Chapter 3. Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
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Jon Hamilton Lihong Wang creates the sort of medical technology you'd expect to find on the starship Enterprise. Wang, a professor of biomedical engineering at Washington University in St. Louis, has already helped develop instruments that can detect individual cancer cells in the bloodstream and oxygen consumption deep within the body. He has also created a camera that shoots at 100 billion frames a second, fast enough to freeze an object traveling at the speed of light. "It's really about turning some of these ideas that we thought were science fiction into fact," says Richard Conroy, who directs the Division of Applied Science & Technology at the National Institute of Biomedical Imaging and Bioengineering. Wang's ultimate goal is to use a combination of light and sound to solve the mysteries of the human brain. The brain is a "magical black box we still don't understand," he says. Wang describes himself as a toolmaker. And when President Obama unveiled his BRAIN initiative a couple of years ago to accelerate efforts to understand how we think and learn and remember, Wang realized that brain researchers really needed a tool he'd been working on for years. "We want to conquer the brain," Wang says. "But even for a mouse brain, which is only a few millimeters thick, we really don't have a technique that allows us to see throughout the whole brain." Current brain-imaging techniques such as functional MRI or PET scans all have drawbacks. They're slow, or not sharp enough, or they can only see things near the surface. So Wang has been developing another approach, one he believes will be fast enough to monitor brain activity in real time and sharp enough to reveal an individual brain cell. © 2015 NPR
Keyword: Brain imaging
Link ID: 21226 - Posted: 07.27.2015
A study showed that scientists can wirelessly determine the path a mouse walks with a press of a button. Researchers at the Washington University School of Medicine, St. Louis, and University of Illinois, Urbana-Champaign, created a remote controlled, next-generation tissue implant that allows neuroscientists to inject drugs and shine lights on neurons deep inside the brains of mice. The revolutionary device is described online in the journal Cell. Its development was partially funded by the National Institutes of Health. “It unplugs a world of possibilities for scientists to learn how brain circuits work in a more natural setting.” said Michael R. Bruchas, Ph.D., associate professor of anesthesiology and neurobiology at Washington University School of Medicine and a senior author of the study. The Bruchas lab studies circuits that control a variety of disorders including stress, depression, addiction, and pain. Typically, scientists who study these circuits have to choose between injecting drugs through bulky metal tubes and delivering lights through fiber optic cables. Both options require surgery that can damage parts of the brain and introduce experimental conditions that hinder animals’ natural movements. To address these issues, Jae-Woong Jeong, Ph.D., a bioengineer formerly at the University of Illinois at Urbana-Champaign, worked with Jordan G. McCall, Ph.D., a graduate student in the Bruchas lab, to construct a remote controlled, optofluidic implant. The device is made out of soft materials that are a tenth the diameter of a human hair and can simultaneously deliver drugs and lights.
Keyword: Brain imaging
Link ID: 21184 - Posted: 07.18.2015
By Chris Foxx Technology reporter Twitter has responded to an epilepsy charity that said two of its online adverts were "irresponsible". The social media giant had uploaded two short videos on Vine that featured a looping, rapid succession of flashing colours. "Twitter's ads were dangerous to people living with photo-sensitive epilepsy," said Epilepsy Action's deputy chief executive, Simon Wigglesworth. Twitter told the BBC it had removed the videos on Friday morning. Around one in 3,500 people in the UK has photosensitive epilepsy, according to Epilepsy Action. Seizures can be triggered by flashing lights and bold patterns. An episode of Japanese cartoon Pokemon was famously blamed for triggering convulsions in 1997. "Eighty seven people are diagnosed with epilepsy every day and that first seizure can often come out of nowhere," said Mr Wigglesworth. "For a huge corporation like Twitter to take that risk was irresponsible." The Advertising Standards Authority told the BBC that "marketing communications", even those uploaded on a company's own website, should not include "visual effects or techniques that are likely to adversely affect members of the public with photosensitive epilepsy". It said both online and broadcast adverts in the UK had to adhere to rules made by the Committees of Advertising Practice. "We take very seriously ads in online media that might cause harm to people with photosensitive epilepsy," an ASA spokeswoman told the BBC. Twitter's flashing Vine videos were online for 18 hours before the company removed them. © 2015 BBC
