Neuroscience

ScienceDaily (Apr. 2, 2012) — Testosterone, the primary male sex hormone, appears to have antidepressant properties, but the exact mechanisms underlying its effects have remained unclear. Nicole Carrier and Mohamed Kabbaj, scientists at Florida State University, are actively working to elucidate these mechanisms.

They’ve discovered that a specific pathway in the hippocampus, a brain region involved in memory formation and regulation of stress responses, plays a major role in mediating testosterone’s effects, according to their new report in Biological Psychiatry.

Compared to men, women are twice as likely to suffer from an affective disorder like depression. Men with hypogonadism, a condition where the body produces no or low testosterone, also suffer increased levels of depression and anxiety. Testosterone replacement therapy has been shown to effectively improve mood.

Although it may seem that much is already known, it is of vital importance to fully characterize how and where these effects are occurring so that scientists can better target the development of future antidepressant therapies.

To advance this goal, the scientists performed multiple experiments in neutered adult male rats. The rats developed depressive-like behaviors that were reversed with testosterone replacement.

They also “identified a molecular pathway called MAPK/ERK2 (mitogen activated protein kinase/ extracellular regulated kinase 2) in the hippocampus that plays a major role in mediating the protective effects of testosterone,” said Kabbaj.

This suggests that the proper functioning of ERK2 is necessary before the antidepressant effects of testosterone can occur. It also suggests that this pathway may be a promising target for antidepressant therapies.

Kabbaj added, “Interestingly, the beneficial effects of testosterone were not associated with changes in neurogenesis (generation of new neurons) in the hippocampus as it is the case with other classical antidepressants like imipramine (Tofranil) and fluoxetine (Prozac).”

In results published elsewhere by the same group, testosterone has shown beneficial effects only in male rats, not in female rats.

Source: Science Daily

ScienceDaily (Apr. 2, 2012) — Why do some persons succumb to post-traumatic stress disorder (PTSD) while others who suffered the same ordeal do not? A new UCLA study sheds light on the answer.

UCLA scientists have linked two genes involved in serotonin production to a higher risk of developing PTSD. Published in the April 3 online edition of the Journal of Affective Disorders, the findings suggest that susceptibility to PTSD is inherited, pointing to new ways of screening for and treating the disorder.

"People can develop post-traumatic stress disorder after surviving a life-threatening ordeal like war, rape or a natural disaster," explained lead author Dr. Armen Goenjian, a research professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA. "If confirmed, our findings could eventually lead to new ways to screen people at risk for PTSD and target specific medicines for preventing and treating the disorder."

PTSD can arise following child abuse, terrorist attacks, sexual or physical assault, major accidents, natural disasters or exposure to war or combat. Symptoms include flashbacks, feeling emotionally numb or hyper-alert to danger, and avoiding situations that remind one of the original trauma.

Goenjian and his colleagues extracted the DNA of 200 adults from several generations of 12 extended families who suffered PTSD symptoms after surviving the devastating 1988 earthquake in Armenia.

In studying the families’ genes, the researchers found that persons who possessed specific variants of two genes were more likely to develop PTSD symptoms. Called TPH1 and TPH2, these genes control the production of serotonin, a brain chemical that regulates mood, sleep and alertness — all of which are disrupted in PTSD.

"We suspect that the gene variants produce less serotonin, predisposing these family members to PTSD after exposure to violence or disaster," said Goenjian. "Our next step will be to try and replicate the findings in a larger, more heterogeneous population."

Affecting about 7 percent of Americans, PTSD has become a pressing health issue for a large percentage of war veterans returning from Iraq and Afghanistan. The UCLA team’s discovery could be used to help screen persons who may be at risk for developing PTSD.

"A diagnostic tool based upon TPH1 and TPH2 could enable military leaders to identify soldiers who are at higher risk of developing PTSD, and reassign their combat duties accordingly," observed Goenjian. "Our findings may also help scientists uncover alternative treatments for the disorder, such as gene therapy or new drugs that regulate the chemicals responsible for PTSD symptoms."

According to Goenjian, pinpointing genes connected with PTSD symptoms will help neuroscientists classify the disorder based on brain biology instead of clinical observation. Psychiatrists currently rely on a trial and error approach to identify the best medication for controlling an individual patient’s symptoms.

Serotonin is the target of the popular antidepressants known as SSRIs, or selective serotonin re-uptake inhibitors, which prolong the effect of serotonin in the brain by slowing its absorption by brain cells. More physicians are prescribing SSRIs to treat psychiatric disease beyond depression, including PTSD and obsessive compulsive disorder.

Source: Science Daily

April 1, 2012

Rutgers scientists think they have found a way to prevent and possibly reverse the most debilitating symptoms of a rare, progressive childhood degenerative disease that leaves children with slurred speech, unable to walk, and in a wheelchair before they reach adolescence.

In today’s online edition of Nature Medicine, Karl Herrup, chair of the Department of Cell Biology and Neuroscience in the School of Arts and Sciences provides new information on why this genetic disease attacks the cerebellum – a part of the brain that controls movement coordination, equilibrium, and muscle tone – and other regions of the brain.

Using mouse and human brain tissue studies, Herrup and his colleagues at Rutgers found that in the brain tissue of young adults who died from ataxia-telangiectasia, or A-T disease, a protein known as HDAC4 was in the wrong place. HDAC4 is known to regulate bone and muscle development, but it is also found in the nerve cells of the brain. The protein that is defective in A-T, they discovered, plays a critical role in keeping HDAC4 from ending up in the nucleus of the nerve cell instead of in the cytoplasm where it belongs. In a properly working nerve cell, the HDAC4 in the cytoplasm helps to prevent nerve cell degeneration; however, in the brain tissue of young adults who had died from A-T disease, the protein was in the nucleus where it attacked the histones – the small proteins that coat and protect the DNA.

"What we have found is a double-edged sword," said Herrup. "While the HDAC4 protein protected a neuron’s function when it was in the cytoplasm, it was lethal in the nucleus."

To prove this point, Rutgers scientists analyzed mice, genetically engineered with the defective protein found in children with A-T, as well as wild mice. The animals were tested on a rotating rod to measure their motor coordination. While the normal mice were able to stay on the rod without any problems for five to six minutes, the mutant mice fell off within 15 to 20 seconds.

After being treated with trichostation A (TSA), a chemical compound that inhibits the ability of HDAC4 to modify proteins, they found that the mutant mice were able to stay on the rotating rod without falling off – almost as long as the normal mice.

Although the behavioral symptoms and brain cell loss in the engineered mice are not as severe as in humans, all of the biochemical signs of cell stress were reversed and the motor skills improved dramatically in the mice treated with TSA. This outcome proves that brain cell function could be restored, Herrup said.

"The caveat here is that we have fixed a mouse brain with less devastation and fewer problems than seen in a child with A-T disease," said Herrup. "But what this mouse data says is that we can take existing cells that are on their way to death and restore their function."

Neurological degeneration is not the only life-threatening effect associated with this genetic disease. A-T disease – which occurs in an estimated 1 in 40,000 births – causes the immune system to break down and leaves children extremely susceptible to cancers such as leukemia or lymphoma. There is no known cure and most die in their teens or early 20s. According to the AT Children’s Project, many of those who die at a young age might not have been properly diagnosed, which may, in fact, make the disease even more common.

Herrup says although this discovery does not address all of the related medical conditions associated with the disease, saving existing brain cells – even those that are close to death – and restoring life-altering neurological functions would make a tremendous improvement in the lives of these children.

"We can never replace cells that are lost," said Herrup. "But what these mouse studies indicate is that we can take the cells that remain in the brains of these children and make them work better. This could improve the quality of life for these kids by unimaginable amounts."

Additionally, Herrup says, the research might provide insight into other neurodegenerative diseases. “If this is found to be true, then the work we’ve done on this rare disease of childhood may have a much wider application in helping to treat other diseases of the nervous system, even those that affect the elderly, like Alzheimer’s,” he said.

Provided by Rutgers University 

Source: medicalxpress.com

March 30th, 2012

A new animal model of nerve injury has brought to light a critical role of an enzyme called Nmnat in nerve fiber maintenance and neuroprotection. Understanding biological pathways involved in maintaining healthy nerves and clearing away damaged ones may offer scientists targets for drugs to mitigate neurodegenerative diseases such as Huntington’s and Parkinson’s, as well as aid in situations of acute nerve damage, such as spinal cord injury.

University of Pennsylvanian biologists developed the model in the adult fruit fly, Drosophila melanogaster.

“We are using the basic power of the fly to learn about how neurons are damaged in acute injury situations,” said Nancy Bonini, senior author of the research and a professor in the Department of Biology at Penn. “Our work indicates that Nmnat may be key.”

The research was published in Current Biology. First author on the study is postdoctoral researcher Yanshan Fang, with additional contributions from postdoctoral researcher Lorena Soares and research technicians Xiuyin Teng and Melissa Geary, all of Penn’s Department of Biology.

When a nerve suffers an acute injury — as might be caused by a penetrating wound, for example, or a broken bone that damages nearby tissues — the long projection of the nerve cell, called the axon, can become injured and degenerate. The process by which it disintegrates is known as Wallerian or Wallerian-like degeneration and is an active, orderly process.

Though this function of eliminating damaged nerve cells is crucial, biologists do not have a clear understanding of all of the molecular signaling pathways that govern the process.

Bonini’s lab has previously focused on chronic neurodegenerative diseases but made this foray into acute nerve injury to determine if mechanistic overlaps exist between acute axon injury and chronic neurodegeneration. They first searched for an appropriate nerve tract to target and identified the wing of adult flies as a prime option.

The fly wing is not only translucent and a site of lengthy nerve fibers that can be easily observed, but it can also be cut to cause injury without killing the fly. That way, the researchers can follow the animal’s response to nerve injury for weeks.

Using various reagents to manipulate the fly’s genetic traits, the team confirmed that the cut wing nerve underwent Wallerian degeneration. They then tested versions of Nmnat and another protein called Wld^S, all of which had previously been shown to protect nerves from degeneration, to see if any of these might stop the process. All significantly delayed neurodegeneration. Even a form of Nmnat that hadn’t worked in other animal models suppressed degeneration, although to a lesser extent.

“That indicates that our assay is really sensitive,” Bonini said. “This sensitivity could help us identify genes that have moderate although important functionality at protecting against nerve degeneration.”

Their investigations into the wing nerve also showed that the degenerating axon “died back,” fragmenting first from the axon terminals, the side farthest from the nerve cell body—a pattern similar to what has been seen in other disorders.

Doing more genetic tinkering, the researchers showed that when the animal’s own Nmnat was depleted, the nerves fragmented in the same way as if the axon was physically cut. And when Nmnat and the other “rescue” proteins were added back to these genetically modified flies, they were able to block degeneration, highlighting that Nmnat is critical to maintaining healthy axons.

In a final set of experiments, the biologists sought to narrow where in the nerve cells Nmnat might be working. They focused on mitochondria, the powerhouses of cells. When they created a genetic line of flies that blocked mitochondria from entering the axon fibers, the nerve tract degenerated, again, in a dying-back fashion. Yet now Wld^S and Nmnat failed to prevent axon degeneration, suggesting that those proteins may act on and require the presence of axonal mitochondria to maintain healthy nerves in normal flies.

Flipping that scenario around, they looked to see what happened to the mitochondria of flies upon nerve injury. When they cut the wing nerve axons, the mitochondria rapidly disappeared. Yet they can largely preserve the mitochrondria by increasing expression of Nmnat.

Their results, taken together with the findings of other studies, suggest that Nmnat may stabilize mitochondria in some way in order to keep axons in a healthy state.

“We have some hope that these proteins or their activity may someday serve as drug targets or could provide the foundation for a therapeutic advance,” Bonini said. “But right now, my hope is that the power of the fly model will open up a lot of new directions of research and new pathways that could be targets for development in the future.”

Source: Neuroscience News

16:55 30 March 2012

Sumit Paul-Choudhury, editor

My Soul, 2005, Katharine Dowson (Image: Image courtesy of the artist and GV Art)

LOOKING at your own brain is a humbling and slightly unnerving experience. Mine, depicted in a freshly acquired MRI scan, is startlingly intricate, compact - and baffling. This is as much of a portrait of my own mind as I am ever likely to see. But to my ignorant eyes (which, by way of an eerie bonus, are now looking at their own cross-sections) it looks pretty much like any other brain.

Apparently a more expert eye wouldn’t help. “Whilst all my participants get very excited about seeing their brain for the first time after being scanned, and I frequently get asked ‘What can you tell me about my brain?’, the reality is that the brain will for a long time yet remain a mysterious mass,” says the neuroscientist who scanned my brain, for research purposes. “We must be content with knowing that the ‘I’ is constructed in its intricacies, but we cannot explain how.”

The hope of closing the gap between the physical and mental is presumably what gets neuroscientists up in the morning, but it’s frustrating for a layperson like me. Avowed materialist though I am, I nonetheless rebel against the knowledge that the impassive blob on screen is “me”.

This cognitive dissonance was what I took with me to the opening of Brains, a new show at London’s Wellcome Collection, whose subtitle, “The Mind as Matter”, suggests that its curators sympathise with my materialist perspective. “The neurosciences hold out the prospect of an objective account of consciousness - the soul or mind as nothing more than intricately connected flesh,” reads the introduction. But the bulk of the exhibition is dedicated to whole brains, brain collectors and anatomical paraphernalia, with little explicit reference to the brain’s fine structure, or how it might give rise to thought.

This remit is less restrictive than it might sound. Evolution has seen to it that the most vital of our bodily organs is well guarded against intrusion, and as a by-product, well hidden from inspection. Even today, only a small minority of the population have seen their own brains - and many (unlike me, thankfully) have done so only when they had reason to be fearful of what they found.

So the history of attempts to access, visualise and understand the brain is a rich one. But it’s also well worn, and some of the historical material - elaborate anatomical models, kooky phrenological busts and grim-looking surgical implements - is over-familiar. The scientific objects are more compelling, albeit they also tend to the grotesque - from the arachnid contraptions used to measure skull size to the spools of finely-sliced mouse-brains on tape.

Much of the fascination lies not in the objects themselves, but in the human stories behind them, told in captions whose straight-facedness sometimes comes across as drollery or clinical detachment. Trepanning tools fashioned from flint and animal teeth “would have taken longer to cut through the skull than more modern instruments”, one informs us drily; the American Anthropometric Society was “basically a club to enable the leading men of US science to dissect each other,” says another.

Secluded in the skull, individual brains develop relatively few distinguishing features save those given them by trauma, disease or rare accidents of birth. So brains of note tend to be associated with tales of misfortune. That’s often the case with anatomical specimens, but what’s remarkable about the brains on display here is how much they overlap with criminality. Some of the most striking have been acquired from people whose wickedness in life was deemed sufficient reason to deny them dignity in death. In other cases, the moral equation is reversed, with collectors stepping outside the bounds of decency in their desire to possess the brain; the abhorrent nadir being reached with the probable murder of “feeble” children by Nazi doctors.

