Chapter 3. Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
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By Diana Kwon Stories of cannabis’s abilities to alleviate seizures have been around for about 150 years but interest in medical marijuana has increased sharply in the last decade with the help of legalization campaigns. Credit: ©iStock Charlotte Figi, an eight-year-old girl from Colorado with Dravet syndrome, a rare and debilitating form of epilepsy, came into the public eye in 2013 when news broke that medical marijuana was able to do what other drugs could not: dramatically reduce her seizures. Now, new scientific research provides evidence that cannabis may be an effective treatment for a third of epilepsy patients who, like Charlotte, have a treatment-resistant form of the disease. Last month Orrin Devinsky, a neurologist at New York University Langone Medical Center, and his colleagues across multiple research centers published the results from the largest study to date of a cannabis-based drug for treatment-resistant epilepsy in The Lancet Neurology. The researchers treated 162 patients with an extract of 99 percent cannabidiol (CBD), a nonpsychoactive chemical in marijuana, and monitored them for 12 weeks. This treatment was given as an add-on to the patients’ existing medications and the trial was open-label (everyone knew what they were getting). The researchers reported the intervention reduced motor seizures at a rate similar to existing drugs (a median of 36.5 percent) and 2 percent of patients became completely seizure free. Additionally, 79 percent of patients reported adverse effects such as sleepiness, diarrhea and fatigue, although only 3 percent dropped out of the study due to adverse events. “I was a little surprised that the overall number of side effects was quite high but it seems like most of them were not enough that the patients had to come off the medication,” says Kevin Chapman, a neurology and pediatric professor at the University of Colorado School of Medicine who was not involved in the study. “I think that [this study] provides some good data to show that it's relatively safe—the adverse effects were mostly mild and [although] there were serious adverse effects, it's always hard to know in such a refractory population whether that would have occurred anyway.” © 2016 Scientific American,
Finding out what’s going on in an injured brain can involve several rounds of surgery, exposed wounds and a mess of wires. Perhaps not for much longer. A device the size of a grain of rice can monitor the brain’s temperature and pressure before dissolving without a trace. “This fully degradable sensor is definitely an impressive feat of engineering,” says Frederik Claeyssens, a biomaterials scientist at the University of Sheffield, UK. The device is the latest creation from John Rogers’s lab at the University of Illinois at Urbana-Champaign. They came up with the idea of a miniature dissolvable brain monitor after speaking to neurosurgeons about the difficulties of monitoring brain temperature and pressure in people with traumatic injuries. Unwieldy wires These vital signs are currently measured via an implanted sensor connected to an external monitor. “It works, but the wires coming out of the head limit physical movement and provide a nidus for infection. You can cause additional damage when you pull them out,” says Rogers. It would be better to use a wireless device that doesn’t need to be extracted, he says. So Rogers’s team developed an electronic monitor about a tenth of a millimetre wide and a millimetre long made of silicon and a polymer. These materials, used in tiny amounts, are eventually broken down by the body, and don’t trigger any harmful effects, says Rogers. “The materials individually are safe. The total amount is very small. It’s about 1000 times less than what you’d have in a vitamin tablet.” © Copyright Reed Business Information Ltd.
Keyword: Brain imaging
Link ID: 21799 - Posted: 01.19.2016
Fergus Walsh Medical correspondent UK doctors in Sheffield say patients with multiple sclerosis (MS) are showing "remarkable" improvements after receiving a treatment usually used for cancer. About 20 patients have received bone marrow transplants using their own stem cells. Some patients who were paralysed have been able to walk again. Prof Basil Sharrack, of Sheffield's Royal Hallamshire Hospital, said: "To have a treatment which can potentially reverse disability is really a major achievement." Around 100,000 people in the UK have MS, an incurable neurological condition. Most patients are diagnosed in their 20s and 30s. The disease causes the immune system to attack the lining of nerves in the brain and spinal cord. The treatment - known as an autologous haematopoietic stem cell transplant (HSCT) - aims to destroy the faulty immune system using chemotherapy. It is then rebuilt with stem cells harvested from the patient's own blood. These cells are at such an early stage they've not developed the flaws that trigger MS. Prof John Snowden, consultant haematologist at Royal Hallamshire Hospital, said: "The immune system is being reset or rebooted back to a time point before it caused MS." About 20 MS patients have been treated in Sheffield in the past three years. Prof Snowden added: "It's clear we have made a big impact on patients' lives, which is gratifying." In MS the protective layer surrounding nerve fibres in the brain and spinal cord - known as myelin - becomes damaged. The immune system mistakenly attacks the myelin, causing scarring or sclerosis. © 2016 BBC.
