Neuroscience

May 10, 2012

(Medical Xpress) — A new mathematical model predicting how nerve fibres make connections during brain development could aid understanding of how some cognitive disorders occur.

The model, constructed by scientists at the Queensland Brain Institute (QBI) and School of Mathematics and Physics at the University of Queensland (UQ), gives new insight into how changing chemical levels in nerve fibres can modify nerve wiring underpinning connections in the brain.

Professor Geoff Goodhill says that while scientists have long known that changing these chemical levels can change where nerve fibres grow, only now are they understanding why this is the case.

“Our mathematical model allows us to predict precisely how these chemical levels control the direction in which nerve fibres grow, during both neural development and regeneration after injury,” he said.

Correct brain wiring is fundamental for normal brain function.

Recent discoveries suggest that wiring problems may underpin a number of nervous system disorders including autism, dyslexia, Down syndrome, Tourette’s syndrome and Parkinson’s disease.

The new model, published in the prestigious cell journal Neurondemonstrates the important role mathematics can play in understanding how the brain develops, and perhaps ultimately preventing such disorders. 

Provided by University of Queensland 

Source: medicalxpress.com

May 10, 2012

(Medical Xpress) — Scientists at University of Queensland’s Brain Institute are one step closer to developing new therapies for treating dementia.

QBI’s Dr Jana Vukovic said the work was aimed at understanding the molecular mechanism that may impair learning and memory in the ageing population.

“Ageing slows the production of new nerve cells, reducing the brain’s ability to form new memories,” said Dr Vokovic, who performed the work in the laboratory of Professor Perry Bartlett, the Director of QBI at The University of Queensland.

"But our research shows for the first time that the brain cells usually responsible for mediating immunity, microglia, have an inhibitory effect on memory during ageing.

“Furthermore, they have shown that a molecule produced by nerve cells, fractalkine, can reverse this process and stimulate stem cells to produce new neurons.”

The discovery, published in The Journal of Neuroscience today, came after QBI scientists observed that the increased production of new neurons in mice that were actively running was due to the release of fractalkine in the hippocampus – the brain structure responsible for specific types of learning and memory.

Professor Bartlett said it had been known for some time that exercise increased the production of new nerve cells in the hippocampus in young and even aged mice.

“But this study found that it is fractalkine that appears to be specifically mediating this effect by making the microglia produce factors that activate the stem cells that produce new nerve cells,” he said.

“Once the cells are activated they divide and produce new cells, which underpin the animal’s ability to learn and form memories.

"This means that fractalkine may form the basis for the development of future therapies.

“The discovery is especially exciting because we have found that older animals suffering cognitive decline showed significantly lower levels of fractalkine.

“We are seeking ways of increasing fractalkine levels in patients with cognitive decline, and hoping this may be a new frontline therapy in treating dementia.”

Dr Vukovic said that until relatively recently, it was thought the adult brain was incapable of generating new neurons.

“But work from Professor Bartlett’s laboratory over the past 20 years has demonstrated that the brains of adult animals, including humans, retain the ability to make new nerve cells,” she said.

“The challenge is to find out how to stimulate this production in the aged animal and human where production has slowed.”

The latest work was a significant step toward achieving this goal, she said.

Provided by University of Queensland

Source: medicalxpress.com

May 10, 2012

(Medical Xpress) — How do we build a memory in the brain? It is well known that for animals (and humans) new proteins are needed to establish long-term memories. During learning information is stored at the synapses, the junctions connecting nerve cells. Synapses also require new proteins in order to show changes in their strength (synaptic plasticity). Historically, scientists have focused on the cell body as the place where the required proteins are synthesized. However, in recent years there has been increasing focus on the dendrites and axons (the compartments that meet to form synapses) as a potential site for protein synthesis.

Protein synthesis machines have been observed there as well as a limited number of their templates, the messenger RNA molecules. The limited number of mRNAs observed in dendrites and axons placed constraints on the constellation of proteins that could be synthesized to help synapses work and change. Researchers from Erin Schuman’s lab at the Max Planck Institute (MPI) for Brain Research used new-generation sequencing to directly identify a very large number (over 2500) of new mRNA molecules that are present at the axons and dendrites. Using high-resolution imaging techniques they were able to both quantify and visualize individual mRNA molecules. They published their findings in the latest issue of Neuron.

[Video]
Erin Schuman and her colleagues describe how they were able to detect numerous new mRNAs in the processes of neurons with unprecedented sensitivity. Video: Neuron.

Using microarray approaches and/or in situ hybridization techniques, many different groups had each identified a hundred or so mRNAs that might reside in the dendrites. By analyzing and comparing these studies the Schuman team discovered something surprising: it seems that not a single mRNA type was found in all three studies. This observation made the scientist at the MPI for Brain Research wonder whether the already discovered mRNAs are just the tip of the iceberg and whether there were many more mRNA molecules waiting to be discovered.

In order to find out the researchers dissected the neuropil layer of the rat hippocampus. This layer comprises a high concentration of axons and dendrites, but lacks the cell bodies of pyramidal neurons (the principal cell type in the hippocampus and other brain areas). By using sensitive high-resolution sequencing techniques, mRNAs could be detected which, due to their lower concentrations, were not discovered before. The researchers found an impressive number of 2550 unique mRNAs present at the dendrites and/or axons. To determine the relative abundance in the neuronal cells, the scientists at Erin Schuman’s lab used the Nanostring nCounter, a new technique allowing the high-resolution visualization and quantification of single mRNA molecules. They found that the concentration of mRNAs in the euronal cells varies by three orders of magnitude. Additionally, the researchers were able to classify many of the mRNAs and determine their function in synaptic plasticity. These include signaling molecules, scaffolds and the receptors for neurotransmitter molecules. In addition, many mRNAs coding for protein implicated in diseases like autism were discovered in the dendrites and axons. Finally, by using advanced imaging techniques, the researchers could directly visualize some of the mRNAs in the neuronal dendrites, hundreds of micrometers from the cell body.

These results reveal a previously unappreciated enormous potential for the local protein synthesis machinery to supply, maintain and modify the dendritic and synaptic protein population. It seems that neurons use a local control mechanism much in the same way that modern societies have learned that the most efficient means to distribute goods to the population is to use local distribution centers.

Provided by Max Planck Society

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May 9, 2012 

Efforts to understand how the aging process affects the brain and cognition have expanded beyond simply comparing younger and older adults.

"Everybody ages differently. By looking at genetic variations and individual differences in markers of vascular health, we begin to understand that preventable factors may affect our chances for successful aging," said Wayne State University psychology doctoral student Andrew Bender, lead author of a study supported by the National Institute on Aging of the National Institutes of Health and now in press in the journal Neuropsychologia.

The report, “Age-related Differences in Memory and Executive Functions in Healthy APOE ε4 Carriers: The Contribution of Individual Differences in Prefrontal Volumes and Systolic Blood Pressure,” focuses on carriers of the ε4 variant of the apolipoprotein (APOE) gene, present in roughly 25 percent of the population. Compared to those who possess other forms of the APOE gene, carriers of the ε4 allele are at significantly greater risk for Alzheimer’s, dementia and cardiovascular disease.

Many studies also have shown that nondemented carriers of the APOE ε4 variant have smaller brain volumes and perform less well on cognitive tests than carriers of other gene variants. Those findings, however, are not consistent, and a possible explanation may come from examining interactions between the risky genes and other factors, such as markers of cardiovascular health. Prior research in typical samples of older adults has shown that indeed other vascular risk factors — such as elevated cholesterol, hypertension or diabetes — can exacerbate the impact of the APOE ε4 variant on brain and cognition, but it is unclear if such synergy of risks is present in healthy adults.

Thus, Wayne State researchers evaluated a group of volunteers from 19 to 77 years of age who self-reported as exceptionally healthy on a questionnaire that screened for a number of conditions, representing a “best case scenario” of healthy aging. The research project, led by Naftali Raz, Ph.D., professor of psychology and director of the Lifespan Cognitive Neuroscience Research Program at WSU’s Institute of Gerontology, tested different cognitive abilities known for their sensitivity to aging and the effects of the APOE ε4 variant. Those abilities include speed of information processing, working memory (holding and manipulating information in one’s mind) and episodic memory (memory for events).

Researchers also measured participants’ blood pressure, performed genetic testing to determine which APOE variant participants carried, and measured the volumes of several critical brain regions using a high-resolution structural magnetic resonance imaging brain scan. Bender and Raz showed that for older APOE ε4 carriers, even minor increases in systolic blood pressure (the higher of the two numbers that are reported in blood pressure measures) were linked with smaller volumes of the prefrontal cortex and prefrontal white matter, slower speed of information processing, reduced working memory capacity and worse verbal memory. Notably, they said, that pattern was not evident in those who lacked the ε4 gene variant.

The study concludes that the APOE ε4 gene may make its carriers sensitive to negative effects of relatively subtle elevations in systolic blood pressure, and that the interplay between two risk factors, genetic and physiological, is detrimental to the key brain structures and associated cognitive functions.

"Although genes play a significant role in shaping the effects of age and vascular risk on the brain and cognition, the impact of single genetic variants is relatively small, and there are quite a few of them. Thus, one’s aging should not be seen through the lens of one’s genetic profile," cautioned the study’s authors. They continued, "The negative impact of many genetic variations needs help from other risk factors, and while there isn’t much one can do about genes, a lot can be done about vascular risk factors such as blood pressure or cholesterol."

"Everybody should try to keep those in check, although people with certain genetic variants more so than others." Raz said. "Practically speaking, even with the best deck of genetic cards dealt to you, it still makes sense to reduce risk through whatever works: exercise, diet or, if those fail, medication."

Because the study is part of a longitudinal project, he and Bender said the immediate future task now is to determine how the interaction between risky genes and vascular risk factors affect the trajectory of age-related changes — not differences, as in this cross-sectional study — in brain and cognition.

Provided by Wayne State University

Source: medicalxpress.com

May 9, 2012

Chronic exposure to cocaine reduces the expression of a protein known to regulate brain plasticity, according to new, in vivo research on the molecular basis of cocaine addiction. That reduction drives structural changes in the brain, which produce greater sensitivity to the rewarding effects of cocaine.

The research, led by UB’s Dietz, suggests a potential new target for development of a treatment for cocaine addiction. Credit: Douglas Levere, UB Communications

The finding suggests a potential new target for development of a treatment for cocaine addiction. It was published last month in Nature Neuroscience by researchers at the University at Buffalo and Mount Sinai School of Medicine.

"We found that chronic cocaine exposure in mice led to a decrease in this protein’s signaling," says David Dietz, PhD, assistant professor of pharmacology and toxicology in the School of Medicine and Biomedical Sciences, who did the work while at Mt. Sinai. "The reduction of the expression of the protein, called Rac1, then set in motion a cascade of events involved in structural plasticity of the brain — the shape and growth of neuronal processes in the brain. Among the most important of these events is the large increase in the number of physical protrusions or spines that grow out from the neurons in the reward center of the brain.

"This suggests that Rac1 may control how exposure to drugs of abuse, like cocaine, may rewire the brain in a way that makes an individual more susceptible to the addicted state," says Dietz.

The presence of the spines demonstrates the spike in the reward effect that the individual obtains from exposure to cocaine. By changing the level of expression of Rac1, Dietz and his colleagues were able to control whether or not the mice became addicted, by preventing enhancement of the brain’s reward center due to cocaine exposure.

To do the experiment, Dietz and his colleagues used a novel tool, which allowed for light activation to control Rac1 expression, the first time that a light-activated protein has been used to modulate brain plasticity.

"We can now understand how proteins function in a very temporal pattern, so we could look at how regulating genes at a specific time point could affect behavior, such as drug addiction, or a disease state," says Dietz.

In his UB lab, Dietz is continuing his research on the relationship between behavior and brain plasticity, looking, for example, at how plasticity might determine how much of a drug an animal takes and how persistent the animal is in trying to get the drug.

Provided by University at Buffalo

Source: medicalxpress.com

May 9, 2012

While we often think of memory as a way of preserving the essential idea of who we are, little thought is given to the importance of forgetting to our wellbeing, whether what we forget belongs in the “horrible memories department” or just reflects the minutia of day-to-day living.

Despite the fact that forgetting is normal, exactly how we forget—the molecular, cellular, and brain circuit mechanisms underlying the process—is poorly understood.

Now, in a study that appears in the May 10, 2012 issue of the journal Neuron, scientists from the Florida campus of The Scripps Research Institute have pinpointed a mechanism that is essential for forming memories in the first place and, as it turns out, is equally essential for eliminating them after memories have formed.

"This study focuses on the molecular biology of active forgetting," said Ron Davis, chair of the Scripps Research Department of Neuroscience who led the project. "Until now, the basic thought has been that forgetting is mostly a passive process. Our findings make clear that forgetting is an active process that is probably regulated."

The Two Faces of Dopamine

To better understand the mechanisms for forgetting, Davis and his colleagues studied Drosophila or fruit flies, a key model for studying memory that has been found to be highly applicable to humans. The flies were put in situations where they learned that certain smells were associated with either a positive reinforcement like food or a negative one, such as a mild electric shock. The scientists then observed changes in the flies’ brains as they remembered or forgot the new information.

The results showed that a small subset of dopamine neurons actively regulate the acquisition of memories and the forgetting of these memories after learning, using a pair of dopamine receptors in the brain. Dopamine is a neurotransmitter that plays an important role in a number of processes including punishment and reward, memory, learning and cognition.

But how can a single neurotransmitter, dopamine, have two seemingly opposite roles in both forming and eliminating memories? And how can these two dopamine receptors serve acquiring memory on the one hand, and forgetting on the other?

The study suggests that when a new memory is first formed, there also exists an active, dopamine-based forgetting mechanism—ongoing dopamine neuron activity—that begins to erase those memories unless some importance is attached to them, a process known as consolidation that may shield important memories from the dopamine-driven forgetting process.

The study shows that specific neurons in the brain release dopamine to two different receptors known as dDA1 and DAMB, located on what are called mushroom bodies because of their shape; these densely packed networks of neurons are vital for memory and learning in insects. The study found the dDA1 receptor is responsible for memory acquisition, while DAMB is required for forgetting.

When dopamine neurons begin the signaling process, the dDA1 receptor becomes overstimulated and begins to form memories, an essential part of memory acquisition. Once that memory is acquired, however, these same dopamine neurons continue signaling. Except this time, the signal goes through the DAMB receptor, which triggers forgetting of those recently acquired, but not yet consolidated, memories.

Jacob Berry, a graduate student in the Davis lab who led the experimentation, showed that inhibiting the dopamine signaling after learning enhanced the flies’ memory. Hyperactivating those same neurons after learning erased memory. And, a mutation in one of the receptors, dDA1, produced flies unable to learn, while a mutation in the other, DAMB, blocked forgetting.

Intriguing Issues

While Davis was surprised by the mechanisms the study uncovered, he was not surprised that forgetting is an active process. “Biology isn’t designed to do things in a passive way,” he said. “There are active pathways for constructing things, and active ones for degrading things. Why should forgetting be any different?”

The study also brings into a focus a lot of intriguing issues, Davis said—savant syndrome, for example.

"Savants have a high capacity for memory in some specialized areas," he said. "But maybe it isn’t memory that gives them this capacity, maybe they have a bad forgetting mechanism. This also might be a strategy for developing drugs to promote cognition and memory—what about drugs that inhibit forgetting as cognitive enhancers?"

Provided by The Scripps Research Institute

Source: medicalxpress.com

ScienceDaily (May 9, 2012) — In sports, on a game show, or just on the job, what causes people to choke when the stakes are high? A new study by researchers at the California Institute of Technology (Caltech) suggests that when there are high financial incentives to succeed, people can become so afraid of losing their potentially lucrative reward that their performance suffers.

In the study, each participant was asked to control this virtual object on a screen. The virtual object consisted of two weighted balls connected by a spring. The task was to place the object, which stretched and contracted as a weighted spring would in real life, into a square target within two seconds. (Credit: Image courtesy of California Institute of Technology)

It is a somewhat unexpected conclusion. After all, you would think that the more people are paid, the harder they will work, and the better they will do their jobs — until they reach the limits of their skills. That notion tends to hold true when the stakes are low, says Vikram Chib, a postdoctoral scholar at Caltech and lead author on a paper published in the May 10 issue of the journalNeuron. Previous research, however, has shown that if you pay people too much, their performance actually declines.

