Neuroscience

March 23, 2012

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

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

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

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

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

Provided by Max-Planck-Gesellschaft

Source: medicalxpress.com

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

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

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

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

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

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

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

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

Source: Science Daily

March 22, 2012

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

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

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

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

On-Off Switches and a Hybrid Memory

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

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

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

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

Future Manipulation of the Past

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

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

Provided by The Scripps Research Institute

Source: medicalxpress.com

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

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

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

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

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

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

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

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

Source: Science Daily

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

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

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

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

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

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

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

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

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

Source: Science Daily

March 21, 2012

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

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

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

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

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

Provided by Max-Planck-Gesellschaft

Source: medicalxpress.com

March 21, 2012

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

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

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

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

Provided by Public Library of Science

Source: medicalxpress.com

March 21, 2012

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

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

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

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

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

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

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

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

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

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

Provided by Queen Mary, University of London

Source: medicalxpress.com

March 21, 2012

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

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

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

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

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

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

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

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

Provided by University of Calgary 

Source: medicalxpress.com

March 21, 2012

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

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

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

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

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

Tracking the Flow of Proteins

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

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

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

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

Simple Explanation for Clinically Observed Patterns of Dementia

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

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

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

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

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

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

Provided by New York- Presbyterian Hospital

Source: medicalxpress.com

March 21, 2012

Alzheimer’s disease and other forms of dementia may spread within nerve networks in the brain by moving directly between connected neurons, instead of in other ways proposed by scientists, such as by propagating in all directions, according to researchers who report the finding in the March 22 edition of the journal Neuron.

Led by neurologist and MacArthur Foundation “genius award” recipient William Seeley, MD, from the UCSF Memory and Aging Center, and post-doctoral fellow Helen Juan Zhou, PhD, now a faculty member at Duke-NUS Graduate Medical School in Singapore, the researchers concluded that a nerve region’s connectedness to a disease hot spot trumps overall connectedness, spatial proximity and loss of growth-factor support in predicting its vulnerability to the spread of disease in some of the most common forms of dementia, including Alzheimer’s disease.

The finding, based on new magnetic resonance imaging research (MRI), raises hopes that physicians may be able to use MRI to predict the course of dementias – depending on where within an affected network degenerative damage is first discovered – and that researchers may use these predicted outcomes to determine whether a new treatment is working. Network modeling combined with functional MRI might serve as an intermediate biomarker to gauge drug efficacy in clinical trials before behavioral changes become measurable, according to Seeley.

"Our next goal is to further develop methods to predict disease progression, using these models to create a template for how disease will progress in the brain of an affected individual," Seeley said. "Already this work suggests that if we know the wiring diagram in a healthy brain, we can predict where the disease is going to go next. Once we can predict how the network will change over time we can predict how the patient’s behavior will change over time and we can monitor whether a potential therapy is working."

The new evidence suggests that different kinds of dementias spread from neuron to neuron in similar ways, even though they act on different brain networks, according to Seeley. Seeley’s previous work and earlier clinical and anatomical studies showed that the patterns of damage in the dementias are linked to particular networks of nerve cells, but until now scientists have found it difficult to evaluate in humans their ideas about how this neurodegeneration occurs.

In the current study, the researchers modeled not only the normal nerve network that can be affected by Alzheimer’s disease, but also those networks affected by frontotemporal dementia (FTD) and related disorders, a class of degenerative brain diseases identified by their devastating impact on social behaviors or language skills.

The scientists mapped brain connectedness in 12 healthy people. Then they used data from patients with the five different diseases to map and compare specific regions within the networks that are damaged by the different dementias.

"For each dementia, we looked at four ideas that scientists often bring up to explain how dementia might target brain networks," Seeley said. "The different proposed mechanisms lead to different predictions about how a region’s place in the healthy network affects its vulnerability to disease."

In the “nodal stress” hypothesis, small regions within the brain that serve as hubs to carry heavy signaling traffic would undergo wear and tear that gives rise to or worsens disease. In the “trophic failure” mechanism, breakdowns in connectivity would disrupt transport through the network of growth factors needed to maintain neurons. In the “shared vulnerability” mechanism, specific genes or proteins common to neurons in a network would make them more susceptible to disease. But predictions from the “trans-neuronal spread” mechanism model best fit the network connectivity maps constructed by the researchers.

"The trans-neuronal spread model predicts that the more closely connected a region is to the node of disease onset – which we call the epicenter – then the more vulnerable that region will be once the disease begins to spread," Seeley said. "It’s as if the disease is emanating from a point of origin, but it can reach any given target faster if there is a stronger connection."

The scientists tracked and analyzed linkages within nerve networks that the dementias target. They used a technique called functional connectivity MRI to measure and spatially represent activity in specific regions of key networks in the brains of the healthy subjects. The MRI readout allowed the researchers to model each region within the network as a distinct but interconnected node. They ranked the nodes that most consistently fired together as being the most closely connected.

Across the five diseases investigated in the study, trans-neuronal spread was the proposed mechanism for which the data best matched the predictions. Previous studies of animals and cells in the laboratory also support the idea that disease-related proteins can spread from an affected neuron to other neurons via intercellular connections.

For more than three decades researchers have been noticing that regions affected by Alzheimer’s disease are connected by axons that branch between and connect neurons, Seeley said. Trans-neuronal spread is a proven hallmark of certain rare neurodegenerative diseases – such as Creutzfeldt-Jakob disease – that are propagated by misfolded cell-surface proteins called prions, which induce neighboring proteins to change shape, aggregate and wreak havoc.

While Alzheimer’s disease and FTD are not considered infectious, abnormal protein structures also are implicated in these common dementias. Recent experiments in which researchers transplanted post-mortem, human brain extracts from dementia patients into genetically modified mice have resulted in disease, Seeley said, “But it is difficult to explore these ideas in humans, and we wanted to begin to bridge this knowledge gap.”

Provided by University of California - San Francisco

Source: medicalxpress.com 

March 21, 2012

What characterizes many people with depression, schizophrenia and some other mental illnesses is anhedonia: an inability to gain pleasure from normally pleasurable experiences.

This image shows VTA dopamine neurons (in red) and VTA GABA fibers (in green). Credit: Stuber Lab, UNC-Chapel Hill.

Exactly why this happens is unclear. But new research led by neuroscientists at the University of North Carolina at Chapel Hill School of Medicine may have literally shined a light on the answer, one that could lead to the discovery of new mental health therapies. A report of the study appears March 22 in the journal Neuron.

The study used a combination of genetic engineering and laser technology to manipulate the wiring of a specific population of brain cells deep in a portion of a midbrain area that’s known to promote behavioral responses to reward.

"For many years it’s been known that dopamine neurons in the ventral midbrain, the ventral tegmental area, or VTA, are involved in reward processing and motivation. For example, they’re activated during exposure to drugs of abuse and to naturally rewarding experiences," said study lead author Garret D. Stuber, PhD, assistant professor in the departments of Psychiatry and Cell and Molecular Physiology, and the UNC Neuroscience Center.

"The major focus in our lab is to determine what other sorts of neural circuits or genetically defined neural populations might be modulating the activity of those neurons, whether it’s increasing or decreasing their activity," Stuber said. "In our study we found that activation of the nearby VTA GABAergic neurons directly inhibit the function of dopamine neurons, which is something that’s never been shown before."

In the past, researchers have tried to get a glimpse into the inner workings of the brain using electrical stimulation or drugs, but those techniques couldn’t quickly and specifically change only one type of cell or one type of connection. But optogenetics, a technique that emerged about six years ago, can. 

