Posts tagged neuroscience
Articles and news from the latest research reports.
Why Our Backs Can’t Read Braille: Scientists map sensory nerves in mouse skin
Johns Hopkins scientists have created stunning images of the branching patterns of individual sensory nerve cells. Their report, published online in the journal eLife on Dec. 18, details the arrangement of these branches in skin from the backs of mice. The branching patterns define ten distinct groups that, the researchers say, likely correspond to differences in what the nerves do and could hold clues for pain management and other areas of neurological study.
Each type of nerve cell that the team studied was connected at one end to the spinal cord through a thin, wire-like projection called an axon. On the other side of the cell’s “body” was another axon that led to the skin. The axons branched in specific patterns, depending on the cell type, to reach their targets within the skin. “The complexity and precision of these branching patterns is breath-taking,” says Jeremy Nathans, M.D., Ph.D., a Howard Hughes researcher and professor of molecular biology and genetics at the Institute for Basic Biomedical Sciences at the Johns Hopkins School of Medicine.
Brake on nerve cell activity after seizures discovered
Given that epilepsy impacts more than 2 million Americans, there is a pressing need for new therapies to prevent this disabling neurological disorder. New findings from the neuroscience laboratory of Mark S. Shapiro, Ph.D., at The University of Texas Health Science Center at San Antonio, published Dec. 20 in the high-impact scientific journal, Neuron, may provide hope.
“A large fraction of epilepsy sufferers cannot take drugs for their disorder or the existing drugs do not manage it,” said Dr. Shapiro, professor of physiology in the School of Medicine. “As a result, many opt for surgery to remove the hippocampus, a part of the brain where memories are stored but also where seizures are often localized. The heart-wrenching choice is between their memories and the epilepsy.”
Genes go into action
A major finding of the study is that selected genes get switched on during and after a seizure, sending swarms of signals to reduce uncontrolled firing of nerve cells. A medication that amplifies this response after a person’s initial seizure could thus prevent recurrent seizures and the onset of devastating epilepsy.
Uncontrolled electrical activity by specialized electricity-producing proteins in the brain called “ion channels” triggers epileptic seizures. One in 10 people have a lifetime risk of suffering a seizure, which can occur for a variety of reasons including traumatic brain injury, stroke or drug overdoses.
A powerful brake
Although not all seizures lead to epilepsy, some trigger changes in the brain that heighten the risk of the disorder. Dr. Shapiro’s research sheds light on why most isolated seizures do not lead to full-blown epilepsy, whereas others do. An ion channel called the “M-channel” acts as a powerful “brake” on hyper-excitability in the brain. Another organizational protein, called AKAP79, acting much like an air-traffic controller, calls in more M channels as part of neuroprotective response machinery.
Pharmacological therapy to enhance M-channel gene expression or AKAP79 function “could jump-start this neuroprotective mechanism to prevent a seizure from turning into epilepsy,” Dr. Shapiro said. “Administering it right after a traumatic brain injury could be very effective.”
It was not known that electrical activity could regulate M-channel genes, Dr. Shapiro said. Nor was it known that the AKAP79 organizer protein, which coordinates many aspects of M-channel function, could turn on their genes in a person’s DNA. By increasing M-channel expression in the brain, uncontrolled electrical firing of nerve cells in the brain is sharply controlled.
Mouse experiments
The Shapiro lab team records electrical currents and performs imaging in living nerve cells to measure M-channel activity. This study included inducing seizures in healthy mice. After a seizure, gene expression of M-channels in the hippocampus increased more than 10-fold within 24 hours, Dr. Shapiro said. This protective effect was completely absent in mice lacking the mouse version of the AKAP79 gene.
“Because excessive firing of nerve cells is also involved in chronic pains, such as migraines, mood disorders and hypertension, increasing M-channel signals to reduce nerve-cell firing could also likely be effective in treating those conditions,” Dr. Shapiro said.
Working with mice, Johns Hopkins scientists have discovered that a particular protein helps nerve cells extend themselves along the spinal cord during mammalian development. Their results shed light on the subset of muscular dystrophies that result from mutations in the gene that holds the code for the protein, called dystroglycan, and also show how the nerve and muscle failings of the degenerative diseases are related.
As mammals like mice and humans develop, nerve cells in the brain and spinal cord must form connections with themselves and with muscles to assure proper control of movement. Nerve cells sometimes extend the whole length of the spinal cord to connect sensory nerves bearing information, for example, from the legs to the brain. To do so, nerve cells anchor their “headquarters,” or cell bodies, in one location, and then extend a long, thin projection all the way to their target locations. These projections, or axons, can be 10,000 times longer than the cell body.