By Stephani Sutherland A technique called optogenetics has transformed neuroscience during the past 10 years by allowing researchers to turn specific neurons on and off in experimental animals. By flipping these neural switches, it has provided clues about which brain pathways are involved in diseases like depression and obsessive-compulsive disorder. “Optogenetics is not just a flash in the pan,” says neuroscientist Robert Gereau of Washington University in Saint Louis. “It allows us to do experiments that were not doable before. This is a true game changer like few other techniques in science.” Since the first papers were published on optogenetics in the mid-aughts some researchers have mused about one day using optogenetics in patients, imagining the possibility of an off-switch for depression, for instance. The technique, however, would require that a patient submit to a set of highly invasive medical procedures: genetic engineering of neurons to insert molecular switches to activate or switch off cells, along with threading of an optical fiber into the brain to flip those switches. Spurred on by a set of technical advances, optogenetics pioneer Karl Deisseroth, together with other Stanford University researchers, has formed a company to pursue optogenetics trials in patients within the next several years—one of several start-ups that are now contemplating clinical trials of the technique. Circuit Therapeutics, founded in 2010, is moving forward with specific plans to treat neurological diseases. (It also partners with pharmaceutical companies to help them use optogenetics in animal research to develop novel drug targets for human diseases.) © 2016 Scientific America
Keyword: Pain & Touch
Link ID: 21758 - Posted: 01.07.2016
By Diana Kwon Symptoms come and go in most cases of multiple sclerosis (MS), a chronic disease in which the immune system attacks myelin, the nonconductive sheath that surrounds neurons' axons. Yet 10 to 15 percent of cases are progressive rather than relapsing. This more severe version appears later in life and is marked by steadily worsening symptoms. No treatments are currently available, but that might be about to change. In September pharmaceutical company Hoffmann–La Roche announced positive results from three large clinical trials of ocrelizumab, an injectable antibody medication that targets B cells, for both relapsing and progressive MS. They found that the drug was more effective at treating relapsing MS than interferon beta-1a (Rebif), a top-performing drug now used to treat the disease. Even more exciting, it slowed the advance of symptoms in patients with progressive MS for the entire 12-week duration of the study. “The drug has dramatic effects on relapsing MS, and we finally have our foot in the door with the progressive form,” says Stephen Hauser, a neurologist at the University of California, San Francisco, who was involved in the trials. The fact that ocrelizumab works on both types of MS is a tantalizing clue for scientists trying to understand the root causes of the disease and figure out why the inflammation of the relapsing form eventually turns into progressive degeneration in some patients. “These results give evidence that the inflammatory and the degenerative components of MS are related,” Hauser says. “The big question now is, If we begin treatment really early, can we protect relapsing patients from developing the progressive problems later on?” © 2015 Scientific American
Keyword: Multiple Sclerosis
Link ID: 21724 - Posted: 12.27.2015
When anticonvulsant drugs fail to control epilepsy, surgery can be used as a last resort: removing the part of the brain thought to be the source of someone’s seizures. Unfortunately, this doesn’t always work. A computer model of brain activity could change things for the better by allowing surgeons to more precisely tailor the procedure to the individual. Seizures are caused by sudden surges in electrical activity in the brain. EEG scans made during a seizure can capture what is going on, providing a clue to the part of the brain that needs to be cut out. Even so, the surgery still fails to prevent seizures in 30 per cent of cases. There are other ways to track down the source of someone’s seizures, however. For example, the connectivity of the brain’s neurons and the surface area of affected regions is different in people with epilepsy compared with those who do not have the condition. Frances Hutchings at Newcastle University, UK and her colleagues have shown that these differences can be picked up using a combination of fMRI scans and diffusion tensor imaging (DTI). They used this data to model the brains of 22 people with epilepsy. By simulating the brain’s electrical activity, they were able to see where it went awry and identify the region where seizures were most likely to originate in each individual. © Copyright Reed Business Information Ltd.
