CHICAGO —Using magnetoencephalography (MEG), researchers reported that it takes longer for children with autism to react to sounds than other children — a finding that may help explain the language and communication impairments associated with the disorder.
“We found that signatures of autism are revealed in the timing of brain activity,” said Timothy P.L. Roberts, PhD, vice chairman of research in the department of radiology at Children's Hospital of Philadelphia.
Figure. MEG was used...Image Tools
Speaking here at the annual meeting of the Radiological Society of North America (RSNA) in December, Dr. Roberts said that the more severe a child's autism spectrum disorder (ASD), the greater the delay in processing sounds. Compared with children with normal development, response time was 20 percent to 50 percent longer in the autistic children.
The study was designed to evaluate neuromagnetic-evoked fields, as recorded by MEG, in response to auditory stimuli as possible biomarkers for ASDs.
MEG tracks magnetic fields produced by electrical impulses created as neurons process each sound, and software measures the time it takes for each sound to reach peak processing, Dr. Roberts explained.
In the study, 30 autistic children and 34 controls with normal development, aged 6 to 15 years, had MEG studies while listening to a battery of simple tones and syllables.
Among children with autism, there was a “robust” 20 ms delay in processing a simple tone such as “ah,” compared to controls, he said. The finding remained significant after controlling for age, IQ, and severity of language impairment.
While an average delay of 20 ms in processing a sound “may not sound like much, that is the delay for a single tone. With more syllables, there is a cascade of delays, which may impair the ability of an autistic child to comprehend, Dr. Roberts said.
When the children listened to two-vowel syllables in sequence, such as “ah,” followed by “ou,” for example, the average delay was 40 ms.
As a more complex example, Dr. Roberts used the word elephant. “These kids are on the ‘el,’ while the rest of the world is on ‘phant,’ ” Dr. Roberts said.
Overall, the test had a sensitivity of 82- to 88-percent and a specificity of 70- to 74-percent as a biomarker for ASD.
MEG could also distinguish between children with ASD who have language impairment and children with ASD without language impairment, he said. For example, children with normal development responded to vowel contrasts in about 190 ms, compared with 230 ms for children with ASD and language impairment, and 212 ms for children with ASD and no language impairment.
As for clinical applications, MEG might help in the diagnosis of ASD, particularly while the child is learning to speak, Dr. Roberts said.
Also, since ASD is a spectrum of disorders that affect people to different degrees, the delay is processing sounds might also be “a biomarker that could be used to stratify autism patients,” he said.
Next, he said, the investigators will evaluate children aged 3 to 5 years “to see if there is any value in toddlers with an ambiguous diagnosis” of autism. The researchers have also obtained a grant to study the technique in neonates.
Since language acquisition takes place from birth to around 18 months, the hope “is that these signatures will eventually be revealed in the infant brain to help diagnose autism and allow earlier intervention,” Dr. Roberts said.
The results suggest that “speaking slowly when communicating with autistic children might be a useful intervention,” he said.
Dr. Roberts said he foresees the test also being used to examine children with attention deficit disorder, dyslexia, and other developmental problems.
Jeanne P. Townsend, PhD, associate adjunct professor in the department of neurosciences at the University of California-San Diego (UCSD), and an autism researcher in the university's Division of Research on Aging and Development, said: “The authors conclude that MEG could be useful for studying function in disorders like autism and I couldn't agree more. MEG produces rich data that can tell us pretty precisely when something happened and is also good at telling us where it happened.”
Eric Halgern, PhD, professor of radiology at UCSD, agreed. “Generally speaking, MEG is promising for studying ASD because it provides a direct physiological measurement — that is, direct measurement of electrical currents evoked during word processing.
“Synaptic activity in the brain creates a current inside cells, so MEG offers a direct, instantaneous measurement of intracranial activity,” Dr. Halgern said. “You can look at communication between cells in real time, and that may turn out to be important in ASD because white matter is affected. But functional MRI may still be needed to figure out which part of brain is affected.”
Aysenil Belger, PhD, associate professor and director of neuroimaging research at the University of North Carolina at Chapel Hill, agreed and noted that MEG may offer advantages over other diagnostic techniques.
Figure. DR. TIMOTHY ...Image Tools
“With EEG, for example, you measure the electrical activity from multiple areas of the brain, but you don't have localization. With MEG, you can generate a map. Unlike EEG, MEG offers good temporal and anatomical resolution.
“There are two ways of looking at information processing,” she said. “The older way involves asking what part of the brain is affected. But now it's evident that the disorder is not just anatomical, but also involves an abnormality in connectivity between different brain areas. That's where MEG comes in.”
Dr. Townsend said a battery of different tests might prove most useful. “EEG tells you when something happened, but doesn't tell us where it happened. And fMRI tells us where something happens, but not when it happened. The most powerful way to examine children with autism may be through a combination of techniques.”
CHALLENGES TO CLINICAL APPLICATION
The experts told Neurology Today, however, that the clinical applications for using MEG for diagnosing autism are still years away. Further study is needed, they said.
“We have to determine if there is a core deficit that precedes function development — that is, a processing sound abnormality at age 1 or 2 years that predicts later functional decline. So we need to study young children,” Dr. Belger said.
She added that she also would like to find out how unique this signature is to children with autism. To do that, Dr. Belger said, studies comparing children with ASD to children with other learning disorders such as dyslexia are needed.
If the signature is unique, “changing the way information is presented might enhance autistic children's ability to learn,” she said.
Dr. Halgern added that slower speech is an intervention worth trying, “but that is a big leap from here. First, we have to show it is useful in early diagnosis of ASD. Then, we need a clinical treatment study with random assignment to the intervention and controls.”
Dr. Roberts said there are some major stumbling blocks to overcome. One is availability: Currently, there are about 100 MEG centers worldwide, only a handful of which are in the US — including one at Children's Hospital of Philadelphia and one at Cincinnati Children's Hospital, he said.
Another major issue is cost, as the price tag for the machine alone is about $2 million, “and it's about $3 million to $5 million with the facility,” he said.
ARTICLE IN BRIEF
Investigators reported that MEG measures showed that the more severe a child's autism spectrum disorder, the greater the delay in processing sounds.