Posts tagged science
Articles and news from the latest research reports.
(Image caption: MRI images from a neurotypical control (left) and an adult with complete agenesis of the corpus callosum (right). The corpus callosum is indicated in red, fading as the fibers enter the hemispheres in order to suggest that they continue on. The anterior commissure is indicated by light aqua. The image illustrates the dramatic lack of inter hemispheric connections in callosal agenesis. Credit: Lynn Paul/Caltech)
Research Update: An Autism Connection
Building on their prior work, a team of neuroscientists at Caltech now report that rare patients who are missing connections between the left and right sides of their brain—a condition known as agenesis of the corpus callosum (AgCC)—show a strikingly high incidence of autism. The study is the first to show a link between the two disorders.
The findings are reported in a paper published April 22, 2014, in the journal Brain.
The corpus callosum is the largest connection in the human brain, connecting the left and right brain hemispheres via about 200 million fibers. In very rare cases it is surgically cut to treat epilepsy—causing the famous “split-brain” syndrome, for whose discovery the late Caltech professor Roger Sperry received the Nobel Prize. People with AgCC are like split-brain patients in that they are missing their corpus callosum—except they are born this way. In spite of this significant brain malformation, many of these individuals are relatively high-functioning individuals, with jobs and families, but they tend to have difficulty interacting with other people, among other symptoms such as memory deficits and developmental delays. These difficulties in social behavior bear a strong resemblance to those faced by high-functioning people with autism spectrum disorder.
"We and others had noted this resemblance between AgCC and autism before," explains Lynn Paul, lead author of the study and a lecturer in psychology at Caltech. But no one had directly compared the two groups of patients. This was a challenge that the Caltech team was uniquely positioned to do, she says, since it had studied patients from both groups over the years and had tested them on the same tasks.
"When we made detailed comparisons, we found that about a third of people with AgCC would meet diagnostic criteria for an autism spectrum disorder in terms of their current symptoms," says Paul, who was the founding president of the National Organization for Disorders of the Corpus Callosum.
The research was done in the laboratory of Ralph Adolphs, Bren Professor of Psychology and Neuroscience and professor of biology at Caltech and a coauthor of the study. The team looked at a range of different tasks performed by both sets of patients. Some of the exercises that involved certain social behaviors were videotaped and analyzed by the researchers to assess for autism. The team also gave the individuals questionnaires to fill out that measured factors like intelligence and social functioning.
"Comparing different clinical groups on exactly the same tasks within the same lab is very rare, and it took us about a decade to accrue all of the data," Adolphs notes.
One important difference between the two sets of patients did emerge in the comparison. People with autism spectrum disorder showed autism-like behaviors in infancy and early childhood, but the same type of behaviors did not seem to emerge in individuals with AgCC until later in childhood or the teen years.
"Around ages 9 through 12, a normally formed corpus callosum goes through a developmental ‘growth spurt’ which contributes to rapid advances in social skills and abstract thinking during those years," notes Paul. "Because they don’t have a corpus callosum, teens with AgCC become more socially awkward at the age when social skills are most important."
According to Adolphs, it is important to note that AgCC can now be diagnosed before a baby is born, using high-resolution ultrasound imaging during pregnancy. This latest development also opens the door for some exciting future directions in research.
"If we can identify people with AgCC already before birth, we should be in a much better position to provide interventions like social skills training before problems arise," Paul points out. "And of course from a research perspective it would be tremendously valuable to begin studying such individuals early in life, since we still know so little both about autism and about AgCC."
For example, the team would like to discern at what age subtle difficulties first appear in AgCC individuals, and at what point they start looking similar to autism, as well as what happens in the brain during these changes.
"If we could follow a baby with AgCC as it grows up, and visualize its brain with MRI each year, we would gain such a wealth of knowledge," Adolphs says.
Deep Brain Stimulation for Obsessive-Compulsive Disorder Releases Dopamine in the Brain
Some have characterized dopamine as the elixir of pleasure because so many rewarding stimuli – food, drugs, sex, exercise – trigger its release in the brain. However, more than a decade of research indicates that when drug use becomes compulsive, the related dopamine release becomes deficient in the striatum, a brain region that is involved in reward and behavioral control.
