Posts tagged neuroimaging
Articles and news from the latest research reports.
Blood Test Accurately Diagnoses Concussion and Predicts Long Term Cognitive Disability
A new blood biomarker correctly predicted which concussion victims went on to have white matter tract structural damage and persistent cognitive dysfunction following a mild traumatic brain injury (mTBI). Researchers in the Perelman School of Medicine at the University of Pennsylvania, in conjunction with colleagues at Baylor College of Medicine, found that the blood levels of a protein called calpain-cleaved αII-spectrin N-terminal fragment (SNTF) were twice as high in a subset of patients following a traumatic injury. If validated in larger studies, this blood test could identify concussion patients at increased risk for persistent cognitive dysfunction or further brain damage and disability if returning to sports or military activities.
More than 1.5 million children and adults suffer concussions each year in the United States, and hundreds of thousands of military personal endure these mild traumatic brain injuries worldwide. Current tests are not capable of determining the extent of the injury or whether the injured person will be among the 15-30 percent who experience significant, persistent cognitive deficits, such as processing speed, working memory and the ability to switch or balance multiple thoughts.
"New tests that are fast, simple, and reliable are badly needed to predict who may experience long-term effects from concussions, and as new treatments are developed in the future, to identify who should be eligible for clinical trials or early interventions," said lead author Robert Siman, PhD, research professor of Neurosurgery at Penn. "Measuring the blood levels of SNTF on the day of a brain injury may help to identify the subset of concussed patients who are at risk of persistent disability."
In a study published yesterday in Frontiers in Neurology, Penn and Baylor researchers evaluated blood samples and diffusion tensor images from a subgroup of 38 participants in a larger study of mTBI with ages ranging from 15 to 25 years old. 17 had sustained a head injury caused by blunt trauma, acceleration or deceleration forces, 13 had an orthopaedic injury, and 8 were healthy, uninjured, demographically matched controls.
In taking neuropsychological and cognitive tests over the course of three months, results within the mTBI group varied considerably, with some patients performing as well as the healthy controls throughout, while others showed impairment initially that resolved by three months, and a third group with cognitive dysfunction persisting through three months. The nine patients who had abnormally high levels of SNTF (7 mTBI and 2 orthopaedic patients) also had significant white matter damage apparent in radiological imaging.
"The blood test identified SNTF in some of the orthopaedic injury patients as well, suggesting that these injuries could also lead to abnormalities in the brain, such as a concussion, that may have been overlooked with existing tests," said Douglas Smith, MD, director of the Penn Center for Brain Injury and Repair and professor of Neurosurgery. "SNTF as a marker is consistent with our earlier research showing that calcium is dumped into neurons following a traumatic brain injury, as SNTF is a marker for neurodegeneration driven by calcium overload."
The blood test given on the day of the mild traumatic brain injury showed 100 percent sensitivity to predict concussions leading to persisting cognitive problems, and 75 percent specificity to correctly rule out those without functionally harmful concussions. If validated in larger studies, a blood test measuring levels of SNTF could be helpful in diagnosing and predicting risk of long term consequences of concussion. The Penn and Baylor researchers hope to determine the robustness of these findings with a second larger study, and determine the best time after concussion to measure SNTF in the blood in order to predict persistent brain dysfunction. The team also wants to evaluate their blood test for identifying when repetitive concussions begin to cause brain damage and persistent disability.
(Source: uphs.upenn.edu)
Glowing Worms Illuminate Roots of Behavior
A research team at Worcester Polytechnic Institute (WPI) and The Rockefeller University in New York has developed a novel system to image brain activity in multiple awake and unconstrained worms. The technology, which makes it possible to study the genetics and neural circuitry associated with animal behavior, can also be used as a high-throughput screening tool for drug development targeting autism, anxiety, depression, schizophrenia, and other brain disorders.
Image: Neurons in the worms (marked by arrows) glow as the animals sense attractive odors.
The team details their technology and early results in the paper “High-throughput imaging of neuronal activity in Caenorhabditis elegans,” published on-line in advance of print by the journal Proceedings of the National Academy of Sciences.