Sara Reardon Manipulating brain circuits with light and drugs can cause ripple effects that could muddy experimental results. In the tightly woven networks of the brain, tugging one neuronal thread can unravel numerous circuits. Because of that, the authors of a paper1 published in Nature on 9 December caution that techniques such as optogenetics — activating neurons with light to control brain circuits — and manipulation with drugs could lead researchers to jump to unwarranted conclusions. In work with rats and zebra finches, neuroscientist Bence Ölveczky of Harvard University in Cambridge, Massachusetts, and his team found that stimulating one part of the brain to induce certain behaviours might cause other, unrelated parts to fire simultaneously, and so make it seem as if these circuits are also involved in the behaviour. According to Ölveczky, the experiments suggest that although techniques such as optogenetics may show that a circuit can perform a function, they do not necessarily show that it normally performs that function. “I don’t want to say other studies have been wrong, but there is a danger to overinterpreting,” he says. Ölveczky and his colleagues discovered these discrepancies by chance while studying rats that they had trained to press a lever in a certain pattern. They injected a drug called muscimol, which temporarilty shuts off neurons, into a part of the motor cortex that is involved in paw movement. The animals were no longer able to perform the task, which might be taken as evidence that neurons in this brain region were necessary to its performance. © 2015 Nature Publishing Group
Keyword: Brain imaging
Link ID: 21690 - Posted: 12.10.2015
Angus Chen Parents of children with severe epilepsy have reported incredible recoveries when their children were given cannabidiol, a derivative of marijuana. The drug, a non-psychoactive compound that occurs naturally in cannabis, has been marketed with epithets like Charlotte's Web and Haleigh's Hope. But those parents were taking a risk; there has been no clinical data on cannabidiol's safety of efficacy as an anti-epileptic. This week, doctors are presenting the first studies trying to figure out if cannabidiol actually works. They say the studies' results are promising, but with a grain of salt. The largest study being presented at the American Epilepsy Society meeting in Philadelphia this week was started in 2014 with 313 children from 16 different epilepsy centers around the country. Over the course of the three-month trial, 16 percent of the participants withdrew because the cannabidiol was either ineffective or had adverse side-effects, says Dr. Orrin Devinsky, a neurologist at the New York University Langone Medical Center and lead author on the study. But for the 261 patients that continued taking cannabidiol, the number of convulsive seizures, called grand mal or tonic-clonic seizures, went down by about half on average. Devinsky says that some children continued to experience benefits on cannabidiol after the trial ended. "In the subsequent periods, which are very encouraging, 9 percent of all patients and 13 percent of those with Dravet Syndrome epilepsy were seizure-free. Many have never been seizure-free before," he says. It's one of several [at least four. checking] papers on cannabidiol being presented this week at the American Epilepsy Society meeting in Philadelphia. © 2015 npr
A woman born incapable of feeling pain has been hurt for the first time – thanks to a drug normally prescribed for opioid overdoses. She was burned with a laser, and quite liked the experience. The breakthrough may lead to powerful new ways to treat painful conditions such as arthritis. Only a handful people around the world are born unable to feel pain. These individuals can often suffer a range of injuries when they are young. Babies with the condition tend to chew their fingers, toes and lips until they bleed, and toddlers can suffer an increased range of knocks, tumbles and encounters with sharp or hot objects. The disorder is caused by a rare genetic mutation that results in a lack of ion channels that transport sodium across sensory nerves. Without these channels, known as Nav1.7 channels, nerve cells are unable to communicate pain. Researchers quickly sought to make compounds that blocked Nav1.7 channels, thinking they might be able to block pain in people without the disorder. “It looked like a fantastic drug target,” says John Wood at University College London. “Pharma companies went bananas and made lots of drugs.” But while a few compounds saw some success, none brought about the total pain loss seen in people who lack the channel naturally. © Copyright Reed Business Information Ltd.
