Posts tagged science
Articles and news from the latest research reports.
Senses of sight and sound separated in children with autism
Like watching a foreign movie that was badly dubbed, children with autism spectrum disorders (ASD) have trouble integrating simultaneous information from their eyes and their ears, according to a Vanderbilt study published today in The Journal of Neuroscience.
The study, led by Mark Wallace, Ph.D., director of the Vanderbilt Brain Institute, is the first to illustrate the link and strongly suggests that deficits in the sensory building blocks for language and communication can ultimately hamper social and communication skills in children with autism.
“There is a huge amount of effort and energy going into the treatment of children with autism, virtually none of it is based on a strong empirical foundation tied to sensory function,” Wallace said. “If we can fix this deficit in early sensory function then maybe we can see benefits in language and communication and social interactions.”
And the findings could have much broader applications because sensory functioning is also changed in developmental disabilities such as dyslexia and schizophrenia, Wallace said.
In the study, Vanderbilt researchers compared 32 typically developing children ages 6-18 years old with 32 high-functioning children with autism, matching the groups in virtually every possible way including IQ.
Study participants worked through a battery of different tasks, largely all computer generated. Researchers used different types of audiovisual stimuli such as simple flashes and beeps, more complex environmental stimuli like a hammer hitting a nail, and speech stimuli, and asked the participants to tell them whether the visual and auditory events happened at the same time.
The study found that children with autism have an enlargement in something known as the temporal binding window (TBW), meaning the brain has trouble associating visual and auditory events that happen within a certain period of time.
“Children with autism have difficulty processing simultaneous input from audio and visual channels. That is, they have trouble integrating simultaneous information from their eyes and their ears,” said co-author Stephen Camarata, Ph.D., professor of Hearing and Speech Sciences. “It is like they are watching a foreign movie that was badly dubbed, the auditory and visual signals do not match in their brains.”
A second part of the study found that children with autism also showed weaknesses in how strongly they “bound” or associated audiovisual speech stimuli.
“One of the classic pictures of children with autism is they have their hands over their ears,” Wallace said. “We believe that one reason for this may be that they are trying to compensate for their changes in sensory function by simply looking at one sense at a time. This may be a strategy to minimize the confusion between the senses.”
Wallace noted that the recently-released Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5), which serves as a universal authority for psychiatric diagnosis, now acknowledges sensory processing as a core deficit in autism.
Breast cancer spreads to brain by masquerading as neurons
Often, several years can pass between the time a breast cancer patient successfully goes into remission and a related brain tumor develops. During that time, the breast cancer cells somehow hide, escaping detection as they grow and develop. Now City of Hope researchers have found out how.
Breast cancer cells disguise themselves as neurons, becoming “cellular chameleons,” the scientists found. This allows them to slip undetected into the brain and, from there, develop into tumors.
The discovery is being heralded as “a tremendous advance in breast cancer research.”
Although breast cancer is a very curable disease – with more than 95 percent of women with early-stage disease surviving after five years – breast cancer that metastasizes to the brain is difficult to fight. In fact, only about 20 percent of patients survive a year after diagnosis.
"There remains a paucity of public awareness about cancer’s relentless endgame," said Rahul Jandial, M.D., Ph.D., a City of Hope neurosurgeon who headed the breast-cancer-and-brain-tumor study, published online ahead of print this week in the Proceedings of the National Academy of Sciences.
"Cancer kills by spreading. In fact, 90 percent of all cancer mortality is from metastasis," Jandial said. "The most dreaded location for cancer to spread is the brain. As we have become better at keeping cancer at bay with drugs such as Herceptin, women are fortunately living longer. In this hard-fought life extension, brain metastases are being unmasked as the next battleground for extending the lives of women with breast cancer."
He added: “I have personally seen my neurosurgery clinic undergo a sharp rise in women with brain metastases years – and even decades – after their initial diagnosis.”
Jandial and other City of Hope scientists wanted to explore how breast cancer cells cross the blood-brain barrier – a separation of the blood circulating in the body from fluid in the brain – without being destroyed by the immune system.
“If, by chance, a malignant breast cancer cell swimming in the bloodstream crossed into the brain, how would it survive in a completely new, foreign habitat?” said Jandial in a recent interview with New Scientist.
Jandial and his team’s hypothesis: Given that the brain is rich in many brain-specific types of chemicals and proteins, perhaps breast cancer cells that could exploit these resources by assuming similar properties would be the most likely to flourish. These cancer cells could deceive the immune system by blending in with the neurons, neurotransmitters, other types of proteins, cells and chemicals.
