Neuroscience

June 17, 2012

A collaborative research team led by Professor Tadashi ISA from The National Institute for Physiological Sciences, The National Institutes of Natural Sciences and Fukushima Medical University and Kyoto University, developed a “double viral vector transfection technique” which can deliver genes to a specific neural circuit by combining two new kinds of gene transfer vectors. With this method, they found that “indirect pathways”, which were suspected to have been left behind when the direct connection from the brain to motor neurons (which control muscles) was established in the course of evolution, actually plays an important role in the highly developed dexterous hand movements. This study was supported by the Strategic Research Program for Brain Sciences by the MEXT of Japan. This research result will be published in Nature (June 17th, advance online publication).

It is said that the higher primates including human beings accomplished explosive evolution by having acquired the ability to move hands skillfully. It has been thought that this ability to move individual fingers is a result of the evolution of the direct connection from the cerebrocortical motor area to motor neurons of the spinal cord which control the muscles. On the other hand, in lower animals with clumsy hands, such as cats or rats, the cortical motor area is connected to the motor neurons, only through interneurons of the spinal cord. Such “indirect pathway”remains in us, primates, without us fully understanding its functions. Is this “phylogenetically old circuit” still in operation? Or maybe suppressed since it is obstructive? The conclusion was not attached to this argument.

The collaborative research team led by Professor Tadashi ISA, Project Assistant Professor Masaharu KINOSHITA from The National Institute for Physiological Sciences, The National Institutes of Natural Sciences and Fukushima Medical University and Kyoto University developed “the double viral vector transfection technique”which can deliver genes to a specific neural circuit by combining two new kinds of gene transfer vectors.

With this method, they succeeded in the selective and reversible suppression of the propriospinal neurons (spinal interneurons mediating the indirect connection from cortical motor area to spinal motor neurons)

The results revealed that “indirect pathways” play an important role in dexterous hand movements and finally a longtime debate has come to a close.

The key component of this discovery was”the double viral vector transfection technique”in which one vector is retrogradely transported from the terminal zone back to the neuronal cell bodies and the other is transfected at the location of their cell bodies. The expression of the target gene is regulated only in the cells with double transfection by the two vectors. Using this technique, they succeeded in the suppression of the propriospinal neuron selectively and reversibly.

Such an operation was possible in mice in which the inheritable genetic manipulation of germline cells were possible, but impossible in primates until now.

Using this method, further development of gene therapy targeted to a specific neural circuit can be expected.

Professor Tadashi ISA says “this newly developed double viral vector transfection technique can be applied to the gene therapy of the human central nervous system, as we are the same higher primates.

And this is the discovery which reverses the general idea that the spinal cord is only a reflex pathway, but also plays a pivotal role in integrating the complex neural signals which enable dexterous movements.”

Provided by National Institute for Physiological Sciences

Source: medicalxpress.com

ScienceDaily (June 16, 2012) — A link between unconscious conflicts and conscious anxiety disorder symptoms have been shown, lending empirical support to psychoanalysis.

Data from the experiment showing that subliminal exposure to words related to a person’s unconscious conflict, followed by supraliminal exposure to words related to their anxiety symptoms, led to different alpha wave patterns compared with other scenarios. (Credit: Image courtesy of University of Michigan Health System)

An experiment that Sigmund Freud could never have imagined 100 years ago may help lend scientific support for one of his key theories, and help connect it with current neuroscience.

June 16 at the 101st Annual Meeting of the American Psychoanalytic Association, a University of Michigan professor who has spent decades applying scientific methods to the study of psychoanalysis will present new data supporting a causal link between the psychoanalytic concept known as unconscious conflict, and the conscious symptoms experienced by people with anxiety disorders such as phobias.

Howard Shevrin, Ph.D., emeritus professor of psychology in the U-M Medical School’s Department of Psychiatry, will present data from experiments performed in U-M’s Ormond and Hazel Hunt Laboratory.

The research involved 11 people with anxiety disorders who each received a series of psychoanalytically oriented diagnostic sessions conducted by a psychoanalyst.

From these interviews the psychoanalysts inferred what underlying unconscious conflict might be causing the person’s anxiety disorder. Words capturing the nature of the unconscious conflict were then selected from the interviews and used as stimuli in the laboratory. They also selected words related to each patient’s experience of anxiety disorder symptoms. Although these words differed from patient to patient, results showed that they functioned in the same way.

These verbal stimuli were presented subliminally at one thousandth of a second, and supraliminally at 30 milliseconds. A control category of stimuli was added that had no relationship to the unconscious conflict or anxiety symptom. While the stimuli were presented to the patients, scalp electrodes record the brain responses to them.

In a previous experiment Shevrin had demonstrated that time-frequency features, a type of brain activity, showed that patients grouped the unconscious conflict stimuli together only when they were presented subliminally. But the conscious symptom-related stimuli showed the reverse pattern — brain activity was better grouped together when patients viewed those words supraliminally.

"Only when the unconscious conflict words were presented unconsciously could the brain see them as connected," Shevrin notes. "What the analysts put together from the interview session made sense to the brain only unconsciously."

However, the experimental design in this first experiment did not allow for directly comparing the effect of the unconscious conflict stimuli on the conscious symptom stimuli.

To obtain evidence for that next level, the unconscious conflict stimuli were presented immediately prior to the conscious symptom stimuli and a new measurement was made, of the brain’s own alpha wave frequency, at 8-13 cycles per second, that had been shown to inhibit various cognitive functions.

Highly significant correlations, suggesting an inhibitory effect, were obtained when the amount of alpha generated by the unconscious conflict stimuli were correlated with the amount of alpha associated with the conscious symptom alpha — but only when the unconscious conflict stimuli were presented subliminally. No results were obtained when control stimuli replaced the symptom words. The fact that these findings are a function of inhibition suggests that from a psychoanalytic standpoint that repression might be involved.

"These results create a compelling case that unconscious conflicts cause or contribute to the anxiety symptoms the patient is experiencing," says Shevrin, who also holds an emeritus position in the Department of Psychology in U-M’s College of Literature, Science and the Arts. "These findings and the interdisciplinary methods used — which draw on psychoanalysis, cognitive psychology, and neuroscience — demonstrate that it is possible to develop an interdisciplinary science drawing upon psychoanalytic theory."

He notes that a prominent critic of psychoanalysis and Freudian theory, Adolf Grunbaum, Ph.D., professor of the philosophy of science at the University of Pittsburgh, has expressed satisfaction that the new results, when added to previous evidence, show that fundamental psychoanalytic concepts can indeed be tested in empirical ways.

For more than 40 years, Shevrin has led a team that has pushed at the boundaries between the disciplines of neuroscience, cognitive psychology, and psychoanalysis, looking for evidence that Freudian concepts such as the unconscious and repression could be documented through physical measures of brain activity. His work has explored the territory where neurobiology, thoughts, emotions and behavior meet.

In 1968 he published the first report of brain responses to unconscious visual stimuli in Science, thus providing strong objective evidence for the existence of the unconscious at a time when most scientists were skeptical of Freud’s ideas. In that same study, he showed that unconscious perceptions are processed in different ways from conscious perceptions, a finding consistent with Freud’s views on how the unconscious works.

In recent years, exchanges between Grunbaum and Shevrin explored the nature of the evidence for the existence and impact of unconscious conflicts. In a 1992 publication, the first study referred to, Grunbaum agreed that Shevrin had obtained objective brain based evidence for the existence of unconscious conflict, but Grunbaum noted that he had not shown that these conflicts caused psychiatric symptoms. His response to being informed of the new findings was an email stating: “I am satisfied.”

Source: Science Daily

Adrian Owen has found a way to use brain scans to communicate with people previously written off as unreachable. Now, he is fighting to take his methods to the clinic.

Adrian Owen still gets animated when he talks about patient 23. The patient was only 24 years old when his life was devastated by a car accident. Alive but unresponsive, he had been languishing in what neurologists refer to as a vegetative state for five years, when Owen, a neuro-scientist then at the University of Cambridge, UK, and his colleagues at the University of Liège in Belgium, put him into a functional magnetic resonance imaging (fMRI) machine and started asking him questions.

Incredibly, he provided answers. A change in blood flow to certain parts of the man’s injured brain convinced Owen that patient 23 was conscious and able to communicate. It was the first time that anyone had exchanged information with someone in a vegetative state.

Patients in these states have emerged from a coma and seem awake. Some parts of their brains function, and they may be able to grind their teeth, grimace or make random eye movements. They also have sleep–wake cycles. But they show no awareness of their surroundings, and doctors have assumed that the parts of the brain needed for cognition, perception, memory and intention are fundamentally damaged. They are usually written off as lost.

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ScienceDaily (June 15, 2012) — People make complex judgements about a person from looking at their face that are based on a range of factors beyond simply their race and gender, according to findings of new research funded by the Economic and Social Research Council (ESRC).

The findings question a long-held belief that people immediately put a person they meet into a limited number of social categories such as: female or male; Asian, Black, Latino or White; and young or old.

Dr Kimberly Quinn at the University of Birmingham found that people ‘see’ faces in a multiple of ways. This could have wider importance in understanding stereotyping and discrimination because it has implications on whether and how people categorise others.

Categorisation is not done purely on the physical features of the face in front of us, but depends on other information as well, including whether the person is already known and whether the person is believed to share other important identities with us.

"How we perceive faces is not just a reflection of what’s in those faces," Dr Quinn said. "We are not objective; we bring our current goals and past knowledge to every new encounter. And this happens really quickly — within a couple of hundred milliseconds of seeing the face."

Dr Quinn and her colleagues explored social categories such as sex, race and age; physical attributes such as attractiveness; personality traits such as trustworthiness; and emotional states such as anger, sadness and happiness.

She found that although social categories are used to gather information on faces, these can be easily undermined. This research found that we reject simple stereotypes when something about the situation alerts us to the fact the stereotype does not tell the whole story. If we take, for example, a racial group and the corresponding stereotype of members of that group as unintelligent, seeing a person in that group playing an intellectual game such as chess would tell us to cancel out the stereotype.

In order to investigate the causes, mechanisms, and results of social categorisation, Dr Quinn used techniques from cognitive psychology and neuroscience to investigate how people process faces. The research was designed to provide insight into when and why people categorise others according to social group membership.

Their findings differ from previous research that adopted a ‘dual process’ approach and assumed people initially categorised faces based on factors such as gender, race or age before determining whether to stereotype them or to see them as unique individuals.

Dr Quinn’s findings were more consistent with a single process that initially focuses on ‘coarse’ information that is easy to detect, and then immediately starts to include more fine-grained processing as time elapses. This model allows for either categorisation or more individuated processing to emerge, and does not assume that categorisation always comes before recognising unique identities — thereby allowing for more diverse outcomes than previously thought.

Further information: http://www.esrc.ac.uk/my-esrc/grants/RES-061-23-0130/read

Source: Science Daily

ScienceDaily (June 15, 2012) — Researchers at The University of Nottingham have identified three sets of genetic markers that could potentially pave the way for new diagnostic tools for a deadly type of brain tumour that mainly targets children.

The study, published in the latest edition of the journal Lancet Oncology, was led by Professor Richard Grundy at the University’s Children’s Brain Tumour Research Centre and Dr Suzanne Miller, a post doctoral research fellow in the Centre.

It focuses on a rare and aggressive cancer called Central Nervous System primitive neuro-ectodermal brain tumours. Patients with CNS PNET have a very poor prognosis and current treatments, including high dose chemotherapy and cranio-spinal radiotherapy are relatively unsuccessful and have severe lifelong side-effects. This is particularly the case in very young children.

Despite the need for new and more effective treatments, little research has been done to examine the underlying causes of CNS PNET, partly due to their rarity. The Nottingham study aimed to identify molecular markers as a first step to improving the treatments and therapies available to fight the cancer.

The Nottingham team collaborated with researchers at the Hospital for Sick Kids in Toronto, Canada, to perform an International study collecting 142 CNS PNET samples from 20 institutions in nine countries.

Professor Richard Grundy said: “Following our earlier research we realised that an international effort was needed to bring sufficient numbers of cases together to make the breakthrough we needed to better understand this disease or indeed diseases identified in our study. The next step is to translate this knowledge into improving treatments.”

By studying the genetics of the tumours, they discovered that instead of one cancer, the tumours have three sub-types featuring distinct genetic abnormalities and leading to different outcomes for patients.

They found that each group had its own genetic signature through subtle differences in the way they expressed two genetic markers, LIN28 and OLIG2.

When compared with clinical factors including age, survival and metastases (the spread of the tumours through the body), they discovered that group 1 tumours (primitive neural) were found most often in the youngest patients and had the poorest survival rates. Patients with group 3 tumours had the highest incidence of metastases at diagnosis.

Ultimately, the research has identified the two genetic markers LIN28 and OLIG2 as a promising basis for more effective tools for diagnosing and predicting outcomes for young patients with these types of brain tumours.

The research was funded by the Canadian Institute of Health Research, the Brainchild/Sick Kids Foundation and the Samantha Dickson Brain Tumour Trust.

Chief Executive of Samantha Dickson Brain Tumour Trust, Sarah Lindsell, said: “As the UK’s leading brain tumour charity, and the largest dedicated funder of brain tumour research, we are delighted that our investment has led to such significant success. It is great to see that understanding of these tumours is improving — this is desperately needed given the poor outcomes for children with this tumour. Samantha Dickson Brain Tumour Trust is proud to have been instrumental in this work.”

Source: Science Daily

ScienceDaily (June 15, 2012) — A study recently published in the Endocrine Society’s Journal of Clinical Endocrinology and Metabolism (JCEM) suggests that vitamin D — when taken with calcium — can reduce the rate of mortality in seniors, therefore providing a possible means of increasing life expectancy.

During the last decade, there has been increasing recognition of the potential health effects of vitamin D. It is well known that calcium with vitamin D supplements reduces the risk of fractures. The present study assessed mortality among patients randomized to either vitamin D alone or vitamin D with calcium. The findings from the study found that the reduced mortality was not due to a lower number of fractures, but represents a beneficial effect beyond the reduced fracture risk.

"This is the largest study ever performed on effects of calcium and vitamin D on mortality," said Lars Rejnmark, PhD, of Aarhus University Hospital in Denmark and lead author of the study. "Our results showed reduced mortality in elderly patients using vitamin D supplements in combination with calcium, but these results were not found in patients on vitamin D alone."

In this study, researchers used pooled data from eight randomized controlled trials with more than 1,000 participants each. The patient data set was composed of nearly 90 percent women, with a median age of 70 years. During the three-year study, death was reduced by 9 percent in those treated with vitamin D with calcium.

"Some studies have suggested calcium (with or without vitamin D) supplements can have adverse effects on cardiovascular health," said Rejnmark. "Although our study does not rule out such effects, we found that calcium with vitamin D supplementation to elderly participants is overall not harmful to survival, and may have beneficial effects on general health."

Source: Science Daily

ScienceDaily (June 15, 2012) — Exposure to low doses of Bisphenol A (BPA) during gestation had immediate and long-lasting, trans-generational effects on the brain and social behaviors in mice, according to a recent study accepted for publication in the journal Endocrinology, a publication of The Endocrine Society.

BPA is a human-made chemical present in a variety of products including food containers, receipt paper and dental sealants and is now widely detected in human urine and blood. Public health concerns have been fueled by findings that BPA exposure can influence brain development. In mice, prenatal exposure to BPA is associated with increased anxiety, aggression and cognitive impairments.

"We have demonstrated for the first time to our knowledge that BPA has trans-generational actions on social behavior and neural expression," said Emilie Rissman, PhD, of the University of Virginia School of Medicine and lead author of the study. "Since exposure to BPA changes social interactions in mice at a dose within the reported human levels, it is possible that this compound has trans-generational actions on human behavior. If we banned BPA tomorrow, pulled all products with BPA in them, and cleaned up all landfills tomorrow it is possible, if the mice data generalize to humans, that we will still have effects of this compound for many generations."

In this study, female mice received chow with or without BPA before mating and throughout gestation. Plasma levels of BPA in supplemented female mice were in a range similar to those measured in humans. Juveniles in the first generation exposed to BPA in utero displayed fewer social interactions as compared with control mice. The changes in genes were most dramatic in the first generation (the offspring of the mice that were exposed to BPA in utero), but some of these gene changes persisted into the fourth generation.

"BPA is a ubiquitous chemical, it is in the air, water, our food, and our bodies," said Rissman. "It is a man-made chemical, and is not naturally occurring in any plant or animal. The fact that it can change gene expression in mice, and that these changes are heritable, is cause for us to be concerned about what this may mean for human health."

