Chapter 3. Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
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By Karen Weintraub Paul Barney had his first seizure four days after his fourth birthday. By the time he was 10, his mom worried that if they didn’t get the seizures under control soon, he might lose IQ points along with his ready smile. When Brian Manning, 11, had a seizure on the school playground – instead of in his bed as usual – his parents knew it was time for drastic action. He’d already had brain surgery once, but doctors said he might need five or six more operations. Or he could have one, to completely remove the right half of his brain. Both boys have epilepsy and recently underwent surgery at Boston Children’s Hospital. And both represent the promise and frustration of epilepsy treatment today. Patients have more options, and there is more awareness, less stigma, and a better understanding of epilepsy than there has ever been. But available medications can’t control seizures in about one-third of patients, including Paul and Brian, and while surgery is safer, it still comes with high risks. It also remains unclear what causes the electrical disturbance in patients’ brains that triggers seizures. Roughly 1 in 26 Americans will develop epilepsy at some point in life – more than will have autism, AIDS, or Parkinson’s disease. Some patients do fine between seizures and can function normally. In others, their brains are constantly being disrupted, like a radio station filled with static, according to Dr. Blaise Bourgeois the director of the Division of Epilepsy and Clinical Neurophysiology at Boston Children’s. © 2012 NY Times Co.
Link ID: 17156 - Posted: 08.13.2012
Duncan Graham-Rowe A skull implant that can detect an epileptic seizure and deliver therapeutic electrical impulses can reduce the length of these events by 60% in rats. The device, tested on nine rats with a ‘petit mal’ form of epilepsy, is described today in Science1. Most electrical stimulation devices, such as those that deliver deep-brain stimulation (DBS) to treat Parkinson’s disease and depression, operate continuously, delivering impulses regardless of the patient’s brain activity. But this can cause a range of undesirable side effects, such as headaches. Seizure-responsive versions of DBS devices are coming to market, such as the Responsive Neurostimulator System developed by NeuroPace, based in Mountain View, California. The system is awaiting approval by the US Food and Drug Administration and will be aimed at adults with certain types of partial-onset seizures, which tend to be localized to certain regions of the brain. But as the name implies, DBS uses electrodes that penetrate the brain, which can also carry certain risks, such as a worsening of epilepsy symptoms. In the latest study, György Buzsáki, a neuroscientist at the New York University School of Medicine, and his colleagues used a less invasive approach that involves transcranial electrical stimulation (TES) of neurons using electrodes implanted in the skull. This technique has been shown to be effective at modifying the brain's cortical (outermost) neurons, which become abnormally excited during epileptic seizures. To detect the onset of a seizure, recording electrodes that detect neural activity were implanted on the brain's surface. © 2012 Nature Publishing Group,
Link ID: 17148 - Posted: 08.11.2012
By Julie Appleby, An increasing number of psychiatrists and hospitals — as well as entrepreneurs opening rTMS centers around the country — are betting that there are millions of people like Curtis, discouraged by depression treatments that have proved unsuccessful and willing to pony up thousands of dollars for the possibility of relief. The treatment, which has been approved by the Food and Drug Administration, is covered by Medicare in five states, but few private insurers pay for it routinely. While rTMS has ardent supporters, its effectiveness is still debated, and there is little evidence showing how long the results last. The technique has been shown to work better than a placebo, but the proportion of patients who show complete relief ranges widely, from as few as 10 percent to as many as 57 percent, according to various studies. The debate has huge implications, not just for many of the 14 million Americans who suffer from major depression every year but also for businesses eyeing a potentially lucrative market and insurers weighing whether to cover it. About half of those 14 million Americans seek relief through psychotherapy and prescription drug treatment, according to an evaluation by the federal Agency for Healthcare Research and Quality. But studies show that antidepressants provide complete cessation of symptoms only about a third of the time. Magnetic stimulation is aimed at patients with such “treatment-resistant depression.” Supporters say rTMS is worth the cost — between $6,000 and $12,000 for the four-to-six-week treatment — because it enables people such as Curtis to resume productive lives. Skeptics question the price tag in light of uncertain benefits. © 1996-2012 The Washington Post
