Neuroscience
Month
August 9, 2012
MIT study reveals changes in brain activity as children learn to read other people’s behavior.
When you try to read other people’s thoughts, or guess why they are behaving a certain way, you employ a skill known as theory of mind. This skill, as measured by false-belief tests, takes time to develop: In children, it doesn’t start appearing until the age of 4 or 5.
Several years ago, MIT neuroscientist Rebecca Saxe showed that in adults, theory of mind is seated in a specific brain region known as the right temporo-parietal junction (TPJ). Saxe and colleagues at MIT have now shown how brain activity in the TPJ changes as children learn to reason about others’ thoughts and feelings.
The findings suggest that the right TPJ becomes more specific to theory of mind as children age, taking on adult patterns of activity over time. The researchers also showed that the more selectively the right TPJ is activated when children listen to stories about other people’s thoughts, the better those children perform in tasks that require theory of mind.
The paper, published in the July 31 online edition of the journal Child Development, lays the groundwork for exploring theory-of-mind impairments in autistic children, says Hyowon Gweon, a graduate student in Saxe’s lab and lead author of the paper.
“Given that we know this is what typically developing kids show, the next question to ask is how it compares to autistic children who exhibit marked impairments in their ability to think about other people’s minds,” Gweon says. “Do they show differences from typically developing kids in their neural activity?”
Saxe, an associate professor of brain and cognitive sciences and associate member of MIT’s McGovern Institute for Brain Research, is senior author of the Child Development paper. Other authors are Marina Bedny, a postdoc in Saxe’s lab, and David Dodell-Feder, a graduate student at Harvard University.
August 8, 2012
Researchers capture evolutionary dynamics in a new theoretical framework that could help explain some of the mysteries of how and why species change over time.
Although the qualitative description of evolution – its observed behavior and characteristics – is well-established, a comprehensive quantitative theory that captures general evolution dynamics is still lacking. There are also many lingering mysteries surrounding the story of life on Earth, including the question of why sex is such a prevalent reproductive strategy. A team of scientists from the Chinese Academy of Sciences; Jilin University in Jilin, China; and the State University of New York at Stony Brook, led by Prof. Jin Wang, has examined some of these puzzles from a physical science prospective. They propose a new theory of evolution with two ingredients: the underlying emergent “fitness” landscape and an associated evolutionary force called “curl flux,” which causes species to move through the emergent fitness landscape in a spiraling manner.
The researchers captured evolutionary relationships in a system of equations. They then created quantitative pictures that visualized evolutionary pathways as journeys through a mountainous terrain of peaks and valleys of biological fitness. The key breakthrough beyond the conventional quantitative theory of evolution is the emergent curl flux, which is generated by interactions between individuals within or across species. The underlying emergent landscape gradient and the curl flux act together as a “Yin and Yang” duality pair to determine the dynamics of general evolution, says Wang. An example of similar behavior is the particle and wave duality that determines the dynamics of the quantum world, he notes. The researchers also note that this combined effect is analogous to the way electric and magnetic forces both act on electrons.
The new theory provides a physical foundation for general evolution dynamics. The researchers found that interactions between individuals of different species can give rise to the curl flux. This can sustain an endless evolution that does not lead to areas of higher relative fitness, even if the physical environment is unchanged.
This finding offers a theoretical framework to explain the Red Queen Hypothesis, which states that species continually evolve in order to fend off parasites that are themselves continually evolving. The hypothesis, first proposed by evolutionary biologist Leigh Van Valen in 1973, gets its name from the character of the Red Queen in Lewis Carroll’s book Through the Looking-Glass, who observed that in her world it was necessary to keep running just to stay in one place. The idea of endless co-evolution through the maintenance of the genetic variation due to the curl flux could help explain the benefits of sexual reproduction, since the mixing and matching of genes preserves a greater diversity of traits. When a species’ arms race with a co-evolving parasite takes an unexpected twist, a previously unnecessary trait could suddenly turn into the key to surviving. In the co-evolving world, there is no guarantee for “survival of the fittest” and it is often necessary to keep running for survival.
Source: PHYS.ORG
August 8, 2012 By Lia Samson
(Phys.org) — In a recent paper, Aleksander Ellis of the University of Arizona Eller College of Management and a colleague demonstrate that lack of sleep can cause deviant behavior at work.
Early 2011 saw a spate of reports in the media about air traffic controllers sleeping on the job as a result of sleep deprivation. The potential harm from this behavior is obvious, but what about the average office job? Can sleep deprivation cause counterproductive, or even unethical, behavior in organizations?
“Over the past decade, Americans have been getting less and less sleep, and estimates are that this trend will continue,” said Professor of Management and Organizations Aleksander Ellis, the Charles and Candice Nelson Fellow. “In fact, in certain industries, lack of sleep is worn as a badge of honor.”
In a recent paper published in the Academy of Management Journal, Ellis and co-author Michael Christian of Kenan-Flagler Business School at the University of North Carolina-Chapel Hill demonstrate that lack of sleep can cause deviant behavior.