By Ariel Sabar In televised remarks from the East Room of the White House on April 2, 2013, President Obama unveiled a scientific mission as grand as the Apollo program. The goal wasn’t outer space, but a frontier every bit as bewitching: the human brain. Obama challenged the nation’s “most imaginative and effective researchers” to map in real time the flickerings of all 100 billion nerve cells in the brain of a living person, a voyage deep into the neural cosmos never attempted at so fine a scale. A panoramic view of electric pulses pinballing across the brain could lead to major new understandings of how we think, remember and learn, and how ills from autism to Alzheimer’s rewire our mental circuitry. “We have a chance to improve the lives of not just millions,” the president said, “but billions of people on this planet.” The next month, six miles from the White House, a Harvard professor named Florian Engert grabbed a mic and, in front of the nation’s top neuroscientists, declared Obama’s effort essentially futile. “We have those data now,” said Engert, who, in a room full of professorial blazers and cardigans, was wearing a muscle shirt that afforded ample views of his bulging biceps. “We discovered they’re actually not all that useful.” (“I think whole-brain imaging is just a bunch of bull----,” is how he put it to me later.) To the other researchers, he must have sounded like a traitor. Engert, who is 48, was basically the first person on the planet to observe a brain in the wall-to-wall way Obama envisioned. He and his colleagues had done it with a sci-fi-worthy experiment that recorded every blip of brain activity in a transparent baby zebrafish, a landmark feat published just a year earlier in the marquee scientific journal Nature. For Engert to suggest that the president’s brain quest was bunk was a bit like John Glenn returning from orbit and telling JFK not to bother with a lunar landing.
Keyword: Brain imaging
Link ID: 21119 - Posted: 07.02.2015
By GARY MARCUS SCIENCE has a poor track record when it comes to comparing our brains to the technology of the day. Descartes thought that the brain was a kind of hydraulic pump, propelling the spirits of the nervous system through the body. Freud compared the brain to a steam engine. The neuroscientist Karl Pribram likened it to a holographic storage device. Many neuroscientists today would add to this list of failed comparisons the idea that the brain is a computer — just another analogy without a lot of substance. Some of them actively deny that there is much useful in the idea; most simply ignore it. Often, when scientists resist the idea of the brain as a computer, they have a particular target in mind, which you might call the serial, stored-program machine. Here, a program (or “app”) is loaded into a computer’s memory, and an algorithm, or recipe, is executed step by step. (Calculate this, then calculate that, then compare what you found in the first step with what you found in the second, etc.) But humans don’t download apps to their brains, the critics note, and the brain’s nerve cells are too slow and variable to be a good match for the transistors and logic gates that we use in modern computers. If the brain is not a serial algorithm-crunching machine, though, what is it? A lot of neuroscientists are inclined to disregard the big picture, focusing instead on understanding narrow, measurable phenomena (like the mechanics of how calcium ions are trafficked through a single neuron), without addressing the larger conceptual question of what it is that the brain does. This approach is misguided. Too many scientists have given up on the computer analogy, and far too little has been offered in its place. In my view, the analogy is due for a rethink. To begin with, all the standard arguments about why the brain might not be a computer are pretty weak. Take the argument that “brains are parallel, but computers are serial.” Critics are right to note that virtually every time a human does anything, many different parts of the brain are engaged; that’s parallel, not serial. © 2015 The New York Times Company
Keyword: Brain imaging
Link ID: 21099 - Posted: 06.27.2015
