Neuroscience
Month
ScienceDaily (Aug. 22, 2012) — A low dose of the sedative clonazepam alleviated autistic-like behavior in mice with a mutation that causes Dravet syndrome in humans, University of Washington researchers have shown.
(Credit: © Vasiliy Koval / Fotolia)
Dravet syndrome is an infant seizure disorder accompanied by developmental delays and behavioral symptoms that include autistic features. It usually originates spontaneously from a gene mutation in an affected child not found in either parent.
Studies of mice with a similar gene mutation are revealing the overly excited brain circuits behind the autistic traits and cognitive impairments common in this condition. The research report appears in the Aug. 23 issue of Nature. Dr William Catterall, professor and chair of pharmacology at the UW, is the senior author.
Dravet syndrome mutations cause loss-of-function of the human gene called SCN1A. People or mice with two copies of the mutation do not survive infancy; one copy results in major disability and sometimes early death. The mutation causes malformation in one type of sodium ion channels, the tiny pores in nerve cells that produce electrical signals by gating the flow of sodium ions.
The Catteralll lab is studying these defective ion channels and their repercussion on cell-to-cell signaling in the brain. They also are documenting the behavior of mice with this mutation, compared to their unaffected peers. Their findings may help explain how the sporadic gene mutations that cause Dravet syndrome lead to its symptoms of cognitive deficit and autistic behaviors.
Scientists at Georgia State University have found that the ability to hear is lessened when, as a result of injury, a region of the brain responsible for processing sounds receives both visual and auditory inputs.
Yu-Ting Mao, a former graduate student under Sarah L. Pallas, professor of neuroscience, explored how the brain’s ability to change, or neuroplasticity, affected the brain’s ability to process sounds when both visual and auditory information is sent to the auditory thalamus.
The study was published in the Journal of Neuroscience.
The auditory thalamus is the region of the brain responsible for carrying sound information to the auditory cortex, where sound is processed in detail.
When a person or animal loses input from one of the senses, such as hearing, the region of the brain that processes that information does not become inactive, but instead gets rewired with input from other sensory systems.
In the case of this study, early brain injury resulted in visual inputs into the auditory thalamus, which altered how the auditory cortex processes sounds.
The cortical “map” for discriminating different sound frequencies was significantly disrupted, she explained.
“One of the possible reasons the sound frequency map is so disrupted is that visual responsive neurons are sprinkled here and there, and we also have a lot of single neurons that respond to both light and sound,” Pallas said. “So those strange neurons sprinkled there probably keeps the map from forming properly.”
Mao also discovered reduced sensitivity and slower responses of neurons in the auditory cortex to sound.
Finally, the neurons in the auditory cortex were less sharply tuned to different frequencies of sound.
“Generally, individual neurons will be pretty sensitive to one sound frequency that we call their ‘best frequency,’” Pallas said. “We found that they would respond to a broader range of frequencies after the rewiring with visual inputs.”
While Pallas’ research seeks to create a basic understanding of brain development, knowledge gained from her lab’s studies may help to give persons who are deaf, blind, or have suffered brain injuries ways to keep visual and auditory functions from being compromised.
“Usually we think of plasticity as a good thing, but in this case, it’s a bad thing,” she said. “We would like to limit the plasticity so that we can keep the function that’s supposed to be there.”
Source: Georgia State University
22 August 2012 by Jim Giles
More than a year after it won the quiz show Jeopardy!, IBM’s supercomputer is learning how to help doctors diagnose patients
IT IS more than a year since Watson, IBM’s famous supercomputer, opened a new frontier for artificial intelligence by beating human champions of the quiz show Jeopardy!. Now Watson is learning to use its language skills to help doctors diagnose patients.
Progress is most advanced in cancer care, where IBM is working with several US hospitals to build a virtual physicians’ assistant. “It’s a machine that can read everything and forget nothing,” says Larry Norton, a doctor at the Memorial Sloan-Kettering Cancer Center in New York, who is collaborating with IBM.
When playing Jeopardy!, Watson analysed each question in a bid to guess what it was about. Then it looked for possible answers in its database, made up of sources such as encyclopaedias, scoring each according to the evidence associated with it and answering with the highest rated answer. The system takes a similar approach when dealing with medical questions, although in this case it draws on information from medical journals and clinical guidelines.
To test the system, Watson was first tasked with answering questions taken from Doctor’s Dilemma, a competition for trainee doctors that takes place at the annual meeting of the American College of Physicians. Watson was given 188 questions that it had not seen before and achieved around 50 per cent accuracy - not bad for an early test, but hardly ideal (Artificial Intelligence, doi.org/h6m).
To improve, Watson is now absorbing records - tens of thousands at Sloan-Kettering alone - of treatments and outcomes associated with individual patients. Given data on a new patient, Watson looks for information on those with similar symptoms, as well as the treatments that have been the most successful. The idea is it will give doctors a range of possible diagnoses and treatment options, each with an associated level of confidence. The result will be a system that its creators say can suggest nuanced treatment plans that take into account factors like drug interactions and a patient’s medical history.
