Posts tagged neuroimaging
Articles and news from the latest research reports.
The Anorexic Brain
Neuroimaging improves understanding of eating disorder
In a spacious hotel room not far from the beach in La Jolla, Calif., Kelsey Heenan gripped her fiancé’s hand. Heenan, a 20-year-old anorexic woman, couldn’t believe what she was hearing. Walter Kaye, director of the eating disorders program at the University of California, San Diego, was telling a handful of rapt patients and their family members what the latest brain imaging research suggested about their disorder.
It’s not your fault, he told them.
Heenan had always assumed that she was to blame for her illness. Kaye’s data told a different story. He handed out a pile of black-and-white brain scans — some showed the brains of healthy people, others were from people with anorexia nervosa. The scans didn’t look the same. “People were shocked,” Heenan says. But above all, she remembers, the group seemed to sigh in relief, breathing out years of buried guilt about the disorder. “It’s something in the way I was wired — it’s something I didn’t choose to do,” Heenan says. “It was pretty freeing to know that there could be something else going on.”
Years of psychological and behavioral research have helped scientists better understand some signs and triggers of anorexia. But that knowledge hasn’t straightened out the disorder’s tangled roots, or pointed scientists to a therapy that works for everyone. “Anorexia has a high death rate, it’s expensive to treat and people are chronically ill,” says Kaye.
Kaye’s program uses a therapy called family-based treatment, or FBT, to teach adolescents and their families how to manage anorexia. A year after therapy, about half of the patients treated with FBT recover. In the world of eating disorders, that’s success: FBT is considered one of the very best treatments doctors have. To many scientists, that just highlights how much about anorexia remains unknown.
Kaye and others are looking to the brain for answers. Using brain imaging tools and other methods to explore what’s going on in patients’ minds, researchers have scraped together clues that suggest anorexics are wired differently than healthy people. The mental brakes people use to curb impulsive instincts, for example, might get jammed in people with anorexia. Some studies suggest that just a taste of sugar can send parts of the brain barrelling into overdrive. Other brain areas appear numb to tastes — and even sensations such as pain. For people with anorexia, a sharp pang of hunger might register instead as a dull thud.
The mishmash of different brain imaging data is just beginning to highlight the neural roots of anorexia, Kaye says. But because starvation physically changes the brain, researchers can run into trouble teasing out whether glitchy brain wiring causes anorexia, or vice versa. Still, Kaye thinks understanding what’s going on in the brain may spark new treatment ideas. It may also help the eating disorder shake off some of its noxious stereotypes.
“One of the biggest problems is that people do not take this disease seriously,” says James Lock, an eating disorders researcher at Stanford University who cowrote the book on family-based treatment. “No one gets upset at a child who has cancer,” he says. “If the treatment is hard, parents still do it because they know they need to do it to make their child well.”
Pop culture often paints anorexics as willful young women who go on diets to be beautiful, he says. But, “you can’t just choose to be anorexic,” Lock adds. “The brain data may help counteract some of the mythology.”
Beyond dieting
A society that glamorizes thinness can encourage unhealthy eating behaviors in kids, scientists have shown. A 2011 study of Minnesota high school students reported that more than half of girls had dieted within the past year. Just under a sixth had used diet pills, vomiting, laxatives or diuretics.
But a true eating disorder goes well beyond an unhealthy diet. Anorexia involves malnutrition, excessive weight loss and often faulty thinking about one of the body’s most basic drives: hunger. The disorder is also rare. Less than 1 percent of girls develop anorexia. The disease crops up in boys too, but adolescent girls — especially in wealthy countries such as the U.S., Australia and Japan — are most likely to suffer from the illness.
As the disease progresses, people with anorexia become intensely afraid of getting fat and stick to extreme diets or exercise schedules to drop pounds. They also misjudge their own weight. Beyond these diagnostic hallmarks, patients’ symptoms can vary. Some refuse to eat, others binge and purge. Some live for years with the illness, others yo-yo between weight gain and loss. Though most anorexics gain back some weight within five years of becoming ill, anorexia is the deadliest of all mental disorders.
Though anorexia tends to run in families, scientists haven’t yet hammered out the suite of genes at play. Some individuals are particularly vulnerable to developing an eating disorder. In these people, stressful life changes, such as heading off to college, can tip the mental scales toward anorexia.
For decades, scientists have known that anorexic children behave a little differently. In school and sports, anorexic kids strive for perfection. Though Heenan, a former college basketball player, didn’t notice her symptoms creeping in until the end of high school, she remembers initiating strict practice regimens as a child. Starting in second grade, Heenan spent hours perfecting her jump shot, shooting the ball again and again until she had the technique exactly right — until her form was flawless.
“It’s very rare for me to see a person with anorexia in my office who isn’t a straight-A student,” Lock says. Even at an early age, people who later develop the eating disorder tend to exert an almost superhuman ability to practice, focus or study. “They will work and work and work,” says Lock. “The problem is they don’t know when to stop.”
In fact, many scientists think anorexics’ brains might be wired for willpower, for good and ill. Using new imaging tools that let scientists watch as a person’s mental gears grind through different tasks, researchers are starting to pin down how anorexic brains work overtime.
Different wiring: Studies of the brains of people with anorexia have revealed a number of complex brain circuits that show changes in activity compared with healthy people. Medical RF, adapted by M. Atarod
Control signs
To glimpse the circuits that govern self-control, experimental neuropsychologist Samantha Brooks uses functional magnetic resonance imaging, or fMRI, a tool that measures and maps brain activity. Last year, she and colleagues scanned volunteers as they imagined eating high-calorie foods, such as chocolate cake and French fries, or using inedible objects such as clothespins piled on a plate. One result gave Brooks a jolt. A center of self-control in anorexics’ brains sprung to life when the volunteers thought about food — but only in the women who severely restricted their calories, her team reported March 2012 in PLOS ONE.