Source: Science Daily

June 15, 2012

The research led by Newcastle University’s Dr Mark Cunningham and Professor Miles Whittington and supported by the Dr Hadwen Trust for Humane Research, indicates a novel electrical bio-marker in humans.

The brain produces electrical rhythms and using EEG - electrodes on the scalp - researchers were able to monitor the brain patterns in patients with epilepsy. Both in patients and in brain tissue samples the team were able to witness an abnormal brain wave noticeable due to its rapidly increasing frequency over time.

Comparing these to a musical ‘glissando’, an upwards glide from one pitch to another, the team found that this brain rhythm is unique to humans and they believe it could be related to epilepsy.

Dr Cunningham, senior lecturer in Neuronal Dynamics at Newcastle University said: “We were able to examine EEG collected from patients with drug resistant epilepsy who were continually monitored over a two week period. During that time we noticed patterns of electrical activity with rapidly increasing frequency, just like glissandi, emerging in the lead-up to an epileptic seizure.”

"We are in the early days of the work and we want to investigate this in a larger group of patients but it may offer a promising insight into when a seizure is going to start."

Professor Whittington added: “Classical composers such as Gustav Mahler are famous for using notes of rapidly increasing pitch – called glissando - to convey intense expressions of anticipation. Similarly we identified glissando-like patterns of brain electrical activity generated in anticipation of seizures in patients with epilepsy.”

The team recorded electrical activity taken from patients in Newcastle and Glasgow with the help of collaborators Dr Roderick Duncan and Dr Aline Russell and worked in collaboration with the Epilepsy Surgery Group at Newcastle General Hospital part of the Newcastle Hospitals NHS Foundation Trust.

Having received permission from patients to use brain tissue removed during an operation to cure their seizures, the team were able to observe and study in great detail glissando discharges in slices of this human epileptic tissue maintained in the lab.

Publishing in Epilepsia online, the team discovered that glissandi are highly indicative of pathology associated with human epilepsy and, unlike other forms of epileptic activity studied previously, are extremely difficult to reproduce in normal, non-epileptic brain tissue. The team worked with Professor Roger Traub at the IBM Watson Research Centre in New York to provide predictions using highly detailed computational models. By manipulating the chemical conditions surrounding human epileptic brain tissue according to these predictions, they discovered that glissandi did not require any of the conventional chemical connections between nerve cells thought to underlie most brain functions. Instead, glissandi were generated by a combination of large changes in the pH of the tissue, specific electrical properties of certain types of nerve cell and, most importantly, direct electrical connections between these nerve cells.

"This work also suggests that given the lengths one has to go to reproduce this experimentally in rodents that the glissandi may be a unique feature of the human epileptic brain," explains Dr Cunningham.

Dr Kailah Eglington, Chief Executive of the Dr Hadwen Trust, said: “Of all human brain disorders, epilepsy research ranks as one that currently employs substantial numbers of laboratory animals worldwide.

"Dr Cunningham’s work at Newcastle University aims to address the shortcomings of existing animal-based research by removing animals from the equation and addressing the issue directly in humans."

Provided by Newcastle University

Source: medicalxpress.com

June 15, 2012

The first large non-commercial study to investigate whether the main active constituent of cannabis (tetrahydrocannabinol or THC) is effective in slowing the course of progressive multiple sclerosis (MS) shows that there is no evidence to suggest this; although benefits were noted for those at the lower end of the disability scale.

The CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study was carried out by researchers from the Peninsula College of Medicine and Dentistry (PCMD), Plymouth University. The study was funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership, the Multiple Sclerosis Society and the Multiple Sclerosis Trust.

The preliminary results of CUPID are to be presented by lead researcher Professor John Zajicek at the Association of British Neurologists’ Annual Meeting in Brighton on Tuesday 29th May.

CUPID enrolled nearly 500 people with MS from 27 centres around the UK, and has taken eight years to complete. People with progressive MS were randomised to receive either THC capsules or identical placebo capsules for three years, and were carefully followed to see how their MS changed over this period. The two main outcomes of the trial were a disability scale administered by neurologists (the Expanded Disability Status Scale), and a patient report scale of the impact of MS on people with the condition (the Multiple Sclerosis Impact Scale 29).

Overall the study found no evidence to support an effect of THC on MS progression in either of the main outcomes. However, there was some evidence to suggest a beneficial effect in participants who were at the lower end of the disability scale at the time of enrolment but, as the benefit was only found in a small group of people rather than the whole population, further studies will be needed to assess the robustness of this finding. One of the other findings of the trial was that MS in the study population as a whole progressed slowly, more slowly than expected. This makes it more challenging to find a treatment effect when the aim of the treatment is that of slow progression.

As well as evaluating the potential neuroprotective effects and safety of THC over the long-term, one of the aims of the CUPID study was to improve the way that clinical trial research is done by exploring newer methods of measuring MS and using the latest statistical methods to make the most of every piece of information collected. This analysis will continue for several months. The CUPID study will therefore provide important information about conducting further large scale clinical trials in MS.

Professor John Zajicek, Professor of Clinical Neuroscience at PCMD, Plymouth University, said: “To put this study into context: current treatments for MS are limited, either being targeted at the immune system in the early stages of the disease or aimed at easing specific symptoms such as muscle spasms, fatigue or bladder problems. At present there is no treatment available to slow MS when it becomes progressive. Progression of MS is thought to be due to death of nerve cells, and researchers around the world are desperately searching for treatments that may be ‘neuroprotective’. Laboratory experiments have suggested that certain cannabis derivatives may be neuroprotective.”

He added: “Overall our research has not supported laboratory based findings and shown that, although there is a suggestion of benefit to those at the lower end of the disability scale when they joined CUPID, there is little evidence to suggest that THC has a long term impact on the slowing of progressive MS.”

Dr Doug Brown, Head of Biomedical Research at the MS Society, said: “There are currently no treatments for people with progressive MS to slow or stop the worsening of disability. The MS Society is committed to supporting research in this area and this was an important study for us to fund. While this study sadly suggests THC is ineffective at slowing the course of progressive MS, we will not stop our search for effective treatments. We are encouraged by the possibility shown by this study that THC may have potential benefits for some people with MS and we welcome further investigation in this area.”

Provided by The Peninsula College of Medicine and Dentistry

Source: medicalxpress.com

June 15, 2012 By Angela Herring

Object manip­u­la­tion or tool use is almost a uniquely human trait, said Dagmar Sternad, director of Northeastern’s Action Lab, a research group inter­ested in move­ment coor­di­na­tion. “Not only does it require cer­tain cog­ni­tive abil­i­ties but also dis­tinct motor abilities.”

Professor Dagmar Sternad and postdoctoral researcher C.J. Hasson show that we subconsciously adjust our “safety margin” when we move a dynamic object like a cup of coffee based on the amount of variability in the situation. Credit: John Guillemin

Simply moving one’s own body, for instance by directing a hand toward a coffee cup, requires the orga­ni­za­tion of var­ious phys­i­o­log­ical sys­tems including the cen­tral and periph­eral ner­vous sys­tems and the mus­cu­loskeletal system.

Once the hand grasps and picks up the cup, the ques­tions become even more com­pli­cated. What if the cup is filled with liquid? At this point, the com­plexity of the con­trol problem bal­loons — the pres­ence of the liquid intro­duces non­linear fluid dynamics with the risk of a spill because of the inherent vari­ability in one’s movement.

Sternad, a pro­fessor of , biology, elec­trical and com­puter engi­neering and physics and post­doc­toral researcher C.J. Hasson are inter­ested in how we adapt our move­ment strate­gies when inter­acting with dynamic objects in the environment.

In a recent paper pub­lished in the Journal of Neu­ro­phys­i­ology, Hasson and Sternad explored the ques­tion by looking at the everyday task of manip­u­lating a cup of coffee. They show that how we adapt our move­ment strate­gies is directly related to the amount of vari­ability and reli­a­bility in our sur­round­ings and ourselves.

“Because we’re humans and not machines, we’re noisy and vari­able,” said Hasson. “We can’t expect that a move­ment will unfold exactly as we planned it.”

For the study, 18 healthy par­tic­i­pants vis­ited the Action Lab to play a video game, wherein they attempted to move a vir­tual cup filled with vir­tual liquid across a large video screen. Instead of a normal video-game con­troller, sub­jects moved the vir­tual cup by grasping a manip­u­landum — a large robotic arm. Sim­ilar to the real-life sce­nario, the robot sim­u­lated the forces one would feel from the weight of the object and the sloshing of the liquid in the cup.

They asked par­tic­i­pants to move the cup across the screen within a com­fort­able time of two sec­onds, a task for which there is an infi­nite number of pos­si­bil­i­ties. You could move fast for one second and slow for one second, slow for a half second and then fast for one and a half sec­onds. The team hypoth­e­sized that par­tic­i­pants would nat­u­rally adapt a safe move­ment strategy with prac­tice — and they did.

But the most intriguing result, said Hasson, was that the size of each participant’s safety margin —or how close they let the liquid get to the edge of the cup — could be pre­dicted by how vari­able they were in their move­ments. Those with more vari­ability tended to adapt a “safer” strategy with a larger safety margin.

“If you have a large safety margin and I move with a small margin, the ques­tion is, ‘Why am I more risky than you?’” Hasson said. “Well, you may find that I am much more con­sis­tent in my move­ments, so I don’t need a big safety margin. If you’re more vari­able, you need a larger safety margin.”

The results have impli­ca­tions in assessing elderly patients and patients of motor dis­or­ders such as cere­bral palsy. “If vari­ability deter­mines the move­ments that you do, maybe that’s an inter­ven­tion point,” said Sternad.

Provided by Northeastern University

Source: medicalxpress.com

June 15, 2012

Researchers from the Peninsula College of Medicine and Dentistry, University of Exeter, in collaboration with colleagues from Rutgers University, Newark and University College London, have furthered understanding of the mechanism by which the cells that insulate the nerve cells in the peripheral nervous system, Schwann cells, protect and repair damage caused by trauma and disease.

The findings of the study, published on-line by the Journal of Neuroscience and supported by the Wellcome Trust, are exciting in that they point to future therapies for the repair and improvement of damage to the peripheral nervous system.

The peripheral nervous system is the part of the nervous system outside the brain and the spinal cord. It regulates almost every aspect of our bodily function, carrying sensory information that allows us to feel the sun on our face and motor information, that allows us to move. It also controls the functions of all the organs of the body.

Damage can occur through trauma: it can occur in diabetic neuropathy (suffered by almost half of those with diabetes) and patients with common inherited conditions such as Charcot-Marie-Tooth (CMT) disease. There can be a wide range of symptoms, from loss of sensation in the hands and feet to problems with digestion, blood pressure regulation, sexual function and bladder control.

Schwann cells provide the insulation, or myelin sheath, for the nerve cells that carry electrical impulses to and from the spinal cord. Schwann cells, because of their plasticity, are able to revert back to an immature ‘repair’ cell to repair damage to the peripheral nervous system. The level of repair is remarkably good but incomplete repair, perhaps after the severance of a nerve, may lead to long-term loss of function and pain.

The ability of Schwann cells to demyelinate can make them susceptible to the disease process seen in conditions such as CMT. CMT affects one in 2500people, so is a comparatively common inherited disease of the nervous system. Mutations in the many different genes in CMT can cause cycles of repair and re-insulation (re-myelination) which lead to long-term damage and the death of both Schwann and nerve cells. There is currently no therapy for CMT and patients experience increased sensory and motor problems which may lead to permanent disability.

The research team believes that its work to understand the ability of Schwann cells to revert back to an immature state and stimulate repair will lead to therapies to improve damage from severe trauma and break the cycle of damage caused by CMT. They also believe that there may also be potential to improve repair in cases of diabetic neuropathy.

They have identified a DNA binding protein, cJun, as a key player in the plasticity that allows a Schwann cell to revert back to the active repair state. cJun may be activated by a number of pathways that convey signals from the surface of the Schwann cell to the nucleus. One such pathway, the p38 Mitogen Activated Protein Kinase Pathway, appears to play a vital role: it is activated after PNS damage and may promote the process of repair; conversely it may be abnormally activated in demyelinating diseases such as CMT.

Professor David Parkinson, Associate Professor in Neuroscience, Peninsula College of Medicine and Dentistry, University of Exeter, said: “The findings of our research are exciting because we have pinpointed and are understanding the mechanism by which our bodies can repair damage to the peripheral nervous system. With further investigation, this could well lead to therapies to repair nerve damage from trauma and mitigate the damage which relates to common illnesses, such as CMT.”

Provided by The Peninsula College of Medicine and Dentistry

Source: medicalxpress.com

June 15, 2012

Whether or not a neuron transmits an electrical impulse is a function of many factors. European research is using a heady mixture of techniques – molecular, microscopy and electrophysiological – to identify the necessary input for nerve transmission in the cortex.

Credit: Thinkstock

In the central nervous system (CNS), a nerve cell or neuron has a ‘forest’ of elaborate dendritic trees arising from the cell body. These literally receive many thousands of synapses (junctions that allow transmission of a signal) at positions around the tree. These inputs then are able to generate an impulse, or ‘spike’, known as an action potential at the initial part of the axon.

Previous research has confirmed that an activated synapse will generate an electric signal as a result of neurotransmitters released from pre-synaptic axons. Electrical recordings from the neocortex have confirmed that, in line with the cable theory prediction, that modulation of potential at the dendrite is highly distance-dependent from the cell body or soma.

The ‘Information processing in distal dendrites of neocortical layer 5 pyramidal neurons’ (Channelrhodopsin) project aimed to shed more light on how more distal sites in the ‘tree’ influence the action potential of the post-synaptic neuron. Furthermore, they investigated exactly how dendritic spikes can be generated, another issue about which there is little information so far.

Recent research has highlighted the importance of activation of N-methyl-D-aspartate (NMDA) receptors to bring about the production of a signal that will proceed to the soma and then result in a spike. There is also indirect evidence that interneurons targeting dendrites can control level of dendrite excitability.

Channelrhodopsin scientists simultaneously recorded the pre- and post-synaptic electrical recordings of identified interneurons and a special type of neuron, pyramidal cells that are primary excitation units in the mammalian cortex.

The project team first characterised the different types of inhibitory neuron deep in the cortex in layer 5 at apical tuft dendrites. The researchers then showed that a special type of inhibitory interneuron in the outer layer of the neocortex can suppress dendritic spiking in layer 5.

Project results show that a superficial inhibitory neuron can impact information processing in a specific pyramidal neuron. The research will have massive implications for neuroscience and help to unravel the integrative operations of CNS neurons.

Provided by CORDIS

Source: medicalxpress.com

ScienceDaily (June 14, 2012) — Rockville, Md. — Scientists have found new evidence that people spot a face in the crowd more quickly when teeth are visible — whether smiling or grimacing — than a face with a particular facial expression. The new findings, published in the Journal of Vision, counters the long held “face-in -the-crowd” effect that suggests only angry looking faces are detected more readily in a crowd.

Examples of stimuli — closed mouth and open mouth with visible teeth — presented in the experiment. (Credit: ARVO)

"The research concerned with the face-in-the-crowd effect essentially deals with the question of how we detect social signals of friendly or unfriendly intent in the human face," said author Gernot Horstmann, PhD, of the Center for Interdisciplinary Research and Department of Psychology at Bielefeld University, Germany. "Our results indicate that, contrary to previous assertions, detection of smiles or frowns is relatively slow in crowds of neutral faces, whereas toothy grins and snarls are quite easily detected."

In two studies, the researchers asked subjects to search for a happy or an angry face within a crowd of neutral faces, and measured the search speed. While the search was relatively slow when emotion was signaled with a closed mouth face, the speed search doubled when emotion was signaled with an open mouth and visible teeth. This was the case for both happy and angry faces, and happy faces were found even somewhat faster than angry faces.

Horstmann and his colleagues conducted these experiments as a result of discrepancies in previous studies that investigated visual search for emotional faces. According to the research team, the inconsistent results with respect to which of the two expressions are found faster — the happy face or the angry face — suggested that the emotional expression category could not be the only important factor determining the face-in- the-crowd effect.

The scientists believe this new study may explain the discrepancies. “This will probably inspire researchers to clarify whether emotion and, in particular, threat plays an additional, unique role in face detection,” said Horstmann.

Source: Science Daily

ScienceDaily (June 14, 2012) — An international team of researchers’ study of the spatial patterns of the spread of obesity suggests America’s bulging waistlines may have more to do with collective behavior than genetics or individual choices. The team, led by City College of New York physicist Hernán Makse, found correlations between the epidemic’s geography and food marketing and distribution patterns.