Elizabeth Gibney A simple injection is now all it takes to wire up a brain. A diverse team of physicists, neuroscientists and chemists has implanted mouse brains with a rolled-up, silky mesh studded with tiny electronic devices, and shown that it unfurls to spy on and stimulate individual neurons. The implant has the potential to unravel the workings of the mammalian brain in unprecedented detail. “I think it’s great, a very creative new approach to the problem of recording from large number of neurons in the brain,” says Rafael Yuste, director of the Neurotechnology Center at Columbia University in New York, who was not involved in the work. If eventually shown to be safe, the soft mesh might even be used in humans to treat conditions such as Parkinson’s disease, says Charles Lieber, a chemist at Harvard University on Cambridge, Massachusetts, who led the team. The work was published in Nature Nanotechnology on 8 June1. Neuroscientists still do not understand how the activities of individual brain cells translate to higher cognitive powers such as perception and emotion. The problem has spurred a hunt for technologies that will allow scientists to study thousands, or ideally millions, of neurons at once, but the use of brain implants is currently limited by several disadvantages. So far, even the best technologies have been composed of relatively rigid electronics that act like sandpaper on delicate neurons. They also struggle to track the same neuron over a long period, because individual cells move when an animal breathes or its heart beats. © 2015 Nature Publishing Group
Keyword: Brain imaging
Link ID: 21034 - Posted: 06.09.2015
by Hal Hodson Electricity is the brain's language, and now we can speak to it without wires or implants. Nanoparticles can be used to stimulate regions of the brain electrically, opening up new ways to treat brain diseases. It may even one day allow the routine exchange of data between computers and the brain. A material discovered in 2004 makes this possible. When "magnetoelectric" nanoparticles (MENs) are stimulated by an external magnetic field, they produce an electric field. If such nanoparticles are placed next to neurons, this electric field should allow them to communicate. To find out, Sakhrat Khizroev of Florida International University in Miami and his team inserted 20 billion of these nanoparticles into the brains of mice. They then switched on a magnetic field, aiming it at the clump of nanoparticles to induce an electric field. An electroencephalogram showed that the region surrounded by nanoparticles lit up, stimulated by this electric field that had been generated. "When MENs are exposed to even an extremely low frequency magnetic field, they generate their own local electric field at the same frequency," says Khizroev. "In turn, the electric field can directly couple to the electric circuitry of the neural network." Khizroev's goal is to build a system that can both image brain activity and precisely target medical treatments at the same time. Since the nanoparticles respond differently to different frequencies of magnetic field, they can be tuned to release drugs. © Copyright Reed Business Information Ltd
Keyword: Brain imaging
Link ID: 21033 - Posted: 06.09.2015
By Esther Hsieh Imagine you are enjoying your golden years, driving to your daily appointment for some painless brain zapping that is helping to stave off memory loss. That's the hope of a new study, in which people who learned associations (such as a random word and an image) after transcranial magnetic stimulation (TMS) were better able to learn more pairings days and weeks later—with no further stimulation needed. TMS uses a magnetic coil placed on the head to increase electrical signaling a few centimeters into the brain. Past studies have found that TMS can boost cognition and memory during stimulation, but this is the first to show that such gains can last even after the TMS regimen is completed. In the new study, which was published in Science, neuroscientists first used brain imaging to identify the associative memory network of 16 young, healthy participants. This network, based around the hippocampus, glues together things such as sights, places, sounds and time to form a memory, explains neuroscientist Joel Voss of Northwestern University, a senior author of the paper. Next, the researchers applied TMS behind the left ear of each participant for 20 minutes for five consecutive days to stimulate this memory network. To see if participants' associative memory improved, one day after the stimulation regimen finished they were tested for their ability to learn random words paired with faces. Subjects who had had TMS performed 33 percent better, compared with those who received placebo treatments, such as sham stimulation. © 2015 Scientific American
Richard Harris American medicine is heading into new terrain, a place where a year's supply of drugs can come with a price tag that exceeds what an average family earns. Pharmacy benefit manager Express Scripts says last year more than half a million Americans racked up prescription drug bills exceeding $50,000. Barbara Haedtke of Portland, Ore., knows this all too well. When she was diagnosed with multiple sclerosis in 2001 at the age of 35, she was prescribed Avonex, at a cost of around $10,000 a year. Her health insurance paid most of that until she and her husband found themselves without jobs during an economic downturn. "We were in the hole, and so $10,000 was a lot of money," she says. "Under the best circumstances it's a lot of money, but then particularly