The control center, two golf ball–sized chunks of tissue called the dorsolateral prefrontal cortex, or DLPFC, helps stamp out primitive urges. “They put a brake on your impulsive behaviors,” says Brooks, now at the University of Cape Town in South Africa.
For Brooks, discovering the DLPFC data was like finding a tiny vein of gold in a heap of granite. The control center could be the nugget that reveals how anorexics clamp down on their appetites. So she and her colleagues devised an experiment to test anorexics’ DLPFC. Using a memory task known to engage the brain region, the researchers quizzed volunteers while showing them subliminal images. The quizzes tested working memory, the mental tool that lets people hold phone numbers in their heads while hunting for a pen and paper. Compared with healthy people, anorexics tended to get more answers right, Brooks’ team wrote June 2012 in Consciousness and Cognition. “The patients were really good,” Brooks says. “They hardly made any mistakes.”
A turbocharged working memory could help anorexics hold on to rules they set for themselves about food. “It’s like saying ‘I will only eat a salad at noon, I will only eat a salad at noon,’ over and over in your mind,” says Brooks. These mantras may become so ingrained that an anorexic person can’t escape them.
But looking at subliminal images of food distracted anorexics from the memory task. “Then they did just as well as the healthy people,” Brooks says. The results suggest that anorexic people might tap into their DLPFC control circuits when faced with food.
James Lock has also seen signs of self-control circuits gone awry in people with eating disorders. In 2011, he and colleagues scanned the brains of teenagers with different eating disorders while signaling them to push a button. While volunteers lay inside the fMRI machine, researchers flashed pictures of different letters on an interior screen. For every letter but “X,” Lock’s group told the teens to push a button. During the task, anorexic teens who obsessively cut calories tended to have more active visual circuits than healthy teens or those with bulimia, a disorder that compels people to binge and purge. The result isn’t easy to explain, says Lock. “Anorexics may just be more focused in on the task.”
Bulimics’ brains told a simpler story. When teens with bulimia saw the letter “X,” broad swaths of their brains danced with activity — more so than the healthy or calorie-cutting anorexic volunteers, Lock’s team reported in the American Journal of Psychiatry. For bulimics, controlling the impulse to push the button may take more brain power than for others, Lock says.
Though the data don’t reveal differences in self-control between anorexics and healthy people, Lock thinks that anorexics’ well-documented ability to swat away urges probably does have signatures in the brain. He notes that his study was small, and that the “healthy” people he used as a control group might have shared similarities with anorexics. “The people who tend to volunteer are generally pretty high performers,” he says. “The chances are good that my controls are a little bit more like anorexics than bulimics.”
Still, Lock’s results offered another flicker of proof that people with eating disorders might have glitches in their self-control circuits. A tight rein on urges could help steer anorexics toward illness, but the parts of their brain tuned into rewards, such as sugary snacks, may also be a little off track.
Sugar low
When an anorexic woman unexpectedly gets a taste of sugar (yellow) or misses out on it (blue), her brain’s reward circuitry shows more activity than a healthy-weight or obese woman’s. Anorexics’ reward-processing systems may be out of order. Credit: G. Frank et al/ Neuropsychopharmacology 2012
For many anorexics, food just doesn’t taste very good. A classic symptom of the disorder is anhedonia, or trouble experiencing pleasure. Parts of Heenan’s past reflect the symptom. When she was ill, she had trouble remembering favorite dishes from childhood, for example — a blank spot common to anorexics. “I think I enjoyed some things,” she says. Beyond frozen yogurt, she can’t really rattle off a list.
After Heenan started seriously restricting her calories in college, only one aspect of food made her feel satisfied. Skipping, rather than eating, meals felt good, she says. Some of Heenan’s symptoms may have stemmed from frays in her reward wiring, the brain circuitry connecting food to pleasure. In the past few years, researchers have found that the chemicals coursing through healthy people’s reward circuits aren’t quite the same in anorexics. And studies in rodents have linked chemical changes in reward circuitry to under- and overeating.
To find out whether under- and overweight people had altered brain chemistry, eating disorder researcher Guido Frank of the University of Colorado Denver studied anorexic, healthy-weight and obese women. He and his colleagues trained volunteers to link images, such as orange or purple shapes, with the taste of a sweet solution, slightly salty water or no liquid. Then, the researchers scanned the women’s brains while showing them the shapes and dispensing tiny squirts of flavors. But the team threw in a twist: Sometimes the flavors didn’t match up with the right images.
When anorexics got an unexpected hit of sugar, a surge of activity bloomed in their brains. Obese people had the opposite response: Their brains didn’t register the surprise. Healthy-weight women fit somewhere in the middle, Frank’s team reported August 2012, in Neuropsychopharmacology. While obese people might not be sensitive to sweets anymore, a little sugar rush goes a long way for anorexics. “It’s just too much stimulation for them,” Frank says.
One of the lively regions in anorexics’ brains was the ventral striatum, a lump of nerve cells that’s part of a person’s reward circuitry. The lump picks up signals from dopamine, a chemical that rushes in when most people see a sugary treat.
Frank says that it’s possible cutting calories could sculpt a person’s brain chemistry, but he thinks some young people are just more likely to become sugar-sensitive than others. Frank suspects anorexics’ dopamine-sensing equipment might be out of alignment to begin with. And he may be onto something. Recently, researchers in Kaye’s lab at UCSD showed that the same chemical that makes people perk up when a coworker brings in a box of doughnuts might actually trigger anxiety in anorexics.