Laura Sanders Taking a pregnancy hormone staves off multiple sclerosis relapses, a small clinical trial suggests. The results hint at a potential therapy for women who suffer from MS, a debilitating disease in which the body’s immune system attacks the insulation that wraps around nerve cell fibers. A curious observation kicked off this line of research: Pregnancy offers a temporary reprieve for women with MS. Since that discovery, in the 1990s, scientists have been testing whether certain pregnancy hormones might combat MS in women who aren’t pregnant. In addition to a standard MS drug, 164 women with MS received either a placebo or estriol, an estrogen made by the placenta that peaks toward the end of pregnancy. After two years, women who received estriol had an average of 0.25 relapses a year, while women who received the placebo had 0.37 relapses a year, UCLA neurologist Rhonda Voskuhl and colleagues write online November 24 in Lancet Neurology. Researchers don’t know whether estriol would have similar effects in men with MS. The results warrant a larger clinical trial, the authors say. An accompanying commentary in the same issue of Lancet Neurology questions the results, though. MS specialist Annette Langer-Gould of Kaiser Permanente in Pasadena, Calif., raises methodological issues and writes that pregnancy comes with a host of changes that could be responsible for protection from MS. © Society for Science & the Public 2000 - 2015.
By Seth Fletcher To solve the mysteries of the brain, scientists need to delicately, precisely monitor neurons in living subjects. Brain probes, however, have generally been brute-force instruments. A team at Harvard University led by chemist Charles Lieber hopes that silky soft polymer mesh implants will change this situation. So far the researchers have tested the mesh, which is embedded with electronic sensors, in living mice. Once it has been proved safe, it could be used in people to study how cognition arises from the action of individual neurons and to treat diseases such as Parkinson's. © 2015 Scientific American
Keyword: Brain imaging
Link ID: 21645 - Posted: 11.20.2015
By Simon Makin Optogenetics is probably the biggest buzzword in neuroscience today. It refers to techniques that use genetic modification of cells so they can be manipulated with light. The net result is a switch that can turn brain cells off and on like a bedside lamp. The technique has enabled neuroscientists to achieve previously unimagined feats and two of its inventors—Karl Deisseroth of Stanford University and the Howard Hughes Medical Institute and Ed Boyden of Massachusetts Institute of Technology—received a Breakthrough Prize in the life sciences on November 8 in recognition of their efforts. The technology is able to remotely control motor circuits—one example is having an animal run in circles at the flick of a switch. It can even label and alter memories that form as a mouse explores different environments. These types of studies allow researchers to firmly establish a cause-and-effect relationship between electrical activity in specific neural circuits and various aspects of behavior and cognition, making optogenetics one of the most widely used methods in neuroscience today. As its popularity soars, new tricks are continually added to the optogenetic arsenal. The latest breakthroughs, promise to deliver the biggest step forward for the technology since its inception. Researchers have devised ways of broadening optogenetics to enter into a dynamic dialogue with the signals moving about inside functioning brains. © 2015 Scientific American
Keyword: Brain imaging
Link ID: 21621 - Posted: 11.10.2015
Susan Milius Electric eels are even more shocking than biologists thought. When prey fights back, eels just — curl their tails. Muscle has evolved “into a battery” independently in two groups of fishes, explains Kenneth Catania of Vanderbilt University in Nashville. Smaller species send out slight tingles of electric current that detect the fish’s surroundings in murky nighttime water. People can handle these small fishes and not feel even a tickle. But touching the bigger Electrophorus electricus (a member of a South American group of battery-included fishes)“is reminiscent of walking into an electric fence on a farm,” Catania says. (He knows, unintentionally, from experience.) The modified muscle that works as an electricity-generating organ in the eel has just on/off power. But eels have a unique way of intensifying the effect, Catania reports October 28 in Current Biology. Catania has tussled with eels using what he calls his electric eel chew toy — a dead fish on a stick with electrodes inside the carcass to measure current. When fighting difficult prey Iike the recalcitrant toy, eels curl their tails toward the fish struggling in their jaws. This bend puts the electrically negative tail-end of the long battery organ closer to the electrically positive front end, effectively concentrating the electric field on the prey. An eel’s tail curl can double the strength of the electric field convulsing the prey. © Society for Science & the Public 2000 - 2015.