In this study, the scientists used a transgenic animal with a foreign gene that has been inserted into its genome to express a bacterial enzyme that can cause DNA recombination only in GABA neurons and not dopamine cells. Using a gene transfer method developed at UNC and with the animal anesthetized, the Stuber team transferred light-sensitive proteins called “opsins” – derived from algae or bacteria that need light to grow – into the VTA, targeting GABA cells. The presence of these foreign opsins in GABA neurons allows researchers to excite or inhibit them by pumping light from a laser into brain tissue.

The animals were then tested in different reward situations, simple tasks in which they were trained to associate a cue with a sugar water reward from a bottle or were given the opportunity to drink the reward by “free licking,” where they could drink as much as they want.

Then, via optical fibers, the researchers shined laser beams onto the genetically manipulated GABA neurons, activating them for 5 seconds during the cue period followed by reward. And on another day, they activated the neurons during reward consumption, when the animals were actively engaged in drinking the sugar water.

"And what we saw when we activated the cells during the cue period, or reward anticipation, it didn’t do anything to the behavioral response at all; they showed no difference compared to non-stimulated animals," Stuber explained.

"And when they were actively engaging with the sucrose, we did see we could disrupt their reward consumption when we activated those cells. They immediately disengaged from drinking, stopped drinking the sucrose solution. And when the stimulus stopped, they would then return back and continue to drink it again."

During the “free licking” sessions, optical stimulation of GABA neurons resulted in disruption of sucrose consumption. The animals stopped drinking.

Using sophisticated electrophysiology and cell chemistry measures, the study team could monitor the activity of the GABA and dopamine neurons. They found a direct link between GABA activation and dopamine suppression.

"So basically, it appears that these GABA neurons located in the VTA are just microns away from dopamine and are negative regulators of dopamine function," Stuber proposes.

"When they become active, their basic job is to suppress dopamine release. A dysfunction in these GABA neurons might potentially underlie different aspects of neuropsychiatric illness, such as depression. Thus, we could think of them as a new physiological target for various aspects of neuropsychiatric diseases."

Provided by University of North Carolina School of Medicine

March 21, 2012

Investigators at the Stanford University School of Medicine have shown that removing a matched set of molecules that typically help to regulate the brain’s capacity for forming and eliminating connections between nerve cells could substantially aid recovery from stroke even days after the event. In experiments with mice, the scientists demonstrated that when these molecules are not present, the mice’s ability to recover from induced strokes improved significantly.

Importantly, these beneficial effects grew over the course of a full week post-stroke, suggesting that, in the future, treatments such as drugs designed to reproduce the effects in humans might work even if given as much as several days after a stroke occurs. The only currently available stroke treatment — tissue plasminogen activator, or tPA — must be given within a few hours of a stroke to be effective, and patients’ brains must first be scanned to determine whether this treatment is appropriate. Moreover, while tPA limits the initial damage caused by a stroke, it doesn’t help the brain restore or replace lost connections between nerve cells, which is essential to recovery.

The mice in the study had been genetically bioengineered to lack certain molecules that one of the Stanford researchers had previously shown to play a major role in modulating the ease with which key nerve-cell connections are made, strengthened, weakened or destroyed in the brain. The molecules in question include “K” and “D,” two of the 50 or so members of the so-called MHC class-1 complex, which plays a key role in the function of the immune system. Alternatively, when a receptor called PirB, which binds to these MHC molecules, is not present, the same improved outcome from stroke happens — significant, because receptors make good drug targets.

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March 20, 2012

A personality profile marked by overly gregarious yet anxious behavior is rooted in abnormal development of a circuit hub buried deep in the front center of the brain, say scientists at the National Institutes of Health. They used three different types of brain imaging to pinpoint the suspect brain area in people with Williams syndrome, a rare genetic disorder characterized by these behaviors. Matching the scans to scores on a personality rating scale revealed that the more an individual with Williams syndrome showed these personality/temperament traits, the more abnormalities there were in the brain structure, called the insula.

The severity of abnormalities in insula (red structure near bottom of brain), gray matter volume (left) and brain activity (right) predicted the extent of aberrant personality traits in Williams syndrome patients — as reflected in their scores (red dots) on personality rating scales (WSPP). Credit: Karen Berman, M.D., NIMH Clinical Brain Disorders Branch

"Scans of the brain’s tissue composition, wiring, and activity produced converging evidence of genetically-caused abnormalities in the structure and function of the front part of the insula and in its connectivity to other brain areas in the circuit," explained Karen Berman, M.D., of the NIH’s National Institute of Mental Health (NIMH).

Berman, Drs. Mbemda Jabbi, Shane Kippenham, and colleagues, report on their imaging study in Williams syndrome online in the journal Proceedings of the National Academy of Sciences.

"This line of research offers insight into how genes help to shape brain circuitry that regulates complex behaviors – such as the way a person responds to others – and thus holds promise for unraveling brain mechanisms in other disorders of social behavior," said NIMH Director Thomas R. Insel, M.D.

Long distance connections, white matter, between the insula and other parts of the brain are aberrant in Williams syndrome. Neuronal fibers of normal controls (left) extend further than those of Williams syndrome patients (right). Picture shows diffusion tensor imaging data from each patient superimposed on anatomical MRI of the median patient. Credit: Karen Berman, M.D., NIMH Clinical Brain Disorders Branch

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March 19th, 2012

Stowers researchers present a new model for how the brain is organized to process odor information.

Glomeruli in the olfactory bulb (shown in green), the first waystation for incoming olfactory signals, plays an important role in the processing and identification of smells. Image adapted from press release image courtesy of Limei Ma, Stowers Institute for Medical Research.

Just like a road atlas faithfully maps real-world locations, our brain maps many aspects of our physical world: Sensory inputs from our fingers are mapped next to each other in the somatosensory cortex; the auditory system is organized by sound frequency; and the various tastes are signaled in different parts of the gustatory cortex.

The olfactory system was believed to map similarly, where groups of chemically related odorants – amines, ketones, or esters, for example – register with clusters of cells that are laid out next to each other. When researchers at the Stowers Institute for Medical Research traced individual odor molecules’ signal deep into the brain, they found evidence that this “chemotopic” hypothesis of olfaction is insufficient, paving the way for a new model of how the sense of smell works, and how it came about.

“When we mapped the individual chemical features of different odorants, they mapped all over the olfactory bulb, which processes incoming olfactory information,” says Associate Investigator C. Ron Yu, PhD, who led the study published in this week’s online edition of the Proceedings of the National Academy of Sciences. “From the animal’s perspective that makes perfect sense. The chemical structure of an odor molecule is not what’s important to them. They really just want to learn about their environment and associate olfactory information with food or other relevant information.”

The brain receives information about odors from olfactory receptors, which are embedded in the membrane of sensory neurons in the nasal cavity. Any time an odor molecule interacts with a receptor, an electrical signal travels to so-called glomeruli in the olfactory bulb. Each glomerulus receives input from olfactory receptor neurons expressing only one type of olfactory receptor. The overall glomerular activation patterns within the olfactory bulb are thought to represent specific odors.

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March 19, 2012

Cerebral edemas are accumulations of fluid into the intra- or extracellular spaces of the brain and it can result from several factors such as stroke or head trauma, among others.

Cerebral edema is a serious problem in neurology. While in other organs swelling does not lead to an urgent situation, in the brain it leads to coma and death. Although there are therapeutic solutions such as surgery, more effective treatments are needed.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy (affects the white matter) of genetic origin. MLC can be considered as a model of chronic edema, as patients suffering from birth a high accumulation of water.

A study of the pathophysiology of this rare disease has uncovered one mechanism that destabilizes the homeostatic balance of brain cells causing edema. This study is published in the latest issue of the journal Neuron. The journal accompanies the paper with a commentary of the editor and an explanatory video on its website.