Link ID: 17139 - Posted: 08.08.2012
By Laura Sanders A much-maligned molecule that is devastating in the brain may have therapeutic potential outside it. The sticky amyloid-beta protein, which piles up in the brains of people with Alzheimer’s disease, actually reverses paralysis in mice with symptoms of multiple sclerosis. The unexpected finding, published in the Aug. 1 Science Translational Medicine, could mean that A-beta or molecules like it may one day form the basis of a treatment for multiple sclerosis in people. In MS, rogue immune cells penetrate the brain and spinal cord and attack myelin, a substance that is necessary to keep neural impulses moving at full speed. Damage and inflammation from this attack can leave a person with paralysis, numbness, vision problems and extreme fatigue. A-beta is found in the brains of people with MS, but scientists do not know precisely what effect it has there, if any. To investigate that question, study coauthor Lawrence Steinman of Stanford University and colleagues tried injecting A-beta into mice’s abdomens, thinking it would worsen symptoms. “We expected that either nothing would happen or the disease would worsen because this is an infamous, villainous molecule,” he says. Instead, the mice got better. In several different kinds of mice designed to have symptoms similar to the human disease, A-beta injections into the body reduced paralysis and lowered brain inflammation. “The outcome was unmistakable,” Steinman says. © Society for Science & the Public 2000 - 2012
By RODNEY MUHUMUZA KITGUM, Uganda — Augustine Languna's eyes welled up and then his voice failed as he recalled the drowning death of his 16-year-old daughter. The women near him looked away, respectfully avoiding the kind of raw emotion that the head of the family rarely displayed. "What is traumatizing us," he said after regaining his composure, "is that the well where she died is where we still go for drinking water." Joyce Labol was found dead about three years ago. As she bent low to fetch water from a pond a half mile from Languna's compound of thatched huts, an uncontrollable spasm overcame her. The teen was one of more than 300 young Ugandans who have died as a result of the mysterious illness that is afflicting more and more children across northern Uganda and in pockets of South Sudan. The disease is called nodding syndrome, or nodding head disease, because those who have it nod their heads and sometimes go into epileptic-like fits. The disease stunts children's growth and destroys their cognition, rendering them unable to perform small tasks. Some victims don't recognize their own parents. Ugandan officials say some 3,000 children in the East African country suffer from the affliction. Some caregivers even tie nodding syndrome children up to trees so that they don't have to monitor them every minute of the day. Beginning Monday, Uganda hosts a four-day international conference on nodding syndrome that health officials believe will lead to a clearer understanding of the mysterious disease. © 2012 NBCNews.com
by Andy Coghlan Treating disease by stimulating brain cells with light is a step closer to reality following the first demonstration that the technique can improve mental performance in monkeys. Two monkeys performed better on simple computer tasks after light was used to boost the activity of brain cells necessary for the task. "For the first time, we were able to change behaviour in primates with our technique," says Wim Vanduffel of Massachusetts General Hospital in Charlestown, who is head of the group that performed the experiment. Known as optogenetics, the method has the potential to treat conditions such as epilepsy, where the light could temporarily deactivate the brain cells that cause seizures, or Parkinson's disease, where it can activate cells that make dopamine, the neurotransmitter vital for controlling mobility that those with Parkinson's lack. Previously, it has been used in nematode worms to trigger them to lay eggs, and mice to relieve depression and paralysis. Researchers have also used it in monkeys, but only on single, isolated neurons. Vanduffel and his colleagues wanted to see if they could extend this to entire networks of cells, boosting a monkey's ability to perform a simple computer-based task. Natural performance enhancers First, Vanduffel's team scanned the two monkeys' brains using functional magnetic resonance imaging while they followed a green dot on a computer screen. From the scans, the researchers could tell that the monkeys relied on an area of the brain called the arcuate sulcus to do the task. © Copyright Reed Business Information Ltd.
