Posts tagged neuroscience

ScienceDaily (July 16, 2012) — Post-traumatic stress disorder (PTSD) is more treatable than previously thought. A novel method has shown to be remarkably effective. The method, called Narrative Exposure Therapy (NET), is an intervention aimed at reducing symptoms of post-traumatic stress.

In an on-going Norwegian study, exposure therapy has been used with asylum seekers and refugees who have survived the ordeal of torture.

"According to previous studies, these patients do not benefit from traditional psychological therapy. In our study, however, 60 per cent show a marked improvement, and approximately 20 per cent show no symptoms of PTSD after treatment," says Håkon Stenmark, a PhD candidate at the Norwegian University of Science and Technology’s Department of Neuroscience, and has conducted the study in collaboration with colleague and fellow PhD candidate Joar Øverås Halvorsen.

Describing traumatic events

"Narrative" simply means telling a story. In exposure therapy the patient constructs a narration of his life while focusing on a detailed report of traumatic experiences. In a typical therapy session, the patient is given a rope to symbolize his or her life, from early childhood up to the present date.

The patient then describes the events in his life, good and bad, in chronological order. For every good memory the patient places a flower on the rope, and for every bad memory, a stone.

"I was blindfolded and seated in the prison’s interrogation room. I received multiple blows all over my body, and had no way of anticipating where I would be beaten next, the patient recalls with great difficulty."

The therapist is sitting at the opposite end of the table, listening attentively. Everything is written down, as it might prove useful later. The written account may be used in an application for asylum, or even as documentation for Amnesty International.

"Electrodes were fastened to my toes, and I was told I would be given electric shocks. The next thing I knew, a skinny man with a cigarette in his mouth turned the nob. The pain was excruciating, and my whole body tensed up."

"This is just one example. Although the patients are of different nationalities, and have been subjected to different kinds of torture, they share similar stories," Stenmark says.

Flashbacks and learning problems

Torture can result in a range of symptoms, depending on the method of torture as well as the duration of the ordeal. Nonetheless, symptoms typically fall into three main categories: ‘Reliving’ the event, avoidance and arousal. “A patients who is reliving torture may have flashbacks of the event, or episodes of repeated nightmares. Avoidance reactions are typically displayed as an extreme fear of the police or anybody who might resemble the abuser. People with these symptoms will try to isolate themselves and avoid people in general. Symptoms of arousal may result in difficulties concentrating, irritability, or having trouble falling or staying asleep,” Stenmark explains.

The classic symptom of PTSD is an inability to concentrate. As a consequence, sufferers often have learning difficulties and end up losing their jobs.

The brain’s “alarm system”

Existing trials are showing promising results with regards to exposure therapy. But why the method works in the first place, and the exact mechanisms behind it, have yet to be verified.

The most prominent theory is that exposure therapy changes the way fear is ‘wired’ in the memory. Simply stated, there is a part of the brain known as the brain’s ‘alarm system’, which enables us to respond to dangerous stimuli.

"During therapy the patient describes the traumatic event in a safe setting, while re-experiencing his or her emotions. In the process, the patient learns that the memories are not dangerous in themselves. The event was threatening when it occurred, but the memory the patient has today is not," Stenmark explains.

The goal of exposure therapy is to reduce the overall symptoms of PTSD, thereby increasing levels of functioning. Stenmark stresses that this is especially important for asylum seekers and refugees, as they often face additional challenges in Norwegian society.

Narrative exposure therapy was developed by trauma specialists working in refugee camps in Africa and Asia. To date, exposure therapy is not widely used in other parts of the world, which makes Øverås Halvorsen and Stenmark’s study the largest of its kind in the western world.

Source: Science Daily

ScienceDaily (July 16, 2012) — While Spider-Man is capturing the imagination of theatergoers, real-life spider men in Upstate New York are working intently to save a young boy’s life.

UB researchers are developing a treatment for muscular dystrophy using a peptide found in the venom of a Chilean rose tarantula. (Credit: Image courtesy of University at Buffalo)

It all began in 2009, when Jeff Harvey, a stockbroker from the Buffalo suburbs, discovered that his grandson, JB, had Duchenne muscular dystrophy. The disease is fatal. It strikes only boys, causing their muscles to waste away.