Supermarket. Physicists found correlations between the obesity epidemic’s geography and food marketing and distribution patterns. (Credit: © flashpics / Fotolia)

"We found there is a relationship between the prevalence of obesity and the growth of the supermarket economy," Professor Makse said. "While we can’t claim causality because we don’t know whether obesity is driven by market forces or vice versa, the obesity epidemic can’t be solved by focus on individual behavior."

The teams findings, published online this week in Scientific Reports, come as a policymakers are starting to address the role of environmental factors in obesity. For example, in New York Mayor Michael Bloomberg wants to limit serving sizes of soda sweetened with sugar to 16 ounces as a way to combat obesity.

The World Health Organization considers obesity a global epidemic similar to cancer or diabetes. It is a non-communicable disease for which no prevention strategy has been able to contain the spread.

Because obesity is related to increased calorie intake and physical inactivity, prevention has focused on changing individuals’ behaviors. However, prevalence of non-communicable diseases shows spatial clustering, and the spread of obesity has shown “high susceptibility to social pressure and global economic drivers.”

Professor Makse and his colleagues hypothesized that these earlier findings suggest collective behavior plays a more significant role in the spread of the epidemic than individual factors such as genetics and lifestyle choices. To study collective behavior’s role, they implemented a statistical clustering analysis based on the physics on the critical phenomena.

Using county-level microdata provided by the U.S. Centers for Disease Control Behavior Risk Factor Surveillance Systems for 2004 through 2008, they investigated spatial correlations for specific years. Over that time span, the pattern of the spreading of the epidemic, which has Greene County, Ala., as its epicenter, has shown that two clusters spanning distances of 1,000 kilometers have emerged; one along the Appalachian Mountains, the second in the lower Mississippi River valley.

The spatial map of obesity prevalence in the United States shows that neighboring areas tend to have similar percentages of their populations considered obese, i.e. have a body mass index greater than or equal to 30. Such areas are considered obesity clusters, and their spread can be seen in the maps from 2004 to 2008.

To assess the properties of these spatial arrangements, the researchers calculated an equal-time, two-point correlation function that measured the influence of a set of characteristics in one county on another county at a given distance. The characteristics studied were population density, prevalence of adult obesity and diabetes, cancer mortality rates and economic activity.

The researchers said the form of the correlations in obesity were reminiscent of those in physical systems at a critical point of second-order phase transition. Such systems are uncorrelated and characterized by short-range vanishing fluctuations when they are not at a critical stage.

However, at critical points long-range correlations appear, and these may signal the emergence of strong critical fluctuations in the spreading of obesity and diabetes. Consequently, they concluded the clustering patterns found in obesity were the result of “collective behavior, which may not merely be the consequence of fluctuations in individual habits.”

Professor Makse and his colleagues believe the correlations of fluctuations in the prevalence of obesity may be linked to demographic and economic variables. To test this hypothesis, they compared the spatial characteristics of industries associated with food production and sales, e.g. supermarkets, food and beverage stores, restaurants and bars, to other sectors of the economy.

Their analysis of spatial fluctuations in food economic activity gave rise to the same anomalous values as obesity and diabetes. Areas with above-average concentrations of food-related businesses had high-than-normal prevalence of obesity and diabetes.

In future studies, Professor Makse plans to apply physics concepts to measure the spread of cancer and diabetes. “The basic idea is that if a non-communicable disease is spreading like a virus, then environmental factors have to be at work,” he said. “If only genetics determined obesity, we wouldn’t have seen the correlations.”

Source: Science Daily

ScienceDaily (June 14, 2012) — The first U.S. population prevalence study of mutations in the gene that causes fragile X syndrome, the most common inherited form of intellectual disability, suggests the mutation in the gene — and its associated health risks — may be more common than previously believed.

Writing this month (June 2012) in the American Journal of Medical Genetics, a team of Wisconsin researchers reports that the cascade of genetic amino acid repeats, which accumulate over generations and culminate in the mutation of a single gene causing fragile X, is occurring with more frequency among Americans than previously believed. The study also shows that as the genetic basis for the condition is passed from generation to generation and amplified, risks to neurological and reproductive health emerge in many carriers.

"The premutation of this condition is much more prevalent than we previously thought and there are some clinical risks associated with that," explains Marsha Mailick Seltzer, director of the University of Wisconsin-Madison Waisman Center, who led the new study.

Fragile X is caused by the unexplained runaway expansion of a set of amino acid repeats in a single X chromosome gene known as FMR1. When fully mutated, the gene fails to express and produce a protein that’s required for healthy brain development. The syndrome, which is more common in boys, results in a spectrum of intellectual disability.

However, before the gene fully mutates, carriers of the faulty gene exhibit a smaller number of elevated repeats, which expand as the gene is passed from generation to generation. Normal FMR1 genes exhibit anywhere from five to 40 repeats. Carriers with a premutation may have anywhere from 55 to 200. Those with between 45 and 54 repeats are characterized as falling into a “gray zone.” Carriers of gray zone expansions often pass the mutation on to their children who themselves are at greater risk of having the premutation, and in subsequent generations the risk of a full mutation causing fragile X syndrome is high.

The goal of the new study was to calculate the prevalence in a U.S. population of the premutation and the gray zone. The research was based on data from the Wisconsin Longitudinal Study (WLS), also known as the “Happy Days study,” which for more than 50 years has tracked the careers, family life, health and education of more than 10,000 graduates of Wisconsin’s high school class of 1957.

Using genetic samples from 6,747 WLS participants, the team led by Seltzer, an expert on developmental disability and family life, found that 1 in 151 females and 1 in 468 males carry the fragile X premutation while 1 in 35 females and 1 of every 42 males fall into the gray zone.

"The prevalence is high, the second highest reported in the world literature," says Seltzer, noting that the incidence of fragile X varies by population and is higher in some places such as Israel, and lower in others like Asia.

The expansion of the FMR1 gene is known to vary across ethnic groups. The sample in the WLS study is primarily white and of northern European descent.

People with the premutation are more likely to have a child with disability; to have neurological symptoms such as numbness, dizziness and faintness; and, for women, to experience early menopause. Although these symptoms have been recognized previously in clinical studies, the WLS data represent an unbiased sample and supports those observations.

"This study confirms that there are health risks associated with the premutation," says Seltzer. "People with the premutation have a higher probability of neurological and reproductive problems. There is a significant public health burden."

Source: Science Daily

ScienceDaily (June 14, 2012) — No effective treatments are currently available for the prevention or cure of Alzheimer’s disease (AD), the most frequent form of dementia in the elderly. The most recognized risk factors, advancing age and having the apolipoprotein E Ɛ4 gene, cannot be modified or treated. Increasingly, scientists are looking toward other risk factors to identify preventive and therapeutic strategies. Much attention recently has focused on the metabolic syndrome (MetS), with a strong and growing body of research suggesting that metabolic disorders and obesity may play a role in the development of dementia.

A new supplement to the Journal of Alzheimer’s Disease provides a state-of-the-art assessment of research into the link between metabolic syndrome and cognitive disorders. The supplement is guest edited by Vincenza Frisardi, of the Department of Neurological and Psychiatric Sciences, University of Bari, and the Geriatric Unit and Gerontology-Geriatrics Research Laboratory, IRCCS, Foggia, Italy, and Bruno P. Imbimbo, Research and Development Department, Chiesi Farmaceutici, Parma, Italy.

The prevalence of MetS and obesity has increased over the past several decades. MetS is a cluster of vascular and metabolic risk factors including obesity, hypertension, an abnormal cholesterol profile, and impaired blood glucose regulation. “Although molecular mechanisms underlying the relationship between MetS and neurological disorders are not fully understood, it is becoming increasingly clear that cellular and biochemical alterations observed in MetS may represent a pathological bridge between MetS and various neurological disorders,” explains Dr. Frisardi.

Type 2 diabetes (T2D) has been linked with cognitive impairment in a number of studies. The risk for developing both T2D and AD increases proportionately with age, and evidence shows that individuals with T2D have a nearly twofold higher risk of AD than nondiabetic individuals.

Paula I. Moreira, Faculty of Medicine and Center for Neuroscience and Cell Biology, University of Coimbra, Portugal, outlines some of the likely mechanisms. Both AD and T2D present similar abnormalities in the mitochondria, which play a pivotal role in cellular processes that impair their ability to regulate oxidation in the cell. Human amylin, a peptide that forms deposits in the pancreatic cells of T2D patients, shares several properties with amyloid-ß plaques in the Alzheimer’s brain. Insulin resistance is another feature shared by both disorders. Impairment of insulin signalling is directly involved in the development of tau tangles and amyloid ß (Aß) plaques. “Understanding the key mechanisms underlying this deleterious interaction may provide opportunities for the design of effective therapeutic strategies,” Dr. Moreira notes.

In another article, author, José A. Luchsinger of the Division of General Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, notes that while there seems to be little dispute that T2D can cause cerebrovascular disease and vascular cognitive impairment, whether T2D can cause late onset AD remains to be determined. “Although the idea is highly speculative, the association between T2D and cognitive impairment may not be causal. Several lines of evidence provide some support to the idea that late onset Alzheimer’s disease could cause T2D, or that both could share causal pathways,” he notes. He reviews epidemiological, imaging, and pathological studies and clinical trials to provide insight. “Given the epidemic of T2D in the world, it’s important to determine whether the association between T2D and cognitive impairment, particularly late onset AD, is causal and if so, what are the mechanisms underlying it.”

Dr. Frisardi notes that most efforts by the pharmaceutical industry have been directed against the production and accumulation of amyloid-ß. “Unfortunately, these efforts have not produced effective therapies yet, since the exact mechanisms of AD are largely unknown. Given that the onset of AD most likely results from the interaction of genetic and environmental factors, the research agenda should consider new platforms of study, going beyond the monolithic outlook of AD, by synthesizing epidemiological, experimental, and biological data under a unique pathophysiological model as a point of reference for further advances in the field.”

Source: Science Daily

June 14, 2012

Visual and auditory stimuli that elicit high levels of engagement and emotional response can be linked to reliable patterns of brain activity, a team of researchers from The City College of New York and Columbia University reports. Their findings could lead to new ways for producers of films, television programs and commercials to predict what kinds of scenes their audiences will respond to.

"Peak correlations of neural activity across viewings can occur in remarkable correspondence with arousing moments of the film,” the researchers said in an article published in the journal Frontiers in Human Neuroscience. “Moreover, a significant reduction in neural correlation occurs upon a second viewing of the film or when the narrative is disrupted by presenting its scenes scrambled in time.”

The researchers used EEG (electroencephalography), which measures electrical activity across the scalp, to collect data on brainwaves of 20 human subjects, who were shown scenes from three films with repeat viewings. Two films, Alfred Hitchcock’s “Bang! You’re Dead” and Sergio Leone’s “The Good, the Bad and the Ugly,” contained moments of high drama expected to trigger responses. The third, an amateur film of people walking on a college campus, was used as a control.

"We found moments of high correlation (between brainwave activity during separate viewings) and moments when this did not occur," said Dr. Lucas C. Parra, Herbert G. Kayser Professor of Biomedical Engineering in CCNY’s Grove School of Engineering, and a corresponding author. "By looking at patterns of oscillation we could tell at which moments a person was particularly engaged. Additionally, we could see whether the correlation occurred across subjects and repeated viewings."

[Video: Reading the Brain during Film Viewing]
Video of EEG readings during scenes from “Bang, You’re Dead”

Measurements along the EEG alpha activity scale show the degree of attentiveness in a person, he explained. When the oscillations are strong, a person is relaxed, i.e. not engaged. When a person is very attentive, alpha activity is low.

Peaks in engagement were correlated to three kinds of scenes, said Dr. Jasek Dmochowski, a post-doctoral fellow in the Grove School and a corresponding author. They included moments with powerful visual cues, such as a close-up on the gun in “Bang! You’re Dead,” scenes with ominous music in which the visual component was not significant, and meaningful scene changes.

The researchers found significantly less neural correlation on participants’ second viewings and when scenes were scrambled and shown out of sequence. “Following a narrative is complex and involves a lot of distributed processing. When a person doesn’t have a sense of the narrative there is much less correlation (across views of the same or another subject),” Dr. Dmochowski said.

Having demonstrated the correlations between intense stimuli and brainwave reliability, the research team now wants to locate where in the brain the response occurs, Professor Parra said. He wants to deploy a combination of EEG and magnetic resonance imaging to “get the best of both worlds:” the fine temporal resolution of EEG and the detailed imagery of MRI.

The team sees several potential applications for the ability to quantify levels of engagement, including neuro-marketing, quantitative assessment of entertainment, measuring the impact of narrative discourse and the study of attention deficit disorders. “Advertisers would love to know where and when an ad is engaging,” he noted.

"The potential to measure engagement is huge since this provides an objective way to collect data," added Dr. Dmochowski, who currently is investigating whether there is a correlation between social media usage and brain activity in young people while watching “The Walking Dead,” a drama series on the American Movie Classics cable network.

"We are mining Twitter to measure the depth of watching," he continued. "We think there will be many correlations between scenes that elicit social media responses and neural signatures, and we can look at both positive and negative responses."

Provided by City College of New York

Source: medicalxpress.com

ScienceDaily (June 13, 2012) — Ever wonder why Jimi Hendrix’s rendition of “The Star-Spangled Banner” moved so many people in 1969 or why the music in the shower scene of “Psycho” still sends chills down your spine?

Jimi Hendrix (Credit: Public domain image, courtesy of UCLA)

A UCLA-based team of researchers has isolated some of the ways in which distorted and jarring music is so evocative, and they believe that the mechanisms are closely related to distress calls in animals.

They report their findings in the latest issue of the peer-reviewed scientific journal Biology Letters, which publishes online June 12.

"Music that shares aural characteristics with the vocalizations of distressed animals captures human attention and is uniquely arousing," said Daniel Blumstein, one of the study’s authors and chair of the UCLA Department of Ecology and Evolutionary Biology.

Read More →

ScienceDaily (June 13, 2012) — Children who are skilled in understanding how shapes fit together to make recognizable objects also have an advantage when it comes to learning the number line and solving math problems, research at the University of Chicago shows.

The work is further evidence of the value of providing young children with early opportunities in spatial learning, which contributes to their ability to mentally manipulate objects and understand spatial relationships, which are important in a wide range of tasks, including reading maps and graphs and understanding diagrams showing how to put things together. Those skills also have been shown to be important in Science Technology, Engineering and Math (STEM) fields.

Scholars at UChicago have shown, for instance, that working with puzzles and learning to identify shapes are connected to improved spatial understanding and better achievement, particularly in geometry. A new paper, however, is the first to connect robust spatial learning with better comprehension of other aspects of mathematics, such as arithmetic.

"We found that children’s spatial skills at the beginning of first and second grades predicted improvements in linear number line knowledge over the course of the school year," said Elizabeth Gunderson, a UChicago postdoctoral scholar who is lead author of the paper, "The Relation Between Spatial Skill and Early Number Knowledge: The Role of the Linear Number Line," published in the current issue of the journal Development Psychology.

In addition to finding the importance of spatial learning to improving understanding of the number line, the team also showed that better understanding of the number line boosted mathematics performance on a calculation task.

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ScienceDaily (June 13, 2012) — Wake up, America, and lose some weight — it’s keeping you tired and prone to accidents. Three studies being presented June 13 at sleep 2012 conclude that obesity and depression are the two main culprits making us excessively sleepy while awake.

Researchers at Penn State examined a random population sample of 1,741 adults and determined that obesity and emotional stress are the main causes of the current “epidemic” of sleepiness and fatigue plaguing the country. Insufficient sleep and obstructive sleep apnea also play a role; both have been linked to high blood pressure, heart disease, stroke, depression, diabetes, obesity and accidents.

"The ‘epidemic’ of sleepiness parallels an ‘epidemic’ of obesity and psychosocial stress," said Alexandros Vgontzas, MD, the principal investigator for the three studies. "Weight loss, depression and sleep disorders should be our priorities in terms of preventing the medical complications and public safety hazards associated with this excessive sleepiness."

In the Penn State cohort study, 222 adults reporting excessive daytime sleepiness (EDS) were followed up 7½ years later. For those whose EDS persisted, weight gain was the strongest predicting factor. “In fact, our results showed that in individuals who lost weight, excessive sleepiness improved,” Vgontzas said.

Adults from that same cohort who developed EDS within the 7½-year span also were studied. The results show for the first time that depression and obesity are the strongest risk factors for new-onset excessive sleepiness. The third study, of a group of 103 research volunteers, determined once again that depression and obesity were the best predictors for EDS.