(Image: Science Museum, London)

The collection’s examples of brains being voluntarily donated are equally remarkable. Persuading someone to donate this most personal of organs is a tough sell, and the historical portion of the exhibition makes much of how appeals to ego have persuaded the great and good to offer up their brains for post-mortem examination. More recently, medical study has provided motivation for would-be donors. Particularly poignant is the tale of Anita Newcomb McGee, a female US army surgeon who gave up her nine-month old son’s brain, along with a photograph and a sketch of his head, with the words “I want him to benefit the world in some way if possible.”

But this altruism is tempered by the fact that brains, unlike many of our other “charismatic organs”, cannot conceivably be transplanted. The knowledge that someone else might gain life from my gifted heart is a powerful incentive to donate, but I have less incentive to be generous with my brain - though it would seem that distinction is not made by those who do donate. Perhaps reluctant donors might be won over by the moving photos compiled by artist Ania Dabrowska and social scientist Bronwyn Parry of cheerful would-be donors ranging from an ex-soldier to a headmistress.

And one of the exhibition’s stand-out exhibits might provide further reassurance: a documentary video of anatomists at London’s Hammersmith Hospital painstakingly and precisely slicing donated brains into half-centimetre wedges in near-silence. Or perhaps not. This is well sanctioned, respectful science being conducted on freely donated organs for the betterment of human health and knowledge; and yet it nonetheless provokes one of my fellow spectators into muttering, very much to herself: “Wrong, wrong, wrong”. For myself, I find the video one of the most compelling exhibits — perhaps the only one that prompts me to contemplate offering myself up for more than a non-invasive scan in the service of medical science.

Less clear-cut, for me, are the nearby sections of Einstein’s brain, preserved under deeply dubious circumstances after his death. Clearly, there’s a certain fascination associated with perhaps the most famous brain there ever was; but Einstein’s brain is no more legible than any other, and the slim prospect that scientific insights can be gleaned from its study seems poor recompense for the undignified proxying of a great mind by illicitly-obtained fragments of tissue.

(Image: Wellcome Library, London. Wellcome Images)

The final insult: an accompanying 3D-printed replica of the entire organ, reconstructed for a TV documentary from archive photographs. This absurd resin relic epitomises, for me, the extent to which the objects on display at the Wellcome are imbued with significance by the knowledge that they were once the seats of consciousness. It’s the minds of the audience, rather than the brains on display, that are doing the work.

The Wellcome show confronts its visitors with the gulf between our hard-won knowledge about the form of the brain and our as-yet-meagre understanding of its function, much as my scan did to me. It didn’t narrow the gap between the grey image of my brain and my sense of self; if anything, it widened it. But it did make me appreciate what an amazing gap it is, and marvel anew at the work of those who are seeking to close it.

Brains: The mind as matter is showing at the Wellcome Collection in London until 17 June.

Source: New Scientist

March 30, 2012

A team of neuroscientists from the Institute of Psychiatry (IoP) at King’s College London have developed a digital atlas of the human brain for iPad. The ‘Brain’ App is the first of its kind, and is based on cutting edge neuro-imaging research from the NatBrainLab at the IoP. 

Image taken from the ‘Brain’ Study Room

Dr. Marco Catani, Head of the NatBrainLab who led the development of the App with Dr. Flavio Dell’Acqua and Dr. Michel Thiebaut de Schotten, said: “For 10 years our lab has pioneered the use of highly advanced neuro-imaging techniques. This is the first time that imaging methods usually only applied to research have been used in an educational App. It’s very exciting to see our work transformed into such an accessible, fun and beautiful tool.”

Image taken from the ‘Brain’ Dissection Room

Two types of scans were used to develop the content of ‘Brain’ – results from an MRI scan reveal the structural properties of the brain, and images from a Diffusion Tractography scan allow the user to identify connections in the brain. 

The App is split into two virtual rooms. The Dissection Room allows the user to play with a 3D human brain, select individual structures and ‘pull’ them apart to visualize their anatomical features. The Study Room then offers a more thorough explanation of functional aspects and their relationship to neurological and psychiatric disorders. 

Dr. Catani adds: “The interactive nature of our App really allows you to explore the depths of the neural network and appreciate the complexity of the human brain. Because the content is based directly on research, the finished product is an accurate reflection of the real thing.”

Dr. Catani and his team are now working towards developing the next version of the App. By integrating scans from several different brains into the programme, they hope to be able to offer the user the chance to see directly how the brain develops from childhood to old age and the direct effect of different age-related disorders on the brain.

The App is currently being used by Dr. Catani and his colleagues to teach MSc students neuroscience.

Provided by King’s College London

Source: medicalxpress.com

March 30, 2012

(HealthDay) — Electrocorticography (ECoG) signals from patients with chronic motor dysfunction represent motor information that may be useful for controlling prosthetic arms, according to a study published in the March issue of the Annals of Neurology.

To investigate whether ECoG signals recorded from chronically paralyzed patients and whether those signals can be applied to control a prosthetic, Takufumi Yanagisawa, M.D., Ph.D., of the Osaka University Medical School in Japan, and colleagues recorded ECoG signals from sensorimotor cortices of 12 patients while they attempted to carry out three to five simple hand and elbow movements. Sensorimotor function was normal in five patients, moderately impaired due to central nervous system lesions sparing the cortex in four patients, and severely impaired due to peripheral nervous system lesion or amputation in three patients.

The researchers found that the high gamma power (80 to 150 Hz) of the ECoG signals during movements was responsive to different types of movement and provided the best information for movement classification. In all patients, the classification performance was significantly better than chance, although for patients with severely impaired motor function the differences between ECoG power modulations during different types of movement were significantly fewer. Cortical representations tended to overlap each other in impaired patients. One moderately impaired patient and three non-paralyzed patients successfully controlled a prosthetic arm using the classification method in real time.

"ECoG signals appear useful for prosthetic arm control and may provide clinically feasible motor restoration for patients with paralysis but no injury of the sensorimotor cortex," the authors write.

Abstract

Source: medicalxpress.com

March 30, 2012

An estimated 2.2 million people in the United States live with epilepsy, a complex brain disorder characterized by sudden and often unpredictable seizures. The highest rate of onset occurs in children and older adults, and it affects people of all ethnicities and socio-economic backgrounds, yet this common disorder is widely misunderstood. Epilepsy refers to a spectrum of disorders with seizures that vary in type, cause, severity, and frequency. Many people do not know the causes of epilepsy or what measures to take if they witness a seizure. A new report from the Institute of Medicine highlights numerous gaps in the knowledge and management of epilepsy and recommends actions for improving the lives of those with epilepsy and their families and promoting better understanding of the disorder.

Effective treatments for epilepsy are available but access to treatment and timely referrals to specialized care are often lacking, the report’s expert committee found. Reaching rural and underserved populations, as well as providing state-of-the art care for people with persistent seizures, is particularly crucial. The report’s recommendations for expanding access to patient-centered health care include early identification and treatment of epilepsy and associated health conditions, implementing measures that assess quality of care, and establishing accreditation criteria and processes for specialized epilepsy centers. In addition, the wide variety of health professionals who care for those with epilepsy need improved knowledge and skills to provide the highest quality health care.

Some causes of epilepsy, such as traumatic brain injury, infection, and stroke, are preventable. Prevention efforts should continue for these established risk factors, as well as for recurring seizures in people with epilepsy and depression, and for epilepsy-related causes of death, the report says.

People with epilepsy need additional education and skills to optimally manage their disorder. Consistent delivery of accurate, clearly communicated health information from sources that include health care professionals and epilepsy organizations can better prepare those with epilepsy and their families to cope with the disorder and its consequences, the report says. Accurate, current data on the extent and consequences of epilepsy and its associated health conditions are especially needed to inform policymakers and identify opportunities for reducing the burden of epilepsy.

Living with epilepsy can affect employment, driving ability, and many other aspects of quality of life. The report stresses the importance of improved access to a range of community services, including vocational, educational, transportation, transitional care, and independent living assistance as well as support groups. The committee urged collaboration among federal agencies, state health departments, and relevant epilepsy organizations to improve and integrate these services and programs, particularly at state and local levels.

Misperceptions about epilepsy persist and a focus on raising public awareness and knowledge is needed, the report adds. Educating community members such as teachers, employers, and others on how to manage seizures could help improve public understanding of epilepsy. The report suggests several strategies for stakeholders to improve public knowledge of the disorder, including forming partnerships with the media, establishing advisory councils, and engaging people with epilepsy and their families to serve as advocates and educators within their communities.

Provided by National Academy of Sciences

Source: medicalxpress.com

March 30, 2012

Researchers want to help the Army better camouflage its soldiers and break the enemy’s efforts to hide.

Researchers Jay Hegde and Xing Chen are using functional MRI to look at the brains of study participants learning how to break camouflage in order to help identify soldiers who will be good at it and identify better ways to teach it. Credit: Phil Jones, GHSU Photographer

"We want to make our camouflage unbreakable and we want to break the camouflage of the enemy," said Dr. Jay Hegde, neuroscientist in the Medical College of Georgia at Georgia Health Sciences University.

Hegde and GHSU Postdoctoral Fellow Dr. Xing Chen are using a relatively simple technique they developed to teach civilian volunteers to break camouflage. They flash a series of camouflage pictures on a computer screen, providing about a half second after each to spot, for instance, a face in a sea of mushrooms. A green light signals a correct answer and a red light signals an incorrect answer. The computer-generated images include distractions to make the difficult task even more challenging.

They are finding that an hour of daily training in as little as two weeks results in proficiency for 60 percent of the mostly college and graduate school students who have signed up for their training. The Army’s current approach is taking soldiers into battlefield situations to hone these skills.

As part of a three-year grant from the Office of Army Research, the researchers want to determine which parts of the brain light up when trained snipers break camouflage.

"We need to figure out how the expert camouflage-breakers do it," Hegde said. "We want to figure out what parts of the brain are most responsive when people break camouflage and, a related experiment is what part of the brain changes its response when people learn to break camouflage." Their techniques include functional magnetic resonance imaging to measure blood flow activity as an indicator of brain cell activity.

Figuring out which parts of the brain are involved could give the Army and others a better way to identify future first-rate snipers and objectively assess instructional efforts.

"If you are the Dean of the Army Sniper Corps and want to develop top-notch snipers, you don’t want to spend a year training them before giving up on half of them," Hegde said. A brain scan could help signal whose relevant areas are well developed and, consequently, have natural skill. 

Early evidence points toward two regions of the temporal lobe, found on either side of the brain and known to have a role in speech and vision. A region called the fusiform gyrus – which plays a role in facial recognition and lights up when people become experts at recognizing various objects, such as a particular bird species – may be important in breaking camouflage as well.

Hegde suspects that expertise at breaking camouflage stems from the fusiform gyrus in combination with some other area(s) of the brain. And, because good recognition skills don’t typically translate from one area to another, he also suspects that the parts of the brain involved vary with the object of their attention. For example, the ability to easily recognize the make and model of a car doesn’t guarantee skill at breaking camouflage and Hegde notes that some military snipers aren’t good at game-hunting.

Vision happens when light enters the retina where photoreceptor cells turn it into signals that are interpreted by the brain. “If there is a whole lot of light falling on them, they send a lot of signals, beep, beep, beep,” he said in rapid succession. “If there is a little bit of light they fire slowly.” The brain connects the dots to form a familiar face or landscape. Camouflage complicates the task – the difference between recognizing a mountain goat against a clear blue sky and finding a moth among a pile of fall leaves.

"Here is the beautiful thing that we are finding out: if you know what you are looking for, the next time you can break the camouflage of the moth. Without knowing what you are looking for, the picture also is ambiguous," Hegde said.

Provided by Georgia Health Sciences University

Source: medicalxpress.com

ScienceDaily (Mar. 30, 2012) — Human attention to a particular portion of an image alters the way the brain processes visual cortex responses to that image.

A schematic diagram of the contrast discrimination task, showing the focal cue trial (top row) and the distributed cue trial (bottom row). The contrast within the top right circle increases from the first interval (second column) to the second interval (fourth column). The third column is the interstimulus interval. (Credit: Copyright 2011 Elsevier Inc.)

Our ability to ignore some, but not other stimuli, allows us to focus our attention and improve our performance on a specific task. The ability to respond to visual stimuli during a visual task hinges on altered brain processing of responses within the visual cortex at the back of the brain, where visual information is first received from the eyes. How this occurs was recently demonstrated by an international team of researchers led by Justin Gardner at the RIKEN Brain Science Institute in Wako.

In a contrast discrimination task, the researchers showed three observers a stimulus of a group of four circles, each containing grey and white bars that created stripes of different contrasts. After a short pause, the researchers showed the circles again, but the contrast within one of the circles was different. The observers were instructed to choose which group of circles contained the higher contrast.

In ‘focal cue trials’, an arrow directed the observers’ attention to a particular circle. In ‘distributed cue’ trials’, four arrows directed their attention diffusely, across all four circles. Gardner and colleagues found that the observers’ performance was better in the focal cue trials.

Using a magnetic resonance imaging (MRI) scanner, the research team was able to map the precise location within the visual cortex that was activated by the visual information within each of the four circles. During the contrast discrimination task, Gardner and colleagues could therefore measure the observers’ visual cortex activity elicited by the stimuli. In this way, they could correlate brain activity in the visual cortex with the observers’ attention and their choice of contrasting circles.

Visual cortex responses tended to be largest when the observers were paying attention to a particular target circle, and smallest when they were ignoring a circle. The researchers determined that the largest visual cortex responses to the stimuli guided the eventual choice of each observer, leading to enhanced performance on the visual task.

"We used computational modeling to test various hypotheses about how attention affects brain processing of visual information to improve behavioral performance," explains Gardner. "We concluded that the observers’ attention causes their brains to select the largest cortical response to guide contrast choice, since we found that an ‘efficient selection’ model best explained the behavioral and fMRI data," he says.

If the findings extend to other senses, such as hearing, researchers may begin to understand how humans make sense of a perceptually cluttered world.

Source: Science Daily

ScienceDaily (Mar. 29, 2012) — A type of cell plentiful in the brain, long considered mainly the stuff that holds the brain together and oft-overlooked by scientists more interested in flashier cells known as neurons, wields more power in the brain than has been realized, according to new research published March 29 in Science Signaling.

Human astrocytes. (Credit: Image courtesy of University of Rochester Medical Center)

Neuroscientists at the University of Rochester Medical Center report that astrocytes are crucial for creating the proper environment for our brains to work. The team found that the cells play a key role in reducing or stopping the electrical signals that are considered brain activity, playing an active role in determining when cells called neurons fire and when they don’t.

That is a big step forward from what scientists have long considered the role of astrocytes — to nurture neurons and keep them healthy.

"Astrocytes have long been called housekeeping cells — tending to neurons, nurturing them, and cleaning up after them," said Maiken Nedergaard, M.D., D.M.Sc., professor of Neurosurgery and leader of the study. "It turns out that they can influence the actions of neurons in ways that have not been realized."

Proper brain function relies on billions of electrical signals — tiny molecular explosions, really — happening remarkably in sync. Recalling the face of a loved one, swinging a baseball bat, walking down the street — all those actions rely on electrical signals passed instantly along our nerves like a molecular hot potato from one brain cell to another.