"One of our major objectives is to understand the neural signals that direct behavior—how sensory information is processed through a network of neurons leading to specific decisions and responses," said Dirk Albrecht, PhD, assistant professor of biomedical engineering at WPI and senior author of the paper. Albrecht led the research team both at WPI and at Rockefeller, where he served previously as a postdoctoral researcher in the lab of Cori Bargmann, PhD, a Howard Hughes Medical Institute Investigator and a co-author of the new paper.
To study neuronal activity, Albrecht’s lab uses the tiny worm Caenorhabditis elegans (C. elegans), a nematode found in many environments around the world. A typical adult C. elegans is just 1 millimeter long and has 969 cells, of which 302 are neurons. Despite its small size, the worm is a complex organism able to do all of the things animals must do to survive. It can move, eat, mate, and process environmental cues that help it forage for food or react to threats. As a bonus for researchers, C.elegans is transparent. By using various imaging technologies, including optical microscopes, one can literally see into the worm and watch physiological processes in real time.
Numerous studies have been done by “worm labs” around the world exploring various neurological processes in C. elegans. These have typically been done using one worm at a time, with the animal’s body fixed in place on a slide. In their new paper, Albrecht’s team details how they imaged, recorded, and analyzed specific neurons in multiple animals as they wormed their way around a custom-designed microfluidic array, called an arena, where they were exposed to favorable or hostile sensory cues.
Specifically, the team engineered a strain of worms with neurons near the head that would glow when they sensed food odors. In experiments involving up to 23 worms at a time, Albrecht’s team infused pulses of attractive or repulsive odors into the arena and watched how the worms reacted. In general, the worms moved towards the positive odors and away from the negative odors, but the behaviors did not always follow this pattern. “We were able to show that the sensory neurons responded to the odors similarly in all the animals, but their behavioral responses differed significantly,” Albrecht said. “These animals are genetically identical, and they were raised together in the same environment, so where do their different choices come from?”
In addition to watching the head neurons light up as they picked up odor cues, the new system can trace signaling through “interneurons.” These are pathways that connect external sensors to the rest of the network (the “worm brain”) and send signals to muscle cells that adjust the worm’s movement based on the cues. Numerous brain disorders in people are believed to arise when neural networks malfunction. In some cases the malfunction is dramatic overreaction to a routine stimulus, while in others it is a lack of appropriate reactions to important cues. Since C. elegans and humans share many of the same genes, discovering genetic causes for differing neuronal responses in worms could be applicable to human physiology. Experimental compounds designed to modulate the action of nerve cells and neuronal networks could be tested first on worms using Albrecht’s new system. The compounds would be infused in the worm arena, along with other stimuli, and the reaction of the worms’ nervous systems could be imaged and analyzed.
"The basis of our work is to combine biomedical engineering and neuroscience to answer some of these fundamental questions and hopefully gain insight that would be beneficial for understanding and eventually treating human disorders," Albrecht said.
(Source: wpi.edu)
Your Brain Sees Things You Don’t
University of Arizona doctoral degree candidate Jay Sanguinetti has authored a new study, published online in the journal Psychological Science, that indicates that the brain processes and understands visual input that we may never consciously perceive.
The finding challenges currently accepted models about how the brain processes visual information.
A doctoral candidate in the UA’s Department of Psychology in the College of Science, Sanguinetti showed study participants a series of black silhouettes, some of which contained meaningful, real-world objects hidden in the white spaces on the outsides.
Saguinetti worked with his adviser Mary Peterson, a professor of psychology and director of the UA’s Cognitive Science Program, and with John Allen, a UA Distinguished Professor of psychology, cognitive science and neuroscience, to monitor subjects’ brainwaves with an electroencephalogram, or EEG, while they viewed the objects.
"We were asking the question of whether the brain was processing the meaning of the objects that are on the outside of these silhouettes," Sanguinetti said. "The specific question was, ‘Does the brain process those hidden shapes to the level of meaning, even when the subject doesn’t consciously see them?"
The answer, Sanguinetti’s data indicates, is yes.
Study participants’ brainwaves indicated that even if a person never consciously recognized the shapes on the outside of the image, their brains still processed those shapes to the level of understanding their meaning.
"There’s a brain signature for meaningful processing," Sanguinetti said. A peak in the averaged brainwaves called N400 indicates that the brain has recognized an object and associated it with a particular meaning.