William Audeh, a doctor at Cedars-Sinai Medical Center in Los Angeles, who is working with IBM, says the last few months have involved “filling Watson’s brain” with medical data. Watson is answering basic questions based on the treatment guidelines that are published by medical societies and is showing “very positive” results, he adds.
The technology is particularly useful in oncology because doctors struggle to keep up with the explosion of genomic and molecular data generated about each cancer type. This means it can take years for findings to translate into medical practice. By contrast, Watson can absorb new results and relay them to doctors quickly, together with an estimate of their potential usefulness. “Watson really has great potential,” says Audeh. “Cancer needs it most because it’s becoming so complicated so quickly.”
The IBM system could also approve treatment requests more quickly. At WellPoint, one of the largest insurers in the US, nurses use guidelines and patient history to determine if a request is in line with company policy. Nurses are now training Watson by feeding it test requests and observing the answers. Progress is good and the system could be deployed next year, says WellPoint’s Cindy Wakefield. “Now it can take up to a couple of days,” she says. “We hope Watson can return the accurate recommendation in a matter of minutes.”
Source: NewScientist
August 21, 2012 by Kathleen Raven
Stem cell treatment could lower inflammation levels and demonstrate whether autism is an autoimmune disease
Image: Nature News
Families with autistic children must navigate a condition where questions outnumber the answers, and therapies remain sparse and largely ineffective. A clinical trial being conducted by the Sutter Neuroscience Institute in Sacramento, California to address this situation began recruiting participants today for a highly experimental stem cell therapy for autism. The institute plans to find 30 autistic children between ages 2 and 7 with cord blood banked at the privately-run Cord Blood Registry, located about 100 miles west of the institute. Already one other clinical trial, with 37 total participants between ages 3 and 12 years old, has been completed in China. The researchers affiliated with Beike Biotechnology in Shenzhen, the firm that sponsored the study, have not yet published any papers from that the trial, which used stem cells from donated cord blood. Mexican researchers are currently recruiting kids for yet another type of autism stem cell trial that will harvest cells from the participant’s fat tissue.
But for each of these officially registered trials, many more undocumented stem cell therapy treatments take place for clients who are willing to pay enough. “Our research is important because many people are going to foreign countries and spending a lot of money on therapy that may not be valid,” says Michael Chez, a pediatric neurologist and lead investigator of the study at Sutter.
A major difference between the Sutter trial and those in China is that his will use the child’s own stem cells, rather than those from a donor. Chez hypothesizes that one way autologous stem cell infusion might work is by reducing inflammation within the body’s immune system. This would answer previous research that suggests that autism may be an autoimmune disease. “One of our exploratory goals will be to look at inflammatory markers in cells,” he says.
The study’s primary goal, however, will be assessing changes in patients’ speaking and understanding of vocabulary. For each individual, researchers will create a baseline benchmark that establishes current skill levels. The group will be evenly divided, with one initially receiving an infusion of their own, unmodified cord blood stem cells and the other a placebo treatment of saline injection. Six months later, all of the children will be tested on their ability to comprehend and form words. The groups will then be switched. In the course of the 13-month-long study, both groups will receive only one stem cell therapy infusion.
Not all stem cell scientists who study neurodevelopmental diseases are ready to invest great hope that the autism stem cell trial will succeed. “I wish I could tell you I’m optimistic about the end results,” says James Carroll, a pediatric neurologist at the Georgia Health Sciences University in Augusta who began a clinical trial two years ago to better understand how stem cell therapy affects patients with cerebral palsy. “But so far we have not seen any kind of miraculous recovery in our cerebral palsy patients. I would be delighted if that changes.”
Members in the stem cell therapy patient community think Chez will have no shortage of volunteers for the trial. Jeremy Lowey, who lives in Sacramento and has struggled with a rare condition known as non-verbal learning disorder, arranged for his own stem cell therapy treatment in India last year, which he called life-changing. He receives numerous Facebook requests from parents of autistic children who are curious to know more. He always begins his conversations by saying, “Go slowly and think hard about your decision.”
Source: Scientific American
ScienceDaily (Aug. 21, 2012) — Together with his team, Prof. Christoph Ploner, director of the Department of Neurology at the Virchow campus, examined a professional cellist who suffered from encephalitis caused by a herpes virus. As a result of the inflammation, the patient developed serious disturbances in memory.
Both his memory for the past (retrograde amnesia), as well as the acquisition of new information (anterograde amnesia) were affected. Whereas the patient was unable to recount any events from his private or professional life, or remember any of his friends or relatives, he retained a completely intact musical memory. Furthermore, he was still able to sight-read and play the cello.
For the systematic examination of his musical memory, Dr. Carsten Finke, Nazli Esfahani and Prof. Christoph Ploner developed various tests that take the beginning of his amnesia into account. In comparison to amateur musicians and professional musicians from the Berlin Philharmonic, the patient showed a normal musical memory in all tests. He not only remembered music pieces from the past, but was also able to retain music he had never heard before.
