.

Without both, progressive clinical decline associated with AD in cognitively healthy older individuals is “not significantly different from zero,” reports a team of scientists at the University of California, San Diego School of Medicine in the April 23 online issue of the Archives of Neurology.

"I think this is the biggest contribution of our work," said Rahul S. Desikan, MD, PhD, research fellow and resident radiologist in the UC San Diego Department of Radiology and first author of the study. "A number of planned clinical trials – and the majority of Alzheimer’s studies – focus predominantly on a-beta. Our results highlight the importance of also looking at p-tau, particularly in trials investigating therapies to remove a-beta. Older, non-demented individuals who have elevated a-beta levels, but normal p-tau levels, may not progress to Alzheimer’s, while older individuals with elevated levels of both will likely develop the disease."

The findings also underscore the importance of p-tau as a target for new approaches to treating patients with conditions ranging from mild cognitive impairment (MCI) to full-blown AD. An estimated 5.4 million Americans have AD. It’s believed that 10 to 20 percent of Americans age 65 and older have MCI, a risk factor for AD. Some current therapies appear to delay clinical AD onset, but the disease remains irreversible and incurable.

"It may be that a-beta initiates the Alzheimer’s cascade," said Desikan. "But once started, the neurodegenerative mechanism may become independent of a-beta, with p-tau and other proteins playing a bigger role in the downstream degenerative cascade. If that’s the case, prevention with anti-a-beta compounds may prove efficacious against AD for older, non-demented individuals who have not yet developed tau pathology. But novel, tau-targeting therapies may help the millions of individuals who already suffer from mild cognitive impairment or Alzheimer’s disease." 

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April 23, 2012

Research shows that many treatments can help prevent migraine in certain people, yet few people with migraine who are candidates for these preventive treatments actually use them, according to new guidelines issued by the American Academy of Neurology. The guidelines, which were co-developed with the American Headache Society, will be announced at the American Academy of Neurology’s 64th Annual Meeting in New Orleans and published in the April 24, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology.

"Studies show that migraine is underrecognized and undertreated," said guideline author Stephen D. Silberstein, MD, FACP, FAHS, of Jefferson Headache Center at Thomas Jefferson University in Philadelphia and a Fellow of the American Academy of Neurology. "About 38 percent of people who suffer from migraine could benefit from preventive treatments, but only less than a third of these people currently use them."

Unlike acute treatments, which are used to relieve the pain and associated symptoms of a migraine attack when it occurs, preventive treatments usually are taken every day to prevent attacks from occurring as often and to lessen their severity and duration when they do occur.

"Some studies show that migraine attacks can be reduced by more than half with preventive treatments," Silberstein said.

The guidelines, which reviewed all available evidence on migraine prevention, found that among prescription drugs, the seizure drugs divalproex sodium, sodium valproate and topiramate, along with the beta-blockers metoprolol, propranolol and timolol, are effective for migraine prevention and should be offered to people with migraine to reduce the frequency and severity of attacks. The seizure drug lamotrigine was found to be ineffective in preventing migraine.

The guidelines also reviewed over-the-counter treatments and complementary treatments. The guideline found that the herbal preparation Petasites, also known as butterbur, is effective in preventing migraine. Other treatments that were found to be probably effective are the nonsteroidal anti-inflammatory drugs fenoprofen, ibuprofen, ketoprofen, naproxen and naproxen sodium, subcutaneous histamine and complementary treatments magnesium, MIG-99 (feverfew) and riboflavin.

Silberstein noted that while people do not need a prescription from a physician for these over-the-counter and complementary treatments, they should still see their doctor regularly for follow-up. “Migraines can get better or worse over time, and people should discuss these changes in the pattern of attacks with their doctors and see whether they need to adjust their dose or even stop their medication or switch to a different medication,” said Silberstein. “In addition, people need to keep in mind that all drugs, including over-the-counter drugs and complementary treatments, can have side effects or interact with other medications, which should be monitored.”

Provided by American Academy of Neurology
Source: medicalxpress.com 

April 22, 2012

A key protein, which may be activated to protect nerve cells from damage during heart failure or epileptic seizure, has been found to regulate the transfer of information between nerve cells in the brain. The discovery, made by neuroscientists at the University of Bristol and published in Nature Neuroscience and PNAS, could lead to novel new therapies for stroke and epilepsy.