"It happens about 400 milliseconds after the image is shown, less than a half a second," said Peterson. "As one looks at brainwaves, they’re undulating above a baseline axis and below that axis. The negative ones below the axis are called N and positive ones above the axis are called P, so N400 means it’s a negative waveform that happens approximately 400 milliseconds after the image is shown."
The presence of the N400 peak indicates that subjects’ brains recognize the meaning of the shapes on the outside of the figure.
"The participants in our experiments don’t see those shapes on the outside; nonetheless, the brain signature tells us that they have processed the meaning of those shapes," said Peterson. "But the brain rejects them as interpretations, and if it rejects the shapes from conscious perception, then you won’t have any awareness of them."
"We also have novel silhouettes as experimental controls," Sanguinetti said. "These are novel black shapes in the middle and nothing meaningful on the outside."
The N400 waveform does not appear on the EEG of subjects when they are seeing truly novel silhouettes, without images of any real-world objects, indicating that the brain does not recognize a meaningful object in the image.
"This is huge," Peterson said. "We have neural evidence that the brain is processing the shape and its meaning of the hidden images in the silhouettes we showed to participants in our study."
The finding leads to the question of why the brain would process the meaning of a shape when a person is ultimately not going to perceive it, Sanguinetti said.
"The traditional opinion in vision research is that this would be wasteful in terms of resources," he explained. "If you’re not going to ultimately see the object on the outside why would the brain waste all these processing resources and process that image up to the level of meaning?"
"Many, many theorists assume that because it takes a lot of energy for brain processing, that the brain is only going to spend time processing what you’re ultimately going to perceive," added Peterson. "But in fact the brain is deciding what you’re going to perceive, and it’s processing all of the information and then it’s determining what’s the best interpretation."
"This is a window into what the brain is doing all the time," Peterson said. "It’s always sifting through a variety of possibilities and finding the best interpretation for what’s out there. And the best interpretation may vary with the situation."
Our brains may have evolved to sift through the barrage of visual input in our eyes and identify those things that are most important for us to consciously perceive, such as a threat or resources such as food, Peterson suggested.
In the future, Peterson and Sanguinetti plan to look for the specific regions in the brain where the processing of meaning occurs.
"We’re trying to look at exactly what brain regions are involved," said Peterson. "The EEG tells us this processing is happening and it tells us when it’s happening, but it doesn’t tell us where it’s occurring in the brain."
"We want to look inside the brain to understand where and how this meaning is processed," said Peterson.
Images were shown to Sanguinetti’s study participants for only 170 milliseconds, yet their brains were able to complete the complex processes necessary to interpret the meaning of the hidden objects.
"There are a lot of processes that happen in the brain to help us interpret all the complexity that hits our eyeballs," Sanguinetti said. "The brain is able to process and interpret this information very quickly."
Sanguinetti’s study indicates that in our everyday life, as we walk down the street, for example, our brains may recognize many meaningful objects in the visual scene, but ultimately we are aware of only a handful of those objects.
The brain is working to provide us with the best, most useful possible interpretation of the visual world, Sanguinetti said, an interpretation that does not necessarily include all the information in the visual input.
![Researcher Seeks to Help Those Who Can’t Speak for Themselves
When people appear comatose, how can we know their wishes?
A Michigan Technological University researcher says many non-communicative individuals may actually be able to express themselves better than is widely thought.
Syd Johnson, assistant professor of philosophy, has just published a paper in the American Journal of Bioethics: Neuroscience that argues that even patients with severe brain injuries could have more self-determination and empowerment. “New research with people using just their brains to communicate reveals that more of them might be able to make their own decisions,” she says.
Those decisions can literally be life and death, and the first question a caregiver should ask is “How do we determine if they are capable—as an ordinary person would be—of making these decisions?” Johnson asks.
She says because of their brain injuries, many have limited attention spans or movement/speech disorders that make it very difficult to communicate. “That’s why it’s important to find ways of assessing their wellbeing other than by asking them,” she says. “Being able to do that would open up the possibility of assessing quality of life even in those who have never been able to communicate, such as infants or people born with severe cognitive disabilities.”
And that leads to the tough questions, Johnson points out.
“Who makes the decision that someone desires, or not, to live in this state? Who makes the life assessment for people: to treat them or to allow them to die.”