"The findings show that musical memory is organized at least partially independent of the hippocampus, a brain structure that is central to memory formation," says Carsten Finke, the primary author of the study. "It is possible that the enormous significance of music throughout all times and in all cultures contributed to the development of an independent memory for music."
Carsten Finke and his colleagues hope that the intact musical memory in patients with amnesia can be used to stimulate other memory content. In this way, perhaps a particular melody can be connected to a person or an everyday task, for example taking medicine.
Source: Science Daily
ScienceDaily (Aug. 21, 2012) — New magnetic resonance imaging (MRI) research shows that changes in brain blood flow associated with vein abnormalities are not specific for multiple sclerosis (MS) and do not contribute to its severity, despite what some researchers have speculated. Results of the research are published online in the journal Radiology.
"MRI allowed an accurate evaluation of cerebral blood flow that was crucial for our results," said Simone Marziali, M.D., from the Department of Diagnostic Imaging at the University of Rome Tor Vergata in Rome.
MS is a disease of the central nervous system in which the body’s immune system attacks the nerves. There are different types of MS, and symptoms and severity vary widely. Recent reports suggest a highly significant association between MS and chronic cerebrospinal venous insufficiency (CCSVI), a condition characterized by compromised blood flow in the veins that drain blood from the brain. This strong correlation has generated substantial attention from the scientific community and the media in recent years, raising the possibility that MS can be treated with endovascular procedures like stent placement. However, the role of brain blood flow alterations on MS patients is still unclear.
To investigate this further, Italian researchers compared brain blood flow in 39 MS patients and 26 healthy control participants. Twenty-five of the MS patients and 14 of the healthy controls were positive for CCSVI, based on Color-Doppler-Ultrasound (CDU) findings. The researchers used dynamic susceptibility contrast-enhanced (DSC) MRI to assess blood flow in the brains of the study groups. DSC MR imaging offers more accurate assessment of brain blood flow than that of CDU. MRI and CDU were used to assess two different anatomical structures.
While CCSVI-positive patients showed decreased cerebral blood flow and volume compared with their CCSVI-negative counterparts, there was no significant interaction between MS and CCSVI for any of the blood flow parameters. Furthermore, the researchers did not find any correlation between the cerebral blood flow and volume in the brain’s white matter and the severity of disability in MS patients.
The results suggest that CCSVI is not a pathological condition correlated with MS, according to Dr. Marziali, but probably just an epiphenomenon — an accessory process occurring in the course of a disease that is not necessarily related to the disease. This determination is important because, to date, studies of the prevalence of CCSVI in MS patients have provided inconclusive results.
"This study clearly demonstrates the important role of MRI in defining and understanding the causes of MS," Dr. Marziali said. "I believe that, in the future, it will be necessary to use powerful and advanced diagnostic tools to obtain a better understanding of this and other diseases still under study."
Source: Science Daily
Does some fine madness yield great artists, writers, and scientists? The evidence is growing for a significant link between bipolar disorder and creative temperament and achievement.
People with bipolar disorder swing repeatedly from depression to euphoria and hyperactivity, or intensely irritable mood states. Sometimes likened to being on an emotional rollercoaster, each swing up then down affects one’s behaviour, energy levels, thought patterns and sleep.
Also known as manic-depressive illness, bipolar disorder is strongly genetically linked, passing down through each generation of an affected family. It is fairly common and very treatable with modern medicines and psychotherapy.
21 August 2012 by Lois Rogers
Thousands of otherwise healthy people put up with a level of sleep deprivation that would drive the rest of us insane. But they are not the usual candidates for insomnia, such as shift workers or those with severe mental illness. Instead, they belong to a newly identified group of people born without the ‘comfort’ genes needed for easy sleep.
This means they are immune to the feeling of warmth and relaxation which sends an average person off to sleep within 15 minutes. Their genes are designed instead to maintain a state of mental alertness. This makes normal, prolonged sleep impossible so they sleep fitfully, in only short bursts. Even then, their lack of ‘comfort’ genes may mean they struggle to get comfortable, fussing about the bedding or finding their sleeping position.
There are other so-called insomnia genes — some cause repeated periods of wakefulness in the small hours of the night or at the slightest disturbance, or drive an affected person to leap out of bed raring to start the day at 4am, but leave them exhausted by 4pm. Until recently, insomnia was considered a purely psychological complaint triggered by stress, grief, or sleep disruption as a result of shift work or jet lag.
But doctors are now unravelling the genetic explanation of why at least one-third of us have intermittent or constant sleep problems. Even so, it’s already thought there could be six or more different types of insomnia linked to genes. This means it will be possible to develop drugs to block the effect of the chemical signals they produce.
ScienceDaily (Aug. 21, 2012) — Working with units of material so small that it would take 50,000 to make up one drop, scientists are developing the profiles of the contents of individual brain cells in a search for the root causes of chronic pain, memory loss and other maladies that affect millions of people.
They described the latest results of this one-by-one exploration of cells or “neurons” from among the millions present in an animal brain at the 244th National Meeting & Exposition of the American Chemical Society (ACS), the world’s largest scientific society. The meeting, expected to attract almost 14,000 scientists and others from around the world, continues in Philadelphia through Thursday, with 8,600 presentations on new discoveries in science and other topics.