[Video]

Researchers from IDIBELL, the University of Barcelona (UB) and CIBERER (Spanish Network Research Centre on Rare Diseases) have found that one function of the protein GlialCAM, which is genetically altered in patients with MLC, is to regulate the activity of the channel that allows the passage of chloride ions between brain cells to regulate ion and fluid balance.

When this protein is lacked, the channel is not working properly and the fluid builds up in the brain glial cells forming edema.

Raul Estevez, director of this work, and Virginia Nunes, a partner of the study, believe that the importance of this finding is twofold. “On one hand”, explains Virginia Nunes, “it allows us to better understand the pathophysiology of this disease minority” and “on the other hand”, Raul Estevez continues, “we have identified a mechanism that can open doors to treatments based on the activation of this channel to restore homeostatic balance and perhaps treat brain edema in general.”

Both researchers agree to say that this case demonstrates that the investigation of a rare disease that affects a small proportion of the population can serve as a model to identify mechanisms to think of new treatments for common diseases.

MLC Leukodistophy

Megalencephalic Leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy that appears during the first year of life, characterized by macrocephaly (oversized head). A few years later, it appears a slow neurological deterioration with ataxia (lack of motor coordination) and spasms. Magnetic resonance techniques revealed inflammation of the cerebral white matter and subcortical cysts, particularly in the anterior temporal regions.

In the 75% of MLC patients it has been identified mutations in the gene MLC1, which cause the disease. Virginia Nunes and Raul Estevez have recently identified a second gene causing MLC, named GlialCAM.

In the present study they have been identified precisely a GlialCAM protein as an ion channel subunit chloride that allows its entering and exiting the brain so that the cells can regulate the homeostatic balance.

Provided by IDIBELL-Bellvitge Biomedical Research Institute

Source: medicalxpress.com

March 19, 2012

University of Alberta led research may have discovered how memories are encoded in our brains.

Scientists understand memory to exist as strengthened synaptic connections among neurons. However components of synaptic membranes are relatively short-lived and frequently re-cycled while memories can last a lifetime.

Based on this information, U of A physicist and lead researcher Jack Tuszynski, his graduate student Travis Craddock and University of Arizona professor Stuart Hameroff investigated the molecular mechanism of memory encoding in neurons.

The team looked into structures at the cytoskeletal level of brain structure. They found components that fit together and were capable of creating the information processing and storage capacity that the brain needs to form and retain memory.

The practical implications of understanding the mechanism of memory encoding are enormous.

"This could open up amazing new possibilities of dealing with memory loss problems, interfacing our brains with hybrid devices to augment and ‘refresh’ our memories," says Tuszynski. "More importantly, it could lead to new therapeutic and preventive ways of dealing with neurological diseases such as Alzheimer’s and dementia, whose incidence is growing very rapidly these days."

Provided by University of Alberta

Source: medicalxpress.com

March 19, 2012

Patients with relapsing onset Multiple Sclerosis (MS) who consumed alcohol, wine, coffee and fish on a regular basis took four to seven years longer to reach the point where they needed a walking aid than people who never consumed them. However the study, published in the April issue of the European Journal of Neurology, did not observe the same patterns in patients with progressive onset MS.

The authors say that the findings suggest that different mechanisms might be involved in how disability progresses in relapsing and progressive onset MS.

Researchers asked patients registered with the Flemish MS Society to take part in a survey, which included questions on themselves, their MS and their current consumption of alcohol, wine, coffee, tea, fish and cigarettes.

The 1,372 patients who agreed to take part were also asked to indicate whether they had reached stage six on the zero to ten stage Expanded Disability Status Scale (EDSS) and, if so, when this had happened.

"MS is a chronic, often disabling disease that attacks the central nervous system" explains lead author Dr Marie D’hooghe from the National MS Center at Melsbroek, Belgium. "The clinical symptoms, progression of disability and severity of MS are unpredictable and vary from one person to another.

"Two major MS onset types can be distinguished. Progressive onset MS is characterised by a gradual worsening of neurological function from the beginning, whereas patients with relapsing onset MS patients experience clearly defined attacks of worsening neurologic function with partial or full remission.

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March 19, 2012

An antioxidant combination of vitamin E, vitamin C and α-lipoic acid (E/C/ALA) was not associated with changes in some cerebrospinal fluid biomarkers related to Alzheimer disease in a randomized controlled trial, according to a study published Online First by Archives of Neurology.

Oxidative damage in the brain is associated with aging and is widespread in Alzheimer disease (AD) patients. Some observational studies have suggested that an antioxidant-rich diet may reduce the risk of AD, but antioxidant randomized clinical trials in AD have had mixed results, the authors write in their study background.

Douglas R. Galasko, M.D., of the University of California, San Diego, and colleagues examined changes in cerebrospinal fluid (CSF) biomarkers related to Alzheimer disease and oxidative stress, cognition and function.

The study included 78 patients from the Alzheimer’s Disease Cooperative Study (ADCS) Antioxidant Biomarker study who were divided into one of three groups: 800 IU/per day of vitamin E (α-tocopherol) plus 500 mg/per day of vitamin C plus 900 mg/per day of α-lipoic acid (E/C/ALA); 400 mg of coenzyme Q (CoQ) three times a day; or placebo. Sixty-six patients provided serial CSF specimens adequate for biochemical analyses during the 16-week trial.

"The combination of E/C/ALA did not affect CSF biomarkers related to Αβ, tau or P-tau (which are related to AD)," the authors comment.

The E/C/ALA group did see a lowering of CSF F2-isoprostane levels suggesting a reduction of oxidative stress in the brain, the results indicate. However, the treatment raised caution about faster cognitive decline as assessed by the Mini-Mental State Examination (MMSE).

"It is unclear whether the relatively small reduction in CSF F2-isoprostane level seen in this study may lead to clinical benefits in AD. The more rapid MMSE score decline raises a caution and indicates that cognitive performance would need to be assessed if a longer-term clinical trial of this antioxidant combination is considered," the authors conclude.

The authors also note the results indicate that while CoQ was safe and well tolerated in patients, the absence of a biomarker signal in CSF suggests that CoQ, at the tested dose, does not improve indices of oxidative stress or neurodegeneration.

"These results do not support further clinical trial development of CoQ in AD," the researchers conclude.

Provided by JAMA and Archives Journals

Source: medicalxpress.com

ScienceDaily (Mar. 19, 2012) — Researchers from Chalmers and the University of Gothenburg have shown that nanocellulose stimulates the formation of neural networks. This is the first step toward creating a three-dimensional model of the brain. Such a model could elevate brain research to totally new levels, with regard to Alzheimer’s disease and Parkinson’s disease, for example.

Nerve cells growing on a three-dimensional nanocellulose scaffold. One of the applications the research group would like to study is destruction of synapses between nerve cells, which is one of the earliest signs of Alzheimer’s disease. Synapses are the connections between nerve cells. In the image, the functioning synapses are yellow and the red spots show where synapses have been destroyed. (Credit: Illustration: Philip Krantz, Chalmers)

Over a period of two years the research group has been trying to get human nerve cells to grow on nanocellulose.

"This has been a great challenge," says Paul Gatenholm, Professor of Biopolymer Technology at Chalmers.‟Until recently the cells were dying after a while, since we weren’t able to get them to adhere to the scaffold. But after many experiments we discovered a method to get them to attach to the scaffold by making it more positively charged. Now we have a stable method for cultivating nerve cells on nanocellulose."