Some experts have attributed this decline to too much motivation: they think that, faced with the prospect of earning an extra chunk of cash, you might get so excited that you will fail to do the task properly. But now, after looking at brain-scan data of volunteers performing a specific motor task, the Caltech team says that what actually happens is that you become worried about losing your potential prize. The researchers also found that the more someone is afraid of loss, the worse they perform.

In the study, each participant was asked to control a virtual object on a screen by moving an index finger that had a tracking device attached to it. The virtual object consisted of two weighted balls connected by a spring. The task was to place the object, which stretched and contracted as a weighted spring would in real life, into a square target within two seconds.

The researchers controlled for individual skill levels by customizing the size of the target so that everyone would have the same success rate. That way, people who happened to be really good or bad at this task would not skew the data.

After a training period, the subjects were asked to perform the task while inside an fMRI machine, which measures blood flow in the brain — a proxy for brain activity, since wherever a brain is active, it needs extra oxygen, and thus a larger volume of blood. By monitoring blood flow, the researchers can pinpoint areas of the brain that turn on when a particular task is performed.

The task began with the researchers offering the participants a randomized range of rewards — from $0 to $100 — if they could successfully place the object into the square within the time limit. At the end of hundreds of trials — each with varying reward amounts — the participant was given their reward, based on the result of just one of the trials, picked at random.

As expected, the team found that performance improved as the incentives increased — but only when the cash reward amounts were at the low end of the spectrum. Once the rewards passed a certain threshold, which depended on the individual, performance began to fall off.

Incentives are known to activate a part of your brain called the ventral striatum, Chib says; the researchers thus expected to see the ventral striatum become increasingly active as they bumped up the prizes. And if the conventional thought were correct — that the reason for the observed performance decline was over-motivation — they would expect the striatum to continue showing a lot of activation when the incentives became high enough for performance to suffer.

What they found, instead, was that when the participants were shown their potential rewards, activity in the striatum did indeed increase with rising incentives. But once the volunteers started doing the task, striatal activity decreased with rising incentives. They also noticed that the less activity they saw in a participant’s striatum, the worse that person performed on the task.

Other studies have shown that decreasing striatal activity is related to fear or aversion to loss, Chib says. “When people see the incentive that they’re being offered, they initially encode it as a gain,” he explains. “But when they’re actually doing the task, the thing that causes them to perform poorly is that they worry about losing a potential incentive they haven’t even received yet.” He adds, “We’re showing loss aversion even though there are no explicit losses anywhere in the task — that’s very strange and something you really wouldn’t expect.”

To further test their hypothesis, Chib and his colleagues decided to measure how loss-averse each participant was. They had the participants play a coin-flip game in which there was an equal chance they could win or lose varying amounts of money.

Each participant was offered varying potential win-loss amounts ($20-$20, $20-$10, $20-$5, for example), and then given the opportunity to either accept each possible gamble or decline it. The win-loss ratio at which the subjects chose to take the gamble provided a measure of how loss-averse each person was; someone willing to gamble even when they might win or lose $20 is less loss-averse than someone who is only willing to gamble if they can win $20 but only lose $5.

Once the numbers had been crunched and compared to the original experiment, it turned out that the more averse a participant was, the worse they did on the task when the stakes were high. And for a particularly loss-aversive person, the threshold at which their performance started to decline did not have to be very high. “If you’re more loss-averse, it really hurts you,” Chib says. “You’re going to reach peak performance at a lower incentive level, and your performance is also going to be worse for higher incentives.”

"Previously, it’s been shown that the ventral striatum is involved in mediating performance increases in response to rising incentives," says John O’Doherty, professor of psychology and coauthor of the paper. "But our study shows that changes in activity in this same region can, under certain situations, also lead to worsening performance."

While this study only involved a specific motor task and financial incentives, these results may well be universal, says Shinsuke Shimojo, the Gertrude Baltimore Professor of Experimental Psychology and another coauthor of the study. “The implications and applications can include any sort of decision making that contains high stakes and uncertainties, such as business and politics.”

These findings, the researchers say, might be used to develop new ways to motivate people to perform better or to train them to be less loss-averse. “This loss aversion can be an important way of deciding how to set up incentive mechanisms and how to figure out who’s going to perform well and who isn’t,” Chib says. “If you can train somebody to be less loss-averse, maybe you can help them avoid performing poorly in stressful situations.”

Source: Science Daily

May 9, 2012

How well people with newly diagnosed epilepsy respond to their first drug treatment may signal the likelihood that they will continue to have more seizures, according to a study published in the May 9, 2012, online issue ofNeurology, the medical journal of the American Academy of Neurology.

"Our research shows a pattern based on how a person responds to initial treatment and specifically, to their first two courses of drug treatment," said study author Patrick Kwan, MD, PhD, with the University of Melbourne in Australia.

For the study, 1,098 people from Scotland between the ages of nine and 93 with newly diagnosed epilepsy were followed for as long as 26 years after being given their first drug therapy. Participants were considered seizure-free if they had no seizures for at least a year without changes in their treatment. If they had further seizures, a second drug was chosen to be given alone or to be added to the first. If seizures continued, a third drug regimen was selected, and the process continued for up to nine drug regimens.

The study found that 50 percent of the people were seizure-free after the first drug tried, 13 percent were seizure-free after the second drug regimen tried and 4 percent were seizure-free after the third drug regimen tried. Less than two percent of the participants stopped having seizures on additional drug treatment courses up to the seventh one tried, and none became seizure-free after that.

The research also found that 37 percent of people in the study became seizure-free within six months of treatment. Another 22 percent became seizure-free after more than six months of starting treatment. Both groups continued to be seizure-free. However, 16 percent had fluctuating periods of seizure freedom and relapses, and 25 percent were never seizure-free for one year.

At the end of the study, 749 people (68 percent) were seizure-free and 678 people (62 percent) were on only one drug. The results were independent of the age when the person had the first seizure or the type of epilepsy.

"A person who doesn’t respond well to two courses of epilepsy drug treatment should be further evaluated to verify an epilepsy diagnosis and to identify whether surgery is the best next step," said Patricia E. Penovich, MD, with the Minnesota Epilepsy Group PA and the University of Minnesota School of Medicine in St. Paul, Minn., and a Fellow with the American Academy of Neurology, who wrote an accompanying editorial on the study.

Provided by American Academy of Neurology

Source: medicalxpress.com

May 9, 2012

In 1619, the pioneering astronomer Johannes Kepler published Harmonices Mundi in which he analyzed data on the movement of planets and asserted that the laws of nature governing the movements of planets show features of harmonic relationships in music. In so doing, Kepler provided important support for the, then controversial, model of the universe proposed by Copernicus.

In the latest issue of Biological Psychiatry, researchers at the University of California in San Diego suggest that careful analyses of the electrical signals of brain activity, measured using electroencephalography (EEG), may reveal important harmonic relationships in the electrical activity of brain circuits.

The underlying premise is a simple one - that brain function is expressed by circuits that fire, and therefore generate oscillating EEG signals, at different frequencies.

High frequency EEG activity called gamma, for example, might reflect the activity of fast-spiking cells which are often a subclass of inhibitory nerve cells containing parvalbumin. Represented musically, this would be a high pitch, i.e., toward the right side of the piano.

Lower frequency EEG activity, called theta, might come from cells that fire with a lower frequency.

As circuits interact with each other, one would see different “musical combinations”, like the chords of music, emerging in the EEG signal. Abnormalities in the structure and function of brain circuits would be reflected in cacophonous music, chords where the musical “voices” are firing at the wrong rate (pitch), volume (amplitude), or timing.

It is increasingly evident that schizophrenia is a disorder characterized by disturbances in the “music of the brain hemispheres.” This new report describes relationships between low- and high-frequency EEG oscillations in the human brain produced when high frequency auditory stimuli are presented to a research subject. The authors observed relatively slower oscillations and reduced cross-phase synchrony (for example, peak of theta coinciding with peak of gamma) in schizophrenia patients compared to healthy study participants.

Dr. John Krystal, Editor of Biological Psychiatry, commented, “The new findings highlight the importance of understanding the relationships between different circuits. It seems that cortical abnormalities in schizophrenia disturb brain function, in part, by disturbing the ‘tuning’ of brain circuits in relation to each other.”

Provided by Elsevier

Source: medicalxpress.com

May 9th, 2012

This family comprises a cluster of six genes that may be altered in neurological conditions, such as Parkinson’s and Charcot-Marie-Tooth disease.

A team headed by Eduardo Soriano at the Institute for Research in Biomedicine (IRB Barcelona) has published a study in Nature Communications describing a new family of six genes whose function regulates the movement and position of mitochondria in neurons. Many neurological conditions, including Parkinson’s and various types of Charcot-Marie-Tooth disease, are caused by alterations of genes that control mitochondrial transport, a process that provides the energy required for cell function.

“We have identified a set of new genes that are highly expressed in the nervous system and have a specific function in a biological process that is crucial for the activity and viability of the nervous system”, explains Eduardo Soriano, head of the Neurobiology and Cell Regeneration group at IRB Barcelona and full professor at the University of Barcelona (UB).

By means of comparative genomic analyses, the scientists have discovered that these genes are found only in more evolved mammals, the so-called Eutharia, these characterized by internal fertilization and development. “This finding indicates the relevance of mitochondrial biology. When the brain evolved in size, function and structure, the mitochondrial transport process also became more complex and probably required additional regulatory mechanisms”, says Soriano. “Likewise, given the origin of the gene cluster, in the transition between primitive mammals, such as marsupials (kangaroos) and the remaining placental mammals, it is tempting to propose that the cluster is linked to the increased complexity of the cerebral cortex in the lineage that leads to humans”, adds the full UB professor Jordi Garcia-Fernàndez, collaborator in the study.

In the image, red indicates the localization of mitochondria in a neuron. The new proteins described help to regulate their positions in the cell. Image adapted from IRB Barcelona press release image.

Correct brain function is highly energy-demanding. However, this energy must be finely distributed throughout neurons —cells that have ramifications that can reach up to tens of centimetres in length, from the brain to the limbs. This cluster of genes forms part of the “wheel” machinery of mitochondria and regulates the localization of each cell on the basis of its energy requirements. “These genes would be like an extra control in cellular mitochondrial trafficking and they interact with the major proteins associated with the regulation of mitochondrial transport”, explains Soriano.

Another striking characteristic of these new proteins is that they are found both in mitochondria, the function of which has already been described, and in the cell nucleus, where their function is unknown. “They may also be involved in the regulation of gene expression, a possibility that we are now studying”. In addition to their potential involvement in brain pathologies, the researchers believe that these proteins may be related to metabolic diseases and cancer.

Source: Neuroscience News

May 9, 2012

Researchers have developed a new technique which allows them to measure brain activity in large populations of nerve cells at the resolution of individual cells. The technique, reported today in the journal Nature, has been developed in zebrafish to represent a simplified model of how brain regions work together to flexibly control behaviour.

Our thoughts and actions are the product of large populations of nerve cells, called neurons, working in harmony, often millions at a time. Measuring brain activity during behaviour at detailed resolution in these groups of cells has proved extremely challenging. Currently, scientists are restricted to measuring their activity in individual brain areas of, for example, moving rats, typically in less than a few hundred neurons.

Dr Misha Ahrens, a Sir Henry Wellcome Postdoctoral Fellow based at Harvard University and the University of Cambridge, worked with colleagues to develop a technique which allows neuroscientists to study as many as 2,000 neurons simultaneously, anywhere in the brain of a transparent zebrafish. Their work was funded by the Wellcome Trust and the National Institutes of Health.

Dr Ahrens and colleagues created a virtual environment for zebrafish, which allowed them to measure activity in the neurons as the fish ‘moved’. In reality, the zebrafish was paralysed to allow the researchers to image its brain; the fish perceived to ‘move’ through the virtual environment by activating their motor neuron axons, the cells responsible for generating movement.

Zebrafish are often used as a simple organism to study genetics and characteristics of the nervous system that are conserved in humans . They are genetically modifiable, so by manipulating the fish’s genetic make-up, Dr Ahrens and colleagues created a fish in which all neurons contained a particular protein that increases its fluorescence when the cells are active. The fish are transparent and so the team were able to use a laser-scanning microscope, to see activity in any neuron in the brain of the fish, and up to 2,000 neurons simultaneously.

Dr Ahrens explains: “Our behaviour is determined by thousands, possibly millions, of nerve cells working in harmony. The zebrafish performs complex behaviors, with a brain of about 100,000 neurons, almost all of which are accessible to optical recording of neural activity. Our new technique will help us examine how large networks mediate behaviour, while at the same time telling us what each individual cell is doing.”

Using the technique, Dr Ahrens and colleagues asked the question: dozebrafish adapt their behaviour in response to changes in their environment? To do this, they manipulated the virtual environment to simulate the fish suddenly becoming more “muscular”. This served as a simplified version of what happens when the brain needs to adapt the way it drives behavior, for example, when water temperature changes the efficacy of the muscles, or when the fish gets injured.

Dr Ahrens adds: “The paralyzed fish in the virtual world do indeed adapt their behaviour, by adjusting the amount of impulses the brain sends to the muscles. They also ‘remember’ this change for a while. Imaging the brain everywhere during this behaviour, we identified certain brain regions that were involved, most notably the cerebellum and related structures. This technique opens the possibility that eventually, the behaviour may be used to gain insights into human motor control and motor control deficits.

"Our own motor control is continuously recalibrating itself in a similar way to the fish’s to cope with ever changing conditions of our body and environment, such as when we injure a leg, or if we’re walking on a slippery floor or carrying a heavy bag. The zebrafish’s behaviour is an ultra-simplified version of this and we have been able to gain some insight into how its brain structures drive behaviour. This might someday help us understand how damage to certain brain regions in humans affects the way in which the brain integrates sensory information to control body movements."

Understanding the brain is one of the Wellcome Trust’s five strategic challenges.

Provided by Wellcome Trust

Source: medicalxpress.com

May 9, 2012

Research published in the May 10 issue of the journal Neuron, describes a potential new therapeutic approach for improving memory and modifying disease progression in patients with amnestic mild cognitive impairment. The study finds that excess brain activity may be doing more harm than good in some conditions that cause mild cognitive decline and memory impairment.

Elevated activity in specific parts of the hippocampus, a brain region involved in memory, is often seen in disorders associated with an increased risk for Alzheimer’s disease. Amnestic mild cognitive impairment (aMCI), where memory is worse than would be expected for a person’s age, is one such disorder. “In the case of early aMCI, it has been suggested that the increased hippocampal activation may serve a beneficial function by recruiting additional neural resources to compensate for those that are lost,” explains senior study author, Dr. Michela Gallagher, from Johns Hopkins University. “However, animal studies have raised the alternative view that this excess activation may be contributing to memory impairment.”

Dr. Gallagher and colleagues tested how a reduction of hippocampal activity would impact human patients with aMCI. The researchers used a low dose of a drug used clinically to treat epilepsy, for the purpose of reducing hippocampal activity in subjects with aMCI to levels that were similar to activity levels in healthy, age-matched subjects in a control group. The researchers found that treatment with the drug improved performance on a memory task. These findings point to the therapeutic potential of reducing excess activation in the hippocampus in aMCI.

The results also have broader significance as elevated activity in the hippocampus is also observed in other conditions that are thought to precede Alzheimer’s disease, and may be one of the underlying mechanisms of neurodegeneration. “Apart from a direct role in memory impairment, there is concern that elevated activity in vulnerable neural networks could be causing additional damage and, possibly, widespread disease-related degeneration that underlies cognitive decline and the conversion to Alzheimer’s disease,” concludes Dr. Gallagher. “Therefore, reducing the elevated activity in the hippocampus may help to restore memory and protect the brain.”

Provided by Cell Press

More information: Bakker et al.: “Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment.”,DOI:10.1016/j.neuron.2012.03.023

Source: medicalxpress.com

Released: 5/9/2012 11:20 AM EDT

Newswise — After completing the first study of its kind, researchers at McMaster University have discovered that very early musical training benefits children even before they can walk or talk.

They found that one-year-old babies who participate in interactive music classes with their parents smile more, communicate better and show earlier and more sophisticated brain responses to music.

The findings were published recently in the scientific journals Developmental Science and Annals of the New York Academy of Sciences.