Jonathan Sweedler, Ph.D., a pioneer in the field, explained in a talk at the meeting that knowledge of the chemistry occurring in individual brain cells would provide the deepest possible insights into the causes of certain diseases and could point toward new ways of diagnosis and treatment. Until recently, however, scientists have not had the technology to perform such neuron-by-neuron research.
"Most of our current knowledge about the brain comes from studies in which scientists have been forced to analyze the contents of multiple nerve cells, and, in effect, average the results," Sweedler said. He is with the University of Illinois at Urbana-Champaign and also serves as editor-in-chief of Analytical Chemistry, which is among ACS’ more than 40 peer-reviewed scientific journals. “That approach masks the sometimes-dramatic differences that can exist even between nerve cells that are shoulder-to-shoulder together. Suppose that only a few cells in that population are changing, perhaps as a disease begins to take root or starts to progress or a memory forms and solidifies. Then we would miss those critical changes by averaging the data.”
However, scientists have found it difficult to analyze the minute amounts of material inside single brain cells. Those amounts are in the so-called “nanoliter” range, units so small that it would take 355 billion nanoliters to fill a 12-ounce soft-drink can. Sweedler’s group spent much of the past decade developing the technology to analyze the chemicals found in individual cells — a huge feat with a potentially big pay-off. “We are using our new approaches to understand what happens in learning and memory in the healthy brain, and we want to better understand how long-lasting, chronic pain develops,” he said.
The 85 billion neurons in the brain are highly interconnected, forming an intricate communications network that makes the complexity of the Internet pale in comparison. The neural net’s chemical signaling agents and electrical currents orchestrate a person’s personality, thoughts, consciousness and memories. These connections are different from person to person and change over the course of a lifetime, depending on one’s experiences. Even now, no one fully understands how these processes happen.
To get a handle on these complex workings, Sweedler’s team and others have zeroed in on small sections of the central nervous system ― the brain and spinal cord ― using stand-ins for humans such as sea slugs and laboratory rats. Sweedler’s new methods enable scientists to actually select areas of the nervous system, spread out the individual neurons onto a glass surface, and one-by-one analyze the proteins and other substances inside each cell.
One major goal is to see how the chemical make-up of nerve cells changes during pain and other disorders. Pain from disease or injuries, for instance, is a huge global challenge, responsible for 40 million medical appointments annually in the United States alone.
Sweedler reported that some of the results are surprising, including tests on cells in an area of the nervous system involved in the sensation of pain. Analysis of the minute amounts of material inside the cells showed that the vast majority of cells undergo no detectable change after a painful event. The chemical imprint of pain occurs in only a few cells. Finding out why could point scientists toward ways of blocking those changes and in doing so, could lead to better ways of treating pain.
Source: Science Daily
Controlling the amount of oxygen that stem cells are exposed to can significantly increase the effectiveness of a procedure meant to combat an often fatal form of muscular dystrophy, according to Purdue University research.
A genetic mutation in patients with Duchenne muscular dystrophy causes the constant breakdown of muscles and gradual depletion of stem cells that are responsible for repairing the damage and progressive muscle wasting. A healthy stem cell tends to duplicate in a regular pattern that creates one copy of itself that continues to function as a stem cell, and a differentiated cell, which performs a specific function. In a healthy person, a torn or damaged muscle would be repaired through this process.
Stem cell therapy - implanting healthy stem cells to combat tissue wasting - has shown promise against muscular dystrophy and other neurodegenerative diseases, but few of the implanted stem cells survive the procedure. Shihuan Kuang, a Purdue assistant professor of animal sciences, and Weiyi Liu, a postdoctoral research associate, showed that survival of implanted muscle stem cells could be increased by as much as fivefold in a mouse model if the cells are cultured under oxygen levels similar to those found in human muscles.
"Stem cells survive in a microenvironment in the body that has a low oxygen level," Kuang said. "But when we culture cells, there is a lot of oxygen around the petri dish. We wanted to see if less oxygen could mimic that microenvironment. When we did that, we saw that more stem cells survived the transplant."
Liu thinks that’s because the stem cells grown in higher oxygen levels acclimate to their surroundings. When they’re injected into muscles with lower oxygen levels, they essentially suffocate.
"By contrast, in our study the cells become used to the host environment when they are conditioned under low oxygen levels prior to transplantation," Liu said.
In the mouse model, Kuang and Liu saw more stem cells survive the transplants, and those stem cells retained their ability to duplicate themselves.
"When we lower the oxygen level, we can also maintain the self-renewal process," Kuang said. "If these stem cells self-renew, they should never be used up and should continue to repair damaged muscle."
The findings, reported in the journal Development, shows promise for increasing the effectiveness of stem cell therapy for patients with Duchenne muscular dystrophy, which affects about one in 3,500 boys starting at about 3-5 years old. The disease, which confines almost all patients to wheelchairs by their 20s, is often fatal as muscles that control the abilities to breathe and eat deteriorate.