Mixed signals
Usually a rush of dopamine triggers euphoria or a boost of energy, says Ursula Bailer, a psychiatrist and neuroimaging researcher at UCSD. Anorexics don’t seem to pick up those good feelings.
When Bailer and colleagues gave volunteers amphetamine, a drug known to trigger dopamine release, and then asked them to rate their feelings, healthy people stuck to a familiar script. The drug made them feel intensely happy, Bailer’s team described March 2012 in the International Journal of Eating Disorders. Researchers linked the volunteers’ happy feelings to a wave of dopamine flooding the brain, using an imaging technique to track the chemical’s levels.
But anorexics said something different. “People with anorexia didn’t feel euphoria — they got anxious,” Bailer says. And the more dopamine coursing through anorexics’ brains, the more anxious they felt. Anorexics’ reaction to the chemical could help explain why they steer clear of food — or at least foods that healthy people find tempting. “Anorexics don’t usually get anxious if you give them a plate of cucumbers,” Bailer says.
Beyond the anxiety finding, one other aspect of the study sticks out: Instead of examining sick patients, Bailer, Kaye and colleagues recruited women who had recovered from anorexia. By studying people whose brains are no longer starving, Kaye’s team hopes to sidestep the chicken-and-egg question of whether specific brain signatures predispose people to anorexia or whether anorexia carves those signatures in the brain.
Though Kaye says that there’s still a lot scientists don’t know about anorexia, he’s convinced it’s a disorder that starts in the brain. Compared with healthy children, anorexic children’s brains are getting different signals, he says. “Parents have to realize that it’s very hard for these kids to change.”
Kaye thinks imaging data can help families reframe their beliefs about anorexia, which might help them handle tough treatments. He thinks the data can also offer new insights into therapies tailored for anorexics’ specific traits.
Sensory underload
One trait Kaye has focused on is anorexics’ sense of awareness of their bodies. Peel back the outer lobes of the brain by the temples, and the bit that handles body awareness pops into view. These regions, little islands of tissue called the insula, are one of the first brain areas to register pain, taste and other sensations. When people hold their breath, for example, and feel the panicky claws of air hunger, “the insula lights up like crazy,” Kaye says.
Kaye and colleagues have shown that the insulas of people with anorexia seem to be somewhat dulled to sensations. In a recent study, his team strapped heat-delivering gadgets to volunteers’ arms and cranked the devices to painfully hot temperatures while measuring insula activity via fMRI.
Compared with healthy volunteers, bits of recovered anorexics’ insulas dimmed when the researchers turned up the heat. But when researchers simply warned that pain was coming, other parts of the brain region flared brightly, Kaye’s team reported in January in the International Journal of Eating Disorders. For people who have had anorexia, actually feeling pain didn’t seem as bad as anticipating it. “They don’t seem to be sensing things correctly,” says Kaye.
If anorexics can’t detect sensations like pain properly, they may also have trouble picking up other signals from the body, such as hunger. Typically when people get hungry, their insulas rev up to let them know. And in healthy hungry people, a taste of sugar really gets the insula excited. For anorexics, this hunger-sensing part of the brain seems numb. Parts of the insula barely perked up when recovered anorexic volunteers tasted sugar, Kaye’s team showed this June in the American Journal of Psychiatry. The findings “may help us understand why people can starve themselves and not get hungry,” Kaye says.
Though the brain region that tells people they’re hungry might have trouble detecting sweet signals, some reward circuits seem to overreact to the same cues. Combined with a tendency to swap happiness for anxiety, and a mental vise grip on behavior, anorexics might have just enough snags in their brain wiring to tip them toward disease.
Now, Kaye’s group hopes to tap neuroimaging data for new treatment ideas. One day, he thinks doctors might be able to help anorexics “train” their insulas using biofeedback. With real-time brain scanning, patients could watch as their insulas struggle to pick up sugar signals, and then practice strengthening the response. More effective treatment options could potentially spare anorexics the relapses many patients suffer.
Heenan says she’s one of the lucky ones. Four years have passed since she first saw the anorexic brain images at UCSD. In the months following her treatment, Heenan and her family worked together to rebuild her relationship with food. At first, her fiancé picked out all her meals, but step by step, Heenan earned autonomy over her diet. Today, Heenan, a coordinator for Minneapolis’ public schools, is married and has a new puppy. “Life can be good,” she says. “Life can be fun. I want other people to know the freedom that I do.”
Searching for treatments
The bowl of pasta sitting in front of Kelsey Heenan didn’t look especially scary.
Spaghetti, chopped asparagus and chunks of chicken glistened in an olive oil sauce. Usually, such savory fare might make a person’s mouth water. But when Heenan’s fiancé served her a portion, she started sobbing. “You can’t do this to me,” she told him. “I thought you loved me!”
Heenan was confronting her “fear foods” at the Eating Disorders Center for Treatment and Research at UCSD. Therapists in her treatment program, Intensive Multi-Family Therapy, spend five days teaching anorexic patients and families about the disorder and how to encourage healthy eating. “There’s no blame,” says Christina Wierenga, a clinical neuropsychologist at UCSD. “The focus is just on having the parent refeed the child.” Therapists lay out healthy meals and portion sizes for teens, bolster parents’ self-confidence and hammer home the dangers of not eating. Heenan compares the experience to boot camp. But by the end of her time at the center, she says, “I was starting to see glimpses of what life could be like as a healthy person.”
Treatment options for anorexia include a broad mix of behavioral and medication-based therapies. Most don’t work very well, and many lack the support of evidence-based trials. Hospitalizing patients can boost short-term weight gain, “but when people go home they lose all the weight again,” says Stanford University’s James Lock, one of the architects of family-based treatment. That treatment is currently considered the most effective therapy for adolescent anorexics.
