Novel mechanism uncovered for attention in the brain

Main Category: Neurology / Neuroscience
Article Date: 30 Jul 2013 - 0:00 PDT Current ratings for:
Novel mechanism uncovered for attention in the brain

The ability to pay attention to relevant information while ignoring distractions is a core brain function. Without the ability to focus and filter out "noise," we could not effectively interact with our environment. Despite much study of attention in the brain, the cellular mechanisms responsible for the effects of attention have remained a mystery... until now.

In a study appearing in the journal Nature, researchers from Dartmouth's Geisel School of Medicine and the University of California Davis studied communications between synaptically connected neurons under conditions where subjects shifted their attention toward or away from visual stimuli that activated the recorded neurons. Using this highly sensitive measure of attention's influence on neuron-to-neuron communication, they were able to demonstrate that attention operates at the level of the synapse to improve sensitivity to incoming signals, sharpen the precision of these signals, and selectively boost the transmission of attention-grabbing information while reducing the level of noisy or attention-disrupting information.

The results point to a novel mechanism by which attention shapes perception by selectively altering presynaptic weights to highlight sensory features among all the noisy sensory input.

"While our findings are consistent with other reported changes in neuronal firing rates with attention, they go far beyond such descriptions, revealing never-before tested mechanisms at the synaptic level," said study co-author Farran Briggs, PhD, assistant professor of Physiology and Neurobiology at the Geisel School of Medicine.

In addition to expanding our understanding of brain, this study could help people with attention deficits resulting from brain injury or disease, possibly leading to improved screening and new treatments.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our neurology / neuroscience section for the latest news on this subject.

For more information about this study, please click here.

The research was supported by grants from the National Institute of Health's (NIH) National Eye Institute (grant #s EY18683 to F.B., EY013588 to W.M.U.) and from NIH's National Institute of Mental Health (grant # MH055714 to G.R.M.). Funding support also provided to G.R.M. and W.M.U from the National Science Foundation (grant #s BCS-0727115 and 1228535).

The Geisel School of Medicine at Dartmouth

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New approach for studying deadly brain cancer

Main Category: Cancer / Oncology
Also Included In: Neurology / Neuroscience
Article Date: 25 Jul 2013 - 1:00 PDT Current ratings for:
New approach for studying deadly brain cancer

Human glioblastoma multiforme, one of the most common, aggressive and deadly forms of brain cancer, is notoriously difficult to study. Scientists have traditionally studied cancer cells in petri dishes, which have none of the properties of the brain tissues in which these cancers grow, or in expensive animal models.

Now a team of engineers has developed a three-dimensional hydrogel that more closely mimics conditions in the brain. In a paper in the journal Biomaterials, the researchers describe the new material and their approach, which allows them to selectively tune up or down the malignancy of the cancer cells they study.

The new hydrogel is more versatile than other 3-D gels used for growing glioma (brain cancer) cells in part because it allows researchers to change individual parameters - the gel's stiffness, for example, or the presence of molecular signals that can influence cancer growth - while minimally altering its other characteristics, such as porosity.

Being able to adjust these traits individually will help researchers tease out important features associated with the initial growth of a tumor as well as its response to clinical therapies, said University of Illinois chemical and biomolecular engineering professor Brendan Harley, who led the study with postdoctoral researcher Sara Pedron and undergraduate student Eftalda Becka. Harley is an affiliate of the Institute for Genomic Biology at Illinois.

The researchers found that they could increase or decrease the malignancy of glioma cells in their hydrogel simply by adding hyaluronic acid, a naturally occurring carbohydrate found in many tissues, especially the brain.

Hyaluronic acid (HA) is a key component of the extracellular matrix that provides structural and chemical support to cells throughout the body. HA contributes to cell proliferation and cell migration, and local changes in HA levels have been implicated in tumor growth.

"Hyaluronic acid is one of the major building blocks in the brain," Harley said. "The structure of a newly forming brain tumor has some of this HA within it, but there's also a lot of the HA in the brain surrounding the tumor."