For that to happen, the molecular brew of chemicals like sodium, calcium and potassium that brain cells reside in must be just right — and astrocytes help to maintain that balanced environment. For instance, when a neuron sends an impulse, or fires, levels of potassium surrounding the cell jump dramatically, and those levels must come down immediately for the brain to work properly. Scientists have long known that that’s a job for astrocytes — sopping up excess potassium, ending the nerve pulse, and restoring the cells so they can fire again immediately.

In the paper in Science Signaling, Nedergaard’s team discovered an expanded role for astrocytes. The team learned that in addition to simply absorbing excess potassium, astrocytes themselves can cause potassium levels around the neuron to drop, putting neuronal signaling to a stop.

"Far from only playing a passive role, astrocytes can initiate the uptake of potassium in a way that affects neuronal activity," said Nedergaard. "It’s a simple, yet powerful mechanism for astrocytes to rapidly modulate neuronal activity."

Nedergaard has investigated the secret lives of astrocytes for more than two decades. She has shown how the cells communicate using calcium to signal. Nearly 20 years ago in a paper in Science, she pioneered the idea that glial cells like astrocytes communicate with neurons and affect them. Since then, has been a lot of speculation by other scientists that chemicals call gliotransmitters, such as glutamate and ATP, are key to this process.

In contrast, in the latest research Nedergaard’s team found that another signaling system involving potassium is at work. By sucking up potassium, astrocytes quell the firing of neurons, increasing what scientists call “synaptic fidelity.” Important brain signals are crisper and clearer because there is less unwanted activity or “chatter” among neurons that should not be firing. Such errant neuronal activity is linked to a plethora of disorders, including epilepsy, schizophrenia, and attention-deficit disorder.

"This gives us a new target for a disease like epilepsy, where signaling among brain cells is not as controlled as it should be," said Nedergaard, whose team is based in the Division of Glia Disease and Therapeutics of the Center for Translational Neuromedicine. of the Department of Neurosurgery

The first authors of the paper are Fushun Wang, Ph.D., research assistant professor of Neurosurgery; and graduate student Nathan Anthony Smith. They did much of the work by using a sophisticated laser-based system to monitor the activity of astrocytes in the living brain of rats and mice. The work by Smith, a graduate student in the University’s neuroscience program, was supported by a Kirschstein National Research Service Award from the National Institute of Neurological Disorders and Stroke (NINDS).

Other authors from Rochester include Takumi Fujita, Ph.D., post-doctoral associate; Takahiro Takano, Ph.D., assistant professor; Qiwu Xu, technical associate; and Lane Bekar, Ph.D., formerly research assistant professor, now at the University of Saskatchewan. Also contributing were Akemichi Baba of Hyogo University of Health Sciences in Japan, and Toshio Matsuda of Osaka University in Japan.

Nedergaard notes that the complexity and size of our astrocytes is one of few characteristics that differentiate our brains from rodents. Our astrocytes are bigger, faster, and much more complex in both structure and function. She has found that astrocytes contribute to conditions like stroke, Alzheimer’s, epilepsy, and spinal cord injury.

"Astrocytes are integral to the most sophisticated brain processes," she added.

Source: Science Daily

ScienceDaily (Mar. 29, 2012) — Certain genes and proteins that promote growth and development of embryos also play a surprising role in sending chemical signals that help adults learn, remember, forget and perhaps become addicted, University of Utah biologists have discovered.

This is a microscope image of the roundworm or nematode C. elegans with its nervous system glowing green due to labeling with a green jellyfish protein. (Credit: Penelope Brockie, University of Utah.)

"We found that these molecules and signaling pathways [named Wnt] do not retire after development of the organism, but have a new and surprising role in the adult. They are called back to action to change the properties of the nervous system in response to experience," says biology Professor Andres Villu Maricq, senior author of the new study in the March 30 issue of the journal Cell.

The study was performed in C. elegans — the millimeter-long roundworm or nematode — which has a nervous system that serves as a model for those of vertebrate animals, including humans.

Because other Wnt pathways in worms are known to work in humans too, the researchers believe that Wnt genes, the Wnt proteins they produce and so-called “Wnt signaling” also are involved in human learning, memory and forgetting.

"Almost certainly what we have discovered is going on in our brain as well," Maricq says. And because a worm nerve-signal "receptor" in the study is analogous to a human nicotine receptor involved in addiction, schizophrenia and some other mental disorders, some of the genes identified in the worm study "represent possible new targets for treatment of schizophrenia and perhaps addiction," he adds.

Wnt genes and their proteins already were known to “pattern the development and distribution of organs in the body” during embryo development, and to be responsible for various cancers and developmental defects when mutated, he says.

Maricq conducted the study with these Utah biologists: doctoral students Michael Jensen and Dane Maxfield; postdoctoral researchers Michael M. Francis, Frederic Hoerndli and Rui Wang; undergraduate Erica Johnson; Penelope Brockie, a research associate professor; and David M. Madsen, a senior research specialist.

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March 29, 2012

(Medical Xpress) — Brain stimulation can markedly improve people’s ability to solve highly complex problems, a recent University of Sydney study suggests.

(L-R) Professor Allan Snyder and Richard Chi found brain stimulation helped people solve a puzzle.

The findings by Professor Allan Snyder and Richard Chi, from the University of Sydney, are published in Neuroscience Letters.

"The results suggest non-invasive brain stimulation could assist people in solving tasks that appear straightforward but are inherently difficult," said Professor Snyder.

Our minds have evolved to solve certain problems effortlessly, yet we struggle to solve others that appear simple but require us to apply an unfamiliar paradigm, to ‘think outside the box’.

The famous ‘nine dots puzzle’. Can you join them using only four straight lines without taking your pen off the page?

"As an example we have taken the famous nine dots problem, where you are asked to join all the dots with four straight lines without taking the pen off the page," Professor Snyder said.

"Surprisingly, investigations over the last century show that almost no one can do this."

Now the researchers have shown that more than 40 percent of the people they tested were able to solve the nine dots problem after receiving 10 minutes of safe, non-invasive brain stimulation.

Specifically the left anterior temporal lobe of the brain is inhibited while simultaneously the right anterior temporal lobe is excited, employing a technique known as transcranial direct current stimulation.

Using the same procedure the researchers have previously reported success in amplifying insight and memory.

Chi and Snyder suggest that their unique brain stimulation protocol could ultimately enable people to “escape the tricks our minds impose on us,” as Professor Snyder describes it, and solve tasks that appear deceptively simple.

Provided by University of Sydney

Source: medicalxpress.com

March 29, 2012

The first atlas of the surface of the human brain based upon genetic information has been produced by a national team of scientists, led by researchers at the University of California, San Diego School of Medicine and the VA San Diego Healthcare System. The work is published in the March 30 issue of the journal Science.

This is a genetic clustering map of the brain, left lateral view. Credit: UC San Diego School of Medicine

The atlas reveals that the cerebral cortex – the sheet of neural tissue enveloping the brain – is roughly divided into genetic divisions that differ from other brain maps based on physiology or function. The genetic atlas provides scientists with a new tool for studying and explaining how the brain works, particularly the involvement of genes.

"Genetics are important to understanding all kinds of biological phenomena," said William S. Kremen, PhD, professor of psychiatry at the UC San Diego School of Medicine and co-senior author with Anders M. Dale, PhD, professor of radiology, neurosciences, and psychiatry, also at the UC San Diego School of Medicine.

According to Chi-Hua Chen, PhD, first author and a postdoctoral fellow in the UC San Diego Department of Psychiatry, “If we can understand the genetic underpinnings of the brain, we can get a better idea of how it develops and works, information we can then use to ultimately improve treatments for diseases and disorders.”

The human cerebral cortex, characterized by distinctive twisting folds and fissures called sulci, is just 0.08 to 0.16 inches thick, but contains multiple layers of interconnected neurons with key roles in memory, attention, language, cognition and consciousness.

Other atlases have mapped the brain by cytoarchitecture – differences in tissues or function. The new map is based entirely upon genetic information derived from magnetic resonance imaging (MRI) of 406 adult twins participating in the Vietnam Era Twin Registry (VETSA), an ongoing longitudinal study of cognitive aging supported in part by grants from the National Institutes of Health (NIH). It follows a related study published last year by Kremen, Dale and colleagues that affirmed the human cortical regionalization is similar to and consistent with patterns found in other mammals, evidence of a common conservation mechanism in evolution.

"We are excited by the development of this new atlas, which we hope will help us understand aging-related changes in brain structure and cognitive function now occurring in the VETSA participants," said Jonathan W. King, PhD, of the National Institute on Aging, part of the NIH.

The atlas plots genetic correlations between different points on the cortical surface of the twins’ brains. The correlations represent shared genetic influences and reveal that genetic brain divisions do not map one-to-one with traditional brain divisions that are based on structure and function. “Yet, the pattern of this genetic map still suggests that it is neuroanatomically meaningful,” said Kremen.

Kremen said the genetic brain atlas may be especially useful for scientists who employ genome-wide association studies, a relatively new tool that looks for common genetic variants in people that may be associated with a particular trait, condition or disease.

Provided by University of California - San Diego

Source: medicalxpress.com

March 29, 2012

The brain appears to be wired more like the checkerboard streets of New York City than the curvy lanes of Columbia, Md., suggests a new brain imaging study. The most detailed images, to date, reveal a pervasive 3D grid structure with no diagonals, say scientists funded by the National Institutes of Health.

Curvature in this DSI image of a whole human brain turns out to be folding of 2-D sheets of parallel neuronal fibers that cross paths at right angles. This picture came from the new Connectom scanner. Credit: Van Wedeen, M.D., Martinos Center and Dept. of Radiology, Massachusetts General Hospital and Harvard University Medical School

"Far from being just a tangle of wires, the brain’s connections turn out to be more like ribbon cables — folding 2D sheets of parallel neuronal fibers that cross paths at right angles, like the warp and weft of a fabric," explained Van Wedeen, M.D., of Massachusetts General Hospital (MGH), A.A. Martinos Center for Biomedical Imaging and the Harvard Medical School. "This grid structure is continuous and consistent at all scales and across humans and other primate species."

Wedeen and colleagues report new evidence of the brain’s elegant simplicity March 30, 2012 in the journal Science. The study was funded, in part, by the NIH’s National Institute of Mental Health (NIMH), the Human Connectome Project of the NIH Blueprint for Neuroscience Research, and other NIH components.

"Getting a high resolution wiring diagram of our brains is a landmark in human neuroanatomy," said NIMH Director Thomas R. Insel, M.D. "This new technology may reveal individual differences in brain connections that could aid diagnosis and treatment of brain disorders."

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March 28, 2012 By Kimm Fesenmaier

(Medical Xpress) — When jurors sentencing convicted criminals are instructed to weigh not only facts but also tricky emotional factors, they rely on parts of the brain associated with sympathy and making moral judgments, according to a new paper by a team of neuroscientists. Using brain-imaging techniques, the researchers, including Caltech’s Colin Camerer, found that the most lenient jurors show heightened levels of activity in the insula, a brain region associated with discomfort and pain and with imagining the pain that others feel.

The findings provide insight into the role that emotion plays in jurors’ decision-making processes, indicating a close relationship between sympathy and mitigation.

In the study, the researchers, led by Makiko Yamada of National Institute of Radiological Sciences in Japan, considered cases where juries were given the option to lessen the sentences for convicted murderers. In such cases with “mitigating circumstances,” jurors are instructed to consider factors, sometimes including emotional elements, that might cause them to have sympathy for the criminal and, therefore, shorten the sentence. An example would be a case in which a man killed his wife to spare her from a more painful death, say, from a terminal illness. 

"Finding out if jurors are weighing sympathy reasonably is difficult to do, objectively," says Colin Camerer, the Robert Kirby Professor of Behavioral Finance and Economics at Caltech. "Instead of asking the jurors, we asked their brains."

The researchers scanned the brains of citizens (potential jurors) while the participants read scenarios adapted from actual murder cases with mitigating circumstances. In some cases, the circumstances were sympathy-inducing; in others, where, for example, a man became enraged when an ex-girlfriend refused him, they were not. The scientists used functional magnetic resonance imaging (fMRI), a type of brain scanning that tracks increases in oxygenated blood flow, indicating heightened brain activity. The participants also had their brains scanned when they determined whether to lessen the sentences, and by how much.  

The team found that sympathy activated the dorsomedial prefrontal cortex, precuneus, and temporo-parietal junction—brain regions associated with moral conflict and thinking about the feelings of others. Similarly, the jurors had increased activity in these regions during sentencing when the mitigating circumstances earned their sympathy. In those cases, they also delivered shorter hypothetical sentences.

In addition to Camerer and Yamada, coauthors on the new paper, “Neural circuits in the brain that are activated when mitigating criminal sentences,” are Saori Fujie, Harumasa Takano, Hiroshi Ito, Tetsuya Suhara, and Hidehiko Takahashi of the National Institute of Radiological Sciences; Motoichiro Kato of the Keio University of Medicine; and Tetsuya Matsuda of Tamagawa University Brain Science Institute. Yamada is also affiliated with Tamagawa University Brain Science Institute and Kyoto University School of Medicine; she and Takahashi are additionally affiliated with the Japan Science and Technology Agency.

More information: Neural circuits in the brain that are activated when mitigating criminal sentences 

Provided by California Institute of Technology

Source: medicalxpress.com

March 28, 2012 by Stuart Mason Dambrot

(Medical Xpress) — College and cramming – often where’s there’s one, the other is not far behind. That said, however, it has been recognized since the late 1800s that repeated periodic exposure to the same material leads to better retention than does a single en masse session. Nevertheless, the phenomenon’s neurobiological processes have remained poorly understood, although activity-dependent synaptic plasticity – notably long-term potentiation (LTP) of glutamatergic transmission – is believed to enable rapid storage of new information. Recently, researchers at the University of California in Irvine and the Scripps Research Institute in Jupiter, Florida determined that hippocampal activity can enhance LTP through theta burst stimulation (TBS) – but only when the affected synapses receive, after a long delay, a secondary TBS. The researchers describe mechanisms that maximize synaptic changes that optimally encode new memory by requiring long delays learning-related TBS activity.

A second theta burst train expands the pool of F-actin-enriched spines. (A) Fluorescent phalloidin labeling in CA1 stratum radiatum. (Scale bar = 10 μm). (B) Counts of densely phalloidin-positive spines in slices collected 15 or 75 min after TBS1 (gray bars) or 15 min after TBS2 delayed by 60 min (black bar). (C) Traces show responses to two successive bursts separated by 200 ms (red for second response). (D) Counts of TBS1-induced phalloidin labeling for vehicle (gray) and CX614-treated (blue) slices. (E) Pretreatment with CX614 (blue line) caused a 70% increase in the magnitude of LTP induced by TBS1; this was accompanied by a loss of TBS2-induced potentiation. Image Copyright © 2012 PNAS, doi: 10.1073/pnas.1120700109

Gavin Rumbaugh (Scripps Research Institute) discussed the challenges he, Gary Lynch (University of California) and their team encountered in the study. “The field is trying to understand the neurobiology of new learning, and in particular, how learning induces an even more complex biology to keep new information in our neural circuits,” Rumbaugh tells Medical Xpress. “Over the recent decade, it has become clear that plasticity at individual synapses is a way that neural circuits store information. However, it remains unclear how properties of synapses influence key aspects of learning and memory.”