In a 2010 clinical trial, half of teens who underwent FBT maintained a normal weight a year after therapy. In contrast, only a fifth of teens treated with adolescent-focused individual therapy, which aims to help kids cope with emotions without using starvation, hit the healthy weight goal.
Few good options exist for adult anorexics, a group notorious for dropping out of therapy. New work hints that cognitive remediation therapy, or CRT, which uses cognitive exercises to change anorexics’ behaviors, has potential. After two months of CRT, only 13 percent of patients abandoned treatment, and most regained some weight, Lock and colleagues reported in the April International Journal of Eating Disorders. Researchers still need to find out, however, if CRT helps patients keep weight on long-term.
(Source: sciencenews.org)
A new tool for brain research
Physicists and neuroscientists from The University of Nottingham and University of Birmingham have unlocked one of the mysteries of the human brain, thanks to new research using functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG).
The work will enable neuroscientists to map a kind of brain function that up to now could not be studied, allowing a more accurate exploration of how both healthy and diseased brains work.
Functional MRI is commonly used to study how the brain works, by providing spatial maps of where in the brain external stimuli, such as pictures and sounds, are processed. The fMRI scan does this by detecting indirect changes in the brain’s blood flow in response to changes in electrical signalling during the stimulus.
Combining techniques
A signal change that happens after the stimulus has stopped is also observed with the fMRI scan. This is called the post-stimulus signal and up until now it has not been used to study how the brain works because its origin was uncertain.
In novel experiments, the research team has now combined fMRI techniques with EEG, which measures electrical activity in the brain, to show that the post-stimulus signal also actually reflects changes in brain signalling.
18 healthy volunteers were monitored by using EEG to measure the electrical activity generated by their brains’ neurons (the signalling cells) while simultaneously recording fMRI measurements. A stimulus of electrical pulses was used to activate the part of the brain that controls movement in the right thumb.
The scientists then compared the EEG and fMRI signals and found that they both vary in the same way after the stimulus stops. This provides compelling evidence that the post-stimulus fMRI signal is a measure of neuronal activity rather than just changes in the brain’s blood flow. Curiously, the team also found the post-stimulus fMRI signal was not consistent, even though the stimulus input to the brain was the same each time. This natural variability in the brain response was also reflected by the EEG activity and the researchers suggest that this signal might help the brain make the transition from processing stimuli back to their internal thoughts in different ways.
New window
Dr Karen Mullinger from The University of Nottingham’s Sir Peter Mansfield Magnetic Resonance Centre said: “This work opens a new window of time in the fMRI signal in which we can look at what the brain is doing. It may also open up new research avenues in exploring the function of the healthy brain and the study of neurological diseases.”
Dr Stephen Mayhew from Birmingham University Imaging Centre said “We do not know what the exact role of the post-stimulus activity is or why this response is not always consistent when the stimulus input to the brain is the same. We have already secured funding through the Birmingham-Nottingham Strategic Collaboration Fund to continue this research into further understanding of human brain function using combinations of neuroimaging methods.”
Director of the Sir Peter Mansfield Magnetic Resonance Centre, Professor Peter Morris, said: “Functional magnetic resonance imaging is the main tool available to cognitive neuroscientists for the investigation of human brain function. The demonstration in this paper, that the secondary fMRI response (the post-stimulus undershoot) is not simply a passive blood flow response, but is directly related to synchronous neural activity, as measured with EEG, heralds an exciting new chapter in our understanding of the workings of the human mind.”
The work has been funded by the Medical Research Council (MRC), Engineering and Physical Science Research Council (EPSRC), The University of Nottingham Anne McLaren Fellowships and University of Birmingham Fellowship and is published in the Proceedings of the National Academy of Sciences (PNAS).
(Source: nottingham.ac.uk)
Speedier scans reveal new distinctions in resting and active brain
A boost in the speed of brain scans is unveiling new insights into how brain regions work with each other in cooperative groups called networks.
Scientists at Washington University School of Medicine in St. Louis and the Institute of Technology and Advanced Biomedical Imaging at the University of Chieti, Italy, used the quicker scans to track brain activity in volunteers at rest and while they watched a movie.
“Brain activity occurs in waves that repeat as slowly as once every 10 seconds or as rapidly as once every 50 milliseconds,” said senior researcher Maurizio Corbetta, MD, the Norman J. Stupp Professor of Neurology. “This is our first look at these networks where we could sample activity every 50 milliseconds, as well as track slower activity fluctuations that are more similar to those observed with functional magnetic resonance imaging (fMRI). This analysis performed at rest and while watching a movie provides some interesting and novel insights into how these networks are configured in resting and active brains.”
Understanding how brain networks function is important for better diagnosis and treatment of brain injuries, according to Corbetta.
The study appears online in Neuron.
Researchers know of several resting-state brain networks, which are groups of different brain regions whose activity levels rise and fall in sync when the brain is at rest. Scientists used fMRI to locate and characterize these networks, but the relative slowness of this approach limited their observations to activity that changes every 10 seconds or so. A surprising result from fMRI was that the spatial pattern of activity (or topography) of these brain networks is similar at rest and during tasks.
In contrast, a faster technology called magnetoencephalography (MEG) can detect activity at the millisecond level, letting scientists examine waves of activity in frequencies from slow (0.1-4 cycles per second) to fast (greater than 50 cycles per second).
“Interestingly, even when we looked at much higher temporal resolution, brain networks appear to fluctuate on a relatively slow time scale,” said first author Viviana Betti, PhD, a postdoctoral researcher at Chieti. “However, when the subjects went from resting to watching a movie, the networks appeared to shift the frequency channels in which they operate, suggesting that the brain uses different frequencies for rest and task, much like a radio.”