Source: Purdue University
ScienceDaily (Aug. 21, 2012) — How abnormal protein deposits in the brains of Alzheimer’s patients disrupt the signalling between nerve cells has now been reported by researchers in Bochum and Munich, led by Dr. Thorsten Müller from the Medizinisches Proteom-Center of the Ruhr-Universität, in the journal Molecular and Cellular Proteomics. They varied the amount of APP protein and related proteins associated with Alzheimer’s disease in cell cultures, and then analysed how this manipulation affected other proteins in the cell. The result: the amount of APP present was related to the amount of an enzyme that is essential for the production of neurotransmitters and therefore for communication amongst nerve cells.
Mass spectrometer: The proteins are injected into the apparatus via a very thin needle. (Credit: © RUB-Pressestelle, Marion Nelle)
Proteomics: analysing all the proteins of the cells at once
Amyloid plaques are a characteristic feature of Alzheimer’s disease. They consist largely of cleavage products of the so-called amyloid precursor protein APP, which occur in excess in the brains of Alzheimer’s patients. What role APP plays in healthy people and why the abnormal accumulation of amyloid disrupts the regular functioning of the brain is still largely unclear. To understand the function of APP, the RUB researchers established a new cell model. The new cells produced only a very small amount of APP. What impact this had on all the other proteins of these cells was examined by the researchers through the use of mass spectrometry, among other things. With this method they identified over 2000 proteins and determined their concentrations. They were looking specifically for molecules whose concentrations in the newly established low-APP cells were different than in the reference cells that contained normal amounts of APP.
Abnormal protein able to curb neurotransmitter production
"One candidate has particularly caught our attention, this being the enzyme methionine adenosyltransferase II, alpha, MAT2A for short," Thorsten Müller said. Among other things, the enzyme is crucially involved in the production of neurotransmitters. Low-APP cells contained less MAT2A than the reference cells. To confirm the connection between the "Alzheimer’s protein" APP and the neurotransmitter-producing MAT2A, the team studied tissue samples from the brains of deceased Alzheimer’s patients and from healthy individuals. In the tissue of the Alzheimer’s patients there was less MAT2A than in the healthy samples. These results suggest that APP and MAT2A concentrations are related and are linked to the synthesis of neurotransmitters. "Our results point to a new mechanism by which the defective cleavage of the APP protein in Alzheimer’s disease could be directly related to altered neurotransmitter production," Müller said. "As a result, the signal transduction of nerve cells could be disrupted, which, over an extended period, could possibly also cause the death of cells."
Source: Science Daily
Aug. 20, 2012 by Quinn Eastman
People with Parkinson’s disease performed markedly better on a test of working memory after a night’s sleep, and sleep disorders can interfere with that benefit, researchers have shown.
The ability of sleep to improve scores on a test of working memory specifically depends on how much slow wave sleep Parkinson’s patients obtain, researchers have found.
While the classic symptoms of Parkinson’s disease include tremors and slow movements, Parkinson’s can also affect someone’s memory, including “working memory.” Working memory is defined as the ability to temporarily store and manipulate information, rather than simply repeat it. The use of working memory is important in planning, problem solving and independent living.
The findings underline the importance of addressing sleep disorders in the care of patients with Parkinson’s, and indicate that working memory capacity in patients with Parkinson’s potentially can be improved with training. The results also have implications for the biology of sleep and memory.
The results were published this week in the journal Brain.
"It was known already that sleep is beneficial for memory, but here, we’ve been able to analyze what aspects of sleep are required for the improvements in working memory performance," says postdoctoral fellow Michael Scullin, who is the first author of the paper. The senior author is Donald Bliwise, professor of neurology at Emory University School of Medicine.
The performance boost from sleep was linked with the amount of slow wave sleep, or the deepest stage of sleep. Several research groups have reported that slow wave sleep is important for synaptic plasticity, the ability of brain cells to reorganize and make new connections.
Sleep apnea, the disruption of sleep caused by obstruction of the airway, interfered with sleep’s effects on memory. Study participants who showed signs of sleep apnea, if it was severe enough to lower their blood oxygen levels for more than five minutes, did not see a working memory test boost.
In this study, participants took a “digit span test,” in which they had to repeat a list of numbers forward and backward. The test was conducted in an escalating fashion: the list grows incrementally until someone makes a mistake. Participants took the digit span test eight times during a 48-hour period, four during the first day and four during the second. In between, they slept.
Repeating numbers in the original order is a test of short-term memory, while repeating the numbers in reverse order is a test of working memory.
"Repeating the list in reverse order requires some effort to manipulate the numbers, not just spit them back out again," Scullin says. "It’s also a purely verbal test, which is important when working with a population that may have motor impairments."
54 study participants had Parkinson’s disease, and 10 had dementia with Lewy bodies: a more advanced condition, where patients may have hallucinations or fluctuating cognition as well as motor symptoms. Those who had dementia with Lewy bodies saw no working memory boost from the night’s rest. As expected, their baseline level of performance was lower than the Parkinson’s group.