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March 28, 2012

Recent clinical studies have shown that general anesthesia can be harmful to infants, presenting a dilemma for both doctors and parents. But new research at Wake Forest Baptist Medical Center may point the way to treatment options that protect very young children against the adverse effects of anesthesia.

As detailed in a study published in the March 23 online edition of the journal Neuroscience, Wake Forest Baptist scientists explored a number of strategies designed to prevent anesthesia-induced damage to the brain in infants.

Using an animal model, the researchers tested the effectiveness of a fragment of a neuroprotective protein called ADNP, as well as vitamin D3, a low-level dose of anesthetic and aspirin. They found that three of the four strategies tested protected the brain from injury induced by 20 mg ketamine, a commonly used general anesthetic.

"What didn’t work was aspirin, which was a surprise because aspirin is known to protect the brain from injury," said Christopher P. Turner, Ph.D., assistant professor of neurobiology and anatomy at Wake Forest Baptist and lead author of the study. "In fact, in our study aspirin actually increased the severity of injury from the anesthesia, possibly because it prevents the generation of substances that may be neuroprotective."

Turner and his team studied rats at ages equivalent to children from birth to age 4.

In separate tests, the rodents were injected with: NAP, a peptide fragment of activity-dependent neuroprotective protein (ADNP), 15 minutes before ketamine was administered; two 20-mg doses of vitamin D3, at 24 hours and at 15 minutes before 20 mg ketamine; a non-toxic (5 mg) doses of ketamine 24 hours before a toxic dose of 20 mg ketamine was administered; and a 30-mg dose of aspirin 15 minutes before exposure to ketamine.

The Turner lab found that NAP, vitamin D3 and prior exposure to low (non-toxic) ketamine could all prevent injury from exposure to a toxic (20 mg) level of ketamine. However, aspirin appeared to enhance ketamine-induced injury.

"We designed our studies to give doctors several possible treatment options because not all of these strategies may work in clinical applications," Turner said. "However, because vitamin D3 is already in clinical use, our findings show that it is quite promising with few risks. Further, NAP is currently in clinical trials to diminish the severity of other types of brain injury, so we feel this discovery represents a breakthrough for anesthesia-induced neurotoxicity. However, there may be a critical window of efficacy for NAP, which we need to explore further.

"Of all the approaches that our team studied, using a low dose of ketamine may be both the simplest and most cost-effective, as it suggests children can be pre-treated with the same anesthesia that will be used when they undergo general surgery," Turner added. "In essence, a low-level dose of ketamine primes the child’s brain so that the second, higher dose is not as lethal, much like an inoculation."

Provided by Wake Forest Baptist Medical Center

Source: medicalxpress.com

March 28, 2012

(Medical Xpress) — While stimulants may improve unengaged workers’ performance, a new University of British Columbia study suggests that for others, caffeine and amphetamines can have the opposite effect, causing workers with higher motivation levels to slack off.

The study – published online today by Nature’s Neuropsychopharmacology – explored the impacts of stimulants on “slacker” rats and “worker” rats, and sheds important light on why stimulants might affect people differently, a question that has long been unclear. It also suggests that patients being treated with stimulants for a range of illnesses may benefit from more personalized treatment programs.

“Every day, millions of people use stimulants to wake up, stay alert and increase their productivity – from truckers driving all night to students cramming for exams,” says Jay Hosking, a PhD candidate in UBC’s Dept. of Psychology, who led the study. “These findings suggest that some stimulants may actually have an opposite effect for people who naturally favour the difficult tasks of life that come with greater rewards.”

Hosking says some individuals are more willing to concentrate and exert effort to achieve their goals than others. However, little is known about the brain mechanisms determining how much cognitive effort one will expend in decision-making for accomplishing tasks.

Hosking and study co-author Catharine Winstanley, a professor in UBC’s Dept. of Psychology, found that rats – like humans – show varying levels of willingness to expend high or low degrees of mental effort to obtain food rewards. When presented with stimulants, the “slacker” rats that typically avoided challenges worked significantly harder when given amphetamines, while “worker” rats that typically embraced challenges were less motivated by caffeine or amphetamine.

While more research is needed to understand the brain mechanisms at work, the study suggests that the amount of mental attention people devote to achieving their goals may play a role in determining how stimulants drugs affect them, Hosking says.

Winstanley, a Michael Smith Foundation for Health Research scholar, says people with psychiatric illnesses, brain injuries and Attention Deficit Hyperactivity Disorder (ADHD) may benefit from treatment programs with greater personalization, noting that patients often use stimulants to counter drowsiness and fatigue from their conditions and treatments, with mixed results.

Provided by University of British Columbia

Source: medicalxpress.com

ScienceDaily (Mar. 27, 2012) — Just as the familiar sugar in food can be bad for the teeth and waistline, another sugar has been implicated as a health menace and blocking its action may have benefits that include improving long-term memory in older people and treating cancer.

Blocking the action of a sugar could boost memory and even fight cancer. The neuron on the left has CREB with O-GlcNAc and is short. The neuron on the right does not have that form of CREB and is long. (Credit: Linda Hsieh-Wilson, Ph.D.)

Progress toward finding such a blocker for the sugar — with the appropriately malicious-sounding name “oh-glick-nack” — was the topic of a report presented at the 243rd National Meeting & Exposition of the American Chemical Society (ACS) in San Diego on March 27.

Linda Hsieh-Wilson, Ph.D., explained that the sugar is not table sugar (sucrose), but one of many other substances produced in the body’s cells that qualify as sugars from a chemical standpoint. Named O-linked beta-N-acetylglucosamine — or “O-GlcNAc” — it helps in orchestrating health and disease at their origins, inside the billions of cells that make up the body. O-GlcNAc does so by attaching to proteins that allow substances to pass in and out of the nucleus of cells, for instance, and helping decide whether certain genes are turned on or off. In doing so, O-GlcNAc sends signals that may be at the basis of cancer, diabetes, Alzheimer’s disease and other disorders. Research suggests, for instance, that proteins loaded up with too much O-GlcNAc can’t function normally.

At the ACS meeting, Hsieh-Wilson described how research in her lab at the California Institute of Technology and Howard Hughes Medical Institute implicate O-GlcNAc in memory loss and cancer. The research emerged from Hsieh-Wilson’s use of advanced lab tools for probing a body process that involves attachment of sugars like O-GlcNAc to proteins. Called protein glycosylation, it helps nerves and other cells communicate with each other in ways that keep the body coordinated and healthy. When O-GlcNAc is attached to a protein, that binding process is known as O-GlcNAc glycosylation.

Hsieh-Wilson’s team screened the entire mammalian brain for all O-GlcNAc-glycosylated proteins, using a new process that her laboratory developed. They identified more than 200 proteins bearing O-GlcNAc attachments or tags, many for the first time. The research was done in mice, stand-ins for humans in research that cannot be done on people. Some of the proteins carrying O-GlcNAc were involved in regulating processes like drug addiction and securing long-term storage of memories.

O-GlcNAc’s effects on one particular protein, CREB, got the scientists’ attention. CREB is a key substance that turns on and regulates the activity of genes. Many of the genes in cells are inactive at any given moment. Substances like CREB, termed transcription factors, turn genes on. Hsieh-Wilson found that when O-GlcNAc attached to CREB, CREB’s ability to turn on genes was impaired. When the researchers blocked O-GlcNAc from binding CREB, the mice developed long-term memories faster than normal mice.

Could blocking O-GlcNAc boost long-term memory in humans?

"We’re far from understanding what happens in humans," Hsieh-Wilson emphasized. "Completely blocking O-GlcNAc might not be desirable. Do you really want to sustain all memories long-term, even of events that are best forgotten? How would blocking the sugar from binding to other proteins affect other body processes? There are a lot of unanswered questions. Nevertheless, this research could eventually lead to ways to improve memory."

In a related study, Hsieh-Wilson found that O-GlcNAc interacted with another protein in ways that encourage the growth of cancer cells, suggesting that blocking its attachment might protect against cancer or slow the growth of cancer. And indeed, in mouse experiments, blocking O-GlcNAc resulted in much smaller tumors.

Again, a treatment for humans based on this discovery is far in the future, but the study singles out O-GlcNAc as a potential new target for developing anti-cancer drugs.

Source: Science Daily

March 27, 2012

A hallmark of human intelligence is the ability to efficiently adapt to uncertain, changing and open-ended environments. In such environments, efficient adaptive behavior often requires considering multiple alternative behavioral strategies, adjusting them, and possibly inventing new ones. These reasoning, learning and creative abilities involve the frontal lobes, which are especially well developed in humans compared to other primates. However, how the frontal function decides to create new strategies and how multiple strategies can be monitored concurrently remain largely unknown.

In a new study, published March 27 in the online, open-access journal PLoS Biology, Anne Collins and Etienne Koechlin of Ecole Normale Supérieure and Institut National de la Santé et de la Recherche Médicale, France, examine frontal lobe function using behavioral experiments and computational models of human decision-making. They find that human frontal function concurrently monitors no more than three/four strategies but favors creativity, i.e. the exploration and creation of new strategies whenever no monitored strategies appear to be reliable enough.

The researchers asked one hundred participants to find “3-digit pin codes” by a method of trial and error, under a variety of conditions. They then developed a computational model that predicted the responses produced by participants, which also revealed that participants made their choices by mentally constructing and concurrently monitoring up to three distinct behavioral strategies; flexibly associating digits, motor responses and expected auditory feedbacks.

"This is a remarkable result, because the actual number of correct codes varied across sessions. This suggests that this capacity limit is a hard constraint of human higher cognition," said Dr. Koechlin. Consistently, the performance was significantly better in sessions including no more than three repeated codes.

Furthermore, the researchers found that the pattern of participants’ responses derived from a decision system that strongly favors the exploration of new behavioral strategies: “The results provide evidence that the human executive system favors creativity for compensating its limited monitoring capacity” explained Dr. Koechlin. “It favors the exploration of new strategies but restrains the monitoring and storage of uncompetitive ones. Interestingly, this ability to regulate creativity varied across participants and critically explains individual variations in performances. We believe our study may also help to understand the biological foundations of individual differences in decision-making and adaptive behavior”.

Provided by Public Library of Science

Source: medicalxpress.com

ScienceDaily (Mar. 27, 2012) — Cognitive training including puzzles, handicrafts and life skills are known to reduce the risk, and help slow down the progress, of dementia amongst the elderly. A new study published in BioMed Central’s open access journal BMC Medicine showed that cognitive training was able to improve reasoning, memory, language and hand eye co-ordination of healthy, older adults.

It is estimated that by 2050 the number of people over 65 years old will have increased to 1.1 billion worldwide, and that 37 million of these will suffer from dementia. Research has already shown that mental activity can reduce a person’s risk of dementia but the effect of mental training on healthy people is less well understood. To address this researchers from China have investigated the use of cognitive training as a defence against mental decline for healthy older adults who live independently.

To be recruited onto the trial participants had to be between 65 and 75 years old, and have good enough eyesight, hearing, and communication skills, to be able to complete all parts of the training. The hour long training sessions occurred twice a week, for 12 weeks, and the subjects were provided with homework. Training included a multi-approach system tackling memory, reasoning, problem solving, map reading, handicrafts, health education and exercise, or focussing on reasoning only. The effect of booster training, provided six months later, was also tested.

The results of the study were positive. Profs Chunbo Li and Wenyuan Wu who led the research explained, “Compared to the control group, who received no training, both levels of cognitive training improved mental ability, although the multifaceted training had more of a long term effect. The more detailed training also improved memory, even when measured a year later and booster training had an additional improvement on mental ability scores.”

This study shows that cognitive training therapy may prevent mental decline amongst healthy older people and help them to continue independent living longer in their advancing years.

Source: Science Daily

ScienceDaily (Mar. 26, 2012) — Working with genetically engineered mice and the genomes of thousands of people with schizophrenia, researchers at Johns Hopkins say they now better understand how both nature and nurture can affect one’s risks for schizophrenia and abnormal brain development in general.

The green neurons have reduced DISC1 protein. Red neurons have less effective GABA. (Credit: Johns Hopkins Medicine)

The researchers reported in the March 2 issue of Cell that defects in a schizophrenia-risk genes and environmental stress right after birth together can lead to abnormal brain development and raise the likelihood of developing schizophrenia by nearly one and half times.

"Our study suggests that if people have a single genetic risk factor alone or a traumatic environment in very early childhood alone, they may not develop mental disorders like schizophrenia," says Guo-li Ming, M.D., Ph.D., professor of neurology and member of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. "But the findings also suggest that someone who carries the genetic risk factor and experiences certain kinds of stress early in life may be more likely to develop the disease."

Pinpointing the cause or causes of schizophrenia has been notoriously difficult, owing to the likely interplay of multiple genes and environmental triggers, Ming says. Searching for clues at the molecular level, the Johns Hopkins team focused on the interaction of two factors long implicated in the disease: Disrupted-in-Schizophrenia 1 (DISC1) protein, which is important for brain development, and GABA, a brain chemical needed for normal brain function.

To find how these factors impact brain development and disease susceptibility, the researchers first engineered mice to have reduced levels of DISC1 protein in one type of neuron in the hippocampus, a region of the brain involved in learning, memory and mood regulation. Through a microscope, they saw that newborn mouse brain cells with reduced levels of DISC1 protein had similar sized and shaped neurons as those from mice with normal levels of DISC1 protein. To change the function of the chemical messenger GABA, the researchers engineered the same neurons in mice to have more effective GABA. Those brain cells looked much different than normal neurons, with longer appendages or projections. Newborn mice engineered with both the more effective GABA and reduced levels of DISC1 showed the longest projections, suggesting, Ming said, that defects in both DISC1 and GABA together could change the physiology of developing neurons for the worse.

Meanwhile, other researchers at University of Calgary and at the National Institute of Physiological Sciences in Japan had shown in newborn mice that changes in environment and routine stress can impede GABA from working properly during development. In the next set of experiments, the investigators paired reducing DISC1 levels and stress in mice to see if it could also lead to developmental defects. To stress the mice, the team separated newborns from their mothers for three hours a day for ten days, then examined neurons from the stressed newborns and saw no differences in their size, shape and organization compared with unstressed mice. But when they similarly stressed newborn mice with reduced DISC1 levels, the neurons they saw were larger, more disorganized and had more projections than the unstressed mouse neurons. The projections, in fact, went to the wrong places in the brain.

Next, to see if their results in mice correlated to suspected human schizophrenia risk factors, the researchers compared the genetic sequences of 2,961 schizophrenia patients and healthy people from Scotland, Germany and the United States. Specifically, they determined if specific variations of DNA letters found in two genes, DISC1 and a gene for another protein, NKCC1, which controls the effect of GABA, were more likely to be found in schizophrenia patients than in healthy individuals. They paired 36 DNA “letter” changes in DISC1 and two DNA letter variations in NKCC1 — one DNA letter change per gene — in all possible combinations. Results showed that if a person’s genome contained one specific combination of single DNA letter changes, then that person is 1.4 times more likely than people without these DNA changes to develop schizophrenia. Having these single DNA letter changes in either one of these genes alone did not increase risk.