“Many past studies of musical training have focused on older children,” says Laurel Trainor, director of the McMaster Institute for Music and the Mind. “Our results suggest that the infant brain might be particularly plastic with regard to musical exposure.”

Trainor, together with David Gerry, a music educator and graduate student, received an award from the Grammy Foundation in 2008 to study the effects of musical training in infancy. In the recent study, groups of babies and their parents spent six months participating in one of two types of weekly music instruction.

One music class involved interactive music-making and learning a small set of lullabies, nursery rhymes and songs with actions. Parents and infants worked together to learn to play percussion instruments, take turns and sing specific songs.

In the other music class, infants and parents played at various toy stations while recordings from the popular Baby Einstein series played in the background.

Before the classes began, all the babies had shown similar communication and social development and none had previously participated in other baby music classes.

“Babies who participated in the interactive music classes with their parents showed earlier sensitivity to the pitch structure in music,” says Trainor. “Specifically, they preferred to listen to a version of a piano piece that stayed in key, versus a version that included out-of-key notes. Infants who participated in the passive listening classes did not show the same preferences. Even their brains responded to music differently. Infants from the interactive music classes showed larger and/or earlier brain responses to musical tones.”

The non-musical differences between the two groups of babies were even more surprising, say researchers.

Babies from the interactive classes showed better early communication skills, like pointing at objects that are out of reach, or waving goodbye. Socially, these babies also smiled more, were easier to soothe, and showed less distress when things were unfamiliar or didn’t go their way.

While both class types included listening to music and all the infants heard a similar amount of music at home, a big difference between the classes was the interactive exposure to music.

“There are many ways that parents can connect with their babies,” says study coordinator Andrea Unrau. “The great thing about music is, everyone loves it and everyone can learn simple interactive musical games together.”

Source: newswise

Released: 5/9/2012 11:00 AM EDT 

Newswise — “Practice makes perfect,” the saying goes. Optimal performance, however, can require more than talent, effort, and repetition. Training the brain to reduce stress through neurofeedback can remove barriers and enhance one’s innate abilities.

An article in the journal Biofeedback presents the narrative of a young cellist who was able to realize the potential of his talent and eliminate debilitating migraine headaches. This case study is part of a special section in the Spring 2012 issue focusing on optimal functioning.

Enhancing people’s performance in business, performing and visual arts, academia, and sports can be realized through biofeedback and neurofeedback training. Tools of stress reduction, mental imagery training, psychology, and psycho-physiological technology are combined to help people reach their goals.

The author and practitioner in this case study has combined her work and study in the fields of theater, social work, and neurofeedback. In her practice, she coaches clients to achieve outstanding performances. For example, a singer can better understand and interpret a musical selection, allowing that singer to better convey the emotion of the music, resulting in a noticeably improved performance.

William, the young musician, sought relief from migraine headaches that were affecting him almost daily. His therapy, however, did not take the approach of treating the headaches, but of focusing on William as a person and as a performer. By improving his functionality, working through moments of obsessiveness, self-criticism, fear, and anxiety, the headaches could also be resolved.

William’s therapist conducted neurofeedback — using sensors to read his brainwaves, analyzing these with NeuroOptimal™ software, and then giving feedback to the brain through a visual display and sound. With this information, the brain can learn to self-correct. This technology assists in getting people past that moment when they obsess over whether they have given the correct answer or hit the right note.

NeuroOptimal feedback, guided imagery, and coaching about decisions regarding his music helped William move beyond the difficulties he encountered. During his senior recital at his college, he was able to give a relaxed, confident performance that was met with a standing ovation.

Full text of the article, “William’s Story: A Case Study in Optimal Performance,” Biofeedback, Volume 40, Issue 1, Spring 2012, is available at http://www.aapb-biofeedback.com/

Source: newswise

ScienceDaily (May 8, 2012) — Whether it’s a line from a movie, an advertising slogan or a politician’s catchphrase, some statements take hold in people’s minds better than others. But why?

Cornell researchers who applied computer analysis to a database of movie scripts think they may have found the secret of what makes a line memorable.

The study suggests that memorable lines use familiar sentence structure but incorporate distinctive words or phrases, and they make general statements that could apply elsewhere. The latter may explain why lines such as, “You’re gonna need a bigger boat” or “These aren’t the droids you’re looking for” (accompanied by a hand gesture) have become standing jokes. You can use them in a different context and apply the line to your own situation.

While the analysis was based on movie quotes, it could have applications in marketing, politics, entertainment and social media, the researchers said.

"Using movie scripts allowed us to study just the language, without other factors. We needed a way of asking a question just about the language, and the movies make a very nice dataset," said graduate student Cristian Danescu-Niculescu-Mizil, first author of a paper to be presented at the 50th Annual Meeting of the Association for Computational Linguistics July 8-14 in Jeju, South Korea.

The study grows out of ongoing work on how ideas travel across networks.

"We’ve been looking at things like who talks to whom," said Jon Kleinberg, a professor of computer science who worked on the study, "but we hadn’t explored how the language in which an idea was presented might have an effect."

To address that, they collaborated with Lillian Lee, a professor of computer science who specializes in computer processing of natural human language.

They obtained scripts from about 1,000 movies, and a database of memorable quotes from those movies from the Internet Movie Database. Each quote was paired with another from the movie’s script, spoken by the same character in the same scene and about the same length, to eliminate every factor except the language itself. Obi-Wan Kenobi, for example, also said, “You don’t need to see his identification,” but you don’t hear that a lot.

They asked a group of people who had not seen the movies to choose which quote in the pairs was most memorable. Two patterns emerged to identify the memorable choice: distinctiveness and generality.

Then the researchers programmed a computer with linguistic rules reflecting these concepts. A line will be less general if it contains third-person pronouns and definite articles (which refer to people, objects or events in the scene) and uses past tense (usually referring to something that happened previously in the story). Distinctive language can be identified by comparison with a database of news stories. The computer was able to choose the memorable quote an average of 64 percent of the time.

Later analysis also found subtle differences in sound and word choice: Memorable quotes use more sounds made in the front of the mouth, words with more syllables and fewer coordinating conjunctions.

In a further test, the researchers found that the same rules applied to popular advertising slogans.

Although teaching a computer how to write memorable dialogue is probably a long way off, applications might be developed to monitor the work of human writers and evaluate it in progress, Kleinberg suggested.

The researchers have set up a website where you can test your skill at identifying memorable movie quotes, and perhaps contribute some data to the research, at www.cs.cornell.edu/~cristian/memorability.html

Source: Science Daily

ScienceDaily (May 8, 2012) — Researchers at the University of Alabama at Birmingham hope to one day use fluorescent light bulbs to slow nearsightedness, which affects 40 percent of American adults and can cause blindness.

In an early step in that direction, results of a study found that small increases in daily artificial light slowed the development of nearsightedness by 40 percent in tree shrews, which are close relatives of primates.

The team, led by Thomas Norton, Ph.D., professor in the UAB Department of Vision Sciences, presented the study results May 8 at the 2012 Association for Research in Vision and Ophthalmology annual meeting in Ft. Lauderdale.

People can see clearly because the front part of the eye bends light and focuses it on the retina in back. Nearsightedness, also called myopia, occurs when the physical length of the eye is too long, causing light to focus in front of the retina and blurring images.

Myopia has many causes, some related to inheritance and some to the environment. Research in recent years had, for instance, suggested that children who spent more time outdoors, presumably in brighter outdoor light, had less myopia as young adults. That raised the question of whether artificial light, like sunlight, could help reduce myopia development, without the risks of prolonged sun exposure, such as skin cancer and cataracts.

"Our hope is to develop programs that reduce the rate of myopia using energy efficient, fluorescent lights for a few hours each day in homes or classrooms," said John Siegwart, Ph.D., research assistant professor in UAB Vision Sciences and co-author of the study. "Trying to prevent myopia by fixing defective genes through gene therapy or using a drug is a multi-year, multimillion-dollar effort with no guarantee of success. We hope to make a difference just with light bulbs."

Sorting through theories

Work over 25 years had shown that putting a goggle over one eye of a study animal, one that lets in light but blurs images, causes the eye to grow too long, which in turn causes myopia. Other past studies had shown that elevated light levels could reduce myopia under these conditions, whether the light was produced by halogen lamps, metal halide bulbs or daylight. The current study is the first to show that the development of myopia can be slowed by increasing daily fluorescent light levels.

One prevailing theory on myopia-related shape changes in the eye is that they are caused by the blurriness of images experienced while reading or doing other near-work chores. Another holds some people develop myopia because they have low levels of vitamin D, which goes up with exposure to sunlight and could explain the connection between outdoor light and reduced myopia. A third theory, one reinforced by the current results, is that bright light causes an increase in levels of dopamine, a signaling molecule in the retina.

To test the theories, the team used a goggle that lets in light but no images to produce myopia in one eye of each tree shrew. They found that a group exposed to elevated fluorescent light levels for eight hours per day developed 47 percent less myopia than a control group exposed to normal indoor lighting, even though the images were neither more nor less blurry. They also found that animals fed vitamin D supplements developed myopia just like ones without the supplement. Given these results, the team is now experimenting with light levels and treatment times to see if a short, bright light treatment could be effective. They have also begun studies looking at the effect of elevated light on retinal dopamine levels as it relates to the reduction of myopia.

"If we can find the best kind of light, treatment period and light level, we’ll have the scientific justification to begin studies raising light levels in schools, for instance," said Norton. "Compact fluorescent bulbs use much less electricity than standard light bulbs, and future programs raising light levels will have more impact the less expensive they are."

Source: Science Daily

ScienceDaily (May 8, 2012) — Can blindness or other forms of visual deprivation really enhance our other senses such as hearing or touch? While this theory is widely regarded as being true, there are still many questions about the science behind it.

New findings from a Canadian research team investigating this link suggest that not only is there a real connection between vision and other senses, but that connection is important to better understand the underlying mechanisms that can quickly trigger sensory changes. This may demystify the true potential of human adaptation and, ultimately, help develop innovative and effective methods for rehabilitation following sensory loss or injury.

François Champoux, director of the University of Montreal’s Laboratory of Auditory Neuroscience Research, will present his team’s research and findings at the Acoustics 2012 meeting in Hong Kong, May 13-18, a joint meeting of the Acoustical Society of America (ASA), Acoustical Society of China, Western Pacific Acoustics Conference, and the Hong Kong Institute of Acoustics.

Studies have shown, in terms of hearing, that blind people are better at localizing sound. One study even suggested that blindness might improve the ability to differentiate between sound frequencies. “The supposed enhanced tactile abilities have been studied at a greater degree and can be seen as early as days or even minutes following blindness,” says Champoux. “This rapid change in auditory ability hasn’t yet been clearly demonstrated.”

Two big questions about blindness and enhanced abilities remain unanswered: Can blindness improve more complex auditory abilities and, if so, can these changes be triggered after only a few minutes of visual deprivation, similar to those seen with tactile abilities?

"When we speak or play a musical instrument, the sounds have specific harmonic relations. In other words, if we play a certain note on a piano, that note has many related ‘layers.’ However, we don’t hear all of these layers because our brain simply associates them all together and we only hear the lowest one," Champoux explains.

It’s through this complex computation based on specific components of the sound that the brain can interpret and distinguish auditory signals coming from different people or instruments. The ability to identify harmonicity — the harmonic relation between sounds — is one of the most powerful factors involved in interpreting our auditory surroundings.

"Harmonicity can easily be evaluated using a simple task in which similar harmonic layers are set up and one of them is gradually modified until the individual notices two layers instead of one," says Champoux. "In our study, healthy individuals completed such a task while blindfolded. This task was administered twice, separated by a 90-minute interval during which the participants conversed with the experimenter in a quiet room. Half of the participants kept the blindfold on during the interval period, depriving them of all visual input, while the other half removed their blindfolds."

They found no significant differences between the two groups in their ability to differentiate harmonicity prior to visual deprivation. However, the results of the testing session following visual deprivation revealed that visually deprived individuals performed significantly better than the group that took their blindfolds off.

"Regardless of the neural basis for such an enhancement, our results suggest that the potential for change in auditory perception is much greater than previously assumed," Champoux notes.

Source: Science Daily

ScienceDaily (May 8, 2012) — Listening to amplified music for less than 1.5 hours produces measurable changes in hearing ability that may place listeners at risk of noise-induced hearing loss, new research shows. While further research is needed to firmly establish this risk, the investigation is significant because it provides the first acoustical data for a new method to assess the potential harm from a widespread cultural behavior: “leisure listening” to amplified music, whether in live environments or through headphones.

A team of Danish acoustics researchers present the results of their preliminary study at the Acoustics 2012 meeting in Hong Kong, May 13-18, a joint meeting of the Acoustical Society of America (ASA), Acoustical Society of China, Western Pacific Acoustics Conference, and the Hong Kong Institute of Acoustics. Their goal is to help develop recommendations for how sound engineers, musicians, event organizers, and the general public should safely enjoy amplified music so they are protected from hearing loss — just as workers are now protected by occupational health standards.

Explains Rodrigo Ordonez, Ph.D., lead scientist of the Danish team from Aalborg University’s Department of Electronic Systems: “Modern low-distortion, high-power loudspeaker systems and headphones make it easy for people to be exposed to potentially harmful sound levels at discotheques, concerts, or while using portable music players.”

He adds that in the realm of industrial noise and work-related sound exposures, decades of experience and personal tragedy — many workers lost hearing from factory conditions — has produced the hearing-damage risk criteria currently used. Based on well-documented acoustical parameters, these criteria outline measurement procedures and expected impact on hearing.

"Yet when it comes to musical sound exposure — and in particular, amplified music — it is not known if the same measures used for industrial noise will accurately describe the effects on hearing and the risk these behaviors pose," Dr. Ordonez says.

To investigate the potential health risk from amplified music, the team measured sounds known as “otoacoustic emissions” as an index of auditory function. These are sounds generated within the inner ear in response to sound stimuli, and they can be measured in the ear canals of people who have healthy hearing. Research shows that otoacoustic emissions disappear when the inner ear is damaged. In this study, the researchers measured otoacoustic emissions to gauge changes in hearing ability before and after exposure to amplified music, testing this method in a live concert environment. Comparing how these two sets of measures change after a sound exposure with the acoustical parameters of the amplified music can lead to a better understanding of how our hearing is affected.

Results revealed two main findings: One is that it is possible to measure changes in hearing after exposures of relatively short duration, less than 1.5 hours. The second is that there are noticeable individual differences in sound exposure levels, as well as in the changes on otoacoustic emissions produced by similar exposure conditions.

Next steps in the team’s work include refining their measurement methods and describing the biophysical effects and mechanics that music sound levels have on individuals. Ultimately they hope to provide data and a scientific rationale on which to establish damage risk criteria for music sound exposure.

Source: Science Daily

ScienceDaily (May 8, 2012) — Although we have little awareness that we are doing it, we spend most of our lives filtering out many of the sounds that permeate our lives and acutely focusing on others — a phenomenon known as auditory selective attention. In research that could some day lead to the development of improved devices allowing users to control things like wheelchairs through thought alone, hearing scientists at the University of Washington (UW) are attempting to tease apart the process.

The work will be presented at the Acoustics 2012 meeting in Hong Kong, May 13-18, a joint meeting of the Acoustical Society of America (ASA), Acoustical Society of China, Western Pacific Acoustics Conference, and the Hong Kong Institute of Acoustics.

Auditory selective attention is extremely important in everyday life, notes UW postdoctoral researcher Ross Maddox. “In situations as mundane as ordering your morning cup of coffee, you must focus on the barista while tuning out the loud hiss of the espresso machine and the annoying cell phone conversation happening in line right behind you,” says Maddox. “However, the mechanisms behind selective attention are still not well understood.” In addition, some individuals suffer from Central Auditory Processing Disorder (CAPD), “which means they have normal hearing when tested by an audiologist,” he says, “but they are completely lost in loud settings like restaurants and airports.”

To determine how auditory selective attention works — and perhaps how it fails in people with CAPD — Maddox, along with Adrian K.C. Lee, an assistant professor of speech and hearing sciences, and colleague Willy Cheung, created laboratory situations that promoted the breakdown of the process. The researchers had 10 subjects try to focus their attention on just one target sound — a continuously repeating utterance of a single letter — among a total of 4, 6, 8, or 12 such sounds. The subjects had to determine when an “oddball” item (the letter “R,” chosen because it doesn’t rhyme with any other letter) was inserted into the target sound stream.