New research now published in Biological Psychiatry from the Academic Medical Center in Amsterdam suggests that dopamine release is increased in obsessive-compulsive disorder (OCD) and may be normalized by the therapeutic application of deep brain stimulation (DBS).
To conduct the study, the authors recruited clinically stable outpatients with OCD who had been receiving DBS therapy for greater than one year. The patients then underwent three single photon emission computerized tomography (SPECT) imaging scans to measure dopamine availability in the brain.
In order to evaluate the effect of DBS, these scans were conducted during chronic DBS, 8 days after DBS had been discontinued, and then after DBS was resumed. Designing the study in this manner also allowed the researchers to measure the relationship between dopamine availability and symptoms.
During the chronic DBS phase, patients showed increased striatal dopamine release compared to healthy volunteers. When DBS was turned off, patients showed worsening of symptoms and reduced dopamine release, which was reversed within one hour by the resumption of DBS. This observation suggests that enhancing striatal dopamine signaling may have some therapeutic effects for treatment-resistant symptoms of OCD.
First author Dr. Martijn Figee further explained, “DBS of the nucleus accumbens decreased central dopamine D2 receptor binding potential indicative of DBS-induced dopamine release. As dopamine is important for reward-motivated behaviors, these changes may explain why DBS is able to restore healthy behavior in patients suffering from OCD, but potentially other disorders involving compulsive behaviors, such as eating disorders or addiction.”
The patients selected for participation in this study had previously been non-responsive to traditional pharmacological therapies that target the dopamine system. These findings suggest that the effectiveness of DBS for OCD may be related to its ability to compensate for an underlying dysfunction of the dopaminergic system. The DBS-related stimulatory increase in dopamine appears to aid patients by improving their control over obsessive-compulsive behaviors.
“It is exciting to see circuit-based DBS linked to molecular brain imaging. This is a strategy that may shed light into the mechanisms through which this treatment can produce positive clinical change,” said Dr. John Krystal, Editor of Biological Psychiatry.
He also noted, “It would be interesting to know whether the patients who do respond to dopamine-blocking antipsychotic medications commonly prescribed for OCD symptoms have a different underlying disturbance in dopamine function than the patients enrolled in this study who failed to respond to these medications. Nonetheless, the findings of this study raise the possibility that some deficits in dopamine signaling in the brain that might be targeted by novel treatments may prevent adequate response to conventional treatments for this disorder.”
(Image: © Thom Graves)
Coming soon: a brain implant to restore memory
In the next few months, highly secretive US military researchers say they will unveil new advances toward developing a brain implant that could one day restore a wounded soldier’s memory.
The Defense Advanced Research Projects Agency (DARPA) is forging ahead with a four-year plan to build a sophisticated memory stimulator, as part of President Barack Obama’s $100 million initiative to better understand the human brain.
The science has never been done before, and raises ethical questions about whether the human mind should be manipulated in the name of staving off war injuries or managing the aging brain.
Controlling fear by modifying DNA
For many people, fear of flying or of spiders skittering across the lounge room floor is more than just a momentary increase in heart rate and a pair of sweaty palms.
It’s a hard-core phobia that can lead to crippling anxiety, but an international team of researchers, including neuroscientists from The University of Queensland’s Queensland Brain Institute (QBI), may have found a way to silence the gene that feeds this fear.
QBI senior research fellow Dr Timothy Bredy said the team had shed new light on the processes involved in loosening the grip of fear-related memories, particularly those implicated in conditions such as phobia and post-traumatic stress disorder.
Dr Bredy said they had discovered a novel mechanism of gene regulation associated with fear extinction, an inhibitory learning process thought to be critical for controlling fear when the response was no longer required.
“Rather than being static, the way genes function is incredibly dynamic and can be altered by our daily life experiences, with emotionally relevant events having a pronounced impact,” Dr Bredy said.
He said that by understanding the fundamental relationship between the way in which DNA functions without a change in the underlying sequence, future targets for therapeutic intervention in fear-related anxiety disorders could be developed.