"Now that we have identified the precise genetic risks, we can rationally search for drugs that correct these defects," says Hongjun Song, Ph.D., co-author, professor of neurology and director of the Stem Cell Program at the Institute for Cell Engineering.

Source: Science Daily

ScienceDaily (Mar. 26, 2012) — Repeated stress triggers the production and accumulation of insoluble tau protein aggregates inside the brain cells of mice, say researchers at the University of California, San Diego School of Medicine in a new study published in the March 26 Online Early Edition of the Proceedings of the National Academy of Sciences.

Exposing mice to 14 days of repeated stress resulted in an accumulation of insoluble phosphorylated tau protein aggregates in brain cells, visualized in this electron micrograph. (Credit: Image courtesy of Robert Rissman, UC San Diego)

The aggregates are similar to neurofibrillary tangles or NFTs, modified protein structures that are one of the physiological hallmarks of Alzheimer’s disease. Lead author Robert A. Rissman, PhD, assistant professor of neurosciences, said the findings may at least partly explain why clinical studies have found a strong link between people prone to stress and development of sporadic Alzheimer’s disease (AD), which accounts for up to 95 percent of all AD cases in humans.

"In the mouse models, we found that repeated episodes of emotional stress, which has been demonstrated to be comparable to what humans might experience in ordinary life, resulted in the phosphorylation and altered solubility of tau proteins in neurons," Rissman said. "These events are critical in the development of NFT pathology in Alzheimer’s disease."

The effect was most notable in the hippocampus, said Rissman, a region of the brain linked to the formation, organization and storage of memories. In AD patients, the hippocampus is typically the first region of the brain affected by tau pathology and the hardest-hit, with substantial cell death and shrinkage.

Not all forms of stress are equally threatening. In earlier research, Rissman and colleagues reported that acute stress — a single, passing episode — does not result in lasting, debilitating long lasting changes in accumulation of phosphorylated tau. Acute stress-induced modifications in the cell are transient, he said, and on the whole, probably beneficial.

"Acute stress may be useful for brain plasticity and helping to facilitate learning. Chronic stress and continuous activation of stress pathways may lead to pathological changes in stress circuitry. It may be too much of a good thing." As people age, perhaps their neuronal circuits do too, he said, becoming less robust and perhaps less capable of completely rebounding from the effects of stress.

"Age is the primary, known risk factor for Alzheimer’s disease. It may be that as we age, our neurons just aren’t as plastic as they once were and some succumb."

The researchers observed that stress cues impacted two key corticotropin-releasing factor receptors, suggesting a target for potential therapies. Rissman noted drugs already exist and are in human trials (for other conditions) that modulate the activity of these receptors.

"You can’t eliminate stress. We all need to be able to respond at some level to stressful stimuli. The idea is to use an antagonist molecule to reduce the effects of stress upon neurons. The stress system can still respond, but the response in the brain and hippocampus would be toned down so that it doesn’t result in harmful, permanent damage."

The authors dedicate this work to long time mentor and colleague, Dr. Wylie Vale, whose years of pioneering work deciphering and describing the stress system were fundamental to this paper. Vale passed away earlier this year at the age of 70.

Source: Science Daily

ScienceDaily (Mar. 26, 2012) — Individuals with major depressive disorder (MDD) often undergo multiple courses of antidepressant treatment during their lives. This is because the disorder can recur despite treatment and because finding the right medication for a specific individual can take time.

While the relationship between prior treatment and the brain’s response to subsequent treatment is unknown, a new study by UCLA researchers suggests that how the brain responds to antidepressant medication may be influenced by its remembering of past antidepressant exposure.

Interestingly, the researchers used a harmless placebo as the key to tracking the footprints of prior antidepressant use.

Aimee Hunter, the study’s lead author and an assistant professor of psychiatry at UCLA’s Semel Institute for Neuroscience and Human Behavior, and colleagues showed that a simple placebo pill, made to look like actual medication for depression, can “trick” the brain into responding in the same manner as the actual medication.

The report was published online March 23 in the journal European Neuropsychopharmacology.

The investigators examined changes in brain function in 89 depressed persons during eight weeks of treatment, using either an antidepressant medication or a similar-looking placebo pill. They set out to compare the two treatments — medication versus placebo — but they also added a twist: They separately examined the data for subjects who had never previously taken an antidepressant and those who had.

The researchers focused on the prefrontal cortex, an area of the brain thought to be involved in planning complex cognitive behavior, personality expression, decision-making and moderating social behavior, all things depressed people wrestle with.

Brain changes were assessed using electroencephalograph (EEG) measures developed at UCLA by study co-authors Dr. Ian Cook, UCLA’s Miller Family Professor of Psychiatry, and Dr. Andrew Leuchter, a professor of psychiatry and director of the Laboratory of Brain, Behavior and Pharmacology at UCLA’s Semel Institute. The EEG measure, recorded from scalp electrodes, is linked to blood flow in the cerebral cortex, which suggests the level of brain activity.

The antidepressant medication given during the study appeared to produce slight decreases in prefrontal brain activity, regardless of whether subjects had received prior antidepressant treatment during their lifetime or not. (A decrease in brain activity is not necessarily a bad thing, the researchers note; with depression, too much activity in the brain can be as bad as too little.)

However, the researchers observed striking differences in the power of placebo, depending on subjects’ prior antidepressant use. Subjects who had never been treated with an antidepressant exhibited large increases in prefrontal brain activity during placebo treatment. But those who had used antidepressant medication in the past showed slight decreases in prefrontal activity — brain changes that were indistinguishable from those produced by the actual drug.

"The brain’s response to the placebo pill seems to depend on what happened previously — on whether or not the brain has ever ‘seen’ antidepressant medication before," said Hunter, who is a member of the placebo research team at the Laboratory of Brain, Behavior and Pharmacology. "If it has seen it before, then the brain’s signature ‘antidepressant-exposure’ response shows up."

According to Hunter, the effect looks conspicuously like a classical conditioning phenomenon, wherein prior exposure to the actual drug may have produced the specific prefrontal brain response and subsequent exposure to the cues surrounding drug administration — the relationship with the doctor or nurse, the medical treatment setting, the act of taking a prescribed pill and so forth — came to elicit a similar brain response through ‘conditioning’ or ‘associative learning.’

While medication can have a powerful effect on our physiology, said Hunter, “the behaviors and cues in the environment that are associated with taking medication can come to elicit their own effects. One’s personal treatment history is one of the many factors that influence the overall effects of treatment.”

Still, she noted, there are other possible explanations, and further research is needed to tease out changes in brain function that are related to antidepressant exposure, compared with brain changes that are related to clinical improvement during treatment.

Source: Science Daily

ScienceDaily (Mar. 26, 2012) — Smoking alters the impact of a schizophrenia risk gene. Scientists from the universities of Zurich and Cologne demonstrate that healthy people who carry this risk gene and smoke process acoustic stimuli in a similarly deficient way as patients with schizophrenia. Furthermore, the impact is all the stronger the more the person smokes.

Schizophrenia has long been known to be hereditary. However, as a melting pot of disorders with different genetic causes is concealed behind manifestations of schizophrenia, research has still not been able to identify the main gene responsible to this day.

In order to study the genetic background of schizophrenia, the frequency of particular risk genes between healthy and ill people has mostly been compared until now. Pharmacopyschologist Professor Boris Quednow from University Hospital of Psychiatry, Zurich, and Professor Georg Winterer’s workgroup at the University of Cologne have now adopted a novel approach. Using electroencephalography (EEG), the scientists studied the processing of simple acoustic stimuli (a sequence of similar clicks). When processing a particular stimulus, healthy people suppress the processing of other stimuli that are irrelevant to the task at hand. Patients with schizophrenia exhibit deficits in this kind of stimulus filtering and thus their brains are probably inundated with too much information. As psychiatrically healthy people also filter stimuli with varying degrees of efficiency, individual stimulus processing can be associated with particular genes.

Smokers process stimuli less effectively

In a large-scale study involving over 1,800 healthy participants from the general population, Boris Quednow and Georg Winterer examined how far acoustic stimulus filtering is connected with a known risk gene for schizophrenia: the so-called “transcription factor 4” gene (TCF4). TCF4 is a protein that plays a key role in early brain development. As patients with schizophrenia often smoke, the scientists also studied the smoking habits of the test subjects.

The data collected shows that psychiatrically healthy carriers of the TCF4 gene also filter stimuli less effectively — like people who suffer from schizophrenia. It turned out that primarily smokers who carry the risk gene display a less effective filtering of acoustic impressions. This effect was all the more pronounced the more the people smoked. Non-smoking carriers of the risk gene, however, did not process stimuli much worse. “Smoking alters the impact of the TCF4 gene on acoustic stimulus filtering,” says Boris Quednow, explaining this kind of gene-environment interaction. “Therefore, smoking might also increase the impact of particular genes on the risk of schizophrenia.”

The results could also be significant for predicting schizophrenic disorders and for new treatment approaches, says Quednow and concludes: “Smoking should also be considered as an important cofactor for the risk of schizophrenia in future studies.” A combination of genetic (e.g. TCF4), electrophysiological (stimulus filtering) and demographic (smoking) factors could help diagnose the disorder more rapidly or also define new, genetically more uniform patient subgroups.

Source: Science Daily

ScienceDaily (Mar. 26, 2012) — Though autism is often not diagnosed until the age of three, some children begin to show signs of developmental delay before they turn a year old. While not all infants and toddlers with delays will develop autism spectrum disorders (ASD), experts point to early detection of these signs as key to capitalizing on early diagnosis and intervention, which is believed to improve developmental outcomes.

According to Dr. Rebecca Landa, director of the Center for Autism and Related Disorders at the Kennedy Krieger Institute in Baltimore, Md., parents need to be empowered to identify the warning signs of ASD and other communication delays.

"We want to encourage parents to become good observers of their children’s development so that they can see the earliest indicators of delays in a baby’s communication, social and motor skills," says Dr. Landa, who also cautions that some children who develop ASD don’t show signs until after the second birthday or regress after appearing to develop typically.

For the past decade, Dr. Landa has followed infant siblings of children with autism to identify red flags of the disorder in their earliest form. Her research has shown that diagnosis is possible in some children as young as 14 months and sparked the development of early intervention models that have been shown to improve outcomes for toddlers showing signs of ASD as young as one and two years old.

Dr. Landa recommends that as parents play with their infant (6 — 12 months), they look for the following signs that have been linked to later diagnosis of ASD or other communication disorders:

1. Rarely smiles when approached by caregivers 2. Rarely tries to imitate sounds and movements others make, such as smiling and laughing, during simple social exchanges 3. Delayed or infrequent babbling 4. Does not respond to his or her name with increasing consistency from 6 — 12 months 5. Does not gesture to communicate by 10 months 6. Poor eye contact 7. Seeks your attention infrequently 8. Repeatedly stiffens arms, hands, legs or displays unusual body movements such as rotating the hands on the wrists, uncommon postures or other repetitive behaviors 9. Does not reach up toward you when you reach to pick him or her up 10. Delays in motor development, including delayed rolling over, pushing up and crawling

"If parents suspect something is wrong with their child’s development, or that their child is losing skills, they should talk to their pediatrician or another developmental expert," says Dr. Landa. "Don’t adopt a ‘wait and see’ perspective. We want to identify delays early in development so that intervention can begin when children’s brains are more malleable and still developing their circuitry."

Source: Science Daily

March 26, 2012

A meta-analysis of previously published studies found that the ratio of blood plasma amyloid-β (Aβ) peptides Aβ42:Aβ40 was significantly associated with development of Alzheimer disease and dementia, according to a report published Online First by Archives of Neurology.

"Plasma levels of amyloid-β (Aβ) peptides have been a principal focus of the growing literature on blood-based biomarkers, but studies to date have varied in design, assay methods, and sample size, making it difficult to readily interpret the overall data," the authors write as background in the study.

Alain Koyama, S.M., then of Harvard School of Public Health and Brigham and Women’s Hospital, Boston, now with the University of California, San Francisco, and colleagues conducted a meta-analysis of 13 previously published studies to examine the association between plasma amyloid-β and development of dementia, Alzheimer disease (AD) and cognitive decline.

The 13 studies included in the analysis had a total of 10,303 participants, and were published between 1995 and 2011. The studies also included measurement of at least one relevant plasma amyloid-β species (Aβ40, Aβ42, or Aβ42: Aβ40 ratio) and reported an effect estimate for dementia, AD or cognitive decline.

The authors found that lower Aβ42: Aβ40 ratios were significantly associated with development of Alzheimer disease and dementia, with most studies in the analysis reporting similar findings. Plasma levels of Aβ40 and Aβ42 alone, however, were not significantly associated with either outcome.

"In conclusion, despite the limitations of existing research and heterogeneity across the studies considered, this systematic review and meta-analysis suggests that the ratio of plasma Aβ42: Aβ40 may have value in predicting the risk for later development of dementia or AD and merits further investigation."

More information: Arch Neurol. Published online March 26, 2012. doi:10.1001/archneurol.2011.1841

Provided by JAMA and Archives Journals

Source: medicalxpress.com

March 26, 2012

Dr. Judith Edersheim, co-founder and co-director of the Center for Law, Brain and Behavior at Massachusetts General Hospital, explores how neuroscience can enhance the pursuit of justice.

Dr. Judith Edersheim of the Center for Law, Brain and Behavior delivered the 13th annual Francine and Michael Saferstein Memorial Lecture in Forensic Science on Tuesday. Photo by Dominick Reuter.

“If neuroscience could shed light on mental states, it might be able to illuminate whether someone meant the crime or intended to harm someone,” Edersheim told approximately 200 students, faculty, staff and community members who filled Northeastern’s Raytheon Amphitheater on Tuesday for the 13th annual Francine and Michael Saferstein Memorial Lecture in Forensic Science.

The lecture series — which is co-sponsored by the Barnett Institute of Chemical and Biological Analysis and the School of Criminology and Criminal Justice — was established by forensic scientist Richard Saferstein in memory of his wife and child, who were killed in 1978 when a bomb discharged inside the family’s garage.

Barry Karger — the James L. Waters Chair in Analytical Chemistry in Northeastern’s College of Science and director of the Barnett Institute of Chemical and Biological Analysis — introduced Edersheim by praising her for “performing a broad range of psychiatric evaluations in criminal and civil forensic settings.”

Edersheim, who holds both an MD and JD, said “neurolaw” is similar to  “neuropolitics” and “neuromarketing,” in that the field tries to incorporate both neuroscience and psychology into a more established practice.

One’s genetic composition as well as the electrical activity and physical structure of the working brain, she explained, can all be explored to shed light on the question of criminal responsibility.

But Edersheim added a note of caution in taking this approach: If biology single-handedly determines behavior, then the very notion of free will becomes compromised. Technological, procedural, constitutional and deterministic limitations, she said, must all be considered when applying neuroscience to the law.

“The science has to be respected in the community and it has to be peer reviewed,” Edersheim said. “It has to be reliable, reproducible and there have to be known error rates. Judges are gatekeepers and they should keep evidence out that doesn’t meet those tests.”

Edersheim also addressed the constitutionality of neurolaw. If brain scans are examples of involuntary search and seizure or if they force defendants to unwillingly incriminate themselves, then the procedure, she said, could be in violation of the Fourth and Fifth amendments, respectively.