it was really difficult." Barbara Haedtke says she's grateful for a drug-company program that helps cover copays, but doesn't know how long she'll get that benefit. The drug company gave her the medication at no charge until she once again had a job with insurance, and for that, she says, she's really grateful. But the story doesn't end there. Haedtke used Avonex for about a decade and watched with disbelief as the price more than tripled. She's now taking a new drug, Tecfidera, that's priced even higher — $66,000 a year, according to her pharmacy receipt. The drug is supposed to help reduce the number of episodes that characterize multiple sclerosis, a disease in which nerve fibers gradually degenerate, causing muscle weakness, numbness, loss of balance and even paralysis. © 2015 NPR
Nick Davis Mood disorders such as depression are devastating to sufferers, and hugely costly to treat. The most severe form of depression, often called clinical depression or major depressive disorder (MDD), increases the person’s likelihood of suicide and contributes significantly to a person’s disability-adjusted life years (DALYs), a measure of quality of life taking into account periods of incapacity. The healthcare burden of MDD is large in most countries, especially when the person requires a stay in hospital. Putting these factors together, it’s clear we need to develop effective treatments to combat depression. The mechanisms of depressive disorders are not well understood, and it seems likely that there is no single cause. Most modern therapies use drugs that target neurotransmitters – the chemicals that carry signals between neurons. For example, the class of drugs known as SSRIs, or selective serotonin reuptake inhibitors, prevent the neurotransmitter serotonin from being reabsorbed by a neuron; this means that more serotonin is available to wash around between the nerve cells, and is more likely to activate cells in the brain networks that area affected in MDD. But SSRIs and other drugs are not a pharmacological ‘free lunch’. Drug treatments for depression are ineffective for many people, cause side-effects, and may lose their therapeutic effect over time. For these reasons, many researchers are searching for alternative treatments for MDD that overcome these problems, and are more effective or less unpleasant. One potential treatment involves the use of pulses of magnetic energy over the head to target the brain’s mood circuits. This technique, called transcranial magnetic stimulation (TMS), may potentially address some of the problems of pharmaceutical treatments, but we still don’t know exactly how it works, or how effective it will be in treating MDD. © 2015 Guardian News and Media Limited
Link ID: 20946 - Posted: 05.18.2015
Backyard Brains. For 235 years we have been trying to isolate, understand, and analyze the elusive action potential, and here we tell the story that continues today. The progress of understanding Action Potentials can be classed into three main endeavors: 1. Amplification The amplifiers that gave us the first hint of the electrical impulses generated by neurons came from biological tissue itself! Scientists of the 18th and early 19th century used the contractions of muscles as "bioamplifiers" to indirectly measure neural firing. Using friction machines (spark generators), Leyden jars (primitive capacitors), or Voltaic Piles (the first batteries), electrical stimuli could be delivered to motor neurons that were still attached to muscles. The electrical stimulation would cause the nerve to fire action potentials (so people hypothesized), the muscle would then contract, and the force of contraction could be measured with a spring. With increasing electrical stimuli strength (thus more action potentials in the motor neurons), the muscle would contract with increasing force. This technique worked, but led to vigorous debates as to whether the neural tissue was actually generating its own action potentials at all, or whether the muscle contraction was just a direct result of electrical stimulation. By the mid-19th century, galvanometers had been invented, and it was possible to see that nerves were indeed generating their own action potentials. These galvanometers exploited the then new technology of electromagnets. For example, Emil de Bois-Reymond built by hand a type of galvanometer with 24,000 turns around an iron plate. When the nerve fired action potentials, a metal needle suspended by the plate would deflect. These devices worked, but the needle movement was not fast enough to separate the 1 ms individual action potentials, and the machines occupied a lot of time to construct. © 2009-2015 Backyard Brains
Link ID: 20944 - Posted: 05.18.2015