"The primary finding connecting our three studies are that depression and obesity are the main risk factors for both new-onset and persistent excessive sleepiness," Vgontzas said.

In the Penn State cohort study, the rate of new-onset excessive sleepiness was 8 percent, and the rate of persistent daytime sleepiness was 38 percent. Like insufficient sleep and obstructive sleep apnea, EDS also is associated with significant health risks and on-the-job accidents.

Source: Science Daily

ScienceDaily (June 13, 2012) — Research into alcohol’s effect on juvenile rats shows they have an ability to build up a physical, but not cognitive, tolerance over the short term — a finding that could have implications for adolescent humans, according to Baylor University psychologists.

The research findings are significant because they indicate that blood alcohol concentration levels alone may not fully account for impaired orientation and navigation ability, said Jim Diaz-Granados, Ph.D., professor and chair of psychology and neuroscience at Baylor. He co-authored the study, published in the journal Brain Research.  “There’s been a lot of supposition about the reaction to blood alcohol levels,” Diaz-Granados said. “We use the blood alcohol level to decide if someone is going to get arrested, because we think that a high level means impairment. But here we see a model where we can separate that out. You may have a tolerance in metabolism, but just because your blood alcohol concentration is less than the legal limit doesn’t mean your behavior isn’t impaired.”

"More research is needed to fully understand how adolescents react to alcohol, but this contributes a piece to the puzzle," said study co-author Douglas Matthews, Ph.D., a research scientist at Baylor and an associate professor in Psychology at Nanyang Technological University in Singapore.

The study was conducted in the Baylor Addiction Research Center of Baylor’s Department of Psychology and Neuroscience in Baylor’s College of Arts & Sciences.

More than half of under-age alcohol use is due to binge drinking, according to the Substance Abuse and Mental Health Services Administration, and “when initial alcohol use occurs during adolescence, it increases the chance of developing alcoholism later in life,” said lead study author Candice E. Van Skike, a doctoral candidate in psychology at Baylor. Researchers have long been interested in whether adolescents react differently to alcohol than adults and how alcohol use affects their brains when they reach adulthood, but Baylor researchers also wanted to test the short-term effect of alcohol on adolescents’ brains in terms of memory about space and dimension.

In the study, 96 rats were trained to navigate a water maze to an escape platform. Half were exposed to alcohol vapor in chambers for 16 hours a day over four days (a method to approximate binge-like alcohol intake), while others were exposed only to air. After a 28-hour break, some were injected with alcohol, then both groups tested again in the maze. A comparison found that those who had undergone the chronic intermittent ethanol exposure built up a metabolic tolerance. They were better able to eliminate alcohol from their systems than ones who had been exposed only to air, based on a comparison of the blood ethanol concentrations of the two groups after they had been injected with alcohol later. While the alcohol-injected rats swam as hard and as fast as the others, their ability to find the escape platform was impaired.

Previous research at Baylor led by Matthews showed that adolescents are less sensitive than adults to motor impairment during alcohol intake because a particular neuron fires more slowly in adults who are drinking. The lack of sensitivity may be part of the reason adolescents do not realize they have had too much to drink.

"It’s difficult to compare metabolic and cognitive tolerance in adults with those of juveniles, because many studies that have looked at the cognitive aspect of chronic ethanol exposure didn’t measure blood alcohol concentration levels," Van Skike said. "It would be an interesting comparison to make, and it is an avenue for future research."

Other research has shown that high levels of alcohol consumption during human adolescence are mirrored in animals. Adolescent rats consume two to three times more ethanol than adults relative to body weight, suggesting that adolescents are who drink are pre-disposed to do so in binges.

Source: Science Daily

ScienceDaily (June 13, 2012) — Normally, male California mice are surprisingly doting fathers, but new research published in the journal Physiological and Biochemical Zoology suggests that high anxiety can turn these good dads bad.

Unlike most rodents, male and female California mice pair up for life with males providing extensive parental care, helping deliver the pups, lick them clean, and keep them warm during their first few weeks of life. Experienced fathers are so paternal that they’ll even take care of pups that aren’t theirs. “If we place a male California mouse in a test cage and present it with an unknown pup, experienced fathers will quickly start to lick and huddle with it,” said Trynke de Jong, a post-doctoral researcher at University of California, Riverside.

Inexperienced males, on the other hand, aren’t always so loving. “Virgin males show more variability,” de Jong explained. “They may behave paternally, or they may ignore the pup, or even attack it. We want to understand what triggers these three behavioral responses in virgin males.”

De Jong and her colleagues thought this variability might have something to do with social status. In other species — including another rodent, Mongolian gerbils — dominant virgin males are more likely than subordinate ones to kill pups. Perhaps social status influences parenting in California mice as well.

To test this, de Jong and her colleagues paired up 12 virgin males in six enclosures, and performed several tests to see which was dominant. First was a food competition. “If a cornflake is dropped in the cage, the more dominant male will manage to eat most of it,” de Jong said. The researchers also observed each mouse’s urine marking. “Dominant males will make more, smaller, and more widespread marks than subordinate males,” said de Jong

After determining the mightier mouse in each pair, the team tested parental behavior by introducing a pup. Contrary to the hypothesis, scores on the dominance tests did not predict whether a male licked or huddled up to the pup. However, the research did turn up signs that anxiety, not status, plays a role in paternal behavior.

Males who shied away from urinating the middle of a new enclosure — a behavioral signal that a mouse is anxious — were slower to approach a pup. Further tests showed that less paternal males had higher levels of the vasopressin in their brains. Vasopressin is a hormone that is strongly associated with stress and anxiety.

"Our findings support the theory that vasopressin may alter the expression of paternal behavior depending on the emotional state of the animal," de Jong said. She believes these results could shed light on the role of stress in paternal care in other mammals — including humans.

Source: Science Daily

ScienceDaily (June 13, 2012) — Human-derived stem cells can spontaneously form the tissue that develops into the part of the eye that allows us to see, according to a study published by Cell Press in the 5th anniversary issue of the journal Cell Stem Cell. Transplantation of this 3D tissue in the future could help patients with visual impairments see clearly.

This is a human ES cell-derived optic cup generated in our self-organization culture (culture day 26). Bright green, neural retina; off green, pigment epithelium; blue, nuclei; red, active myosin (strong in the inner surface of pigment epithelium). (Credit: Nakano et al. Cell Stem Cell Volume 10 Issue 6)

"This is an important milestone for a new generation of regenerative medicine," says senior study author Yoshiki Sasai of the RIKEN Center for Developmental Biology. "Our approach opens a new avenue to the use of human stem cell-derived complex tissues for therapy, as well as for other medical studies related to pathogenesis and drug discovery."

During development, light-sensitive tissue lining the back of the eye, called the retina, forms from a structure known as the optic cup. In the new study, this structure spontaneously emerged from human embryonic stem cells (hESCs) — cells derived from human embryos that are capable of developing into a variety of tissues — thanks to the cell culture methods optimized by Sasai and his team.

The hESC-derived cells formed the correct 3D shape and the two layers of the optic cup, including a layer containing a large number of light-responsive cells called photoreceptors. Because retinal degeneration primarily results from damage to these cells, the hESC-derived tissue could be ideal transplantation material.

Beyond the clinical implications, the study will likely accelerate the acquisition of knowledge in the field of developmental biology. For instance, the hESC-derived optic cup is much larger than the optic cup that Sasai and collaborators previously derived from mouse embryonic stem cells, suggesting that these cells contain innate species-specific instructions for building this eye structure. “This study opens the door to understanding human-specific aspects of eye development that researchers were not able to investigate before,” Sasai says.

Source: Science Daily

ScienceDaily (June 13, 2012) — With their potential to treat a wide range of diseases and uncover fundamental processes that lead to those diseases, embryonic stem (ES) cells hold great promise for biomedical science. A number of hurdles, both scientific and non-scientific, however, have precluded scientists from reaching the holy grail of using these special cells to treat heart disease, diabetes, Alzheimer’s and other diseases.

The Salk researchers found that embryonic stem cells cycle in and out of a state from which they can develop into any kind of tissue. Here, red fluorescent “reporter” molecules indicate that these early embryonic cells are exhibiting genetic activity indicative of this flexible state. (Credit: Courtesy of the Salk Institute for Biological Studies)

In a paper published June 13 in Nature, scientists at the Salk Institute for Biological Studies report discovering that ES cells cycle in and out of a “magical state” in the early stages of embryo development, during which a battery of genes essential for cell potency (the ability of a generic cell to differentiate, or develop, into a cell with specialized functions) is activated. This unique condition, called totipotency, gives ES cells their unique ability to turn into any cell type in the body, thus making them attractive therapeutic targets.

"These findings," says senior author Samuel L. Pfaff, a professor in Salk’s Gene Expression Laboratory, "give new insight into the network of genes important to the developmental potential of cells. We’ve identified a mechanism that resets embryonic stem cells to a more youthful state, where they are more plastic and therefore potentially more useful in therapeutics against disease, injury and aging."

ES cells are like silly putty that can be induced, under the right circumstances, to become specialized cells-for example, skin cells or pancreatic cells-in the body. In the initial stages of development, when an embryo contains as few as five to eight cells, the stem cells are totipotent and can develop into any cell type. After three to five days, the embryo develops into a ball of cells called a blastocyst. At this stage, the stem cells are pluripotent, meaning they can develop into almost any cell type. In order for cells to differentiate, specific genes within the cells must be turned on.

Pfaff and his colleagues performed RNA sequencing (a new technology derived from genome-sequencing to monitor what genes are active) on immature mouse egg cells, called oocytes, and two-cell-stage embryos to identify genes that are turned on just prior to and immediately following fertilization. Pfaff’s team discovered a sequence of genes tied to this privileged state of totipotency and noticed that the genes were activated by retroviruses adjacent to the stem cells.

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June 13, 2012

Researchers from Boston University School of Medicine (BUSM) have identified a novel group of proteins that accumulate in the brains of patients with Alzheimer’s disease. These findings, which appear online in the Journal of Neuroscience, may open up novel approaches to diagnose and stage the progression likelihood of the disease in Alzheimer patients.

Alzheimer’s disease is presumed to be caused by the accumulation of β-amyloid, which then induces aggregation of a neuronal protein, called tau, and neurodegeneration ensues. The diagnosis of Alzheimer’s disease focuses on β-amyloid and tau protein, with much attention focusing on radiolabeled markers that bind to β-amyloid (such as the compound PiB). However, imaging β-amyloid is problematic because many cognitively normal elderly have large amounts of β-amyloid in their brain, and appear as “positives” in the imaging tests.

Therapeutic approaches for Alzheimer’s disease generally have focused on β-amyloid because the process of producing a neurofibrillary tangle composed on tau protein has been poorly understood. Hence, few tau therapies have been developed. According to the researchers, this study makes important advances on both of these fronts.

The BUSM researchers identified a new group of proteins, termed RNA-binding proteins, which accumulate in the brains of patients with Alzheimer’s disease, and are present at much lower levels in subjects who are cognitively intact. The group found two different proteins, both of which show striking patterns of accumulation. “Proteins such as TIA-1 and TTP, accumulate in neurons that accumulate tau protein, and co-localize with neurofibrillary tangles. These proteins also bind to tau, and so might participate in the disease process,” explained senior author Benjamin Wolozin, MD, PhD, a professor in the departments of pharmacology and neurology at BUSM. “A different RNA binding protein, G3BP, accumulates primarily in neurons that do not accumulate pathological tau protein. This observation is striking because it shows that neurons lacking tau aggregates (and neurofibrillary tangles) are also affected by the disease process,” he added.

The researchers believe this work opens up novel approaches to diagnose and stage the likelihood of progression by quantifying the levels of these RNA-binding protein biomarkers that accumulate in the brains of Alzheimer patients.

Wolozin’s group also pursued the observation that some of the RNA binding proteins bind to tau protein, and tested whether one of these proteins, TIA-1, might contribute to the disease process. Previously, scientists have demonstrated that TIA-1 spontaneously aggregates in response to stress as a normal part of the stress response. Wolozin and his colleagues hypothesize that since TIA-1 binds tau, it might stimulate tau aggregation during the stress response. They introduced TIA-1 into neurons with tau protein, and subjected the neurons to stress. Consistent with their hypothesis, tau spontaneously aggregated in the presence of TIA-1, but not in the absence. Thus, the group has potentially identified an entirely novel mechanism to induce tau aggregates de novo. In future work, the group hopes to use this novel finding to understand how neurofibrillary tangles for in Alzheimer’s disease and to screen for novel compounds that might inhibit the progression of Alzheimer’s disease.

Provided by Boston University Medical Center

Source: medicalxpress.com

June 13, 2012

(Medical Xpress) — Consciousness is a selective process that allows only a part of the sensory input to reach awareness. But up to today it has yet to be clarified which areas of the brain are responsible for the content of conscious perception. Theofanis Panagiotaropoulos and his colleagues - researchers at the Max Planck Institute for Biological Cybernetics in Tübingen and University Pompeu Fabra in Barcelona - have now discovered that the content of consciousness is not localized in a unique cortical area, but is most likely an emergent property of global networks of neuronal populations.

Neurons in the lateral prefrontal cortex represent the content of consciousness. The red trace depicts neural activity (neuronal discharges) in the lateral prefrontal cortex when a stimulus is consciously perceived for 1 second while the green trace depicts neural activity when the same stimulus is suppressed from awareness. Credit: MPI for Biological Cybernetics

The question which parts of the brain are responsible for the things that reach our awareness is one of the main puzzles in neurobiology today. Previous research on the brains of primates has shown that neurons in primary and secondary cortices provide poor representation of visual consciousness. In contrast, the neurons in the temporal lobe seem to reliably reflect the actual conscious perception of a visual stimulus. These findings indicated that not all parts of the brain are responsible for the content of conscious awareness. Nevertheless, the question whether only one of the brain’s areas is responsible for the content of perception or whether more regions are involved in the process has so far remained unanswered.

The Max Planck scientists in Tübingen led by Nikos Logothetis have now addressed this issue using electrophysiological methods to monitor the neural activity in the lateral prefrontal cortex of macaque monkeys during ambiguous visual stimulation. The visual stimuli used allow for multiple perceptual interpretations, even though the actual input remained the same. In doing so, Panagiotaropoulos and his team were able to show that the electrical activity monitored in the lateral prefrontal cortex correlates with what the macaque monkeys actually perceive.

They thus concluded that visual awareness is not only reliably reflected in the temporal lobe, but also in the lateral prefrontal cortex of primates. The results depict that the neuronal correlates of consciousness are embedded in this area, which has a direct connection to premotor and motor areas of the brain, and is therefore able to directly affect motor output. These findings support the “frontal lobe hypothesis” of conscious visual perception established in 1995 by the researchers Crick (the co-discoverer of the structure of the DNA molecule) and Koch that awareness is related to neural activity with direct access to the planning stages of the brain.

The results support this theory in so far as they show that the lateral prefrontal cortex is involved in the process of visual awareness. However, the fact that neural activity in two different cortical areas reflects conscious perception shows that the decision which sensory input reaches our awareness is most likely not made in a unique cortical area but, rather, that a global network of neurons from different areas of the brain is responsible for it. “Our results therefore broaden the hypothesis and create new questions regarding the cortical mechanisms of visual awareness”, Panagiotaropoulos explains. In the near future the group is going to record the electrical activity in both regions simultaneously.

By this they will try to find out which of the two areas is activated first and draw conclusions on how the two areas interact with each other during conscious perception. This may lead to a better understanding of why only certain things reach our awareness and others remain suppressed.

Provided by Max Planck Society

Source: medicalxpress.com

June 13, 2012

(HealthDay) — Women with multiple sclerosis (MS) who undergo in vitro fertilization (IVF) are at greater risk of relapse after treatment, particularly if they receive gonadotrophin releasing hormone (GnRH) agonists or if IVF fails, according to a study published online June 11 in the Journal of Neurology, Neurosurgery & Psychiatry.

Women with multiple sclerosis who undergo in vitro fertilization (IVF) are at greater risk of relapse after treatment, particularly if they receive gonadotrophin releasing hormone agonists or if IVF fails, according to a study published online June 11 in the Journal of Neurology, Neurosurgery & Psychiatry.

Noting that pregnancy and treatment with sex steroids can affect the relapse rate in patients with MS, Laure Michel, M.D., from Hôpital Laennec in Nantes, France, and colleagues analyzed data from 32 women with MS who had undergone 70 IVF treatments during an 11-year study period: 48 with GnRH agonists and 19 with GnRH antagonists.