Link ID: 17098 - Posted: 07.28.2012
A widely prescribed drug for multiple sclerosis may not slow the disease from progressing, a British Columbia study shows. Beta interferons are prescribed for the relapse-remitting form of MS, which affects about 85 per cent of people with the disease in Canada. As the name suggests, people with relapsing-remitting MS have flare-ups when new symptoms appear or olds ones return or worsen. There are also periods of remission with partial or full recovery. "In clinical trial situations, it has been quite evident for years that patients receiving beta interferon treatment have reduced frequency of relapses as well as reduced frequency of new lesions seen on MRI," Dr. Joel Oger, who is also a neurologist with the UBC Hospital MS Clinic, said in a release. "This study following a large number of patients for a long time in 'real life situation' does not show an association of the beta interferons with long term disability and tends to confirm a more modern way of understanding MS: relapses may not be responsible for long term disability in all patients and another mechanism might be at work as well." The study in Wednesday's issue of the Journal of the American Medical Association compared 868 people prescribed the drug with 829 who were untreated as well as 959 who were treated before interferon beta was approved. © CBC 2012
Keyword: Multiple Sclerosis
Link ID: 17058 - Posted: 07.18.2012
By Dwayne Godwin and Jorge Cham In 1953, Henry Molaison underwent radical surgery in an attempt to stop his epileptic seizures... © 2012 Scientific American,
Analysis by Sheila Eldred If you've seen "Silence of the Lambs," you probably remember the scene where the lights go out on Jodie Foster and the unseen Buffalo Bill reaches out to her. That's because at that moment, your brain was probably at its peak of engagement, according to a study by a team of researchers from The City College of New York and Columbia University. "Peak correlations of neural activity across viewings can occur in remarkable correspondence with arousing moments of the film," the researchers wrote in the journal "Moreover, a significant reduction in neural correlation occurs upon a second viewing of the film or when the narrative is disrupted by presenting its scenes scrambled in time." Tense scenes present prime conditions for peak brain activity. They usually contain at least two of the three components identified by the researchers as most engaging: powerful visual cues, ominous music, and meaningful scene changes. To make the correlation, the researchers hooked 20 subjects up to EEG devices (electroencephalography measures electrical activity across the scalp) as they showed scenes from three films: Alfred Hitchcock's "Bang! You're Dead," Sergio Leone's "The Good, the Bad and the Ugly," and an amateur film of people walking on a college campus as a control. © 2012 Discovery Communications, LLC
Ewen Callaway A genetic test could help to determine whether a multiple sclerosis patient would benefit from a promising therapy. Like diabetes, most forms of cancer and other common diseases, there is no single gene that causes the autoimmune condition multiple sclerosis (MS). Dozens of genetic variations act in concert with environmental factors to cause the debilitating neurological disease. Yet a single genetic variant may explain why drugs that treat other autoimmune diseases tend to make MS symptoms worse, and could identify other MS patients who might benefit from the therapies. Researchers say that the findings, which are published online in Nature1, also highlight how genome-wide association studies (GWAS) can yield useful medical insights. GWAS compare thousands of people who have a particular disease, detailing hundreds of thousands of genetic variations between them. The goal is to identify variations that are more common in people with the condition than in healthy people. Most such studies uncover scores of genetic variants associated with the disease in question, each increasing a person’s chances of developing the condition by a small percentage. Such is the case for a DNA letter in the gene that encodes the protein called tumour necrosis factor receptor 1 (TNFR1). The protein senses a potent immune molecule called tumour necrosis factor (TNF) that destroys cancerous cells but that is also implicated in autoimmune disease. People of European ancestry who have two ‘A’s at that particular spot on the genome are 12% more likely to develop MS than those with two ‘G’s at that spot. © 2012 Nature Publishing Group