"Most studies systematically degrade sounds and measure the effects on listeners’ performance," Maddox explains. "Here, we made the target sound as easy to distinguish from all the other sounds present as possible, and tested the upper limit on the number of sounds a listener could tune out, given all these acoustical advantages."

Unsurprisingly, it is harder to tune in to just one stream when the number of streams increases. However, study subjects did better than expected — successfully identifying the target 70 percent of the time in the most difficult conditions. Repeating letters faster did make the task harder — although with faster repetition, listeners more quickly learn what the letter they’re listening to sounds like, “so there is a tradeoff involved when deciding on repetition speed,” Maddox says.

The work, Maddox and colleagues say, is a first step toward developing an auditory brain-computer interface (BCI) — a device that reads brain activity to allow users to control computers or machines such as wheelchairs. “We hope to create a system that presents a user with an auditory ‘menu’ of sounds — similar to the letter streams here — and allows the listener to make a choice by reading their brainwaves to determine which sound they are focusing on. The more sound streams a user is able to tune out, the more menu options we can present at a single time.”

Source: Science Daily

ScienceDaily (May 8, 2012) — People of all ages and cultures gesture while speaking, some much more noticeably than others. But is gesturing uniquely tied to speech, or is it, rather, processed by the brain like any other manual action?

Scientists have discovered that actual actions on objects, such as physically stirring a spoon in a cup, have less of an impact on the brain’s understanding of speech than simply gesturing as if stirring a spoon in a cup. (Credit: Image courtesy of Acoustical Society of America (ASA))

A U.S.-Netherlands research collaboration delving into this tie discovered that actual actions on objects, such as physically stirring a spoon in a cup, have less of an impact on the brain’s understanding of speech than simply gesturing as if stirring a spoon in a cup. This is surprising because there is less visual information contained in gestures than in actual actions on objects. In short: Less may actually be more when it comes to gestures and actions in terms of understanding language.

Spencer Kelly, associate professor of Psychology, director of the Neuroscience program, and co-director of the Center for Language and Brain at Colgate University, and colleagues from the National Institutes of Health and Max Planck Institute for Psycholinguistics will present their research at the Acoustics 2012 meeting in Hong Kong, May 13-18, a joint meeting of the Acoustical Society of America (ASA), Acoustical Society of China, Western Pacific Acoustics Conference, and the Hong Kong Institute of Acoustics.

Among their key findings is that gestures — more than actions — appear to make people pay attention to the acoustics of speech. When we see a gesture, our auditory system expects to also hear speech. But this is not what the researchers found in the case of manual actions on objects.

Just think of all the actions you’ve seen today that occurred in the absence of speech. “This special relationship is interesting because many scientists have argued that spoken language evolved from a gestural communication system — using the entire body — in our evolutionary past,” points out Kelly. “Our results provide a glimpse into this past relationship by showing that gestures still have a tight and perhaps special coupling with speech in present-day communication. In this way, gestures are not merely add-ons to language — they may actually be a fundamental part of it.”

A better understanding of the role hand gestures play in how people understand language could lead to new audio and visual instruction techniques to help people overcome major challenges with language delays and disorders or learning a second language.

What’s next for the researchers? “We’re interested in how other types of visual inputs, such as eye gaze, mouth movements, and facial expressions, combine with hand gestures to impact speech processing. This will allow us to develop even more natural and effective ways to help people understand and learn language,” says Kelly.

Source: Science Daily

May 8, 2012

Psychologists at Bangor University believe that they have glimpsed for the first time, a process that takes place deep within our unconscious brain, where primal reactions interact with higher mental processes. Writing in the Journal of Neuroscience, they identify a reaction to negative language inputs which shuts down unconscious processing.

For the last quarter of a century, psychologists have been aware of, and fascinated by the fact that our brain can process high-level information such as meaning outside consciousness. What the psychologists at Bangor University have discovered is the reverse- that our brain can unconsciously ‘decide’ to withhold information by preventing access to certain forms of knowledge.

The psychologists extrapolate this from their most recent findings working with bilingual people. Building on their previous discovery that bilinguals subconsciously access their first language when reading in their second language; the psychologists at the School of Psychology and Centre for Research on Bilingualism have now made the surprising discovery that our brain shuts down that same unconscious access to the native language when faced with a negative word such as war, discomfort, inconvenience, and unfortunate.

They believe that this provides the first proven insight to a hither-to unproven process in which our unconscious mind blocks information from our conscious mind or higher mental processes.

This finding breaks new ground in our understanding of the interaction between emotion and thought in the brain. Previous work on emotion and cognition has already shown that emotion affects basic brain functions such as attention, memory, vision and motor control, but never at such a high processing level as language and understanding.

Key to this is the understanding that people have a greater reaction to emotional words and phrases in their first language- which is why people speak to their infants and children in their first language despite living in a country which speaks another language and despite fluency in the second. It has been recognised for some time that anger, swearing or discussing intimate feelings has more power in a speaker’s native language. In other words, emotional information lacks the same power in a second language as in a native language.

Dr Yan Jing Wu of the University’s School of Psychology said: “We devised this experiment to unravel the unconscious interactions between the processing of emotional content and access to the native language system. We think we’ve identified, for the first time, the mechanism by which emotion controls fundamental thought processes outside consciousness.

"Perhaps this is a process that resembles the mental repression mechanism that people have theorised about but never previously located."

So why would the brain block access to the native language at an unconscious level?

Professor Guillaume Thierry explains: “We think this is a protective mechanism. We know that in trauma for example, people behave very differently. Surface conscious processes are modulated by a deeper emotional system in the brain. Perhaps this brain mechanism spontaneously minimises negative impact of disturbing emotional content on our thinking, to prevent causing anxiety or mental discomfort.”

He continues: “We were extremely surprised by our finding. We were expecting to find modulation between the different words- and perhaps a heightened reaction to the emotional word - but what we found was the exact opposite to what we expected- a cancellation of the response to the negative words.”

The psychologists made this discovery by asking English-speaking Chinese people whether word pairs were related in meaning. Some of the word pairs were related in their Chinese translations. Although not consciously acknowledging a relation, measurements of electrical activity in the brain revealed that the bilingual participants were unconsciously translating the words. However, uncannily, this activity was not observed when the English words had a negative meaning.

Provided by Bangor University

Source: medicalxpress.com

May 8th, 2012

Nanotechnology scientists and memory researchers at the Kiel University redesigned a mental learning process using electronic circuits.

The bell rings and the dog starts drooling. Such a reaction was part of studies performed by Ivan Pavlov, a famous Russian psychologist and physiologist and winner of the Nobel Prize for Physiology and Medicine in 1904. His experiment, nowadays known as “Pavlov’s Dog”, is ever since considered as a milestone for implicit learning processes. By using specific electronic components scientists form the Technical Faculty and the Memory Research at the Kiel University together with the Forschungszentrum Jülich were now able to mimic the behavior of Pavlov`s dog. The study “An Electronic Version of Pavlov’s Dog” is published in the current issue of Advanced Functional Materials (huwp 12012).

Digital and biological information processing are based on fundamentally different principles. Modern computers are able to work on mathematical-logical problems at an extremely high pace. In fact, procedures in the computer’s central processing unit and in the storage media run serially. While digital computers have shown immense success throughout the years in certain fields, they reveal weaknesses when it comes to pattern recognition and cognitive tasks. “However, to imitate biological information processing systems recognition and cognitive tasks are essential. Mammal brains – and therefore also the brains of humans – decode information in complex neuronal networks of synapses with up to 10¹⁴ (100 Trillion) connections. However, the connectivity between neurons is not fixed. “Learning means that new connections between neurons are created, or existing connections are reinforced or weakened”, says PD Dr. Thorsten Bartsch of the Clinic for Neurology. This is called neuronal plasticity.

Kiel scientists teach electronic circuits to memorize reactions. Source: Kohlstedt

Is it possible to design neural circuits with electronic devices to mimic learning? At this crossroad between neurobiology, material science and nanoelectronics, scientists from the University of Kiel are collaborating with their colleagues from the Research Center Jülich. Now, they have succeeded in electronically recreating the classical “Pavlov’s Dog” experiment. “We used memristive devices in order to mimic the associative behaviour of Pavlov’s dog in form of an electronic circuit”, explains Professor Hermann Kohlstedt, head of the working group Nanoelectronics at the University of Kiel.

Memristors are a class of electronic circuit elements which have only been available to scientists in an adequate quality for a few years. They exhibit a memory characteristic in form of hysteretic current-voltage curves consisting of high and low resistance branches.  In dependence on the prior charge flow through the device these resistances can vary.  Scientists try to use this memory effect in order to create networks that are similar to neuronal connections between synapses. “In the long term, our goal is to copy the synaptic plasticity onto electronic circuits. We might even be able to recreate cognitive skills electronically”, says Kohlstedt. The collaborating scientific working groups in Kiel and Jülich have taken a small step toward this goal.

The project set-up consisted of the following: two electrical impulses were linked via a memristive device to a comparator. The two pulses represent the food and the bell in Pavlov’s experiment. A comparator is a device that compares two voltages or currents and generates an output when a given level has been reached. In this case, it produces the output signal (representing saliva) when the threshold value is reached. In addition, the memristive element also has a threshold voltage that is defined by physical and chemical mechanisms in the nano-electronic device. Below this threshold value the memristive device behaves like any ordinary linear resistor. However, when the threshold value is exceeded, a hysteretic (changed) current-voltage characteristic will appear.

“During the experimental investigation, the food for the dog (electrical impulse 1) resulted in an output signal of the comparator, which could be defined as salivation. Unlike to impulse 1, the ring of the bell (electrical impulse 2) was set in such a way that the compartor’s output stayed unaffected – meaning no salivation”, describes Dr. Martin Ziegler, scientist at the Kiel University and the first-author of the publication. After applying both impulses simultaneously to the memristive device, the threshold value was exceeded. The working group had activated the memristive memory function. Multiple repetitions led to an associative learning process within the circuit – similar to Pavlov’s dogs. “From this moment on, we had only to apply electrical impulse 2 (bell) and the comparator generated an output signal, equivalent to salivation”, says Ziegler and is very pleased with these results. Electrical impulse 1 (feed) triggers the same reaction as it did before the learning. Hence, the electric circuit shows a behaviour that is termed classical conditioning in the field of psychology. Beyond that, the scientists were able to prove that the electrical circuit is able to unlearn a particular behaviour if both impulses were not longer applied simultaneously.

Information on “Pavlov’s dog”

In Behavioural Psychology, Pavlov’s experiments with dogs are considered as milestones to understand implicit learning in biological systems. In the early 20^th century, Ivan Pavlov was able to show that dogs reacted indifferently towards the impulse “bell” and “food” when these were presented separately. After combining those two impulses (food and bell) in multiple repetitions, the dogs associated both impulses with each other. As a result, the dogs produced a higher amount of saliva, now even hearing the bell alone. This method is called classical conditioning and can be generalized to various combinations of certain impulses.

Nanotechnology scientists and memory researchers have published research results concerning “Pavlov’s Dog”. Credit: Advanced Functional Materials (huwp 2012)

Source: Neuroscience News

ScienceDaily (May 8, 2012) — New research from the Royal College of Surgeons in Ireland (RCSI) published in Nature’s Neuropsychopharmacology has shown physical changes to exist in specific brain areas implicated in schizophrenia following the use of cannabis during adolescence. The research has shown how cannabis use during adolescence can interact with a gene, called the COMT gene, to cause physical changes in the brain.

The COMT gene provides instructions for making enzymes which breakdown a specific chemical messenger called dopamine. Dopamine is a neurotransmitter that helps conduct signals from one nerve cell to another, particularly in the brains reward and pleasure centres. Adolescent cannabis use and its interaction with particular forms of the COMT gene have been shown to cause physical changes in the brain as well as increasing the risk of developing schizophrenia.

Dr Áine Behan, Department of Physiology, RCSI and lead author on the study said ‘This is the first study to show that the combined effects of the COMT gene with adolescent cannabis use cause physical changes in the brain regions associated with schizophrenia. It demonstrates how genetic, developmental and environmental factors interact to modulate brain function in schizophrenia and supports previous behavioural research which has shown the COMT gene to influence the effects of adolescent cannabis use on schizophrenia-related behaviours.

The three areas of the brain assessed in this study were found to show changes in cell size, density and protein levels.

'Increased knowledge on the effects of cannabis on the brain is critical to understanding youth mental health both in terms of psychological and psychiatric well-being,' Dr Behan continued.

Source: Science Daily

ScienceDaily (May 8, 2012) — Antidepressive drugs reduce the mortality rate of schizophrenic patients, while treatment with bensodiazepines greatly increases it, especially as regards suicide. Giving several antipsychotics simultaneously, however, seems to have no effect at all. This according to a new study examining different drug combinations administered to patients with schizophrenia.

"We weren’t aware that the beneficial effects of antidepressives were so powerful," says Jari Tiihonen, professor of clinical psychiatry at Karolinska Institutet’s Department of Clinical Neuroscience.

The study followed 2,588 Finns who had recently developed schizophrenia from the time of their initial admission to hospital for an average of four years. By accessing the Finnish registers, the researchers were then able to ascertain the effects of different drug combinations on the mortality risk within the group.

A total of 160 people died in the study, most commonly from external causes such as drowning, poisoning or violent crime, something that affected 57 people. Thirty-five of these cases were suicide, which made it and cardiovascular disease the two main causes of death.

The researchers found that when taking bensodiazepines, the participants ran a 91 per cent higher risk of early death than at times when these drugs were not used. By far the most common cause of death was suicide, and most deaths occurred with patients who had been taking their bensodiazepines for longer than four weeks.

"The increased suicide risk for patients with long-standing benzodiazepine use may be partly attributable to the possible development of withdrawal symptoms when the drugs run out," says Professor Tiihonen. "These symptoms, which can be severe severe anxiety and insomnia, might have affected some of the patients’ decisions to commit suicide. It’s therefore extremely important that bensodiazepines are discontinued gradually rather than abruptly over a period of weeks or months and in consultation with a doctor."

"The temporary acute use of benzodiazepines is justifiable if the patient is suffering a great deal of anxiety," he continues. "But benzodiazepines should be discontinued within a month according to psychiatric recommendations, which doctors must start following and respecting."

During the periods the participants took antidepressive drugs, they ran a 43 per cent lower mortality risk than during the periods when these drugs were not used. Antipsychotics had no effect on mortality if the patients were on multiple prescriptions simultaneously.

"People think that it’s dangerous to treat patients with schizophrenia with more than one antipsychotic drug, but there is nothing to back that up, says Professor Tiihonen. "I believe that most doctors prescribe several antipsychotics if their patients are not helped by just one kind, and our study finds no link between this and increased mortality during a four year follow-up. But it does mean more adverse effects, such as the risk of weight-gain, which also impacts the health in the long run, so the recommended attitude is still one of restraint."

Source: Science Daily

ScienceDaily (May 8, 2012) — It is increasingly recognized that chronic psychotropic drug treatment may lead to structural remodeling of the brain. Indeed, clinical studies in humans present an intriguing picture: antipsychotics, used for the treatment of schizophrenia and psychosis, may contribute to cortical gray matter loss in patients, whereas lithium, used for the treatment of bipolar disorder and mania, may preserve gray matter in patients.

However, the clinical significance of these structural changes is not yet clear. There are many challenges in executing longitudinal, controlled, and randomized studies to evaluate this issue in humans, particularly because there are also many confounding factors, including illness severity, illness duration, and other medications, when studying patients.

It is therefore critical to develop animal models to inform the clinical research. To accomplish this, a group of researchers at King’s College London, led by Dr. Shitij Kapur, developed a rat model using clinically relevant drug exposure and matched clinical dosing in combination with longitudinal magnetic resonance imaging. They administered either lithium or haloperidol (a common antipsychotic) to rats in doses equivalent to those received by humans. The rats received this treatment daily for eight weeks, equivalent to 5 human years, and underwent brain scans both before and after treatment.

Dr. Kapur explained their findings, “Using this approach, we observed that chronic treatment with haloperidol leads to decreases in cortical gray matter, whilst lithium induced an increase, effects that were reversible after drug withdrawal.” Gray matter was decreased by 6% after haloperidol treatment, but increased by 3% after lithium treatment.