The range of potential patients runs the gamut from grandparents to infants, Johnson says. Sometimes you can’t ask them, including those with cognitive disabilities, but sometimes you can.
She acknowledges the complexity of the issue, especially when decisions involve quality of life. “We assume they don’t want to live that way, but sometimes, are they okay?”
She uses the example of locked-in syndrome, where patients can blink “yes” or “no.” A majority says they are doing okay.
“So, then do we make a decision based on what we think it is like to be in that position?” Johnson says.
Many people adjust to this new way of life, she says, and it’s important for caregivers to get into their mind, to recognize what might be a foreign viewpoint for an able-bodied person.
“Then there are the misdiagnosed,” Johnson says. “As many as 40 percent could be conscious at some level, even in a permanent vegetative state. Even in a nursing home, it can be that no one is assessing them, and they might improve. Nobody is diagnosing anymore, and they are treated as if they are not ever going to get better.”
Researchers around the globe have begun to address these issues, and new evidence is coming in, thanks in part to fMRI: functional magnetic resonance imaging—a technique that directly measures the blood flow in the brain that can provide information on brain activity.
“Even EEGs [electroencephalograms, which measure electrical activity in the brain] can be used,” she says. “The patients can be asked questions and given two things to think about for answers: playing tennis for yes, walking around in their house for no. And different parts of their brain will light up. People can be conscious while appearing outwardly unconscious.”
The end-result could mean reassessing the quality of life, Johnson says. Some patients can be asked—the so-called “covertly aware” patients who are conscious but can communicate only with technological assistance.
“Just as importantly, we might be able to use technology to objectively measure aspects of quality of life even in patients who cannot communicate at all,” Johnson says.
The ethical issues loom.
“A person’s quality of life is inherently subjective, and the aim of quality of life assessment has always been to find ways to objectively measure that subjective state of being,” she says. “New technologies like fMRI might be able to provide a different kind of objective assessment of subjective wellbeing—by looking at brain activity—in those individuals who are unable to tell us how they’re doing.”](http://40.media.tumblr.com/ce0e8428706a17904c2f68ea5825b39a/tumblr_mvxwqpuv7I1rog5d1o1_500.jpg)
Researcher Seeks to Help Those Who Can’t Speak for Themselves
When people appear comatose, how can we know their wishes?
A Michigan Technological University researcher says many non-communicative individuals may actually be able to express themselves better than is widely thought.
Syd Johnson, assistant professor of philosophy, has just published a paper in the American Journal of Bioethics: Neuroscience that argues that even patients with severe brain injuries could have more self-determination and empowerment. “New research with people using just their brains to communicate reveals that more of them might be able to make their own decisions,” she says.
Those decisions can literally be life and death, and the first question a caregiver should ask is “How do we determine if they are capable—as an ordinary person would be—of making these decisions?” Johnson asks.
She says because of their brain injuries, many have limited attention spans or movement/speech disorders that make it very difficult to communicate. “That’s why it’s important to find ways of assessing their wellbeing other than by asking them,” she says. “Being able to do that would open up the possibility of assessing quality of life even in those who have never been able to communicate, such as infants or people born with severe cognitive disabilities.”
And that leads to the tough questions, Johnson points out.
“Who makes the decision that someone desires, or not, to live in this state? Who makes the life assessment for people: to treat them or to allow them to die.”
The range of potential patients runs the gamut from grandparents to infants, Johnson says. Sometimes you can’t ask them, including those with cognitive disabilities, but sometimes you can.
She acknowledges the complexity of the issue, especially when decisions involve quality of life. “We assume they don’t want to live that way, but sometimes, are they okay?”
She uses the example of locked-in syndrome, where patients can blink “yes” or “no.” A majority says they are doing okay.
“So, then do we make a decision based on what we think it is like to be in that position?” Johnson says.
Many people adjust to this new way of life, she says, and it’s important for caregivers to get into their mind, to recognize what might be a foreign viewpoint for an able-bodied person.
“Then there are the misdiagnosed,” Johnson says. “As many as 40 percent could be conscious at some level, even in a permanent vegetative state. Even in a nursing home, it can be that no one is assessing them, and they might improve. Nobody is diagnosing anymore, and they are treated as if they are not ever going to get better.”