Scientists have identified why a once-promising class of drugs do not help people with multiple sclerosis. An Oxford University team say an genetic variant linked to MS means the drugs which work for patients with other autoimmune diseases will not work for them. The team, writing in Nature, say the drugs can actually make symptoms worse. Experts say the work shows how a person's genetic make-up could affect how they responded to treatment. The drugs, called anti-TNFs, work for patients with rheumatoid arthritis and inflammatory bowel disease, but they have not done so for patients with MS and researchers were unsure why. The Oxford University team looked at one particular genetic variant, found in a gene called TNFRSF1A, which has previously been associated with the risk of developing MS. The normal, long version of the protein sits on the surface of cells and binds the TNF signalling molecule, which is important for a number of processes in the body. But the team discovered the variant caused the production of an altered, shortened version which "mops up" TNF, preventing it from triggering signals - essentially the same thing that TNF blocking drugs do. BBC © 2012
Analysis by Jesse Emspak The phrase, "use your brainpower" may soon become literal. Engineers at MIT have developed a tiny prototype fuel cell that creates electricy from the body's natural sugars. The fuel cell could be used to power brain implants for treating epilepsy, Parkinson's diseases and paralysis. Currently, devices implanted in the body are typically powered by lithium-ion batteries, but they have a limited lifetime and need to be replaced. Opening up the body to replace a battery is not something doctor like to do, but doing it in the brain is even less desirable. The researchers, led by Rahul Sarpeshkar, an associate professor of electrical engineering and computer science, built the fuel cell using a platinum catalyst at one end and a layer of carbon nanotubes at the other. It rests on a silicon chip, allowing it to be connected to electronics that would be used in brain implants. coughing robot As glucose passes over the platinum, electrons and hydrogen ions are stripped off as it is oxidized. That's what makes the current. At the other end of the cell, oxygen mixes with the hydrogen to make water when it hits the layer of single-walled carbon nanotubes. The cell produces up to 180 microwatts, enough to power a brain implant that might send signals to bypass damaged region, or stimulate part of the brain (a treatment used in disorders such as Parkinson's). © 2012 Discovery Communications, LLC.
Link ID: 16982 - Posted: 06.28.2012
A diet high in cholesterol may help people with a fatal genetic disease which damages the brain, according to early studies in mice. Patients with Pelizaeus-Merzbacher disease struggle to produce a fatty sheath around their nerves, which is essential for function. A study, published in Nature Medicine, showed that a high-cholesterol diet could increase production. The authors said the mice "improved dramatically". Pelizaeus-Merzbacher disease (PMD) is one of many leukodystrophies in which patients struggle to produce the myelin sheath. It protects nerve fibres and helps messages pass along the nerves. Without the sheath, messages do not travel down the nerve - resulting in a range of problems including movement and cognition. Researchers at the Max Planck Institute of Experimental Medicine, in Germany, performed a trial on mice with the disease and fed them a high cholesterol diet. The first tests were on mice when they were six weeks old, after signs of PMD had already emerged. Those fed a normal diet continued to get worse, while those fed a cholesterol-enriched diet stabilised. BBC © 2012
by Dennis Normile YOKOHAMA, JAPAN—For more than a decade, stem cell therapies have been touted as offering hope for those suffering from genetic and degenerative diseases. The promise took another step toward reality last week with announcements here at the annual meeting of the International Society for Stem Cell Research (ISSCR) that two groups are moving forward with human clinical research, one focusing on a rare genetic neurological disease and the other for the loss of vision in the elderly. StemCells Inc. of Newark, California, reported encouraging results of an initial human trial using human neural stem cells to treat Pelizaeus-Merzbacher disease (PMD). PMD is a progressive and fatal disorder in which a genetic mutation inhibits the normal growth of myelin, a protective material that envelopes nerve fibers in the brain. Without myelin, nerve signals are lost, and the patient, usually an infant, suffers degenerating motor coordination and other neurological symptoms. In her presentation, Ann Tsukamoto, StemCells' vice president for research, said the company chose to test its neural stem cell approach on PMD because there is currently no treatment for the condition and a diagnosis can be confirmed by genetic testing and magnetic resonance imaging. "This creates an opportunity for early intervention when it can best help." The company has created banks of highly purified neural stem cells that are isolated from adult neural tissue. Injected into rodents, the cells don't form tumors; rather, they migrate through the animals' brains, where they differentiate into various types of neural cells including the cells that create the myelin that protects nerve fibers. When neural stem stems were injected into in mice, they showed "robust engraftment and migration, the formation of new myelin," Tsukamoto said. © 2010 American Association for the Advancement of Science