Fragment of rat brain simulated in supercomputer Moheb Costandi A controversial European neuroscience project that aims to simulate the human brain in a supercomputer has published its first major result: a digital imitation of circuitry in a sandgrain-sized chunk of rat brain. The work models some 31,000 virtual brain cells connected by roughly 37 million synapses. The goal of the Blue Brain Project, which launched in 2005 and is led by neurobiologist Henry Markram of the Swiss Federal Institute of Technology in Lausanne (EPFL), is to build a biologically-detailed computer simulation of the brain based on experimental data about neurons' 3D shapes, their electrical properties, and the ion channels and other proteins that different cell types typically produce (see ‘Brain in a box’). Such a simulation would provide deep insights into the way the brain works, says Markram. But other neuroscientists have argued that it will reveal no more about the brain’s workings than do simpler, more abstract simulations of neural circuitry — while sucking up a great deal of computing power and resources. The initiative has links with the Human Brain Project, a €1-billion (US$1.1-billion), decade-long initiative which Markram helped persuade the European Commission to fund, and which also aims to advance supercomputer brain simulation. It launched in 2013, with Markram as co-leader, although this March its leadership was switched and its scientific programme altered, after criticism of the way it was being managed. © 2015 Nature Publishing Group
Keyword: Brain imaging
Link ID: 21494 - Posted: 10.09.2015
A new drug for multiple sclerosis can cut relapses by almost 50% more than the current standard treatment, its manufacturer claims, raising the hopes of sufferers of the disease. The Swiss pharmaceutical giant Roche announced the headline results for its drug, ocrelizumab, but has not published the detailed outcome of its trials. The announcement was warmly welcomed by patients, not least because Roche claims the drug also has an impact on a form of the disease, called primary-progressive, which affects 10-15% of people with MS in the UK and for which there are no treatments. Roche claimed it cut disability in those patients by nearly a quarter. “These phase three trial results will provide a great deal of hope for people with primary-progressive MS, who currently don’t have any treatments available that can slow down the worsening of their condition,” said Nick Rijke, the MS Society’s executive director for policy and research. “Finding effective treatments for multiple sclerosis is our number one priority at the MS Society and this is a big moment. The drug was compared in the trials with Rebif, an established drug made by Merck that reduces relapses by about a third. Ocrelizumab – which does not yet have a brand name – was said to cut annual relapses by 46% and 47% compared with Rebif in the two trials. The biggest advantage, however, may be that it is claimed to cause fewer side effects than the established drug. © 2015 Guardian News and Media Limited
by Sarah Schwartz People with multiple sclerosis who got less sun exposure and had higher body mass as young adults developed the disease sooner than those who spent more time in the sun and were a normal weight, a new study finds. In a study of over 1,100 Danish people with MS — a nervous system condition that causes muscle weakness and pain — patients who were overweight at age 20 developed multiple sclerosis an average of 1.5 years sooner than patients of normal weight. And subjects who reported spending time in the sun every summer’s day during adolescence developed the disease 1.8 years later, on average, than patients who got less sun exposure, Danish researchers report online October 7 in Neurology. The results echo earlier work that found a link between adolescent obesity and risk of MS. And sun exposure may increase patients’ levels of vitamin D, which has been shown to protect against the disease, the researchers say. © Society for Science & the Public 2000 - 2015
James Gorman Turning certain brain cells on and off with light — a technique called optogenetics — is one of the most important tools in neuroscience. It allows scientists to test basic ideas about how brains work. But because waves of visible light don’t penetrate living tissue well, the technique requires the insertion of a conduit for the light into the brain— a very thin fiber optic cable. For the first time, researchers say, they have done the same with ultrasound, opening the way to a noninvasive way to probe the functions of neurons. They call the technique sonogenetics. They achieved this in a microscopic worm, a creature so simple that it doesn’t have a brain. But it does have neurons, which have a great deal in common with the neurons in more complex animals that make up the brain and nervous system. If the technique works in more complex animals, it would mean a noninvasive way to do basic research, and perhaps even treat brain circuits. “Previous studies have shown if you use ultrasound, you can manipulate the nervous system,” said Sreekanth H. Chalasani of the Salk Institute in San Diego and senior author of a recent report in Nature Communications that describes the research. But, he said, nobody had shown that, with genetic modifications, specific neurons could be targeted. “It’s going to be a viable technique,” said William Tyler, a neuroscientist at Arizona State University, who said the ability to zero in on one neuron or a group of neurons without having to insert anything into the body was “unparalleled.” © 2015 The New York Times Company