Researchers around the globe have begun to address these issues, and new evidence is coming in, thanks in part to fMRI: functional magnetic resonance imaging—a technique that directly measures the blood flow in the brain that can provide information on brain activity.
“Even EEGs [electroencephalograms, which measure electrical activity in the brain] can be used,” she says. “The patients can be asked questions and given two things to think about for answers: playing tennis for yes, walking around in their house for no. And different parts of their brain will light up. People can be conscious while appearing outwardly unconscious.”
The end-result could mean reassessing the quality of life, Johnson says. Some patients can be asked—the so-called “covertly aware” patients who are conscious but can communicate only with technological assistance.
“Just as importantly, we might be able to use technology to objectively measure aspects of quality of life even in patients who cannot communicate at all,” Johnson says.
The ethical issues loom.
“A person’s quality of life is inherently subjective, and the aim of quality of life assessment has always been to find ways to objectively measure that subjective state of being,” she says. “New technologies like fMRI might be able to provide a different kind of objective assessment of subjective wellbeing—by looking at brain activity—in those individuals who are unable to tell us how they’re doing.”
Social symptoms in autistic children may be caused by hyper-connected neurons
The brains of children with autism show more connections than the brains of typically developing children do. What’s more, the brains of individuals with the most severe social symptoms are also the most hyper-connected. The findings reported in two independent studies published in the Cell Press journal Cell Reports (1, 2) on November 7th are challenge the prevailing notion in the field that autistic brains are lacking in neural connections.
The findings could lead to new treatment strategies and new ways to detect autism early, the researchers say. Autism spectrum disorder is a neurodevelopmental condition affecting nearly 1 in 88 children.
"Our study addresses one of the hottest open questions in autism research," said Kaustubh Supekar of Stanford University School of Medicine of his and his colleague Vinod Menon’s study aimed at characterizing whole-brain connectivity in children. "Using one of the largest and most heterogeneous pediatric functional neuroimaging datasets to date, we demonstrate that the brains of children with autism are hyper-connected in ways that are related to the severity of social impairment exhibited by these children."
In the second Cell Reports study, Ralph-Axel Müller and colleagues at San Diego State University focused specifically on neighboring brain regions to find an atypical increase in connections in adolescents with a diagnosis of autism spectrum disorder. That over-connection, which his team observed particularly in the regions of the brain that control vision, was also linked to symptom severity.
"Our findings support the special status of the visual system in children with heavier symptom load," Müller said, noting that all of the participants in his study were considered "high-functioning" with IQs above 70. He says measures of local connectivity in the cortex might be used as an aid to diagnosis, which today is based purely on behavioral criteria.
For Supekar and Menon, these new views of the autistic brain raise the intriguing possibility that epilepsy drugs might be used to treat autism.
"Our findings suggest that the imbalance of excitation and inhibition in the local brain circuits could engender cognitive and behavioral deficits observed in autism," Menon said. That imbalance is a hallmark of epilepsy as well, which might explain why children with autism so often suffer with epilepsy too.
"Drawing from these observations, it might not be too far fetched to speculate that the existing drugs used to treat epilepsy may be potentially useful in treating autism," Supekar said.
(Source: eurekalert.org)
Personal reflection triggers increased brain activity during depressive episodes
Research by the University of Liverpool has found that people experiencing depressive episodes display increased brain activity when they think about themselves.
Using functional magnetic resonance imaging (fMRI) brain imaging technologies, scientists found that people experiencing a depressive episode process information about themselves in the brain differently to people who are not depressed.
British Queen
Researchers scanned the brains of people in major depressive episodes and those that weren’t whilst they chose positive, negative and neutral adjectives to describe either themselves or the British Queen - a figure significantly removed from their daily lives but one that all participants were familiar with.
Professor Peter Kinderman, Head of the University’s Institute of Psychology, Health and Society, said: “We found that participants who were experiencing depressed mood chose significantly fewer positive words and more negative and neutral words to describe themselves, in comparison to participants who were not depressed.
“That’s not too surprising, but the brain scans also revealed significantly greater blood oxygen levels in the medial superior frontal cortex – the area associated with processing self-related information – when the depressed participants were making judgments about themselves.