The researchers found that there were significantly more relapses in the three months after IVF (annualized relapse rate [ARR], 1.60), compared with one year before (ARR, 0.68) or three months before (ARR, 0.80). The increase in relapses was significantly associated with GnRH agonist use (P = 0.025) and failed IVF (P = 0.019).

"MS patients should be aware of a possible increased risk of MS relapse after IVF, particularly if the procedure does not result in a pregnancy," Michel and colleagues conclude. "Furthermore, because there is a reasonable doubt that GnRH agonists may make patients more prone to such an increase in relapse rate, GnRH antagonists might be preferred for IVF protocols.”

Source: medicalxpress.com

ScienceDaily (June 12, 2012) — As science rushes to develop safe weight loss drugs, a new research report approaches this problem from an entirely new angle: What if there were a pill that would make you want to exercise harder? It may sound strange, but a new research report appearing online in The FASEB Journal suggests that it might be possible. That’s because a team of Swiss researchers found that when a hormone in the brain, erythropoietin (Epo), was elevated in mice, they were more motivated to exercise.

In addition, the form of erythropoietin used in these experiments did not elevate red blood cell counts. Such a treatment has obvious benefits for a wide range of health problems ranging from Alzheimer’s to obesity, including mental health disorders for which increased physical activity is known to improve symptoms.

"Here we show that Epo increases the motivation to exercise," said Max Gassmann, D.V.M., a researcher involved in the work from the Institute of Veterinary Physiology, Vetsuisse-Faculty and Zurich Center for Integrative Human Physiology at the University of Zurich in Switzerland. "Most probably, Epo has a general effect on a person’s mood and might be used in patients suffering from depression and related diseases."

To make this discovery, Gassmann and colleagues used three types of mice: those that received no treatment, those that were injected with human Epo, and those that were genetically modified to produce human Epo in the brain. Compared to the mice that did not have any increase in Epo, both mouse groups harboring human Epo in the brain showed significantly higher running performance without increases in red blood cells.

"If you can’t put exercise in a pill, then maybe you can put the motivation to exercise in a pill instead," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “As more and more people become overweight and obese, we must attack the problem from all angles. Maybe the day will come when gyms are as easily found as fast food restaurants.”

Source: Science Daily

ScienceDaily (June 12, 2012) — Researchers in France and Sweden have discovered how one of the body’s own proteins is involved in generating chronic pain in rats. The results, which also suggest therapeutic interventions to alleviate long-lasting pain, are reported in The EMBO Journal.

Chronic pain is persistent and often difficult to treat. It is due, at least in part, to changes in molecular signalling events that take place in neurons, alterations that can ultimately disrupt the transmission of nerve signals from the spinal cord to the brain.

"We are fortunate to have a wide range of technologies that allow us to look more precisely at the molecular events that lead to the onset of chronic pain in animals," said Marc Landry, lead author of the study and Professor at the University of Bordeaux.

"Our results show that the levels of the naturally occurring protein 14-3-3 zeta are higher in the spinal cord of rats that have chronic pain. Moreover, we have been able to demonstrate how 14-3-3 zeta triggers changes in the signalling pathway that leads to the symptoms of chronic pain."

The 14-3-3 zeta protein disrupts the interaction between the two subunits of the GABA_B receptor, a protein complex found on the surface of nerve cells. GABA_B receptors are G-protein coupled receptors, a family of receptors that regulate many physiological processes and which are frequently targeted for drug development.

The researchers used antibody labelling and microscopy techniques to investigate the molecular interactions of the signalling proteins. In cells and living animals, they were able to show that the 14-3-3 zeta protein interacts directly with the B1 subunit of the GABA_B receptor. This interaction impairs the effective signalling of the receptor and limits the pain-relieving effects of the GABA_B receptor under conditions of chronic pain.

The researchers also showed that the treatment of rats with a specific small interfering RNA (siRNA) or a competing peptide, molecules that interfere with the action of the 14-3-3 zeta protein, inhibited chronic pain.

"The impairment of the GABA_B receptor by 14-3-3 zeta is a novel mechanism for the modulation of chronic pain,” said Landry. “We see potential in combining the use of inhibitors that interfere with the action of 14-3-3 zeta together with existing drug treatments like Baclofen for chronic pain. Targeting the GABA_B dissociation process may be of therapeutic interest since it may allow classical pain killers to be more effective.”

Source: Science Daily

ScienceDaily (June 12, 2012) — A team led by investigators at the Stanford University School of Medicine has found that the most common genetic risk factor for Alzheimer’s disease disrupts brain function in healthy, older women but has little impact on brain function in healthy, older men. Women harboring the gene variant, known to be a potent risk factor for Alzheimer’s disease, show brain changes characteristic of the neurodegenerative disorder that can be observed before any outward symptoms manifest.

Both men and women who inherit two copies (one from each parent) of this gene variant, known as ApoE4, are at extremely high risk for Alzheimer’s. But the double-barreled ApoE4 combination is uncommon, affecting only about 2 percent of the population, whereas about 15 percent of people carry a single copy of this version of the gene.

The Stanford researchers demonstrated for the first time the existence of a gender distinction among outwardly healthy, older people who carry the ApoE4 variant. In this group, women but not men exhibit two telltale characteristics that have been linked to Alzheimer’s disease: a signature change in their brain activity, and elevated levels of a protein called tau in their cerebrospinal fluid.

One implication of the study, published June 13 in the Journal of Neuroscience, is that men revealed by genetic tests to carry a single copy of ApoE4 shouldn’t be assumed to be at elevated risk for Alzheimer’s, a syndrome afflicting about 5 million people in the United States and nearly 30 million worldwide. The new findings also may help explain why more women than men develop this disease, said Michael Greicius, MD, assistant professor of neurology and neurological sciences and medical director of the Stanford Center for Memory Disorders. Most critically, identifying the prominent interaction between ApoE4 and gender opens a host of new experimental avenues that will allow Greicius’ team and the field generally to better understandhow ApoE4 increases risk for Alzheimer’s disease.

For every three women with Alzheimer’s disease, only about two men have the neurodegenerative disorder, said Greicius, the study’s senior author. (The first author is Jessica Damoiseaux, PhD, a postdoctoral scholar in Greicius’ laboratory. They collaborated with colleagues at the University of California-San Francisco and UCLA.) True, women live longer than men do, on average, and old age is by far the greatest risk factor for Alzheimer’s, Greicius said. “But the disparity in Alzheimer’s risk persists even if you correct for the difference in longevity,” he said. “This disparate impact of ApoE4 status on women versus men might account for a big part of the skewed gender ratio.”

Besides age, another well-studied major risk factor is genetic: possession of a particular version of the gene known as ApoE. This gene is a recipe for a protein involved in transporting cholesterol into cells — an important job, as cholesterol is a crucial constituent of all cell membranes including those of nerve cells. And nerve cells are constantly responding to experience by developing or enhancing small, bulblike electrochemical contacts to other nerve cells, or diminishing or abolishing them. For all these processes, efficient cholesterol transport is critical.

The ApoE protein comes in three versions, each the product of a slightly differing version of the ApoE gene: E2, E3 or E4. Most people have two copies of the E3 version of ApoE. A small percentage carries one copy of E3 and one of E2, and even fewer two copies of E2. The protein specified by the E4 gene version seems to be somewhat defective in comparison to the one encoded by either E2 or the much more common E3. Thus, while only about 10-15 percent of the population carries one copy of E4 (or, much less commonly, two), more than 50 percent of people who develop Alzheimer’s are E4 carriers.

But, as it turns out, the heightened risk E4 imposes may be largely restricted to women.

To demonstrate this, the scientists first obtained functional MRI scans of 131 healthy people, with a median age of 70, to examine connections in the brain’s memory network. They used sophisticated brain-imaging analysis to show that in older women carrying the E4 variant, this network of interconnected brain regions, which normally share a synchronized pattern of activity, exhibit a loss of that synchrony — a pattern typically seen in Alzheimer’s patients. In healthy, older women (but not men) with at least one E4 allele, activity in a brain area called the precuneus appeared be out of synch with other regions whose firing patterns generally are closely coordinated.

The brain-imaging technique Greicius and his colleagues used is known as functional-connectivity magnetic resonance imaging, or fcMRI. Performed on “resting” subjects, who remain in the scanner awake but not focusing on any particular task, fcMRI can discern on the order of 20 different brain networks, each consisting of a set of dispersed brain regions that are physically connected by nerve tracts and whose pulses of activity are synchronized, or in phase. Greicius, Damoiseaux and their associates have previously shown that the synchronous firing pattern of one network in particular, critical to memory function and known as the “default mode network,” is specifically targeted by Alzheimer’s and deteriorates as the disease progresses.

To independently confirm their imaging-based observations, the scientists assessed records from a large public database compiled from the Alzheimer’s Disease Neuroimaging Initiative, a multi-site study of healthy aging and Alzheimer’s disease. The Stanford study focused on the healthy 55- to 90-year-old volunteers who had agreed to undergo a spinal tap and have their cerebrospinal fluid analyzed.

From this database the Greicius team extracted the records of 91 subjects, with an average age of 75, and divided them into four groups representing women with or without a copy of the E4 variant, and men with or without a copy. For each group, they checked recorded concentrations of a protein named tau in these subjects’ cerebrospinal fluid. Elevated tau levels in cerebrospinal fluid are a key biomarker of Alzheimer’s disease. The results — the CSF of women, but not men, who carried at least one E4 allele was substantially enriched in tau — confirmed the brain-imaging findings.

The tau findings constitute another first. “It was only possible to see these differences in tau levels when we separated the patients by gender,” Greicius said.

Notably, all the men and women participating in the Journal of Neuroscience study were screened for cognitive status. Only those whose ability to think and remember appeared normal for their age were admitted. Thus, the observed changes in brain activity and CSF composition were occurring well before the onset of classic Alzheimer’s symptoms such as memory loss, disorientation and dementia. It may someday be practical to substitute fcMRI, which is noninvasive, for a spinal tap as a diagnostic tool, Greicius said.

Source: Science Daily

June 12, 2012

One of the brain’s jobs is to help us figure out what’s important enough to be remembered. Scientists at Yerkes National Primate Research Center, Emory University have achieved some insight into how fleeting experiences become memories in the brain.

Their experimental system could be a way to test or refine treatments aimed at enhancing learning and memory, or interfering with troubling memories. The results were published recently in the Journal of Neuroscience.

The researchers set up a system where rats were exposed to a light followed by a mild shock. A single light-shock event isn’t enough to make the rat afraid of the light, but a repeat of the pairing of the light and shock is, even a few days later.

"I describe this effect as ‘priming’," says the first author of the paper, postdoctoral fellow Ryan Parsons. "The animal experiences all sorts of things, and has to sort out what’s important. If something happens just once, it doesn’t register. But twice, and the animal remembers."

Parsons was working with Michael Davis, PhD, Robert W. Woodruff professor of psychiatry and behavioral sciences at Emory University School of Medicine, who has been studying the molecular basis for fear memory for several years.

Even though a robust fear memory was not formed after the first priming event, at that point Parsons could already detect chemical changes in the amygdala, part of the brain critical for fear responses. Long term memory formation could be blocked by infusing a drug into the amygdala. The drug inhibits protein kinase A, which is involved in the chemical changes Parsons observed.

It is possible to train rats to become afraid of something like a sound or a smell after one event, Parsons says. However, rats are less sensitive to light compared with sounds or smells, and a relatively mild shock was used.

Fear memories only formed when shocks were paired with light, instead of noise or nothing at all, for both the priming and the confirmation event. Parsons measured how afraid the rats were by gauging their “acoustic startle response” (how jittery they were in response to a loud noise) in the presence of the light, compared to before training began.

Scientists have been able to study the chemical changes connected with the priming process extensively in neurons in culture dishes, but not as much in live animals. The process is referred to as “metaplasticity,” or how the history of the brain’s experiences affects its readiness to change and learn.

"This could be a good model for dissecting the mechanisms involved in learning and memory,” Parsons says. “We’re going to be able to look at what’s going on in that first priming event, as well as when the long-term memory is triggered.”

"We believe our findings might help explain how events are selected out for long-term storage from what is essentially a torrent of information encountered during conscious experience," Parsons and Davis write in their paper.

Provided by Emory University

Source: medicalxpress.com

ScienceDaily (June 12, 2012) — UCC scientists have shown that brain levels of serotonin, the ‘happy hormone’ are regulated by the amount of bacteria in the gut during early life. Their research is being published June 12 in the international psychiatry journal, Molecular Psychiatry.

Happy children. UCC scientists have shown that brain levels of serotonin, the ‘happy hormone’ are regulated by the amount of bacteria in the gut during early life. (Credit: © Marzanna Syncerz / Fotolia)

This research shows that normal adult brain function depends on the presence of gut microbes during development. Serotonin, the major chemical involved in the regulation of mood and emotion, is altered in times of stress, anxiety and depression and most clinically effective antidepressant drugs work by targeting this neurochemical.

Scientists at the Alimentary Pharmabiotic Centre in UCC used a germ-free mouse model to show that the absence of bacteria during early life significantly affected serotonin concentrations in the brain in adulthood. The research also highlighted that the influence is sex dependent, with more marked effects in male compared with female animals. Finally, when the scientists colonized the animals with bacteria prior to adulthood, they found that many of the central nervous system changes, especially those related to serotonin, could not be reversed indicating a permanent imprinting of the effects of absence of gut flora on brain function.

This builds on earlier work, from the Cork group and others, showing that a microbiome-gut-brain axis exists that is essential for maintaining normal health which can affect brain and behavior. The research was carried out by Dr Gerard Clarke, Professor Fergus Shanahan, Professor Ted Dinan and Professor John F Cryan and colleagues at the Alimentary Pharmabiotic Centre in UCC.

"As a neuroscientist these findings are fascinating as they highlight the important role that gut bacteria play in the bidirectional communication between the gut and the brain, and opens up the intriguing opportunity of developing unique microbial-based strategies for treatment for brain disorders," said Professor John F Cryan, senior author on the publication and Head of the Department of Anatomy & Neuroscience at UCC.

This research has multiple health implications as it shows that manipulations of the microbiota (e.g. by antibiotics, diet, or infection) can have profound knock-on effects on brain function. “We’re really excited by these findings” said lead author Dr Gerard Clarke. “Although we always believed that the microbiota was essential for our general health, our results also highlight how important our tiny friends are for our mental wellbeing.”

Source: Science Daily

ScienceDaily (June 12, 2012) — In a study published June 12 in the journal Molecular Psychiatry, researchers from the Twins Early Development Study at King’s College London’s Institute of Psychiatry studied data from more than 6700 families relating to 45 childhood characteristics, from IQ and hyperactivity to height and weight. They found that genetic and environmental contributions to these characteristics vary geographically in the UK and have published their results online as a series of nature-nurture maps.

Newborn twins. (Credit: © pojoslaw / Fotolia)

Our development, health and behaviour are determined by complex interactions between our genetic make-up and the environment in which we live. For example, we may carry genes that increase our risk of developing type 2 diabetes, but if we eat a healthy diet and get sufficient exercise, we may not develop the disease. Similarly, someone may carry genes that reduce his or her risk of developing lung cancer, but heavy smoking may still lead to the disease.

The UK-based Twins Early Development Study follows more than 13,000 pairs of twins, both identical and non-identical, born between 1994 and 1996. When the twins were age 12, the researchers carried out a broad survey to assess a wide range of cognitive abilities, behavioural (and other) traits, environments and academic achievement in 6759 twin pairs. The researchers then designed an analysis that reveals the UK’s genetic and environmental hotspots, something which had never been done before.

"These days we’re used to the idea that it’s not a question of nature or nurture; everything, including our behaviour, is a little of both," explains Dr Oliver Davis, a Sir Henry Wellcome Postdoctoral Fellow at King’s College London’s Institute of Psychiatry. "But when we saw the maps, the first thing that struck us was how much the balance of genes and environments can vary from region to region."

"Take a trait like classroom behaviour problems. From our maps we can tell that in most of the UK around 60 per cent of the difference between people is explained by genes. However, in the South East genes aren’t as important: they explain less than half of the variation. For classroom behaviour, London is an ‘environmental hotspot’."

The maps give the researchers a global overview of how the environment interacts with our genomes, without homing in on particular genes or environments. However, the patterns have given them important clues about which environments to explore in more detail.

"The nature-nurture maps help us to spot patterns in the complex data and to try to work out what’s causing these patterns," says Dr Davis. "For our classroom behaviour example, we realised that one thing that varies more in London is household income. When we compare maps of income inequality to our nature-nurture map for classroom behaviour, we find income inequality may account for some of the pattern.