Previous studies have used hydrogels made out of nothing but hyaluronic acid to study gliomas, Harley said. "The problem there is that HA is structurally not very strong." It also is difficult to adjust the amount of HA that the glioma cells are exposed to if their environment is 100 percent HA, he said.

In the new study, Pedron observed how glioma cells behaved in two different hydrogels - one based on methacrylated gelatin (GelMA) and the other using a more conventional polyethylene glycol (PEG) biomaterial. These two materials vary in one important trait: GelMA is a naturally derived material that contains adhesive sites that allow cells to latch onto it; synthetic PEG does not.

"The purpose of having these two systems was to isolate the effect of HA on glioma cells," Pedron said. If changing HA levels produced different effects in different gels, that would indicate that the gels were contributing to those effects, she said.

Instead, Harley and Pedron found that additions of HA to glioma cells had "very similar" effects in both materials. Adding too little or too much HA led to reduced malignancy, while incorporating just enough HA led to significantly enhanced malignancy. This held true for multiple types of glioblastoma multiforme cells. This suggests that "it's the HA itself that is likely the cause for this malignant change," Harley said.

"If you have a material that allows you to selectively tune up or down malignancy, that will allow you to ask lots of questions about treatment methods for more malignant or less malignant forms of glioma. It also will allow scientists to try to get a response that's closer to what you see in the body," he said.

"If you talk to pathologists, they'll say a biomaterial will never allow you to grow a full brain tumor, which is probably true," Harley said. "But it's realistic to think that a well-designed biomaterial will allow you to study aspects of glioma growth and treatment in a way that's much richer than simply looking in a petri dish and much more accessible than trying to study tumor development within the brain itself."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject.

The U. of I. department of chemical and biomolecular engineering, the Institute for Genomic Biology and the Campus Research Board supported this research.

University of Illinois at Urbana-Champaign

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'Marijuana in adolescence can cause permanent brain damage'

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Article Date: 26 Jul 2013 - 8:00 PDT Current ratings for:
'Marijuana in adolescence can cause permanent brain damage'

New research may give backing to parents telling teens to "just say no." A study in mice from the University of Maryland School of Medicine reveals that regular use of marijuana during adolescence could damage brain function, potentially increasing the risk for schizophrenia and other psychiatric problems.

The study, which was recently published in Neuropsychopharmacology, had scientists examining cortical oscillations - patterns of the brain's neuron activity - in mice. These oscillations become abnormal when schizophrenia or other psychiatric disorders are present.

Researchers exposed young mice to low doses of tetrahydrocannabinol (THC), which is the active ingredient present in marijuana, for 20 days. Then the mice were returned to their family to continue developing.

When the mice became adults, the scientists discovered that their cortical oscillations were severely modified, and the mice showed signs of impaired cognitive functions.

Sylvina Mullins Raver from the University of Maryland says: "The striking finding is that, even though the mice were exposed to very low drug doses, and only for a brief period during adolescence, their brain abnormalities persisted into adulthood."

Interestingly, the researchers originally set out to test a hypothesis that marijuana use effects cortical oscillations in adults. But when they repeated the experiment on adult mice who had never been exposed to the drug previously, they found that both the oscillations and cognitive behavior stayed normal.

So, it appears that adolescence is the period of development when marijuana use can take its biggest toll. Senior author Dr. Asaf Keller adds:

"We looked at the different regions of the brain. The back of the brain develops first, and the frontal parts of the brain develop during adolescence.

We found that the frontal cortex is much more affected by the drugs during adolescence. This is the area of the brain that controls executive functions, such as planning and impulse control. It is also the area most affected in schizophrenia."

Now that marijuana has been legalized in 19 US states and the District of Columbia, the study's results about long-term effects of marijuana use are particularly relevant. The authors point to controversy spanning back to 20 years ago about whether or not marijuana use can cause permanent damage and contribute to psychiatric disorders.

