Scientists at Albert Einstein College of Medicine of Yeshiva University have shown that high-functioning autism spectrum disorder (ASD) children appear to outgrow a critical social communication disability. Younger children with ASD have trouble integrating the auditory and visual cues associated with speech, but the researchers found that the problem clears up in adolescence. The study was published today in the online edition of the journal Cerebral Cortex.
“This is an extremely hopeful finding,” said lead author John Foxe, Ph.D., professor of pediatrics and in the Dominick P. Purpura Department of Neuroscience, as well as director of research of the Children’s Evaluation and Rehabilitation Center at Einstein. “It suggests that the neurophysiological circuits for speech in these children aren’t fundamentally broken and that we might be able to do something to help them recover sooner.”
According to Dr. Foxe, the ability to integrate “heard” and “seen” speech signals is crucial to effective communication. “Children who don’t appropriately develop this capacity have trouble navigating educational and social settings,” he said.
In a previous study, Dr. Foxe and his colleagues demonstrated that children with ASD integrate multisensory information such as sound, touch and vision differently from typically developing children. Among typically developing children, multisensory integration (MSI) abilities were known to continue improving late into childhood. The current study looked at whether one aspect of MSI — integrating audio and visual speech signals — continues to develop in high-functioning children with ASD as well.
In the study, 222 children ages 5 to 17, including both typically developing children and high-functioning children with ASD, were tested for how well they could understand speech with increasing levels of background noise. In one test, the researchers played audio recordings of simple words. In a second test, the researchers played a video of the speaker articulating the words, but no audio. A third test presented the children with both the audio and video recordings.
The test mimics the so-called “cocktail party” effect: a noisy environment with many different people talking. In such settings, people naturally rely on both auditory and facial clues to understand what another person is saying. “You get a surprisingly big boost out of lip-reading, compared with hearing alone,” said Dr. Foxe. “It’s an integrative process.”
In the first test (audio alone), the children with ASD performed almost as well as typically developing children across all age groups and all background noise levels. In the second test (video alone), the children with ASD performed significantly worse than the typically developing children across all age groups and all background noise levels. “But the typically developing children didn’t perform very well, either,” said Dr. Foxe. “Most people are fairly terrible at lip-reading.”
In the third test (audio and video), the younger children with ASD, ages 6 to 12, performed much worse than the typically developing children of the same age, particularly at higher levels of background noise. However, among the older children, there was no difference in performance between the typically developing and children with ASD.
“In adolescence, something amazing happens and the kids with ASD begin to perform like the typically developing kids,” said Dr. Foxe. “At this point, we can’t explain why. It may be a function of a physiological change in their brain or of interventions they’ve received, or both. That is something we need to explore.”
The researchers acknowledge some limitations to their study. “Instead of doing a cross-sectional study like this, where we tested children at various ages, we would prefer to do a longitudinal study that would involve the same kids who’d be followed over the years from childhood through adolescence,” Dr. Foxe said. “We also need to find a way to study what is happening with low- and mid-functioning children with ASD. They are much less tolerant of testing and thus harder to study.”
According to the researchers, the work highlights the need to develop more effective therapies to help ASD children better integrate audio and visual speech signals. “We are beginning to work on that,” said Dr. Foxe.
The paper is titled “Severe Multisensory Speech Integration Deficits in High-Functioning School-Aged Children with an Autism Spectrum Disorder (ASD) and their Resolution during Early Adolescence.” Other Einstein contributors are Sophie Molholm, Ph.D., Victor Del Bene, Daniella Blanco, Hans-Peter Frey and Lars Ross, Ph.D. Additional coauthors are Natalie Russo, Ph.D., at Syracuse University (Syracuse, NY) and Dave Saint-Amour at Université du Québec à Montréal (Montreal, Canada).
This study was primarily supported by a grant from the National Institute of Mental Health (MH085322), part of the National Institutes of Health. Pilot support was provided by Cure Autism Now, the Wallace Research Foundation, Fondation du Quebec de Recherche sur la Societe et la Culture, and the Canadian Institute of Health Research.
Key enzymes are found to have a ‘profound effect’ across dozens of genes linked to autism, the insight could help illuminate environmental factors behind autism spectrum disorder and contribute to a unified theory of how the disorder develops
Problems with a key group of enzymes called topoisomerases can have profound effects on the genetic machinery behind brain development and potentially lead to autism spectrum disorder (ASD), according to research announced today in the journal Nature. Scientists at the University of North Carolina School of Medicine have described a finding that represents a significant advance in the hunt for environmental factors behind autism and lends new insights into the disorder’s genetic causes.