In a report published in the journal Neuron on Dec. 6, the authors suggest that, during fetal development, axons extend themselves along specific pathways created by dystroglycan.
More than a century after it was first identified, Harvard scientists are shedding new light on a little-understood neural feedback mechanism that may play a key role in how the olfactory system works in the brain.
As described in a December 19 paper in Neuron by Venkatesh Murthy, Professor of Molecular and Cellular Biology, researchers have, for the first time, described how that feedback mechanism works by identifying where the signals go, and which type of neurons receive them. Three scientists from the Murthy lab were involved in the work: Foivos Markopoulos, Dan Rokni and David Gire.
"The image of the brain as a linear processor is a convenient one, but almost all brains, and certainly mammalian brains, do not rely on that kind of pure feed-forward system," Murthy explained. "On the contrary, it now appears that the higher regions of the brain which are responsible for interpreting olfactory information are communicating with lower parts of the brain on a near-constant basis."
Though researchers have known about the feedback system for decades, key questions about its precise workings, such as which neurons in the olfactory bulb receive the feedback signals, remained a mystery, partly because scientists simply didn’t have the technological tools needed to activate individual neurons and individual pathways.
"One of the challenges with this type of research is that these feedback neurons are not the only neurons that come back to the olfactory bulb," Murthy explained. "The challenge has always been that there’s no easy way to pick out just one type of neuron to activate."
To do it, Murthy and his team turned to a technique called optogenetics.
Using a virus that has been genetically-modified to produce a light-sensitive protein, Murthy and his team marked specific neurons, which become active when hit with laser light. Researchers were then able to trace the feedback mechanism from the brain’s processing centers back to the olfactory bulb.
Reaching that level of precision was critical, Murthy explained, because while olfactory bulb contains many “principal” neurons which are responsible for sending signals on to other parts of the brain, it is also packed with interneurons, which appear to play a role in formatting olfactory information as it comes into the brain.
(Image: BigStock)
Western University-led research debunks the IQ myth
After conducting the largest online intelligence study on record, a Western University-led research team has concluded that the notion of measuring one’s intelligence quotient or IQ by a singular, standardized test is highly misleading.
The findings from the landmark study, which included more than 100,000 participants, were published in the journal Neuron.
Utilizing an online study open to anyone, anywhere in the world, the researchers asked respondents to complete 12 cognitive tests tapping memory, reasoning, attention and planning abilities, as well as a survey about their background and lifestyle habits.
"The uptake was astonishing," says Owen, the Canada Excellence Research Chair in Cognitive Neuroscience and Imaging and senior investigator on the project. "We expected a few hundred responses, but thousands and thousands of people took part, including people of all ages, cultures and creeds from every corner of the world."
The results showed that when a wide range of cognitive abilities are explored, the observed variations in performance can only be explained with at least three distinct components: short-term memory, reasoning and a verbal component.
No one component, or IQ, explained everything. Furthermore, the scientists used a brain scanning technique known as functional magnetic resonance imaging (fMRI), to show that these differences in cognitive ability map onto distinct circuits in the brain.
With so many respondents, the results also provided a wealth of new information about how factors such as age, gender and the tendency to play computer games influence our brain function.
"Regular brain training didn’t help people’s cognitive performance at all yet aging had a profound negative effect on both memory and reasoning abilities," says Owen.
Hampshire adds, “Intriguingly, people who regularly played computer games did perform significantly better in terms of both reasoning and short-term memory. And smokers performed poorly on the short-term memory and the verbal factors, while people who frequently suffer from anxiety performed badly on the short-term memory factor in particular”.
To continue the groundbreaking research, the team has launched a new version of the tests at http://www.cambridgebrainsciences.com/theIQchallenge
"To ensure the results aren’t biased, we can’t say much about the agenda other than that there are many more fascinating questions about variations in cognitive ability that we want to answer," explains Hampshire.
(Image by Lasse Kristensen/Shutterstock)
The empathy machine
…Let’s dwell for a moment on ‘Silver Blaze’ (1892), Arthur Conan Doyle’s story of the gallant racehorse who disappeared, and his trainer who was found dead, just days before a big race. The hapless police are stumped, and Sherlock Holmes is called in to save the day. And save the day he does — by putting himself in the position of both the dead trainer and the missing horse. Holmes speculates that the horse is ‘a very gregarious creature’. Surmising that, in the absence of its trainer, it would have been drawn to the nearest town, he finds horse tracks, and tells Watson which mental faculty led him there. ‘See the value of imagination… We imagined what might have happened, acted upon that supposition, and find ourselves justified.’
Holmes takes an imaginative leap, not only into another human mind, but into the mind of an animal. This perspective-taking, being able to see the world from the point of view of another, is one of the central elements of empathy, and Holmes raises it to the status of an art.