By GREGORY HICKOK IN 1890, the American psychologist William James famously likened our conscious experience to the flow of a stream. “A ‘river’ or a ‘stream’ are the metaphors by which it is most naturally described,” he wrote. “In talking of it hereafter, let’s call it the stream of thought, consciousness, or subjective life.” While there is no disputing the aptness of this metaphor in capturing our subjective experience of the world, recent research has shown that the “stream” of consciousness is, in fact, an illusion. We actually perceive the world in rhythmic pulses rather than as a continuous flow. Some of the first hints of this new understanding came as early as the 1920s, when physiologists discovered brain waves: rhythmic electrical currents measurable on the surface of the scalp by means of electroencephalography. Subsequent research cataloged a spectrum of such rhythms (alpha waves, delta waves and so on) that correlated with various mental states, such as calm alertness and deep sleep. Researchers also found that the properties of these rhythms varied with perceptual or cognitive events. The phase and amplitude of your brain waves, for example, might change if you saw or heard something, or if you increased your concentration on something, or if you shifted your attention. But those early discoveries themselves did not change scientific thinking about the stream-like nature of conscious perception. Instead, brain waves were largely viewed as a tool for indexing mental experience, much like the waves that a ship generates in the water can be used to index the ship’s size and motion (e.g., the bigger the waves, the bigger the ship). Recently, however, scientists have flipped this thinking on its head. We are exploring the possibility that brain rhythms are not merely a reflection of mental activity but a cause of it, helping shape perception, movement, memory and even consciousness itself. What this means is that the brain samples the world in rhythmic pulses, perhaps even discrete time chunks, much like the individual frames of a movie. From the brain’s perspective, experience is not continuous but quantized. © 2015 The New York Times Company
By Kira Peikoff I draw an uneasy breath as I step into a bright purple office on the 14th floor of Boston’s Prudential Building. I am shown to a small conference table, where I take a seat and await the experiment. A palm-size triangular module is affixed above my right eye. It connects to a single-use strip of electrodes stuck onto my forehead and running down the back of my neck. This is Thync, the latest in transcranial direct current stimulation, or tDCS. The manufacturer says the device, to come out later this year, can alter the user’s mood in minutes via electric current. With a connected smartphone app, the mood-impaired subject chooses one of two settings: “calm vibes” or “energy vibes.” I tap “calm vibes” and wait. Somehow, I am having a hard time picturing myself unwinding at home this way while my husband sips a glass of Merlot. Thync is the latest in a wave of wearable gadgets offering so-called noninvasive brain stimulation. Until recently, it was mostly hobbyists — nine-volt batteries stuck to their heads — who experimented with tDCS as a means of improving concentration, verbal and computation abilities, and creativity. But in the last few years, several companies have introduced slick consumer devices, among them Foc.us, whose headset and controller cost $298, and The Brain Stimulator, whose advanced starter kit costs $150. In January, the journal Brain Stimulation published the largest meta-analysis of tDCS to date. After examining every finding replicated by at least two research groups, leading to 59 analyses, the authors reported that one session of tDCS failed to show any significant benefit for users. © 2015 The New York Times Company
Link ID: 20891 - Posted: 05.05.2015
By Ashley Yeager The image is made using Brainbow, a technique developed in 2007 that inserts genes for fluorescent proteins into animals. When activated, the proteins illuminate some cells in a range of colors. While most researchers use Brainbow to visualize connections between nerve cells in the brain, Alain Chédotal of the Institut de la Vision in Paris and colleagues customized the technique to trace networks of cells called oligodendrocytes. These cells wrap a material called myelin, the biological equivalent of electrical insulation, around long strands of nerve cells that transmit electrical signals in the brain and throughout the body. How oligodendrocytes work together to wrap nerve fibers in myelin becomes evident in Brainbow photos of the roughly 3-millimeter-long optic nerve, the team reports in the April Glia. The myelin shields the precious link between brain and eyes. Studying interactions among oligodendrocytes as well as the cells’ reactions to various drugs may lead to improved therapies for multiple sclerosis, a disease caused by the destruction of myelin. Citations L. Dumas et al. Multicolor analysis of oligodendrocyte morphology, interactions, and development with Brainbow. Glia. Vol. 63, April 2015, p. 699. doi: 10.1002/glia.22779 © Society for Science & the Public 2000 - 2015.