By Justin Moyer, On June 9, Commerce Secretary John Bryson was hospitalized after his reported involvement in three auto accidents. Although details were not disclosed, the White House confirmed that he had a seizure. On July 30, 2007, Chief Justice John Roberts collapsed on a boat dock at his Maine summer home. Although that seizure was Roberts’s second, he offered little explanation. When Time magazine asked “Does Justice Roberts Have Epilepsy?,” Roberts didn’t answer, and he hasn’t in five years. Reading these stories, I wish public figures such as Roberts and Bryson would talk publicly about their conditions. They should do this not because they are legally compelled to or because their health may affect their work. They should do it because hiding their problems makes it seem like their problems are worth hiding. I received a diagnosis of epilepsy in 2001, at age 24. My seizures are generalized, meaning they strike my whole brain and body. Without warning, I lose consciousness for several minutes and remain disoriented for a few hours. Later, I have no memory of the episode save muscle aches and a sore mouth from biting my tongue. My seizures are idiopathic: They have no known cause. They can be controlled with levetiracetam, a medication that regulates brain neurotransmitters. © 1996-2012 The Washington Post
Link ID: 16930 - Posted: 06.19.2012
By Nathan Seppa By delving into the components of protective nerve coatings that get damaged in multiple sclerosis, scientists have identified a handful of lipid molecules that appear to be attacked by an immune system run amok. Bolstering the supply of these lipids might help preserve these nerve coatings and, in the process, knock back the inflammation that contributes to their destruction, researchers report in the June 6 Science Translational Medicine. In MS patients, rogue antibodies assault myelin, the fatty sheath that insulates nerves and facilitates signaling. Inflammation exacerbates the attack on myelin and the cells that make it. But other details of MS, including the roles of myelin lipids, have been less clearly understood. “I think this is a very good study,” says Francisco Quintana, an immunologist at Harvard Medical School. “Overall, there are not many papers on lipids in MS. Technically, they are challenging and require a lot of expertise.” To explore the role of lipids, the researchers studied spinal fluid from people with MS, healthy people and patients with other neurological disorders. Tests on the fluid showed that antibodies targeted four lipids more often in MS patients than in the other groups. Examination of autopsied brains from MS patients and people without MS revealed that, in the MS patients, these four lipids were depleted at the sites where the nerve coatings were damaged. © Society for Science & the Public 2000 - 2012
Keyword: Multiple Sclerosis
Link ID: 16886 - Posted: 06.07.2012
By ALASTAIR GEE In November 2008, when he was just 6, William Moller had his first epileptic seizure, during a reading class at school. For about 20 seconds, he simply froze in place, as if someone had pressed a pause button. He could not respond to his teacher. This is known as an absence seizure, and over the next year William, now 10, who lives with his family in Brooklyn, went from having one or two a day to suffering constant seizures. Not all were absence seizures; others were frightening tonic-clonics, also known as grand mals, during which he lost consciousness and convulsed. The seizures often came while he was eating. As his body went rigid, William dropped his food and his eyes rolled back into their sockets. If he seized while standing, he suddenly crashed to the ground — in a corridor, in the driveway, on the stairs. “It’s the scariest thing for any mother to hear that thump, and each time he would hit his head, so it only made things worse and worse,” said his mother, Elisa Moller, a pediatric nurse. William is among the one-third of epilepsy sufferers who do not respond, or respond only poorly, to anti-epileptic medications. Now he and others with refractory epilepsy are benefiting from treatment that targets inflammation, the result of new research into how epilepsy damages the brain. “Many of us theorize that the two are tied — inflammation causes seizures, and seizures cause inflammation,” said Orrin Devinsky, director of the Comprehensive Epilepsy Center at the New York University Langone Medical Center and William’s doctor. “Over time, both of them may feed off each other.” © 2012 The New York Times Company