In one part of the study, for instance, the researchers asked a group of subjects to respond to an email that contained colloquial language and misspellings. One of the sleep-deprived subjects responded with an unprofessional, personal attack. This is just one example Ellis and Christian cite to demonstrate how sleep deprivation reduces self-control and increases hostility.
Ellis and Christian are currently working on a parallel project that examines how sleep deprivation affects the tendency of individuals to behave unethically by conforming to the behavior of unethical authority figures.
Source: PHYS.ORG
August 8th, 2012
The brain has billions of neurons, arranged in complex circuits that allow us to perceive the world, control our movements and make decisions. Deciphering those circuits is critical to understanding how the brain works and what goes wrong in neurological disorders.
MIT neuroscientists have now taken a major step toward that goal. In a new paper appearing in the Aug. 9 issue of Nature, they report that two major classes of brain cells repress neural activity in specific mathematical ways: One type subtracts from overall activation, while the other divides it.
“These are very simple but profound computations,” says Mriganka Sur, the Paul E. Newton Professor of Neuroscience and senior author of the Nature paper. “The major challenge for neuroscience is to conceptualize massive amounts of data into a framework that can be put into the language of computation. It had been a mystery how these different cell types achieve that.”
Neuroscientists report that two major classes of brain cells repress neural activity in specific mathematical ways: One type subtracts from overall activation, while the other divides it.
The findings could help scientists learn more about diseases thought to be caused by imbalances in brain inhibition and excitation, including autism, schizophrenia and bipolar disorder.
Lead authors of the paper are grad student Caroline Runyan and postdoc Nathan Wilson. Forea Wang ’11, who contributed to the work as an MIT undergraduate, is also an author of the paper.
A fine balance
There are hundreds of different types of neuron in the brain; most are excitatory, while a smaller fraction are inhibitory. All sensory processing and cognitive function arises from the delicate balance between these two influences. Imbalances in excitation and inhibition have been associated with schizophrenia and autism.
“There is growing evidence that alterations in excitation and inhibition are at the core of many subsets of neuropsychiatric disorders,” says Sur, who is also the director of the Simons Center for the Social Brain at MIT. “It makes sense, because these are not disorders in the fundamental way in which the brain is built. They’re subtle disorders in brain circuitry and they affect very specific brain systems, such as the social brain.”
In the new Nature study, the researchers investigated the two major classes of inhibitory neurons. One, known as parvalbumin-expressing (PV) interneurons, targets neurons’ cell bodies. The other, known as somatostatin-expressing (SOM) interneurons, targets dendrites — small, branching projections of other neurons. Both PV and SOM cells inhibit a type of neuron known as pyramidal cells.
To study how these neurons exert their influence, the researchers had to develop a way to specifically activate PV or SOM neurons, then observe the reactions of the target pyramidal cells, all in the living brain.
First, the researchers genetically programmed either PV or SOM cells in mice to produce a light-sensitive protein called channelrhodopsin. When embedded in neurons’ cell membranes, channelrhodopsin controls the flow of ions in and out of the neurons, altering their electrical activity. This allows the researchers to stimulate the neurons by shining light on them.
The team combined this with calcium imaging inside the target pyramidal cells. Calcium levels reflect a cell’s electrical activity, allowing the researchers to determine how much activity was repressed by the inhibitory cells.
“Up until maybe three years ago, you could only just blindly record from whatever cell you ran into in the brain, but now we can actually target our recording and our manipulation to well-defined cell classes,” Runyan says.
Taking a circuit apart
In this study, the researchers wanted to see how activation of these inhibitory neurons would influence how the brain processes visual input — in this case, horizontal, vertical or tilted bars. When such a stimulus is presented, individual cells in the eye respond to points of light, then convey that information to the thalamus, which relays it to the visual cortex. The information stays spatially encoded as it travels through the brain, so a horizontal bar will activate corresponding rows of cells in the brain.
Those cells also receive inhibitory signals, which help to fine-tune their response and prevent overstimulation. The MIT team found that these inhibitory signals have two distinct effects: Inhibition by SOM neurons subtracts from the total amount of activity in the target cells, while inhibition by PV neurons divides the total amount of activity in the target cells.
“Now that we finally have the technology to take the circuit apart, we can see what each of the components do, and we found that there may be a profound logic to how these networks are naturally designed,” Wilson says.
These two types of inhibition also have different effects on the range of cell responses. Every sensory neuron responds only to a particular subset of stimuli, such as a range of brightness or a location. When activity is divided by PV inhibition, the target cell still responds to the same range of inputs. However, with subtraction by SOM inhibition, the range of inputs to which cells will respond becomes narrower, making the cell more selective.
Increased inhibition by PV neurons also changes a trait known as the response gain — a measurement of how much cells respond to changes in contrast. Inhibition by SOM neurons does not alter the response gain.
The researchers believe this type of circuit is likely repeated throughout the brain and is involved in other types of sensory perception, as well as higher cognitive functions.
Sur’s lab now plans to study the role of PV and SOM inhibitory neurons in a mouse model of autism. These mice lack a gene called MeCP2, giving rise to Rett Syndrome, a rare disease that produces autism-like symptoms as well as other neurological and physical impairments. Using their new technology, the researchers plan to test the hypothesis that a lack of neuronal inhibition underlies the disease.