The research team, led by Professor Jeremy Henley and Dr Jack Mellor from Bristol’s Medical School, has identified a protein, known as SUMO, responsible for controlling the chemical processes which reduce or enhance protection mechanisms for nerve cells in the brain.

These key SUMO proteins produce subtle responses to the brain’s activity levels to regulate the amount of information transmitted by kainate receptors - responsible for communication between nerve cells and whose activation can lead to epileptic seizures and nerve cell death.

Protein function is controlled by altering their structure in processes that can be independent or inter-related including phosphorylation, ubiquitination and SUMOylation. In the present work it is shown that phosphorylation of kainate receptors on its own promotes their activity. However, phosphorylation also facilitates SUMOylation of kainate receptors that reduces their activity. Thus there is a dynamic and delicate interplay between phosphorylation and SUMOylation that regulates kainate receptor function.

This fine balance between phosphorylation and SUMOylation is dependent on brain activity levels where damaging activity that occurs during stroke or epilepsy will enhance SUMOylation and therefore reduce kainate receptor function to protect nerve cells.

Dr Mellor, Senior Lecturer from the University’s School of Physiology and Pharmacology, said: “Kainate receptors are a somewhat mysterious but clearly very important group of proteins that are known to be involved in a number of diseases including epilepsy. However, we currently know little about what makes kainate receptors so important. Likewise, we also know that SUMO proteins play an important role in neuroprotection. These findings provide a link between SUMO and kainate receptors that increases our understanding of the processes that nerve cells use to protect themselves from excessive and abnormal activity.”

Professor Henley added: “This work is important because it gives a new perspective and a deeper understanding of how the flow of information between cells in the brain is regulated. The team has found that by increasing the amount of SUMO attached to kainate receptors – which would reduce communication between the cells – could be a way to treat epilepsy by preventing over-excitation of the brain’s nerve cells.”

The research follows on from previous findings published in Nature(447, 321-325) that discovered SUMO proteins target the brain’s kainate receptors altering their cellular location.

Provided by University of Bristol

Source: medicalxpress.com

April 22, 2012

New research from Mount Sinai Medical Center in New York reveals that repeated exposure to cocaine decreases the activity of a protein necessary for normal functioning of the brain’s reward system, thus enhancing the reward for cocaine use, which leads to addiction. Investigators were also able to block the ability of repeated cocaine exposure, to induce addiction. The findings, published online April 22 in the journal Nature Neuroscience, provide the first evidence of how cocaine changes the shape and size of neuron rewards in a mouse model.

Repeated exposure to cocaine decreases the expression of a protein necessary for normal functioning of the brain’s reward system, thus enhancing the reward for cocaine use and stimulating addiction. Using the protein’s light-activated form in real time, in a technique known as optogenetics, investigators were also able to block repeated cocaine exposure from enhancing the brain’s reward center from cocaine. Even though the results are very early and many steps will be important in moving from mice to humans, the researchers say that the finding opens the door to a new direction for treatment for cocaine addiction.

"There are virtually no medication regimens for cocaine addiction, only psychotherapy, and some early work with vaccines," said the study’s senior investigator, Eric Nestler, MD, PhD, Nash Family Professor of Neuroscience, Chairman of the Neuroscience and Director of the Friedman Brain Institute at Mount Sinai School of Medicine. The protein, Rac1, is found in many cells in mice, rats, monkeys, and humans, and it is known to be involved in controlling the growth of nerve cells.

Investigators “knocked out,” or deleted, the gene responsible for Rac1 production, or injected a virus to enhance expression of Rac1.

"The research gives us new information on how cocaine affects the brain’s reward center and how it could potentially be repaired," said Dr. Nestler. "This is the first case in the brain in vivo where it’s been possible to control the activity of a protein, inside nerve cells in real time. Our findings reveal new pathways and target — a proof of principle study really — for treatment of cocaine addiction."

Provided by The Mount Sinai Hospital / Mount Sinai School of Medicine

Source: medicalxpress.com

ScienceDaily (Apr. 22, 2012) — A key protein, which may be activated to protect nerve cells from damage during heart failure or epileptic seizure, has been found to regulate the transfer of information between nerve cells in the brain. The discovery, made by neuroscientists at the University of Bristol and published in Nature Neuroscience and PNAS, could lead to novel new therapies for stroke and epilepsy.