By REUTERS NEW YORK — The mouse walked, the mouse stopped; the mouse ignored a bowl of food, then scampered back and gobbled it up, and it was all controlled by neuroscientists, researchers reported on Thursday. The study, describing a way to manipulate a lab animal's brain circuitry accurately enough to turn behaviors both on and off, is the first to be published under President Barack Obama's 2013 BRAIN Initiative, which aims to advance neuroscience and develop therapies for brain disorders. The point of the remote-control mouse is not to create an army of robo-rodents. Instead, neuroscientists hope to perfect a technique for identifying brain wiring underlying any behavior, and control that behavior by activating and deactivating neurons. If scientists are able do that for the circuitry involved in psychiatric or neurological disorders, it may lead to therapies. That approach reflects a shift away from linking such illnesses to "chemical imbalances" in the brain, instead tracing them to miswiring and misfiring in neuronal circuits. "This tool sharpens the cutting edge of research aimed at improving our understanding of brain circuit disorders, such as schizophrenia and addictive behaviors," said Dr. Francis Collins, director of the National Institutes of Health, which funded the $1 million study. The technique used to control neurons is called DREADDs (designer receptors exclusively activated by designer drugs). Brain neurons are genetically engineered to produce a custom-made - "designer" - receptor. When the receptor gathers in a manmade molecule that fits like a key in a lock, the neuron is activated. © 2015 The New York Times Company
Keyword: Brain imaging
Link ID: 20881 - Posted: 05.04.2015
By Emily DeMarco Mice and rats communicate in the ultrasonic frequency range, and it’s thought that cats evolved the ability to hear those high-pitched squeaks to better hunt their prey. Now, a new study suggests that sensitivity to higher pitched sounds may cause seizures in some older cats. After receiving reports of the problem, nicknamed the “Tom and Jerry syndrome” because of how the cartoon cat is often startled by sounds, researchers surveyed cat owners and examined their pets’ medical records, looking for insight into the types and durations of seizures and the sounds that provoked them. In 96 cats, they found evidence of the syndrome they call feline audiogenic reflex seizures. The most common types of seizure-eliciting sounds included crinkling tinfoil, clanking a metal spoon on a ceramic feeding bowl, and clinking glass. The severity of the seizure ranged from brief muscle jerks to more serious episodes where the cat lost consciousness and stiffened and jerked for several minutes, the researchers report online today in the Journal of Feline Medicine and Surgery. Both pedigree and nonpedigree cats were susceptible, although one breed was common: Thirty of the 96 cats were Birmans (pictured). Because the seizures coincided with old age—the average age of onset was 15 years—veterinarians could miss the disorder while dealing with the felines’ other health issues, the researchers say. Minimizing exposure to the problematic sounds and preliminary, therapeutic trials with levetiracetam—an anticonvulsant medication used to control epilepsy—among a small sample of the cats seemed to help limit the occurrence of seizures. © 2015 American Association for the Advancement of Science.
Jon Hamilton The simple act of thinking can accelerate the growth of many brain tumors. That's the conclusion of a paper in Cell published Thursday that showed how activity in the cerebral cortex affected high-grade gliomas, which represent about 80 percent of all malignant brain tumors in people. "This tumor is utilizing the core function of the brain, thinking, to promote its own growth," says Michelle Monje, a researcher and neurologist at Stanford who is the paper's senior author. In theory, doctors could slow the growth of these tumors by using sedatives or other drugs to reduce mental activity, Monje says. But that's not a viable option because it wouldn't eliminate the tumor and "we don't want to stop people with brain tumors from thinking or learning or being active." Even so, the discovery suggests other ways to slow down some of the most difficult brain tumors, says Tracy Batchelor, who directs the neuro-oncology program at Massachusetts General Hospital and was not involved in the research. "We really don't have any curative treatments for high-grade gliomas," Batchelor says. The discovery of a link between tumor growth and brain activity "has opened up a window into potential therapeutic interventions," he says. The discovery came from a team of scientists who studied human glioma tumors implanted in mouse brains. The scientists used a technique called optogenetics, which uses light to control brain cells, to increase the activity of cells near the tumors. © 2015 NPR
Link ID: 20846 - Posted: 04.25.2015
By Antonio Regalado Various powerful new tools for exploring and manipulating the brain have been developed over the last few years. Some use electronics, while others use light or chemicals. At one MIT lab, materials scientist Polina Anikeeva has hit on a way to manufacture what amounts to a brain-science Swiss Army knife. The neural probes she builds carry light while collecting and transmitting electricity, and they also have tiny channels through which to pump drugs. That’s an advance over metal wires or silicon electrodes conventionally used to study neurons. Anikeeva makes the probes by assembling polymers and metals into large-scale blocks, or preforms, and then stretching them into flexible, ultrathin fibers. Multifunctional fibers offer new ways to study animal behavior, since they can record from neurons as well as stimulating them. New types of medical technology could also result. Imagine, as Anikeeva does, bionic wiring that bridges a spinal-cord injury, collecting electrical signals from the brain and transmitting them to the muscles of a paralyzed hand. Anikeeva made her first multifunctional probe while studying at Stanford. It was crude: she simply wrapped metal wires around a glass filament. But this made it possible to combine standard electrode measurements with a new technology, optogenetics, in which light is fired at neurons to activate them or shut them down.