"Of course, this is just one example. There are any number of environments that vary geographically in the UK, from social environments like healthcare or education provision to physical environments like altitude, the weather or pollution. Our approach is all about tracking down those environments that you wouldn’t necessarily think of at first."

It may be relatively easy to explain environmental hotspots, but what about the genetic hotspots that appear on the maps: do people’s genomes vary more in those regions? The researchers believe this is not the case; rather, genetic hotspots are areas where the environment exposes the effects of genetic variation.

For example, researchers searching for gene variants that increase the risk of hay fever may study populations from two regions. In the first region people live among fields of wind-pollinated crops, whereas the second region is miles away from those fields. In this second region, where no one is exposed to pollen, no one develops hay fever; hence any genetic differences between people living in this region would be invisible.

By contrast, in the first region, where people live among the fields of crops, they will all be exposed to pollen and differences between the people with a genetic susceptibility to hay fever and the people without will stand out. That would make the region a genetic hotspot for hay fever.

"The message that these maps really drive home is that your genes aren’t your destiny. There are plenty of things that can affect how your particular human genome expresses itself, and one of those things is where you grow up," says Dr Davis.

Source: Science Daily

June 12, 2012

Financial loss can lead to irrational behavior. Now, research by Weizmann Institute scientists reveals that the effects of loss go even deeper: Loss can compromise our early perception and interfere with our grasp of the true situation. The findings, which recently appeared in the Journal of Neuroscience, may also have implications for our understanding of the neurological mechanisms underlying post-traumatic stress disorder.

The experiment was conducted by Dr. Rony Paz and research student Offir Laufer of the Neurobiology Department. Subjects underwent a learning process based on classic conditioning and involving money. They were asked to listen to a series of tones composed of three different notes. After hearing one note, they were told they had earned a certain sum; after a second note, they were informed that they had lost some of their money; and a third note was followed by the message that their bankroll would remain the same. According to the findings, when a note was tied to gain, or at least to no loss, the subjects improved over time in a learned task – distinguishing that note from other, similar notes. But when they heard the “lose money” note, they actually got worse at telling one from the other.

Functional MRI (fMRI) scans of the brain areas involved in the learning process revealed an emotional aspect: The amygdala, which is tied to emotions and reward, was strongly involved. The researchers also noted activity in another area in the front of the brain, which functions to moderate the emotional response. Subjects who exhibited stronger activity in this area showed less of a drop in their abilities to distinguish between tones.

Paz: “The evolutionary origins of that blurring of our ability to discriminate are positive: If the best response to the growl of a lion is to run quickly, it would be counterproductive to distinguish between different pitches of growl. Any similar sound should make us flee without thinking. Unfortunately, that same blurring mechanism can be activated today in stress-inducing situations that are not life-threatening – like losing money – and this can harm us.”

That harm may even be quite serious: For instance, it may be involved in post-traumatic stress disorder. If sufferers are unable to distinguish between a stimulus that should cause a panic response and similar, but non-threatening, stimuli, they may experience strong emotional reactions in inappropriate situations.

This perceptional blurring may even expand over time to encompass a larger range of stimuli. Paz intends to investigate this possibility in future research.

Provided by Weizmann Institute of Science

Source: medicalxpress.com

June 12, 2012

You pick up your cell phone and dial the new number of a friend. Ten numbers. One. Number. At. A. Time. Because you haven’t actually typed the number before, your brain handles each button press separately, as a sequence of distinct movements.

This image shows identified brain regions linked to the parsing (left) and concatenation (right) processes involved in motor chunking. Trials with greater parsing showed increased activation of the left prefrontal and parietal cortex and trials with greater concatenation showed increased activation of the putamen. Credit: Photo by Nicholas Wymbs

After dialing the number a few more times, you find yourself typing it out as a series of three successive bursts of movement: the area code, the first three numbers, the last four numbers. Those three separate chunks allow you to type the number faster, and with greater precision. Eventually, dialed often enough, the number is stored in your brain as one chunk. Who needs speed dial?

"You can think about a chunk as a rhythm," said Nicholas Wymbs, a postdoctoral researcher in UC Santa Barbara’s Department of Psychological and Brain Sciences, and the lead author of a new study on motor chunking in the journal Neuron, published by Cell Press. “We highlight the two-part process that seems to occur when we are chunking. This is demonstrated by the rhythm we use when typing the phone number: rapid bursts of finger movements that are interspersed by pauses.”

The rhythm is the human brain taking information and processing it in an efficient way, according to Wymbs. “On one level, the brain is going to try to divide up, or parse, long sequences of movement,” he said. “This parsing process functions to group or cluster movements in the most efficient way possible.”

But it is also in our brain’s best interest to assemble single or short strings of movements into longer, integrated sequences so that a complex behavior can be made with as little effort as possible. “The motor system in the brain wants to output movement in the most computational, low-cost way as possible,” Wymbs said. “With this integrative process, it’s going to try to bind as many individual motor movements into a fluid, uniform movement as it possibly can.”

This diagram illustrates how the subjects in the experiment used their left hands to respond to the “notes” on a button box. Credit: Illustration by Nicholas Wymbs

The two processes are at odds with each other, and it’s how the brain reconciles this struggle during motor learning that intrigues Wymbs and the study’s other authors, including Scott Grafton, professor of psychology and director of the UCSB Brain Imaging Center. “What we are interested in is functional plasticity of the brain –– how the brain changes when we learn actions, or motor sequences as we refer to them in this paper,” Wymbs said.

The study was conducted using human subjects in the Magnetic Resonance Imaging (MRI) scanner in the Brain Imaging Center. The experiment involved three days of training with people performing and practicing three separate motor sequences for up to 200 trials each during the collection of functional MRI data. The subjects were all right-handed but they were asked to learn the sequences using the four fingers of their left hands. Participants practiced the sequences during the operation of the MRI scanner by tapping out responses with a button box that looked like a set of piano keys, with long, rectangular buttons.

"People would see a static image shown on a video screen that detailed the sequence to be typed out," Wymbs said. "They’re lying down inside the scanner and they see this image above their eyes. Interestingly, some people reported that the images looked like something out of (the video game) Guitar Hero, and, indeed, it does look a bit like guitar tablature. They would have to type out the ‘notes’ from left to right, as you normally would when reading music.

"After practicing a sequence for 200 trials, they would get pretty good at it," Wymbs added. "After awhile, the note patterns become familiar. At the start of the training, it would take someone about four and a half seconds to complete each sequence of 12 button presses. By the end of the experiment, the average participant could produce the same sequence in under three seconds."

The researchers’ goal was to look at which areas of the brain support the two-part process of chunking. “We feel that the motor process, or the concatenation process as we refer to it in the paper, tends to take over as you continue to practice and continue to learn the sequences,” Wymbs said. “That’s the one that’s tied to the motor output system –– the thing that’s actually accomplishing what we set out to do.”

With the experience of repeating a motor sequence, such as typing out a phone number, speaking, typing on a computer, or even texting, it becomes more automatic. “With automaticity comes the recruitment of core motor output regions,” Wymbs said.

The scientists discovered that the putamen –– a brain region that is critically important to movement –– supports the concatenation process of motor chunking, with robust connectivity to parts of the brain that are intimately tied to the output of skilled motor behavior. On the other hand, they found that cortical regions in the left hemisphere respond more during the parsing process of motor chunking. “These regions have been linked to the manipulation of motor information, which is something that we probably do more of when we just begin to learn the sequences as chunks,” Wymbs said.

"Initially, when you’re doing one of these 12-element sequences, you want to pause,” Wymbs added. “That would evoke more of the parsing mechanism. But then, over time, as you learn a sequence so that it becomes more automatic, and the concatenation process takes over and it wants to put all of these individual elements into a single fluid behavior.”

According to Wymbs, the findings could have implications for the study and diagnosis of Parkinson’s and other diseases of the motor system that involve action. “We show here that there are two potentially competing systems that lead to the isolation of different systems that both work to allow us to process things efficiently when we’re learning,” Wymbs said.

Provided by University of California - Santa Barbara

Source: medicalxpress.com

ScienceDaily (June 12, 2012) — Studying how nerve cells send and receive messages, Johns Hopkins scientists have discovered new ways that genetic mutations can disrupt functions in neurons and lead to neurodegenerative disease, including amyotrophic lateral sclerosis (ALS).

Neurons are shown in green. A normal neuron is on the left and p150glued mutant neuron is on the right. The red cargo accumulates in the mutant but not in the normal neuron. Areas with the highest cargo accumulation are yellow at the tip of the neuron. (Credit: Image courtesy of Johns Hopkins Medicine)

In a report published April 26 in Neuron, the research team says it has discovered that a mutation responsible for a rare, hereditary motor neuron disease called hereditary motor neuropathy 7B (HMN7B) disrupts the link between molecular motors and the nerve cell tip where they reside. This mutation results in the production of a faulty protein that prevents material from being transported from the cell’s edge, which is located at the muscle and extends back toward its “body” in the central nervous system. In pinpointing how and where this cargo transport is disrupted, the scientists are now closer to understanding mechanisms underlying this condition and ALS.

"An important question we need to answer is how defects in proteins that normally perform important cellular functions for neurons lead to disease," says Alex Kolodkin, Ph.D., a Howard Hughes Medical Institute Investigator and professor of neuroscience at the Johns Hopkins University School of Medicine. "A major issue in understanding neurodegenerative diseases is determining how certain proteins that are expressed in all types of neurons, or even in all cells in the body, can lead to devastating effects in one, or a few, subsets of neurons." Kolodkin notes that many neurodegenerative diseases involve proteins that serve general functions required in nearly every type of cell in the body, including the transport of material between different parts of a cell, yet certain alterations in these proteins can result in specific neurological disorders.

One particular protein, p150glued, is known to play a role in at least two of these disorders, HMN7B, which is similar to ALS, and Perry syndrome, which leads to symptoms similar to Parkinson’s disease. p150glued is part of a larger complex of proteins that forms a molecular “motor” capable of transporting various molecules and other “cargo” from the nerve end toward the cell body. To better understand how mutations in p150glued lead to HMN7B and Perry syndrome, the researchers turned to fruit flies, which are easy to genetically manipulate and where the same protein has been well studied.

They engineered the fruit fly p150glued protein to contain the same mutations as those implicated in the two diseases and used microscopy techniques that enable them to follow in live cells the movement of fluorescently tagged cargo along motor neurons.

They found, surprisingly, that the movement of cargo along the length of the cell was normal. However, at the far end of the cell, they found that the HMN7B-associated mutation caused an unusually large accumulation of cargo. “This was an unexpected finding,” says Thomas Lloyd, M.D., Ph.D., an assistant professor in neurology and neuroscience at the Johns Hopkins School of Medicine. “We need to better understand how this is causing disease.”

Using flies engineered to contain mutations in other motor proteins, and again watching cargo transport in live cells, the team found that p150glued works in concert with another motor to control cargo transport. Their results suggest that when p150glued is compromised, this control is lost and cargo accumulates at the nerve end, leading to disease.

"It’s still unclear how these two different mutations in different regions of the same protein cause very distinct neurodegenerative diseases," Lloyd says. Encouraged by their results, the team plans to continue using fruit flies to unravel the molecular mechanisms underlying these diseases.

Source: Science Daily

ScienceDaily (June 11, 2012) — The world needs new antibiotics to overcome the ever increasing resistance of disease-causing bacteria — but it doesn’t need the side effect that comes with some of the most powerful ones now available: hearing loss. Today, researchers report they have developed a new approach to designing antibiotics that kill even “superbugs” but spare the delicate sensory cells of the inner ear.

These delicate hair cells from the inner ear of mice were tested to see the effects of powerful antibiotics on structures that are crucial to hearing. At left, cells that were exposed to the antibiotic gentamycin showed signs of high levels of damaging free radicals (seen in green). But cells treated with the veterinary drug apramycin. shown at right, didn’t show these effects — adding to evidence that this drug could be used to treat humans without damaging hearing. (Credit: University of Michigan, Schacht laboratory)

Surprisingly, they have found that apramycin, an antibiotic already used in veterinary medicine, fits this bill — setting the stage for testing in humans.

In a paper published online in the Proceedings of the National Academy of Sciences, a team from Switzerland, England and the University of Michigan show apramycin’s high efficacy against bacteria, and low potential for causing hearing loss, through a broad range of tests in animals. That testing platform is now being used to evaluate other potential antibiotics that could tackle infections such as multidrug-resistant tuberculosis.

The research aims to overcome a serious limitation of aminoglycoside antibiotics, a class of drugs which includes the widely used kanamycin, gentamicin and amikacin.

While great at stopping bacterial infections, these drugs also cause permanent partial hearing loss in 20 percent of people who take them for a short course, and up to 100 percent of people who take them over months or years, for example to treat tuberculosis or lung infections in cystic fibrosis.

U-M researcher Jochen Schacht, Ph.D., a professor of biological chemistry and otolaryngology and director of the Kresge Hearing Research Institute at the U-M Medical School, has spent decades studying why these drugs cause this “ototoxicity” — a side effect that makes doctors hesitant to prescribe them. Hearing damage has also caused patients to discontinue treatment before their antibiotic prescription is over, potentially allowing drug-resistant strains of bacteria to flourish.

Schacht has found that the drugs produce damaging free radicals inside the hair cells of the inner ear. Hair cells, named for the tiny sound-sensing hairs on their surface, are the linchpin of hearing — and once destroyed, cannot be regrown.

In the new paper, Schacht and his research group joined teams led by University of Zurich microbiologist Erik Böttger, and structural biologist and Nobel Prize winner Venkatraman Ramakrishnan of England’s Medical Research Council Laboratory of Molecular Biology, as well as scientists from ETH Zurich. Each team brought its particular expertise to the issue, and after four years of work they developed and tested this new approach to designing antibiotics.

"Aminoglycosides are some of the most valuable broad-spectrum antibiotics and indispensable drugs today, but we need new options to combat drug-resistant bacteria. Importantly, we must find ways to overcome their ototoxicity," Schacht says. "Instead of the trial-and-error approach of the past, this new hypothesis-driven tactic allows us to design drugs with simultaneous attention toward both antibacterial action and impact on hair cells."

According to the World Health Organization, about 440,000 new cases of multidrug-resistant tuberculosis emerge annually, causing at least 150,000 deaths worldwide. Aminoglycoside antibiotics, while carefully controlled in the U.S., Europe, and other developed countries are available over the counter in many developing nations, leading to overuse that makes it even easier for drug-resistant strains of many kinds of bacteria to emerge and spread.

The new paper outlines a rational approach to designing drugs to combat this threat without ototoxicity, based on a theoretical framework that emerged from the work of the three laboratories and centers around the role of ribosomes, the structures inside the cell that “read” DNA and translate the genetic message into proteins. Böttger’s lab, at the Institut für Medizinische Mikrobiologie which he directs, studies aminoglycoside effects on mitochondrial ribosomes and antibacterial activity with an eye toward designing new ones. Ramakrishnan’s lab studies ribosomes, and partners from ETH Zurich also collaborated.

Aminoglycosides bind to the ribosomes inside bacterial cells, preventing the ability to produce proteins. But while the drugs spare most human ribosomes, they can attach to ribosomes in the mitochondria of cells, which are similar to bacterial ribosomes.

Consistent with U-M-generated theories about ototoxicity, the drugs then cause the production of free radicals in such quantities that they overwhelm the hair cells’ defense mechanisms — destroying the cells and causing hearing loss.

The team’s approach is to design drugs that more specifically target bacterial ribosomes over mitochondrial ribosomes, simultaneously testing the impact on hair cells as well as the ability to kill bacteria. In this way, the researchers try to avoid creating antibiotics that harm hearing.

They are already using the platform employed for this study — which involves cells from mouse ears, and tests of hearing and hair cell damage in guinea pigs — to test other promising novel drugs synthesized based on the theoretical framework that was driving the current research.

Meanwhile, the team hopes to launch a clinical trial of apramycin, an antibiotic that could prove immediately useful because multidrug-resistant TB and lung-infecting bacteria have not shown resistance to the drug yet.

The research also lends more evidence to support the use of antioxidants to protect the hearing of patients taking current aminoglycoside antibiotics. Schacht has already led a clinical trial in China that showed a major reduction in hearing loss if aspirin was given at the same time as aminoglycoside antibiotics. “This kind of protection is important, while we search for the long-term answer to drug resistance without ototoxicity,” he says.