"These important observations clarify conflicting findings from clinical trials by removing many of the confounding effects," commented Dr. John Krystal, Editor of Biological Psychiatry. "Whether these changes in brain structure underlie the benefits or side effects of these medications remain to be seen. However, they point to brain effects of established medications that are not well understood, but which may hold clues to new treatment approaches."

"Whilst these intriguing findings are consistent with available clinical data, it should be noted these studies were done in normal rats, which do not capture the innate pathology of either schizophrenia or bipolar disorder," Kapur added. "Moreover, because the mechanism(s) of these drug effects remain unknown, further studies are required, and one should be cautious in drawing clinical inferences. Nevertheless, our study demonstrates a new and powerful model system for further investigation of the effects of psychotropic drug treatment on brain morphology."

Source: Science Daily

May 8, 2012

Researchers at the Medical Research Council (MRC) Toxicology Unit at the University of Leicester have identified a major pathway leading to brain cell death in mice with neurodegenerative disease. The team was able to block the pathway, preventing brain cell death and increasing survival in the mice.

In human neurodegenerative diseases, including Alzheimer’s, Parkinson’s and prion diseases, proteins “misfold” in a variety of different ways resulting in the build up of misshapen proteins. These form the plaques found in Alzheimer’s and the Lewy bodies found in Parkinson’s disease. 
  
The researchers studied mice with neurodegeneration caused by prion disease, as these mouse models currently provide the best animal representation of human neurodegenerative disorders, where it is known that the build up of misshapen proteins is linked with brain cell death. 
  
They found that the build up of misfolded proteins in the brains of these mice activates a natural defence mechanism in cells, which switches off the production of new proteins. This would normally switch back ‘on’ again, but in these mice the continued build-up of misshapen protein keeps the switch turned ‘off’. This is the trigger point leading to brain cell death, as those key proteins essential for nerve cell survival are not made. 
  
By injecting a protein that blocks the ‘off’ switch of the pathway, the scientists were able to restore protein production, independently of the build up of misshapen proteins, and halt the neurodegeneration. The brain cells were protected, protein levels and synaptic transmission (the way in which brain cells signal to each other) were restored and the mice lived longer, even though only a very small part of their brain had been treated. 
  
Misshapen proteins in human neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, also over-activate this fundamental pathway controlling protein synthesis in the brains of patients, which represents a common target underlying these different clinical conditions. The scientists’ results suggest that treatments focused on this pathway could be protective in a range of neurodegenerative disease in which misshapen proteins are building up and causing neurons to die. 
  
Professor Giovanna Mallucci, who led the team, said: “What’s exciting is the emergence of a common mechanism of brain cell death across a range of different neurodegenerative disorders and activated by the different misfolded proteins in each disease. The fact that in mice with prion disease we were able to manipulate this mechanism and protect the brain cells means we may have a way forward in how we treat other disorders. Instead of targeting individual misfolded proteins in different neurodegenerative diseases, we may be able to target the shared pathways and rescue brain cell degeneration irrespective of the underlying disease.” 
  
Professor Hugh Perry, chair of the MRC’s Neuroscience and Mental Health Board, said: “Neurodegenerative diseases such as Alzheimer’s and Parkinson’s are debilitating and largely untreatable conditions. Alzheimer’s disease and related disorders affect over seven million people in Europe, and this figure is expected to double every 20 years as the population ages across Europe. The MRC believes that research such as this, which looks at the fundamental mechanisms of these devastating diseases, is absolutely vital. Understanding the mechanism that leads to neuronal dysfunction prior to neuronal loss is a critical step in finding ways to arrest disease progression.”

Provided by Medical Research Council 

Source: medicalxpress.com

May 8, 2012

(Medical Xpress) — Having a fat head may not be a bad thing, according to new findings at The Johns Hopkins University. As reported in the February 9 issue of Neuron, Hopkins researchers have made a significant discovery as to how adding fat molecules to proteins can influence the brain circuitry controlling cognitive function, including learning and memory.

“When you learn something, you strengthen and inhibit certain transmissions and sculpt a particular circuit. Recall [or memory] is using that circuit again,” says Richard L. Huganir, Ph.D., professor and director of the Solomon H. Snyder Department of Neuroscience at Johns Hopkins. His team’s latest finding describes for the first time how one protein chemically alters another in this circuit strengthening process and represents another step toward understanding a key part of how memories are made and maintained within the brain, something researchers believe could provide a pathway toward treating disorders like Alzheimer’s and schizophrenia.

In studying the molecular underpinnings of learning and memory, Huganir and his team have focused on one of several processes in which a molecule is tagged by another molecule of fat. Tagging sends the molecules to a particular destination within a cell. Specifically, the team has studied DHHC5, which is known to add a fat molecule to other proteins. Until now it was not known which proteins receive this tag.

The scientists suspected a target molecule would need to bind DHHC5, which would then transfer fat onto it. To determine what DHHC5 could bind, they used it as bait in a large pool of rat brain proteins to fish for those that stuck to DHHC5. Within that pool, DHHC5 bound four different proteins, researchers found. Using a computer program, they compared these with other proteins implicated in learning and memory. All four shared similarity with the brain protein known as GRIP1, mutations of which have been linked to disorders such as autism. The scientists then tested GRIP1 and DHHC5 directly and found that they bound each other as well. Next, they put GRIP1 into human kidney cells, either by itself or with DHHC5, and analyzed each group of cells to see what happened. They found that only the GRIP1 proteins that were added to cells with DHHC5 were tagged with fat. From this they concluded that DHHC5 does indeed tag GRIP1 with fat.

The researchers then wanted to know if this process happens in a brain. However, they needed a way to look into a living cell and be able to tell apart GRIP1 that had a fat tag and GRIP1 that didn’t. They designed two distinct GRIP1 proteins: one permanently tagged with fat, and another mutated so that it could never be tagged. They added color markers to both proteins so they could track them under a microscope, and then added one type or the other to living brain cells. The fat-tagged proteins seemed to form clusters extending to the cell’s edges in a pattern resembling that of cellular recycling-center proteins. The untagged proteins, in contrast, seemed to diffuse around the center of the cell. From this, the team concluded that DHHC5 tags proteins like GRIP1 with fat to send them to be recycled.

According to Huganir, protein recycling is critical for strengthening and maintaining memory circuits. Since GRIP1 is involved with recycling, it may be important in this critical aspect of memory formation. Huganir believes some day researchers could learn how to control this mechanism and reverse the disease process for disorders like Alzheimer’s and schizophrenia.

“Some day we may be able to inhibit or activate these molecules,” Huganir says. “These molecules are involved in mediating everything in the brain, all behaviors.”

Provided by Johns Hopkins University

Source: medicalxpress.com

May 7th, 2012

New research provides the strongest evidence to date that psychopathy is linked to specific structural abnormalities in the brain.

The study, published in Archives of General Psychiatry and led by researchers at King’s College London is the first to confirm that psychopathy is a distinct neuro-developmental sub-group of anti-social personality disorder (ASPD).

Most violent crimes are committed by a small group of persistent male offenders with ASPD. Approximately half of male prisoners in England and Wales will meet diagnostic criteria for ASPD. The majority of such men are not true psychopaths (ASPD-P). They are characterised by emotional instability, impulsivity and high levels of mood and anxiety disorders. They typically use aggression in a reactive way in response to a perceived threat or sense of frustration.

However, about one third of such men will meet additional diagnostic criteria for psychopathy (ASPD+P). They are characterised by a lack of empathy and remorse, and use aggression in a planned way to secure what they want (status, money etc.). Previous research has shown that psychopaths’ brains differ structurally from healthy brains, but until now, none have examined these differences within a population of violent offenders with ASPD.

Dr Nigel Blackwood from the Institute of Psychiatry at King’s and lead author of the study says: ‘Using MRI scans we found that psychopaths had structural brain abnormalities in key areas of their ‘social brains’ compared to those who just had ASPD. This adds to behavioural and developmental evidence that psychopathy is an important subgroup of ASPD with a different neurobiological basis and different treatment needs.

‘There is a clear behavioural difference amongst those diagnosed with ASPD depending on whether or not they also have psychopathy. We describe those without psychopathy as ‘hot-headed’ and those with psychopathy as ‘cold-hearted’. The ‘cold-hearted’ psychopathic group begin offending earlier, engage in a broader range and greater density of offending behaviours, and respond less well to treatment programmes in adulthood, compared to the ‘hot-headed’ group. We now know that this behavioural difference corresponds to very specific structural brain abnormalities which underpin psychopathic behaviour, such as profound deficits in empathising with the distress of others.’

The researchers used Magnetic Resonance Imaging (MRI) to scan the brains of 44 violent adult male offenders diagnosed with Anti-Social Personality Disorder (ASPD). Crimes committed included murder, rape, attempted murder and grievous bodily harm. Of these, 17 met the diagnosis for psychopathy (ASPD+P) and 27 did not (ASPD-P). They also scanned the brains of 22 healthy non-offenders.

The study found that ASPD+P offenders displayed significantly reduced grey matter volumes in the anterior rostral prefrontal cortex and temporal poles compared to ASPD-P offenders and healthy non-offenders. These areas are important in understanding other people’s emotions and intentions and are activated when people think about moral behaviour. Damage to these areas is associated with impaired empathising with other people, poor response to fear and distress and a lack of ‘self-conscious’ emotions such as guilt or embarrassment.

Dr Blackwood explains: ‘Identifying and diagnosing this sub-group of violent offenders with brain scans has important implications for treatment. Those without the syndrome of psychopathy, and the associated structural brain damage, will benefit from cognitive and behavioural treatments. Optimal treatment for the group of psychopaths is much less clear at this stage.’

Source: Neuroscience News

ScienceDaily (May 7, 2012) — Greater purpose in life may help stave off the harmful effects of plaques and tangles associated with Alzheimer’s disease, according to a new study by researchers at Rush University Medical Center.

Greater purpose in life may help stave off the harmful effects of plaques and tangles associated with Alzheimer’s disease, according to a new study. (Credit: © Nejron Photo / Fotolia)

The study is published in the May issue of the Archives of General Psychiatry.

"Our study showed that people who reported greater purpose in life exhibited better cognition than those with less purpose in life even as plaques and tangles accumulated in their brains," said Patricia A. Boyle, PhD.

"These findings suggest that purpose in life protects against the harmful effects of plaques and tangles on memory and other thinking abilities. This is encouraging and suggests that engaging in meaningful and purposeful activities promotes cognitive health in old age."

Boyle and her colleagues from the Rush Alzheimer’s Disease Center studied 246 participants from the Rush Memory and Aging Project who did not have dementia and who subsequently died and underwent brain autopsy. Participants received an annual clinical evaluation for up to approximately 10 years, which included detailed cognitive testing and neurological exams.

Participants also answered questions about purpose in life, the degree to which one derives meaning from life’s experiences and is focused and intentional. Brain plaques and tangles were quantified after death. The authors then examined whether purpose in life slowed the rate of cognitive decline even as older persons accumulated plaques and tangles.

While plaques and tangles are very common among persons who develop Alzheimer’s dementia (characterized by prominent memory loss and changes in other thinking abilities), recent data suggest that plaques and tangles accumulate in most older persons, even those without dementia. Plaques and tangles disrupt memory and other cognitive functions.

Boyle and colleagues note that much of the Alzheimer’s research that is ongoing seeks to identify ways to prevent or limit the accumulation of plaques and tangles in the brain, a task that has proven quite difficult. Studies such as the current one are needed because, until effective preventive therapies are discovered, strategies that minimize the impact of plaques and tangles on cognition are urgently needed.

"These studies are challenging because many factors influence cognition and research studies often lack the brain specimen data needed to quantify Alzheimer’s changes in the brain," Boyle said. "Identifying factors that promote cognitive health even as plaques and tangles accumulate will help combat the already large and rapidly increasing public health challenge posed by Alzheimer’s disease."

The Rush Memory and Aging Project, which began in 1997, is a longitudinal clinical-pathological study of common chronic conditions of aging. Participants are older persons recruited from about 40 continuous care retirement communities and senior subsidized housing facilities in and around the Chicago Metropolitan area. More than 1,500 older persons are currently enrolled in the study.

Source: Science Daily

ScienceDaily (May 7, 2012) — Antipsychotic medications are increasingly prescribed in the US, but they can cause serious side effects including rapid weight gain, especially in children. In the first study of its kind, researchers at Zucker Hillside Hospital and the Feinstein Institute for Medical Research identified a gene that increases weight gain in those treated with commonly-used antipsychotic drugs.

These findings were published in the May issue of Archives of General Psychiatry.

Second-generation antipsychotics (SGAs) were used as the treatment in this study. SGAs are commonly used to treat many psychotic and nonpsychotic disorders. However, it is important to note that these SGAs are associated with substantial weight gain, including the development of obesity and other cardiovascular risk factors. The weight gain side effect of SGAs is significant because it often results in a reduced life expectancy of up to 30 years in those who suffer from chronic and severe mental illnesses. The weight gain also prompts some to stop taking the medication, adversely impacting their quality of life.

In this genome-wide association study (GWAS), researchers first evaluated a group of pediatric patients in the US being treated for the first time with antipsychotics. They then replicated the result in three independent groups of patients who were in psychiatric hospitals in the United States and Germany or participating in European antipsychotic drug trials. The gene that was identified to increase weight gain, MC4R or melanocortin 4 receptor, has been previously identified as being linked to obesity and type 2 diabetes. In the new study, it was found that patients gained up to 20 pounds when on treatment.

"This study offers the prospect of being able to identify individuals who are at greatest risk for severe weight gain following antipsychotic treatment," said Anil Malhotra, MD, investigator at the Zucker Hillside Hospital Department of Psychiatry Research and Feinstein Institute for Medical Research. "We hope that those who are at risk could receive more intensive or alternative treatment that would reduce the potential for weight gain and we are currently conducting studies to identify such treatment."

Additional Details About the Study

Researchers conducted the first GWAS of SGA-induced weight gain in patients carefully monitored for medication adherence who were undergoing initial treatment with SGAs. To confirm results, they next assessed three independent replication cohorts: 1) a cohort of adult subjects undergoing their first treatment with a single SGA (clozapine), 2) a cohort of adult subjects treated with the same SGAs as in our discovery sample, and 3) a cohort of adult subjects in the first episode of schizophrenia and enrolled in a randomized clinical trial of antipsychotic drugs. The discovery cohort consisted of 139 pediatric patients undergoing first exposure to SGAs. The 3 additional cohorts consisted of 73, 40, and 92 subjects. Patients in the discovery cohort were treated with SGAs for 12 weeks. Additional cohorts were treated for 6 and 12 weeks.

This GWAS yielded 20 single-nucleotide polymorphisms at a single locus exceeding a statistical threshold of P10-5. This locus, near the melanocortin 4 receptor (MC4R) gene, overlaps a region previously identified by large-scale GWAS of obesity in the general population. Effects were recessive, with minor allele homozygotes gaining extreme amounts of weight during the 12-week trial. These results were replicated in 3 additional cohorts, with rs489693 demonstrating consistent recessive effects; meta-analysis revealed a genome-wide significant effect. Moreover, consistent effects on related metabolic indices, including triglyceride, leptin, and insulin levels were observed.

Source: Science Daily

ScienceDaily (May 7, 2012) — Depressive symptoms that are present in midlife or in late life are associated with an increased risk of developing dementia, according to a report in the May issue of Archives of General Psychiatry, a JAMA Network publication.

Nearly 5.3 million individuals in the United States have Alzheimer disease (AD) and the resulting health care costs in 2010 were roughly $172 billion, the authors write as background information in the study. “Prevalence and costs of AD and other dementias are projected to rise dramatically during the next 40 years unless a prevention or a cure can be found. Therefore, it is critical to gain a greater understanding of the key risk factors and etiologic underpinnings of dementia from a population-based perspective,” the authors write.

Deborah E. Barnes, Ph.D., M.P.H., of the University of California, San Francisco and the San Francisco Veterans Affairs Medical Center, and colleagues evaluated data from 13,535 long-term Kaiser Permanente members and examined depressive symptoms assessed in midlife (1964-1973) and in late life (1994-2000) and risks of developing dementia, Alzheimer disease (AD) and vascular dementia (VaD; dementia resulting from brain damage from impaired blood flow to the brain).