In the study, the scientists asked one group of volunteers to either rest or watch the movie during brain scans. A second group was asked to watch the movie and look for event boundaries, moments when the plot or characters or other elements of the story changed. They pushed a button when they noticed these changes.
As in previous studies, most subjects recognized similar event boundaries in the movie. The MEG scans showed that the communication between regions in the visual cortex was altered near the movie boundaries, especially in networks in the visual cortex.
“This gives us a hint of how cognitive activity dynamically changes the resting-state networks,” Corbetta said. “Activity locks and unlocks in these networks depending on how the task unfolds. Future studies will need to track resting-state networks in different tasks to see how correlated activity is dynamically coordinated across the brain.”
(Source: news.wustl.edu)
Brain chemistry changes in children with autism offer clues to earlier detection and intervention
Between ages three and 10, children with autism spectrum disorder exhibit distinct brain chemical changes that differ from children with developmental delays and those with typical development, according to a new study led by University of Washington researchers.
The finding that early brain chemical alterations tend to normalize during the course of development in children with ASD gives new insight to efforts to improve early detection and intervention. The findings were reported July 31 in the Journal of the American Medical Assocation Psychiatry.
“In autism, we found a pattern of early chemical alterations at the cellular level that over time resolved – a pattern similar to what others have seen with people who have had a closed head injury and then got better,” said Stephen R. Dager, a UW professor of radiology and adjunct professor of bioengineering and associate director of UW’s Center on Human Development and Disability.
Neva Corrigan, a senior research fellow in radiology, was first author and Dager corresponding author of the study, titled “Atypical Developmental Patterns of Brain Chemistry in Children with Autism Spectrum Disorder.”
“The brain developmental abnormalities we observed in the children with autism are dynamic, not static. These early chemical alterations may hold clues as to specific processes at play in the disorder and, even more exciting, these changes may hold clues to reversing these processes,” Dager said.
In the study, scientists compared brain chemistry among three groups of children: those with a diagnosis of ASD, those with a diagnosis of developmental delay, and those considered typically developing. The researchers used magnetic resonance spectroscopic imaging, a type of MRI, to measure tissue-based chemicals in three age groups: 3-4 years, 6-7 years and 9-10 years.
One of the chemicals measured, N-acetylaspartate (NAA), is thought to play an important role in regulating synaptic connections and myelination. Its levels are decreased in people with conditions such as Alzheimer’s, traumatic brain injury or stroke. Other chemicals examined in the study – choline, creatine, glutamine/glutamate and myo-inositol – help characterize brain tissue integrity and bioenergetic status.
A notable finding concerned changes in gray matter NAA concentration: In scans of the 3- to 4-year-olds, NAA concentrations were low in both the ASD and developmentally delayed groups. By 9 to 10 years, NAA levels in the children with ASD had caught up to the levels of the typically developing group, while low levels of NAA persisted in the developmentally delayed group.
“A substantial number of kids with early, severe autism symptoms make tremendous improvements. We’re only measuring part of the iceberg, but this is a glimmer that we might be able to find a more specific period of vulnerability that we can measure and learn how to do something more proactively,” said Annette Estes, a co-author of the study and director of the UW Autism Center. She is an associate professor of speech and hearing sciences.
Study co-author Dennis Shaw, a UW professor of radiology and director of MRI at Seattle Children’s, observed that the findings “parallel some of the early brain structural differences we and others have found on MRI that also appear to normalize over time in children with autism. These chemical findings will help to better establish the timing and mechanisms underlying genetic abnormalities known to be involved in at least some cases of autism.”
Dager and UW colleagues are currently using more advanced MRI methods to study infants at risk for ASD because of an older sibling with autism.
“We’re looking prospectively at these children starting at 6 months to determine if we can detect very early alterations in brain cell signaling or related cellular disruption that may precede early, subtle clinical symptoms of ASD.”
Despite the encouraging finding, science has yet to pinpoint the when, what and why of autism’s inception, an event often likened to the flipping of a switch. Discovering the earliest period that a child’s brain starts to develop a profile of ASD is crucial because, as the study acknowledged, “even a relatively brief period of abnormal signaling between glial cells and neurons during early development would likely have a lasting effect” on how a child’s brain network develops.
This study also suggests that developmental delay and autism spectrum disorder are distinct disorders having different underlying brain mechanisms and treatment considerations, Dager said.
“Autism appears to have a different pathophysiology and different early biological course than idiopathic developmental disorder. There are differences in their underlying biological processes; this supports the notion that ASD is different from developmental delay and challenges the notion that the increasing prevalence of autism merely reflects a re-categorization of symptoms between autism and intellectual disabilities.”
Second known case of patient developing synesthesia after brain injury
About nine months after suffering a stroke, the patient noticed that words written in a certain shade of blue evoked a strong feeling of disgust. Yellow was only slightly better. Raspberries, which he never used to eat very often, now tasted like blue – and blue tasted like raspberries.
High-pitched brass instruments—specifically the brass theme from James Bond movies—elicited feelings of ecstasy and light blue flashes in his peripheral vision and caused large parts of his brain to light up on an MRI. Music played by a euphonium, a tenor-pitched brass instrument, shut down those sensations.
The patient said he was initially frightened by the mixed messages his brain was sending him and the conflicting senses he was experiencing. He was so worried that something was seriously wrong with him that he raised it with a nurse only as he was leaving an appointment at St. Michael’s Hospital in downtown Toronto.
Physicians and researchers immediately recognized he had synesthesia, a neurological condition in which people experience more than one sense at the same time. They may “see” words or numbers as colours, hear sounds in response to smells or feel something in response to sight.
Most synesthetes are born with the condition, and include some of the world’s most famous authors and artists, including author Vladimir Nabakov, composer Franz Liszt, painter Vasily Kandinsky and singer-songwriter Billy Joel.