When the nerve cells finally attached to the scaffold they began to develop and generate contacts with one another, so-called synapses. A neural network of hundreds of cells was produced. The researchers can now use electrical impulses and chemical signal substances to generate nerve impulses, that spread through the network in much the same way as they do in the brain. They can also study how nerve cells react with other molecules, such as pharmaceuticals.

The researchers are trying to develop ‟artificial brains,” which may open entirely new possibilities in brain research and health care, and eventually may lead to the development of biocomputers. Initially the group wants to investigate destruction of synapses between nerve cells, which is one of the earliest signs of Alzheimer’s disease. For example, they would like to cultivate nerve cells and study how cells react to the patients’ spinal fluid.

In the future this method may be useful for testing various pharmaceutical candidates that could slow down the destruction of synapses. In addition, it could provide a better alternative to experiments on animals within the field of brain research in general.

The ability to cultivate nerve cells on nanocellulose is an important step ahead since there are many advantages to the material.

‟Pores can be created in nanocellulose, which allows nerve cells to grow in a three-dimensional matrix. This makes it extra comfortable for the cells and creates a realistic cultivation environment that is more like a real brain compared with a three-dimensional cell cultivation well,” says Paul Gatenholm.

Paul Gatenholm says that there are a number of new biomedical applications for nanocellulose. He is currently also leading other projects that use the material, for example a project where researchers are using nanocellulose to develop cartilage to create artificial outer ears. His research group has previously developed artificial blood vessels made of nanocellulose, which are being evaluated in pre-clinical studies.

Research on new application areas for nanocellulose is of major strategic significance for Sweden. Several projects are financed by the Knut and Alice Wallenberg Foundation and being conducted in collaboration between Chalmers and KTH within the Wallenberg Wood Science Center, WWSC.

Facts about nanocellulose: Nanocellulose is a material that consists of nanosized cellulose fibers. Typical dimensions are widths of 5 to 20 nanometers and lengths of up to 2,000 nanometers. Nanocellulose can be produced by bacteria that spin a close-meshed structure of cellulose fibers. It can also be isolated from wood pulp through processing in a high-pressure homogenizer.

Source: Science Daily

March 16, 2012 By Anne Trafton 

Alan Jasanoff. Credit: Allegra Boverman

After finishing his PhD in molecular biophysics, Alan Jasanoff decided to veer away from that field and try looking into some of the biggest questions in neuroscience: How do we perceive things? What happens in our brains when we make decisions?

After a few months, however, he realized that he didn’t have the tools he wanted to use — so he decided to start making his own.

Jasanoff, who recently earned tenure in MIT’s Department of Biological Engineering, now specializes in developing novel brain-imaging agents that can reveal information more detailed than other human brain-imaging techniques such as fMRI and PET, and more comprehensive than traditional neuroscience measurements such as microscopy and electrode recordings. With the new tools, he is also beginning to explore some of the fundamental questions that first drew him into neuroscience.

Neuroscientists commonly use fMRI, which measures blood flow in the brain, as a proxy for neural activity. In the past several years, Jasanoff has developed sensors that can be used with fMRI to image brain activity more directly, by measuring levels of neurotransmitters (the chemicals that carry messages between neurons) and calcium, which enters neurons when they fire.

Using those sensors, Jasanoff has started exploring how positive reinforcement influences behavior and decision making in animals. His work could also be applicable to fields outside of neuroscience, because intracellular signaling molecules such as calcium “are really ubiquitous — not just in neuronal signaling but signaling throughout the body, during development, immune-cell activity and so on,” says Jasanoff, who is an associate member of MIT’s McGovern Institute for Brain Research and an associate professor of biological engineering, nuclear science and engineering, and brain and cognitive sciences.

[Video]

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March 16, 2012

Distinct patterns of activity— which may indicate a predisposition to care for infants — appear in the brains of adults who view an image of an infant face — even when the child is not theirs, according to a study by researchers at the National Institutes of Health and in Germany, Italy, and Japan.

Seeing images of infant faces appeared to activate in the adult’s brains circuits that reflect preparation for movement and speech as well as feelings of reward.

The findings raise the possibility that studying this activity will yield insights into care giving behavior, but also in cases of child neglect or abuse.

"These adults have no children of their own. Yet images of a baby’s face triggered what we think might be a deeply embedded response to reach out and care for that child," said senior author Marc H. Bornstein, Ph.D., head of the Child and Family Research Section of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the NIH institute that collaborated on the study.

While the researchers recorded participants’ brain activity, the participants did not speak or move. Yet their brain activity was typical of patterns preceding such actions as picking up or talking to an infant, the researchers explained. The activity pattern could represent a biological impulse that governs adults’ interactions with small children.

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March 15th, 2012

Researchers have identified the first gene mutation associated with a chronic and often fatal form of neuroblastoma that typically strikes adolescents and young adults. The finding provides the first clue about the genetic basis of the long-recognized but poorly understood link between treatment outcome and age at diagnosis.

The study involved 104 infants, children and young adults with advanced neuroblastoma, a cancer of the sympathetic nervous system. Investigators discovered the ATRX gene was mutated only in patients age 5 and older. The alterations occurred most often in patients age 12 and older. These older patients were also more likely than their younger counterparts to have a chronic form of neuroblastoma and die years after their disease is diagnosed.

The findings suggest that ATRX mutations might represent a new subtype of neuroblastoma that is more common in older children and young adults. The work is from the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project (PCGP). The study appears in the March 14 edition of the Journal of the American Medical Association.

If validated, the results may change the way doctors think about this cancer, said co-author Richard Wilson, PhD, director of The Genome Institute at Washington University School of Medicine in St. Louis.

“This suggests we may need to think about different treatment strategies for patients depending on whether or not they have the ATRX mutation,” he says.

Neuroblastoma accounts for 7 percent to 10 percent of all childhood cancers and about 15 percent of pediatric cancer deaths. In about 50 percent of patients, the disease has already spread when the cancer is discovered.

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March 15, 2012

In Batten disease, a rare but fatal neurodegenerative disorder in infants and children, proteins (shown in pink) accumulate in the brain and contribute to mental decline, paralysis and seizures. In mice with the infantile form of the disease, combination treatment with gene therapy and bone marrow transplantation reduced the buildup of proteins, dramatically increasing life span and improving motor function. Credit: Mark Sands, Ph.D

Infants with Batten disease, a rare but fatal neurological disorder, appear healthy at birth. But within a few short years, the illness takes a heavy toll, leaving children blind, speechless and paralyzed. Most die by age 5.

There are no effective treatments for the disease, which can also strike older children. And several therapeutic approaches, evaluated in mouse models and in young children, have produced disappointing results.

But now, working in mice with the infantile form of Batten disease, scientists at Washington University School of Medicine in St. Louis and Kings College London have discovered dramatic improvements in life span and motor function by treating the animals with gene therapy and bone marrow transplants.

The results are surprising, the researchers say, because the combination therapy is far more effective than either treatment alone. Gene therapy was moderately effective in the mice, and bone marrow transplants provided no benefit, but together the two treatments created a striking synergy.

The research is online in the Annals of Neurology.

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ScienceDaily (Mar. 15, 2012) — Odds are, you’re not going to make it all the way through this article without thinking about something else. In fact, studies have found that our minds are wandering half the time, drifting off to thoughts unrelated to what we’re doing — did I remember to turn off the light? What should I have for dinner?

Odds are, you’re not going to make it all the way through this article without thinking about something else. In fact, studies have found that our minds are wandering half the time, drifting off to thoughts unrelated to what we’re doing — did I remember to turn off the light? What should I have for dinner? (Credit: © Yuri Arcurs / Fotolia)

A new study investigating the mental processes underlying a wandering mind reports a role for working memory, a sort of a mental workspace that allows you to juggle multiple thoughts simultaneously.

