Researchers measure blood flow and neural network connectivity to uncover impairments.

A team of UCLA scientists has found that brain areas linked to social behaviors are both underdeveloped and insufficiently networked in youths with high functioning autism spectrum disorder (ASD) compared to study participants without ASD.

The findings, which appear in the 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 the disorder, says study first author Kay Jann, a postdoctoral researcher in the UCLA Department of Neurology.

The study advances the basic understanding of the ASD brain, Jann said.

“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. “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 non-invasive, requiring no injections of radioactive tracers.

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

“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,” said study senior author Danny J.J. Wang, an associate professor of neurology at UCLA.

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.

The hypothesis researchers were testing is that ASD might be caused by increased or decreasedconnectivity 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. “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. 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.

This is important because, as a brain develops, blood flow is generally 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.

Researchers say this is consistent with structural MRI findings of enlarged brain size and an overabundance of neurons in ASD, due to the fact that 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. “This is not what we found in our ASD participants.”

Going forward, the team will 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.

About this autism research

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

Funding: This study was supported by grants from the National Institute of Child Health and Human Development (P50 HD055784), National Institute of Mental Health (1R01-MH080892), the Garen & 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.

Source: Kim Irwin – UCLA

Image Source: The image is in the public domain

Original Research: Full open access research for “Altered resting perfusion and functional connectivity of default mode network in youth with autism spectrum disorder” by Kay Jann, Leanna M. Hernandez, Devora Beck-Pancer, Rosemary McCarron, Robert X. Smith, Mirella Dapretto and Danny J. J. Wang in Brain and Behavior. Published online September 2015 doi:10.1002/brb3.358

Abstract

Altered resting perfusion and functional connectivity of default mode network in youth with autism spectrum disorder

Background

Neuroimaging studies can shed light on the neurobiological underpinnings of autism spectrum disorders (ASD). Studies of the resting brain have shown both altered baseline metabolism from PET/SPECT and altered functional connectivity (FC) of intrinsic brain networks based on resting-state fMRI. To date, however, no study has investigated these two physiological parameters of resting brain function jointly, or explored the relationship between these measures and ASD symptom severity.

Methods

Here, we used pseudo-continuous arterial spin labeling with 3D background-suppressed GRASE to assess resting cerebral blood flow (CBF) and FC in 17 youth with ASD and 22 matched typically developing (TD) children.

Results

A pattern of altered resting perfusion was found in ASD versus TD children including frontotemporal hyperperfusion and hypoperfusion in the dorsal anterior cingulate cortex. We found increased local FC in the anterior module of the default mode network (DMN) accompanied by decreased CBF in the same area. In our cohort, both alterations were associated with greater social impairments as assessed with the Social Responsiveness Scale (SRS-total T scores). While FC was correlated with CBF in TD children, this association between FC and baseline perfusion was disrupted in children with ASD. Furthermore, there was reduced long-range FC between anterior and posterior modules of the DMN in children with ASD.

Conclusion

Taken together, the findings of this study – the first to jointly assess resting CBF and FC in ASD – highlight new avenues for identifying novel imaging markers of ASD symptomatology.

“Altered resting perfusion and functional connectivity of default mode network in youth with autism spectrum disorder” by Kay Jann, Leanna M. Hernandez, Devora Beck-Pancer, Rosemary McCarron, Robert X. Smith, Mirella Dapretto and Danny J. J. Wang in Brain and Behavior. Published online September 2015 doi:10.1002/brb3.358

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