“Thoughts may be subject to constitutional protection,” Edersheim explained, adding that the law and the brain “live in different worlds.”

The law, she said, gives us a set of rules we must abide by, but we must decide as a society whether neurobiological explanations of human behavior should matter when determining criminality.

Edersheim said the Center for Law, Brain and Behavior has an “operational philosophy for the faithful translation of law into neuroscience,” meaning that courtroom use of neurological and biological data should be limited to instances when the science is inextricably and causally linked to a behavior.

Provided by Northeastern University

Source: medicalxpress.com

ScienceDaily (Mar. 26, 2012) — A new study, using brain imaging technology, reveals structural adaptations in short-track speed skaters’ brains which are likely to explain their extraordinary balance and co-ordination skills.

Short track speed skaters. (Credit: © sarah besson / Fotolia)

The work by Im Joo Rhyu from the Korea University College of Medicine, and colleagues, is published online in Springer’s journal Cerebellum.

The cerebellum in the brain plays an essential role in balance control, coordinated movement, and visually guided movement, which are key abilities required for short-track speed skaters as they glide on perfectly smooth ice, cornering and passing at high speeds. Previous studies have shown that damage to the cerebellum results in impaired balance and coordination. In addition, structural changes in the brain have been documented following training of complex motor skills, in both jugglers and basketball players for instance. Are these changes sports-specific?

To assess the effect of short-track speed skating training on the relative structure and size of the two brain hemispheres, the authors analyzed brain MRI scans of 16 male professional short-track speed skaters. They compared them to scans of 18 non-skaters, who did not engage in regular exercise.

They found that skaters had larger right hemispheres of the cerebellum and vermian lobules VI-VII (the lobes connecting the left and right parts of the cerebellum) than non-skaters. These results suggest that the specialized abilities of balance and coordination in skaters are associated with a certain amount of flexibility in the structure of the right hemisphere of the cerebellum and vermian VI-VII.

Why do the structural changes occur to the right side of the cerebellum? Gliding on smooth ice requires specialized abilities to control dynamic balance and coordination. During cornering at high speed, short-track speed skaters turn only to the left while maintaining balance on their right foot. Standing on the right foot activates the right lobes of the cerebellum.

In addition, learning a visually guided task is thought to occur in the right side of the brain. Therefore the larger volume of the right hemisphere of the cerebellum in these skaters is likely to be associated with the type of movements which the sport requires, for strong visual guidance while cornering and passing.

The authors conclude: “Short-track speed skaters’ specialized abilities of balance and coordination stimulate specific structural changes in the cerebellum, following extensive training. These changes reflect the effects of extraordinary abilities of balance and coordination on the right region of the brain.”

Source: Science Daily

March 26, 2012 by Bob Yirka

(Medical Xpress) — A research team made up of people from a wide variety of biological sciences has found that mice fed a diet high in fat tend to see an increase in the number of neurons created in the hypothalamus, a region of the brain associated with regulating energy use in the body. The team, as they describe in their paper published in Nature Neuroscience, write that the increase in neurons occurs in a part of the hypothalamus called the median eminence, which lies outside the blood-brain barrier.

Hypothalamic proliferative zone. For more details, Nature Neuroscience (2012) doi:10.1038/nn.3079

Suspecting that something unusual goes on with the hypothalamus and the median eminence in particular, when mice eat more fat, the research team put a group of mice on a diet very high in it. In the lab, mice are usually fed a diet that is approximately thirty five percent fat, which keeps them from gaining weight. In this study, the fat content was raised to sixty percent, which of course caused the mice to get fat. But, the team found, it also caused the creation of new brain cells in the median eminence to increase, from one to five percent.

Next the researchers forced the mouse brains to stop creating new brain cells while continuing to feed the mice the high fat diet. And surprisingly, the mice weight gain slowed and the mice demonstrated more energy. Adding to the good news was the fact that the median eminence lies outside of the blood-brain area (a separation of blood and brain fluid that prevents many materials in blood from reaching brain cells) meaning that the possibility of developing a therapy based on this research to help humans lose weight might be possible.

The researchers are quick to point out however, that there is no evidence yet that increased neuron production occurs in people who eat extra amounts of fat, or even in any other animal. They also say they don’t yet understand why new neuron growth occurs when mice are fed a high fat diet, but speculate that it may have something to do with detecting chemicals in the bloodstream and responding by sending signals to the rest of the hypothalamus.

More information: Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche, Nature Neuroscience (2012) doi:10.1038/nn.3079

Source: medicalxpress.com

March 26, 2012 By Angela Herring

All human languages contain two levels of structure, said Iris Berent, a psychology professor in Northeastern’s College of Science. One is syntax, or the ordering of words in a sentence. The other is phonology, or the sound structure of individual words.

Berent — whose research focuses on the phonological structure of language — examines the nature of linguistic competence, its origins and its interaction with reading. While previous studies have all centered on adult language acquisition, she is now working with infants to address two core questions.

“First,” she said, “do infants have the capacity to encode phonological rules? And, second, are some phonological rules innate?”

To address the first issue, Berent collaborated with neuroscientists Janet Werker, of the University of British Columbia, and Judit Gervain, of the Paris-based Centre National de la Recherche Scientifique.

By utilizing an optical brain imaging technique called near-infrared spectroscopy, or NIRS, the researchers found that newborns have the capacity to learn linguistic rules. This finding — published this month in the Journal of Cognitive Neuroscience — suggests that the neural foundations of language acquisition are present at birth.

Armed with this knowledge, Berent has begun conducting behavioral studies on more than two-dozen infants to explore whether linguistic rules are innate or entirely learned.

“We want to see whether infants prefer certain sound patterns to others even if neither occurs in their language,” Berent explained. “For instance, we know that human languages prefer sequences such as bnog over bdog. Would six-month-old infants show this preference even if their language (English) does not include either sequence?”

For the study, each child is placed in front of a video screen that displays an image pulsing in coordination with rotating sounds, such as “bnog” and “bdog.” Berent hypothesized that infants would look longer at the video screen when they hear sounds to which they are innately biased.

Preliminary results have upheld the hypothesis, but Berent is still accepting new subjects for the study. Her entire research program forms part of a new book called “The Phonological Mind,” which will be published by Cambridge University Press this year.

Provided by Northeastern University

Source: medicalxpress.com

March 26, 2012

(Medical Xpress) — Storytelling is a skill not everyone can master, but even the most crashing bore gets help from their audience’s brain which ‘talks over’ their monotonous quotes, according to scientists.

Researchers from the University of Glasgow’s Institute of Neuroscience and Psychology investigated the ‘voice-selective’ areas of the brain and revealed that when listening to someone monotonously repeating direct speech quotations, the brain will ‘talk over’ the speaker to make the quotes more vivid.

Previously, the researchers had shown the brain ‘talks’ when silently reading direct quotations.

Dr Bo Yao, the principal investigator of the study, said: “You may think the brain need not produce its own speech while listening to one that is already available.

“But, apparently, the brain is very picky on the speech it hears. When the brain hears monotonously-spoken direct speech quotations which it expects to be more vivid, the brain simply ‘talks over’ the speech it hears with more vivid speech utterances of its own.”

Dr Bo Yao explains why the brain ‘talks over’ boring speech: 

[Audio]

The research was conducted by Dr Yao and colleagues Professor Pascal Belin and Professor Christoph Scheepers within the Institute’s Centre for Cognitive Neuroimaging.

The team enlisted 18 participants in the study and scanned their brains using functional magnetic resonance imaging (fMRI) while they listened to audio clips of short stories containing direct or indirect speech quotations. The direct speech quotations — e.g., Mary said excitedly: “The latest Sherlock Holmes film is fantastic!” – were either spoken ‘vividly’ or ‘monotonously’ (i.e., with or without much variation in speech melody).

The results showed that listening to monotonously spoken direct speech quotations increased brain activity in the ‘voice-selective areas’ of the brain. These voice-selective areas – originally discovered by Prof Belin – are certain areas of the auditory cortex which are particularly interested in human voices when stimulated by actual speech sounds perceived by the ears.

However, the present and previous studies also reveal that these areas can be activated by different linguistic reporting styles – such as direct versus indirect speech.

Prof Scheepers said: “Direct speech quotations are generally assumed to be more vivid and perceptually engaging than indirect speech quotations as they are more frequently associated with depictions of voices, facial expressions and co-speech gestures.

“When the brain does not receive actual stimulation of auditory speech during silent reading, it tends to produce its own to enliven written direct speech quotations – a phenomenon commonly referred to as the ‘inner voice’ during silent reading. Now it appears the brain does the same even when listening to monotonously-spoken direct speech quotations.”

Dr Yao added: “This research demonstrates that human speech processing is an active process in which the brain generates models for the incoming speech utterances in order to predict actual auditory input.

“By doing so, the brain attempts to optimise the processing of the incoming speech, ensuring more speedy and accurate responses.

“These predictions are probably grounded in our past experiences in which direct speech is frequently associated with vivid depictions of the reported speaker’s voice whereas indirect speech is usually stated in a more flat and steady tone.

“The brain’s ‘talking over’ monotonously spoken direct quotes seems to reflect that it tries to bridge the incongruence between the expected speech utterances (vivid) and the actually perceived speech (monotonous) by simulating or imagining the expected vivid vocal depictions.

“We believe that such a simulation mechanism is an integral part of language comprehension — we naturally recruit our sensory and motor systems to interpret the language input. Language processing, in this sense, is embodied.”

The research paper ‘Brain “talks over” boring quotes: Top-down activation of voice-selective areas while listening to monotonous direct speech quotations’ is published in NeuroImage.

Provided by University of Glasgow

Source: medicalxpress.com 

March 24, 2012

(HealthDay) — Neurodegenerative diseases may be characterized by specific regions of the brain that are critical network epicenters, with disease-related vulnerability associated with shorter paths to the epicenter and greater total connectional flow, according to a study published in the March 22 issue of Neuron.

Neurodegenerative diseases may be characterized by specific regions of the brain that are critical network epicenters, with disease-related vulnerability associated with shorter paths to the epicenter and greater total connectional flow, according to a study published in the March 22 issue of Neuron.

To investigate how intrinsic connectivity in health predicts regional vulnerability to neurodegenerative disease, Juan Zhou, Ph.D., from the University of California in San Francisco, and colleagues used task-free functional magnetic resonance imaging to identify the healthy intrinsic connectivity patterns seeded by brain regions vulnerable to five neurodegenerative diseases (Alzheimer’s disease, behavioral variant frontotemporal dementia, semantic dementia, progressive nonfluent aphasia, and corticobasal syndrome).

The investigators found that, for each neurodegenerative disease, specific regions emerged as critical network epicenters, and their normal connectivity profile was most similar to the disease-linked pattern of atrophy. In healthy subjects, greater disease-related vulnerability was consistently associated with regions with shorter functional paths to the epicenters and also with higher total connectional flow.

"These findings best fit a transneuronal spread model of network-based vulnerability. Molecular pathological approaches may help clarify what makes each epicenter vulnerable to its targeting disease and how toxic protein species travel between networked brain structures," the authors write.

More information: Abstract

Source: medicalxpress.com

ScienceDaily (Mar. 24, 2012) — Researchers are suggesting that there is a link between the number of friends you have and the size of the region of the brain — known as the orbital prefrontal cortex — that is found just above the eyes. A new study shows that this brain region is bigger in people who have a larger number of friendships.

Friends. Researchers are suggesting that there is a link between the number of friends you have and the size of the region of the brain — known as the orbital prefrontal cortex — that is found just above the eyes. (Credit: © Rido / Fotolia)

Their study is published on 1 February 2012 in the journal, Proceedings of the Royal Society B.

The research was carried out as part of the British Academy Centenary ‘Lucy to Language’ project, led by Professor Robin Dunbar of the University of Oxford in a collaboration with Dr Joanne Powell and Dr Marta Garcia-Finana at Liverpool University, Dr Penny Lewis at Manchester University and Professor Neil Roberts at Edinburgh University.

The study suggests that we need to employ a set of cognitive skills to maintain a number of friends (and the keyword is ‘friends’ as opposed to just the total number of people we know). These skills are described by social scientists as ‘mentalising’ or ‘mind-reading’- a capacity to understand what another person is thinking, which is crucial to our ability to handle our complex social world, including the ability to hold conversations with one another. This study, for the first time, suggests that our competency in these skills is determined by the size of key regions of our brains (in particular, the frontal lobe).

Professor Dunbar, from the Institute of Cognitive and Evolutionary Anthropology, explained: ‘“Mentalising” is where one individual is able to follow a natural hierarchy involving other individuals’ mind states. For example, in the play ‘Othello’, Shakespeare manages to keep track of five separate mental states: he intended that his audience believes that Iago wants Othello to suppose that Desdemona loves Cassio [the italics signify the different mind states]. Being able to maintain five separate individuals’ mental states is the natural upper limit for most adults.’

The researchers took anatomical MR images of the brains of 40 volunteers at the Magnetic Resonance and Image Analysis Research Centre at the University of Liverpool to measure the size of the prefrontal cortex, the part of the brain used in high-level thinking. Participants were asked to make a list of everyone they had had social, as opposed to professional, contact with over the previous seven days. They also took a test to determine their competency in mentalising.

Professor Robin Dunbar, said: ‘We found that individuals who had more friends did better on mentalising tasks and had more neural volume in the orbital frontal cortex, the part of the forebrain immediately above the eyes. Understanding this link between an individual’s brain size and the number of friends they have helps us understand the mechanisms that have led to humans developing bigger brains than other primate species. The frontal lobes of the brain, in particular, have enlarged dramatically in humans over the last half million years.’

Dr Joanne Powell, from the Department of Psychology, University of Liverpool, said: ‘Perhaps the most important finding of our study is that we have been able to show that the relationship between brain size and social network size is mediated by mentalising skills. What this tells us is that the size of your brain determines your social skills, and it is these that allow you have many friends.’

Professor Dunbar said: ‘All the volunteers in this sample were postgraduate students of broadly similar ages with potentially similar opportunities for social activities. Of course, the amount of spare time for socialising, geography, personality and gender all influence friendship size, but we also know that at least some of these factors, notably gender, also correlate with mentalising skills. Our study finds there is a link between the ability to read how other people think and social network size.’

Professor Dunbar’s research was funded by the British Academy Centenary Research Project and by the British Academy Research Professorship. His research has already examined the different brain sizes of different species, but this study looks at the differences within species. Professor Dunbar published a paper last year, which found that people living near to the Poles needed larger brains for visual processing because of the dimmer light conditions.

Source: Science Daily

ScienceDaily (Mar. 23, 2012) — Nodding off in class may not be such a bad idea after all. New research from the University of Notre Dame shows that going to sleep shortly after learning new material is most beneficial for recall.

New research shows that going to sleep shortly after learning new material is most beneficial for recall. (Credit: © Claudia Nagel / Fotolia)

Notre Dame psychologist Jessica Payne and colleagues studied 207 students who habitually slept for at least six hours per night. Participants were randomly assigned to study declarative, semantically related or unrelated word pairs at 9 a.m. or 9 p.m., and returned for testing 30 minutes, 12 hours or 24 hours later. Declarative memory refers to the ability to consciously remember facts and events, and can be broken down into episodic memory (memory for events) and semantic memory (memory for facts about the world). People routinely use both types of memory every day — recalling where we parked today or learning how a colleague prefers to be addressed.