“Our study shows the magnitude of what can happen if topoisomerases are impaired,” said senior study author Mark Zylka, PhD, associate professor in the Neuroscience Center and the Department of Cell Biology and Physiology at UNC. “Inhibiting these enzymes has the potential to profoundly affect neurodevelopment — perhaps even more so than having a mutation in any one of the genes that have been linked to autism.”
The study could have important implications for ASD detection and prevention.
“This could point to an environmental component to autism,” said Zylka. “A temporary exposure to a topoisomerase inhibitor in utero has the potential to have a long-lasting effect on the brain, by affecting critical periods of brain development. “
This study could also explain why some people with mutations in topoisomerases develop autism and other neurodevelopmental disorders.
Topiosomerases are enzymes found in all human cells. Their main function is to untangle DNA when it becomes overwound, a common occurrence that can interfere with key biological processes.
Most of the known topoisomerase-inhibiting chemicals are used as chemotherapy drugs. Zylka said his team is searching for other compounds that have similar effects in nerve cells. “If there are additional compounds like this in the environment, then it becomes important to identify them,” said Zylka. “That’s really motivating us to move quickly to identify other drugs or environmental compounds that have similar effects — so that pregnant women can avoid being exposed to these compounds.”
Zylka and his colleagues stumbled upon the discovery quite by accident while studying topotecan, a topoisomerase-inhibiting drug that is used in chemotherapy. Investigating the drug’s effects in mouse and human-derived nerve cells, they noticed that the drug tended to interfere with the proper functioning of genes that were exceptionally long — composed of many DNA base pairs. The group then made the serendipitous connection that many autism-linked genes are extremely long.
“That’s when we had the ‘Eureka moment,'” said Zylka. “We realized that a lot of the genes that were suppressed were incredibly long autism genes.”
Of the more than 300 genes that are linked to autism, nearly 50 were suppressed by topotecan. Suppressing that many genes across the board — even to a small extent — means a person who is exposed to a topoisomerase inhibitor during brain development could experience neurological effects equivalent to those seen in a person who gets ASD because of a single faulty gene.
The study’s findings could also help lead to a unified theory of how autism-linked genes work. About 20 percent of such genes are connected to synapses — the connections between brain cells. Another 20 percent are related to gene transcription — the process of translating genetic information into biological functions. Zylka said this study bridges those two groups, because it shows that having problems transcribing long synapse genes could impair a person’s ability to construct synapses.
“Our discovery has the potential to unite these two classes of genes — synaptic genes and transcriptional regulators,” said Zylka. “It could ultimately explain the biological mechanisms behind a large number of autism cases.”
The study’s coauthors include Benjamin Philpot (co-senior author), Terry Magnuson, Ian King, Chandri Yandava, Angela Mabb, Hsien-Sung Huang, Brandon Pearson, J. Mauro Calabrese, Joshua Starmer and Joel Parker from UNC and Jack S. Hsiao and Stormy Chamberlain of the University of Connecticut Health Center.
Surgically implanted electrodes could treat severe cases of the syndrome
Web edition: January 25, 2013
The results are the first to use brain stimulation to alleviate symptoms of autism. Scientists caution that interpreting the results broadly is impossible without larger, systematic studies, but even so neurosurgeon Ali Rezai of the Ohio State University Wexner Medical Center in Columbus calls the boys’ gains “intriguing and promising.”
Researchers have become increasingly interested in deep brain stimulation, a technique in which surgically implanted electrodes act as brain pacemakers. For the last two decades, deep brain stimulation has found use treating movement disorders such as the tremors that accompany Parkinson’s disease (SN: 4/11/09, p.11). More recently, scientists have begun experimenting with the technique to treat behavioral and mental problems, including depression, obsessive-compulsive disorder and severe anxiety.
The boy in the study, who was 13 at the time of his experimental surgery, suffered from severe autism symptoms: He couldn’t talk or make eye contact, woke up screaming repeatedly during the night, and habitually injured himself so badly that His parents restrained him almost constantly to protect him. Multiple rounds of psychiatric drugs failed to stave off his worsening symptoms.
In an effort to help him, doctors led by Volker Sturm of the University Hospital of Cologne in Germany implanted electrodes into the boy’s brain. Through trial and error, the doctors realized that stimulating a part of the amygdala, a brain structure important for emotions and memory, improved the boy’s symptoms. Stimulating other brain areas had no effect or worsened his symptoms.
After eight weeks of continuous electrical stimulation, the boy shifted on a clinical scale that measures irritability from “severely ill” to “moderately ill.” The boy also improved on a scale that measures autism symptoms. He began to make eye contact and was better able to control his behavior.