Source: Neuroscience News
ScienceDaily (Aug. 8, 2012) — Stressed and non-stressed people use different brain regions and different strategies when learning. This has been reported by the cognitive psychologists PD Dr. Lars Schwabe and Professor Oliver Wolf from the Ruhr-Universität Bochum in the Journal of Neuroscience. Non-stressed individuals applied a deliberate learning strategy, while stressed subjects relied more on their gut feeling. “These results demonstrate for the first time that stress has an influence on which of the different memory systems the brain turns on,” said Lars Schwabe.
The experiment: Stress due to ice-water
The data from 59 subjects were included in the study. Half of the participants had to immerse one hand into ice-cold water for three minutes under video surveillance. This stressed the subjects, as hormone assays showed. The other participants had to immerse one of their hands just in warm water. Then both the stressed and non-stressed individuals completed the so-called weather prediction task. The subjects looked at playing cards with different symbols and learned to predict which combinations of cards announced rain and which sunshine. Each combination of cards was associated with a certain probability of good or bad weather. People apply differently complex strategies in order to master the task. During the weather prediction task, the researchers recorded the brain activity with MRI.
Two routes to success
Both stressed and non-stressed subjects learned to predict the weather according to the symbols. Non-stressed participants focused on individual symbols and not on combinations of symbols. They consciously pursued a simple strategy. The MRI data showed that they activated a brain region in the medial temporal lobe — the hippocampus, which is important for long-term memory. Stressed subjects, on the other hand, applied a more complex strategy. They made their decisions based on the combination of symbols. They did this, however, subconsciously, i.e. they were not able to formulate their strategy in words. The result of the brain scans was also accordingly: In the case of the stressed volunteers the so-called striatum in the mid-brain was activated — a brain region that is responsible for more unconscious learning. “Stress interferes with conscious, purposeful learning, which is dependent upon the hippocampus,” concluded Lars Schwabe. “So that makes the brain use other resources. In the case of stress, the striatum controls behaviour — which saves the learning achievement.”
Source: Science Daily
8-Aug-2012
The molecular missteps that disrupt brain function in the most common form of adult-onset muscular dystrophy have been revealed in a new study published by Cell Press. Myotonic dystrophy is marked by progressive muscle wasting and weakness, as well as excessive daytime sleepiness, memory problems, and mental retardation. A new mouse model reported in the August 9 issue of the journal Neuron reproduces key cognitive and behavioral symptoms of this disease and could be used to develop drug treatments, which are currently lacking.
The red dots are the toxic RNAs accumulating in the nucleus (blue) of a myotonic dystrophy cell (these are induced pluripotent stem, or iPS, cells) and the green is a neuronal marker. Credit: Charizanis et al., Neuron.
"The new animal model reproduces important aspects of myotonic dystrophy brain disease, so this model may be useful to develop biomarkers and test future drug therapies," says senior study author Maurice Swanson of the University of Florida.
Previous studies had shown that mutated genes underlying the disease produce toxic ribonucleic acids (RNAs) during transcription, and these RNAs cause the production of incorrect forms of proteins in muscle tissue by blocking the actions of a protein called MBNL1. As a result, proteins typically found in fetal muscles increase in abundance, while the normal suite of proteins found in adult muscles decrease in number. However, until now, it was not clear whether molecular abnormalities similar to those in muscle tissue of individuals with mytonic dystrophy also occur in the brain, resulting in the cognitive neurological problems.
In the new study, Swanson and his team focused on a related protein called MBNL2, which is found in the brain. They developed a new mouse model that lacked a functional Mbnl2 gene. These animals experienced an increase in the amount of rapid eye movement sleep as well as learning and memory deficits, similar to human patients.
The researchers also found extensive evidence of toxic RNAs in the hippocampus, as well as signs that fetal proteins were being produced in the brains of adult mutants. This pattern was also evident in the autopsied brain tissue of humans who had myotonic dystrophy. “This study should accelerate our understanding of how myotonic dystrophy mutations impact brain development and function,” Swanson says.
Source: EurekAlert!
By Lisa Cosgrove | August 7, 2012
It is part of the human condition to have implicit biases—and remain blissfully ignorant of them. Academic researchers, scientists, and clinicians are no exception; they are as marvelously flawed as everyone else. But it is not the cognitive bias that’s the problem. Rather, the denial that there is a problem is where the issues arise. Indeed, our capacity for self-deception was beautifully captured in the title of a recent book addressing researchers’ self-justificatory strategies, Mistakes Were Made (But Not by Me).
Illustration by Dusan Petricic
Decades of research have demonstrated that cognitive biases are commonplace and very difficult to eradicate, and more recent studies suggest that disclosure of financial conflicts of interest may actually worsen bias. This is because bias is most often manifested in subtle ways unbeknownst to the researcher or clinician, and thus is usually implicit and unintentional. For example, although there was no research misconduct or fraud, re-evaluations of liver tissue of rats exposed to the drug dioxin resulted in different conclusions about the liver cancer in those rats: compared to the original investigation, an industry-sponsored re-evaluation identified fewer tissue slides as cancerous and this finding affected policy recommendations (water quality standards were weakened). (See also Brown, Cold Spring Harbor Laboratory Press, 13–28, 1991.) This example is just one of many that points to a genericrisk that a financial conflict of interest may compromise research or undermine public trust.