The Toronto patient is only the second known person to have acquired synesthesia as a result of a brain injury, in this case a stroke. His case was described in the August issue of the journal Neurology by Dr. Tom Schweizer, a neuroscientist and director of the Neuroscience Research Program at St. Michael’s Li Ka Shing Knowledge Institute.
Dr. Schweizer examined the patient’s brain activity in a functional MRI and compared it to six men of similar age (45) and education (18 years) as each listened to the James Bond Theme and a euphonium solo.
When the James Bond Theme was played, large areas of the patient’s brain lit up including the thalamus (the brain’s information switchboard), the hippocampus (which deals with memory and spatial navigation) and the auditory cortex (which processes sound).
"The areas of the brain that lit up when he heard the James Bond Theme are completely different from the areas we would expect to see light up when people listen to music," Dr. Schweizer said. "Huge areas on both sides of the brain were activated that were not activated when he listened to other music or other auditory stimuli and were not activated in the control group."
The patient and members of the control group also viewed 10-second blocks of words presented in black (which elicits no emotional response in the patient), yellow (mild disgust response) and blue (intense disgust response).
Reading blue letters produced extensive activity in the parts of the patient’s brain responsible for sensory information and processing emotional stimuli and similar but less intense responses for yellow letters. Control groups showed no heightened brain activity in response to the different coloured letters.
Dr. Schweizer said the fact that the patient had very targeted and specific responses to certain stimuli – and that these responses were not experienced by the control group – suggests that his synesthesia was caused as his brain tried to repair itself after his stroke and got cross-wired.
The patient’s stroke occurred in the thalamus, the brain’s central relay station. That’s the same part of the brain affected by the only other reported case of acquired synesthesia.
(Source: eurekalert.org)
How to learn successfully even under stress
Predicting the weather under stress
The team from Bochum has examined 80 subjects, 50 per cent of whom were given a drug blocking mineralocorticoid receptors in the brain. The remaining participants took a placebo drug. Twenty participants from each group were subjected to a stress-inducing experience. Subsequently, all participants underwent a learning test, the so-called weather prediction task. The subjects were shown playing cards with different symbols and had to learn which combinations of cards meant rain and which meant sunshine. The researchers used MRI to record the respective brain activity.
Learning unconsciously or consciously
There are two different approaches to master the weather prediction test: some subjects tried consciously to formulate a rule that would enable them to predict sunshine and rain. Others learned unconsciously to give the right answer, following their gut feeling, as it were. The team of Lars Schwabe demonstrated in August 2012 that, under stress, the brain prefers unconscious to conscious learning. “This switch to another memory system happens automatically,” says Lars Schwabe. “It makes sense for the organism to react in this manner. Thus, learning efficiency can be maintained even under stress.” However, this works only with fully functional mineralocorticoid receptors. Once the researchers blocked these receptors by applying the drug Spironolactone, the participants switched over to the unconscious strategy less frequently, thus demonstrating a poorer learning efficiency.
Effects also visible in brain activity
These effects also became evident in MRI data. Usually, stress causes the brain activity to shift from the hippocampus – a structure for conscious learning – to the dorsal striatum, which manages unconscious learning. However, this stress-induced switch took place only in the placebo group, not in subjects who had been given the mineralocorticoid receptor blocker. Consequently, the mineralocorticoid receptors play a crucial role in enabling the brain to adapt to stressful situations.
(Image: Shutterstock)
Brain study aims to improve dyslexia treatment
Neuroscientist Sarah Laszlo wants to understand what’s going on in children’s brains when they’re reading. Her research may untangle some of the mysteries surrounding dyslexia and lead to new methods of treating America’s most common learning disorder.
“The brain can reveal things that aren’t necessarily visible on the surface,” she says. “It can tell you things about what’s going wrong that you can’t find out by giving a kid a test or asking him to read out loud.”
Laszlo, who joined Binghamton’s psychology department in 2011, recently received a five-year, $400,763grant from the National Science Foundation’s Early Career Development (CAREER) Program, the agency’s most prestigious award for young researchers. The funding will enable her to conduct a five-year brain activity study of 150 children with and without dyslexia.
Rather than lumping all children with dyslexia into one group, as many previous brain-imaging studies have done, Laszlo’s project will help to establish types and degrees of the disorder.
Her lab uses electroencephalography, or EEG, as a non-invasive way to measure the electrical signals sent between brain cells when they’re communicating with each other. Study participants — kids in kindergarten through fourth grade — wear a cap outfitted with special sensors while playing a computerized reading game.
These scans produce massive amounts of data: The cap’s 10 sensors collect readings 500 times per second for 45 minutes. That’s one reason that brain activity studies are expensive and time-consuming. It’s also the reason that a study of just 150 children is the largest study of its kind.
Kara Federmeier, a professor of psychology at the University of Illinois, says it’s not just the scale of the study that’s impressive; it’s also the project’s duration. “Sarah will be able to assess how the brain transitions from immature reading processes to mature reading processes,” Federmeier says. “Her project promises to provide important, novel data that may be critical for informing educational practices about teaching reading and clinical practices for assessing reading-related difficulties.”
Why study this disorder in particular? Laszlo notes that there are significant, sometimes lifelong consequences of growing up with dyslexia. Many dyslexic children don’t do as well in school as they might otherwise, which limits their career opportunities. Some also encounter social problems. “This has the potential to help a lot of people,” she says.
Laszlo hopes to identify the brain signatures of people with dyslexia and have a clear idea of how to help them. “Once you understand what’s going on in the brain,” she says, “you can do a better job of designing treatments.”