Dr. Keller adds: "There is likely a genetic susceptibility, and then you add marijuana during adolescence and it becomes the trigger."

The research team will continue to study the changes in cortical oscillations with a view to potentially reverse the effects some day.

"We are hoping we will learn more about schizophrenia and other psychiatric disorders, which are complicated conditions," Dr. Keller says.

Written by Marie Ellis

Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today Visit our alcohol / addiction / illegal drugs section for the latest news on this subject.

“Adolescent Cannabinoid Exposure Permanently Suppresses Cortical Oscillations in Adult Mice,” Sylvina M Raver, Sarah P Haughwout and Asaf Keller, Neuropsychopharmacology, doi:10.1038/npp.2013.164, published online 4 July 2013.

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Key brain circuits identified that control compulsive drinking in rats

Main Category: Alcohol / Addiction / Illegal Drugs
Article Date: 24 Jul 2013 - 1:00 PDT Current ratings for:
Key brain circuits identified that control compulsive drinking in rats

A research team led by scientists from the Ernest Gallo Clinic and Research Center at the University of California, San Francisco has identified circuitry in the brain that drives compulsive drinking in rats, and likely plays a similar role in humans.

The scientists found they could reduce compulsive drinking in rats by inhibiting key neural pathways that run between the prefrontal cortex, which is involved with higher functions such as critical thinking and risk assessment, and the nucleus accumbens, a critical area for reward and motivation.

The authors noted that there are already several FDA-approved medications that target activity in these pathways, thus potentially opening an accelerated track to new treatments for compulsive drinking.

The study describing their finding was published online recently in Nature Neuroscience.

The study was conducted on rats that regularly drank 20 percent alcohol. The rats drank both unmixed alcohol and alcohol mixed with extremely bitter quinine, said senior investigator F. Woodward Hopf, PhD, an assistant adjunct professor of neurology at UCSF.

Hopf explained that this alcohol-quinine solution, which he described as "like a vodka tonic without the sugar," is often used as a rodent model of compulsive drinking, or "drinking in the face of negative consequences." In rats, he said, the negative consequence is the bitter taste, while in humans who drink compulsively, "the negative consequences are profound: people continue to drink despite the potential loss of jobs, marriages, freedom, even their lives."

In the United States, alcoholism is estimated to cost $224 billion per year - almost $2 per drink - mostly from lost productivity and crime, and leads to 100,000 preventable deaths per year.

The drinking rats showed a notable increase in the NMDA receptor (NMDAR), which lead author Taban Seif, PhD, a Gallo Center researcher, called "a molecule that excites the brain." When the rats were injected with an NMDAR blocker, their consumption of quinine-laced alcohol dropped significantly, while regular alcohol use was unaffected. "In other words, only the compulsive drinking was affected," said Seif.

The team then focused its research on connections from two specific regions of the rats' prefrontal cortex where they had discovered the presence of unusual types of NMDARs: the medial prefrontal cortex, which mediates conflict during decision-making, and the insula, which is critical for self-awareness and feelings. "In a non-addict, these brain areas tell you when something is potentially harmful and bad, and to run away as fast as possible," said Hopf. "But if you're a compulsive drinker, it seems instead that they give you a comforting pat on the back, in effect telling you it's OK to have another drink, nothing to worry about."

Using a technique called optogenetics, the scientists inserted halorhodopsin, a light-sensitive protein, into these areas. They then used fiber-optic cables implanted in the rats' brains to send pulses of laser light that activated the halorhodopsin, which in turn inhibited the regions' connections to the nucleus accumbens. The researchers found that rats inhibited in this way drank significantly less quinine-laced alcohol, while their intake of regular alcohol solution remained unaffected.

"The fact that we reduced the rats' compulsive drinking using two different methods - an NMDAR blocker and direct inhibition of connections - tells us that we have probably identified the right areas," said Hopf.

The next logical step for the research team, said Hopf, would be to work with clinical researchers on an NMDAR blocker trial in human subjects.