Hoping to help his grandson, Harvey searched Google for promising muscular dystrophy treatments and, in a moment of serendipity, stumbled upon University at Buffalo scientist Frederick Sachs, PhD.

Sachs was a professor of physiology and biophysics who had been studying the medical benefits of venom. In the venom of the Chilean rose tarantula, he and his colleagues discovered a protein that held promise for keeping muscular dystrophy at bay. Specifically, the protein helped stop muscle cells from deteriorating.

Within months of getting in touch, Harvey and Sachs co-founded Tonus Therapeutics, a pharmaceutical company devoted to developing the protein as a drug. Though the treatment has yet to be tested in humans, it has helped dystrophic mice gain strength in preliminary experiments.

The therapy is not a cure. But if it works in humans, it could extend the lives of children like JB for years — maybe even decades.

Success can’t come quickly enough.

JB, now four, can’t walk down the stairs alone. When he runs, he waddles. He receives physical therapy and takes steroids as a treatment. While playing tee ball one recent day, he confided to his grandfather, “When I grow up, I want to be a baseball player.” It was a heartbreaking moment.

"Oh, I would be thrilled if you could be a baseball player," Harvey remembers replying. He’s doing everything he can to make sure that JB — and other boys like him — can live out their dreams.

Source: Science Daily

July 16th, 2012

Spinal Muscular Atrophy affects one in 6,000 children and has no known cure.

A team of University of Missouri researchers has found that introducing a missing gene into the central nervous system could help extend the lives of patients with Spinal Muscular Atrophy (SMA) – the leading genetic cause of infantile death in the world.

SMA is a rare genetic disease that is inherited by one in 6,000 children who often die young because there is no cure. Children who inherit SMA are missing a gene that produces a protein which directs nerves in the spine to give commands to muscles.

The MU team, led by Christian Lorson, professor in the Department of Veterinary Pathobiology and the Department of Molecular Microbiology and Immunology, introduced the missing gene into mice born with SMA through two different methods: intravenously and directly into the mice’s central nervous systems. While both methods were effective in extending the lives of the mice, Lorson found that introducing the missing gene directly into the central nervous system extended the lives of the mice longer.

Mice born with spinal muscular atrophy typically only live five or six days. Researchers introduced the SMN gene into the mice’s central nervous systems and were able to extend their lives 10-25 days longer. The mice in the picture have spinal muscular atrophy.

“Typically, mice born with SMA only live five or six days, but by introducing the missing SMN gene into the mice’s central nervous systems, we were able to extend their lives 10-25 days longer than SMA mice who go untreated,” said Lorson, who works in the MU Bond Life Sciences Center and the College of Veterinary Medicine. “While this system is still not perfect, what our study did show is that the direct administration of the missing gene into the central nervous system provides some degree of rescue and a profound extension of survival.”

There are several different types of SMA that appear in humans, depending on the age that symptoms begin to appear. Lorson believes that introducing the missing gene through the central nervous system is a way to potentially treat humans regardless of what SMA type they have.

“This is a treatment method that is very close to being a reality for human patients,” Lorson said. “Clinical trials of SMA treatment using gene therapy are likely to begin in next 12-18 months, barring any unforeseen problems.”

Source: Neuroscience News

July 16, 2012

Can you teach an old dog (or human) new tricks? Yes, but it might take time, practice, and hard work before he or she gets it right, according to Hans Schroder and colleagues from Michigan State University in the US. Their work shows that when rules change, our attempts to control our actions are accompanied by a loss of attention to detail. Their work is published online in the Springer journal Cognitive, Affective, & Behavioral Neuroscience.

In order to adapt to changing conditions, humans need to be able to modify their behavior successfully. Overriding the rules we adhere to on a daily basis requires substantial attention and effort, and we do not always get it right the first time. When we switch between two or more tasks, we are slower and more likely to commit errors, which suggests switching tasks is a costly process. This may explain why it is so hard to learn from our mistakes when rules change.

The authors explain: “Switching the rules we use to perform a task makes us less aware of our mistakes. We therefore have a harder time learning from them. That’s because switching tasks is mentally taxing and costly, which leads us to pay less attention to the detail and therefore make more mistakes.”