Today, the best-case scenario is that children with dyslexia receive interventions that enable them to get up to speed on reading aloud. But they may continue to lag behind their peers when it comes to comprehension, fluency and speed. “The treatments we have now don’t always fix the underlying problem,” Laszlo says. “They just put a Band-Aid on it. And when you go to do more complicated things, like reading larger passages, the Band-Aid doesn’t help.”
How to Participate
Participants in Sarah Laszlo’s Reading Brain Project play a computerized reading game while researchers measure their brain activity. Children in kindergarten through fourth grade are eligible for the Binghamton University study and will receive $50 or an equivalent gift for their time. To sign up your child, call 607-269-7271 or e-mail readingbrain@binghamton.edu. For more details, visit www.binghamton.edu/reading-brain.
(Source: discovere.binghamton.edu)
Migraine is Associated with Variations in Structure of Brain Arteries
The network of arteries supplying blood flow to the brain is more likely to be incomplete in people who suffer migraine, a new study by researchers in the Perelman School of Medicine at the University of Pennsylvania reports. Variations in arterial anatomy lead to asymmetries in cerebral blood flow that might contribute to the process triggering migraines.
The arterial supply of blood to the brain is protected by a series of connections between the major arteries, termed the “circle of Willis” after the English physician who first described it in the 17th century. People with migraine, particularly migraine with aura, are more likely to be missing components of the circle of Willis.
Migraine affects an estimated 28 million Americans, causing significant disability. Experts once believed that migraine was caused by dilation of blood vessels in the head, while more recently it has been attributed to abnormal neuronal signals. In this study, appearing in PLOS ONE, researchers suggest that blood vessels play a different role than previously suspected: structural alterations of the blood supply to the brain may increase susceptibility to changes in cerebral blood flow, contributing to the abnormal neuronal activity that starts migraine.
"People with migraine actually have differences in the structure of their blood vessels - this is something you are born with," said the study’s lead author, Brett Cucchiara, MD, Associate Professor of Neurology. "These differences seem to be associated with changes in blood flow in the brain, and it’s possible that these changes may trigger migraine, which may explain why some people, for instance, notice that dehydration triggers their headaches."
In a study of 170 people from three groups - a control group with no headaches, those who had migraine with aura, and those who had migraine without aura - the team found that an incomplete circle of Willis was more common in people with migraine with aura (73 percent) and migraine without aura (67 percent), compared to a headache-free control group (51 percent). The team used magnetic resonance angiography to examine blood vessel structure and a noninvasive magnetic resonance imaging method pioneered at the University of Pennsylvania, called Arterial spin labeling (ASL), to measure changes in cerebral blood flow.
"Abnormalities in both the circle of Willis and blood flow were most prominent in the back of the brain, where the visual cortex is located. This may help explain why the most common migraine auras consist of visual symptoms such as seeing distortions, spots, or wavy lines,” said the study’s senior author, John Detre, MD, Professor of Neurology and Radiology.
Both migraine and incomplete circle of Willis are common, and the observed association is likely one of many factors that contribute to migraine in any individual. The researchers suggest that at some point diagnostic tests of circle of Willis integrity and function could help pinpoint this contributing factor in an individual patient. Treatment strategies might then be personalized and tested in specific subgroups.
Haste and waste on neuronal pathways
Researchers of the Department of Biosystems Science and Engineering of ETH Zurich were able to measure the speed of neuronal signal conduction along segments of single axons in neuronal cultures by using a high-resolution electrical method. The bioengineers are now searching for plausible explanations for the large conduction speed variations.
To write this little piece of text, the brain sends commands to arms and fingers to tap on the keyboard. Neuronal cells with their cable-like extensions, such as axons, transfer this information as electrical pulses that trigger muscles to move. The axonal signal speed can be to up to 100m/s in myelinated axons along the spinal cord. For a long time, scientists assumed that axonal signal conduction is by and large digital: either there is a signal, “1”, or there is no signal, “0”.
Strong propagation speed variations
Now, a team of researchers under Douglas Bakkum and Andreas Hierlemann at the Department BSSE of ETH Zurich in Basel presents evidence that there may be more to axons than only digital signal conduction. They could directly measure and demonstrate that the speed of an axonal signal varies considerably within different segments of the very same axon by placing hundreds of electrodes along the axon. Moreover, the velocity pattern changed from day to day or within hours as did the morphology and position of the axon.
The exact meaning of these speed variations and the origin cannot be explained yet, as there is too little information available about axonal conduction. This may, to a large part, be a consequence of the tiny diameter of the axons. The length of an axon can be more than a meter, e.g., in the spinal cord, but the average diameter is in between 80 nm and a few micrometers. This small diameter makes any measurement of axonal potentials difficult, which, of course, also renders establishing the mechanisms that may produce the large speed variations a difficult task.
Unclear cause
Up to now, only hypotheses concerning these speed variations exist. The temporal characteristics of axonal conduction may form part of the overall information processing abilities of ensembles of neurons or contribute to how neurons adapt to new information. The research group plans on further investigating these effects in collaboration with researchers in other disciplines and research institutions that have complementary expertise and technologies. The related research work is also facilitated through Hierlemann’s 5-year ERC Advanced Grant and Bakkum’s SNF Ambizione Grant awarded in 2010/2011. However, the researchers do not expect a fast elucidation of the axonal speed variations. Considering the small dimensions of axons, it will probably take years to collect conclusive evidence.
Up to now, a detailed and long-term investigation of signals of ensembles of neurons and their axons was hardly possible. The BSSE research group, during the last 10 years, devoted a lot of time and efforts to develop the high-resolution microelectronic chips, hosting thousands of microelectrodes. The now published, detailed and precise axonal propagation speed measurements reward the scientists for their investment and validate the approach. “We hope to acquire important new evidence with our technology,” they state. Other technologies have not yet provided a high enough spatio-temporal resolution to characterize details of axonal signal conduction.