Usually, when we think of empathy, it evokes feelings of warmth and comfort, of being intrinsically an emotional phenomenon. But perhaps our very idea of empathy is flawed. The worth of empathy might lie as much in the ‘value of imagination’ that Holmes employs as it does in the mere feeling of vicarious emotion. Perhaps that cold rationalist Sherlock Holmes can help us reconsider our preconceptions about what empathy is and what it does.
Though the scientific literature on empathy is complex, a recent review in Nature Neuroscience by a team of researchers from Harvard and Columbia including Jamil Zaki and Kevin Ochsner has distilled the phenomenon into three central stages. The first stage is ‘experience sharing’, or feeling someone else’s emotions as if they were your own — scared when they are scared, happy when they are happy, and so on. The second stage is ‘mentalising’, or consciously considering those states and their sources, and trying to work through understanding them. The final stage is ‘prosocial concern’, or being motivated to act — wanting, for example, to reach out to someone in pain. However, you don’t need all three to experience empathy. Instead, you can view these as three points on an empathetic continuum: first, you feel; then, you feel and you understand; and finally, you feel, understand, and are compelled to act on your understanding. It seems that the defining thing here is the feeling that accompanies all those stages.
Orangutans Have a Big Idea
Even when they are very young, orangutans may start to form ideas about their world—specifically, how and when to use certain tools. That’s the conclusion of a new study, which indicates that ape cultural traditions may not be that different from our own.
Like humans, orangutans have behavioral traditions that vary by region. Orangutans in one area use tools, for example, whereas others don’t. Take the island of Sumatra, in western Indonesia. By the age of 6 or 7, orangutans from swampy regions west of Sumatra’s Alas River use sticks to probe logs for honey. Yet researchers have never observed this “honey-dipping” among orangutans in coastal areas east of the water.
How do such differences arise? Many experts say that social learning is key—that the apes figure out how to honey-dip by watching others. But even the most careful field researcher can have difficulty proving this, says Yale University anthropologist David Watts. Wild apes are always responding to their environment, he says. And it may be influencing their behavior far more than social learning.
MRIs Reveal Signs of Brain Injuries Not Seen in CT Scans
Hospital MRIs may be better at predicting long-term outcomes for people with mild traumatic brain injuries than CT scans, the standard technique for evaluating such injuries in the emergency room, according to a clinical trial led by researchers at UCSF and the San Francisco General Hospital and Trauma Center (SFGH).
Published this month in the journal Annals of Neurology, the study led by UCSF neuroradiologist Esther Yuh, MD, PhD, followed 135 people treated for mild traumatic brain injuries over the past two years at one of three urban hospitals with level-one trauma centers: SFGH, the University of Pittsburgh Medical Center and University Medical Center Brackenridge in Austin, Texas. The study was called the NIH-funded TRACK-TBI (Transforming Research and Clinical Knowledge in Traumatic Brain Injury).
All 135 patients with mild traumatic brain injuries received CT scans when they were first admitted, and all were given MRIs about a week later. Most of them (99) had no detectable signs of injury on a CT scan, but more than a quarter (27/99) who had a “normal” CT scans also had detectable spots on their MRI scans called “focal lesions,” which are signs of microscopic bleeding in the brain.
Spotting these focal lesions helped the doctors predict whether the patients were likely to suffer persistent neurological problems. About 15 percent of people who have mild traumatic brain injuries do suffer long-term neurological consequences, but doctors currently have no definitive way of predicting whether any one patient will or not.
“This work raises questions of how we’re currently managing patients via CT scan,” said the study’s senior author Geoff Manley, MD, PhD, the chief of neurosurgery at SFGH and vice-chair of the Department of Neurological Surgery at UCSF. “Having a normal CT scan doesn’t, in fact, say you’re normal,” he added.
Better Precision Tools Needed for Head Injuries
At least 1.7 million Americans seek medical attention every year for acute head injuries, and three-quarters of them have mild traumatic brain injuries – which generally do not involve skull fractures, comas or severe bleeding in the brain but have a variety of more mild symptoms, such as temporary loss of consciousness, vomiting or amnesia.
The U.S. Centers for Disease Control and Prevention estimates that far more mild traumatic brain injuries may occur each year in the United States but the true number is unknown because only injuries severe enough to bring someone to an emergency room are counted.
Most of those who do show up at emergency rooms are treated and released without being admitted to the hospital. In general, most people with mild traumatic brain injuries recover fully, but about one in six go on to develop persistent, sometimes permanent, disability.