Participants with Parkinson’s who were taking dopamine-enhancing medications saw their performance on the digit span test jump up between the fourth and fifth test. On average, they could remember one more number backwards. The ability to repeat numbers backward improved, even though the ability to repeat numbers forward did not.
Patients needed to be taking dopamine-enhancing medications to see the most performance benefit from sleep. Patients not taking dopamine medications, even though they had generally had Parkinson’s for less time, did not experience as much of a performance benefit. This may reflect a role for dopamine, an important neurotransmitter, in memory.
Scullin and Bliwise are planning an expanded study of sleep and working memory, in healthy elderly people as well as patients with neurodegenerative diseases.
"Many elderly people go through a decline in how much slow wave sleep they experience, and this may be a significant contributor to working memory difficulties," Scullin says.
Source: Emory
20 August 2012 by Kayt Sukel
Some people can recall what happened on almost every day of their lives. Unlocking their secrets could shed light on the way all our memories work
IT WAS an email that memory researcher James McGaugh found hard to believe. The sender, a 34-year-old housewife named Jill Price, was claiming that she could recall key events on any date back to when she was about 12, as well as what she herself had done each day.
"Some people call me the human calendar," she wrote, "while others run out of the room in fear. But the one reaction I get from everyone who finds out about this ‘gift’ is amazement. I run my entire life through my head every day and it drives me crazy!"
McGaugh invited Price to his lab, making sure he had to hand a copy of 20th Century Day by Day, a book that lists important events by date. He opened the book to random pages and asked Price what had happened on those days. “Whether it was a plane crash or some elections or a movie star doing an outrageous thing, she was dead on,” he recalls. “Time and time again.”
That was in June 2000. McGaugh’s group has worked closely with Price ever since, and has discovered she is one of a select few with similar abilities. These individuals are neither autistic savants nor masters of mnemonic-based tricks of recall, yet they can remember key events from almost every day of their lives. Learning more about their abilities and how their brains are wired should lead to insights into the nature of human memory.
Intrigued by McGaugh’s findings, I arranged to visit his lab at the University of California, Irvine, to find out how these people live with such unusual abilities - and what it is like for the researchers working with them. “It never ceases to amaze me,” says McGaugh’s colleague, Aurora LePort. “Some of them can remember every day you give them.” She says studying people whose powers of recall seem to be enhanced, rather than impaired, offers us a new tool to explore memory.
It is certainly fair to say that most of our knowledge of memory derives from looking at memory loss. The classic case is that of Henry Molaison (better known as “HM”), who had surgery nearly 60 years ago to treat severe epilepsy. In a misguided attempt to remove the source of the seizures, several parts of the brain were cut out, including both hippocampi, curled up ridges on either side of the brain.
For HM, the consequences were catastrophic. Although he could still recall his early life, he was no longer able to lay down memories of things that happened to him after the surgery. Every day, the researchers studying his condition had to introduce themselves anew. Intriguingly, though, he could perform tasks that used short-term memory, like retaining a phone number for a few minutes.
Thanks to HM and many other people with neurological problems caused by head injuries and strokes, we now know that there are different kinds of remembering. Our short-term memories last up to about a minute, unless they are reinforced, or “rehearsed” through further repetition. While much about the neuroscience of memory remains mysterious, our hippocampi seem to be involved in turning these fleeting impressions into long-term memories, which are thought to be stored in the temporal lobes on either side of the brain.
Long-term memories can be subdivided into semantic ones to do with concepts, such as the fact that London is the UK capital, and autobiographical memories, about everyday events that we experience. Price has no special abilities with regard to her short-term or semantic memory, but when it comes to autobiographical memory, her scores are off the chart.
ScienceDaily (Aug. 20, 2012) — The more that we understand the brain, the more complex it becomes. The same can be said about the genetics and neurobiology of psychiatric disorders. For “Mendelian” disorders, like Huntington disease, mutation of a single gene predictably produces a single clinical disorder, following relatively simple genetic principals. Compared to Mendelian disorders, understanding bipolar disorder has been extremely challenging. Its biology is not well understood and its genetics are complex.
In a new paper, Dr. Inti Pedroso and colleagues utilize an integrative approach to probe the biology of bipolar disorder. They combined the results of three genome-wide association studies, which examined the association of common gene variants with bipolar disorder throughout the genome, and a study of gene expression patterns in post-mortem brain tissue from people who had been diagnosed with bipolar disorder. The findings were analyzed within the context of how brain proteins relate to each other based on the Human Protein Reference Database protein-protein interaction network.
"None of our research approaches provides us with sufficient information, by itself, to understand the neurobiology of psychiatric disorders. This innovative paper wrestles with this challenge in a creative way that helps us to move forward in thinking about the neurobiology of bipolar disorder," commented Dr. John Krystal, Editor of Biological Psychiatry.
Dr. Pedroso explained, “We combined information about genetic variation from thousands of cases and controls with brain gene expression data and information from protein databases to identify networks of genes and proteins in the brain that are key in the development of bipolar disorder.”
The analysis resulted in the ability to define risk gene variants that were deemed functional, by virtue of the association with changes in gene expression levels, and to group these functional gene variants in biologically meaningful pathways.