“This research leads the way for further studies into the psychological and neural processes that accompany depressed mood. Understanding more about how people evaluate themselves when they are depressed, and how neural processes are involved could lead to improved understanding and care.”
Dr May Sarsam, from the Mersey Care NHS Trust, said: “This study explored the difference in medical and psychological theories of depression. It showed that brain activity only differed when depressed people thought about themselves, not when they thought about the Queen or when they made other types of judgements, which fits very well with the current psychological theory.
Equally important
“Thought and neurochemistry should be considered as equally important in our understanding of mental health difficulties such as depression.”
Depression is associated with extensive negative feelings and thoughts. Nearly one-fifth of adults experience anxiety or depression, with the conditions affecting a higher proportion of women than men.
The research, in collaboration with the Mersey Care NHS Trust and the Universities of Manchester, Edinburgh and Lancaster, is published in PLOS One.
Quantity, not just quality, in new Stanford brain scan method
Researchers used magnetic resonance imaging to quantify brain tissue volume, a critical measurement of the progression of multiple sclerosis and other diseases.
Imagine that your mechanic tells you that your brake pads seem thin, but doesn’t know how long they will last. Or that your doctor says your child has a temperature, but isn’t sure how high. Quantitative measurements help us make important decisions, especially in the doctor’s office. But a potent and popular diagnostic scan, magnetic resonance imaging (MRI), provides mostly qualitative information.
An interdisciplinary Stanford team has now developed a new method for quantitatively measuring human brain tissue using MRI. The team members measured the volume of large molecules (macromolecules) within each cubic millimeter of the brain. Their method may change the way doctors diagnose and treat neurological diseases such as multiple sclerosis.
"We’re moving from qualitative – saying something is off – to measuring how off it is," said Aviv Mezer, postdoctoral scholar in psychology. The team’s work, funded by research grants from the National Institutes of Health, appears in the journal Nature Medicine.
Mezer, whose background is in biophysics, found inspiration in seemingly unrelated basic research from the 1980s. In theory, he read, magnetic resonance could quantitatively discriminate between different types of tissues.
"Do the right modifications to make it applicable to humans," he said of adapting the previous work, "and you’ve got a new diagnostic."
Previous quantitative MRI measurements required uncomfortably long scan times. Mezer and psychology Professor Brian Wandell unearthed a faster scanning technique, albeit one noted for its lack of consistency.
"Now we’ve found a way to make the fast method reliable," Mezer said.
Mezer and Wandell, working with neuroscientists, radiologists and chemical engineers, calibrated their method with a physical model – a radiological “phantom” – filled with agar gel and cholesterol to mimic brain tissue in MRI scans.
The team used one of Stanford’s own MRI machines, located in the Center for Cognitive and Neurobiological Imaging, or CNI. Wandell directs the two-year-old center. Most psychologists, he said, don’t have that level of direct access to their MRI equipment.
"Usually there are many people between you and the instrument itself," Wandell said.
This study wouldn’t have happened, Mezer said, without the close proximity and open access to the instrumentation in the CNI.
Their results provided a new way to look at a living brain.
MRI images of the brain are made of many “voxels,” or three-dimensional elements. Each voxel represents the signal from a small volume of the brain, much like a pixel represents a small volume of an image. The fraction of each voxel filled with brain tissue (as opposed to water) is called the macromolecular tissue volume, or MTV. Different areas of the brain have different MTVs. Mezer found that his MRI method produced MTV values in agreement with measurements that, until now, could only come from post-mortem brain specimens.
This is a useful first measurement, Mezer said. “The MTV is the most basic entity of the structure. It’s what the tissue is made of.”
The team applied its method to a group of multiple sclerosis patients. MS attacks a layer of cells called the myelin sheath, which protects neurons the same way insulation protects a wire. Until now, doctors typically used qualitative MRI scans (displaying bright or dark lesions) or behavioral tests to assess the disease’s progression.
Myelin comprises most of the volume of the brain’s “white matter,” the core of the brain. As MS erodes myelin, the MTV of the white matter changes. Just as predicted, Mezer and Wandell found that MS patients’ white matter tissue volumes were significantly lower than those of healthy volunteers. Mezer and colleagues at Stanford School of Medicine are now following up with the patients to evaluate the effect of MS drug therapies. They’re using MTV values to track individual brain tissue changes over time.