An image of a hippocampal neuron. (Credit: Inma Gonzalez-Gonzalez)

The research team, led by Professor Jeremy Henley and Dr Jack Mellor from Bristol’s Medical School, has identified a protein, known as SUMO, responsible for controlling the chemical processes which reduce or enhance protection mechanisms for nerve cells in the brain.

These key proteins produce subtle responses to the brain’s activity levels to regulate the amount of information transmitted by kainate receptors — responsible for communication between nerve cells and whose activation can lead to epileptic seizures and nerve cell death.

Protein function is controlled by altering their structure in processes that can be independent or inter-related including phosphorylation, ubiquitination and SUMOylation. In the present work it is shown that phosphorylation of kainate receptors on its own promotes their activity. However, phosphorylation also facilitates SUMOylation of kainate receptors that reduces their activity. Thus there is a dynamic and delicate interplay between phosphorylation and SUMOylation that regulates kainate receptor function.

This fine balance between phosphorylation and SUMOylation is dependent on brain activity levels where damaging activity that occurs during stroke or epilepsy will enhance SUMOylation and therefore reduce kainate receptor function to protect nerve cells.

Dr Mellor, Senior Lecturer from the University’s School of Physiology and Pharmacology, said: “Kainate receptors are a somewhat mysterious but clearly very important group of proteins that are known to be involved in a number of diseases including epilepsy. However, we currently know little about what makes kainate receptors so important. Likewise, we also know that SUMO proteins play an important role in neuroprotection. These findings provide a link between SUMO and kainate receptors that increases our understanding of the processes that nerve cells use to protect themselves from excessive and abnormal activity.”

Professor Henley added: “This work is important because it gives a new perspective and a deeper understanding of how the flow of information between cells in the brain is regulated. The team has found that by increasing the amount of SUMO attached to kainate receptors — which would reduce communication between the cells — could be a way to treat epilepsy by preventing over-excitation of the brain’s nerve cells.”

The research follows on from previous findings published in Nature that discovered SUMO proteins target the brain’s kainate receptors altering their cellular location.

Source: Science Daily

ScienceDaily (Apr. 22, 2012) — Engineers at the University of Sheffield have developed a method of assisting nerves damaged by traumatic accidents to repair naturally, which could improve the chances of restoring sensation and movement in injured limbs.

Scanning electron microscopy images of the structures fabricated by (left) 2PP and (right) microreplication techniques. (Credit: Image courtesy of University of Sheffield)

In a collaborative study with Laser Zentrum Hannover (Germany) published April 23, 2012 in the journal Biofabrication, the team describes a new method for making medical devices called nerve guidance conduits or NGCs.

The method is based on laser direct writing, which enables the fabrication of complex structures from computer files via the use of CAD/CAM (computer aided design/manufacturing), and has allowed the research team to manufacture NGCs with designs that are far more advanced than previously possible.

Currently patients with severe traumatic nerve damage suffer a devastating loss of sensation and/or movement in the affected limb. The traditional course of action, where possible, is to surgically suture or graft the nerve endings together. However, reconstructive surgery often does not result in complete recovery.

"When nerves in the arms or legs are injured they have the ability to re-grow, unlike in the spinal cord; however, they need assistance to do this," said University of Sheffield Professor of Bioengineering, John Haycock. "We are designing scaffold implants that can bridge an injury site and provide a range of physical and chemical cues for stimulating this regrowth."

The new conduit is made from a biodegradable synthetic polymer material based on polylactic acid and has been designed to guide damaged nerves to re-grow through a number of small channels.

"Nerves aren’t just like one long cable, they’re made up of lots of small cables, similar to how an electrical wire is constructed," said lead author Dr Frederik Claeyssens, of the University’s Department of Materials Science and Engineering. "Using our new technique we can make a conduit with individual strands so the nerve fibres can form a similar structure to an undamaged nerve."

Once the nerve is fully regrown, the conduit biodegrades naturally. The team hopes that this approach will significantly increase recovery for a wide range of peripheral nerve injuries.

In laboratory experiments, nerve cells added to the polymer conduit grew naturally within its channelled structure and the research team is now working towards clinical trials.

"If successful we anticipate these scaffolds will not just be applicable to peripheral nerve injury, but could also be developed for other types of nerve damage too. The technique of laser direct writing may ultimately allow production of scaffolds that could help in the treatment of spinal cord injury" said Dr Claeyssens.

"What’s exciting about this work is that not only have we designed a new method for making nerve guide scaffolds which support nerve growth, we´ve also developed a method of easily reproducing them through micromolding.