Depressive symptoms were present in 14.1 percent of study participants in midlife only, 9.2 percent in late life only and 4.2 percent in both. During six years of follow-up, 22.5 percent of patients were diagnosed with dementia; 5.5 percent with Alzheimer disease and 2.3 percent with VaD.

When examining AD and VaD separately, patients with late-life depressive symptoms had a two-fold increase in AD risk, and patients with midlife and late-life symptoms had more than a three-fold increase in VaD risk.

"Our findings suggest that chronic depression during the life course may be etiologically associated with an increased risk of dementia, particularly VaD, whereas depression that occurs for the first time in late life is likely to reflect a prodromal stage of dementia, in particular AD," the authors conclude.

Source: Science Daily

ScienceDaily (May 7, 2012) — The deletion of part of a gene that plays a role in the synthesis of carnitine — an amino acid derivative that helps the body use fat for energy — may play a role in milder forms of autism, said a group of researchers led by those at Baylor College of Medicine and Texas Children’s Hospital.

"This is a novel inborn error of metabolism," said Dr. Arthur Beaudet, chair of molecular and human genetics at BCM and a physician at Texas Children’s Hospital, and the senior author of the report that appears online in the Proceedings of the National Academy of Sciences. "How it is associated with the causes of autism is as yet unclear. However, it could point to a means of treatment or even prevention in some patients."

Deletion leads to imbalance

Beaudet and his international group of collaborators believe the gene deletion leads to an imbalance in carnitine in the body. Meat eaters receive about 75 percent of their carnitine from their diet. However, dietary carnitine levels are low in vegetarians and particularly in vegans. In most people, levels of carnitine are balanced by the body’s ability to manufacture its own carnitine in the liver, kidney and brain, starting with a modified form of the amino acid lysine.

Carnitine deficiency has been identified when not enough is absorbed through the diet or because of medical treatments such as kidney dialysis. Genetic forms of carnitine deficiency also exist, which are caused when too much carnitine is excreted through the kidneys.

In this new inborn error, there is a deletion in the second exon — the protein-coding portion of a gene — of the TMLHE gene, which includes the genetic code for the first enzyme in the synthesis of carnitine (TMLHE stands for trimethyllysine epsilon which encodes the enzyme trimethyllysine dioxygenase).

Studies in the laboratory that identified the deletion were led by Dr. Patricia B.S. Celestino-Soper, as a graduate student in Beaudet’s laboratory at BCM, and by Dr. Sara Violante, a graduate student in the laboratory of Dr. Frédéric M. Vaz of the Academic Medical Center in Amsterdam.

Frequency of deletion

To determine the frequency of the gene deletion, Beaudet and his colleagues tested male autism patients who were the only people with the disorder in their families (simplex families) from the Simons Simplex Collection, the South Carolina Early Autism Project and Houston families. In collaboration with laboratories and researchers in Nashville, Los Angeles, Paris, New York, Toronto and Cambridge (United Kingdom), they tested affected male siblings in families with more than one male case of autism (multiplex families).

When they looked at the TMLHE genes in males affected by autism and compared them to normal controls, they found that the gene alteration is a fairly common one, occurring in as many as one in 366 males unaffected by autism. It was not significantly more common in males within families in which there is only one person with autism. However, it is nearly three times more common in families with two or more boys with autism.

No syndromic form

Beaudet said most of the affected males with the deletion did not have syndromic autism that is frequently associated with other serious diseases. In many instances, syndromic autism affects physical development as well as cognitive, which is reflected in their facial features as well as other parts of their bodies. None of the six boys affected with autism (where information was available) had the syndromic form of disease. Their intelligence quotients and cognitive scores varied, with some being far below normal and others normal.

"Most of the males we identified with the TMLHE deficiency were apparently normal as adults," said Beaudet, although detailed information on learning and behavior was not available on these "control" males. "The gene deletion is neither necessary nor sufficient in itself to cause autism."

"TMLHE deficiency itself is likely to be a weak risk factor for autism, but we need to do more studies to replicate our results," Beaudet said. He estimated that at the rates found in his study, the deficiency might be a factor in about 170 males born with autism per year in the United States. This would equate to about one-half of one percent of autism cases.

The authors from Amsterdam found major increases in some carnitine-related chemicals and absence of others in both urine and plasma. These metabolic alterations were found to be predictive of the dysfunction of the TMLHE gene and therefore can be used to identify males with this disorder.

It remains uncertain whether TMLHE deficiency is benign or causes autism by affecting the function of neurons through toxic accumulation or deficiency of a variety of chemical metabolites.

"We believe that the most attractive hypothesis at this time is that the increased risk of autism is modified by dietary intake of carnitine from birth through the first few years of life," said Beaudet.

He and his colleagues are undertaking three studies to further their understanding of the TMLHE deficiency. In one, they will attempt to replicate the findings in multiplex families. In a second, they will study carnitine levels in the cerebrospinal fluid of infants with autism — both those who have the gene deficiency and those who do not. In a third study, they plan to begin giving boys under age 5 with autism carnitine or a related supplement and determine whether this improves the behavior of those with the TMLHE deficiency and those without.

Source: Science Daily

ScienceDaily (May 7, 2012) — One of the world’s most important fossils has a story to tell about the brain evolution of modern humans and their ancestors, according to Florida State University evolutionary anthropologist Dean Falk.

Taung surrounded by a juvenile chimp skull and human skull, the latter having a fontanelle and metopic suture. The metopic suture is visible on the frontal lobe of Taung’s endocast. (Credit: CT-based images by M. Ponce de León and Ch. Zollikofer, University of Zurich)

The Taung fossil — the first australopithecine ever discovered — has two significant features that were analyzed by Falk and a group of anthropological researchers. Their findings, which suggest brain evolution was a result of a complex set of interrelated dynamics in childbirth among new bipeds, were published May 7 in the Proceedings of the National Academy of Sciences.

"These findings are significant because they provide a highly plausible explanation as to why the hominin brain might grow larger and more complex," Falk said.

The first feature is a “persistent metopic suture,” or unfused seam, in the frontal bone, which allows a baby’s skull to be pliable during childbirth as it squeezes through the birth canal. In great apes — gorillas, orangutans and chimpanzees — the metopic suture closes shortly after birth. In humans, it does not fuse until around 2 years of age to accommodate rapid brain growth.

The second feature is the fossil’s endocast, or imprint of the outside surface of the brain transferred to the inside of the skull. The endocast allows researchers to examine the brain’s form and structure.

After examining the Taung fossil, as well as huge numbers of skulls belonging to apes and humans, as well as corresponding 3-D CT (three-dimensional computed tomographic) scans, and taking into account the fossil record for the past 3 million years, Falk and her colleagues noted three important findings: The persistent metopic suture is an adaptation for giving birth to babies with larger brains; is related to the shift to a rapidly growing brain after birth; and may be related to expansion in the frontal lobes.

"The persistent metopic suture, an advanced trait, probably occurred in conjunction with refining the ability to walk on two legs," Falk said. "The ability to walk upright caused an obstretric dilemma. Childbirth became more difficult because the shape of the birth canal became constricted while the size of the brain increased. The persistent metopic suture contributes to an evolutionary solution to this dilemma."

The later fusion of the metopic suture is most likely an adaptation of hominins who walked upright to be able to more easily give birth to babies with relatively large brains. The unfused seam is also related to the shift to rapidly growing brains after birth, an advanced human-like feature as compared to apes.

"The later fusion was also associated with evolutionary expansion of the frontal lobes, which is evident from the endocasts of australopithecines such as Taung," Falk said.

The Taung fossil, which is estimated to be around 2½ million years old, was discovered in 1924 in Taung, South Africa. It became the “type specimen,” or main model, of the genus Australopithecus africanus when it was announced in 1925.

An australopithecine is any species of the extinct generaAustralopithecus or Paranthropus that lived in Africa, walked on two legs and had relatively small brains.

Source: Science Daily

May 7, 2012

A study on a handful of people with suspected mild Alzheimer’s disease (AD) suggests that a device that sends continuous electrical impulses to specific “memory” regions of the brain appears to increase neuronal activity. Results of the study using deep brain stimulation, a therapy already used in some patients with Parkinson’s disease and depression, may offer hope for at least some with AD, an intractable disease with no cure.

"While our study was designed mainly to establish safety, involved only six people and needs to be replicated on a larger scale, we don’t have another treatment for AD at present that shows such promising effects on brain function," said the study’s first author, Gwenn Smith, Ph.D., a professor in the Department of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine. The research, published in the Archives of Neurology, was conducted while Smith was on the faculty at the University of Toronto, and will be continuing at Toronto, Hopkins and other U.S. sites in the future. The study was led by Andres M. Lozano, chairman of the Department of Neurosurgery at the University of Toronto.

One month and one year after implanting a device that allows for continuous electrical impulses to the brain, Smith and her colleagues performed PET scans that detect changes in brain cells’ metabolism of glucose, and found that patients with mild forms of AD showed sustained increases in glucose metabolism, an indicator of neuronal activity. The increases, the researchers say, were larger than those found in patients who have taken the drugs currently marketed to fight AD progression. Other imaging studies have shown that a decrease in glucose metabolism over the course of a year is typical in AD. Alzheimer’s disease cannot be precisely diagnosed by brain biopsies until after death.

The team observed roughly 15 percent to 20 percent increases in glucose metabolism after one year of continuous stimulation. The increases were observed, to a greater extent, in patients with better outcomes in cognition, memory and quality of life. In addition, the stimulation increased connectivity in brain circuits associated with memory.

Deep brain stimulation (DBS) requires surgical implantation of a brain pacemaker, which sends electrical impulses to specific parts of the brain. For the study, surgeons implanted a tiny electrode able to deliver a low-grade electrical pulse close to the fornix, a key nerve tract in brain memory circuits. The researchers — most with the University of Toronto — reported few side effects in the six subjects they tested. Just as importantly, says Smith, was seeing that DBS appeared to reverse the downturn in brain metabolism that typically comes with AD.

AD is a progressive and lethal dementia that mostly strikes the elderly. It affects memory, thinking and behavior. Estimates vary, but experts suggest that as many as 5.1 million Americans may have AD and that, as baby boomers age, prevalence will skyrocket. Smith says decades of research have yet to lead to clear understanding of its causes or to successful treatments that stop progression.

The trial of DBS came about, Smith reports, when Lozano used DBS of the fornix to treat an obese man. The procedure, designed to target the regions of the brain involved in appetite suppression, unexpectedly had significant increases in his memory. Inspired, the scientists persisted through rigorous ethical and scientific approvals before their AD phase I safety study could begin.

Smith, who also is director of the Division of Geriatric Psychiatry and Neuropsychiatry at Johns Hopkins Bayview Medical Center, is an authority on mapping the brain’s glucose metabolism in aging and psychiatric disease. It was Smith’s earlier analysis of AD patients’ PET scans that revealed their distinct pattern of lowered brain metabolism. She determined that specific parts of the temporal and parietal cerebral cortex — memory network areas of the brain where AD’s earliest pathology surfaces— became increasingly sluggish with time.

Provided by Johns Hopkins Medical Institutions

Source: medicalxpress.com

ScienceDaily (May 7, 2012) — Badly controlled diabetes are known to affect the brain causing memory and learning problems and even increased incidence of dementia, although how this occurs is not clear. But now a study in mice with type 2 diabetes has discovered how diabetes affects a brain area called hippocampus causing memory loss, and also how caffeine can prevent this. 

Curiously, the neurodegeneration that Rodrigo Cunha  from the Centre for Neuroscience and Cell Biology of the University of Coimbra in Portugal see caused by diabetes is the same that occurs at the first stages of several neurodegenerative diseases, including Alzheimer’s and Parkinson’s, suggesting that caffeine (or drugs with similar mechanism) could help them too.

 Type 2 diabetes (which accounts for about 90%of all diabetic cases) is a full blown public health disaster – 285 million people affected worldwide (6.4% of the world population) with numbers expected to almost double by 2030. And this without counting pre-diabetic individuals. The problem is that the disease is triggered by obesity, sedentary lifestyle and bad eating habits (although there is also a genetic predisposition), all of which are increasingly widespread. 

Diabetes is caused by high levels of sugar in the blood, and in type 2 this occurs because the body becomes increasingly resistant to insulin –the hormone that allows the cells to take the sugar from the blood to use it as “fuel” – resulting in toxic high levels of sugar  in the blood that damage nerves and blood vessels and, with time, cause severe complications

 In the study out now in the journal PLoS , João Duarte, Rodrigo Cunha and colleagues take advantage of a new mouse model of diabetes type 2, which, like humans, develops the disease in adults as result of a high-fat diet, to look at one of the least understood complications of diabetes – the disease effect on the brain, more specifically, on memory. They also investigate a possible protective effect by caffeine as this psychostimulant has been suggested to prevent memory loss in a series of neurodegenerative diseases, maybe even in diabetes, although how this happens is not known. And when we consider that coffee is the world leading beverage right after water, with about 500 billion cups consumed annually, this, if true, needs to be better understood.

With that aim  the Portuguese researchers compared four groups of mice - diabetic or normal animals without or with caffeine (equivalent to 8 cups of coffee a day) in their water – to find that long-term consumption of caffeine not only diminished the weight gain and the high levels of blood sugar typical of diabetes, but also prevented the mice’s memory loss (diabetic animals had significantly poorer memory than normal ones). This confirmed that caffeine could, in fact, protect against diabetes as well as prevent memory impairment, probably by interfering with the neurodegeneration caused by toxic sugar levels.

To investigate this, next, the researchers looked at a brain region linked to memory and learning, which is often atrophied in diabetics, called hippocampus. And in fact, diabetic mice had abnormalities in this area showing synaptic degeneration (synapses are the structures at the end of each neuron used to communicate between neurons) and astrogliosis (an abnormal increase of the cells that surround neurons normally as result of the deathof nearby neurons). Both phenomena are known to affect memory and caffeine consumption  prevented the abnormalities.

But to be able to develop drugs based on caffeine’s protective effect, it was necessary to understand its molecular mechanisms. So next the researchers looked at the only brain molecules known to respond to caffeine – the adenosine receptors A1R and A2AR - in the hippocampus. And here, A2AR seemed to be the key for caffeine’s memory rescue since its density - which increases with noxious insults - was high in diabetic animals but normal in those treated with caffeine. This agrees with the previous studies that showed that A2AR inhibition protected against synaptic degeneration and memory dysfunction.

In conclusion, Duarte and Cunha’s work – using an animal model of diabetes type 2 that closely mimics the human form of the disease – suggests that diabetes affects memory by causing synaptic degeneration, astrogliosis and increased levels of A2AR. The study indicates as well that chronic consumption of caffeine can prevent the neurodegeneration and the memory impairment. And this not only in diabetes, since synaptic degeneration and astrogliosis are both part of a cascade of events common to several neurodegenerative diseases, suggesting that caffeine (or similar drugs) could help them too through the same mechanisms.

So does this means that we should drink eight cups of coffee a day to prevent memory loss in old age or diabetes? 

Not really as Rodrigo Cunha, the team leader explains: “Indeed, the dose of caffeine shown to be effective is just too excessive. All we can take from here is that a moderate consumption of caffeine should afford a moderate benefit, but still a benefit. Such experimental design is common in pre-clinical studies: in order to highlight a clear benefit, one dramatises the tested doses. But it’s an important first step. Our ultimate goal is the design of a drug more potent and selective (i.e. with less potential side effects) than caffeine itself; animal studies enable us to pinpoint the likely target of caffeine with protective benefits in type 2 diabetes. So now we will be testing chemical derivates of caffeine, which act as selective adenosine A2A receptor antagonists,to try to prevent diabetic encephalopathy. It might turn out to be a therapeutic breakthrough for this devastating disease”. 

And a breakthrough in a disease that is already affecting 6.4% of the population and growing can never come too soon.

Source: Science Daily

ScienceDaily (May 7, 2012) — Elderly people with pre-diabetes and type 2 diabetes suffer from an accelerated decline in brain size and mental capacity in as little as two years according to new research presented at the joint International Congress of Endocrinology/European Congress of Endocrinology in Florence, Italy. 

An Australian research team led by Associate Professor Katherine Samaras (Garvan Institute of Medical Research) found that the aging brain is vulnerable to worsening blood sugar levels even before type 2 diabetes is diagnosable.