A total of 67 undergraduates took part in the study. They were asked to wear a cap, which recorded electrical activity in the brain. They then performed a computer task that is easy to make mistakes on. Specifically, the participants were shown letter strings like “MMMMM” or “NNMNN” and were told to follow a simple rule: if ‘M’ is in the middle, press the left button; if ‘N’ is in the middle, press the right button. After they had followed this rule for almost 50 trials, they were instructed to perform the same task, but with the rules reversed i.e. now if ‘M’ is in the middle, press the right button; and if ‘N’ is in the middle, press the left button.

When the rules were reversed, participants made more consecutive errors. They were more likely to get it wrong twice in a row. This showed they were less apt to bounce back and learn from their mistakes. Reversing the rules also produced greater control-related and less error-awareness brain activity.

These results suggest that when rules are reversed, our brain works harder to juggle the two rules - the new rule and the old rule - and stay focused on the new rule. When we spend brain energy juggling these two rules, we have less brain power available for recognizing our mistakes.

Provided by Springer

Source: medicalxpress.com

ScienceDaily (July 16, 2012) — Far from processing every word we read or hear, our brains often do not even notice key words that can change the whole meaning of a sentence, according to new research from the Economic and Social Research Council (ESRC).

After a plane crash, where should the survivors be buried?

If you are considering where the most appropriate burial place should be, you are not alone. Scientists have found that around half the people asked this question, answer it as if they were being asked about the victims not the survivors.

Similarly, when asked “Can a man marry his widow’s sister?” most people answer “yes” — effectively answering that it would indeed be possible for a dead man to marry his bereaved wife’s sister.

What makes researchers particularly interested in people’s failure to notice words that actually don’t make sense, so called semantic illusions, is that these illusions challenge traditional models of language processing which assume that we build understanding of a sentence by deeply analysing the meaning of each word in turn.

Instead semantic illusions provide a strong line of evidence that the way we process language is often shallow and incomplete.

Professor Leuthold at University of Glasgow led a study using electroencephalography (EEG) to explore what is happening in our brains when we process sentences containing semantic illusions.

By analysing the patterns of brain activity when volunteers read or listened to sentences containing hard-to-detect semantic anomalies — words that fit the general context even though they do not actually make sense — the researchers found that when a volunteer was tricked by the semantic illusion, their brain had not even noticed the anomalous word.

Analyses of brain activity also revealed that we are more likely to use this type of shallow processing under conditions of higher cognitive load — that is, when the task we are faced with is more difficult or when we are dealing with more than one task at a time.

The research findings not only provide a better understanding of the processes involved in language comprehension but, according to Professor Leuthold, knowing what is happening in the brain when mistakes occur can help us to avoid the pitfalls,such as missing critical information in textbooks or legal documents, and communicate more effectively.

There are a number of tricks we can use to make sure we get the correct message across: “We know that we process a word more deeply if it is emphasised in some way. So, for example in a news story, a newsreader can stress important words that may otherwise be missed and these words can be italicised to make sure we notice them when reading,” said Professor Leuthold.

The way we construct sentences can also help reduce misunderstandings, he explained: “It’s a good idea to put important information first because we are more likely to miss unusual words when they are near the end of a sentence. Also, we often use an active sentence construction such as ‘Bob ate the apple’ because we make far more mistakes answering questions about a sentence with a passive construction — for example ‘The apple was eaten by Bob’.”

The study findings also suggest that we should avoid multi-tasking when we are reading or listening to an important message: “For example, talking to someone on the phone while driving on a busy motorway or in town, or doing some homework while listening to the newsmight lead to more shallow processing,” said Professor Leuthold.

Source: Science Daily

July 16, 2012

A nationwide consortium of scientists at 20 institutions, led by a principal faculty member at the Harvard Stem Cell Institute (HSCI), has used stem cells to take a major step toward developing personalized medicine to treat Parkinson’s disease.