“This may be achieved through the selective enhancement of memory for fear extinction by targeting genes that are subject to this novel mode of epigenetic regulation,” he said.
Mr Xiang Li, a PhD candidate and the study’s lead author, said fear extinction was a clear example of rapid behavioural adaptation, and that impairments in this process were critically involved in the development of fear-related anxiety disorders.
“What is most exciting is that we have revealed an epigenetic state that appears to be quite specific for fear extinction,” Mr Li said.
Dr Bredy said this was the first comprehensive analysis of how fear extinction was influenced by modifying DNA.
“It highlights the adaptive significance of experience-dependent changes in the chromatin landscape in the adult brain,” he said.
The collaborative research is being done by a team from QBI, the University of California, Irvine, and Harvard University.
The study was published this month in the Proceedings of the National Academy of Sciences of the United States of America.
Tell-tail MRI image diagnosis for Parkinson’s disease
An image similar in shape to a Swallow’s tail has been identified as a new and accurate test for Parkinson’s disease. The image, which depicts the healthy state of a group of cells in the sub-region of the human brain, was singled out using 3T MRI scanning technology – standard equipment in clinical settings today.
The research was led by Dr Stefan Schwarz and Professor Dorothee Auer, experts in neuroradiology in the School of Medicine at The University of Nottingham and was carried out at the Queen’s Medical Centre in collaboration with Dr Nin Bajaj, an expert in Movement Disorder Diseases at the Nottingham University Hospitals NHS Trust.
The findings have been published in the open access academic journal PLOS one.
The work builds on a successful collaboration with Professor Penny Gowland at the Sir Peter Mansfield Magnetic Resonance Centre at The University of Nottingham.
‘The ‘Swallow Tail’ Appearance of the Healthy Nigrosome – A New Accurate Test of Parkinson’s Disease: A Case-Control and Retrospective Cross-Sectional MRI Study at 3T’ – describes how the absence of this imaging sign can help to diagnose Parkinson’s disease using standard clinical Magnetic Resonance Scanners.
Parkinson’s disease is a progressive neurodegenerative disorder which destroys brain cells that control movement. Around 127,000 people in the UK have the disease. Currently there is no cure but drugs and treatments can be taken to manage the symptoms.
The challenges of diagnosing Parkinson’s
Until now diagnosing Parkinson’s in clinically uncertain cases has been limited to expensive nuclear medical techniques. The diagnosis can be challenging early in the course of the condition and in tremor dominant cases. Other non-licensed diagnostic techniques offer a varying range of accuracy, repeatability and reliability but none of them have demonstrated the required accuracy and ease of use to allow translation into standard clinical practice.
Using high resolution, ultra high filed 7T magnetic resonance imaging the Nottingham research team has already pinpointed the characteristic pathology of Parkinson’s with structural change in a small area of the mid brain known as the substantia nigra. The latest study has shown that these changes can also be detected using 3T MRI technology which is accessible in hospitals across the country. They subsequently coined the phrase the ‘swallow tail appearance’ as an easy recognizable sign of the healthy appearing substantia nigra which is lost in Parkinson’s disease. A total of 114 high-resolution scans were reviewed and in 94 per cent of cases the diagnosis was accurately made using this technique.
New findings give new hope
Dr Schwarz said: “This is a breakthrough finding as currently Parkinson’s disease is mostly diagnosed by identifying symptoms like stiffness and tremor. Imaging tests to confirm the diagnosis are limited to expensive nuclear medical techniques which are not widely available and associated with potentially harmful ionizing radiation.
“Using Magnetic Resonance Imaging (no ionizing radiation involved and much cheaper than nuclear medical techniques) we identified a specific imaging feature which has great similarity to a tail of a swallow and therefore decided to call it the ‘swallow tail sign’. This sign is absent in Parkinson’s disease.”
People Rely on What They Hear to Know What They’re Saying
You know what you’re going to say before you say it, right? Not necessarily, research suggests. A study from researchers at Lund University in Sweden shows that auditory feedback plays an important role in helping us determine what we’re saying as we speak. The study is published in Psychological Science, a journal of the Association for Psychological Science.