Imagine you see your neighbor upon arriving home one day and schedule a lunch date. On your way to add it to your calendar, you stop to turn off the drippy faucet, feed the cat, and add milk to your grocery list. The capacity that allows you to retain the lunch information through those unrelated tasks is working memory.

The new study, published online March 14 in the journal Psychological Science by Daniel Levinson and Richard Davidson at the University of Wisconsin-Madison and Jonathan Smallwood at the Max Planck Institute for Human Cognitive and Brain Science, reports that a person’s working memory capacity relates to the tendency of their mind to wander during a routine assignment. Lead author Levinson is a graduate student with Davidson, a professor of psychology and psychiatry, in the Center for Investigating Healthy Minds at the UW-Madison Waisman Center.

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ScienceDaily (Mar. 14, 2012) — The meal is pushed way, untouched. Loss of appetite can be a fleeting queasiness or continue to the point of emaciation. While it’s felt in the gut, more is going on inside the head.

New findings are emerging about brain and body messaging pathways that lead to loss of appetite, and the systems in place to avoid starvation.

Today, scientists report in Nature about a brain circuit that mediates the loss of appetite in mice. The researchers also discovered potential therapeutic targets within the pathway. Their experimental results may be valuable for developing new treatments for a variety of eating disorders. These include unrelenting nausea, food aversions, and anorexia nervosa, a condition in which a person no longer wants to eat enough to maintain a normal weight.

The senior author of the paper is Dr. Richard D. Palmiter, University of Washington professor of biochemistry and an investigator with the Howard Hughes Medical Institute. His co-authors are Dr. Qi Wu, formerly of the UW and now at the Eagles Diabetes Research Center and Department of Pharmacology at Carver College of Medicine, University of Iowa, and Dr. Michael S. Clark of the UW Department of Psychiatry and Behavioral Sciences. Palmiter is known for co-developing the first transgenic mice in the 1980s with Dr. Ralph Brinster at the University of Pennsylvania. His more recent studies are of chemicals that nerve cells use to communicate with each other, their roles in mouse brain development and function, and their relation to behavior.

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ScienceDaily (Mar. 14, 2012) — The difficulties that many women describe as memory problems when menopause approaches are real, according to a study published recently  in the journal Menopause, the journal of the North American Menopause Society.

The findings won’t come as a surprise to the millions of women who have had bouts of forgetfulness or who describe struggles with “brain fog” in their late 40s and 50s. But the results of the study, by scientists at the University of Rochester Medical Center and the University of Illinois at Chicago who gave women a rigorous battery of cognitive tests, validate their experiences and provide some clues to what is happening in the brain as women hit menopause.

"The most important thing to realize is that there really are some cognitive changes that occur during this phase in a woman’s life," said Miriam Weber, Ph.D., the neuropsychologist at the University of Rochester Medical Center who led the study. "If a woman approaching menopause feels she is having memory problems, no one should brush it off or attribute it to a jam-packed schedule. She can find comfort in knowing that there are new research findings that support her experience. She can view her experience as normal."

The study is one of only a handful to analyze in detail a woman’s brain function during menopause and to compare those findings to the woman’s own reports of memory or cognitive difficulties.

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ScienceDaily (Mar. 14, 2012) — People with symptoms suggesting rapid eye movement sleep behavior disorder, or RBD, have twice the risk of developing mild cognitive impairment (MCI) or Parkinson’s disease within four years of diagnosis with the sleep problem, compared with people without the disorder, a Mayo Clinic study has found.

The researchers published their findings recently in the Annals of Neurology.

One of the hallmarks of rapid eye movement (REM) sleep is a state of paralysis. In contrast, people with rapid eye movement sleep behavior disorder, appear to act out their dreams when they are in REM sleep. Researchers used the Mayo Sleep Questionnaire to diagnose probable RBD in people who were otherwise neurologically normal. Approximately 34 percent of people diagnosed with probable RBD developed MCI or Parkinson’s disease within four years of entering the study, a rate 2.2 times greater than those with normal rapid eye movement sleep.

"Understanding that certain patients are at greater risk for MCI or Parkinson’s disease will allow for early intervention, which is vital in the case of such disorders that destroy brain cells. Although we are still searching for effective treatments, our best chance of success is to identify and treat these disorders early, before cell death," says co-author Brad Boeve, M.D., a Mayo Clinic neurologist.

Previous studies of Mayo Clinic patients have shown that an estimated 45 percent of people who suffer from RBD will develop a neurodegenerative syndrome such as mild cognitive impairment or Parkinson’s disease within five years of diagnosis.

RBD, MCI and Parkinson’s Disease

"This study is the first to quantify the risk associated with probable RBD in average people, not clinical patients, and it shows that we can predict the onset of some neurodegenerative disorders simply by asking a few critical questions," says lead author Brendon P. Boot, M.D., a behavioral neurologist. Dr. Boot was at Mayo Clinic when the study was conducted. He is now at Harvard University.

• MCI is an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. It involves problems with memory, language, thinking and judgment that are greater than typical age-related changes.
• An estimated 500,000 Americans suffer from Parkinson’s disease, which is characterized by tremor or shakiness, stiffness of the limbs and trunk, slowness of movement, and impaired balance and coordination. 

Source: Science Daily

ScienceDaily (Mar. 14, 2012) — How are 100 billion cells created, each with specific duties? The human brain is evidence that nature can achieve this. Researchers at Linköping University in Sweden have now taken a step closer to solving this mystery.

The magenta-colored structures are nerve cells that use odourant receptor 47b, which senses pheromones. Expression of this receptor is controlled by the transcription factor E93. When E93 is removed, the neurons lose their ability to fulfill their task do detect pheromones, as evidenced by the deactivation of the fluorescent proteins (image to the right). The glowing, green cells, that use olfactory receptor 92a, are not affected because they are controlled by other transcription factors. (Credit: Image courtesy of Linkoeping Universitet)

"Knowledge about the mechanisms that diversify neurons and keep them diverse is necessary in order to cultivate and replace nerve cells in the future," says Mattias Alenius, Assistant Professor of Neuroscience, who has published his research breakthrough in the current issue of the journal PLoS Biology.

Alenius and his research team at the Department of Experimental and Clinical Medicine seek the answer to this pivotal question from a smaller perspective: the fruit fly’s olfactory system.

The humble fly’s olfactory system consists of 1200 olfactory neurons (humans have six million) divided into 34 groups. Each group responds to a particular set of odours, since all the neurons of the group use only one of the olfactory receptors present in the fly’s antennas. Together, the receptors provide the fly with the ability to distinguish between thousands of odours: one olfactory receptor — one neuron group, simple yet complex.

Alenius and his colleagues are the first to go through all of the fruit fly’s 753 gene regulatory genes, called transcription factors. They have identified a set of seven that, in different combinations, are required to create each of the 34 neuron groups in the antenna. A surprising finding is that most transcription factors perform two tasks simultaneously: they can activate odorant receptors’ expression; while at the same time turning off others in the same cell.

Alenius explains, “This is one of the many tricks that are useful to know for the future if you want to make and cultivate each of the many thousands of nerve cell groups that make up our brains.”

Source: Science Daily

March 14, 2012

Earlier evidence out of UCLA suggested that meditating for years thickens the brain (in a good way) and strengthens the connections between brain cells. Now a further report by UCLA researchers suggests yet another benefit.

Eileen Luders, an assistant professor at the UCLA Laboratory of Neuro Imaging, and colleagues, have found that long-term meditators have larger amounts of gyrification (“folding” of the cortex, which may allow the brain to process information faster) than people who do not meditate. Further, a direct correlation was found between the amount of gyrification and the number of meditation years, possibly providing further proof of the brain’s neuroplasticity, or ability to adapt to environmental changes.