"What is interesting is that we have a new drug which could perhaps treat compulsive aspects of drinking," said Hopf, "but only if you are in conflict about your drinking - if you care. Any therapy with NMDAR blockers would need a strong behavioral and cognitive component to make sure the patient stayed mentally engaged."

Seif and Hopf also plan further experimental studies focusing on how the insula drives behavior and connects to other areas of the brain.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our alcohol / addiction / illegal drugs section for the latest news on this subject.

Co-authors of the paper are Shao-Ju Chang, Jeffrey A Simms, Stuart L. Gibb, PhD, and Jahan Dadgar of the Gallo Center; Billy T. Chen, PhD, and Brandon K. Harvey of the National Institute on Drug Abuse; Dorit Ron, PhD, of the Gallo Center and UCSF; Robert O. Messing, MD, of the Gallo Center and UCSF at the time of the research and currently of the University of Texas at Austin; and Antonello Bonci, MD, of the Gallo Center, UCSF and the Johns Hopkins University, Baltimore, MD.

The study was supported by funds from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse and the State of California through UCSF.

University of California - San Francisco

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Key brain circuits identified that control compulsive drinking in rats

Main Category: Alcohol / Addiction / Illegal Drugs
Article Date: 24 Jul 2013 - 1:00 PDT Current ratings for:
Key brain circuits identified that control compulsive drinking in rats

A research team led by scientists from the Ernest Gallo Clinic and Research Center at the University of California, San Francisco has identified circuitry in the brain that drives compulsive drinking in rats, and likely plays a similar role in humans.

The scientists found they could reduce compulsive drinking in rats by inhibiting key neural pathways that run between the prefrontal cortex, which is involved with higher functions such as critical thinking and risk assessment, and the nucleus accumbens, a critical area for reward and motivation.

The authors noted that there are already several FDA-approved medications that target activity in these pathways, thus potentially opening an accelerated track to new treatments for compulsive drinking.

The study describing their finding was published online recently in Nature Neuroscience.

The study was conducted on rats that regularly drank 20 percent alcohol. The rats drank both unmixed alcohol and alcohol mixed with extremely bitter quinine, said senior investigator F. Woodward Hopf, PhD, an assistant adjunct professor of neurology at UCSF.

Hopf explained that this alcohol-quinine solution, which he described as "like a vodka tonic without the sugar," is often used as a rodent model of compulsive drinking, or "drinking in the face of negative consequences." In rats, he said, the negative consequence is the bitter taste, while in humans who drink compulsively, "the negative consequences are profound: people continue to drink despite the potential loss of jobs, marriages, freedom, even their lives."

In the United States, alcoholism is estimated to cost $224 billion per year - almost $2 per drink - mostly from lost productivity and crime, and leads to 100,000 preventable deaths per year.

The drinking rats showed a notable increase in the NMDA receptor (NMDAR), which lead author Taban Seif, PhD, a Gallo Center researcher, called "a molecule that excites the brain." When the rats were injected with an NMDAR blocker, their consumption of quinine-laced alcohol dropped significantly, while regular alcohol use was unaffected. "In other words, only the compulsive drinking was affected," said Seif.

The team then focused its research on connections from two specific regions of the rats' prefrontal cortex where they had discovered the presence of unusual types of NMDARs: the medial prefrontal cortex, which mediates conflict during decision-making, and the insula, which is critical for self-awareness and feelings. "In a non-addict, these brain areas tell you when something is potentially harmful and bad, and to run away as fast as possible," said Hopf. "But if you're a compulsive drinker, it seems instead that they give you a comforting pat on the back, in effect telling you it's OK to have another drink, nothing to worry about."

Using a technique called optogenetics, the scientists inserted halorhodopsin, a light-sensitive protein, into these areas. They then used fiber-optic cables implanted in the rats' brains to send pulses of laser light that activated the halorhodopsin, which in turn inhibited the regions' connections to the nucleus accumbens. The researchers found that rats inhibited in this way drank significantly less quinine-laced alcohol, while their intake of regular alcohol solution remained unaffected.

