Chapter 3. Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
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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
By ABIGAIL ZUGER, M.D. Like creatures battling undersea, pro-life and right-to-die forces are locked in mortal but only intermittently visible combat. The last prominent battle ended almost seven years ago, after the death of Terri Schiavo, the Florida woman with brain damage whose feeding tube was removed by court order in the spring of 2005. Since then, all has been quiet on the surface, belying the continuing turmoil in hospitals and courtrooms over what, exactly, marks the end of life. Invariably, the louder the background tumult, the more useful is the quiet, dispassionate narrative. And so one turns to Dick Teresi’s new book with considerable hope: Surely Mr. Teresi, a veteran science journalist, past editor in chief of Science Digest and Omni, will be the ideal guide through those dim purgatories where life and death can be difficult to distinguish. All starts out promisingly enough. An indefatigable researcher and fluid writer, Mr. Teresi provides a good long riff on death past and present, from the Egyptian mummies, dehydrated into “the deadest people on the planet,” to the ever-hopeful terminally ill of our own age, still flossing their teeth and eating healthy meals in hospice care. Mr. Teresi points out that conclusive signs of death have always been subject to debate. All the great civilizations argued about them, with various expert commentators proposing various fail-safe criteria and yet (Mr. Teresi notes with some pleasure) specifying that they themselves should be left unburied for a few days just to avoid any unfortunate mistakes. © 2012 The New York Times Company
Link ID: 16578 - Posted: 03.27.2012
By ABIGAIL ZUGER, M.D. Just when it seems long past time for the age of memoir to be over — just when it seems impossible that any ailing person with literary inclinations could find anything new to say about illness, and the list of not-to-be-missed “patients are people too” books should be closed and locked — yet another book comes along. And despite all the above, no one with even a passing interest in the experience of illness should miss Robert C. Samuels’s “Blue Water, White Water,” a memoir drafted about 30 years ago and published without fanfare a few months ago; it stands head and shoulders above the crowd. The details are slightly obsolete, to be sure: Mr. Samuels endured his many months of dire illness tethered to a respirator back in the 1980s, the Stone Age of modern intensive-care treatment. Nonetheless, his story from the wrong end of the tubes is timeless; the technology may evolve briskly, but the experience changes glacially, if at all. A former beat reporter for The New York World-Telegram & Sun, Mr. Samuels covers his own story like a pro. He was healthy, 44, just returned from a trip around the world in December 1981, when he got out of bed one morning with a weak left leg. He wandered into the local emergency room half convinced he was imagining things. By the next day he was completely paralyzed with a respirator breathing for him: Guillain-Barré syndrome, an autoimmune disease, was rapidly and efficiently stripping his motor nerves of their myelin sheathing, short-circuiting them all. Only his eyes still moved a little, from left to right. Nothing was wrong with his brain. © 2012 The New York Times Company
By NICHOLAS BAKALAR Surgery for epilepsy is usually seen as a last resort for patients when medications do not work, and it is often delayed for many years after the failure of drug treatment. Now a randomized, controlled trial suggests that surgery as soon as possible after the failure of two antiepileptic drugs is a significantly better approach than continued medical care. Previous studies have shown that patients referred for surgery have had epilepsy for an average of 22 years, and are referred on average more than 10 years after the use of two drugs has failed to stop the seizures. People with continued seizures are at increased risk for drowning and other accidents, depression, progressive loss of memory, and, in younger people, a failure to develop vocational and social skills. Their risk of death is 10 times as high as that of the general population. Researchers studied a group of 38 epilepsy patients, randomly assigning 15 to brain surgery and 23 to continued medical treatment. The surgery involves the removal of a piece of tissue about the size of a walnut from the temporal lobe, the part of the brain just above the ear. The surgery has been performed for many years, but the institution of high-resolution M.R.I. and microsurgical techniques have greatly improved its safety and efficacy. The patients in both groups were similar in age, duration of epilepsy, the number of antiepileptic drugs used and the number of seizures they had had. All had been taking drugs for one to two years without relief. The participants were seen at the study site every three months for two years after the start of the study. A group of specialists who did not know which patients had had surgery evaluated them for seizure type and severity as recorded in patient diaries. The study appears in the March 7 issue of The Journal of the American Medical Association. © 2012 The New York Times Company
Link ID: 16507 - Posted: 03.13.2012
Greg Gage is on a mission to get kids excited about neuroscience by helping them understand how the brain works — in ways that are extremely memorable. He sells $100 kits that teach how neurons work by putting electricity through cockroach limbs and living cockroaches. One of the most amazing and unexpected experiences I had at the TED conference a couple weeks ago was getting to do one of Gage’s experiments myself. I tracked him down after reading that he was one of 25 invited TED fellows, and before I knew it, I was in a random hallway in the bowels of the convention center, wrestling a squirmy cockroach into my own experiment. First, Gage had me anesthetize a cockroach by dousing it in a glass of ice water, then sever one of its legs (they grow back), plug in a couple of electrodes, and then listen and watch neurons through an app on his iPad. There’s actually a really great video of this same experiment, taken from when Gage performed it for an audience of kids. TED just released it today, as part of its new education initiative. In the video, Gage shows how the living neurons in the cockroach leg can be pulsed with bass from music, and then brings out a live beatboxer on stage to show the cockroach leg dancing to the beat. Read that last sentence again, or just watch the video. It’s pretty crazy. © 2005-2012 Dow Jones & Company Inc.