The article appears in the online edition of the journal Frontiers in Human Neuroscience.

The cerebral cortex is the outermost layer of neural tissue. Among other functions, it plays a key role in memory, attention, thought and consciousness. Gyrification or cortical folding is the process by which the surface of the brain undergoes changes to create narrow furrows and folds called sulci and gyri. Their formation may promote and enhance neural processing. Presumably then, the more folding that occurs, the better the brain is at processing information, making decisions, forming memories and so forth.

"Rather than just comparing meditators and non-meditators, we wanted to see if there is a link between the amount of meditation practice and the extent of brain alteration," said Luders. "That is, correlating the number of years of meditation with the degree of folding."

The researchers took MRI scans of 50 meditators, 28 men and 22 women, and compared them to 50 control subjects matched for age, handedness and sex. The scans for the controls were obtained from an existing MRI database, while the meditators were recruited from various meditation venues. The meditators had practiced their craft on average for 20 years using a variety of meditation types — Samatha, Vipassana, Zen and more. The researchers applied a well-established and automated whole-brain approach to measure cortical gyrification at thousands of points across the surface of the brain.

They found pronounced group differences (heightened levels of gyrification in active meditation practitioners) across a wide swatch of the cortex, including the left precentral gyrus, the left and right anterior dorsal insula, the right fusiform gyrus and the right cuneus.

Perhaps most interesting, though, was the positive correlation between the number of meditation years and the amount of insular gyrification.

"The insula has been suggested to function as a hub for autonomic, affective and cognitive integration," said Luders. "Meditators are known to be masters in introspection and awareness as well as emotional control and self-regulation, so the findings make sense that the longer someone has meditated, the higher the degree of folding in the insula."

While Luders cautions that genetic and other environmental factors could have contributed to the effects the researchers observed, still, “The positive correlation between gyrification and the number of practice years supports the idea that meditation enhances regional gyrification.”

Provided by University of California - Los Angeles

Source: medicalxpress.com

March 14, 2012 By Bill Hathaway

The aging brain loses its ability to recognize when it is time to move on to a new task, explaining why the elderly have difficulty multi-tasking, Yale University researchers report.

“The aged brain seems to get lost in transition,” said Mark Laubach, associate professor at the John B. Pierce Laboratory and the Yale School of Medicine, and senior author of a study that appears in the March 14 issue of The Journal of Neuroscience.

Laubach’s team was studying the impact of aging on working memory, the type of memory that allows you to recall that dinner is in the oven when you are talking on the phone. The researchers examined brain activity in the medial prefrontal cortex of young and older rats that is related to spatial working memory — the type of memory that allows you to recall, for example, that mashed potatoes are on the stove and the turkey is in the oven

Based on previous studies, they expected that it would be spatial memory most affected by aging. Instead, the Yale team found that the aged brain seems to lose its ability to respond to cues that indicate when it is time to move on to a new task.

This ability to transition between tasks is critical for many daily activities, such as cooking dinner or handling situations that can arise in the workplace. The brain’s failure to monitor the timing of actions leads people to forget to turn off a burner on the stove while setting the table.

The research team found that neurons in the medial prefrontal cortex of older rats reacted more slowly to signals indicating that reward was available. Conversely, these signals immediately triggered a response in younger rats.

“Neurons in older rats fired fewer spikes in response to reward-predictive cues. The animals failed to respond immediately to the cues. They seemed to be stuck in time,” Laubach said.

Researchers hope that by understanding the mechanisms of working memory, scientists might one day be able to slow or perhaps eliminate deterioration of these brain functions over a lifespan, Laubach said.

Provided by Yale University

Source: medicalxpress.com

March 14, 2012 by Catherine Zandonella

(Medical Xpress) — Princeton University researchers have used a novel virtual reality and brain imaging system to detect a form of neural activity underlying how the brain forms short-term memories that are used in making decisions.

Using a virtual reality maze and brain imaging system, Princeton researchers have detected a form of neural activity the formation of short-term memories used in decision-making. These panels show the view of the virtual reality maze as seen by the mouse. The top panel shows a cue or sign that indicates to the mouse to turn right to receive a water reward. The middle panel shows a cue telling the mouse to turn left. The bottom panel shows the view at the T-intersection of the maze. (Image courtesy of Nature, Christopher Harvey and David Tank)

By following the brain activity of mice as they navigated a virtual reality maze, the researchers found that populations of neurons fire in distinctive sequences when the brain is holding a memory. Previous research centered on the idea that populations of neurons fire together with similar patterns to each other during the memory period.

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March 13, 2012

The next time you set a trap for that rat running around in your basement, here’s something to consider: you are going up against an opponent whose ability to assess the situation and make decisions is statistically just as good as yours.

A Cold Spring Harbor Laboratory (CSHL) study that compared the ability of humans and rodents to make perceptual decisions based on combining different modes of sensory stimuli—visual and auditory cues, for instance—has found that just like humans, rodents also combine multisensory information and exploit it in a “statistically optimal” way — or the most efficient and unbiased way possible.

"Statistically optimal combination of multiple sensory stimuli has been well documented in humans, but many have been skeptical about this behavior occurring in other species," explains Assistant Professor Anne Churchland, Ph.D., a neuroscientist who led the new study. "Our work is the first demonstration of its occurrence in rodents." The study appears in the March 14 issue of the Journal of Neuroscience.

This discovery is exciting, according to Churchland, because it suggests that the same evolutionarily conserved neural circuits underlie this behavior in both humans and rodents. “By observing this behavior in rodents, we have a chance to explore its neural basis – something that is not feasible to do in people,” Churchland says.

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ScienceDaily (Mar. 13, 2012) — A team of neuroscientists led by a Wayne State University School of Medicine professor has discovered stark developmental differences in brain network function in children of parents with schizophrenia when compared to those with no family history of mental illness.

The study, led by Vaibhav Diwadkar, Ph.D., assistant professor of psychiatry and behavioral neurosciences and co-director of the Division of Brain Research and Imaging Neuroscience, was published in the March 2012 issue of the American Medical Association journal Archives of General Psychiatry and is titled, “Disordered Corticolimbic Interactions During Affective Processing in Children and Adolescents at Risk for Schizophrenia Revealed by Functional Magnetic Resonance Imaging and Dynamic Causal Modeling.”

The results provide significant insight into plausible origins of schizophrenia in terms of dysfunctional brain networks in adolescence, demonstrate sophisticated analyses of functional magnetic resonance imaging (fMRI) data and clarify the understanding of developmental mechanisms in normal versus vulnerable brains. The resulting information can provide unique information to psychiatrists.

The study took place over three years, using MRI equipment at Harper University Hospital in Detroit. Using fMRI the researchers studied brain function in young individuals (8 to 20 years of age) as they observed pictures of human faces depicting positive, negative and neutral emotional expressions. Participants were recruited from the metropolitan Detroit area. Because children of patients are at highly increased risk for psychiatric illnesses such as schizophrenia, the team was interested in studying brain network function associated with emotional processing and the relevance of impaired network function as a potential predictor for schizophrenia.

To investigate brain networks, the researchers applied advanced analyses techniques to the fMRI data to investigate how brain regions dynamically communicate with each other. The study demonstrated that children at risk for the illness are characterized by reduced network communication and disordered network responses to emotional faces. This suggests that brain developmental processes are going awry in children whose parents have schizophrenia, suggesting this is a subgroup of interest to watch in future longitudinal studies.

"Brain network dysfunction associated with emotional processing is a potential predictor for the onset of emotional problems that may occur later in life and that are in turn associated with illnesses like schizophrenia," Diwadkar said. "If you clearly demonstrate there is something amiss in how the brain functions in children, there is something you can do about it. And that’s what we’re interested in."