This study points the way to screening patients with Parkinson’s for their particular variation of the disease, and then treating them with drugs shown effective to work on that variation, rather than trying to treat all patients with the same drugs, as is generally done now, notes Ole Isacson, a leader of the study. Credit: B. D. Colen/Harvard Staff

In part supported by the Harvard Miller Consortium for the Development of Nervous System Therapies, the team of scientists created induced pluripotent stem cells (iPS cells) from the skin cells of patients and at-risk individuals carrying genetic mutations implicated in Parkinson’s disease, and used those cells to derive neural cells, providing a platform for studying the disease in human cells outside of patients.

In a paper published in the journal Science Translational Medicine, the researchers report that although approximately 15 genetic mutations are linked to forms of Parkinson’s, many seem to affect the mitochondria, the cell unit that produces most of its energy.

“This is the first comprehensive study of how human neuronal cells can be models of Parkinson’s, and how it might be treated,” said Ole Isacson, a leader of the study, an HSCI principal faculty member, and a Harvard Medical School professor of neurology, based at McLean Hospital’s Neuroregeneration Laboratory.

The researchers determined that certain compounds or drugs could reverse some signs of disease in the cultured cells with specific genetic mutations, and not in cells with other types of mutations, making real the concept of developing drugs that would be prescribed to patients or individuals at risk for Parkinson’s.

The study was launched with federal stimulus funding provided by the National Institutes of Health (NIH) and was continued with funding from HSCI.

“These findings suggest new opportunities for clinical trials of Parkinson’s disease, wherein cell reprogramming technology could be used to identify the patients most likely to respond to a particular intervention,” said Margaret Sutherland, a program director at NIH’s National Institute of Neurological Disorders and Stroke, in a press release.

The new research indicates that compounds that previously have shown promise in treating Parkinson’s in animal studies, including the antioxidant coenzyme Q10, together with the immunosuppressant rapamycin, have differing levels of effectiveness on various genetic forms of Parkinson’s.

Researchers hope that such findings can provide the basis for more specific drugs for individuals with sporadic forms of Parkinson’s.

As Isacson explained in an interview, this study points the way to screening patients with Parkinson’s for their particular variation of the disease, and then treating them with drugs shown effective to work on that variation, rather than trying to treat all patients with the same drugs, as is generally done now.

“We believe that using human stem cells to study the disease is the correct way to go,” Isacson said. “We have the cell type most vulnerable to the disease in a dish. We can study the most vulnerable cells and compare them to the least vulnerable cells. Traditionally, in neurology,” he said, “all patients with the same disease get the same drugs. But they may have the disease for different reasons. This gives us a way to tease out those different reasons, and find different ways to treat them.”

Provided by Harvard University

Source: medicalxpress.com

July 16, 2012

For more than 20 years, doctors have been using cells from blood that remains in the placenta and umbilical cord after childbirth to treat a variety of illnesses, from cancer and immune disorders to blood and metabolic diseases.

This microscope image shows a colony of neurons derived from cord-blood cells using stem cell reprogramming technology. The green and red glow indicates that the cells are producing protein makers found in neurons, evidence that the cord-blood cells did in fact morph into neurons. The blue glow marks the nuclei of the neurons. Credit: Image: Courtesy of Alessandra Giorgetti

Now, scientists at the Salk Institute for Biological Studies have found a new way-using a single protein, known as a transcription factor-to convert cord blood (CB) cells into neuron-like cells that may prove valuable for the treatment of a wide range of neurological conditions, including stroke, traumatic brain injury and spinal cord injury.

The researchers demonstrated that these CB cells, which come from the mesoderm, the middle layer of embryonic germ cells, can be switched to ectodermal cells, outer layer cells from which brain, spinal and nerve cells arise. “This study shows for the first time the direct conversion of a pure population of human cord blood cells into cells of neuronal lineage by the forced expression of a single transcription factor,” says Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory, who led the research team. The study, a collaboration with Fred H. Gage, a professor in Salk’s Laboratory of Genetics, and his team, was published on July 16 in the Proceedings of the National Academy of Sciences.

"Unlike previous studies, where multiple transcription factors were necessary to convert skin cells into neurons, our method requires only one transcription factor to convert CB cells into functional neurons," says Gage.