The team’s results were consistent among five MRI machines.
Mezer and Wandell will next use MRI measurements to monitor brain development in children, particularly as the children learn to read. Wandell’s previous work mapped the neural connections involved in learning to read. MRI scans can measure how those connections form.
"You can compare whether the circuits are developing within specified limits for typical children," Wandell said, "or whether there are circuits that are wildly out of spec, and we ought to look into other ways to help the child learn to read."
Tracking MTV, the team said, helps doctors better compare patients’ brains to the general population – or to their own history – giving them a chance to act before it’s too late.
Neuroimaging study sheds light on mechanisms of cognitive fatigue in MS
A new study by Kessler Foundation scientists sheds light on the mechanisms underlying cognitive fatigue in individuals with multiple sclerosis. Cognitive fatigue is fatigue resulting from mental work rather than from physical labor. Genova H et al: Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging” was published on Nov. 1 in Plos One. This is the first study to use neuroimaging to investigate aspects of cognitive fatigue. The study was funded by grants from the National MS Society and Kessler Foundation.
The study investigated the neural correlates of cognitive fatigue in MS utilizing three neuroimaging approaches: functional magnetic resonance imaging (fMRI), which allows researchers to look at where in the brain activation is associated with a task or an experience; diffusion tensor imaging (DTI), which allows researchers to look at the health of the brain’s white matter; and voxel-based morphometry (VBM), which allows researchers to investigate structural changes in the brain. These three approaches were used to examine how likely it is for an individual to report fatigue(“trait” fatigue), as well as the fatigue an individual feels in the moment (“state” fatigue). This study is the first to use neuroimaging to investigate these two, separable aspects of fatigue.
“We looked specifically at the relationship between individuals ‘self-reported fatigue and objective measures of cognitive fatigue using state-of-the-art neuroimaging,” explained Helen M. Genova, Ph.D., research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation. “The importance of this work lies in the fact that it demonstrates that the subjective feeling of fatigue can be related to brain activation in specific brain regions. This provides us with an objective measure of fatigue, which will have incalculable value as we begin to test interventions designed to alleviate fatigue.”
In Experiment 1, patients were scanned during performance of a task designed to induce cognitive fatigue. Investigators looked at the brain activation associated with “state” fatigue. In Experiment 2, DTI was used to examine where in the brain white matter damage correlated with increased “trait” fatigue in individuals with MS, as assessed by the Fatigue Severity Scale (FSS). The findings of Experiments 1 and 2 support the role of a striato-thalamic-frontal cortical system in fatigue, suggesting a “fatigue-network” in MS.
“Identifying a network of fatigue-related brain regions could reframe the current construct of cognitive fatigue and help define the pathophysiology of this multifaceted yet elusive symptom of MS,” said John DeLuca, Ph.D., VP of Research & Training at Kessler Foundation. “Replication of these findings with larger sample sizes will be an important next step.”
The Visual Brain Colors Black and White Images
The perception and processing of color has fascinated neuroscientists for a long time, as our brain influences our perception of it to such a degree that colors could be called an illusion. One mystery was: What happens in the brain when we look at black-and-white photographs? Do our brains fill in the colors?
Neuroscientists Michael Bannert and Andreas Bartels of the Bernstein Center and the Werner Reichardt Centre for Integrative Neuroscience in Tübingen addressed these questions. In their work, published in the leading scientific journal Current Biology, they showed study participants black-and-white photos of bananas, broccoli, strawberries, and of other objects associated with a typical color (yellow, red and green in the examples above). While doing so, they recorded their subjects’ brain activity using functional imaging. The true purpose of the study was unknown to the subjects, and to distract their attention they were shown slowly rotating objects and told to report the direction in which they were moving.
After recording brain responses to the black and white objects, the scientists presented real colors to their subjects, in the shape of yellow, green, red and blue rings. This allowed them to record the activity of the brain as it responded to different, real colors.
It turned out that the mere sight of black-and-white photos automatically elicited brain activity patterns that specifically encoded colors. These activity patterns corresponded to those that were elicited when the observers viewed real color stimuli. These patterns encoded the typical color of the respective object seen, even though it was presented in black and white. The typical colors of the presented objects could therefore be determined from the brain’s activity, even though they were shown without color.