At the 12-hour retest, memory overall was superior following a night of sleep compared to a day of wakefulness. However, this performance difference was a result of a pronounced deterioration in memory for unrelated word pairs; there was no sleep-wake difference for related word pairs. At the 24-hour retest, with all subjects having received both a full night of sleep and a full day of wakefulness, subjects’ memories were superior when sleep occurred shortly after learning, rather than following a full day of wakefulness.

"Our study confirms that sleeping directly after learning something new is beneficial for memory. What’s novel about this study is that we tried to shine light on sleep’s influence on both types of declarative memory by studying semantically unrelated and related word pairs," Payne says.

"Since we found that sleeping soon after learning benefited both types of memory, this means that it would be a good thing to rehearse any information you need to remember just prior to going to bed. In some sense, you may be ‘telling’ the sleeping brain what to consolidate."

Source: Science Daily

March 23, 2012 by Cathryn Delude

Our fond or fearful memories — that first kiss or a bump in the night — leave memory traces that we may conjure up in the remembrance of things past, complete with time, place and all the sensations of the experience. Neuroscientists call these traces memory engrams.

But are engrams conceptual, or are they a physical network of neurons in the brain? In a new MIT study, researchers used optogenetics to show that memories really do reside in very specific brain cells, and that simply activating a tiny fraction of brain cells can recall an entire memory — explaining, for example, how Marcel Proust could recapitulate his childhood from the aroma of a once-beloved madeleine cookie.

“We demonstrate that behavior based on high-level cognition, such as the expression of a specific memory, can be generated in a mammal by highly specific physical activation of a specific small subpopulation of brain cells, in this case by light,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience at MIT and lead author of the study reported online today in the journal Nature. “This is the rigorously designed 21st-century test of Canadian neurosurgeon Wilder Penfield’s early-1900s accidental observation suggesting that mind is based on matter.”

In that famous surgery, Penfield treated epilepsy patients by scooping out parts of the brain where seizures originated. To ensure that he destroyed only the problematic neurons, Penfield stimulated the brain with tiny jolts of electricity while patients, who were under local anesthesia, reported what they were experiencing. Remarkably, some vividly recalled entire complex events when Penfield stimulated just a few neurons in the hippocampus, a region now considered essential to the formation and recall of episodic memories.

Scientists have continued to explore that phenomenon but, until now, it has never been proven that the direct reactivation of the hippocampus was sufficient to cause memory recall.

Shedding light on the matter

Fast forward to the introduction, seven years ago, of optogenetics, which can stimulate neurons that are genetically modified to express light-activated proteins. “We thought we could use this new technology to directly test the hypothesis about memory encoding and storage in a mimicry experiment,” says co-author Xu Liu, a postdoc in Tonegawa’s lab. 

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ScienceDaily (Mar. 23, 2012) — Insulin resistance in the brain precedes and contributes to cognitive decline above and beyond other known causes of Alzheimer’s disease, according to a new study by researchers from the Perelman School of Medicine at the University of Pennsylvania. Insulin is an important hormone in many bodily functions, including the health of brain cells. The team identified extensive abnormalities in the activity of two major signaling pathways for insulin and insulin-like growth factor in non-diabetic people with Alzheimer’s disease. These pathways could be targeted with new or existing medicines to potentially help resensitize the brain to insulin and possibly slow down or even improve cognitive decline.

This is the first study to directly demonstrate that insulin resistance occurs in the brains of people with Alzheimer’s disease. The study is now online in the Journal of Clinical Investigation.

"Our research clearly shows that the brain’s ability to respond to insulin, which is important for normal brain function, is going offline at some point. Insulin in the brain not only modulates glucose uptake, but also promotes the health of brain cells — their growth, survival, remodeling, and normal functioning. We believe that brain insulin resistance may be an important contributor to the cognitive decline associated with Alzheimer’s disease," said senior author, Steven E. Arnold, MD, professor of Psychiatry and Neurology. Arnold is also the director of the Penn Memory Center, a National Institute on Aging-designated Alzheimer’s Disease Core Center. "If we can prevent brain insulin resistance from occurring, or re-sensitize brain cells to insulin with any of the currently available insulin-sensitizing diabetes medicines, we may be able to slow down, prevent, or perhaps even improve cognitive decline.

The risk of developing Alzheimer’s disease is increased by 50 percent in people with diabetes. Type 2 diabetes is due to insulin resistance and accounts for 90 percent of all diabetes. The defining clinical feature of Type 2 diabetes (and Type 1 “juvenile” diabetes) is hyperglycemia — high levels of sugar in the blood — but there is no evidence that the brain in Alzheimer’s is hyperglycemic. Insulin acts differently in the brain than in the rest of the body. Researchers found that insulin resistance of the brain occurs in Alzheimer’s disease independent of whether someone has diabetes, by excluding people with a history of diabetes from this study.

The investigators used samples of postmortem brain tissue from non-diabetics who had died with Alzheimer’s disease, stimulated the tissue with insulin, and measured how much the insulin activated various proteins in the insulin-signaling pathways. There was less insulin activation in Alzheimer’s cases than in tissue from people who had died without brain disease. Other proteins linked to insulin action in the brain were abnormal in Alzheimer’s disease samples. These abnormalities were highly correlated with episodic memory and other cognitive disabilities in the Alzheimer’s disease patients.

In tissue from people with Alzheimer’s disease and mild cognitive impairment (MCI), researchers found that changes to a protein called insulin receptor substrate-1 (IRS-1 pS636/639 and pS616) in brain cells were linked to the severity of memory impairments regardless of age, sex, diabetes history, or apolipoprotein E (APOE) gene status. Levels of IRS-1 were also significantly associated with, but not likely to affect, the presence of amyloid beta plaques and neurofibrillary tangles, the signature markers of Alzheimer’s disease. This suggests that insulin resistance contributes to cognitive decline independent of the classical pathology of Alzheimer’s disease.

Researchers noted that three insulin-sensitizing medicines are already approved by the FDA for treatment of diabetes. These drugs readily cross the blood-brain barrier and may have therapeutic potential to correct insulin resistance in Alzheimer’s disease and MCI. “Clinical trials would need to be conducted to determine the impact the drugs have on Alzheimer’s disease and MCI in non-diabetic patients,” said Dr. Arnold.

Source: Science Daily

March 23, 2012

One cup or two faces? What we believe we see in one of the most famous optical illusions changes in a split second; and so does the path that the information takes in the brain. In a new theoretical study, scientists of the Max Planck Institute for Dynamics and Self-Organization, the Bernstein Center Göttingen and the German Primate Center now show how this is possible without changing the cellular links of the network. The direction of information flow changes, depending on the time pattern of communication between brain areas. This reorganisation can be triggered even by a slight stimulus, such as a scent or sound, at the right time.

The way how the different regions of the brain are connected with each other plays a significant role for information processing. This processing can be changed by the assembling and disassembling of nerve fibres joining distant brain circuits. But such events are much too slow to explain rapid changes in perception. From experimental studies it was known that the responsible actions must be at least two orders of magnitude faster. The Göttingen scientists now show for the first time that it is possible to change the information flow in a tightly interconnected network in a simple manner.

Many areas of the brain display a rhythmic nerve cell activity. “The interacting brain areas are like metronomes that tick at the same speed and in a distinct temporal pattern,” says the physicist and principal investigator Demian Battaglia. The researchers were now able to demonstrate that this temporal pattern determines the information flow. “If one of the metronomes is affected, e.g. through an external stimulus, then it changes beat, ticking in an altered temporal pattern compared to the others. The other areas adapt to this new situation through self-organisation and start playing a different drum beat as well. It is therefore sufficient to impact one of the areas in the network to completely reorganize its functioning, as we have shown in our model,” explains Battaglia.

The applied perturbation does not have to be particularly strong. “It is more important that the ‘kick’ occurs at exactly the right time of the rhythm,” says Battaglia. This might play a significant role for perception processes: “When viewing a picture, we are trained to recognize faces as quickly as possible – even if there aren’t any,” points out the Göttingen researcher. “But if we smell a fragrance reminiscent of wine, we immediately see the cup in the picture. This allows us to quickly adjust to things that we did not expect, changing the focus of our attention.”

Next, the scientists want to test the model on networks with a more realistic anatomy. They also hope that the findings inspire future experimental studies, as Battaglia says: “It would be fantastic if, in some years, certain brain areas could be stimulated so finely and precisely that the theoretically predicted effects can be measured through imaging methods.”

Provided by Max-Planck-Gesellschaft

Source: medicalxpress.com

ScienceDaily (Mar. 22, 2012) — Anxious people have a heightened sense of smell when it comes to sniffing out a threat, according to a new study by Elizabeth Krusemark and Wen Li from the University of Wisconsin-Madison in the US.

In animals, the sense of smell is an essential tool to detect, locate and identify predators in the surrounding environment. In fact, the olfactory-mediated defense system is so prominent in animals, that the mere presence of predator odors can evoke potent fear and anxiety responses.

Smells also evoke powerful emotional responses in humans. Krusemark and Li hypothesized that in humans, detection of a particular bad smell may signal danger of a noxious airborne substance, or a decaying object that carries disease.

Their work is published online in Springer’s journal Chemosensory Perception. The study is part of a special issue of this journal on neuroimaging the chemical senses.

The researchers exposed 14 young adult participants to three types of odors: neutral pure odor, neutral odor mixture, and negative odor mixture. They asked them to detect the presence or absence of an odor in an MRI scanner. During scanning, the researchers also measured the skin’s ability to conduct electricity (a measure of arousal level) and monitored the subjects’ breathing patterns. Once the odor detection task was over, and the subjects were still in the scanner, they were asked to rate their current level of anxiety. The authors then analyzed the brain images obtained.

They found that as anxiety levels rose, so did the subjects’ ability to discriminate negative odors accurately — suggesting a ‘remarkable’ olfactory acuity to threat in anxious subjects. The skin conductance results showed that anxiety also heightened emotional arousal to smell-induced threats.

The authors uncovered amplified communication between the sensory and emotional areas of the brain in response to negative odors, particularly in anxiety. This increased connectivity could be responsible for the heightened arousal to threats.

Krusemark and Li conclude: “This enhanced sensory-emotional coupling could serve as a critical mechanism to arouse adequate physiological alertness to potential insults.”

Source: Science Daily

March 22, 2012

Scripps Research Institute scientists and their colleagues have successfully harnessed neurons in mouse brains, allowing them to at least partially control a specific memory. Though just an initial step, the researchers hope such work will eventually lead to better understanding of how memories form in the brain, and possibly even to ways to weaken harmful thoughts for those with conditions such as schizophrenia and post traumatic stress disorder.

The results are reported in the March 23, 2012 issue of the journal Science.

Researchers have known for decades that stimulating various regions of the brain can trigger behaviors and even memories. But understanding the way these brain functions develop and occur normally—effectively how we become who we are—has been a much more complex goal.

"The question we’re ultimately interested in is: How does the activity of the brain represent the world?" said Scripps Research neuroscientist Mark Mayford, who led the new study. "Understanding all this will help us understand what goes wrong in situations where you have inappropriate perceptions. It can also tell us where the brain changes with learning."

On-Off Switches and a Hybrid Memory

As a first step toward that end, the team set out to manipulate specific memories by inserting two genes into mice. One gene produces receptors that researchers can chemically trigger to activate a neuron. They tied this gene to a natural gene that turns on only in active neurons, such as those involved in a particular memory as it forms, or as the memory is recalled. In other words, this technique allows the researchers to install on-off switches on only the neurons involved in the formation of specific memories.

For the study’s main experiment, the team triggered the “on” switch in neurons active as mice were learning about a new environment, Box A, with distinct colors, smells and textures.

Next the team placed the mice in a second distinct environment—Box B—after giving them the chemical that would turn on the neurons associated with the memory for Box A. The researchers found the mice behaved as if they were forming a sort of hybrid memory that was part Box A and part Box B. The chemical switch needed to be turned on while the mice were in Box B for them to demonstrate signs of recognition. Alone neither being in Box B nor the chemical switch was effective in producing memory recall.

"We know from studies in both animals and humans that memories are not formed in isolation but are built up over years incorporating previously learned information," Mayford said. "This study suggests that one way the brain performs this feat is to use the activity pattern of nerve cells from old memories and merge this with the activity produced during a new learning session."

Future Manipulation of the Past

The team is now making progress toward more precise control that will allow the scientists to turn one memory on and off at will so effectively that a mouse will in fact perceive itself to be in Box A when it’s in Box B.

Once the processes are better understood, Mayford has ideas about how researchers might eventually target the perception process through drug treatment to deal with certain mental diseases such as schizophrenia and post traumatic stress disorder. With such problems, patients’ brains are producing false perceptions or disabling fears. But drug treatments might target the neurons involved when a patient thinks about such fear, to turn off the neurons involved and interfere with the disruptive thought patterns.

Provided by The Scripps Research Institute

Source: medicalxpress.com

ScienceDaily (Mar. 21, 2012) — Scientists at the Stanford University School of Medicine have shown for the first time how brain function differs in people who have math anxiety from those who don’t.

A series of scans conducted while second- and third-grade students did addition and subtraction revealed that those who feel panicky about doing math had increased activity in brain regions associated with fear, which caused decreased activity in parts of the brain involved in problem-solving.

"The same part of the brain that responds to fearful situations, such as seeing a spider or snake, also shows a heightened response in children with high math anxiety," said Vinod Menon, PhD, the Stanford professor of psychiatry and behavioral sciences who led the research.

In their new study, published online March 20 in Psychological Science, a journal of the Association for Psychological Science, Menon’s team performed functional magnetic resonance imaging brain scans on 46 second- and third-grade students with low and high math anxiety. Outside the fMRI scanner, the children were assessed for math anxiety with a modified version of a standardized questionnaire for adults, and also received standard intelligence and cognitive tests.

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ScienceDaily (Mar. 21, 2012) — Healthy individuals who carry a gene variation linked to an increased risk of autism have structural differences in their brains that may help explain how the gene affects brain function and increases vulnerability for autism. The results of this innovative brain imaging study are described in an article in the groundbreaking neuroscience journal Brain Connectivity, a bimonthly peer-reviewed publication from Mary Ann Liebert, Inc. The article is available free online at the Brain Connectivity website.

"This is one of the first papers demonstrating a linkage between a particular gene variant and changes in brain structure and connectivity in carriers of that gene," says Christopher Pawela, PhD, Co-Editor-in-Chief and Assistant Professor, Medical College of Wisconsin. "This work could lead to the creation of an exciting new line of research investigating the impact of genetics on communication between brain regions."

Although carriers of the common gene variant CNTNAP2 — identified as an autism risk gene — may not develop autism, there is evidence of differences in brain structure that may affect connections and signaling between brain regions. These disruptions in brain connectivity can give rise to functional abnormalities characteristic of neuropsychological disorders such as autism.