The Salk researchers used a retrovirus to introduce Sox2, a transcription factor that acts as a switch in neuronal development, into CB cells. After culturing them in the laboratory, they discovered colonies of cells expressing neuronal markers. Using a variety of tests, they determined that the new cells, called induced neuronal-like cells (iNC), could transmit electrical impulses, signaling that the cells were mature and functional neurons. Additionally, they transferred the Sox2-infused CB cells to a mouse brain and found that they integrated into the existing mouse neuronal network and were capable of transmitting electrical signals like mature functional neurons.

"We also show that the CB-derived neuronal cells can be expanded under certain conditions and still retain the ability to differentiate into more mature neurons both in the lab and in a mouse brain," says Mo Li, a scientist in Belmonte’s lab and a co-first author on the paper with Alessandra Giorgetti, of the Center for Regenerative Medicine, in Barcelona, and Carol Marchetto of Gage’s lab. "Although the cells we developed were not for a specific lineage-for example, motor neurons or mid-brain neurons-we hope to generate clinically relevant neuronal subtypes in the future."

Importantly, says Marchetto, “We could use these cells in the future for modeling neurological diseases such as autism, schizophrenia, Parkinson’s or Alzheimer’s disease.”

Cord blood cells, says Giorgetti, offer a number of advantages over other types of stem cells. First, they are not embryonic stem cells and thus they are not controversial. They are more plastic, or flexible, than adult stem cells from sources like bone marrow, which may make them easier to convert into specific cell lineages. The collection of CB cells is safe and painless and poses no risk to the donor, and they can be stored in blood banks for later use.

"If our protocol is developed into a clinical application, it could aid in future cell-replacement therapies," says Li. "You could search all the cord blood banks in the country to look for a suitable match."

Provided by Salk Institute

Source: medicalxpress.com

ScienceDaily (July 16, 2012) — A team of scientists at The New York Stem Cell Foundation (NYSCF) Laboratory led by Scott Noggle, PhD, NYSCF-Charles Evans Senior Research Fellow for Alzheimer’s Disease, has developed the first cell-based model of Alzheimer’s disease (AD) by reprogramming skin cells of Alzheimer’s patients to become brain cells that are affected in Alzheimer’s. This will allow researchers to work directly on living brain cells suffering from Alzheimer’s, which until now had not been possible. Andrew Sproul, PhD, a postdoctoral associate in Dr. Noggle’s laboratory, will present this work on July 19 at the Alzheimer’s Association International Conference (AAIC) held in Vancouver.

Dr. Noggle and his team reprogrammed skin cell samples taken from twelve patients diagnosed with early-onset Alzheimer’s and from healthy, genetically related individuals into induced pluripotent stem (iPS) cells, which can differentiate into any cell type. The team of scientists used these iPS cells to create cholinergic basal forebrain neurons, the brain cells that are affected in Alzheimer’s. These cells recapitulate the features and cellular-level functions of patients suffering from Alzheimer’s, a devastating disease that affects millions of people globally but for which there is currently no effective treatment.

NYSCF has pioneered the creation of disease models based on the derivation of human cells. Four years ago, a NYSCF-funded team created a cell-based model for ALS, or motor neuron disease, the first patient-specific stem cells created for any disease. The cell-based model for Alzheimer’s builds on this earlier work.

"Patient derived AD cells will prove invaluable for future research advances, as they already have with patient-derived ALS cells," said NYSCF CEO Susan Solomon. "They will be a critical tool in the drug discovery process, as potential drugs could be tested directly on these cells. Although research on animals has provided valuable insight into AD, we aren’t mice, and animals don’t properly reflect the features of the disease we are trying to cure. As we work to find new drugs and treatments our research should focus on actual human sufferers of Alzheimer’s disease," emphasized Ms. Solomon

This cell-based model has already led to important findings. Preliminary results of this NYSCF research, done in collaboration with Sam Gandy, MD, PhD, an international expert in the pathology of Alzheimer’s at Mount Sinai School of Medicine, demonstrated differences in cellular function in Alzheimer’s patients. Specifically, Alzheimer’s neurons produce more of the toxic form of beta amyloid, the protein fragment that makes up amyloid plaques, than in disease-free neurons.