Source: Science Daily

June 11, 2012

Researchers at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital have identified a portion of the brain responsible for determining how far away a sound originates, a process that does not rely solely on how loud the sound is. The investigators’ report, which will appear in the early edition of Proceeding of the National Academy of Sciences, is receiving early online release this week.

This is an image of human cerebral cortex, digitally “inflated” to smooth out normal folds and ridges, showing in red the portion of auditory cortex that responds to the distance from which sounds arrive. Credit: Jyrki Ahveninen, Ph.D., Martinos Center for Biomedical Imaging, Massachusetts General Hospital

"Although sounds get louder when the source approaches us, humans are able to discriminate between loud sounds that come from far away and softer sound from a closer source, suggesting that our brains use distance cues independent of loudness," says Jyrki Ahveninen, PhD, of the Martinos Center, senior author of the PNAS report. "Using functional MRI we found a group of neurons in the auditory cortex sensitive to the distance of sound sources and different from those that process changes in loudness. In addition to providing basic scientific information, our results could help future studies of hearing disorders.”

The human brain has distinct areas for processing sensory information – signals responsible for vision, hearing, taste etc. Studies of the visual cortex, located at the back of the brain, have produced detailed maps of areas handling particular portions of the visual field. But understanding of the auditory cortex, located on the side of the head above and behind the ear, is quite limited. While it is known that the portion of the auditory cortex extending toward the back of the head determines where a sound comes from, exactly how the brain translates complex auditory signals to determine both the location and distance from which a sound originates is not yet known.

In their search for auditory neurons that process sound distance, the research team faced some particular challenges. In research laboratories that study hearing, sounds must be delivered to study participants through headphones, which means the acoustical “space” in which a sound is generated must be simulated. This must be done with exquisite accuracy, since environmental aspects causing sound to reverberate probably contribute to distance perception. Since the MRI equipment itself generates a loud noise, the researchers scanned participants’ brains once every 12 seconds to measure responses to sounds presented during intervening quiet periods.

In the first experiment, study participants – 12 adults with normal hearing – listened to a series of paired sounds of varying degrees of loudness and at simulated distances ranging from 15 to 100 cm and were asked to indicate whether the second sound was closer or farther away than the first. Although the differences in loudness varied randomly, participants were quite accurate in distinguishing the simulated distances of the sounds. Acoustical analysis of the particular sound cues presented indicated that the reverberations produced by a sound, which are more pronounced in a closed environment and for sounds traveling farther, may be more important distance cues than are the differences between sounds perceived by a participant’s two ears.

After the first experiment confirmed the accuracy of the simulated acoustical environment, functional MR images taken while participants listened to another series of paired sounds recorded how activity in the auditory cortex changed in response to sounds of varying loudness and direction as well as during sound of constant levels and silence. The images produced identified a small area that appears to be sensitive to cues indicating distance but not loudness. As far as the investigators know, this is the first time neurons sensitive to sound-source distances have been discovered.

"The identified area is located near other auditory cortical areas that process spatial information," says corresponding author Norbert Kopco, PhD. "This is consistent with a general model of perceptual processing in the brain, suggesting that in hearing, as in vision and other senses, spatial information is processed separately from information about the object’s identity or characteristics such as the musical pitch of sound. Our study also illustrates how important it is to combine expertise from different fields – in our case imaging/physiology, psychology, and computational neuroscience – to advance our understanding of such a complex system as the human brain.”

Provided by Massachusetts General Hospital

Source: medicalxpress.com

ScienceDaily (June 11, 2012) — In a pair of related studies, scientists from the Florida campus of The Scripps Research Institute have identified several proteins that help regulate cells’ response to light — and the development of night blindness, a rare disease that abolishes the ability to see in dim light.

In the new studies, published recently in the journals Proceedings of the National Academy of Sciences (PNAS) and The Journal of Cell Biology, Scripps Florida scientists were able to show that a family of proteins known as Regulator of G protein Signaling (RGS) proteins plays an essential role in vision in a dim-light environment.

"We were looking at the fundamental mechanisms that shape our light sensation," said Kirill Martemyanov, a Scripps Research associate professor who led the studies. "In the process, we discovered a pair of molecules that are indispensible for our vision and possibly play critical roles in the brain."

In the PNAS study, Martemyanov and his colleagues identified a pair of regulator proteins known as RGS7 and RGS11 that are present specifically in the main relay neurons of the retina called the ON-bipolar cells. “The ON-bipolar cells provide an essential link between the retinal light detectors — photoreceptors and the neurons that send visual information to the brain,” explained Martemyanov. “Stimulation with light excites these neurons by opening the channel that is normally kept shut by the G proteins in the dark. RGS7 and RGS11 facilitate the G protein inactivation, thus promoting the opening of the channel and allowing the ON-bipolar cells to transmit the light signal. It really takes a combined effort of two RGS proteins to help the light overcome the barrier for propagating the excitation that makes our dim vision possible.”

In the Journal of Cell Biology study, Martemyanov and his colleagues unraveled another key aspect of the RGS7/RGS11 regulatory response — they identified a previously unknown pair of orphan G protein-coupled receptors (GPCRs) that interact with these RGS proteins and dictate their biological function.

GPCRs are a large family of more than 700 proteins, which sit in the cell membrane and sense various molecules outside the cell, including odors, hormones, neurotransmitters, and light. After binding these molecules, GPCRs trigger the appropriate response inside the cell. However, for many GPCRs the activating molecules have not yet been identified and these are called “orphan” receptors.

The Martemyanov group has found that two orphan GPCRs — GPR158 and GPR179 — recruit RGS proteins and thus help serve as brakes for the conventional GPCR signaling rather than play an active signaling role.

In the case of retinal ON-bipolar cells, GPR179 is required for the correct localization of RGS7 and RGS11. Their mistargeting in animal models lacking GPR179 or human patients with mutations in the GPR179 gene may account for their night blindness, according to the new study. Intriguingly, in the brain GPR158 appears to play a similar role in localizing RGS proteins, but instead of contributing to vision, it helps RGS proteins regulate the m-opioid receptor, a GPCRs that mediates pleasurable and pain-killing effects of opioids.

"We are really in the very beginning of unraveling this new biology and understanding the role of discovered orphan GPR158/179 in regulation of neurotransmitter signaling in the brain and retina," Martemyanov said. "The hope is that better understanding of these new molecules will lead to the design of better treatments for addictive disorders, pain, and blindness."

Source: Science Daily

ScienceDaily (June 11, 2012) — Researchers at the University of Missouri have demonstrated the effectiveness of a potential new therapy for stroke patients in an article published in the journal Molecular Neurodegeneration. Created to target a specific enzyme known to affect important brain functions, the new compound being studied at MU is designed to stop the spread of brain bleeds and protect brain cells from further damage in the crucial hours after a stroke.

In a model of induced stroke in mice, MU researchers have shown the success of a treatment in stopping further bleeding in the brain after a stroke (above). The outlined area shows the stroke damage. (Credit: Image courtesy of University of Missouri School of Medicine)

Stroke is a leading cause of death in the U.S. with more than 800,000 deaths occurring each year from stroke and other cardiac events. Other than surgery, existing emergency treatments for stroke victims such as the use of a tissue plasminogen activator (tPA) must be administered within hours of the stroke onset because of the risk for brain hemorrhaging. The injectable medication can only be used to treat the most common type of stroke that occurs when blood clots block blood flow to the brain, called ischemic stroke.

"For a stroke victim, time is a matter of life and death. While we are still in the research phase for this type of compound, we believe it could be combined with tPA in the future to buy ischemic stroke patients a longer window of time to receive emergency treatment," said Zezong Gu, MD, PhD, the article’s corresponding author and assistant professor of pathology and anatomical sciences at the MU School of Medicine. The new compound being studied also has potential for use in patients experiencing hemorrhagic stroke, which is a less common type of stroke caused by bleeding within the brain, Gu said.

MU researchers collaborated with a team at the University of Notre Dame to study the effects of the new compound, a thiirane class of gelatinase selective inhibitors, on the function of a type of matrix metalloproteinase (MMP) enzyme, particularly MMP-9. MMP-9 is part of a group of more than 20 enzymes or MMPs that are known to contribute to many key pathological events in the brain after stroke, traumatic brain injury and other neurodegenerative events.

In 2005, Gu served as a lead author on a research paper published in the Journal of Neuroscience that identified MMP-9 as a promising target for development of therapeutic drugs for stroke patients. Since then, his lab at MU medical school’s Center for Translational Neuroscience has been studying the function of MMP enzymes and how to inhibit the harmful effects of MMP-9.

"MMPs play a role in the structure of blood vessels in the brain and are also needed in the interactions between cells during development and tissue remodeling," Gu said. "Unregulated, the activity of these enzymes contributes to neurological disorders and stroke. With this compound, we’ve now confirmed a potential method to rescue the blood vessels from the damaging effects of MMP-9 and protect neurons at the same time."

MU researchers successfully used a model of ischemic stroke in mice and studied the effects of the MMP-9 inhibitor compound on brain activity after a stroke.

"Our lab at the Center for Translational Neuroscience is one of only a few in the United States that has successfully induced a blood clot in the brains of mice," said Jiankun Cui, MD, the article’s lead author and assistant professor of pathology and anatomical sciences at the MU School of Medicine. "To be able to study the effectiveness of this potential new treatment under these conditions provides us with a highly unique set of data showing this compound can disrupt key harmful pathological events that occur after a stroke."

Source: Science Daily

ScienceDaily (June 11, 2012) — Out of control competitive aggression could be a result of a lagging neurotransmitter called dopamine, say researchers presenting a study at the Society of Nuclear Medicine’s 2012 Annual Meeting. During a computer game against a putative cheating adversary, participants who had a lower capacity to synthesize this neurotransmitter in the brain were more distracted from their basic motivation to earn money and were more likely to act out with aggression.

Out of control competitive aggression could be a result of a lagging neurotransmitter called dopamine, say researchers. During a computer game against a putative cheating adversary, participants who had a lower capacity to synthesize this neurotransmitter in the brain were more distracted from their basic motivation to earn money and were more likely to act out with aggression. (Credit: © lassedesignen / Fotolia)

For many people, anger is an almost automatic response to life’s challenges. In clinical psychiatry, scientists look at not only the impact of aggressive behavior on the individual, their loved ones and the community but also the triggers in the brain that lead to aggressive response. The neurobiology of aggression is not well understood, but scientists are aware of a relationship between the neurotransmitter serotonin and certain aggressive behaviors. The objective of this study was to explore whether higher levels of another brain chemical called dopamine, involved in pleasure and reward, increased aggressive response in its subjects. To scientists’ surprise, it was not as they first theorized.

"The results of this study were astonishingly opposite of what was previously hypothesized," says Ingo Vernaleken, M.D., lead author of the study and research scientist for the department of psychiatry at RWTH Aachen University in Aachen, Germany. "Subjects with more functional dopaminergic reward-systems were not more aggressive in competitive situations and could concentrate even more on the game. Subjects with lower dopaminergic capacity were more likely to be distracted by the cheating behavior."

In this study, 18 healthy adults in their twenties were tested for aggression using the psychological behavioral task known as the point subtraction aggression paradigm (PSAP). Participants were asked to play a computer game that required them to press a bar multiple times with the incentive of winning money, but they were also told that an adversary in the next room who is able to cheat may steal some of their winnings. What the paranoid participants did not know was that there was no adversary. The computer program is designed to perform randomized deductions of the subjects’ monetary reward to simulate the cheating competitor.The participant had three choices to react: punish the cheater, shield against the adversary by repeatedly pressing a defense button, or continue playing the game in order to maximize their ability to win cash, which indicated resilience.

"The PSAP focuses on aggressive reaction within a competitive situation," says Vernaleken. "Aggression and its neurobiological mechanisms in humans have been only moderately investigated in the past. Furthermore, most of the previous studies mainly covered the more reactive part of aggression, which merely reflects impulsive behavior and appears to be associated merely with the serotonin system. This investigation focuses on the association with the dopaminergic reward-system, which reflects goal-directed aggression."

Subjects’ brains were imaged using positron emission tomography, which provides a range of information about physiological functions inside the body, depending on the imaging probe used. In this investigation, F-18 FDOPA, a biomarker that lights up enzymes’ ability to synthesize this transmitter, was used and the uptake of this drug in the brain was analyzed to gauge the correlation between the participants’ dopamine synthesis capacity and aggressive behavior.

Results of the study showed a significant impact on aggressive response in areas in the brain where dopamine synthesis was present, especially in the basal ganglia, which among other functions include the motivation center. Minimized aggression was associated with higher dopamine levels in both the midbrain and the striatum, which plays a role in planning and executive function. People with greater capacity for dopamine synthesis were more invested in the monetary reward aspect of the PSAP, instead of acting in defense or with aggression against their perceived adversary, whereas subjects with lower capacities had a higher vulnerability to act either aggressive, defensive or both.

"Thus, we think that a well-functioning reward system causes more resilience against provocation," says Vernaleken. "However, we cannot exclude that in a situation where the subject would directly profit from aggressive behavior, in absence of alternatives, the correlation might be the other way around."

Further research is required to explore the link between dopamine and a range of aggressive behavior. More insight into these relationships could potentially lead to new psychological therapies and drug treatments to moderate or prevent aggressive response.

Source: Science Daily

ScienceDaily (June 11, 2012) — An arsenal of Alzheimer’s research revealed at the Society of Nuclear Medicine’s 59th Annual Meeting indicates that beta-amyloid plaque in the brain not only is involved in the pathology of Alzheimer’s disease but may also precede even mild cognitive decline. These and other studies advance molecular imaging for the early detection of beta-amyloid, for which one product is now approved in the United States , as a major push forward in the race for better treatments.

"Diagnosis of Alzheimer’s disease can now be made when the patient first presents symptoms and still has largely preserved mental function," says Christopher Rowe, M.D., a lead investigator for the Australian Imaging, Biomarkers and Lifestyle study of aging (AIBL) and professor of nuclear medicine at Austin Hospital in Melbourne, Australia. "Previously there was an average delay of three years between consulting a doctor over memory concerns and the diagnosis of Alzheimer’s, as the diagnosis required the presence of dementia. When used as an adjunct to other diagnostic measures, molecular imaging can help lead to earlier diagnosis. This may give the patient several years to prepare for dementia while they still have control over their destiny."

According to the World Health Organization, Alzheimer’s disease affects an estimated 18 million people worldwide, and incidence of the disease is expected to double by the year 2025 to 34 million. The National Institute on Aging estimates that as many as 50 percent of Americans aged 85 or older are affected.

Alzheimer’s disease is a chronic and currently incurable neurodegenerative disease. Beta-amyloid burden can begin to build in the brain several years, if not more than a decade, before an individual shows any sign of dementia. Those who go on to develop Alzheimer’s disease not only lose their ability to remember their loved ones but also have difficulty with essential bodily functions such as breathing and swallowing in the late stages of disease.

In one study, researchers used a molecular imaging technique called positron emission tomography (PET), which images physiological patterns in the body. PET was combined with an imaging agent called F-18 florbetaben, which binds to amyloid in the brain. This and other PET agents are drawn to targets in the body and emit a positron signal that is picked up by a scanner. Here molecular imaging was performed in conjunction with clinical and neuropsychological testing in order to better understand the long-term effects of beta amyloid plaques in the brains of older individuals with mild cognitive impairment. Those of the 45 subjects in the study who showed high levels of imaging agent binding during imaging and atrophy of the hippocampus, the memory center, had an 80 percent chance of developing Alzheimer’s disease within two years, researchers said.

"Molecular imaging is proving to be an essential part of Alzheimer’s disease detection," says Rowe. "This and other amyloid imaging techniques will have an increasing role in the earlier and more accurate diagnosis of neurodegenerative conditions such as Alzheimer’s disease due to their ability to measure the actual underlying disease process."

Another AIBL study included 194 healthy participants, 92 people with mild cognitive impairment and 70 subjects with Alzheimer’s disease, and used another imaging agent called C-11 PiB (Pittsburgh compound B) with PET to gauge amyloid burden in the brain. Researchers showed that, in this study group, widespread amyloid plaque build-up preceded cognitive impairment, and those with extensive amyloid burden were at higher risk of cognitive decline.

This and another study mark two of the first studies of their kind focusing on beta amyloid in healthy subjects. In the other study, 137 adults with normal cognitive function aged 30 to 89 years were imaged using PET with F-18 florbetapir, now FDA-approved for the detection of beta amyloid plaques, as well as functional magnetic resonance imaging in order to explore how amyloid build-up affects connections in specific areas of the brain involved in cognition, namely the default mode and salience networks, which are responsible for different states of wakeful rest and alertness. Those with increased amyloid burden in these neural networks were prone to impaired cognitive performance.