While some brain volume loss is a normal part of aging, the researchers found that elderly people with blood sugar levels in flux, as well as type 2 diabetes, lost almost two and a half times more brain volume than their peers over two years. The reduction in size of the frontal lobe — associated with higher mental functions like decision-making, emotional control, and long term memory — has a significant impact on cognitive function and quality of life.

Diabetes is a very common disorder caused by high levels of sugar in the bloodstream. It affects 6.4% (285 million) of the worldwide population and is associated with an increased risk of heart attacks, stroke and damage to the eyes, feet and kidneys. In type 2 diabetes, which accounts for 90% of all cases, insulin — a hormone that allows cells to take sugar from the bloodstream and store it as energy — does not work properly. 344 million people also have pre-diabetes, a condition with mildly elevated blood sugar levels that gives them a 50% risk of developing the disease over ten years.

This research — a follow-up of 312 participants from the Sydney Memory and Ageing Study — compared MRI scans taken from the beginning and end of a two-year period. The participants were elderly community-dwelling Australians aged between 70 and 90 years old (average age 78, 54% male) and free from dementia. At the start of the study 41% had pre-diabetes and 13% had type 2 diabetes.

At the end of the study the participants were divided into four groups: (1) those with normal, stable glucose levels (102 people); (2) those with stable pre-diabetes (120 people); (3) those whose glucose levels had worsened (57 people); and finally, (4) those with type 2 diabetes from the start (33 people).

The MRI scans showed that the normal group lost an average of 18.4 cm3 total brain volume over two years. In comparison, the stable pre-diabetic group lost 1.4 times more brain volume (26.6 cm3). Both the third group (worsening glucose levels) and fourth group (type 2 diabetes) lost 2.3 times the stable group’s brain volume loss (41.7 cm3 and 42.3 cm3, respectively).

The researchers — using statistical models that accounted for other variables — concluded that a person’s blood sugar status after two years can significantly predict their decline in brain volume.

Associate Professor Katherine Samaras, from the Garvan Institute of Medical Research, said:

"These findings highlight the importance of prevention of diabetes. They also emphasise that, in the elderly, clinicians and allied health professionals need to understand that the complexity of diabetes care needs to accommodate expected declines in cognitive function.

"We need to understand why these changes in cognition and brain size occur. Is it due merely to higher blood sugars? Is the brain subject to the toxic effects of glucose, just as peripheral nerves are? To what extent do other factors associated with diabetes also contribute to the decline in brain size and function, for example inflammation or blood fat levels?

"We also need to learn how we can prevent or deter the negative effects of diabetes on the brain."

Source: Science Daily

ScienceDaily (May 7, 2012) — A Kansas State University graduate student is creating a schoolyard that can become a therapeutic landscape for children with autism.

Chelsey King, master’s student in landscape architecture, St. Peters, Mo., is working with Katie Kingery-Page, assistant professor of landscape architecture, to envision a place where elementary school children with autism could feel comfortable and included.

"My main goal was to provide different opportunities for children with autism to be able to interact in their environment without being segregated from the rest of the school," King said. "I didn’t want that separation to occur."

The schoolyard can be an inviting place for children with autism, King said, if it provides several aspects: clear boundaries, a variety of activities and activity level spaces, places where the child can go when overstimulated, opportunities for a variety of sensory input without being overwhelming and a variety of ways to foster communication between peers.

"The biggest issue with traditional schoolyards is that they are completely open but also busy and crowded in specific areas," King said. "This can be too overstimulating for a person with autism."

King researched ways that she could create an environment where children with autism would be able to interact with their surroundings and their peers, but where they could also get away from overstimulation until they felt more comfortable and could re-enter the activities.

"Through this research, I was able to determine that therapies and activities geared toward sensory stimulation, cognitive development, communication skills, and fine and gross motor skills — which traditionally occur in a classroom setting — could be integrated into the schoolyard," King said.

King designed her schoolyard with both traditional aspects — such as a central play area — and additional elements that would appeal to children with autism, including:

* A music garden where children can play with outdoor musical instruments to help with sensory aspects.

* An edible garden/greenhouse that allows hands-on interaction with nature and opportunities for horticulture therapy.

* A sensory playground, which uses different panels to help children build tolerances to difference sensory stimulation.

* A butterfly garden to encourage nature-oriented learning in a quiet place.

* A variety of alcoves, which provide children with a place to get away when they feel overwhelmed and want to regain control.

King created different signs and pictures boards around these schoolyard elements, so that it was easier for children and teachers to communicate about activities. She also designed a series of small hills around the central play areas so that children with autism could have a place to escape and watch the action around them.

"It is important to make the children feel included in the schoolyard without being overwhelmed," King said. "It helps if they have a place — such as a hill or an alcove — where they can step away from it and then rejoin the activity when they are ready.

King and Kingery-Page see the benefits of this type of schoolyard as an enriching learning environment for all children because it involves building sensory experience and communication.

"Most children spend seven to nine hours per weekday in school settings," Kingery-Page said. "Designing schoolyards that are educational, richly experiential, with potentially restorative nature contact for children should be a community concern."

The researchers collaborated with Jessica Wilkinson, a special education teacher who works with children with autism. King designed her schoolyard around Amanda Arnold Elementary School, which is the Manhattan school district’s magnet school for children with autism.

"Although there are no current plans to construct the schoolyard, designing for a real school allowed Chelsey to test principles synthesized from literature against the actual needs of an educational facility," Kingery-Page said. "Chelsey’s interaction with the school autism coordinator and school principal has grounded her research in the daily challenges of elementary education for students with autism."

Source: Science Daily

May 7, 2012

Many of us love massages, but imagine a massage so deep that tissues, organs and cells could also be ‘massaged’.

That’s exactly what Vibroacoustic Therapy, a low frequency sound massage, is clinically proven to do, and new research at U of T suggests that it may help people with debilitating diseases.

“It is basically stimulating the body with very low sound – like sitting on a subwoofer,” said Professor Lee Bartel of the Faculty of Music.  “But it requires special speakers that carry sound almost too low to hear in a way that changes it basically to something you feel instead of hear.”

Bartel and his team in the new Music and Health Research Collaboratory (MaHRC) are exploring the medical effects of low frequency sound and have shown that this therapy can play a key role in reducing the symptoms of Parkinson’s disease.

Vibroacoustic therapy (VAT) consists of low sound frequencies that are transmitted to the body and mind through special transducers that convert the sound to inner body massage. MaHRC associates Heidi Ahonen and Quincy Almeida treated two groups of Parkinson’s patients (20 with dominant tremor symptoms and 20 with slow/rigid movement symptoms) with five minutes of 30 Hz vibration.

Both groups showed improvements in all symptoms, including less rigidity and better walking speed with bigger steps and less tremor.

“There have been several studies using vibration from sound with Parkinson’s,” said Bartel   “It has been known for over 100 years that vibration (like riding in a wagon on cobblestones) helped relieve some symptoms. So the scientific study of the effect of low frequency sound was a natural connection. Also known is that 40 Hz brain waves seem to be carriers of information between the parts of the brain that control movement. So adding extra stimulation in that zone should help that communication and so assist in movement control.”

Bartel, Founding and Acting Director of MaHRC, says the goal of low frequency sound studies with Parkinson’s is to determine which approach is most effective, how much and how often treatment is needed, and whether medication can be reduced. Vibroacoustic Therapy frequencies, between 20 and 100 Hz or pulses per second, correspond to brainwave activities and function that are currently being explored in neuroscience. 

But the effects of Vibroacoustic Therapy extend beyond the brain. It also provides deep physical cellular stimulation to skin, muscles and joints, resulting in decreased pain and increased mobility. Like hand/mechanical massage, vibroacoustic therapy aids circulation, relaxes muscles, and feels good.

Bartel points to research that shows that “several medical conditions including Parkinson’s and neuralgic pain like fibromyalgia, may be related to a common brain mechanism – a brain rhythm disorientation between the inner brain and the outer cortex. Since the rhythmic pulses of music can drive and stabilize these, we speculate that low frequency sound might help in fibromyalgia as well as Parkinson’s.”

Bartel’s team is now looking at the role of vibroacoustic therapy as a treatment for patients with fibromyalgia.

“Although it is too early to form any conclusions, there is encouraging data indicating that treating fibromyalgia patients with doses of 40 Hz sound seems to reduce pain.” 

“It is truly an exciting time for music medicine – the idea of developing audioceuticals (prescribable sound) points to a whole new direction for music therapy, and the potential for MaHRC to lead in this is very exciting for me” said Bartel.      

Provided by University of Toronto

Source: medicalxpress.com

May 6, 2012

Gaining access to the inner workings of a neuron in the living brain offers a wealth of useful information: its patterns of electrical activity, its shape, even a profile of which genes are turned on at a given moment. However, achieving this entry is such a painstaking task that it is considered an art form; it is so difficult to learn that only a small number of labs in the world practice it.

Researchers at MIT and the Georgia Institute of Technology have developed a way to automate a process called whole-cell patch clamping, which involves bringing a tiny hollow glass pipette in contact with the cell membrane of a neuron, then opening up a small pore in the membrane to record the electrical activity within the cell. Credit: Sputnik Animation and MIT McGovern Institute

But that could soon change: Researchers at MIT and the Georgia Institute of Technology have developed a way to automate the process of finding and recording information from neurons in the living brain. The researchers have shown that a robotic arm guided by a cell-detecting computer algorithm can identify and record from neurons in the living mouse brain with better accuracy and speed than a human experimenter.

The new automated process eliminates the need for months of training and provides long-sought information about living cells’ activities. Using this technique, scientists could classify the thousands of different types of cells in the brain, map how they connect to each other, and figure out how diseased cells differ from normal cells.

The project is a collaboration between the labs of Ed Boyden, associate professor of biological engineering and brain and cognitive sciences at MIT, and Craig Forest, an assistant professor in the George W. Woodruff School of Mechanical Engineering at Georgia Tech.

"Our team has been interdisciplinary from the beginning, and this has enabled us to bring the principles of precision machine design to bear upon the study of the living brain," Forest says. His graduate student, Suhasa Kodandaramaiah, spent the past two years as a visiting student at MIT, and is the lead author of the study, which appears in the May 6 issue of Nature Methods.

The method could be particularly useful in studying brain disorders such as schizophrenia, Parkinson’s disease, autism and epilepsy, Boyden says. “In all these cases, a molecular description of a cell that is integrated with [its] electrical and circuit properties … has remained elusive,” says Boyden, who is a member of MIT’s Media Lab and McGovern Institute for Brain Research. “If we could really describe how diseases change molecules in specific cells within the living brain, it might enable better drug targets to be found.”

Read More →

May 6, 2012 

Brain networks may avoid traffic jams at their busiest intersections by communicating on different frequencies, researchers at Washington University School of Medicine in St. Louis, the University Medical Center at Hamburg-Eppendorf and the University of Tübingen have learned.

"Many neurological and psychiatric conditions are likely to involve problems with signaling in brain networks," says co-author Maurizio Corbetta, MD, the Norman J. Stupp Professor of Neurology at Washington University. "Examining the temporal structure of brain activity from this perspective may be especially helpful in understanding psychiatric conditions like depression and schizophrenia, where structural markers are scarce."

The research will be published May 6 in Nature Neuroscience.

Scientists usually study brain networks — areas of the brain that regularly work together — using magnetic resonance imaging, which tracks blood flow. They assume that an increase in blood flow to part of the brain indicates increased activity in the brain cells of that region.

"Magnetic resonance imaging is a useful tool, but it does have limitations," Corbetta says. "It only allows us to track brain cell activity indirectly, and it is unable to track activity that occurs at frequencies greater than 0.1 hertz, or once every 10 seconds. We know that some signals in the brain can cycle as high as 500 hertz, or 500 times per second."

For the new study, conducted at the University Medical Center at Hamburg-Eppendorf, the researchers used a technique called magnetoencephalography (MEG) to analyze brain activity in 43 healthy volunteers. MEG detects very small changes in magnetic fields in the brain that are caused by many cells being active at once. It can detect these signals at rates up to 100 hertz.

"We found that different brain networks ticked at different frequencies, like clocks ticking at different speeds," says lead author Joerg Hipp, PhD, of the University Medical Center at Hamburg-Eppendorf and the University of Tübingen, both in Germany.

For example, networks that included the hippocampus, a brain area critical for memory formation, tended to be active at frequencies around 5 hertz. Networks constituting areas involved in the senses and movement were active between 32 hertz and 45 hertz. Many other brain networks were active at frequencies between eight and 32 hertz. These “time-dependent” networks resemble different airline route maps, overlapping but each ticking at a different rate.

"There have been a number of fMRI studies of depression and schizophrenia showing ‘spatial’ changes in the organization of brain networks," Corbettta says. "MEG studies provide a window into a much richer ‘temporal’ structure. In the future, this might offer new diagnostic tests or ways to monitor the efficacy of interventions in these debilitating mental conditions."

Provided by Washington University School of Medicine

Source: medicalxpress.com

ScienceDaily (May 4, 2012) — Researchers in Spain have found that at least some of the individuals claiming to see the so-called aura of people actually have the neuropsychological phenomenon known as “synesthesia” (specifically, “emotional synesthesia”). This might be a scientific explanation of their alleged ability.

New research suggests that at least some of the individuals claiming to see the so-called aura of people actually have the neuropsychological phenomenon known as “synesthesia” (specifically, “emotional synesthesia”). This might be a scientific explanation of their alleged ability. (Credit: © Nikki Zalewski / Fotolia)

In synesthetes, the brain regions responsible for the processing of each type of sensory stimuli are intensely interconnected. Synesthetes can see or taste a sound, feel a taste, or associate people or letters with a particular color.

The study was conducted by the University of Granada Department of Experimental Psychology Óscar Iborra, Luis Pastor and Emilio Gómez Milán, and has been published in the journal Consciousness and Cognition. This is the first time that a scientific explanation has been provided for the esoteric phenomenon of the aura, a supposed energy field of luminous radiation surrounding a person as a halo, which is imperceptible to most human beings.

In basic neurological terms, synesthesia is thought to be due to cross-wiring in the brain of some people (synesthetes); in other words, synesthetes present more synaptic connections than “normal” people. “These extra connections cause them to automatically establish associations between brain areas that are not normally interconnected,” professor Gómez Milán explains. New research suggests that many healers claiming to see the aura of people might have this condition.

The case of the "Santón de Baza"

One of the University of Granada researchers remarked that “not all ‘healers’ are synesthetes, but there is a higher prevalence of this phenomenon among them. The same occurs among painters and artists, for example.” To carry out this study, the researchers interviewed some synesthetes including a ‘healer’ from Granada, “Esteban Sánchez Casas,” known as"El Santón de Baza".

Many local people attribute “paranormal powers” to El Santón, because of his supposed ability to see the aura of people “but, in fact, it is a clear case of synesthesia,” the researchers explained. According to the researchers, El Santón has face-color synesthesia (the brain region responsible for face recognition is associated with the color-processing region); touch-mirror synesthesia (when the synesthete observes a person who is being touched or is experiencing pain, s/he experiences the same); high empathy (the ability to feel what other person is feeling), and schizotypy (certain personality traits in healthy people involving slight paranoia and delusions). “These capacities make synesthetes have the ability to make people feel understood, and provide them with special emotion and pain reading skills,” the researchers explain.

In the light of the results obtained, the researchers remarked on the significant “placebo effect” that healers have on people, “though some healers really have the ability to see people’s ‘auras’ and feel the pain in others due to synesthesia.” Some healers “have abilities and attitudes that make them believe in their ability to heal other people, but it is actually a case of self-deception, as synesthesia is not an extrasensory power, but a subjective and ‘adorned’ perception of reality,” the researchers state.

Source: Science Daily

May 5, 2012 

In an effort to identify the underlying causes of neurological disorders that impair motor functions such as walking and breathing, UCLA researchers have developed a novel system to measure the communication between stem cell-derived motor neurons and muscle cells in a Petri dish.

The study provides an important proof of principle that functional motor circuits can be created outside of the body using stem cell-derived neurons and muscle cells, and that the level of communication, or synaptic activity, between the cells could be accurately measured by stimulating motor neurons with an electrode and then measuring the transfer of electrical activity into the muscle cells to which the motor neurons are connected.