High-resolution chip developed
The microelectrode array chip of the BSSE research group has 11’000 electrodes within a very small area (3150 electrodes per square millimeter) that record from or stimulate neuronal cells or ensembles. Data from 126 arbitrarily selectable electrodes can be simultaneously recorded by means of custom-developed on-chip microelectronic circuits. The neuronal cells grow directly atop the circuitry units on the microelectronic chip, which is fabricated in industrial complementary-metal-oxide-semiconductor (CMOS) technology. Signals traveling along the axons of the neurons can be measured and localized at high spatial and temporal resolution, owing to the small electrode diameter and tight electrode spacing. Moreover, electrodes can be used to stimulate single axons with the aim to evoke action potentials that propagate back to the respective cell body or soma and elicit action potentials there.
In his opinion, the neuroscience community has underestimated the potential of microelectrodes arrays for quite some time, says Prof. Hierlemann. With the work published now in “Nature Communications”, he hopes to further establish this method. “These results show that the microelectrode array technology is enabling access to data that are currently not accessible through other technologies,” says the bioengineer.
Neurons, axons and signal propagation
Nerve cells or neurons communicate with other neurons via electrical and chemical signals. If an electrical signal within a cell body, close to the axon initial segment, is large enough, it enters the axon and propagates along its length at a high speed. This is achieved by alterations in the so-called resting potential of the axon membrane, which usually has a steady negative value. Sodium ion channels open, and because of a concentration gradient, positively charged sodium ions from outside the axon travel into the axon. As a consequence, the membrane potential is briefly reversed in polarity until potassium channels open and positively charged potassium ions are released into the external liquid. This brief change in membrane potential, a so-called action potential, can be detected with the microelectrode array chip. An action potential travels without attenuation to synapses, neuron-to-neuron junctions, where the electrical signal is translated into a chemical signal: neurotransmitters are released, diffuse through the small synaptic cleft and initiate electrical activity in the neighboring postsynaptic cell. After an action potential event, the original sodium and potassium ion concentrations outside and inside of the axonal membrane and the associated resting potential across the membrane are restored through membrane pumps. The overall duration of an action potential event is on the order of 2 milliseconds.
Reference
Bakkum DJ, Frey U, Radivojevic M, Russell TL, Müller J, Fiscella M, Takahashi H & Hierlemann A. Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites. Nature Communications, first published online 19th July 2013. DOI: 10.1038/ncomms3181
Scientists identify neural origins of hot flashes in menopausal women
A new study from neuroscientists at the Wayne State University School of Medicine provides the first novel insights into the neural origins of hot flashes in menopausal women in years. The study may inform and eventually lead to new treatments for those who experience the sudden but temporary episodes of body warmth, flushing and sweating.
The paper, “Temporal Sequencing of Brain Activations During Naturally Occurring Thermoregulatory Events,” by Robert Freedman, Ph.D., professor of psychiatry and behavioral neurosciences, founder of the Behavioral Medicine Laboratory and a member at the C.S. Mott Center for Human Growth and Development, and his collaborator, Vaibhav Diwadkar, Ph.D., associate professor of psychiatry and behavioral neurosciences, appears in the June issue of Cerebral Cortex, an Oxford University Press journal.
“The idea of understanding brain responses during thermoregulatory events has spawned many studies where thermal stimuli were applied to the skin. But hot flashes are unique because they are internally generated, so studying them presents unique challenges,” said Freedman, the study’s principal investigator. “Our participants had to lie in the MRI scanner while being heated between two body-size heating pads for up to two hours while we waited for the onset of a hot flash. They were heroic in this regard and the study could not have been conducted without their incredible level of cooperation.”
“Menopause and hot flashes are a significant women’s health issue of widespread general interest,” Diwadkar added. “However, understanding of the neural origins of hot flashes has remained poor. The question has rarely been assessed with in vivo functional neuroimaging. In part, this paucity of studies reflects the technical limitations of objectively identifying hot flashes while symptomatic women are being scanned with MRI. Nothing like this has been published because this is a very difficult study to do.”
During the course of a single year, 20 healthy, symptomatic postmenopausal women ages 47 to 58 who reported six or more hot flashes a day were scanned at the School of Medicine’s Vaitkevicius Imaging Center, located in Detroit’s Harper University Hospital.
The researchers collected skin conductance levels to identify the onset of flashes while the women were being scanned. Skin conductance is an electrical measure of sweating. The women were connected to a simple circuit passing a very small current across their chests, Diwadkar said. Changes in levels allowed researchers to identify a hot flash onset and analyze the concurrently acquired fMRI data to investigate the neural precedents and correlates of the event.
The researchers focused on regions like the brain stem because its sub regions, such as the medullary and dorsal raphe, are implicated in thermal regulation, while forebrain regions, such as the insula, have been implicated in the personal perception of how someone feels. They showed that activity in some brain areas, such as the brain stem, begins to rise before the actual onset of the hot flash.
“Frankly, evidence of fMRI-measured rise in the activity of the brain stem even before women experience a hot flash is a stunning result. When this finding is considered along with the fact that activity in the insula only rises after the experience of the hot flash, we gain some insight on the complexity of brain mechanisms that mediate basic regulatory functions,” Diwadkar said.
These results point to the plausible origins of hot flashes in specific brain regions. The researchers believe it is the first such demonstration in academic literature.
They are now evaluating the network-based interactions between the brain regions by using more complex modeling of the fMRI data. “We think that our study highlights the value of using well-designed fMRI paradigms and analyses in understanding clinically relevant questions,” Diwadkar said.
The researchers also are exploring possibilities for integrating imaging with treatment to examine whether specific pharmacotherapies for menopause might alter regional brain responses.
(Source: media.wayne.edu)