"The fact that we reduced the rats' compulsive drinking using two different methods - an NMDAR blocker and direct inhibition of connections - tells us that we have probably identified the right areas," said Hopf.

The next logical step for the research team, said Hopf, would be to work with clinical researchers on an NMDAR blocker trial in human subjects.

"What is interesting is that we have a new drug which could perhaps treat compulsive aspects of drinking," said Hopf, "but only if you are in conflict about your drinking - if you care. Any therapy with NMDAR blockers would need a strong behavioral and cognitive component to make sure the patient stayed mentally engaged."

Seif and Hopf also plan further experimental studies focusing on how the insula drives behavior and connects to other areas of the brain.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our alcohol / addiction / illegal drugs section for the latest news on this subject.

Co-authors of the paper are Shao-Ju Chang, Jeffrey A Simms, Stuart L. Gibb, PhD, and Jahan Dadgar of the Gallo Center; Billy T. Chen, PhD, and Brandon K. Harvey of the National Institute on Drug Abuse; Dorit Ron, PhD, of the Gallo Center and UCSF; Robert O. Messing, MD, of the Gallo Center and UCSF at the time of the research and currently of the University of Texas at Austin; and Antonello Bonci, MD, of the Gallo Center, UCSF and the Johns Hopkins University, Baltimore, MD.

The study was supported by funds from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse and the State of California through UCSF.

University of California - San Francisco

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Speaker's power to act on words influences listeners' brain response

Main Category: Psychology / Psychiatry
Article Date: 24 Jul 2013 - 14:00 PDT Current ratings for:
Speaker's power to act on words influences listeners' brain response

A speaker's power to act on his words influences how a listener perceives the meaning of their message, according to research published July 24 in the open access journal PLOS ONE by Ina Bornkessel-Schlesewsky from the University of Marburg, Germany, and colleagues from other institutions.

For example, listeners are more likely to believe a political figure is capable of acting on the words "Tear down this wall!" than when an ordinary citizen makes the same statement. In this study, researchers presented participants with videotaped statements about politics spoken by a top political decision-maker, a news anchor or an unknown person. In a second scenario, the same people uttered statements related to general world knowledge. Brain responses to implausible statements about current affairs differed when uttered by a political figure as opposed to the other speakers, but implausible general world knowledge statements led to a similar brain response across all three speakers.

The effects occur rapidly, within 150-450 milliseconds of hearing a statement, and demonstrate that a listener's response to a message is immediately influenced by the social status of the speaker, and whether he or she has the power to bring about the state of affairs described by their words. Bornkessel-Schlesewsky explains, "Every day, we hear statements that surprise us because they do not correspond to what we (think we) know about the world. Our study demonstrates that, in understanding such utterances, our brain rapidly takes into account who said them (e.g. a politician versus our neighbor) and whether he or she in fact has the power to act upon what was said."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our psychology / psychiatry section for the latest news on this subject.

Citation: Bornkessel-Schlesewsky I, Krauspenhaar S, Schlesewsky M (2013) Yes, You Can? A Speaker’s Potency to Act upon His Words Orchestrates Early Neural Responses to Message-Level Meaning. PLoS ONE 8(7): e69173. doi:10.1371/journal.pone.0069173

Financial Disclosure: This work was supported by the Max Planck Society for the Advancement of Science,the Interdisciplinary Research Center for Neuroscience at the Johannes Gutenberg- University Mainz and by the LOEWE programme of the German state of Hesse. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interest Statement: The authors have declared that no competing interests exist.

PLOS ONE

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Rat model reveals that information in brain cells' electrical activity combines memory, environment, and state of mind

Main Category: Neurology / Neuroscience
Article Date: 20 Jul 2013 - 0:00 PDT Current ratings for:
Rat model reveals that information in brain cells' electrical activity combines memory, environment, and state of mind

The information carried by the electrical activity of neurons is a mixture of stored memories, environmental circumstances, and current state of mind, scientists have found in a study of laboratory rats. The findings, which appear in the journal PLoS Biology, offer new insights into the neurobiological processes that give rise to knowledge and memory recall.