Indeed, recent neuroscience investigations demonstrate that effective decision-making involves not just cognitive centers but also emotional areas such as the hippocampus and amygdala. This interplay of cognitive-emotional processing allows conflicts of interest to affect decision-making in a way that is hidden from the person making the decision.
Despite these findings, many individuals are dismissive of the idea that researchers’ financial ties to industry are problematic. For example, in a recent essay in The Scientist, Thomas Stossel of Brigham & Women’s Hospital and Harvard Medical School asked, “How could unrestricted grants, ideal for research that follows up serendipitous findings, possibly be problematic? The money leads to better research that can benefit patients.” Many argue that subjectivity in the research process and the potential for bias can be eradicated by strict adherence to the scientific method and transparency about industry relationships. Together, scientists believe, these practices can guarantee evidence-based research that leads to the discovery and dissemination of “objective” scientific truths. The assumption is that the reporting of biased results is a “bad apple” problem—a few corrupt individuals engaging in research fraud. But what we have today is a bad barrel.
Some have begun to use the analytic framework of “institutional corruption” to bring attention to the fact that the trouble is not with a few corrupt individuals hurting an organization whose integrity is basically intact. Institutional corruption refers to the systemic and usually legal—and often accepted and widely defended—practices that bring an organization or institution off course, undermine its mission and effectiveness, and weaken public trust. Although the entire field of biomedicine has come under scrutiny because of concerns about an improper dependence on industry and all medical specialties have struggled with financial conflicts of interest, psychiatry has been particularly troubled, being described by some as having a crisis of credibility.
This credibility crisis has been played out most noticeably in the public controversy surrounding the latest revision to the Diagnostic and Statistical Manual of Mental Disorders (DSM). The DSM is often referred to as the “Bible” of mental disorders, and is produced by the American Psychiatric Association (APA), a professional organization with a long history of industry ties. DSM-5, the revised edition scheduled for publication in May, 2013, has already been criticized for “disease mongering,” or pathologizing normal behavior. Concerns have been raised that because the individuals responsible for making changes and adding new disorders have strong and long-standing financial associations to pharmaceutical companies that manufacture the drugs used to treat these disorders, the revision process may be compromised by undue industry influence.
Researchers, clinicians, and psychiatrists who served on the DSM-IV have pointed out that adding new disorders or lowering the diagnostic threshold of previously included disorders may create “false positives,” individuals incorrectly identified as having a mental disorder and prescribed psychotropic medication. For example, there was a heated debate about pathologizing the normal grieving process if DSM-5 eliminated the bereavement exclusion for major depressive disorder (MDD). The concern was that widening the diagnostic boundaries of depression to include grief as a “qualifying event,” thereby allowing for a diagnosis of MDD just 2 weeks after the loss of a loved one, would falsely identify individuals as depressed. Although it is not the APA’s intent to play handmaiden to industry, the reality is that such a change would result in more people being prescribed antidepressants following the loss of a loved one. In fact, psychiatrist Allen Frances, who chaired the DSM-IV task force, has noted that DSM-5 would be a “bonanza” for drug companies.
After receiving criticism about potential bias in the development of the DSM-IV, the APA required that DSM-5 panel members file financial disclosures. Additionally, during their tenure on the panels they were not allowed to receive more than $10,000 from pharmaceutical companies or have more than $50,000 in stock holdings in pharmaceutical companies (unrestricted research grants were excluded from this policy). The majority of diagnostic panels, however, continue to have the majority of their members with financial ties to the pharmaceutical industry. Specifically, 67 percent of the 12-person panel for mood disorders, 83 percent of the 12-person panel for psychotic disorders, and all 7 members of the sleep/wake disorders panel (which now includes ‘‘Restless Leg Syndrome’’) have ties to the pharmaceutical companies that manufacture the medications used to treat these disorders or to companies that service the pharmaceutical industry.
Clearly, the new disclosure policy has not been accompanied by any reduction in the financial conflicts of interest of DSM panel members. Moreover, Darrel Regier, speaking on behalf of the APA and in defense of DSM panel members with industry ties, told USA Today. “There’s this assumption that a tie with a company is evidence of bias. But these people can be objective.” However, as science has repeatedly shown, transparency alone cannot mitigate bias and is an insufficient solution for protecting the integrity of the revision process. Objectivity is not a product that can be easily secured by adherence to the scientific method. Rather, there is a generic risk that a conflict of interest may result in implicit, unintentional bias. Similarly, as Sinclair Lewis said, “It is difficult to get a man to understand something when his salary depends upon his not understanding it.”
Source: TheScientist
7 August 2012
New NeuRA research shows that the brains of people with schizophrenia may attempt to repair damage caused by the disease, in another example of the adult brain’s capacity to change and grow.
Prof Cyndi Shannon Weickert, Dr Dipesh Joshi and colleagues from Neuroscience Research Australia studied the brains of people with schizophrenia and focussed on one of the hardest-hit regions, the orbitofrontal cortex, which is the part of the brain involved in regulating emotional and social behaviour.