When motor neurons are stimulated, they release neurotransmitters that depolarize the membranes of muscle cells, allowing the entry of calcium and other ions that cause them to contract. By measuring the strength of this activity, one can get a good estimation of the overall health of motor neurons. That estimation could shed light on a variety of neurodegenerative diseasessuch as spinal muscular atrophy and amyotrophic lateral sclerosis, or Lou Gehrig’s disease, in which the communication between motor neurons and muscle cells is thought to unravel, said study senior author Bennett G. Novitch, an assistant professor of neurobiology and a scientist with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

The findings of the study appear May 4, 2012 in PLoS ONE, a peer-reviewed journal of the Public Library of Science.

"Now that we have this method to measure the strength of the communications between motor neurons and muscle cells, we may be able to begin exploring what happens in the earliest stages of motor neuron disease, before neuronal death becomes prevalent," Novitch said. "This can help us to pinpoint where things begin to go wrong and provide us with new clues into therapeutic interventions that could improve synaptic communication and promote neuronal survival."

Novitch said the synaptic communication activity his team was able to create and measure using mouse embryonic stem cell-derived motor neurons and muscle cells looks very similar what is seen in a mouse, validating that their model is a realistic representation of what is happening in a living organism.

"That gives us a good starting point to try to model what happens in cells that harbor genetic mutations that are associated with neurodegenerative diseases,. To do that, we had to first define an activity profile of normal synaptic communication," he said. "Some research suggests that a breakdown in this communication can be an early indication of disease progression or possibly an initiating event. Neurons that cannot effectively transmit information to muscle cells will eventually withdraw their contacts, causing both the neurons and muscle cells to degenerate over time. Hopefully, we can now create disease models that will allow us to study what is happening."

In this study, Novitch and his team, led by Joy Umbach, an associate professor of molecular and medical pharmacology, used mouse embryonic stem cells to create the motor neurons and previously established lines of muscle precursors to produce muscle fibers. They put both cells together in a Petri dish, and the cells were cultured in such a way to encourage communication. Novitch said the team wanted to see if they would naturally form synaptic contacts and whether or not there was neural transmission between them.

In less than a week, the neurons had reached out to the muscle cells and assembled the protein networks needed for synaptic communication, Novitch said.

To measure the connections between the cells, the scientists used a technique called dual patch clamp recording. Pipettes containing stimulating and recording electrodes are inserted into the membranes of the motor neurons and muscle cells, being careful not to injure them. With this method, they were able send an electrical current into the motor neurons and measure responses in the muscle cells, as well as visualize the muscular contractions.

"The in vitro system developed here might accordingly be expanded to assess the underlying cellular and molecular mechanisms that contribute to this decline in synaptic input to motor neurons," the study states. "Thus, in addition to their utility for helping to answer fundamental biological questions, these co-cultures have clear applications in addressing problems of medical significance."

Going forward, Novitch and his team hope to recreate and confirm the work using human stem cell-derived motor neurons and muscle cells and measure the synaptic communications with newly developed optical recording methods, which are less invasive than the patch clamp techniques used in this study.

Provided by University of California, Los Angeles

Source: medicalxpress.com

ScienceDaily (May 3, 2012) — Malfunctioning single proteins can cause disruptions in neuronal junctions leading to autistic forms of behavior. A current study, published in the scientific journal Nature, comes to this conclusion after examining genetically altered mice.

The study, in which scientists from Charité — Universitätsmedizin Berlin and the NeuroCure Cluster of Excellence contributed, thus supports the hypothesis that disruptions in neuronal junctions, i.e. synapses, could be the cause of the development of neuropsychiatric illnesses like autism. The international research team, that included scientists from Ulm University and the Institut Pasteur in Paris, ascribes a key role to the excitatory synapses. This finding could become an important step stone for future autism therapies.

Nerve cells communicate with each other via signal transmission to synaptic junctions. These junctions are stabilized through structural proteins, including the so-called ProSAP1/Shank2 protein. In order to understand the role that this protein has on synapses and ultimately in the development of autism, the researchers genetically modified mice and disabled the relevant protein. The choice of this protein was not arbitrary: In preparation for the current study, a number of the scientists involved found evidence that the mutation of this protein can lead to autism in humans. Various neuronal developmental disorders manifested through distinctive social and communicative behavioral features, as well as stereotyped behaviors are combined under the term of “autism.”

The absence of this structural protein in the mouse model also had visible implications: Animals with the mutated gene are hyperactive and demonstrate compulsive repetitions of particular features — like grooming, for example. In behavioral experiments, peculiarities in social and communicative interaction also become distinct. In the brains of the mice, researchers found noticeable mutations of synaptic junctions — specifically in excitatory synapses. When glutamate transmitters bind to glutamate receptors located at these junctions, the nerve cells become excitatory. If the mouse is lacking this structural protein, the transmitters increasingly find a related structural protein on the excitatory synapses, the ProSAP2/Shank3. This protein has also been implicated in the development of autism. At the same time, the composition of glutamate receptors mutates.

But what happens when this related structural protein in the mice is switched off? This is also examined in the study presented. The conclusion is that, in this case as well, mutations of the excitatory synapses occur. Obviously, both structural molecules alternate in fulfilling regular functions. “The study illustrates the significant role glutamatergic systems play in autism and thus contributes to understanding better synaptic changes in autism,” reports Stephanie Wegener, one of the participating scientists at Charité Berlin. The study is therefore an important part of the essential scientific foundation needed to develop possible therapies for autism.

Source: Science Daily

ScienceDaily (May 3, 2012) — The problems of living with bipolar have been well documented, but a new study by Lancaster University has captured the views of those who also report highly-valued, positive experiences of living with the condition.

Researchers at Lancaster’s Spectrum Centre, which is dedicated to the study of bipolar disorder, interviewed and recorded their views of ten people with a bipolar diagnosis, aged between 24 and 57. Participants in the study reported a number of perceived benefits to the condition ranging from to sharper senses to increased productivity.

The research was designed to explore growing evidence that some people with bipolar value their experiences and in some cases would prefer not to be without the condition.

Participants described a wide range of experiences and internal states that they believed they felt to a far greater intensity than those without the condition. These included increased perceptual sensitivity, creativity, focus and clarity of thought.

Some held (or had previously held) high functioning professional jobs or had been studying for higher level qualifications. They described in detail how they experienced times when tasks that are usually quite difficult or time consuming, would feel incredibly easy and the ability to achieve at a high level during these times was clearly immensely rewarding.

Others expressed the view that they felt ‘lucky’ or even ‘blessed’ to have the condition.

Alan, (not his real name) one of the interviewees, said: “It’s almost as if it opens up something in the brain that isn’t otherwise there, and I see colour much more vividly than I used to……So I think that my access to music and art are something for which I’m grateful to bipolar for enhancing. It’s almost as if it’s a magnifying glass that sits between that and myself.”

Researchers even found some people with bipolar reaped positive experiences from their lows such as greater empathy with the suffering of others.

Dr Fiona Lobban, who led the study, said: “Bipolar Disorder is generally seen as a severe and enduring mental illness with serious negative consequences for the people with this diagnosis and their friends and family. For some people this is very much the case. Research shows that long term unemployment rates are high, relationships are marred by high levels of burden on family and friends and quality of life is often poor. High rates of drug and alcohol misuse are reported for people with this diagnosis and suicide rates are twenty times that of the general population.

"However, despite all these factors researchers and clinicians are aware that that some aspects of bipolar experiences are also highly valued by some people. We wanted to find out what these positive experiences were.

"People were very keen to take part in this study and express views which some felt had to be hidden from the medical profession.

"It is really important that we learn more about the positives of bipolar as focusing only on negative aspects paints a very biased picture that perpetuates the view of bipolar as a wholly negative experience. If we fail to explore the positives of bipolar we also fail to understand the ambivalence of some people towards treatment."

Rita Long from Stockport was not part of the study but can identify with its findings. She was 40 when she was diagnosed with the condition but from her school days she was aware that she experienced the world differently to her twin sister.

"We were making Christmas cakes at school and I was so interested and excited by it and my sister says she remembers watching me and thinking, ‘I really wish I could get that excited about making a Christmas cake’. I noticed things, experienced them with a different level of intensity, we’d be on a walk and I’d be saying look at the colour of this, and my sister would be saying, ‘It’s just a berry’. Socially too, people with bipolar can be quite quick witted, humorous. Until much later in life I just presumed those things were part of my personality.

"I don’t want to underestimate how difficult the bad times can be that some people go through with bipolar but at the same time I feel very passionate about the positives. If we are going to move on as a society — in academia, in business, in entertainment — we need people who will push boundaries. People with bipolar can do that."

Source: Science Daily

ScienceDaily (May 3, 2012) — A team led by scientists at The Scripps Research Institute has shown that an extra copy of a brain-development gene, which appeared in our ancestors’ genomes about 2.4 million years ago, allowed maturing neurons to migrate farther and develop more connections.

A team led by Scripps Research Institute scientists has found evidence that, as humans evolved, an extra copy of a brain-development gene allowed neurons to migrate farther and develop more connections. (Credit: Photo courtesy of The Scripps Research Institute)

What genetic changes account for the vast behavioral differences between humans and other primates? Researchers so far have catalogued only a few, but now it seems that they can add a big one to the list. A team led by scientists at The Scripps Research Institute has shown that an extra copy of a brain-development gene, which appeared in our ancestors’ genomes about 2.4 million years ago, allowed maturing neurons to migrate farther and develop more connections.

Surprisingly, the added copy doesn’t augment the function of the original gene, SRGAP2, which makes neurons sprout connections to neighboring cells. Instead it interferes with that original function, effectively giving neurons more time to wire themselves into a bigger brain.

"This appears to be a major example of a genomic innovation that contributed to human evolution," said Franck Polleux, a professor at The Scripps Research Institute. "The finding that a duplicated gene can interact with the original copy also suggests a new way to think about how evolution occurs and might give us clues to human-specific developmental disorders such as autism and schizophrenia."

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ScienceDaily (May 3, 2012) — UCSF scientists have identified patterns of brain activity in the rat brain that play a role in the formation and recall of memories and decision-making. The discovery, which builds on the team’s previous findings, offers a path for studying learning, decision-making and post-traumatic stress syndrome.

Brain patterns through which the rats see rapid replays of past experiences are fundamental to their ability to make decisions. Disturbing those particular brain patterns impaired the animals’ ability to learn rules based on memories of things that had happened in the past. (Credit: © Oleg Kozlov / Fotolia)

The researchers previously identified patterns of brain activity in the rat hippocampus, a brain region critical for memory storage. The patterns sometimes represented where an animal was in space, and, at other times, represented fast-motion replays of places the animal had been, but no one knew whether these patterns indicated the process of memory formation and recollection.

In the journal Science this week (online May 3, 2012), the UCSF researchers demonstrated that the brain activity is critical for memory formation and recall. Moreover, they showed that the brain patterns through which the rats see rapid replays of past experiences are fundamental to their ability to make decisions. Disturbing those particular brain patterns impaired the animals’ ability to learn rules based on memories of things that had happened in the past.

"We think these memory-replay events are central to understanding how the brain retrieves past experiences and uses them to make decisions," said neuroscientist Loren Frank, PhD, a associate professor of physiology and a member of the Keck Center for Integrative Neuroscience at UCSF, who led the research with Shantanu Jadhav, PhD, a post-doctoral fellow. "They offer insight into how a past experience can have such a profound effect on how we think and feel."

The finding gives scientists a new way to investigate fundamental processes like learning and decision-making in animals and in people. It also may help shed light on memory disorders like post-traumatic stress disorder (PTSD), which is characterized by strong, disturbing and uncontrolled memories.

Without Links to the Past, Rats Face Indecision

Seeking to understand how the recall of specific memories in the brain guides our thinking, Frank and his colleagues built a system for detecting the underlying patterns of neuronal activity in rats. They fitted the animals with electrodes and built a system that enabled them to detect a specific pattern, called a sharp-wave ripple, in the hippocampus. Whenever they detected a ripple, they would send a small amount of electricity into another set of electrodes that would immediately interrupt the ripple event, in effect turning off all memory replay activity without otherwise affecting the brain.

The UCSF researchers knew that these sharp-wave ripples would be activated when the animals had to make choices about which direction to turn as they wended their way toward their reward: a few drops of sweetened condensed milk. These signals seem to be flashes of memory recall, said Frank, a rat’s past knowledge flooding back to inform it on what had happened in the past and where it might go in the future. Squashing the sharp-wave ripples, the UCSF team found, disrupted the recall and subverted the rat’s ability to correctly navigate the maze.

This shows, said Frank, that the sharp-wave ripples are critical for this type of memory recall. Through these brain waves, the rat reprocesses and replays old experiences in a fleeting instant — lessons from the past essential for shaping their perception of the present.

"We think these memory replay events are a fundamental constituent of memory retrieval and play a key role in human perspective and decision-making as well," he said. "These same events have been seen in memory tasks in humans, and now we know they are critical for memory in rats. We think that these fast-forward replays make up the individual elements of our own memories, which jump rapidly from event to event."

Next, the team wants to tease out information about how the rats actually use these memory replay events to make decisions and how amplifying or blocking specific replay events will change the way an animal learns and remembers. They also think that these events could be important for understanding memory problems, as when stressful memories intrude into daily life.

Source: Science Daily

May 3, 2012

Under some conditions, the brains of embryonic chicks appear to be awake well before those chicks are ready to hatch out of their eggs. That’s according to an imaging study published online on May 3 in Current Biology, a Cell Press publication, in which researchers woke chick embryos inside their eggs by playing loud, meaningful sounds to them. Playing meaningless sounds to the embryos wasn’t enough to rouse their brains.

This image shows an X-ray computed-tomography image of the chicken embryo skeleton inside an egg, which shows the developmental stage, together with a positron emission tomography image showing nervous system activity in the brain. Balaban et al., publishing in Current Biology, report the activity in chicken embryo brains is inversely related to behavioral activity, with different sleep-like states emerging for the first time. Playing meaningful sounds selectively induced patterns of embryonic brain activity similar to awake, post-hatching animals. Image 3D rendering by Carmen García-Villalba. Credit: Balaban et al. Current Biology

The findings may have implications not only for developing chicks and other animals, but also for prematurely born infants, the researchers say. Pediatricians have worried about the effects of stimulating brains that are still under construction, especially as modern medicine continues to push back the gestational age at which preemies can reliably survive.

"This work showed that embryo brains can function in a waking-like manner earlier than previously thought—well before birth," said Evan Balaban of McGill University. "Like adult brains, embryo brains also have neural circuitry that monitors the environment to selectively wake the brain up during important events."

That waking-like brain activity appears in a latent but inducible state during the final 20 percent of embryonic life, the researchers found. At that point, sleep-like brain activity patterns also emerge.

Before that major dividing line in development—for the first 80 percent of embryonic life— “embryos are in a state that is neither like sleep nor waking,” Balaban said. He suggests it may be useful to compare that state to what happens when people are comatose or under the influence of anesthesia.

This entire line of work was made possible by a new generation of molecular brain imagers developed by Balaban’s coauthors Juan-José Vaquero and Manuel Desco at the Universidad Carlos III in Madrid. Those state-of-the art machines can detect very small amounts of tracer molecules and pinpoint them to a tiny region of the brain (about 0.7 mm, or less than 3/100ths of an inch).

The researchers say they were surprised to capture waking-like activity before birth. And there were other surprises, too. The embryo brains they observed showed considerable variation in activity, for one.

Before the emergence of sleep and waking patterns of brain activity, the chick embryos in their study exhibited lots of spontaneous movement, even as their higher-brain regions remained inactive. Once the chicks reached that 80 percent mark in development, higher-brain regions began crackling with activity. At the same time, those physical movements ceased as the embryos entered a sleep-like state.

"The last 30 percent of fetal brain development is a more interesting time than we previously thought, because it’s when complex whole-brain functions that depend on coordination of widely separated brain areas first emerge," Balaban said. "Embryos begin to cycle through a variety of brain states and are even capable of showing waking-like brain activity."

That might explain instances of complex fetal and early neonatal learning. “It also raises questions about the longer-term developmental consequences that such brain activity may have, if it is induced before intrinsic brain wiring is sufficiently completed,” Balaban said, “for example, in babies born very prematurely. We are excited by the possibility that the techniques developed here can now be used to provide answers to these questions.”

Provided by Cell Press

Source: medicalxpress.com