Taking samples from brain tumors resulting from breast cancer, Jandial and his team found that the breast cancer cells were exploiting the brain’s most abundant chemical as a fuel source. This chemical, GABA, is a neurotransmitter used for communication between neurons.
When compared to cells from nonmetastatic breast cancer, the metastasized cells expressed a receptor for GABA, as well as for a protein that draws the transmitter into cells. This allowed the cancer cells to essentially masquerade as neurons.”Breast cancer cells can be cellular chameleons (or masquerade as neurons) and spread to the brain,” Jandial said.
Jandial says that further study is required to better understand the mechanisms that allow the cancer cells to achieve this disguise. He hopes that ultimately, unmasking these disguised invaders will result in new therapies.
In Dyslexia, Less Brain Tissue Not to Blame for Reading Difficulties
In people with dyslexia, less gray matter in the brain has been linked to reading disabilities, but now new evidence suggests this is a consequence of poorer reading experiences and not the root cause of the disorder.
It has been assumed that the difference in the amount of gray matter might, in part, explain why dyslexic children have difficulties correctly and fluently mapping the sounds in words to their written counterparts during reading. But this assumption of causality has now been turned on its head.
The findings from anatomical brain studies conducted at Georgetown University Medical Center (GUMC) in the Center for the Study of Learning led by neuroscientist Guinevere Eden, DPhil, were published online today in The Journal of Neuroscience.
The study compared a group of dyslexic children with two different control groups: an age-matched group included in most previous studies, and a group of younger children who were matched at the same reading level as the children with dyslexia.
“This kind of approach allows us to control for both age as well as reading experience,” explains Eden, a professor of pediatrics at GUMC. “If the differences in brain anatomy in dyslexia were seen in comparison with both control groups, it would have suggested that reduced gray matter reflects an underlying cause of the reading deficit. But that’s not what we observed.”
The dyslexic groups showed less gray matter compared with a control group matched by age, consistent with previous findings. However, the result was not replicated when a control group matched by reading level was used as the comparison group with the dyslexics.
“This suggests that the anatomical differences reported in left hemisphere language processing regions appear to be a consequence of reading experience as opposed to a cause of dyslexia,” says Anthony Krafnick, PhD, lead author of the publication. “These results have an impact on how we interpret the previous anatomical literature on dyslexia and it suggests the use of anatomical MRI would not be a suitable way to identify children with dyslexia,” he says.
The work also helps to determine the fine line between experience-induced changes in the brain and differences that are the cause of cognitive impairment. For example, it is known from studies in illiterate people who attain reading skills as adults that this type of learning induces growth of brain matter. Similar learning-induced changes in typical readers may result in discrepancies between them and their dyslexic peers, who have not enjoyed the same reading experiences and thus have not undergone similar changes in brain structure.
Brain Structure Shows Who is Most Sensitive to Pain
Everybody feels pain differently, and brain structure may hold the clue to these differences.
In a study published in the current online issue of the journal Pain, scientists at Wake Forest Baptist Medical Center have shown that the brain’s structure is related to how intensely people perceive pain.
“We found that individual differences in the amount of grey matter in certain regions of the brain are related to how sensitive different people are to pain,” said Robert Coghill, Ph.D., professor of neurobiology and anatomy at Wake Forest Baptist and senior author of the study.
The brain is made up of both grey and white matter. Grey matter processes information much like a computer, while white matter coordinates communications between the different regions of the brain.
The research team investigated the relationship between the amount of grey matter and individual differences in pain sensitivity in 116 healthy volunteers. Pain sensitivity was tested by having participants rate the intensity of their pain when a small spot of skin on their arm or leg was heated to 120 degrees Fahrenheit. After pain sensitivity testing, participants underwent MRI scans that recorded images of their brain structure.
“Subjects with higher pain intensity ratings had less grey matter in brain regions that contribute to internal thoughts and control of attention,” said Nichole Emerson, B.S., a graduate student in the Coghill lab and first author of the study. These regions include the posterior cingulate cortex, precuneus and areas of the posterior parietal cortex, she said.
The posterior cingulate cortex and precuneus are part of the default mode network, a set of connected brain regions that are associated with the free-flowing thoughts that people have while they are daydreaming.
“Default mode activity may compete with brain activity that generates an experience of pain, such that individuals with high default mode activity would have reduced sensitivity to pain,” Coghill said.
Areas of the posterior parietal cortex play an important role in attention. Individuals who can best keep their attention focused may also be best at keeping pain under control, Coghill said.