"This technology could make a huge difference to patients suffering severe nerve damage," he added.

Source: Science Daily

ScienceDaily (Apr. 22, 2012) — Researchers at Columbia University Medical Center (CUMC) have identified a molecular pathway that controls the retention and release of the brain’s stem cells. The discovery offers new insights into normal and abnormal neurologic development and could eventually lead to regenerative therapies for neurologic disease and injury. The findings, from a collaborative effort of the laboratories of Drs. Anna Lasorella and Antonio Iavarone, were published April 22in the online edition of Nature Cell Biology.

Neural stem cells detaching from the vascular niche. (Credit: Anna Lasorella, CUMC /Nature Cell Biology)

The research builds on recent studies, which showed that stem cells reside in specialized niches, or microenvironments, that support and maintain them.

"From this research, we knew that when stem cells detach from their niche, they lose their identity as stem cells and begin to differentiate into specific cell types," said co-senior author Antonio Iavarone, MD, professor of Pathology and Neurology at CUMC.

"However, the pathways that regulate the interaction of stem cells with their niche were obscure," said co-senior author Anna Lasorella, MD, associate professor of Pathology and Pediatrics at CUMC and a member of the Columbia Stem Cell Initiative.

In the brain, the stem cell niche is located in an area adjacent to the ventricles, the fluid-filled spaces within the brain. Neural stem cells (NSCs) within the niche are carefully regulated, so that enough cells are released to populate specific brain areas, while a sufficient supply is kept in reserve.

In previous studies, Drs. Iavarone and Lasorella focused on molecules called Id (inhibitor of differentiation) proteins, which regulate various stem cell properties. They undertook the present study to determine how Id proteins maintain stem cell identity.

The team developed a genetically altered strain of mice in which Id proteins were silenced, or knocked down, in NSCs. In the absence of Id proteins, mice died within 24 hours of birth. Their brains showed markedly lowered NSC proliferative capacity, and their stem cell populations were reduced.

Studies of NSCs from this strain of mice revealed that Id proteins directly regulate the production of a protein called Rap1GAP, which in turn controls Rap1, one of the master regulators of cell adhesion. The researchers found that the Id-Rap1GAP-Rap1 pathway is critical for the adhesion of NSCs to their niche and for NSC maintenance. “There may be other pathways involved, but we believe this is the key pathway,” said Dr. Iavarone. “There is good reason to believe that it operates in other kinds of stem cells, and our labs are investigating this question now.”

"This is a new idea," added Dr. Lasorella. "Before this study, the prevailing wisdom was that NSCs are regulated by the niche components, conceivably through the release of chemical attractants such as cytokines. However, our findings suggest that stem cell identity relies on this mechanism."

More research needs to be done before the findings can be applied therapeutically, Dr. Iavarone said. “Multiple studies show that NSCs respond to insults such as ischemic stroke or neurodegenerative diseases. If we can understand how to manipulate the pathways that determine stem cell fate, in the future we may be able to control NSC properties for therapeutic purposes.”

"Another aspect," added Dr. Lasorella, "is to determine whether Id proteins also maintain stem cell properties in cancer stem cells in the brain. In fact, normal stem cells and cancer stem cells share properties and functions. Since cancer stem cells are difficult to treat, identifying these pathways may lead to more effective therapies for malignant brain tumors."

Stephen G. Emerson, MD, PhD, director of the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center, added that, “Understanding the pathway that allows stem cells to develop into mature cells could eventually lead to more effective, less toxic cancer treatments. This beautiful study opens up a wholly unanticipated way to think about treating brain tumors.”

Source: Science Daily

April 20th, 2012

Multiple disease-related changes progress in parallel through distinct stages.

This schematic illustration shows the experimental arrangement for in vivo two-photon calcium imaging of stimulation-evoked neuronal activity in anesthetized mice. At left, in vivo two-photon image of the visual cortex. The neurons are stained with the calcium indicator dye Oregon Green BAPTA-1 (green, OGB-1) and the astrocytes with Sulforhodamine 101 (yellow, SR101). Right, visual stimuli were projected on a screen placed in front of the eye of the mouse. Image adapted from image credited to Konnerth lab, TU Muenchen.