"iPS cell technology, along with whole genome sequencing, provide our best chance at unravelling the causes of common forms of Alzheimer’s disease," noted Dr. Gandy.

"This collaboration is a great example of how NYSCF is bringing together experts in stem cell technology and clinicians to save and enhance lives by finding better treatments," Ms. Solomon explained.

The research to be reported at the AAIC by Andrew Sproul focused on stem cell models of individuals with presenilin-1 (PSEN1) mutations, a genetic cause of AD. As Dr. Sproul has said, this cell-based model could “revolutionize how we discover drugs to potentially cure Alzheimer’s disease.”

Source: Science Daily

July 16, 2012

Activity lingers longer in certain areas of the brain in those with Alzheimer’s than it does in healthy people, Mayo Clinic researchers who created a map of the brain found. The results suggest varying brain activity may reduce the risk of Alzheimer’s disease. The study, “Non-stationarity in the “Resting Brain’s” Modular Architecture,” was presented at the Alzheimer’s Association International Conference and recently published in the journal PLoS One.

Researchers compared brain activity to a complex network, with multiple objects sharing information along pathways.

"Our understanding of those objects and pathways is limited," says lead author David T. Jones, M.D. "There are regions in the brain that correspond to those objects, and we are not really clear exactly what those are. We need a good mapping or atlas of those regions that make up the network in the brain, which is part of what we were doing in this study."

Researchers examined 892 cognitively normal people taking part in the Mayo Clinic Study of Aging, and set out to create an active map of their brains while the people were “at rest,” not engaged in a specific task. To do this, they employed task-free, functional magnetic resonance imaging to construct an atlas of 68 functional regions of the brain, which correspond to the cities on the road map.

Researchers filled in the roads between these regions by creating dynamic graphic representations of brain connectivity within a sliding time window.

This analysis revealed that there were many roads that could be used to exchange information in the brain, and the brain uses different roads at different times. The question to answer then, said Dr. Jones, is whether or not Alzheimer’s patients used this map and these roads in a different way than their healthy peers.

"What we found in this study was that Alzheimer’s patients tended to spend more time using some roads and less time using other roads, biasing one over the other," he says.

While more research is needed, the researchers say one implication is that how we use our brains may protect us from Alzheimer’s. Dr. Jones says exercise, education, and social contacts may help balance activity in the brain.

"Diversifying the mental space that you explore may actually decrease your risk for Alzheimer’s," he says.

Provided by Mayo Clinic

Source: medicalxpress.com

July 16, 2012

One of the marvels of brain development is the mass migration of nerve cells to their functional position. European research has investigated the molecules required for their successful navigation.

Credit: Thinkstock

Formation of the cerebral cortex during embryonic development requires the migration of billions of cells from their birth position to their final destination. A motile nerve cell must have internal polarity to move in the specified direction. What is more, neurons then have to extend neurites or projections from the cell body to communicate with each other.

The key to this extraordinary feat of organisation lies in cell signalling pathways. The EU-funded Neuronal Polarity project aimed to characterise these cascades important in cerebral cortex development. At a later stage, defective cortical architecture can be responsible for brain pathologies including microcephaly, epilepsy and schizophrenia.

Project scientists showed that in vivo the guanine triphosphatase GTPase Ras-proximate-1 (Rap 1) caused an accumulation of neurons halfway to their destination. The team used time-lapse video microscopy and immunostaining to show that the problem does not lie with motility of the neurons but in a defect in their polarity. Other evidence from motility tests in vitro and the fact that some neurons do actually make it to their destination, albeit slowly, suggest Rap 1 is important for initial polarisation of the neurons.

The transmembrane receptor N-cadherin (Ncad) also has an important function in polarising cortical neurons. Experimental data confirmed that this receptor is involved downstream from Rap 1. Overall, inhibition of Rap 1 reduces Ncad presence.

Neuronal Polarity scientists suggest that Rap 1 activity is important in migrating neurons to maintain a high level of Ncad at the plasma membrane for nerve cells to polarise correctly.

Exactly how Ncad interacts with molecular cascades for neuron polarisation is still under investigation. The Neuronal Polarity project accumulated data on which to base a concrete research path for future investigation.

Provided by CORDIS

Source: medicalxpress.com