“It was particularly interesting that the colors of the objects were only encoded in the primary visual cortex,” says Michael Bannert. The primary visual cortex is one of the first places a visual signal arrives in the brain. Scientists had assumed it simply passed on information about the physical properties of things seen, but was not able to recognize objects or to store color knowledge associated with objects. “This result shows that higher-level prior knowledge – in this case of object-colors – is projected onto the earliest stages of visual processing,” according to Andreas Bartels.
This study represents a significant contribution to answering the question of how prior knowledge contributes to perception on a neuronal basis. The projection of prior knowledge onto the earliest processing stages of the visual brain may facilitate the recognition of objects in difficult and noisy environments, such as in fog, and be relevant for colors in changing light conditions over the course of the day, when the weather is overcast, when we are indoors and so on. On the other hand, if prior knowledge or expectations have too much influence on early visual processing stages, this may account for hallucinations and the pathological perception of illusions.
Neuroscientists Determine How Treatment for Anxiety Disorders Silences Fear Neurons
Excessive fear can develop after a traumatic experience, leading to anxiety disorders such as post-traumatic stress disorder and phobias. During exposure therapy, an effective and common treatment for anxiety disorders, the patient confronts a fear or memory of a traumatic event in a safe environment, which leads to a gradual loss of fear. A new study in mice, published online today in Neuron, reports that exposure therapy remodels an inhibitory junction in the amygdala, a brain region important for fear in mice and humans. The findings improve our understanding of how exposure therapy suppresses fear responses and may aid in developing more effective treatments. The study, led by researchers at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts, was partially funded by a New Innovator Award from the Office of the Director at the National Institutes of Health.
A fear-inducing situation activates a small group of neurons in the amygdala. Exposure therapy silences these fear neurons, causing them to be less active. As a result of this reduced activity, fear responses are alleviated. The research team sought to understand how exactly exposure therapy silences fear neurons.
The researchers found that exposure therapy not only silences fear neurons but also induces remodeling of a specific type of inhibitory junction, called the perisomatic synapse. Perisomatic inhibitory synapses are connections between neurons that enable one group of neurons to silence another group of neurons. Exposure therapy increases the number of perisomatic inhibitory synapses around fear neurons in the amygdala. This increase provides an explanation for how exposure therapy silences fear neurons.
“The increase in number of perisomatic inhibitory synapses is a form of remodeling in the brain. Interestingly, this form of remodeling does not seem to erase the memory of the fear-inducing event, but suppresses it,” said senior author, Leon Reijmers, Ph.D., assistant professor of neuroscience at Tufts University School of Medicine and member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.
Reijmers and his team discovered the increase in perisomatic inhibitory synapses by imaging neurons activated by fear in genetically manipulated mice. Connections in the human brain responsible for suppressing fear and storing fear memories are similar to those found in the mouse brain, making the mouse an appropriate model organism for studying fear circuits.
Mice were placed in a box and experienced a fear-inducing situation to create a fear response to the box. One group of mice, the control group, did not receive exposure therapy. Another group of mice, the comparison group, received exposure therapy to alleviate the fear response. For exposure therapy, the comparison group was repeatedly placed in the box without experiencing the fear-inducing situation, which led to a decreased fear response in these mice. This is also referred to as fear extinction.
The researchers found that mice subjected to exposure therapy had more perisomatic inhibitory synapses in the amygdala than mice who did not receive exposure therapy. Interestingly, this increase was found around fear neurons that became silent after exposure therapy.
“We showed that the remodeling of perisomatic inhibitory synapses is closely linked to the activity state of fear neurons. Our findings shed new light on the precise location where mechanisms of fear regulation might act. We hope that this will lead to new drug targets for improving exposure therapy,” said first author, Stéphanie Trouche, Ph.D., a former postdoctoral fellow in Reijmers’ lab at Tufts and now a medical research council investigator scientist at the University of Oxford in the United Kingdom.
“Exposure therapy in humans does not work for every patient, and in patients that do respond to the treatment, it rarely leads to a complete and permanent suppression of fear. For this reason, there is a need for treatments that can make exposure therapy more effective,” Reijmers added.
(Source: now.tufts.edu)