The study was conducted by Eduard Kelemen, a former graduate student and post-doctoral associate at the State University of New York (SUNY) Downstate Medical Center, and André Fenton, a professor at New York University's Center for Neural Science and Downstate Medical Center. Kelemen is currently a postdoctoral fellow at University of Tuebingen in Germany.

The idea that recollection is not merely a replay of our stored experiences dates back to Plato. He believed that memory retrieval was, in fact, a much more intricate process - a view commonly accepted by today's cognitive psychologists and couched in the theory of constructive recollection. The theory posits that during memory retrieval, information across different experiences may combine during recall to form a single experience. Such a process may explain the prevalence of false memories. For example, studies have shown that people mistakenly recalled seeing a school bus in a movie if the bus was mentioned after they watched the movie.

In addition, other scholarship has shown that a subject's mindset can also influence the retrieved information. For example, looking at a house from the perspective of a homebuyer or a burglar leads to different recollections - potential purchasers may recall the house's leaky roof while would-be burglars may remember where the jewelry is kept.

But while the psychological contours of retrieval are well-documented, very little is known about the neural activity that underlies this process.

With this in mind, Fenton and Kelemen centered their study on the neurophysiological processes rats employ as they solve problems that require memory retrieval. To do so, they employed techniques developed during the last two decades. These involve monitoring the electrical activity of neurons in the rats' hippocampus - the part of the brain used to encode new memories and retrieve old ones. By spotting certain types of neuronal activity, researchers have historically been able to perform what amounts to a mind reading exercise to decode what the rat is thinking and even comprehend the specifics of the rats' memory retrieval.

In their experiments, Fenton and Kelemen tested the viability of a concept, "cross-episode retrieval" - stimulating the brain activity in a given circumstance that was also activated in a previous, distinctive experience.

"Such cross-episode expression of past activity can create opportunities for generating novel associations and new information that was never directly experienced," the authors wrote.

To test their hypotheses, rats were placed in a stable, circular arena, then in a rotating, circular arena of the same size, followed by a return to the stable arena. In the rotating arena condition, the surface turned slowly, making it necessary for the rat to think about its location either in terms of the rotating floor or in terms of the stationary room.

Overall, the results showed district neural activity between the stable and rotating conditions. However, during the rotating task, the researchers intermittently observed "cross-episode retrieval" - that is, at times, neurons expressed patterns of electrical activity under the rotating-arena condition that were similar to those activity patterns that were used in the stable-arena condition. Notably, cross-episode retrieval occurred more frequently when the angular position of the rotating arena was about to complete a full rotation and return to the same position as in the stable condition, demonstrating that retrieval is influenced by the environment.

To show that cross-episode retrieval was influenced by current state of mind, Fenton and Kelemen took advantage of an earlier finding from their experiments: during the arena rotation, neural activity switches between signaling the rat's location in the stationary room and the rat's location on the rotating arena floor. Cross-episode retrieval was also more likely when neuronal activity represented the position of the rat in the stationary room than when it represented positions that rotate with the arena. This showed that retrieval is influenced by internal cognitive variables that are encoded by hippocampal discharge - i.e., a state of mind.

"These experiments demonstrate novel, key features of constructive human episodic memory in rat hippocampal discharge," explained Fenton, "and suggest a neurobiological mechanism for how experiences of different events that are separate in time can nonetheless comingle and recombine in the mind to generate new information that can sometimes amount to valuable, creative insight and knowledge."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our neurology / neuroscience section for the latest news on this subject.

The study was funded by National Science Foundation grants IOS-0725001 and IOS-1146822.

New York University

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'Rat model reveals that information in brain cells' electrical activity combines memory, environment, and state of mind'

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