Most neurons – brain cells that transmit information – are found in tissue near the surface of the brain. However, in the brains of people with schizophrenia, the team found a high density of neurons in deeper areas.
“For over a decade we’ve known about the high density of neurons in deeper brain tissue in people with schizophrenia. Researchers thought these neurons were simply forgotten by the brain, and somehow didn’t die off like they do during development in healthy people,” says Prof Shannon Weickert.
“What we now have is evidence that suggests these neurons are derived from the part of the brain that produces new neurons, and that they may be in the process of moving. We can’t be sure where they are moving to, but given their location it is likely they are on their way to the surface of the brain, the area most affected by schizophrenia,” Prof Shannon Weickert concluded.
How was this study done?
August 7, 2012
(HealthDay) — Using human stem cells, scientists have developed methods to boost the production of red blood cells, according to a new study.
Their discovery could significantly increase the blood supply needed for blood transfusions, the researchers said, and their methods can be used to produce any blood type.
"Being able to produce red blood cells from stem cells has the potential to overcome many difficulties of the current system, including sporadic shortages," Dr. Anthony Atala, editor of the journal Stem Cells Translational Medicine, in which the study appeared, said in a journal news release.
"This team has made a significant contribution to scientists’ quest to produce red blood cells in the lab," said Atala, who is also director of the Wake Forest Institute for Regenerative Medicine.
How does the new process work?
"We combined different cell-expansion protocols into a ‘cocktail’ that increased the number of cells we could produce by 10- to 100-fold," said researcher Eric Bouhassira, of the Albert Einstein College of Medicine in New York City.
Currently, the blood needed for life-saving transfusions is obtained only through donations. As a result, blood can be in short supply, particularly for those with rare blood types. The researchers produced a higher yield of red blood cells by using stem cells from cord blood and circulating blood as well as embryonic stem cells, according to the release.
"The ability of scientists to grow large quantities of red blood cells at an industrial scale could revolutionize the field of transfusion medicine," Bouhassira said. "Collecting blood through a donation-based system is serving us well but it is expensive, vulnerable to disruption and insufficient to meet the needs of some people who need ongoing transfusions. This could be a viable long-term alternative."
Source: medicalxpress.com
August 7, 2012
Investigators at Boston University School of Medicine (BUSM) and Veterans Affairs (VA) Boston Healthcare System have identified a new gene linked to post-traumatic stress disorder (PTSD). The findings, published online in Molecular Psychiatry, indicate that a gene known to play a role in protecting brain cells from the damaging effects of stress may also be involved in the development of PTSD.
The article reports the first positive results of a genome-wide association study (GWAS) of PTSD and suggests that variations in the retinoid-related orphan receptor alpha (RORA) gene are linked to the development of PTSD.
Mark W. Miller, PhD, associate professor at BUSM and a clinical research psychologist in the National Center for PTSD at VA Boston Healthcare System was the study’s principal investigator. Mark Logue, PhD, research assistant professor at BUSM and Boston University School of Public Health and Clinton Baldwin, PhD, professor at BUSM, were co-first authors of the paper.
PTSD is a psychiatric disorder defined by serious changes in cognitive, emotional, behavioral and psychological functioning that can occur in response to a psychologically traumatic event. Previous studies have estimated that approximately eight percent of the U.S. population will develop PTSD in their lifetime. That number is significantly greater among combat veterans where as many as one out of five suffer symptoms of the disorder.
Previous GWAS studies have linked the RORA gene to other psychiatric conditions, including attention-deficit hyperactivity disorder, bipolar disorder, autism and depression.
"Like PTSD, all of these conditions have been linked to alterations in brain functioning, so it is particularly interesting that one of the primary functions of RORA is to protect brain cells from the damaging effects of oxidative stress, hypoxia and inflammation," said Miller.
Participants in the study were approximately 500 male and female veterans and their intimate partners, all of whom had experienced trauma and approximately half of whom had PTSD. The majority of the veterans had been exposed to trauma related to their military experience whereas their intimate partners had experienced trauma related to other experiences, such as sexual or physical assault, serious accidents, or the sudden death of a loved one. Each participant was interviewed by a trained clinician, and DNA was extracted from samples of their blood.
The DNA analysis examined approximately 1.5 million genetic markers for signs of association with PTSD and revealed a highly significant association with a variant (rs8042149) in the RORA gene. The researchers then looked for evidence of replication using data from the Detroit Neighborhood Health Study where they also found a significant, though weaker, association between RORA and PTSD.
"These results suggest that individuals with the RORA risk variant are more likely to develop PTSD following trauma exposure and point to a new avenue for research on how the brain responds to trauma," said Miller.
Provided by Boston University Medical Center
Source: medicalxpress.com
August 06, 2012
To participate successfully in life, it is important to be able to read and write. Nevertheless, many children and adults have difficulties in acquiring these skills and the reason is not always obvious. They suffer from dyslexia which can have a variety of symptoms. Thanks to research carried out by Begoña Díaz and her colleagues at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, a major step forward has been made in understanding the cause of dyslexia. The scientists have discovered an important neural mechanism underlying dyslexia and shown that many difficulties associated with dyslexia can potentially be traced back to a malfunction of the medial geniculate body in the thalamus. The results provide an important basis for developing potential treatments.
