Brain areas linked to social behaviors are both underdeveloped and insufficiently networked in youths with high functioning autism spectrum disorder compared to study participants without ASD, according to UCLA researchers.

OT_News-01The findings, which were published in the September online issue of the peer-reviewed journal Brain and Behavior, provide insight into how the brains of children and adolescents with ASD might be organized differently than youths without ASD, first author Kay Jann, PhD, a postdoctoral researcher in the UCLA neurology department, said in a news release. The study advances the basic understanding of the ASD brain, Jann said in the release.

“The brain controls most of our behavior and changes in how brain areas work and communicate with each other can alter this behavior and lead to impairments associated with mental disorders,” he said in the release. “When you match physiologic changes in the brain with behavioral impairment, you can start to understand the biological mechanisms of this disorder, which may help improve diagnosis, and, in time, treatment.”

The researchers used imaging technology that tracks both brain blood flow — as a measure of energy use — and the organization and strength of connections within intrinsic neural networks.

This was the first time an MRI tool known as arterial spin labeling perfusion was used to study ASD. The technique uses magnetically labeled blood water as a tracer to quantify brain blood flow. The researchers also refined use of existing technology that assesses how well separate brain areas are functionally interconnected. Both techniques are noninvasive, requiring no injections of radioactive tracers.

This approach has been used in other brain disorders such as schizophrenia and has already led to novel insights and alternative treatment approaches.

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Danny J.J. Wang

“In neurocognitive or neuropsychiatric disorders, these two crucial properties — functional organization of the brain and its accompanying energy demands — are often found to be altered,” study senior author Danny J.J. Wang, PhD, an associate professor of neurology at UCLA, said in the release.

In this study, investigators studied 17 youths with high-functioning ASD and 22 typically developing children and adolescents. The groups were matched by age, 7 to 17 years old, gender and IQ scores.

Researchers were testing a hypothesis that ASD might be caused by increased or decreased connectivity within specific neural networks that form the “social brain.” This connectivity can be measured by the amount of blood flow and activity patterns between brain nodes, or neural networks.

“One major brain network, the default mode network, has become a focus of such research, because it is important for social and emotional processes, self-referential thought and in ‘Theory of Mind,’ which is the ability to attribute mental states to one-self and to others,” Wang said in the release. “These are cognitive processes that are to some extent impaired in persons with autism spectrum disorders.”

Imaging the participants while they rested in the scanners revealed significant differences between the two groups, Wang said in the release. Children with ASD exhibited a pattern of widespread increased blood flow, or hyper-perfusion, linked to increased oxygen metabolism in frontal brain areas that are important in navigating social interactions, the study found. This is important because, as a brain develops, blood flow generally is reduced. These signs of continuing hyper-perfusion in ASD participants suggest delayed neurodevelopment in these frontal brain regions associated with socio-emotional cognition, Wang said in the release.

According to researchers, this is consistent with structural MRI findings of enlarged brain size and an overabundance of neurons in ASD, because the synapses of neurons have not been sufficiently pruned as the brain develops. Too many functioning synapses inhibit cognition while requiring extra blood flow.

The research team also discovered reduced long-range connectivity between default mode network nodes located in the front and back of the brain in those with ASD, compared to typical brains. This loss of connectivity means that information cannot flow as it should between distant areas of the brain, which may help explain impairment in social responsiveness, Jann said.

“The architecture of the brain follows a cost-efficient wiring pattern that maximizes functionality with minimal energy consumption,” Jann said in the release. “This is not what we found in our ASD participants.”

The team plans to continue to study the relationship between network connectivity and metabolism in individuals with ASD, extending their work to other relevant brain networks. They’re also seeking to define the range of variation in these factors in the general population.

This study was supported by grants from the National Institute of Child Health and Human Development, National Institute of Mental Health and Garen and Shari Staglin and the International Mental Health Research Organization. Jann has a fellowship funded by the Swiss National Science Foundation and the Swiss Foundation for Grants in Biology and Medicine.

The research team included scientists from the UCLA Ahmanson-Lovelace Brain Mapping Center and the UCLA Department of Psychiatry and Biobehavioral Sciences.

Full study: http://onlinelibrary.wiley.com/doi/10.1002/brb3.358/full