“Our results indicate that speakers listen to their own voices to help specify the meaning of what they are saying,” says researcher Andreas Lind of Lund University, lead author of the study.
Theories about how we produce speech often assume that we start with a clear, preverbal idea of what to say that goes through different levels of encoding to finally become an utterance.
But the findings from this study support an alternative model in which speech is more than just a dutiful translation of this preverbal message:
“These findings suggest that the meaning of an utterance is not entirely internal to the speaker, but that it is also determined by the feedback we receive from our utterances, and from the inferences we draw from the wider conversational context,” Lind explains.
For the study, Lind and colleagues recruited Swedish participants to complete a classic Stroop test, which provided a controlled linguistic setting. During the Stroop test, participants were presented with various color words (e.g., “red” or “green”) one at a time on a screen and were tasked with naming the color of the font that each word was printed in, rather than the color that the word itself signified.
The participants wore headphones that provided real-time auditory feedback as they took the test — unbeknownst to them, the researchers had rigged the feedback using a voice-triggered playback system. This system allowed the researchers to substitute specific phonologically similar but semantically distinct words (“grey”, “green”) in real time, a technique they call “Real-time Speech Exchange” or RSE.
Data from the 78 participants indicated that when the timing of the insertions was right, only about one third of the exchanges were detected.
On many of the non-detected trials, when asked to report what they had said, participants reported the word they had heard through feedback, rather than the word they had actually said. Because accuracy on the task was actually very high, the manipulated feedback effectively led participants to believe that they had made an error and said the wrong word.
Overall, Lind and colleagues found that participants accepted the manipulated feedback as having been self-produced on about 85% of the non-detected trials.
Together, these findings suggest that our understanding of our own utterances, and our sense of agency for those utterances, depend to some degree on inferences we make after we’ve made them.
Most surprising, perhaps, is the fact that while participants received several indications about what they actually said — from their tongue and jaw, from sound conducted through the bone, and from their memory of the correct alternative on the screen — they still treated the manipulated words as though they were self-produced.
This suggests, says Lind, that the effect may be even more pronounced in everyday conversation, which is less constrained and more ambiguous than the context offered by the Stroop test.
“In future studies, we want to apply RSE to situations that are more social and spontaneous — investigating, for example, how exchanged words might influence the way an interview or conversation develops,” says Lind.
“While this is technically challenging to execute, it could potentially tell us a great deal about how meaning and communicative intentions are formed in natural discourse,” he concludes.
Researcher: More study needed on interrogation techniques that measure brain waves
When police in Spain tried to locate two murder victims last year, they sought assistance on places to search from a tool that measured the brain activity of the convicted and confessed killers.
The technology, known as Brain Fingerprinting, developed by the American-based company Government Works Inc., basically seeks to use brain wave data in response to certain stimuli or details to determine whether a person is telling the truth. U.S. courts have sparingly allowed the higher-tech version of the traditional polygraph test or lie detector, and it has aided in both exoneration and conviction in American cases.
As the use of Brain Fingerprinting has expanded beyond the United States, a University of Kansas researcher argues the technology is based on an incorrect assumption about how human memory works.
"At the very least, we need to ask them to do several more methodological checks and make sure that whenever these technologies are used in legal contexts, we make clear the limitations of that technology," said Sarah Robins, an assistant professor of philosophy who studies the philosophy of neuroscience and related issues in neuroethics. “Maybe there’s a stronger claim here that this should never make it into court, but my stance is to say: ‘Let’s think about the technology and the assumptions behind it.’”
Robins details the theoretical issues surrounding Brain Fingerprinting in her essay “Memory Traces, Memory Errors, and the Possibility of Neural Lie Detection,” which will appear in “Brain Theory,” edited by Charles Wolfe. Also in Wolfe’s book, John Symons, a KU professor of philosophy, has co-authored the chapter “Computing with Bodies: Morphology, Function, and Computational Theory.”
Wolfe, a research fellow of the Department of Philosophy and Moral Sciences at the University of Ghent in Belgium, is scheduled to speak at 7 p.m. Friday, May 2, at the Kansas Room of the Kansas Union.