This figure compares the situation in the brain of dyslexics and the control group. The blue area depicts the auditory cortices and the green area represents the medial geniculate bodies. © MPI for Human Cognitive and Brain Sciences
People who suffer from dyslexia have difficulties with identifying speech sounds in spoken language. For example, while most children are able to recognise whether two words rhyme even before they go to school, dyslexic children often cannot do this until late primary school age. Those affected suffer from dyslexia their whole lives. However, there are also always cases where people can compensate for their dyslexia. “This suggests that dyslexia can be treated. We are therefore trying to find the neural causes of this learning disability in order to create a basis for improved treatment options,” says Díaz.
Between five and ten percent of the world’s children suffer from dyslexia, yet very little is know about its causes. Even though those affected do not lack intelligence or schooling, they have difficulties in reading, understanding and explaining individual words or entire texts. The researchers showed that dyslexic adults have a malfunction in a structure that transfers auditory information from the ear to the cortex is a major cause of the impairment: the medial geniculate body in the auditory thalamus does not process speech sounds correctly. “This malfunction at a low level of language processing could percolate through the entire system. This explains why the symptoms of dyslexia are so varied,” says Díaz.
Under the direction of Katharina von Kriegstein, the researchers conducted two experiments in which several volunteers had to perform various speech comprehension tasks. When affected individuals performed tasks that required the recognition of speech sounds, as compared to recognize the voices that pronounced the same speech, magnetic resonance tomography (MRT) recordings showed abnormal responses in the area around the medial geniculate body. In contrast, no differences were apparent between controls and dyslexic participants if the tasks involved only listening to the speech sounds without having to perform a specific task. “The problem, therefore, has nothing to do with sensory processing itself, but with the processing involved in speech recognition,” says Díaz. No differences could be ascertained between the two test groups in other areas of the auditory signalling path.
The findings of the Leipzig scientists combine various theoretical approaches, which deal with the cause of dyslexia and, for the first time, bring together several of these theories to form an overall picture. “Recognising the cause of a problem is always the first step on the way to a successful treatment,” says Díaz. The researchers’ next project is now to study whether current treatment programmes can influence the medial geniculate body in order to make learning to read easier for everyone in the long term.
Source: Max Planck Institute
Advocates of free will can rest easy, for now. A 30-year-old classic experiment that is often used to argue against free will might have been misinterpreted.
Our decision-making process remains hazy (Image: Jannes Glas/Getty)
In the early 1980s, Benjamin Libet, a neuroscientist at the University of California in San Francisco, used electroencephalography (EEG) to record the brain activity of volunteers who had been told to make a spontaneous movement. With the help of a precise timer that the volunteers were asked to read at the moment they became aware of the urge to act, Libet found there was a 200 millisecond delay, on average, between this urge and the movement itself.
But the EEG recordings also revealed a signal that appeared in the brain even earlier, 550 milliseconds, on average, before the action. Called the readiness potential, this has been interpreted as a blow to free will, as it suggests that the brain prepares to act well before we are conscious of the urge to move.
This conclusion assumes that the readiness potential is the signature of the brain planning and preparing to move. “Even people who have been critical of Libet’s work, by and large, haven’t challenged that assumption,” says Aaron Schurger of the National Institute of Health and Medical Research in Saclay, France.
One attempt to do so came in 2009. Judy Trevena and Jeff Miller of the University of Otago in Dunedin, New Zealand, asked volunteers to decide, after hearing a tone, whether or not to tap on a keyboard. The readiness potential was present regardless of their decision, suggesting that it did not represent the brain preparing to move. Exactly what it did mean, though, still wasn’t clear.
Crossing a threshold
Now, Schurger and colleagues have an explanation. They began by posing a question: how does the brain decide to make a spontaneous movement? They looked to other decision-making scenarios for clues. Previous studies have shown that when we have to make a decision based on visual input, for example, assemblies of neurons start accumulating visual evidence in favour of the various possible outcomes. A decision is triggered when the evidence favouring one particular outcome becomes strong enough to tip its associated assembly of neurons across a threshold.
Schurger’s team hypothesised that something similar happens in the brain during the Libet experiment. Volunteers, however, are specifically asked to ignore any external signals before they make a spontaneous movement, so the signal must be internal.
There are random fluctuations of neural activity in the brain. Schurger’s team reasoned that movement is triggered when this neural noise accumulates and crosses a threshold.
To probe the idea, the team first built a computer model of such a neural accumulator. In the model, each time the neural noise crossed a threshold it signified a decision to move. They found that when they ran the model numerous times and looked at the pattern of the neural noise that led up to the decision it looked like a readiness potential.
Next, the team repeated Libet’s experiment, but this time if, while waiting to act spontaneously, the volunteers heard a click they had to act immediately. The researchers predicted that the fastest response to the click would be seen in those in whom the accumulation of neural noise had neared the threshold – something that would show up in their EEG as a readiness potential.