The results implicated genes involved in several neural signaling pathways, including the Notch and Wnt signaling pathways. These pathways are key processes in neurotransmission and brain development and these findings indicate they are also likely to be involved in causing this severe disorder. The authors noted that three features stand out among these genes: i) they localized to the human postsynaptic density, which is crucial for neuronal function; ii) their mouse knockouts present altered behavioral phenotypes; and iii) some are known targets of the pharmacological treatments for bipolar disorder.
Dr. Gerome Breen, senior author on the study and Senior Lecturer at King’s College London Institute of Psychiatry, said, “Our study provides some of the first evidence to show the biochemical and developmental processes involved in causing risk for developing this life-long and costly illness. We have highlighted potential new avenues for new drug treatments and intervention.”
Source: Science Daily
ScienceDaily (Aug. 20, 2012) — Scientific advances in understanding the “addiction circuitry” of the brain may lead to effective treatment for obesity using deep brain stimulation (DBS), according to a review article in the August issue of Neurosurgery, official journal of the Congress of Neurological Surgeons.
Electrical brain stimulation targeting the “dysregulated reward circuitry” could make DBS — already an accepted treatment for Parkinson’s disease — a new option for the difficult-to-treat problem of obesity. Dr. Alexander Taghva of Ohio State University and University of Southern California was lead author of the new review.
New Insights into ‘Reward Circuitry’
Obesity is a major public health problem that is notoriously difficult to treat. Although various approaches can promote weight loss, patients typically gain weight soon after the end of treatment. Drug options have shown limited success, with several products removed from the market because of serious adverse effects. Bariatric surgery is effective in many cases of obesity but has a significant failure rate and is associated with side effects.
Drug treatments for obesity have targeted the homeostatic (self-regulating) mechanism regulating appetite and body weight. The homeostatic mechanism is thought to involve the “feeding center” in the hypothalamus, which produces hormones (such as leptin and insulin) that affect feeding behavior.
Initial experiments exploring DBS as a treatment for obesity have targeted the hypothalamus. However — as with drug options focusing on the homeostatic mechanisms — success has been limited.
Possible Role of DBS for Obesity
More recent studies have explored a different mechanism: specifically, the “reward circuitry,” of the brain. Research has suggested that obesity is associated with a “relative imbalance” of the reward circuitry. Studies show that obese subjects — like those with addictive behaviors — are more impulsive and less able to delay gratification. The reward circuitry is intimately interconnected with the homeostatic mechanisms.
Together, these studies raise the possibility of new DBS approaches to the treatment of obesity. In DBS, a small electrode is surgically placed in a precise location in the brain. A mild electrical current is delivered to stimulate that area of the brain, with the goal of interrupting abnormal activity. Deep brain stimulation has become a standard and effective treatment for movement disorders such as Parkinson’s disease.
Just as stimulation of the brain areas responsible for abnormal movement helps “turn off” tremors in patients with Parkinson’s disease, stimulation of the areas involved in dysregulated reward circuitry might be able to “turn off” abnormal feeding behaviors in obese patients. The authors outline evidence implicating several different brain areas involved in the brain’s reward circuitry — particularly the “frontostriatal circuitry” — which could be useful targets for DBS.
Previous reports in individual patients have suggested that DBS performed for other reasons — particularly severe obsessive-compulsive disorder — have unexpectedly had unpredicted beneficial effects on addictive behaviors like smoking and overeating. Dr. Taghva and colleagues hope their review will open the way to further exploration of DBS as part of new and effective strategies for the treatment of obesity, perhaps in combination with therapies targeting the homeostatic mechanism.
Source: Science Daily
The simple act of picking up a pencil requires the coordination of dozens of muscles: The eyes and head must turn toward the object as the hand reaches forward and the fingers grasp it. To make this job more manageable, the brain’s motor cortex has implemented a system of shortcuts. Instead of controlling each muscle independently, the cortex is believed to activate muscles in groups, known as “muscle synergies.” These synergies can be combined in different ways to achieve a wide range of movements.
This graphic shows the brain, with the motor cortex highlighted in yellow.
Graphic: Christine Daniloff
A new study from MIT, Harvard Medical School and the San Camillo Hospital in Venice finds that after a stroke, these muscle synergies are activated in altered ways. Furthermore, those disruptions follow specific patterns depending on the severity of the stroke and the amount of time that has passed since the stroke.
The findings, published this week in the Proceedings of the National Academy of Sciences, could lead to improved rehabilitation for stroke patients, as well as a better understanding of how the motor cortex coordinates movements, says Emilio Bizzi, an Institute Professor at MIT and senior author of the paper.
“The cortex is responsible for motor learning and for controlling movement, so we want to understand what’s going on there,” says Bizzi, who is a member of the McGovern Institute for Brain Research at MIT. “How does the cortex translate an idea to move into a series of commands to accomplish a task?”