Studying a mouse model of Alzheimer’s disease, neuroscientists at the Technische Universitaet Muenchen have observed correlations between increases in both soluble and plaque-forming beta-amyloid – a protein implicated in the disease process – and dysfunctional developments on several levels: individual cortical neurons, neuronal circuits, sensory cognition, and behavior. Their results, published in Nature Communications, show that these changes progress in parallel and that, together, they reveal distinct stages in Alzheimer’s disease with a specific order in time.

In addition to its well known, devastating effects on memory and learning, Alzheimer’s disease can also impair a person’s sense of smell or vision. Typically these changes in sensory cognition only show themselves behaviorally when the disease is more advanced. A new study sheds light on what is happening in the brain throughout the disease process, specifically with respect to the part of the cerebral cortex responsible for integrating visual information. A team led by Prof. Arthur Konnerth, a Carl von Linde Senior Fellow of the TUM Institute for Advanced Study, has observed Alzheimer’s-related changes in the visual cortex at the single-cell level.

Using a technique called two-photon calcium imaging, the researchers recorded both spontaneous and stimulated signaling activity in cortical neurons of living mice: transgenic mice carrying mutations that cause Alzheimer’s disease in humans, and wild-type mice as a control group. By observing how neuronal signaling responded to a special kind of vision test – in which a simple grating pattern of light and dark bars moves in front of the mouse’s eye – the scientists could characterize the visual circuit as being more or less “tuned” to specific orientations and directions of movement.

Konnerth explains, “Like many Alzheimer’s patients, the diseased mice have impairments in their ability to discriminate visual objects. Our results provide important new insights on the cause that may underlie the impaired behavior, by identifying in the visual cortex a fraction of neurons with a strongly disturbed function.” And within this group, the researchers discovered, there are two subsets of neurons – both dysfunctional, but in completely different ways. One subset, thought to be the first neurons to degenerate, showed no activity at all; the other showed a pathologically high level of activity, rendering these neurons incapable of properly sensing objects in the mouse’s environment. “While around half of the neurons in the visual cortex were disturbed in one way or the other, roughly half responded normally,” notes Christine Grienberger, a doctoral candidate in Konnerth’s institute and first author of this paper. “That could have significant implications for future research in the field of Alzheimer’s disease, as our findings raise the question of whether future work only needs to target this population of neurons that are disturbed in their function.”

The in vivo single-neuron experiments were carried out for three age groups, corresponding to different stages of this progressive, degenerative disease. The results were correlated with other measurements, including soluble beta-amyloid levels and the density of beta-amyloid plaques in the brain tissue. The researchers’ findings show for the first time a progressive decline of function in cortical circuits. “An important conclusion from this study,” Konnerth says, “is that the Alzheimer’s disease-related changes on all levels – including behavior, cortical circuit dysfunction, and the density of amyloid plaques in diseased brains – progress in parallel in a distinct temporal order. In the future, the identification of such stages in patients may help researchers pinpoint stage-specific and effective therapies, with reduced levels of side effects.”

Source: Neuroscience News

April 20th, 2012

A miniature atom-based magnetic sensor developed by the National Institute of Standards and Technology (NIST) has passed an important research milestone by successfully measuring human brain activity.

NIST’s atom-based magnetic sensor, about the size of a sugar cube, can measure human brain activity. Inside the sensor head is a container of 100 billion rubidium atoms (not seen), packaged with micro-optics (a prism and a lens are visible in the center cutout). The light from a low-power infrared laser interacts with the atoms and is transmitted through the grey fiber-optic cable to register the magnetic field strength. The black and white wires are electrical connections. Image adapted from image by Knappe/NIST.

Experiments reported this week in Biomedical Optics Express verify the sensor’s potential for biomedical applications such as studying mental processes and advancing the understanding of neurological diseases.

NIST and German scientists used the NIST sensor to measure alpha waves in the brain associated with a person opening and closing their eyes as well as signals resulting from stimulation of the hand. The measurements were verified by comparing them with signals recorded by a SQUID (superconducting quantum interference device). SQUIDs are the world’s most sensitive commercially available magnetometers and are considered the “gold standard” for such experiments. The NIST mini-sensor is slightly less sensitive now but has the potential for comparable performance while offering potential advantages in size, portability and cost.

The study results indicate the NIST mini-sensor may be useful in magnetoencephalography (MEG), a noninvasive procedure that measures the magnetic fields produced by electrical activity in the brain. MEG is used for basic research on perceptual and cognitive processes in healthy subjects as well as screening of visual perception in newborns and mapping brain activity prior to surgery to remove tumors or treat epilepsy. MEG also might be useful in brain-computer interfaces.