This is exactly what the team found. In those with slower responses to the click, the readiness potential was absent in the EEG recordings.
Spontaneous brain activity
"Libet argued that our brain has already decided to move well before we have a conscious intention to move," says Schurger. "We argue that what looks like a pre-conscious decision process may not in fact reflect a decision at all. It only looks that way because of the nature of spontaneous brain activity."
So what does this say about free will? “If we are correct, then the Libet experiment does not count as evidence against the possibility of conscious will,” says Schurger.
Cognitive neuroscientist Anil Seth of the University of Sussex in Brighton, UK, is impressed by the work, but also circumspect about what it says about free will. “It’s a more satisfying mechanistic explanation of the readiness potential. But it doesn’t bounce conscious free will suddenly back into the picture,” he says. “Showing that one aspect of the Libet experiment can be open to interpretation does not mean that all arguments against conscious free will need to be ejected.”
According to Seth, when the volunteers in Libet’s experiment said they felt an urge to act, that urge is an experience, similar to an experience of smell or taste. The new model is “opening the door towards a richer understanding of the neural basis of the conscious experience of volition”, he says.
Source: NewScientist
Release Date: 08/06/2012
Working with mice, Johns Hopkins researchers say they have figured out how stem cells found in a part of the brain responsible for learning, memory and mood regulation decide to remain dormant or create new brain cells. Apparently, the stem cells “listen in” on the chemical communication among nearby neurons to get an idea about what is stressing the system and when they need to act.
A single parvalbumin-expressing interneuron (red) surrounded by many adult neural stem cells (green) in the brain’s hippocampus. Credit: Gerry Sun
The researchers say understanding this process of chemical signaling may shed light on how the brain reacts to its environment and how current antidepressants work, because in animals these drugs have been shown to increase the number of brain cells. The findings are reported July 29 in the advance online publication of Nature.
“What we learned is that brain stem cells don’t communicate in the official way that neurons do, through synapses or by directly signaling each other,” says Hongjun Song, Ph.D., professor of neurology and director of Johns Hopkins Medicine’s Institute for Cell Engineering’s Stem Cell Program. “Synapses, like cell phones, allow nerve cells to talk with each other. Stem cells don’t have synapses, but our experiments show they indirectly hear the neurons talking to each other; it’s like listening to someone near you talking on a phone.”
The “indirect talk” that the stem cells detect is comprised of chemical messaging fueled by the output of neurotransmitters that leak from neuronal synapses, the structures at the ends of brain cells that facilitate communication. These neurotransmitters, released from one neuron and detected by a another one, trigger receiving neurons to change their electrical charges, which either causes the neuron to fire off an electrical pulse propagating communication or to settle down, squelching further messages.
To find out which neurotransmitter brain stem cells can detect, the researchers took mouse brain tissue, attached electrodes to the stem cells and measured any change in electrical charge after the addition of certain neurotransmitters. When they treated the stem cells with the neurotransmitter GABA – a known signal-inhibiting product the stem cells’ electrical charges changed, suggesting that the stem cells can detect GABA messages.
To find out what message GABA imparts to brain stem cells, the scientists used a genetic trick to remove the gene for the GABA receptor — the protein on the surface of the cell that detects GABA — only from the brain stem cells. Microscopic observation of brain stem cells lacking the GABA receptor over five days showed these cells replicated themselves, or produced glial cells — support cells for the neurons in the brain. Brain stem cells with their GABA receptors intact appeared to stay the same, not making more cells.
Next, the team treated normal mice with valium, often used as an anti-anxiety drug and known to act like GABA by activating GABA receptors when it comes in contact with them. The scientists checked the mice on the second and seventh day of valium use and counted the number of brain stem cells in untreated mice and mice treated with the GABA activator. They found the treated mice had many more dormant stem cells than the untreated mice.
“Traditionally GABA tells neurons to shut down and not continue to propagate a message to other neurons,” says Song. “In this case the neurotransmitter also shuts off the stem cells and keeps them dormant.”
The brain stem cell population in mice (and other mammals, including humans) is surrounded by as many as 10 different kinds of intermingled neurons, says Song, and any number of these may be keeping stem cells dormant. To find out which neurons control the stem cells, the researchers inserted special light-activating proteins into the neurons that trigger the cells to send an electrical pulse, as well as to release neurotransmitter, when light shines on them. By shining light to activate a specific type of neuron and monitoring the stem cells with an electrode, Song’s team showed that one of the three types of neurons tested transmitted a signal to the stem cells causing a change in electrical charge in the stem cells. The neurons messaging the stem cells are parvalbumin-expressing interneurons.
Finally, to see if this stem cell control mechanism aligns with what an animal may be experiencing, the scientists created stress for normal mice by socially isolating them, and did the same in mice lacking GABA receptors in their brain stem cells. After a week, socially isolated normal mice had an increase in the number of stem cells and glial cells. But the socially isolated mice without GABA receptors did not show increases.
“GABA communication clearly conveys information about what brain cells experience of the outside world, and, in this case, keeps the brain stem cells in reserve, so if we don’t need them, we don’t use them up,” says Song.