(Source: news.ku.edu)
Research Shows Strategic Thinking Strengthens Intellectual Capacity
Strategy-based cognitive training has the potential to enhance cognitive performance and spill over to real-life benefit according to a data-driven perspective article by the Center for BrainHealth at The University of Texas at Dallas published in the open-access journal Frontiers in Systems Neuroscience. The research-based perspective highlights cognitive, neural and real-life changes measured in randomized clinical trials that compared a gist-reasoning strategy-training program to memory training in populations ranging from teenagers to healthy older adults, individuals with brain injury to those at-risk for Alzheimer’s disease.
“Our brains are wired to be inspired,” said Dr. Sandra Bond Chapman, founder and chief director of the Center for BrainHeath and Dee Wyly Distinguished University Chair at The University of Texas at Dallas. “One of the key differences in our studies from other interventional research aimed at improving cognitive abilities is that we did not focus on specific cognitive functions such as speed of processing, memory, or learning isolated new skills. Instead, the gist reasoning training program encouraged use of a common set of multi-dimensional thinking strategies to synthesize information and elimination of toxic habits that impair efficient brain performance.”
The training across the studies was short, ranging from 8 to 12 sessions delivered over one to two months in 45 to 60 minute time periods. The protocol focused on three cognitive strategies — strategic attention, integrated reasoning and innovation. These strategies are hierarchical in nature and can be broadly applied to most complex daily life mental activities.
At a basic level, research participants were encouraged to filter competing information that is irrelevant and focus only on important information. At more advanced levels, participants were instructed to generate interpretations, themes or generalized statements from information they were wanting or needing to read, for example. Each strategy built on previous strategies and research participants were challenged to integrate all steps when tackling mental activities both inside and outside of training.
“Cognitive gains were documented in trained areas such as abstracting, reasoning, and innovating,” said Chapman. “And benefits also spilled over to untrained areas such as memory for facts, planning, and problem solving. What’s exciting about this work is that in randomized trials comparing gist reasoning training to memory training, we found that it was not learning new information that engaged widespread brain networks and elevated cognitive performance, but rather actually deeper processing of information and using that information in new ways that augmented brain performance.
Strengthening intellectual capacity is no longer science fiction; what used to seem improbable is now in the realm of reality.”
Positive physical changes within the brain and cognitive improvement across populations in response to strategy-based mental training demonstrate the neuro-regenerative potential of the brain.
“The ability to recognize, synthesize and create the essence of complex ideas and problems to solve are fundamental skills for academic, occupational and real-life success,” Chapman said. “The capacity to enhance cognition and complex neural networks in health, after injury or disease diagnosis will have major implications to preventing, diagnosing and treating cognitive decline and enhancing cognitive performance in youth to prepare them for an unknown future and in middle age to older adults who want to remain mentally robust.”
Stress is contagious. Observing another person in a stressful situation can be enough to make our own bodies release the stress hormone cortisol. This is the conclusion reached by scientists involved in a large-scale cooperation project between the departments of Tania Singer at the Max Planck Institute for Cognitive and Brain Sciences in Leipzig and Clemens Kirschbaum at the Technische Universität Dresden. Empathic stress arose primarily when the observer and stressed individual were partners in a couple relationship and the stressful situation could be directly observed through a one-way mirror. However, even the observation of stressed strangers via video transmission was enough to put some people on red alert. In our stress-ridden society, empathic stress is a phenomenon that should not be ignored by the health care system.
Stress is a major health threat in today’s society. It causes a range of psychological problems like burnout, depression and anxiety. Even those who lead relatively relaxed lives constantly come into contact with stressed individuals. Whether at work or on television: someone is always experiencing stress, and this stress can affect the general environment in a physiologically quantifiable way through increased concentrations of the stress hormone cortisol.
“The fact that we could actually measure this empathic stress in the form of a significant hormone release was astonishing,” says Veronika Engert, one of the study’s first authors. This is particularly true considering that many studies experience difficulties to induce firsthand stress to begin with. The authors found that empathic stress reactions could be independent of (“vicarious stress”) or proportional to (“stress resonance”) the stress reactions of the actively stressed individuals. “There must be a transmission mechanism via which the target’s state can elicit a similar state in the observer down to the level of a hormonal stress response.“
During the stress test, the test subjects had to struggle with difficult mental arithmetic tasks and interviews, while two supposed behavioural analysts assessed their performance. Only five percent of the directly stressed test subjects managed to remain calm; the others displayed a physiologically significant increase in their cortisol levels.