"The effect of beta amyloid in healthy aging is of great interest since this protein is strongly associated with Alzheimer’s disease and may be predictive of the transition from mild cognitive impairment to Alzheimer’s disease," says Michael Devous, Sr., Ph.D., director of neuroimaging at the Alzheimer’s Disease Center at UT Southwestern Medical Center in Dallas, Texas. "Less is known about its impact on cognition in otherwise healthy aging individuals. In addition, brain connectivity in these areas is thought to be sensitive to early changes in brain function caused both by aging itself and by disease processes such as Alzheimer’s disease."

Another study assessed the PET imaging agent C-11 PiB for its ability to detect amyloid plaque in comparison to another imaging agent, 18-F fluorodeoxyglucose (F-18 FDG). The latter acts like glucose, the brain’s primary energy source, to map out the metabolic functioning of the brain. Results of the study showed C-11 PiB amyloid imaging to be a better means of evaluating amyloid patterns in the brain than F-18 FDG imaging. In addition, of the 100 healthy participants, 15 percent were shown to have some amyloid build-up when molecular imaging was performed.

"We are using state-of-the-art, noninvasive PET and MRI technologies to look at some of the earliest developments of Alzheimer’s disease onset in the brains of normal middle-aged people," says Guofan Xu, M.D., Ph.D., lead author of the study and research scientist at the department of nuclear medicine and radiology at the University of Wisconsin located in Madison. "With this we can evaluate whether pathological changes associated with Alzheimer’s disease are happening many years before onset of significant clinical symptoms."

No treatments are currently available to cure or prevent Alzheimer’s disease. With advances in molecular imaging to detect beta amyloid plaques, researchers have an important new tool that may bring the medical community one step closer to making therapies and vaccines a reality for the disease.

Source: Science Daily

June 11, 2012

Scientists studying the Chinese mindfulness meditation known as integrative body-mind training (IBMT) say they’ve confirmed and expanded their findings on changes in structural efficiency of white matter in the brain that can be related to positive behavioral changes in subjects practicing the technique regularly for a month.

In a paper appearing this week in the online Early Edition of the Proceedings of the National Academy of Sciences, scientists Yi-Yuan Tang and Michael Posner report improved mood changes coincided with increased axonal density — more brain-signaling connections — and an expansion of myelin, the protective fatty tissue that surrounds the axons, in the brain’s anterior cingulate region.

Deficits in activation of the anterior cingulate cortex have been associated with attention deficit disorder, dementia, depression, schizophrenia and many other disorders.

IBMT was adapted from traditional Chinese medicine in the 1990s in China, where it is practiced by thousands of people. It differs from other forms of meditation because it depends heavily on the inducement of a high degree of awareness and balance of the body, mind and environment. The meditative state is facilitated through training and trainer-group dynamics, harmony and resonance.

In 2010, research led by Tang, a visiting research professor at the University of Oregon, and Michael I. Posner, professor of psychology at the UO, first reported positive structural changes in brain connectivity, based on functional magnetic resonance imaging, that correlated to behavioral regulation. The study was done in the UO’s Robert and Beverly Lewis Center for Neuroimaging with 45 participating UO undergraduate students.

The new findings came from additional scrutiny of the 2010 study and another that involved 68 undergraduate students at China’s Dalian University of Technology. The researchers revisited data obtained from using an MRI technique known as diffusion tensor imaging. The research team found improved density of the axons involved in brain connections but no change in myelin formation after two weeks. After a month, or about 11 hours of IBMT, both increases in axon density and myelin formation were found as measured by fractional anisotropy, axial diffusivity and radial diffusivity — the important indexes for measuring the integrity of white matter fibers.

"This dynamic pattern of white matter change involving the anterior cingulate cortex, a part of the brain network related to self-regulation, could provide a means for intervention to improve or prevent mental disorders," the authors concluded.

"When we got the results, we all got very excited because all of the other training exercises, like working-memory training or computer-based training, only have been shown to change myelination," Tang said. "We believe these changes may be reflective of the time of training involved in IBMT. We found a different pattern of neural plasticity induced by the training."

"This study gives us a much more detailed picture of what it is that is actually changing," Posner said. "We did confirm the exact locations of the white-matter changes that we had found previously. And now we show that both myelination and axon density are improving. The order of changes we found may be similar to changes found during brain development in early childhood, allowing a new way to reveal how such changes might influence emotional and cognitive development.”

The improved mood changes noted in this and earlier studies are based on self-ratings of subjects based on a standard six-dimensional mood-state measure, said Tang, who is now the director of Texas Tech University’s Neuroimaging Institute and holder of the Presidential Endowed Chair in Neuroscience in TTU’s psychology department.

Tang and Posner first reported findings related to IBMT in 2007, also in PNAS. They found that doing IBMT for five days prior to a mental math test led to low levels of the stress hormone cortisol among Chinese students. The experimental group also showed lower levels of anxiety, depression, anger and fatigue than students in a relaxation control group.

In 2009 in PNAS, Tang and his Chinese colleagues, with assistance from Posner and UO psychology professor Mary K. Rothbart, found that IBMT subjects in China had increased blood flow in the right anterior cingulate cortex after receiving training for 20 minutes a day over five days. Compared with the relaxation group, IBMT subjects also had lower heart rates and skin conductance responses, increased belly breathing amplitude and decreased chest respiration rates.

"These new findings provide fundamental new insights on how the brain responds in positive ways to new inputs and reflect the excellence in cognitive neuroscience research that has defined Michael Posner’s work at the University of Oregon," said Kimberly Andrews Espy, vice president for research and innovation. "The research by professors Posner and Tang also reflects the university’s long-running commitment to collaborate with institutions in Pacific Rim countries."

Provided by University of Oregon

Source: medicalxpress.com

June 11, 2012

A new study shows that changes in walking speed in late life may signal the early stages of dementia known as mild cognitive impairment (MCI). The research is published in the June 12, 2012, print issue of Neurology, the medical journal of the American Academy of Neurology.

"In our study, we used a new technique that included installing infrared sensors in the ceilings of homes, a system designed to detect walking movement in hallways,” said study author Hiroko Dodge, PhD, with Oregon Health and Science University in Portland and a member of the American Academy of Neurology. “By using this new monitoring method, we were able to get a better idea of how even subtle changes in walking speed may correlate with the development of MCI.”

The study involved 93 people age 70 or older who lived alone. Of those, 54 participants had no cognitive impairment, 31 had non-memory related MCI and eight had memory-related MCI. Participants were given memory and thinking tests and had their walking speed monitored at their homes unobtrusively over a three-year period. Participants were placed in groups of slow, moderate or fast based on their average weekly walking speed and how much their walking speed fluctuated at home.

The study found that people with non-memory related MCI were nine times more likely to be slow walkers than moderate or fast walkers and the amount of the fluctuation in walking speed was also associated with MCI.

"Further studies need to be done using larger groups of participants to determine whether walking speed and its fluctuations could be a predictor of future memory and thinking problems in the elderly,” said Dodge. “If we can detect dementia at its earliest phases, then we can work to maintain people’s independence, provide treatments and ultimately develop ways to prevent the disease from developing. Our in-home monitoring approach has a lot of potential to be used for sustaining independence of the elderly.”

Provided by American Academy of Neurology

Source: medicalxpress.com

ScienceDaily (June 11, 2012) — According to the Anxiety and Depression Association of America, one in eight children suffers from an anxiety disorder. And because many anxious children turn into severely anxious adults, early intervention can have a major impact on a patient’s life trajectory. The understandable reluctance to use psychiatric medications when it comes to children means child psychologists are always searching for viable therapeutic alternatives.

Now Prof. Yair Bar-Haim of Tel Aviv University’s School of Psychological Sciences and his fellow researchers are pursuing a new method to address childhood anxiety. Based on a computer program, the treatment uses a technique called Attention Bias Modification (ABM) to reduce anxiety by drawing children away from their tendency to dwell on potential threats, ultimately changing their thought patterns. In its initial clinical trial, the program was as effective as medication and cognitive therapy for children — with several distinct advantages.

The results of the trial were reported in the American Journal of Psychiatry.

Computers instead of capsules

Children are comfortable with computers, explains Prof. Bar-Haim. And because of the potential side effects of medications or the difficulty in obtaining cognitive behavioral therapy, such as the need for highly trained professionals, it is good to have an alternative treatment method. ABM treatments can be disseminated over the Internet or administered by personnel who don’t have to be Ph.D.s. “This could be a game-changer for providing treatment,” he says.

Anxious individuals have a heightened sensitivity towards threats that the average person would ignore, a sensitivity which creates and maintains anxiety, says Prof. Bar-Haim. One of the ways to measure a patient’s threat-related attention patterns is called the dot-probe test. The patient is presented with two pictures or words, one threatening and one neutral. These words then disappear and a dot appears where one of the pictures or words had been, and the patient is asked to press a button to indicate the dot’s location. A fast response time to a dot that appears in the place of the threatening picture or word indicates a bias towards threat.

To turn this test into a therapy, the location of the dot target is manipulated to appear more frequently beneath the neutral word or picture. Gradually, the patient begins to focus on that stimulus instead, predicting that this is where the dot will appear — helping to normalize the attention bias pattern and reduce anxiety.

Prof. Bar-Haim and his colleagues enlisted the participation of 40 pediatric patients with ongoing anxiety disorders and divided them into three groups. The first received the new ABM treatment; the second served as a placebo group where the dot appeared equally behind threatening and neutral images; and the third group was shown only neutral stimuli. Patients participated in one session a week for four weeks, completing 480 dot probe trials each session.

The children’s anxiety levels were measured before and after the training sessions using interviews and questionnaires. In both the placebo group and neutral images group, researchers found no significant change in the patients’ bias towards threatening stimuli. However, in the ABM group, there were marked differences in the participants’ threat bias. By the end of the trial, approximately 33 percent of the patients in this group no longer met the diagnostic criteria for anxiety disorder.

New methods for personalized treatment

These indications of the method’s success in treating children warrant further investigation, says Prof. Bar-Haim. In collaboration with the National Institute of Mental Health in the US, a large international trial involving his computer program is now being carried out at more than 20 sites across five continents.

The more options that exist for patients, the better that clinicians can tailor treatment for their patient’s individual needs, Prof. Bar-Haim observes. There are always patients for whom medication or cognitive therapy is not a viable option, he explains. “Psychological disorders are complex, and not every patient will respond well to every treatment. It’s great to have new methods that have a basis in neuroscience and clinical evidence.”

Source: Science Daily

ScienceDaily (June 11, 2012) — Non-medical prescription drug use by college students is a growing trend on most campuses, according to the U.S. Department of Education’s Higher Education Center for Alcohol, Drug Abuse and Violence Prevention. Due to this trend, Western Illinois University Department of Health Sciences Assistant Professor Amanda Divin and her colleague, Keith Zullig, an associate professor in the West Virginia University School of Public Health, recently conducted and published a study that explores non-medical prescription drug use and depressive symptoms in college students.

Divin and Zullig utilized data from the fall 2008 American College Health Association National College Health Assessment (ACHA-NCHA), a national research survey that addresses seven areas of health and behavior of college students, one of which is alcohol, tobacco and other drug use. The sample used for the study (from the ACHA-NCHA data) contained 26,600 randomly selected college students from 40 campuses in the U.S. The student respondents were asked about their non-medical prescription drug use (including painkillers, stimulants, sedatives and antidepressants) and mental health symptoms within the last year.

According to Divin’s and Zullig’s results, approximately 13 percent of the college-student respondents reported non-medical prescription drug use, with those who reported feeling hopeless, sad, depressed or considered suicide being significantly more likely to report non-medical use of any prescription drug. The results also showed this relationship was more pronounced for females who reported painkiller use. The study — which is titled, “The association between non-medical prescription drug use, depressive symptoms, and suicidality among college students” — will appear in the August 2012 issue of Addictive Behaviors: An International Journal.

"Because prescription drugs are tested by the U.S. Food and Drug Administration and prescribed by a doctor, most people perceive them as ‘safe’ and don’t see the harm in sharing with friends or family if they have a few extra pills left over," Divin explained. "Unfortunately, all drugs potentially have dangerous side effects. As our study demonstrates, use of prescription drugs — particularly painkillers like Vicodin and Oxycontin — is related to depressive symptoms and suicidal thoughts and behaviors in college students. This is why use of such drugs need to be monitored by a doctor and why mental health outreach on college campuses is particularly important."

Divin and Zullig believe the results suggest that students are self-medicating their psychological distress with prescription medications.

"Considering how common prescription sharing is on college campuses and the prevalence of mental health issues during the college years, more investigation in this area is definitely warranted," Divin added. "Our study is just one of the many first steps in exploring the relationship between non-medical prescription drug use and mental health."

Source: Science Daily

ScienceDaily (June 11, 2012) — Sportsmen and women have been known to dope with the blood hormone Epo to enhance their performance. Researchers from the University of Zurich have now discovered, through animal testing, that Epo has a performance-enhancing effect in the brain shortly after an injection by improving oxygen transport in blood. As Epo also increases motivation, it could be useful in treating depression, experts say.

The well-known blood hormone Epo is not only used for medicinal purposes; some athletes misuse it for doping. It boosts the number of red blood cells, thereby increasing the transport of oxygen to the muscles. This leads to improvements in performance, which can especially give endurance athletes such as cyclists or marathon runners the edge.

Epo has immediate impact on exercise performance

In a recently published study, Max Gassmann, a veterinary physiologist from the University of Zurich, proved that Epo also drastically increases motivation in the brain as soon as it has been injected, without the number of red blood cells increasing.

Gassmann’s team tested exercise performance of differently treated mice, studying genetically modified mice that produce human Epo solely in the brain and mice that the researchers had injected with Epo and the hormone reached the brain thus by blood. Both mouse groups exhibited an increased performance on the treadmill compared to the untreated control animals. “We assume that Epo in the brain triggers a motivation boost to increase physical performance,” explains Professor Gassmann. He and his team are now testing the performance-enhancing effect of Epo on volunteers.

Epo probably has an impact on people’s moods, too. It might thus be used in patients who suffer from depression. The latest experiments conducted by a German-Danish research group reveal that Epo can also alleviate the condition of patients suffering from schizophrenia by improving their mental performance.

Source: Science Daily

June 11, 2012

The younger a woman is when she goes through the menopause, the greater may be her risk of having a brain (cerebral) aneurysm, suggests research published online first in the Journal of NeuroInterventional Surgery.

A cerebral aneurysm refers to an abnormal bulging of one of the arteries in the brain, which is often only discovered when it ruptures, causing a potentially fatal and/or disabling bleed.

Women are more prone to cerebral aneurysms than men. And fluctuations in the female hormone oestrogen have been implicated in the development of aneurysms, the incidence of which, along with cardiovascular disease, rises sharply after menopause.

The authors base their findings on 76 postmenopausal women who had had a cerebral aneurysm, which, in most cases had not ruptured, and who were subsequently quizzed about their medical and reproductive histories.

Conditions, such as high blood pressure, diabetes, high cholesterol and an underactive thyroid gland (hypothyroidism) can all boost the risk of a stroke, while the number of pregnancies and the age at which periods start and stop determine lifetime exposure to oestrogen.

This information was then compared with that taken from more than 4,500 women participants of the 2002 National Institute of Child Health and Human Development Contraceptive and Reproductive Experiences Study, and matched for age and educational attainment.

The average age at which women in both groups had started the menopause was similar, and analysis of the results showed that later menopause and use of hormone replacement therapy (HRT) protected against the risk of a cerebral aneurysm, lessening the risk by 21% and 77%, respectively.

Premature menopause - before the age of 40 - had occurred in one in four (26%) of the women who had had an aneurysm compared with around one in five (19%) of those in the comparison group.

And each successive four year increase in the age at which a woman went through the menopause lessened the likelihood of a cerebral aneurysm by around 21%.

Smoking did not seem to be linked to an increase in risk, while alcohol consumption was of borderline significance.

The outcomes for ruptured cerebral aneurysms are poor, with around one in two people who have one likely to die. One in 10 people die before they reach hospital and of those who survive, one in five is severely disabled, say the authors, so finding a potential marker may help to detect the condition earlier.

"Loss of oestrogen earlier in a woman’s life may contribute to the [development] of cerebral aneurysm," conclude the authors, adding that HRT may protect against this. And they suggest: "These data may identify a risk factor for [the development of this condition] and also a potential target for future therapies."

Provided by British Medical Journal

Source: medicalxpress.com