The boy’s parents reported even more dramatic improvements: His anxiety and self-harming behavior lessened and he slept better at night. He also began to enjoy activities such as tasting new foods, going on car rides and even playing with a piano. After six months of stimulation, the previously nonverbal boy began saying a few simple words such as “papa” and “mama.”
The electrodes’ stimulation of the brain seemed to be behind the boy’s improvements. After 44 weeks of treatment, the battery on the device ran out of juice. During a monthlong lull in treatment, the boy’s symptoms grew more severe. Once the battery was replaced, his symptoms improved. Rechargeable batteries, which are now available, may circumvent this interruption for future patients, says Rezai.
The next step is to understand how deep brain stimulation changes the brain, particularly in people with behavioral and cognitive problems, Rezai says. That information could allow clinicians to design better therapies for these complex disorders.
V. Sturm et al. DBS in the basolateral amygdala improves symptoms of autism and related self injurious behavior: A case report and hypothesis on the pathogenesis of the disorder. Frontiers in Human Neuroscience. Published online January 21, 2013. doi:10.3389/fnhum.2012.00341.l Available online: [Go to]
T. Saey. How deep brain stimulation works for Parkinson’s. Science News. Vol. 175, April 11, 2009, p. 11. Available online: [Go to]
Men, scientists, professors and the British are less likely to believe in God than women, children and Americans.
Many children attribute magical properties to physical objects. In one unkind experiment, infants were persuaded that a scientist had invented an apparatus that made an exact duplicate of any article placed inside it. Their favourite stuffed animal was put within, the lights flashed, and with some sleight of hand the child was given the toy back and told that it was a replica. Almost without exception, they rejected it. Somehow, the supposed copy had lost a mysterious quality present within the original. For the tearful subjects, reality involved more than the real.
In another study, nine-year-olds were asked to play a game. They had to choose which of two boxes held a reward. They were told that they were in the presence of an invisible agent, “Princess Alice”, who would make a sign if they touched the wrong one. When they did, the experimenter furtively made a light flicker. Almost all the children changed their choice: they happily accepted the reality of a higher power.
The latest research hints at a strong overlap between belief and adult temperament. Personality can be tested by giving people close-ups of eyes and telling them to identify whether the person is terrified, amused, regretful or flirtatious. They are also asked to respond to statements such as “I find it hard to keep a conversation going” or to spot prime numbers, or patterns in a set of letters.
Men, on average, score worse on the ability to sense emotion (but better on prime numbers, a talent that demands no insight into anyone else’s feelings) than do women; and university professors do worse again, while scientists come at the bottom of the list.
People with autism score even lower. Those severely affected live almost detached from the world around them. They lack empathy, concentrate on themselves and may be obsessed with a particular talent (such as being able to tell what day of the week any date will be), combined with loss of other mental abilities. Children with a milder version of the condition, Asperger’s syndrome, are often clumsy, shy and tongue-tied.
Others do much better, for they have “high-functioning autism”. Such individuals are successful, but have little insight into the emotions of others and often show a deep interest in things mechanical and numerical. The personality type is much more frequent among males than females and, at least in its most severe forms, has a strong genetic component.
On the emotion-sensing tests, those with autism proper do worst, then Asperger’s patients, followed by the high-functioning group, and then — in order — by scientists, professors and men. Women come top.
People with autism are mainly interested in the banal reality of what surrounds them and find it hard to consider the abstract world. They are, as a result, highly resistant to the idea of an invisible deity for whom no tangible evidence exists and whose thoughts cannot be penetrated. Teenagers with the condition are far less likely to express a belief in God than their unaffected classmates. The high-functioning group are also much more willing to class themselves as atheists than are their fellows — and, in decreasing order of scepticism, people with autism, Asperger’s patients, scientists, professors, men and women (in some studies, men are only half as likely to be believers as are their partners).
Perhaps a logical, systematic and self-centred personality is disposed to doubt, while a more responsive mind is more willing to summon up the divine. Believers are in emotional contact with their deity. They feel that He responds to their prayers, knows their thoughts and guides His subjects in their proper paths. They empathise with their angel and accept what they imagine to be his instructions. Those with autism, scientists and men are happier with their own thoughts.
About two thirds of Britons do not regard themselves as religious at all. In the US, the same proportion is sure that God exists — and in a recent poll a majority said that they would be more willing to vote for a Mormon, a Jew or a homosexual as president than an atheist.
When I was a lad, that figure was probably much the same for Wales, but now they are the biggest heathens on the British Isles. To find out why, you need not a scientist but a sociologist.
It’s been there for a while, but I have recently updated parts of it and added a few video’s.
I speak of the section entitled Autism. I implore you to please take some time to read through it.