The results don’t show whether schizophrenia will eventually develop in the subjects. “It doesn’t mean that they have it, or that they will have it,” he said.

"The kids we studied were perfectly normal if you looked at them," he said. "By using functional brain imaging we are trying to get underneath behavior."

"We are able to do this because we can investigate dynamic changes in brain network function by assessing changes in the fMRI signal. This allowed us to capture dramatic differences in how regions in the brain network are interacting with each other," he said.

According to the National Alliance on Mental Illness, schizophrenia affects men and women with equal frequency, but generally manifests in men in their late teens or early 20s, and in women in their late 20s or early 30s.

Source: Science Daily

ScienceDaily (Mar. 13, 2012) — A compound that previously progressed to Phase II clinical trials for cancer treatment slows neurological damage and improves brain function in an animal model of Alzheimer’s disease, according to a new study. The study published the week of March 13 in the Journal of Neuroscience shows that the compound epothilone D (EpoD) is effective in preventing further neurological damage and improving cognitive performance in a mouse model of Alzheimer’s disease (AD). The results establish how the drug might be used in early-stage AD patients.

This is an electron micrographic picture of a cross section of a nerve from an Alzheimer’s model mouse. Structural abnormalities in the nerve are indicated by the arrows. Alzheimer model mice that received the drug epothilone D had a significant reduction in the number of these abnormalities. (Credit: Zhang, et al. The Journal of Neuroscience 2012.)

Investigators from the Perelman School of Medicine at the University of Pennsylvania, led by first author Bin Zhang, MD, PhD, senior research investigator, and senior author Kurt R. Brunden, PhD, Director of Drug Discovery at the Center for Neurodegenerative Disease Research (CNDR), administered EpoD to aged mice that had memory deficits and inclusions within their brains that resemble the tangles formed by misfolded tau protein, a hallmark of AD. In nerve cells, tau normally stabilizes structures called microtubules, the molecular railroad tracks upon which cellular cargo is transported. Tangles may compromise microtubule stability, with resulting damage to nerve cells. A drug that could increase microtubule stability might improve nerve-cell function in AD and other diseases where tangles form in the brain.

EpoD acts by the same microtubule-stabilizing mechanism as the FDA-approved cancer drug paclitaxel (Taxol™). These drugs prevent cancer cell proliferation by over-stabilizing specialized microtubules involved in the separation of chromosomes during the process of cell division. However, the Penn researchers previously demonstrated that EpoD, unlike paclitaxel, readily enters the brain and so may be useful for treating AD and related disorders.

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March 13, 2012

Warm weather may hinder cognitive performance in people with multiple sclerosis (MS), according to results of a Kessler Foundation study e-published online ahead of print by Neurology. An accompanying editorial by Meier & Christodoulou, MS and heat: The smoke and the fire, details the study’s unique aspects, ie, longitudinal followup in a cohort with apparently quiescent disease.

Victoria M. Leavitt, Ph.D., research scientist at Kessler Foundation, is principal investigator for the study, which for the first time, shows a link between warm weather and cognition in people with MS. With more research, this information might help guide people with MS in making life decisions and assist their clinicians in choosing clinical treatment. Scientists may also want to consider the effect of warmer weather on cognition when designing and conducting clinical trials.

Kessler Foundation co-investigators are James F. Sumowski, Ph.D., Research Scientist, Nancy Chiaravalloti, Ph.D., Director of Neuropsychology & Neuroscience Research, and John DeLuca, Ph.D., Vice President for Research. All also have faculty appointments at UMDNJ-New Jersey Medical School.

Memory and processing speed were measured in 40 individuals with MS and 40 healthy people without MS. The study was conducted throughout the calendar year, and the daily temperature at the time of testing was recorded. The results showed that people with MS scored 70 percent higher on the tests on cooler days. There was no connection between daily temperature and cognitive performance for individuals without MS.

To confirm the effect of outdoor temperature, the group examined a separate sample of 45 persons with MS for whom cognitive tests were given at two sessions separated by a 6-month interval. For each person, cognitive performance was worse for testing during the warmer temperature. This finding is particularly important for researchers planning clinical trials with cognitive outcomes, especially since such trials frequently span a 6-month period. If baseline measurements of cognitive function are taken during warm months, the effect of the treatment may be inflated by the temperature effect. Cognitive performance may be a more sensitive indicator of subclinical disease activity than traditional assessments based on sensorimotor or EDSS (Expanded Disability Status score).

Provided by Kessler Foundation

Source: medicalxpress.com

Article Date: 13 Mar 2012 - 1:00 PDT

More than two-thirds of human genes have counterparts in the well-studied fruit fly, Drosophila melanogaster, so although it may seem that humans don’t have much in common with flies, the correspondence of our genetic instructions is astonishing. In fact, there are hundreds of inherited diseases in humans that have Drosophila counterparts.

At the Genetics Society of America’s 53rd Annual Drosophila Research Conference in Chicago, several scientific investigators shared their knowledge of some of these diseases, including ataxia-telangiectasia (A-T), a neurodegenerative disorder; Rett Syndrome, a neurodevelopmental disorder; and kidney stones, a common health ailment. All are the subject on ongoing research using the Drosophila model system.

Andrew Petersen, a graduate student in Dr. David Wassarman’s laboratory at the University of Wisconsin-Madison, discussed his experiments with a fly model of the rare childhood disease ataxia-telangiectasia. A-T causes cell death within the brain, poor coordination, characteristic spidery blood vessels that show through the skin, and susceptibility to leukemias and lymphomas. A-T generally results in a life expectancy of only 25 years.

A-T is normally lethal in flies, but Mr. Petersen induced a mutant that develops symptoms only when the environmental temperature rises above a certain level, allowing Mr. Petersen to control the lethality by varying the fly’s environment. The mutant flies lose their ability to climb up the sides of their vial habitats - a sign of neurodegeneration - and die prematurely. Their glial cells are primarily affected, rather than the neurons that the glia support. In addition, an innate immune response is activated in the compromised glia, a scenario reminiscent of Alzheimer’s and Parkinson’s diseases. “We are one step closer to knowing how these diseases occur and possibly how we can treat them,” Mr. Petersen concluded.

Sarah Certel, Ph.D., assistant professor of biological sciences at the University of Montana-Missoula, works with flies that have been altered to include the human gene MeCP2. This gene controls how neurons use many other genes, and the amount of the protein that it encodes must be within a specific range for the brain to develop normally. Too little of the protein and Rett syndrome results, a disorder on the X chromosome, which exclusively affects females in childhood. (Males with this mutation are generally miscarried or are stillborn.) It causes a constellation of symptoms including characteristic hand-wringing, autism, seizures, cognitive impairment, and loss of mobility. Yet too much of the protein causes similar problems.

In flies, altered levels of the MeCP2 protein affect sleep and aggression. For flies and most model organisms, sleep is inferred as the absence of activity during the day and night. To study sleep, Dr. Certel conducted “actograms” for individual flies. “The actogram records the activities of individually housed flies when they cross an infrared beam,” she explained. The flies’ sleep became fragmented, delayed, and shortened. “We’re studying the link between the cellular changes and behaviors,” she added.

Switching from the brain to the urinary system, it was noted that “Drosophila get kidney stones too” began Julian Dow, Ph.D., professor of molecular and integrative physiology at the University of Glasgow, United Kingdom. The fly version of a kidney is much simpler in design, a quartet of Malpighian tubules that are conveniently transparent.

