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For Release: July 29, 2014

STANFORD, Calif. 鈥� The brains of children with autism are relatively inflexible at switching from rest to task performance, according to a new brain-imaging study from the .

Instead of changing to accommodate a job, connectivity in key brain networks of autistic children looks similar to connectivity in the resting brain. And the greater this inflexibility, the more severe the child鈥檚 manifestations of repetitive and restrictive behaviors that characterize autism, the study found.

The study, published online July 29 in Cerebral Cortex, used functional magnetic resonance imaging, or fMRI, to examine children鈥檚 brain activity at rest and during two tasks: solving simple math problems and looking at pictures of different faces. The study included an equal number of children with and without autism. The developmental disorder, which now affects one of every 68 children in the United States, is characterized by social and communication deficits, repetitive behaviors and sensory problems.

鈥淲e wanted to test the idea that a flexible brain is necessary for flexible behaviors,鈥� said Lucina Uddin, PhD, a lead author of the study. 鈥淲hat we found was that across a set of brain connections known to be important for switching between different tasks, children with autism showed reduced 鈥榖rain flexibility鈥� compared with typically developing peers.鈥� Uddin, who is now an assistant professor of psychology at the University of Miami, was a postdoctoral scholar at Stanford when the research was conducted.

鈥淭he fact that we can tie this neurophysiological brain-state inflexibility to behavioral inflexibility is an important finding because it gives us clues about what kinds of processes go awry in autism,鈥� said , the Rachel L. and Walter F. Nichols, MD, professor of psychiatry and behavioral sciences at Stanford and the senior author of the study.

Tracking shifts in connectivity

The researchers focused on a network of brain areas they have studied before. These areas are involved in making decisions, performing social tasks and identifying relevant events in the environment to guide behavior. The team鈥檚 prior work showed that, in children with autism, activity in these areas was more tightly connected when the brain was at rest than it was in children who didn鈥檛 have autism.

The new research shows that, in autism, connectivity in these networks that can be seen on fMRI scans is fairly similar regardless of whether the brain is at rest or performing a task. In contrast, typically developing children have a larger shift in brain connectivity when they perform tasks.

The study looked at 34 kids with autism and 34 typically developing children. All of the children with autism received standard clinical evaluations to characterize the severity of their disorder. Then, the two groups were split in half: 17 children with autism and 17 typically developing children had their brains scanned with fMRI while at rest and while performing simple arithmetic problems. The remaining children had their brains scanned during two tasks: solving simple math problems and detecting differences among pictures of faces. The facial recognition task was chosen because autism is characterized by social deficits; the math task was chosen to reflect an area in which children with autism do not usually have deficits.

We wanted to test the idea that a flexible brain is necessary for flexible behaviors.

Children with autism performed as well as their typically developing peers on both tasks 鈥� that is, they were as good at distinguishing between the faces and solving the math problems. However, their brain scan results were different. In addition to the reduced brain flexibility, the researchers showed a correlation between the degree of inflexibility and the severity of restrictive and repetitive behaviors, such as performing the same routine over and over or being obsessed with a favorite topic.

鈥淭his is the first study that has examined how the patterns of intrinsic brain connectivity change with a cognitive load in children with autism,鈥� Menon said. The research is the first to demonstrate that brain connectivity in children with autism changes less, relative to rest, in response to a task than the brains of other children, he added.

Guidance for new therapies

鈥淭he findings may help researchers evaluate the effects of different autism therapies,鈥� said , a research associate and the other lead author of the study. 鈥淭herapies that increase the brain鈥檚 flexibility at switching from rest to goal-directed behaviors may be a good target, for instance.鈥�

鈥淲e鈥檙e making progress in identifying a brain basis of autism, and we鈥檙e starting to get traction in pinpointing systems and signaling mechanisms that are not functioning properly,鈥� Menon said. 鈥淭his is giving us a better handle both in thinking about treatment and in looking at change or plasticity in the brain.鈥�

Other Stanford authors of the study are research assistants Charles Lynch, Katherine Cheng, Paola Odriozola and Maria Barth; , clinical associate professor of psychiatry and behavioral sciences and co-director of the Autism and Developmental Disabilities Clinic at Lucile Packard Children鈥檚 Hospital Stanford; , professor emeritus of psychiatry and behavioral sciences; and , postdoctoral scholar.

Feinstein and Menon are members of Stanford鈥檚 Child Health Research Institute.

The study was supported by grants from the International Society for Autism Research, the Singer Foundation, and the (grants K01MH092288, HD047520, HD059205 and MH084164).

Information about Stanford鈥檚 Department of Psychiatry and Behavioral Sciences, which also supported the work, is available at .

Individuals interested in obtaining more information about how they or their children can participate in Menon's ongoing studies of childhood brain development can find more information at . His team seeks research participants ages 6 to 22, both with and without autism.

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