Emily Larson Dennis, Neda Jahanshad, Jeffrey D Rudie, Jesse A Brown, Kori Johnson, Katie McMahon, Greig de Zubicaray, Grant Montgomery, Nicholas Martin, Margaret Wright, Susan Bookheimer, Mirella Dapretto, Arthur Toga, Paul Thompson. Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2. Brain Connectivity, 2012; 120229030236004 DOI: 10.1089/brain.2011.0064

Source: Science Daily

ScienceDaily (Mar. 21, 2012) — Why does inhaling anesthetics cause unconsciousness? New insights into this century-and-a-half-old question may spring from research performed at the National Institute of Standards and Technology (NIST). Scientists from NIST and the National Institutes of Health have found hints that anesthesia may affect the organization of fat molecules, or lipids, in a cell’s outer membrane — potentially altering the ability to send signals along nerve cell membranes.

"A better fundamental understanding of inhaled anesthetics could allow us to design better ones with fewer side effects," says Hirsh Nanda, a scientist at the NIST Center for Neutron Research (NCNR). "How these chemicals work in the body is a scientific mystery that stretches back to the Civil War."

At the turn of the 20th century, doctors suspected inhaled anesthetics had some effect on cell membranes, an animal cell’s outer boundary. Despite considerable investigation, however, no one was able to demonstrate that anesthetics produced changes in the physical properties of membranes large enough to cause anesthesia. But eventually, understanding of membrane function grew more refined as scientists learned more about ion channels.

Ion channels — large proteins embedded in the relatively small lipid molecules forming the membrane — are responsible for conducting electrical impulses along nerve cells in the brain and throughout our body. By a few decades ago, the prevailing theory held that inhaled anesthetics directly interacted with these protein channels, affecting their behavior in some fashion. But no one could find a single type of ion channel that reacted to anesthetics in a way pivotal enough to settle the matter, and the question remained open.

"That’s where we picked up the thread," says Nanda. "We had been looking at how different types of lipid molecules affect ion channels."

While a cell membrane is a highly fluid film made of many different kinds of lipid molecules, the region immediately surrounding an ion channel often consists of a single type of lipids that form a sort of “raft” that is more ordered and less fluid then the rest of the membrane. When the team heard other researchers had found that disrupting these lipid rafts could affect a channel’s function, they put to work their own previous experience working with the channels.

"We decided to test whether inhaled anesthetics could have an effect on rafts in model cell membranes," Nanda says. "No one had thought to ask the question before."

Using the NCNR’s neutron and X-ray diffraction devices as their microscope, the team explored how a model cell membrane responded to two chemicals — inhaled anesthetic, and another that has many of the same chemical properties as anesthetic but does not cause unconsciousness. Their finding showed a distinct difference in the way the lipid rafts responded: Exposing the membranes to an anesthetic caused the rafts to grow disorderly, freely mixing its lipids with the surrounding membrane, but the second chemical had a dramatically smaller effect.

While Nanda says the discovery does not answer the question definitively, he and his co-authors are following up with other experiments that could clarify the issue. “We feel the discovery has opened up an entirely new line of inquiry into this very old puzzle,” he says.

Source: Science Daily

March 21, 2012

Scientists from Germany discovered new functions of brain regions that are responsible for seeing movement.

When observing a fly buzzing around the room, we should have the impression that it is not the fly, but rather the space that lies behind it that is moving. After all, the fly is always fixed in our central point of view. But how does the brain convey the impression of a fly in motion in a motionless field? With the help of functional magnetic resonance imaging (fMRI) scientists from the Werner Reichardt Centre for Integrative Neuroscience and the Max Planck Institute for Biological Cybernetics in Tübingen have identified two areas of the brain that compare the movements of the eye with the visual movements cast onto the retina so as to correctly perceive objects in motion.

The two areas of the brain that are particularly good at reacting to external movements, even during eye movements, are known as V3A and V6. They are located in the upper half in the posterior part of the brain. Area V3A shows a high degree of integration: it reacts to movements around us regardless of whether or not we follow the moving object with our eyes. But the area does not react to visual movements on the retina when eye movements produce them. Area V6 has similar characteristics. In addition, it can perform these functions when we are moving forwards. The calculations the brain has to perform are more complicated in this case: the three-dimensional, expanding forward movement is superimposed onto the two-dimensional lateral movements that are caused by eye movements.

The scientists Elvira Fischer and Andreas Bartels from the Werner Reichardt Centre for Integrative Neuroscience and the Max Planck Institute for Biological Cybernetics have investigated these areas with the help of functional magnetic resonance imaging (fMRI). fMRI is a procedure that can measure brain activity based on local changes in blood flow and oxygen consumption. Participants in the study were shown various visual scenarios whilst undergoing fMRI scanning. For example, they had to follow a small dot with their eyes while it moved across a screen from one side to the other. The patterned background was either stationary or moved at varying speeds, sometimes slower, faster or at the same speed as the dot. Sometimes the dot was stationary while only the background moved. In a total of six experiments the scientists measured brain activity in more than a dozen different scenarios. From this they have been able to discover that V3A and V6, unlike other visual areas in the brain, have a pronounced ability to compare eye movements with the visual signals on the retina. “I am especially fascinated by V3A because it reacts so strongly and selectively to movements in our surroundings. It sounds trivial, but it is an astonishing capability of the brain”, explains Andreas Bartels, project leader of the study.

Whether it is ourselves who move or something else in our surroundings is a problem about which we seldom think, since at the subconscious level our brain constantly calculates and corrects our visual impression. Indeed, patients who have lost this ability to integrate movements in their surroundings with their eye movements can no longer recognize what it is that ultimately is moving: the surroundings or themselves. Every time they move their eyes these patients feel dizzy. Studies such as this bring us one step closer to an understanding of the causes of such illnesses.

Provided by Max-Planck-Gesellschaft

Source: medicalxpress.com

March 21, 2012

Amateurs have a new tool for conducting simple neuroscience experiments in their own garage: the SpikerBox.

As reported in the Mar. 21 issue of the open access journal PLoS ONE, the SpikerBox lets users amplify and listen to neurons’ electrical activity – like those in a cockroach leg or cricket torso – and is appropriate for use in middle or high school educational programs, or by amateurs.

The work was a project from Backyard Brains, a start-up company focused on developing neuroscience educational resources. In the paper, the authors, Timothy Marzullo and Gregory Gage, describe a sample experiment using a cockroach leg stuck with two needles and monitoring the electrical signals. They also provide instructions for using the SpikerBox to answer specific experimental questions, like how neurons carry information about touch, how the brain tells muscles to move, and how drugs affect neurons, and an online portal provides further instructional materials. These are just a few examples of the many ways this tool can be used.

"Our mission is to lower the barrier-to-entry for students interested in learning about the brain. We hope our manuscript finds its way into the hands of high school teachers around the world", says Dr. Marzullo.

Provided by Public Library of Science

Source: medicalxpress.com

March 21, 2012

(Medical Xpress) — People who lose their sight at a later stage in life have a greater spatial awareness than if they were born blind, according to scientists at Queen Mary, University of London.

The study, published in the journal Neuroscience and Biobehavioral Reviews, examined research which looked at the spatial skills of sighted and blind people and found that some spatial tasks need visual experience.

Co-author on the study, Dr. Michael Proulx from Queen Mary’s School of Biological and Chemical Sciences, said: “Numerous studies have tested how humans use vision for knowing the spatial locations of things yet few have examined the other senses and whether people with a visual impairment use the same strategies.

“In reviewing research already available, we found visual experience is necessary for the brain to develop the ability to process multisensory information. We use vision and the other senses to create a mental map of where objects are in relation to other objects and the environment.

“Our findings suggest that there is a sensitive period during which visual experience is necessary for the brain to develop those neurons that can represent the world in this way.”

Lead author Dr. Achille Pasqualotto, also from Queen Mary’s School of Biological and Chemical Sciences, said: “Blindness reveals how well humans can function using the remaining senses, even in a world designed by sighted people for sighted people.

“The brain develops spatial abilities that relate an object’s location to the individual. This makes sense given that a visually impaired person does not see objects at a distance in an environment, but instead acquires their location by personally approaching and identifying them.”

The team is building on their findings now by testing sighted and blind people on a variety of spatial tasks that will explicitly test these findings.

They hope this research will not only reveal the psychological and neural basis for spatial cognition, but also translate into better services for blind persons, such as the development of better navigational tools.

Dr. Proulx said: “We are actively recruiting blind people to participate in our research and we are particularly keen to involve people who have been blind since birth, yet people who lost vision later in life would be welcome to contact us too.”

Provided by Queen Mary, University of London

Source: medicalxpress.com

March 21, 2012

Research at the University of Calgary’s Hotchkiss Brain Institute (HBI) has demonstrated the novel expression of an ion channel in Purkinje cells – specialized neurons in the cerebellum, the area of the brain responsible for movement. Ray W. Turner, PhD, Professor in the Department of Cell Biology & Anatomy and PhD student Jordan Engbers and colleagues published this finding in the January edition of the journal Proceedings of the National Academy of Sciences (PNAS).

This research identifies for the first time that an ion channel called KCa3.1 that was not previously believed to be expressed in the brain is actually present in Purkinje cells. In addition, these researchers demonstrate the mechanism by which this ion channel allows Purkinje cells to filter sensory input in order to coordinate the body’s movements.

The discovery was unexpected, as Engbers explains, “we didn’t specifically go looking for this channel. A lot of time was spent trying to identify the source for an electrical current that we were observing and we finally found ourselves asking ‘what evidence is there that KCa3.1 isn’t in the brain?’ So we ran some tests and all the pieces really fell into place.”

In the cerebellum, sensory input activates neurons called Purkinje cells that have to filter the information and respond only to relevant inputs to produce an appropriate movement response. Although this function of Purkinje cells has been well documented, Engbers and Turner take our understanding a step further by demonstrating that the KCa3.1 ion channel plays a key part in this process - acting as a gatekeeper to filter the enormous amount of incoming information.

As Turner explains, “these cells receive hundreds of thousands of signals every second from the body’s sensory systems. KCa3.1 then allows the cells to filter out the background noise and respond to only the three or four inputs that are particularly relevant”.

Engbers further describes the mechanism by which KCa3.1 filters out the unwanted information, “these channels are activated by an influx of calcium, which generates an inhibitory influence until the correct input is detected. Once the appropriate input is detected, the Purkinje cell responds with a burst of nerve impulses, which in turn initiates the proper motor response.”

This research fills a substantial gap in understanding how neurons in the cerebellum process information. Engbers and Turner expect that continued research will identify KCa3.1 in other areas of the brain and that it will be responsible for several still unexplained phenomena observed in neuronal recordings.

"What we have found will help us understand how the cerebellum functions normally. Now that we have shown the scientific community this new information, we expect that it will become clear that KCa3.1 plays a much wider role in brain function," says Engbers.

Provided by University of Calgary 

Source: medicalxpress.com

March 21, 2012

Researchers at Weill Cornell Medical College have developed a computer program that has tracked the manner in which different forms of dementia spread within a human brain. They say their mathematic model can be used to predict where and approximately when an individual patient’s brain will suffer from the spread, neuron to neuron, of “prion-like” toxic proteins — a process they say underlies all forms of dementia.

Their findings, published in the March 22 issue of Neuron, could help patients and their families confirm a diagnosis of dementia and prepare in advance for future cognitive declines over time. In the future — in an era where targeted drugs against dementia exist — the program might also help physicians identify suitable brain targets for therapeutic intervention, says the study’s lead researcher, Ashish Raj, Ph.D., an assistant professor of computer science in radiology at Weill Cornell Medical College.

"Think of it as a weather radar system, which shows you a video of weather patterns in your area over the next 48 hours," says Dr. Raj. "Our model, when applied to the baseline magnetic resonance imaging scan of an individual brain, can similarly produce a future map of degeneration in that person over the next few years or decades.

"This could allow neurologists to predict what the patient’s neuroanatomic and associated cognitive state will be at any given point in the future. They could tell whether and when the patient will develop speech impediments, memory loss, behavioral peculiarities, and so on," he says. "Knowledge of what the future holds will allow patients to make informed choices regarding their lifestyle and therapeutic interventions.

"At some point we will gain the ability to target and improve the health of specific brain regions and nerve fiber tracts," Dr. Raj says. "At that point, a good prediction of a subject’s future anatomic state can help identify promising target regions for this intervention. Early detection will be key to preventing and managing dementia." 

Tracking the Flow of Proteins

The computational model, which Dr. Raj developed, is the latest, and one of the most significant, validations of the idea that dementia is caused by proteins that spread through the brain along networks of neurons. It extends findings that were widely reported in February that Alzheimer’s disease starts in a particular brain region, but spreads further via misfolded, toxic “tau” proteins. Those studies, by researchers at Columbia University Medical Center and Massachusetts General Hospital, were conducted in mouse models and focused only on Alzheimer’s disease.

In this study, Dr. Raj details how he developed the mathematical model of the flow of toxic proteins, and then demonstrates that it correctly predicted the patterns of degeneration that results in a number of different forms of dementia.

He says his model is predicated on the recent understanding that all known forms of dementia are accompanied by, and likely caused by, abnormal or “misfolded” proteins. Proteins have a defined shape, depending on their specific function — but proteins that become misshapen can produce unwanted toxic effects. One example is tau, which is found in a misfolded state in the brains of both Alzheimer’s patients and patients with frontal temporal dementia (FTD). Other proteins, such as TDP43 and ubiquitin, are also found in FTD, and alpha synuclein is found in Parkinson’s disease.

These proteins are called “prion-like” because misfolded, or diseased, proteins induce the misfolding of other proteins they touch down a specific neuronal pathway. Prion diseases (such as mad cow disease) that involve transmission of misfolded proteins are thought to be infectious between people. “There is no evidence that Alzheimer’s or other dementias are contagious in that way, which is why their transmission is called prion-like.”

Simple Explanation for Clinically Observed Patterns of Dementia

Dr. Raj calls his model of trans-neuronal spread of misfolded proteins “very simple.” It models the same process by which any gas diffuses in air, except that in the case of dementias the diffusion process occurs along connected neural fiber tracts in the brain.

"This is a common process by which any disease-causing protein can result in a variety of dementias," he says.

The model identifies the neural sub-networks in the brain into which misfolded proteins will collect before moving on to other brain areas that are connected by networks of neurons. In the process the proteins alter normal functioning of all brain areas they visit.

"What is new and really quite remarkable is the network diffusion model itself, which acts on the normal brain connectivity network and manages to reproduce many known aspects of whole brain disease patterns in dementias," Dr. Raj says. "This provides a very simple explanation for why different dementias appear to target specific areas of the brain."

In the study, he was able to match patterns from the diffusion model, which traced protein disbursal in a healthy brain, to the patterns of brain atrophy observed in patients with either Alzheimer’s disease or FTD. This degeneration was measured using MRI and other tools that could quantify the amount of brain volume loss experienced in each region of the patient’s brain. Co-author Amy Kuceyeski, Ph.D., a postdoctoral fellow who works with Dr. Raj, helped analyze brain volume measurements in the diseased brains.

"Our study demonstrates that such a spreading mechanism leads directly to the observed patterns of atrophy one sees in various dementias," Dr. Raj says. "While the classic patterns of dementia are well known, this is the first model to relate brain network properties to the patterns and explain them in a deterministic and predictive manner."

Provided by New York- Presbyterian Hospital

Source: medicalxpress.com