“These kinds of structural differences can provide a foundation for the development of better tools for the diagnosis, classification, treatment and even prevention of pain,” he said.
Short circuit in molecular switch intensifies pain
Pain functions as an important alarm signal. It alerts us to potential bodily harm – a hot or sharp object, for example – and motivates us to withdraw from damaging situations. At the cellular level, pain involves the stimulation of a network of pain nerves spread through the skin, mucosa and bodily organs.
Embedded in the cell wall surrounding these nerves are ion channels. These tiny, microscopic pathways respond to stimuli such as extreme cold or heat, mechanical pressure or harmful chemicals. When ion channels open, an electrical signal is created, transmitted to the brain, and interpreted as pain.
In previous research, the team of KU Leuven researchers led by Professor Thomas Voets (Laboratory of Ion Channel Research) and Professor Joris Vriens (Laboratory of Obstetrics and Experimental Gynaecology) discovered that a particular ion channel – TRPM3 – acts as a molecular fire detector: the ion channel detects heat and the hormone pregnenolone sulfate, a precursor to the sex hormones estrogen and testosterone and a trigger for pain and inflammation. In the present study, the researchers were looking for TRPM3 inhibitors that could potentially be used as painkillers.
Short circuit
Surprisingly, their results show that a number of drugs meant as painkillers actually increased pain in mice tested in the study, says Professor Voets: “Normally, when the ion channel is closed, no electrical signal is sent to the brain and therefore no pain is detected. But we found that pain can indeed occur despite a closed ion channel. How? A short circuit in the ion channel. When short-circuiting occurs, the electrical signal effected by a stimulus does not follow the normal pathway through the central pore of the ion channel. Instead, it navigates an alternative path through the surrounding material. This ‘electrical leak’ activates the pain nerves, thus increasing the sensation of pain. This may explain the pain-enhancing side effects of some drugs – such as clotrimazole, a common remedy for yeast infections that often causes unpleasant side effects such as irritation and burning sensations.”
“It is striking that short circuits in the ion channel only occur at high hormone levels. This could explain why some patients experience these side effects while others do not,” says Professor Voets. The researchers hope this new knowledge about TRPM3-dependent pain will contribute to the development of new painkillers with fewer painful side effects.
Recall of stressful events caught in pictures
The study is of patients with conversion disorder (what Freud would have called Hysteria), which is still a very common disorder though rarely discussed or researched today.
“Freud started his whole theory by arguing that patients with hysteria repressed their memories of traumatic events and that this led to their developing their symptoms (of paralysis, for example) - what he called ‘conversion,” said Professor Richard Kanaan from the Department of Psychiatry, University of Melbourne and Austin Health.
“The world has pretty much given up on that theory largely because they thought it couldn’t be tested,” he said.
Published recently in the Journal of the American Medical Association, Psychiatry, the fMRI findings support Freud’s theories for the first time in over a century.
Researchers first painstakingly identified what they thought were the traumatic events that led to them becoming sick using the Life Events and Difficulties Schedule (LEDS) as a guide. This is a well-known psychological measurement for assessing life stress levels and experience.
“We got our patients to remember the traumatic events while we scanned their brains. Results showed something that looked like it could be them repressing their memories and possibly what could be them developing symptoms in response.”
“While it is still a preliminary study, in the history of psychiatry as a science it is potentially a significant breakthrough,” he said.
Scientists Develop Promising Drug Candidates for Pain, Addiction
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have described a pair of drug candidates that advance the search for new treatments for pain, addiction and other disorders.
The two new drug scaffolds, described in a recent edition of The Journal of Biological Chemistry, offer researchers novel tools that act on a demonstrated therapeutic target, the kappa opioid receptor (KOR), which is located on nerve cells and plays a role in the release of the neurotransmitter dopamine. While compounds that activate KOR are associated with positive therapeutic effects, they often also recruit a molecule known as βarrestin2 (beta arrestin), which is associated with depressed mood and severely limits any therapeutic potential.
“Compounds that act at kappa receptors may provide a means for treating addiction and for treating pain; however, there is the potential for the development of depression or dysphoria associated with this receptor target,” said Laura Bohn, a TSRI associate professor who led the study. “There is evidence that the negative feelings caused by kappa receptor drugs may be, in part, due to receptor actions through proteins called beta arrestins. Developing compounds that activate the receptors without recruiting beta arrestin function may serve as a means to improve the therapeutic potential and limit side effects.”
The new compounds are called “biased agonists,” activating the receptor without engaging the beta arrestins.