Link ID: 16503 - Posted: 03.13.2012
Hundreds of Canadian MS patients have gone out of country for a controversial neck vein treatment in recent years. Hundreds of Canadian MS patients have gone out of country for a controversial neck vein treatment in recent years. (CBC) Saskatchewan multiple sclerosis patients hoping to take part in a clinical trial of a controversial treatment may soon get a call from the ministry of health. But only around 10 per cent of those who applied will actually get that call. Deb Jordan, a ministry spokeswoman, said 670 people had signed up as of Thursday, just ahead of the Friday midnight deadline for applications to be part of a two-year, double-blind trial of what has been dubbed liberation therapy. Jordan said patient names will be randomly drawn to determine who will fill 86 spots in the test, which will take place in Albany, N.Y. A successful candidate must be a Saskatchewan resident, under the age of 60 and not had liberation treatment. "Once we verify that information, then the applicant will be forwarded to the folks who are involved in the clinical trial," said Jordan. "I want to also emphasize that the fact that a patient may be drawn does not necessarily mean that they will move on to the clinical trial. © CBC 2012
M. Mitchell Waldrop It wasn't quite the lynching that Henry Markram had expected. But the barrage of sceptical comments from his fellow neuroscientists — “It's crap,” said one — definitely made the day feel like a tribunal. Officially, the Swiss Academy of Sciences meeting in Bern on 20 January was an overview of large-scale computer modelling in neuroscience. Unofficially, it was neuroscientists' first real chance to get answers about Markram's controversial proposal for the Human Brain Project (HBP) — an effort to build a supercomputer simulation that integrates everything known about the human brain, from the structures of ion channels in neural cell membranes up to mechanisms behind conscious decision-making. Markram, a South-African-born brain electrophysiologist who joined the Swiss Federal Institute of Technology in Lausanne (EPFL) a decade ago, may soon see his ambition fulfilled. The project is one of six finalists vying to win €1 billion (US$1.3 billion) as one of the European Union's two new decade-long Flagship initiatives. “Brain researchers are generating 60,000 papers per year,” said Markram as he explained the concept in Bern. “They're all beautiful, fantastic studies — but all focused on their one little corner: this molecule, this brain region, this function, this map.” The HBP would integrate these discoveries, he said, and create models to explore how neural circuits are organized, and how they give rise to behaviour and cognition — among the deepest mysteries in neuroscience. Ultimately, said Markram, the HBP would even help researchers to grapple with disorders such as Alzheimer's disease. “If we don't have an integrated view, we won't understand these diseases,” he declared. © 2012 Nature Publishing Group
Link ID: 16416 - Posted: 02.23.2012
By Laura Sanders Sleep deprivation makes the brain groggy, but as waking hours mount nerve cells grow increasingly jumpy, a new study shows. This amped-up state may explain why seizures and hallucinations can accompany an all-nighter. More generally, the results help clarify what goes wrong in a brain deprived of shut-eye. “It’s an important finding,” says neuroscientist Christopher Colwell of UCLA. “Sleep deprivation is an area of huge interest because most of us do not get enough sleep.” By subjecting six people to a night of sleep deprivation and measuring their brain responses, Marcello Massimini of the University of Milan and colleagues found that people’s brains become more reactive as hours awake accumulate. To look for signs of altered brain function, the team delivered a jolt of magnetic current to the participants’ skulls that kicked off an electrical response in the nerve cells (an effect like the noise made when a hammer strikes a bell). With electrodes on the scalp, the team measured the strength of this electrical response in the frontal cortex, a brain region that’s involved in making executive decisions. After a night of sleep deprivation, participants’ electrical responses were stronger than they were the previous day, the scientists report online February 7 in Cerebral Cortex. This overreaction disappeared after a night’s sleep. The results offer support for a theory of why people sleep: During waking hours, the brain accumulates connections between nerve cells as new things are learned. Sleep, the theory says, sweeps the brain of extraneous clutter, leaving behind only the most important connections. © Society for Science & the Public 2000 - 2012
by Catherine de Lange In an unlikely marriage of quantum physics and neuroscience, tiny particles called quantum dots have been used to control brain cells for the first time. Having such control over the brain could one day provide a non-invasive treatment for conditions such as Alzheimer's disease, depression and epilepsy. In the nearer term, quantum dots could be used to treat blindness by reactivating damaged retinal cells. "Many brain disorders are caused by imbalanced neural activity," says Lih Lin at the University of Washington, Seattle. "Manipulation of specific neurons could permit the restoration of normal activity levels." Methods to stimulate the brain artificially already exist, though each has its drawbacks. Deep brain stimulation is used in Parkinson's disease to trigger brain cell activity and prevent the abnormal signalling that causes debilitating tremors, but placing the electrodes required is highly invasive. Transcranial magnetic stimulation can stimulate brain cells from outside the head, but is not highly targeted and so affects large areas of the brain at once. Researchers in optogenetics can control genetically modified brain cells using light but because of these modifications, the technique is not yet deemed safe to use in humans. Lin's team has now come up with an alternative using quantum dots – light-sensitive, semiconducting particles just a few nanometres in diameter. © Copyright Reed Business Information Ltd.
Link ID: 16382 - Posted: 02.16.2012