Keyword: Brain imaging
Link ID: 20832 - Posted: 04.22.2015
Heidi Ledford An experimental antibody drug aimed at protecting nerves from the ravages of multiple sclerosis offers hope for a new way to combat the neurological disease — if researchers can definitively show that it works. The antibody, anti-LINGO-1, is intended to stimulate regrowth of the myelin sheath, the fatty protective covering on nerve cells that is damaged by multiple sclerosis. Its developer, Biogen of Cambridge, Massachusetts, will present results from a small clinical trial at an American Academy of Neurology meeting this week in Washington DC. If the initial promising results from the trial are confirmed, it will be the first such myelin-regeneration therapy. Other researchers are racing to find more targets and compounds that act similarly. “Once we get a positive result, the field will move very quickly,” says Jack Antel, a neurologist at McGill University in Montreal, Canada. But that excitement is tempered by practical hurdles: there is as yet no proven way to measure remyelination of nerve cells in living humans. Myelin sheaths insulate and support axons, the fibres that transmit signals between nerve cells. In multiple sclerosis, immune attack destroys these sheaths. Stripped of this protective coating, the axons gradually wither away, causing the numbness and muscle spasms that are characteristic of the disease. The 12 drugs approved in the United States to treat multiple sclerosis slow this immune attack — although sometimes with dangerous side effects. But none stops it, says Bruce Trapp, a neuroscientist at the Cleveland Clinic in Ohio. © 2015 Nature Publishing Group
Two drugs already on the market — an antifungal and a steroid — may potentially take on new roles as treatments for multiple sclerosis. According to a study published in Nature today, researchers discovered that these drugs may activate stem cells in the brain to stimulate myelin producing cells and repair white matter, which is damaged in multiple sclerosis. The study was partially funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health. Specialized cells called oligodendrocytes lay down multiple layers of a fatty white substance known as myelin around axons, the long “wires” that connect brain cells. Myelin acts as an insulator and enables fast communication between brain cells. In multiple sclerosis there is breakdown of myelin and this deterioration leads to muscle weakness, numbness and problems with vision, coordination and balance. “To replace damaged cells, the scientific field has focused on direct transplantation of stem cell-derived tissues for regenerative medicine, and that approach is likely to provide enormous benefit down the road. We asked if we could find a faster and less invasive approach by using drugs to activate native nervous system stem cells and direct them to form new myelin. Our ultimate goal was to enhance the body’s ability to repair itself,” said Paul J. Tesar, Ph.D., associate professor at Case Western Reserve School of Medicine in Cleveland, and senior author of the study. It is unknown how myelin-producing cells are damaged, but research suggests they may be targeted by malfunctioning immune cells and that multiple sclerosis may start as an autoimmune disorder. Current therapies for multiple sclerosis include anti-inflammatory drugs, which help prevent the episodic relapses common in multiple sclerosis, but are less effective at preventing long-term disability. Scientists believe that therapies that promote myelin repair might improve neurologic disability in people with multiple sclerosis.