In total, 26 percent of observers who were not directly exposed to any stress whatsoever also showed a significant increase in cortisol. The effect was particularly strong when observer and stressed individual were partners in a couple relationship (40 percent). However, even when watching a complete stranger, the stress was transmitted to ten percent of the observers. Accordingly, emotional closeness is a facilitator but not a necessary condition for the occurrence of empathic stress.
When the observers watched the events directly through a one-way mirror, 30 percent of them experienced a stress response. However, even presenting the stress test only virtually via video transmission was sufficient to significantly increase the cortisol levels of 24 percent of the observers. “This means that even television programmes depicting the suffering of other people can transmit that stress to viewers,” says Engert. “Stress has enormous contagion potential.”
Stress becomes a problem primarily when it is chronic. “A hormonal stress response has an evolutionary purpose, of course. When you are exposed to danger, you want your body to respond with an increase in cortisol,” explains Engert. “However, permanently elevated cortisol levels are not good. They have a negative impact on the immune system and neurotoxic properties in the long term.” Thus, individuals working as caregivers or the family members of chronically stressed individualshave an increased risk to suffer from the potentially harmful consequences of empathic stress. Anyone who is confronted with the suffering and stress of another person, particularly when sustained, has a higher risk of being affected by it themselves.
The results of the study also debunked a common prejudice: men and women actually experience empathic stress reactions with equal frequency. “In surveys however, women tend to assess themselves as being more empathic compared to men’s self-assessments. This self-perception does not seem to hold if probed by implicit measures”
Future studies are intended to reveal exactly how the stress is transmitted and what can be done to reduce its potentially negative influence on society.
The scent of a man
Scientists’ inability to replicate research findings using mice and rats has contributed to mounting concern over the reliability of such studies.
Now, an international team of pain researchers led by scientists at McGill University in Montreal may have uncovered one important factor behind this vexing problem: the gender of the experimenters has a big impact on the stress levels of rodents, which are widely used in preclinical studies.
In research published online April 28 in Nature Methods, the scientists report that the presence of male experimenters produced a stress response in mice and rats equivalent to that caused by restraining the rodents for 15 minutes in a tube or forcing them to swim for three minutes. This stress-induced reaction made mice and rats of both sexes less sensitive to pain.
Female experimenters produced no such effects.
“Scientists whisper to each other at conferences that their rodent research subjects appear to be aware of their presence, and that this might affect the results of experiments, but this has never been directly demonstrated until now,” says Jeffrey Mogil, a psychology professor at McGill and senior author of the paper.
The research team, which included pain experts from Haverford College and the Karolinska Institutet in Sweden and a chemosensory expert from Université de Montreal, found that the effect of male experimenters on the rodents’ stress levels was due to smell. This was shown by placing cotton T shirts, worn the previous night by male or female experimenters, alongside the mice; the effects were identical to those caused by the presence of the experimenters, themselves.
Further experiments proved that the effects were caused by chemosignals, or pheromones, that men secrete from the armpit at higher concentrations than women. These chemosignals signal to rodents the presence of nearby male animals. (All mammals share the same chemosignals).
These effects are not limited to pain. The researchers found that other behavioural assays sensitive to stress were affected by male but not female experimenters or T-shirts.
“Our findings suggest that one major reason for lack of replication of animal studies is the gender of the experimenter – a factor that’s not currently stated in the methods sections of published papers,” says Robert Sorge, a psychology professor at the University of Alabama, Birmingham. Sorge led the study as a postdoctoral fellow at McGill.
The good news, Mogil says, is that “the problem is easily solved by simple changes to experimental procedures. For example, since the effect of males’ presence diminishes over time, the male experimenter can stay in the room with the animals before starting testing. At the very least, published papers should state the gender of the experimenter who performed the behavioral testing.”
(Source: mcgill.ca)