Smoking marijuana may help relieve the muscle tightness and pain of multiple sclerosis, a small U.S. study suggests. Many people with MS often suffer from spasticity, an uncomfortable and disabling condition in which the muscles become tight and difficult to control. Spasticity can be controlled with medications but the symptoms may continue or the anti-spasticity drugs may carry adverse effects such as drowsiness, sedation, and muscle weakness. The medical marijuana used in the study the strength of cigarettes most commonly available in the community at the time of the research. Most trials testing medical marijuana have focused on oral forms. Now a randomized trial has put smoked cannabis to the test against placebo for 30 people with MS whose spasticity resisted treatment. "Using an objective measure, we saw a beneficial effect of inhaled cannabis on spasticity among patients receiving insufficient relief from traditional treatment," Dr. Jody Corey-Bloom, of the department of neuroscience at University of California, San Diego and her co-authors concluded in Monday's issue of the Canadian Medical Association Journal. In the study, the average age of participants was 50 and 63 per cent were female. More than half of the participants needed walking aids and 20 per cent used wheelchairs. Copyright © CBC 2012
Amy Maxmen By tacking drugs onto molecules targeting rogue brain cells, researchers have alleviated symptoms in newborn rabbits that are similar to those of cerebral palsy in children. Cerebral palsy refers to a group of incurable disorders characterized by impairments in movement, posture and sensory abilities. In general, medicines tend to act broadly rather than influence certain sets of cells in the brain. “You don’t expect large molecules to enter the brain, and if they do, you don’t expect them to target specific cells, and immediately act therapeutically — but all of this happened,” says study co-author Rangaramanujam Kannan, a chemical engineer at the Johns Hopkins University School of Medicine in Baltimore, Maryland. The paper is published today in Science Translational Medicine1. According the US Centers for Disease Control and Prevention, approximately 1 in 303 children have cerebral palsy by age 8, which usually results from neurological damage in the womb, caused by, for example, a kink in the umbilical cord that briefly dimishes the foetus' oxygen, or maternal infection. Such injuries lead to the activation of immune cells in the brain called microglia and astrocytes, which cause further inflammation and exacerbate the damage. Calming the cells is difficult, because anti-inflammatory drugs don’t easily cross the blood–brain barrier. And those that do tend to diffuse nonspecifically. “What’s amazing here is that the authors target the drug directly to the microglia,” says Mike Johnston, a paediatric neurologist at the Kennedy Krieger Institute in Baltimore. © 2012 Nature Publishing Group
By Stephen Dougherty In the film Amèlie, the main character is a young eccentric woman who attempts to change the lives of those around her for the better. One day Amèlie finds an old rusty tin box of childhood mementos in her apartment, hidden by a boy decades earlier. After tracking down Bretodeau, the owner, she lures him to a phone booth where he discovers the box. Upon opening the box and seeing a few marbles, a sudden flash of vivid images come flooding into his mind. Next thing you know, Bretodeau is transported to a time when he was in the schoolyard scrambling to stuff his pockets with hundreds of marbles while a teacher is yelling at him to hurry up. We have all experienced this: a seemingly insignificant trigger, a scent, a song, or an old photograph transports us to another time and place. Now a group of neuroscientists have investigated the fascinating question: Can a few neurons trigger a full memory? In a new study, published in Nature, a group of researchers from MIT showed for the first time that it is possible to activate a memory on demand, by stimulating only a few neurons with light, using a technique known as optogenetics. Optogenetics is a powerful technology that enables researchers to control genetically modified neurons with a brief pulse of light. To artificially turn on a memory, researchers first set out to identify the neurons that are activated when a mouse is making a new memory. To accomplish this, they focused on a part of the brain called the hippocampus, known for its role in learning and memory, especially for discriminating places. Then they inserted a gene that codes for a light-sensitive protein into hippocampal neurons, enabling them to use light to control the neurons. © 2012 Scientific American
Link ID: 16582 - Posted: 03.29.2012