The problem, Manley said, is that there is no way to tell which patients are going to have the poor long-term outcomes. Some socioeconomic indicators can help predict prolonged disability, but until now there were no proven imaging features, or blood tests for predicting how well or how fast a patient will recover. Nor is there a consensus on how to treat mild traumatic brain injuries.
“The treatment’s all over the place – if you’re getting treatment at all,” Manley said.
The new work is an important step toward defining a more quantitative way of assessing patients with mild traumatic brain injuries and developing more precision medical tools to detect, monitor and treat them, he added.
If doctors knew which patients were at risk of greater disabilities, they could be followed more closely. Being able to identify patients at risk of long-term consequences would also speed the development of new therapeutics because it would allow doctors to identify patients who would benefit the most from treatment and improve their ability to test potential new drugs in clinical trials.
Excessive alcohol when you’re young could have lasting impacts on your brain
Alcohol misuse in young people causes significant changes in their brain function and structure. This and other findings were recently reviewed by Dr Daniel Hermens from the University of Sydney’s Brain and Mind Research Institute in the journal Cortex.
"Young people are particularly vulnerable to the damaging effects of alcohol misuse," said Dr Hermens.
Most people have their first alcoholic drink during adolescence and while they drink less frequently than adults, they tend to drink more on each occasion - binge drinking.
The early functional signs of brain damage from alcohol misuse are visual, learning, memory and executive function impairments. These functions are controlled by the hippocampus and frontal structures of the brain, which are not fully mature until around 25 years of age.
Structural signs of alcohol misuse include shrinking of the brain and significant changes to white matter.
In his review, Dr Hermens notes that changes in a young person’s brain caused by alcohol misuse could either represent a predisposition (genetic or environmental) to alcohol misuse, or a marker for future risk of ongoing misuse. Whichever it is, there is no doubt that the more frequent the alcohol misuse, the greater the damage and the less likely the brain is to recover from that damage.
"When the toxicity of alcohol stops your brain from laying down new memories, you experience a blackout," said Dr Hermens. Young people who binge drink may only drink once a week, but on a massive night out they may have three to four blackouts, which begins to cause serious damage to their brain.
One of the best predictors of a person having problems with alcohol is their earliest age of first use. But changing the legal drinking age is not the answer. In Australia the legal drinking age is 18, three years earlier than in the US. Despite the difference in legal drinking age, the age of first use is the same between the two countries.
Another key factor affecting young people who drink is mental health, “poor mental health more than doubles a young person’s risk of alcohol and other substance misuse” says Dr Hermens.
The solution lies in education, treatment and prevention. Dr Hermens and his team have been working with NSW Health to prepare a set of guidelines for health carers to identify and respond to early stages of brain impairment in young people resulting from alcohol misuse. They are currently working on a set of educational charts that inform young people of the risks of irresponsible drinking.
It may be possible to use cognitive remediation to change the drinking habits of young drinkers and prevent relapse. At the same time, vitamin supplements or other medicines may effectively treat some of the structural changes, and it may be possible to develop protective agents that can prevent young brains from the damaging effects of alcohol.
"More work needs to be done in this area. Excessive alcohol use accounts for 4 percent of the global burden of disease. We would save a lot of money and improve the quality of life for millions of people if we could prevent the mental and physical problems associated with alcohol misuse" said Dr Hermens.
REM sleep enhances emotional memories
Witnessing a car wreck or encountering a poisonous snake are scenes that become etched in our memories.
But how do we process and store these emotional scenes so that they’re preserved more efficiently than other, more neutral memories?
In a new study published recently in “Frontiers in Integrative Neuroscience,” University of Notre Dame researchers Jessica Payne and Alexis Chambers found that people who experienced rapid eye movement (REM) sleep soon after being presented with an emotionally-charged negative scene — a wrecked car on a street, for example — had superior memory for the emotional object compared to subjects whose sleep was delayed for at least 16 hours. This increased memory for the emotional object corresponded with a diminished memory for the neutral background of the scene, such as the street on which the wrecked car was parked.
These results suggest that the sleeping brain preserves in long-term memory only those scenes that are emotionally salient and aid in adaptation.
“Our results suggest that REM sleep, which has long been thought to play a role in emotional processing and emotional memory, helps us selectively preserve in memory only what is most important and perhaps beneficial to survival,” says Payne, a Notre Dame assistant professor of psychology who specializes in sleep’s impact on memory, creativity and the ability to process new ideas.
We know that emotional events occupy a privileged position in our memories — they shape our personalities, represent defeats and achievements, mark milestones in our lives and often drive anxiety and mood disorders.
This study shows that the sleeping brain doesn’t just consolidate all recently encountered information. It appears to select for consolidation only the most emotional part of the experience, and the evidence suggests that REM sleep critically modulates memory for highly arousing emotional information.
(Image: iStock)