The Scientists Who Never Sleep

Weizmann Institute scientists find themselves on the cutting edge of Autism research, thanks to what started as an attempt to understand what the brain is doing while resting.

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Click photo to download. Caption: Weaker interhemispheric correlations in autism. Credit: Neuron.

At night, Rafael Malach’s brain is busy, doing things only brain scientists dream about.

Malach, a professor at the Weizmann Institute in Rehovot, Israel, and scientists from Carnegie Mellon University and the University of California-San Diego have found, for the first time, a method that can accurately identify a biological sign of autism in very young toddlers.

The scientists initially got involved in studying autism because they wanted to attempt to understand what the brain is doing while resting.

Autism, defined by the U.S National Library of Medicine as a developmental disorder that appears in the first three years of life, affects the brain’s normal development of social and communication skills.  

On its website, the Autism Society states that one percent of the population of children in the U.S. ages 3-17 have an autism spectrum disorder. The estimated prevalence is 1 in 110 births, according to the Department of Health and Human Services, Centers for Disease Control and Prevention.

According to a publication of the National Institute of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, “Different people with autism can have very different symptoms. Health care providers think of autism as a “spectrum” disorder, a group of disorders with similar features. One person may have mild symptoms, while another may have serious symptoms.  But they both have an autism spectrum disorder.”

For the layperson, all this is important as background when entering into the world of Prof. Malach and his right-hand man, post-doctoral fellow Ilan Dinstein, a member of the group who headed this study in the Weizmann Institute’s Neurobiology Department.

“Identifying biological signs of autism has been a major goal for many scientists around the world, both because they may allow early diagnosis, and because they can provide researchers with important clues about the causes and development of the disorder,” said Dr. Dinstein, who received his PhD at New York University.

By scanning the brain activity of sleeping children, the scientists discovered that the autistic brains exhibited significantly weaker synchronization between brain areas tied to language and communication compared to that of non-autistic children.

Malach and Dinstein worked closely with Eric Courchense, PhD, at UCSD, and Marlene Behrmann at Carnegie Mellon. After receiving the MRI scans from Courchense, the Weizmann scientists analyzed the data with help from Behrmann, who has worked on other autism studies.

This study, Dinstein said, was the first time anyone has looked at brains that are so young, toddlers between one and 3-and-a-half years old. The research focused on scans from 70 toddlers.

Click photo to download. Caption: Prof. Rafael Malach. Credit: Courtesy Rafael Malach.

At Weizmann, an institute dedicated to basic scientific research, Malach’s main interest is in Neuroscience, with his main focus brain mechanisms of human visual perception.

Malach is the recipient of the Helen and Martin Kimmel Award for Innovative Investigation and he is the incumbent of the Barbara and Morris L. Levinson Professorial Chair in Brain Research. Malach said a major finding of recent years is that the human brain does not stop its activity when resting, but rather switches to a mode by which brain areas modulate their activity in a slow and coherent manner.

Their studies had shown that even during sleep, the brain does not actually switch off. Rather, the electrical activity of the brain cells switches over to spontaneous fluctuation. These fluctuations are coordinated across the two hemispheres of the brain such that each point on the left is synchronized with its corresponding point in the right hemisphere.

In his laboratory, Malach said his team developed a method for assessing the integrity of such spontaneous brain activity modulations, which are also called “resting state” activity, by measuring to what extent symmetrical brain regions in the left and right hemispheres co-modulate their activations in a similar pattern.  

“In healthy individuals such symmetric cross-hemispheric regions often co-modulate robustly so this relationship could serve as a good basis for comparison,” he added. “Furthermore, we found that these across hemisphere coordinated fluctuations occur also during sleep, allowing the passive examination of brain integrity. Indeed, in sleeping autistic toddlers, the study found that this co-modulation between the two hemispheres is disrupted in specific brain regions previously linked to communication.”  

In sleeping autistic toddlers, scans showed lowered levels of synchronization between the left and right brain areas known to be involved in language and communication. This pattern was not seen either in children with normal development or in those with delayed language development that was not autistic. In fact, the researchers found that this synchronization was strongly tied to the autistic child’s ability to communicate.

The weaker the synchronization, the more severe were the symptoms of autism. Based on the scans, the scientists were able to identify 70 percent of the autistic children between the ages of one and three.

In research that appeared in Neuron, Malach’s team stated that while many scientists believed that faulty lines of communication between different parts of the brain are involved in the spectrum of autism disorders, there was no way to observe this in very young children, who are unable to lie still inside an MRI scanner while they are awake. However, work by Malach’s group and other research groups pointed to a solution.

Nevertheless, Malach is cautious.

“Our study could potentially provide more objective, brain-derived measures,” he said. “But it is very important to emphasize that the research is still at its initial stages and it will be pre-mature at this stage to assume that the results can be already used for diagnostic purposes.”

Dinstein said this biological measurement could eventually help diagnose autism at a very early stage.

“The goal for the near future is to find additional markers that can improve the accuracy and the reliability of the diagnosis,” Dinstein said. “However, it is going to take a few years to be sure this is useful for diagnosis.

It is not trivial to think about what medication you could use to improve synchronization. It’s not clear whether synchronization is the cause of autism or just a byproduct of having autism that would still be useful for identification but would not necessarily be the target for treatment.”

Click photo to download. Caption: Interspheric correlation maps across subjects including a control group, those with language delay, and those with autism. Credit: Neuron.

Posted on November 26, 2011 and filed under Features.