MEG currently relies on SQUID arrays mounted in heavy helmet-shaped flasks containing cryogenic coolants because SQUIDs work best at 4 degrees above absolute zero, or minus 269 degrees Celsius. The chip-scale NIST sensor is about the size of a sugar cube and operates at room temperature, so it might enable lightweight and flexible MEG helmets. It also would be less expensive to mass produce than typical atomic magnetometers, which are larger and more difficult to fabricate and assemble.

“We’re focusing on making the sensors small, getting them close to the signal source, and making them manufacturable and ultimately low in cost,” says NIST co-author Svenja Knappe. “By making an inexpensive system you could have one in every hospital to test for traumatic brain injuries and one for every football team.”

The mini-sensor consists of a container of about 100 billion rubidium atoms in a gas, a low-power infrared laser and fiber optics for detecting the light signals that register magnetic field strength—the atoms absorb more light as the magnetic field increases. The sensor has been improved since it was used to measure human heart activity in 2010. NIST scientists redesigned the heaters that vaporize the atoms and switched to a different type of optical fiber to enhance signal clarity.

The brain experiments were carried out in a magnetically shielded facility at the Physikalisch Technische Bundesanstalt (PTB) in Berlin, Germany, which has an ongoing program in biomagnetic imaging using human subjects. The NIST sensor measured magnetic signals of about 1 picotesla (trillionths of a tesla). For comparison, the Earth’s magnetic field is 50 million times stronger (at 50 millionths of a tesla). NIST scientists expect to boost the mini-sensor’s performance about tenfold by increasing the amount of light detected. Calculations suggest an enhanced sensor could match the sensitivity of SQUIDS. NIST scientists are also working on a preliminary multi-sensor magnetic imaging system in a prelude to testing clinically relevant applications.

Source: Neuroscience News

April 20, 2012 by Bob Yirka 

(Medical Xpress) — Researchers from the University of Groningen Medical Centre in the Netherlands have found that for women at least, watching pornographic videos tends to quiet the part of the brain most heavily involved in looking at and processing things in the immediate environment, suggesting that the brain finds arousal more important during that time than is processing what is actually being seen. The team has published a paper in The Journal of Sexual Medicine describing their findings.

To find out if the primary visual cortex is essentially deactivated during sexual arousal in women, the team enlisted 12 volunteers; all women between the ages of 18 and 47, who had not yet reached menopause. Also each was on oral birth control pills which tend to flatten menstrual cycles and smooth out sexual desire and/or anxiety. Each was shown three videos, one with no sexual connotation, another with mild sexual content, and a third that was full on hard-core porn. While they were watching the videos, the women were also having their brain activity watched via PET scans, which work by measuring blood flow to the various brain regions. It is thought that more blood flow indicates that more brainwork is occurring, which implies that when the brain delegates tasks to different regions, by sending more blood, it is demonstrating that it finds certain activities more important than others.

The team found virtually no difference in brain activity in all of the women when watching the first two videos. When watching the third however, they found that blood flow to the visual cortex was reduced in all of the volunteers indicating that the brain had decided that focusing on arousal was more important than fixating on exactly what was occurring on the screen in front of them (or that women just don’t want to really see what is going on with sex). This is in direct contrast to most other visual activities which tend to cause more blood to flow to the visual cortex to process all of the information that is coming in.

The researchers also suggest their findings help explain why women who exhibit symptoms of anxiety often report sexual problems, as high anxiety is often correlated with increased blood flow to the visual cortex due to the person reacting on a nearly constant basis to visual stimuli. They point out that for people in general, the brain cannot be both anxious and aroused, it generally has to be one or the other, or neither.

Source: medicalxpress.com

April 19th, 2012

Scientists have discovered proof that the evolution of intelligence and larger brain sizes can be driven by cooperation and teamwork, shedding new light on the origins of what it means to be human.

Scientists have discovered proof that the evolution of intelligence and larger brain sizes can be driven by cooperation and teamwork, shedding new light on the origins of what it means to be human. Image adapted from Trinity College Dublin image.

The study appears online in the journal Proceedings of the Royal Society B and was led by scientists at Trinity College Dublin: PhD student, Luke McNally and Assistant Professor Dr Andrew Jackson at the School of Natural Sciences in collaboration with Dr Sam Brown of the University of Edinburgh.