Gut bacteria may influence thoughts and behaviour
The human gut contains a diverse community of bacteria that colonize the large intestine in the days following birth and vastly outnumber our own cells. These so-called gut microbiota constitute a virtual organ within an organ, and influence many bodily functions. Among other things, they aid in the uptake and metabolism of nutrients, modulate the inflammatory response to infection, and protect the gut from other, harmful micro-organisms. A study by researchers at McMaster University in Hamilton, Ontario now suggests that gut bacteria may also influence behaviour and cognitive processes such as memory by exerting an effect on gene activity during brain development.
Image: Brian Stauffer
Jane Foster and her colleagues compared the performance of germ-free mice, which lack gut bacteria, with normal animals on the elevated plus maze, which is used to test anxiety-like behaviours. This consists of a plus-shaped apparatus with two open and two closed arms, with an open roof and raised up off the floor. Ordinarily, mice will avoid open spaces to minimize the risk of being seen by predators, and spend far more time in the closed than in the open arms when placed in the elevated plus maze.
This is exactly what the researchers found when they placed the normal mice into the apparatus. The animals spent far more time in the closed arms of the maze and rarely ventured into the open ones. The germ-free mice, on the other hand, behaved quite differently – they entered the open arms more often, and continued to explore them throughout the duration of the test, spending significantly more time there than in the closed arms.
17 August 2012
A WA study of an isolated population of Eastern European Gypsies known as “Bowlmakers” has unlocked clues about a serious developmental disease - congenital cerebellar ataxia.
Professor Luba Kalaydjieva and Dr Dimitar Azmanov, from The University of Western Australia, say the discovery of an important genetic mutation is likely to inspire other scientific work around the world.
The result of their research for the UWA-affiliated Western Australian Institute for Medical Research (WAIMR) was published online today in the prestigious American Journal of Human Genetics.
It involved working collaboratively with other Australian and European researchers to discover mutations within a gene which has never before been linked to this form of heredity ataxia in humans.
Ataxias are a large group of neurodegenerative disorders that affect the ability to maintain balance, and learn and maintain motor skills. While many genes have already been implicated in hereditary ataxias, understanding their molecular basis is far from complete. New knowledge will help the understanding of normal brain development and function, and the mechanisms of degeneration.
"Gypsies are a founder population," Professor Kalaydjieva said. "They are derived from a small number of ancestors and have remained relatively isolated from surrounding populations. The Bowlmakers - known for their wooden handicrafts such as bowls and spoons - were an ideal group to study because they are a younger sub-isolate, showing limited genetic diversity.
"We studied a novel form of ataxia in 3 families in this ethnic group. Clinical and brain-imaging investigations were done in Bulgaria, in collaboration with radiologists from Sir Charles Gairdner Hospital and Princess Margaret Hospital, and were followed-up by genetic studies at WAIMR and the Walter and Eliza Hall Institute (WEHI), Melbourne.
"Signs of ataxia were detected in early infancy when motor skills like crawling and rolling over did not develop. The affected individuals presented with global developmental delay, ataxia and intellectual deficit. MRI scans showed signs of degeneration of the cerebellum, which is part of the brain controlling motor and learning skills. Overall, the life expectancy is not decreased but the quality of life is severely affected.
"The parents of the affected individuals did not present with any clinical symptoms of the ataxia, suggesting recessive inheritance," Dr Azmanov said. "Our genetic studies showed unique changes in the gene encoding metabotropic glutamate receptor 1 (GRM1), which is important for the normal development of the cerbellar cortex. The mutations inherited by all affected individuals from their unaffected carrier parents dramatically altered the structure of the GRM1 receptor.”
Professor Kalaydjieva said the exact pathogenetic mechanisms leading to the clinical manifestations and cerebellar degeneration are yet to be explained and that this opens novel research avenues for the wider scientific community. ”It also remains to be seen if other ataxia patients around the world carry mutations in GRM1,” she said.
The human genome that researchers sequenced at the turn of the century doesn’t really exist as we know it.
The Human Genome project sequenced “the human genome” and is widely credited with setting in motion the most exciting era of fundamental new scientific discovery since Galileo. That’s remarkable, because in important ways “the human genome” that we have labeled as such doesn’t actually exist.
cosmin4000, istockphoto
Plato essentially asserted that things like chairs and dogs, which we observe in this physical world, and even concepts like virtues, are but imperfect representations or instances of some ideal that exists, but not in the material world. Such a Platonic ideal is “the human genome,” a sequence of about 3 billion nucleotides arrayed across a linear scale of position from the start of chromosome 1 to the end of the sex chromosomes. Whether it was obtained from one person or several has so far been shrouded in secrecy for bioethical reasons, but it makes no real difference. What we call the human genome sequence is really just a reference: it cannot account for all the variability that exists in the species, just like no single dog on earth, real or imagined, can fully incorporate all the variability in the characteristics of dogs.
Nor is the human genome we have a “’normal” genome. What would it mean to be “normal” for the nucleotide at position 1,234,547 on chromosome 11? All we know is that the donor(s) had no identified disease when bled for the cause, but sooner or later some disease will arise. Essentially all available whole genome sequences show potentially disease-producing variants, even including nonfunctional genes, in donors who were unaffected at the time.