Keyword: Brain imaging
Link ID: 21453 - Posted: 09.28.2015
By Diana Kwon Multiple sclerosis (MS) relapses are known to swing with the seasons. Scientists have attributed these fluctuations to the rise and fall of vitamin D production, which is triggered by exposure to seasonal sunlight. Now a new study suggests that melatonin, a hormone that regulates your internal body clock and sleep cycles, could also play a protective role. MS is a disease of the central nervous system in which an abnormal immune response attacks the myelin sheath, or fatty protective layer, around neurons. The resulting degradation slows signaling between the brain and the rest of the body, potentially leading to a wide variety of symptoms that include weakness, vision problems and cognitive changes. The condition may affect as many as 2.3 million people worldwide. The cause of the disease remains unknown, although researchers have started to identify genetic risks and environmental factors, including smoking, viral infections and vitamin D levels in the bloodstream. The latest environmental influence, observed by Mauricio Farez, a neuroscientist at the Raúl Carrea Institute for Neurological Research, and colleagues could involve peak melatonin levels in the body, which occur during the darker months. The researchers assessed a group of 139 multiple sclerosis patients in Buenos Aires and found a 32 percent reduction in the number of relapses in the fall and winter, when people living in the Southern Hemisphere produce more of the hormone, compared with summer and spring. The results are published on the September 10 Cell. © 2015 Scientific American
Helen Shen Neuroscientists have used ultrasound to stimulate individual brain cells in a worm, and hope that the technique — which they call ‘sonogenetics’ — might be adapted to switch on neurons in mice and larger animals. The technique relies on touch-sensitive ‘channel’ proteins, which can be added to particular brain cells through genetic engineering. The channels open when hit by an ultrasonic pulse, which allows ions to flood into a neuron and so causes it to turn on. Ultrasound could be a less-invasive way for researchers to stimulate specific cell types or individual neurons, rather than using implanted electrodes or fibre-optic cables, says neurobiologist Sreekanth Chalasani, at the Salk Institute for Biological Studies in La Jolla, California, who led the study reported today in Nature Communications1. “Our hope is to create a toolbox of different channels that would each respond to different intensities of ultrasound,” he says. "It's a cool new idea, and they show that this could really be feasible," says Jon Pierce-Shimomura, a neuroscientist who studies the nematode Caenorhabditis elegans at the University of Texas at Austin. “This could open a whole new way for manipulating the nervous system non-invasively through genetically encodable tools.” © 2015 Nature Publishing Group,
Keyword: Brain imaging
Link ID: 21417 - Posted: 09.16.2015
By Sarah Schwartz Darkness and light may help prevent multiple sclerosis or fend off its symptoms. People who genetically produce less vitamin D, a compound normally boosted by sun exposure, have a greater risk of multiple sclerosis, researchers find. But the hormone melatonin, which the body produces in response to darkness, may reduce flare-ups for people who have the disease, another team of scientists reports. The studies may help researchers better understand and treat multiple sclerosis, a disease of the nervous system. It causes symptoms including muscle weakness, pain and vision loss in over 2 million people worldwide. Previous studies linked lower vitamin D levels to higher multiple sclerosis risk, but it was unclear whether this relationship was a coincidence. In work appearing August 25 in PLOS Medicine, scientists examined genetic data from thousands of Europeans and found that three genetic changes known to reduce vitamin D levels were associated with increased multiple sclerosis risk. These findings suggest that individuals with a higher risk of developing the disease, such as immediate family members of multiple sclerosis patients, should take steps to ensure they have sufficient levels of vitamin D, says study coauthor Brent Richards, a genetic epidemiologist at McGill University in Montreal. People can raise vitamin D levels to normal by taking an oral supplement. © Society for Science & the Public 2000 - 2015.