Dr. Dow discussed a fly mutant called “rosy,” discovered a century ago, that corresponds to the rare human inborn error of metabolism called xanthinuria type 1, as well as a diet-induced blockage that corresponds to the more common human condition of calcium oxalate kidney stones. In time-lapse video, Dr. Dow showed stones appearing and growing in the Malpighian tubule.

“This was the first time in history that we saw kidney stones form - something that you cannot ethically do in humans,” he said. His research group, in collaboration with Dr. Michael Romero at the Mayo Institute, is now searching for chemical compounds that interfere with the formation of stones and their tendency to accrete into painful obstructions. They’ve already found a way to block a gene responsible for transporting the oxalate, slowing stone formation. With time, this work could help reduce the 250,000 emergency room admissions for kidney stones in the USA annually and the more than $2 billion in health care costs for treating them.

These were only three of several human diseases discussed at the Drosophila Conference. Others included oxidative stress, cancer linked to diabetes, amyloid build-up in Alzheimer’s disease, epilepsy, and muscular dystrophy. There are so many human diseases that have Drosophila counterparts that they are listed in a database called Homophila. Given the number that exist, we are certain to be learning more about our health from the fly in the years ahead.  

Source: Medical News Today

ScienceDaily (Mar. 13, 2012) — One of the trickiest parts of treating brain conditions is the blood brain barrier, a blockade of cells that prevent both harmful toxins and helpful pharmaceuticals from getting to the body’s control center. But, a technique published in JoVE, uses an MRI machine to guide the use of microbubbles and focused ultrasound to help drugs enter the brain, which may open new treatment avenues for devastating conditions like Alzheimer’s and brain cancers.

"It’s getting close to the point where this could be done safely in humans," said paper-author Meaghan O’Reilly, "there is a push towards applications."

The current method of disrupting the blood-brain barrier (BBB) is by using osmotic agents such as mannitol, which suck the water out of the cells that form the barrier, causing the gaps between them to get bigger. Unfortunately, this method opens large areas of the barrier, leaving the brain exposed to toxins.

The benefit of the microbubble technique is that it can be used on a very small area of the BBB. The microbubbles, made of lipids (fats) and gas, are injected into the blood stream. When focused ultrasound is applied, the bubbles expand and contract. It is thought that the force of the movement in the bubbles causes the cells that form the BBB to temporarily separate, which allows drugs to reach the brain.

"Microbubble technology has been around for years, though its applications have mostly been as contrast agents for diagnostic ultrasound," said JoVE Editorial Director, Dr. Beth Hovey. "This newer approach, using ultrasound to help the bubbles permeablize the blood brain barrier, will hopefully allow for better treatment of diseases within the brain."

In this method, O’Reilly and her colleagues use the MRI machine to ensure that the barrier opens, and they can also time how long it takes for it to close, which will be important for when the technique is used on patients.

"The ability of focused ultrasound combined with microbubbles to disrupt the blood brain barrier has been known for over a decade. However, because the actual technique can be challenging — there are critical steps involved — the video article fills a gap in the literature that is a major hindrance to people getting into the field," she said.

Source: Science Daily

ScienceDaily (Mar. 13, 2012) — People often wonder if computers make children smarter. Scientists at the University of California, Berkeley, are asking the reverse question: Can children make computers smarter? And the answer appears to be ‘yes.’

Research indicates that babies and toddlers do most of their learning as they “play.” (Credit: © matka_Wariatka / Fotolia)

UC Berkeley researchers are tapping the cognitive smarts of babies, toddlers and preschoolers to program computers to think more like humans.

If replicated in machines, the computational models based on baby brainpower could give a major boost to artificial intelligence, which historically has had difficulty handling nuances and uncertainty, researchers said

"Children are the greatest learning machines in the universe. Imagine if computers could learn as much and as quickly as they do," said Alison Gopnik a developmental psychologist at UC Berkeley and author of "The Scientist in the Crib" and "The Philosophical Baby."

In a wide range of experiments involving lollipops, flashing and spinning toys, and music makers, among other props, UC Berkeley researchers are finding that children — at younger and younger ages — are testing hypotheses, detecting statistical patterns and drawing conclusions while constantly adapting to changes.

"Young children are capable of solving problems that still pose a challenge for computers, such as learning languages and figuring out causal relationships," said Tom Griffiths, director of UC Berkeley’s Computational Cognitive Science Lab. "We are hoping to make computers smarter by making them a little more like children."

For example, researchers said, computers programmed with kids’ cognitive smarts could interact more intelligently and responsively with humans in applications such as computer tutoring programs and phone-answering robots.

And that’s not all.

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March 12th, 2012

Regular use of cholesterol-lowering statin drugs may be associated with a modest reduction in risk for developing Parkinson disease, particularly among younger patients, according to a study in the March issue of Archives of Neurology, one of the JAMA Archives journals.

Statins are one of the most prescribed classes of drugs in the United States and some researchers have hypothesized that the anti-inflammatory and immunomodulating effects of these medications may be neuroprotective. However, statins also may have unfavorable effects on lowering the level of plasma coenzyme Q10, which may be neuroprotective in patients with Parkinson disease (PD), the researchers write in their study background.

Xiang Gao, M.D., Ph.D., of Brigham and Women’s Hospital and Harvard School of Public Health, Boston, and colleagues conducted a prospective study that included 38,192 men and 90,874 women participating in the Health Professional Follow-up study and the Nurses’ Health study.

During 12 years of follow-up from 1994 to 2006, researchers documented 644 incident PD cases (338 in women and 306 in men).

“In summary, we observed an association between regular use of statins and lower risk of developing PD, particularly among younger patients,” the researchers comment. “However, our results should be interpreted with caution because only approximately 70 percent of users of cholesterol-lowering drugs at baseline were actual statin users. Further, the results were only marginally significant and could be due to chance.”

Researchers note that because they classified the use of any cholesterol-lowering drugs before 2000 as statin use, misclassification was inevitably introduced. They also did not collect information on the use of specific statins, which could have different effects on the central nervous system.

When researchers did observe a significant interaction between statin use and age in relation to PD risk it was among study participants younger than 60 years at the start of follow-up, not among those participants who were older.

The authors note that not only have epidemiologic studies produced mixed results on statin use and PD risk, but statins also may have unfavorable effects on the central nervous system.

“In contrast with use of ibuprofen, which has been consistently found to be inversely associated with PD risk in these cohorts as well as in other longitudinal studies, the overall epidemiological evidence relating stain use to PD risk remains unconvincing,” the authors conclude. “Given the potential adverse effects of statins, further prospective observational studies are needed to explore the potential effects of different subtypes of statin on risk of PD and other neurodegenerative diseases.”
(Arch Neurol. 2012;69[3]:380-384).

Source: Neuroscience News

March 12th, 2012

Scientists from the Monell Center report that seven of 12 related mammalian species have lost the sense of sweet taste. As each of the sweet-blind species eats only meat, the findings demonstrate that a liking for sweets is frequently lost during the evolution of diet specialization.

Previous research from the Monell team had revealed the remarkable finding that both domestic and wild cats are unable to taste sweet compounds due to defects in a gene that controls structure of the sweet taste receptor.

Cats are obligate carnivores, meaning that they subsist only on meat. In the current study, published online in Proceedings of the National Academy of Sciences USA, the Monell scientists next asked whether other strict carnivores have also lost the sweet taste receptor.

To do this, they examined sweet taste receptor genes from 12 related mammalian species with varying dietary habits. They once again found taste loss and to their surprise, it was widespread in the meat-eating species.

Senior author Gary Beauchamp, Ph.D., a behavioral biologist at Monell, comments, “Sweet taste was thought to be nearly a universal trait in animals. That evolution has independently led to its loss in so many different species was quite unexpected.”

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