The researchers constructed computer models of artificial organisms, endowed with artificial brains, which played each other in classic games, such as the ‘Prisoner’s Dilemma’, that encapsulate human social interaction.  They used 50 simple brains, each with up to 10 internal processing and 10 associated memory nodes. The brains were pitted against each other in these classic games.

The game was treated as a competition, and just as real life favours successful individuals, so the best of these digital organisms which was defined as how high they scored in the games, less a penalty for the size of their brains were allowed to reproduce and populate the next generation of organisms.

By allowing the brains of these digital organisms to evolve freely in their model the researchers were able to show that  the transition to cooperative society  leads to the strongest selection for bigger brains. Bigger brains essentially did better as cooperation increased.

The social strategies that emerge spontaneously in these bigger, more intelligent brains show complex memory and decision making. Behaviours like forgiveness, patience, deceit and Machiavellian trickery all evolve within the game as individuals try to adapt to their social environment.

“The strongest selection for larger, more intelligent brains, occurred when the social groups were first beginning to start cooperating, which then kicked off an evolutionary Machiavellian arms race of one individual trying to outsmart the other by investing in a larger brain. Our digital organisms typically start to evolve more complex ‘brains’ when their societies first begin to develop cooperation.” explained Dr Andrew Jackson.

The idea that social interactions underlie the evolution of intelligence has been around since the mid-70s, but support for this hypothesis has come largely from correlative studies where large brains were observed in more social animals.  The authors of the current research provide the first evidence that mechanistically links decision making in social interactions with the evolution of intelligence. This study highlights the utility of evolutionary models of artificial intelligence in answering fundamental biological questions about our own origins.

“Our model differs in that we exploit the use of theoretical experimental evolution combined with artificial neural networks to actually prove that yes, there is an actual cause-and-effect link between needing a large brain to compete against and cooperate with your social group mates.”

“Our extraordinary level of intelligence defines mankind and sets us apart from the rest of the animal kingdom. It has given us the arts, science and language, and above all else the ability to question our very existence and ponder the origins of what makes us unique both as individuals and as a species,” concluded PhD student and lead author Luke McNally.

Source: Neuroscience News

April 19th, 2012

Study shows religious participation and spirituality processed in different cerebral regions.

Scientists have speculated that the human brain features a “God spot,” one distinct area of the brain responsible for spirituality. Now, University of Missouri researchers have completed research that indicates spirituality is a complex phenomenon, and multiple areas of the brain are responsible for the many aspects of spiritual experiences. Based on a previously published study that indicated spiritual transcendence is associated with decreased right parietal lobe functioning, MU researchers replicated their findings. In addition, the researchers determined that other aspects of spiritual functioning are related to increased activity in the frontal lobe.

“We have found a neuropsychological basis for spirituality, but it’s not isolated to one specific area of the brain,” said Brick Johnstone, professor of health psychology in the School of Health Professions. “Spirituality is a much more dynamic concept that uses many parts of the brain. Certain parts of the brain play more predominant roles, but they all work together to facilitate individuals’ spiritual experiences.”

In the most recent study, Johnstone studied 20 people with traumatic brain injuries affecting the right parietal lobe, the area of the brain situated a few inches above the right ear. He surveyed participants on characteristics of spirituality, such as how close they felt to a higher power and if they felt their lives were part of a divine plan. He found that the participants with more significant injury to their right parietal lobe showed an increased feeling of closeness to a higher power.

“Neuropsychology researchers consistently have shown that impairment on the right side of the brain decreases one’s focus on the self,” Johnstone said. “Since our research shows that people with this impairment are more spiritual, this suggests spiritual experiences are associated with a decreased focus on the self. This is consistent with many religious texts that suggest people should concentrate on the well-being of others rather than on themselves.”

Johnstone says the right side of the brain is associated with self-orientation, whereas the left side is associated with how individuals relate to others. Although Johnstone studied people with brain injury, previous studies of Buddhist meditators and Franciscan nuns with normal brain function have shown that people can learn to minimize the functioning of the right side of their brains to increase their spiritual connections during meditation and prayer.

In addition, Johnstone measured the frequency of participants’ religious practices, such as how often they attended church or listened to religious programs. He measured activity in the frontal lobe and found a correlation between increased activity in this part of the brain and increased participation in religious practices.

“This finding indicates that spiritual experiences are likely associated with different parts of the brain,” Johnstone said.

Written by Brad Fischer

Source: Neuroscience News