Source: Johns Hopkins Medicine
6-Aug-2012
Treatment with growth hormone-releasing hormone appears to be associated with favorable cognitive effects among both adults with mild cognitive impairment and healthy older adults, according to a randomized clinical trial published Online First by Archives of Neurology, a JAMA Network publication.
"Growth hormone-releasing hormone (GHRH), growth hormone and insulinlike growth factor 1 have potent effects on brain function, their levels decrease with advancing age, and they likely play a role in the pathogenesis of Alzheimer disease," the authors write as background information in the study.
To examine the effects of GHRH on cognitive function in healthy older adults and in adults with mild cognitive impairment (MCI), Laura D. Baker, Ph.D., of the University of Washington School of Medicine and Veterans Affairs Puget Sound Health Care System, Seattle, and colleagues, conducted a randomized, double-blind, placebo-controlled trial in which participants self-administered daily injections of a form of human GHRH (tesamorelin), or placebo.
The authors enrolled 152 adults ranging in age from 55 to 87 years (average age, 68 years) and 137 participants (76 healthy patients and 61 patients with MCI) successfully completed the study. At baseline, at 10 and 20 weeks of treatment, and after a 10-week washout (30 weeks total), the authors collected blood samples and administered parallel versions of cognitive tests.
Among the original 152 patients enrolled in the study, analysis indicated a favorable effect of GHRH on cognition, which was comparable in adults with MCI and healthy older adults. Analysis among the 137 patients who successfully completed the trial also showed that treatment with GHRH had a favorable effect on cognition among both groups of patients. Although the healthy adults outperformed those with MCI overall, the cognitive benefits relative to placebo was comparable among both groups.
Treatment with GHRH also increased insulin like growth factor 1 levels by 117 percent, which remained within the physiological range, and increased fasting insulin levels within the normal range by 35 percent in adults with MCI but not in healthy adults.
"Our results replicate and expand our earlier positive findings, demonstrating that GHRH administration has favorable effects on cognitive function not only in healthy older adults but also in adults at increased risk of cognitive decline and dementia," the authors conclude. "Larger and longer-duration treatment trials are needed to firmly establish the therapeutic potential of GHRH administration to promote brain health in normal aging and ‘pathological aging.’"
Source: EurekAlert!
August 3, 2012
Scientists have discovered a biological marker that may help to identify which depressed patients will respond to an experimental, rapid-acting antidepressant. The brain signal, detectable by noninvasive imaging, also holds clues to the agent’s underlying mechanism, which are vital for drug development, say National Institutes of Health researchers.
Dr. Zarate views subject in MEG scanner from scanner control room.
The signal is among the latest of several such markers, including factors detectable in blood, genetic markers, and a sleep-specific brain wave, recently uncovered by the NIH team and grantee collaborators. They illuminate the workings of the agent, called ketamine, and may hold promise for more personalized treatment.
"These clues help focus the search for the molecular targets of a future generation of medications that will lift depression within hours instead of weeks," explained Carlos Zarate, M.D., of the NIH’s National Institute of Mental Health (NIMH). "The more precisely we understand how this mechanism works, the more narrowly treatment can be targeted to achieve rapid antidepressant effects and avoid undesirable side effects."
Zarate, Brian Cornwell, Ph.D., and NIMH colleagues report on their brain imaging study online in the journal Biological Psychiatry.
Previous research had shown that ketamine can lift symptoms of depression within hours in many patients. But side effects hamper its use as a first-line medication. So researchers are studying its mechanism of action in hopes of developing a safer agent that works similarly.
Ketamine works through a different brain chemical system than conventional antidepressants. It initially blocks a protein on brain neurons, called the NMDA receptor, to which the chemical messenger glutamate binds. However, it is not known if the drug’s rapid antidepressant effects are a direct result of this blockage or of downstream effects triggered by the blockage, as suggested by animal studies.
To tease apart ketamine’s workings, the NIMH team imaged depressed patients’ brain electrical activity with magnetoencephalography (MEG). They monitored spontaneous activity while subjects were at rest, and activity evoked by gentle stimulation of a finger, before and 6.5 hours after an infusion of ketamine.
It was known that by blocking NMDA receptors, ketamine causes an increase in spontaneous electrical signals, or waves, in a particular frequency range in the brain’s cortex, or outer mantle. Hours after ketamine administration— in the timeframe in which ketamine relieves depression — spontaneous electrical activity in people at rest was the same whether or not the drug lifted their depression.
Electrical activity evoked by stimulating a finger, however, was different in the two groups. MEG imaging made it possible to monitor excitability of the somatosensory cortex, the part of the cortex that registers sensory stimulation. Those who responded to ketamine showed an increased response to the finger stimulation, a greater excitability of the neurons in this part of the cortex.
Such a change in excitability is likely to result, not from the immediate effects of blocking the receptor, but from other processes downstream, in the cascade of effects set in motion by NMDA blockade, say the researchers. Evidence points to changes in another type of glutamate receptor, the AMPA receptor, raising questions about whether the blocking of NMDA receptors is even necessary for ketamine’s antidepressant effect. If NMDA blockade is just a trigger, then targeting AMPA receptors may prove a more direct way to effect a lifting of depression.