Research Associate Lei Zhou, first author of the study with Research Associate Kimberly M. Lovell, added, “The importance of these biased agonists is that we can manipulate the activation of one particular signaling cascade that produces analgesia, but not the other one that could lead to dysphoria or depression.”
The researchers note that the avoidance of depression is particularly important in addiction treatment, where depressed mood can play a role in relapse.
The two drug candidates also have a high affinity and selectivity for KOR over other opioid receptors and are able to pass through the blood-brain barrier. Given these promising attributes, the scientists plan to continue developing the compounds.
(Source: scripps.edu)
Scientific study suggests an association between physical doping and brain doping
Physical doping and brain doping apparently often go hand in hand. A study from Johannes Gutenberg University Mainz (JGU) and Eberhard Karls University in Tubingen revealed that people who engage in physical doping often also take drugs for brain doping. The study was the first of its kind to survey simultaneously the two categories of doping and brain doping. Around 3,000 hobby triathletes were anonymously surveyed using a questionnaire at sporting events in Frankfurt, Regensburg, and Wiesbaden. “The results correlated with earlier findings about doping in leisure and popular sports and brain doping in society as a whole. The findings also illustrated for the first time that physical doping and brain doping often go together, at least for recreational triathletes,” said Mainz University Professor of Sports Medicine Dr. Dr. Perikles Simon.
The study was carried out using the randomized response technique (RRT), which allows for better estimates of unknown cases in response to sensitive questions. It suggested that 13.0 percent of the athletes surveyed had used illegal and banned substances in the twelve months prior to the survey; 15.1 percent were believed to have engaged in brain doping.
When talking about doping substances, a distinction is made between illicit drugs such as cocaine or heroin and banned substances for physical performance enhancement such as anabolic steroids, EPO, or growth hormones. Brain doping is the use of illegal substances and pharmaceuticals such as illegal amphetamines, modafinil or Ritalin to improve mental performance.
The findings indicate that the estimated proportion of men who dope (13.7 percent) is higher than the proportion of women (8.0 percent). The prevalence of doping also seemed to be higher at the European Championships in Frankfurt than at the other triathlons in Regensburg and Wiesbaden. The competitions involved participants taking part in either a classic Ironman with a 4 kilometer swim, 180 kilometer cycle ride, and 42 kilometer marathon or tackling half of the actual Ironman distance.
In their survey carried out during the 2011 season, the scientists interviewed a total of 2,997 triathlon participants. 2,987 questionnaires (99.7 percent) were returned. The study also examined whether there was a correlation between the use of legal and freely available substances for improving physical and mental performance and the use of illegal and banned substances. This would appear to be the case, as athletes who use legal substances to improve their performance also tend to use illegal substances as well.
Finally, another important finding of the study was the sign of a correlation between physical doping and brain doping, which can be found with both legal and illicit substances. The use of legal substances to enhance physical performance is thus relatively often associated with the consumption of substances to improve mental performance, just as there is a correlation between the use of illicit substances for both doping and brain doping. “This indicates that athletes do not actually take the substances to achieve a specific goal, but may show a certain propensity towards performance enhancing substances,” explained Simon. The findings are important to better understand why people take such substances and to be able to provide targeted prevention.
Alzheimer’s disease: 15-minute test could spot early sign of dementia
A simple 15-minute test which can be taken at home can spot the early signs of Alzheimer’s disease, researchers claim.
The exam which can be completed online or by hand, tests language ability, reasoning, problem solving skills and memory.
Results can then be shared with doctors to help spot early symptoms of cognitive issues such as early dementia or Alzheimer’s disease.
The research was published in The Journal of Neuropsychiatry and Clinical Neurosciences.
Ultrasound directed to the human brain can boost sensory performance
Whales, bats, and even praying mantises use ultrasound as a sensory guidance system – and now a new study has found that ultrasound can modulate brain activity to heighten sensory perception in humans.
Virginia Tech Carilion Research Institute scientists have demonstrated that ultrasound directed to a specific region of the brain can boost performance in sensory discrimination. The study, published online Jan. 12 in Nature Neuroscience, provides the first demonstration that low-intensity, transcranial-focused ultrasound can modulate human brain activity to enhance perception.
“Ultrasound has great potential for bringing unprecedented resolution to the growing trend of mapping the human brain’s connectivity,” said William “Jamie” Tyler, an assistant professor at the Virginia Tech Carilion Research Institute, who led the study. “So we decided to look at the effects of ultrasound on the region of the brain responsible for processing tactile sensory inputs.”
