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Brain circuitry in simplex autism

Steven Petersen, Ph.D.
John Constantino, Ph.D.
Washington University in St. Louis


The study of autism is best approached using a variety of disciplines, a practice greatly facilitated by the large amount of data shared among collaborators in the Simons Simplex Collection. Steve Petersen and his colleagues at Washington University in St. Louis plan to contribute new brain imaging data to the mix using a recently developed tool called resting-state functional connectivity MRI (fcMRI).

The new tool measures brain activity at the resting state — not induced by laboratory tasks, as with traditional functional MRI — allowing researchers a glimpse into the innate connections between brain regions. Using this tool, researchers on the project have delineated functionally distinct neural networks associated with processes such as beginning a task, continuing to perform a task, and error feedback.

The researchers have also discovered that these networks mature with age, a process that can be disrupted in neurodevelopmental disorders. These preliminary findings, along with related findings on brain connectivity from other laboratories, led the researchers to hypothesize that the origins of autism could be traced by analyzing the abnormal network connections that are observed at rest between some functional regions of the brain.

The researchers are studying pairs of siblings in which only one sibling has autism, as well as unrelated, healthy controls. The new imaging and analysis techniques will be used to look at networks in various brain regions, including those involved in social behavior, goal-directed actions, and others that may be disrupted in individuals with autism. Half of the subjects will be 9 to 14 years old and the other half 18 to 30 years old, giving the researchers an idea of what the networks look like at a range of ages. The fcMRI data will also be used to reconstruct images of the brain’s surface, which can be linked to behavioral, psychometric and genetic data for each individual.

In a sample of 50 subjects (half with simplex autism, meaning there is only one child with autism in the family), the network structure — or the way in which brain areas are functionally related to each other — appears similar across groups. However, children with autism show increased local strength of connections, as well as decreased strength between sub-network connections. For example, frontal–frontal cortex, and frontal–motor cortex functional connectivity is stronger in children with autism, whereas visual–motor functional connectivity is weaker. This brain-wide, network-based approach to fcMRI contextualizes findings from prior autism studies, revealing altered connectivity within and between distinct brain sub-networks.