The scientists delivered focused ultrasound to an area of the cerebral cortex that corresponds to processing sensory information received from the hand. To stimulate the median nerve – a major nerve that runs down the arm and the only one that passes through the carpal tunnel – they placed a small electrode on the wrist of human volunteers and recorded their brain responses using electroencephalography, or EEG. Then, just before stimulating the nerve, they began delivering ultrasound to the targeted brain region.
The scientists found that the ultrasound both decreased the EEG signal and weakened the brain waves responsible for encoding tactile stimulation.
The scientists then administered two classic neurological tests: the two-point discrimination test, which measures a subject’s ability to distinguish whether two nearby objects touching the skin are truly two distinct points, rather than one; and the frequency discrimination task, a test that measures sensitivity to the frequency of a chain of air puffs.
What the scientists found was unexpected.
The subjects receiving ultrasound showed significant improvements in their ability to distinguish pins at closer distances and to discriminate small frequency differences between successive air puffs.
“Our observations surprised us,” said Tyler. “Even though the brain waves associated with the tactile stimulation had weakened, people actually got better at detecting differences in sensations.”
Why would suppression of brain responses to sensory stimulation heighten perception? Tyler speculates that the ultrasound affected an important neurological balance.
“It seems paradoxical, but we suspect that the particular ultrasound waveform we used in the study alters the balance of synaptic inhibition and excitation between neighboring neurons within the cerebral cortex,” Tyler said. “We believe focused ultrasound changed the balance of ongoing excitation and inhibition processing sensory stimuli in the brain region targeted and that this shift prevented the spatial spread of excitation in response to stimuli resulting in a functional improvement in perception.”
To understand how well they could pinpoint the effect, the research team moved the acoustic beam one centimeter in either direction of the original site of brain stimulation – and the effect disappeared.
“That means we can use ultrasound to target an area of the brain as small as the size of an M&M,” Tyler said. “This finding represents a new way of noninvasively modulating human brain activity with a better spatial resolution than anything currently available.”
Based on the findings of the current study and an earlier one, the researchers concluded that ultrasound has a greater spatial resolution than two other leading noninvasive brain stimulation technologies – transcranial magnetic stimulation, which uses magnets to activate the brain, and transcranial direct current stimulation, which uses weak electrical currents delivered directly to the brain through electrodes placed on the head.
“Gaining a better understanding of how pulsed ultrasound affects the balance of synaptic inhibition and excitation in targeted brain regions – as well as how it influences the activity of local circuits versus long-range connections – will help us make more precise maps of the richly interconnected synaptic circuits in the human brain,” said Wynn Legon, the study’s first author and a postdoctoral scholar at the Virginia Tech Carilion Research Institute. “We hope to continue to extend the capabilities of ultrasound for noninvasively tweaking brain circuits to help us understand how the human brain works.”
“The work by Jamie Tyler and his colleagues is at the forefront of the coming tsunami of developing new safe yet effective noninvasive ways to modulate the flow of information in cellular circuits within the living human brain,” said Michael Friedlander, executive director of the Virginia Tech Carilion Research Institute and a neuroscientist who specializes in brain plasticity. “This approach is providing the technology and proof of principle for precise activation of neural circuits for a range of important uses, including potential treatments for neurodegenerative disorders, psychiatric diseases, and behavioral disorders. Moreover, it arms the neuroscientific community with a powerful new tool to explore the function of the healthy human brain, helping us understand cognition, decision-making, and thought. This is just the type of breakthrough called for in President Obama’s BRAIN Initiative to enable dramatic new approaches for exploring the functional circuitry of the living human brain and for treating Alzheimer’s disease and other disorders.”
A team of Virginia Tech Carilion Research Institute scientists – including Tomokazu Sato, Alexander Opitz, Aaron Barbour, and Amanda Williams, along with Virginia Tech graduate student Jerel Mueller of Raleigh, N.C. – joined Tyler and Legon in conducting the research. In addition to his position at the institute, Tyler is an assistant professor of biomedical engineering and sciences at the Virginia Tech–Wake Forest University School of Biomedical Engineering and Sciences. In 2012, he shared a Technological Innovation Award from the McKnight Endowment for Neuroscience to work on developing ultrasound as a noninvasive tool for modulating brain activity.
“In neuroscience, it’s easy to disrupt things,” said Tyler. “We can distract you, make you feel numb, trick you with optical illusions. It’s easy to make things worse, but it’s hard to make them better. These findings make us believe we’re on the right path.”