John Constantino M.D.

Abstract

• Brain Circuitry in Simplex Autism

  To capitalize on the extensive genetic information the Simons Simplex investigators are now collecting and to fully realize its benefit, the field of autism research would benefit substantially from the perspective and collaboration of cognitive and systems neuroscientists. The proximity of brain imaging researchers to the Simons Simplex site at Washington University and our history of collegial and fruitful collaborations make this an ideal site to undertake this critical step forward. The overarching consideration of this proposal is that autism is, at least in part, a consequence of atypical development of network relationships among specific functional regions in the brain. To explore this hypothesis, we will capitalize on powerful new methods for measuring connectivity in brain networks, one of which involves the measurement of spontaneous activity during resting states (resting state functional connectivity MRI, rs-fcMRI). This offers a unique way of identifying which brain regions tend to activate or de-activate in synchrony with one another, and provides a window of observation on enduring intra-regional connections that reflect the recent developmental course of functional integration between the regions in a given network. In this study, we will employ rs-fcMRI to elucidate abnormal brain circuitry associated with autism. We will compare 60 individuals with autism (across the age range from 9-30 years) with 60 close-aged unaffected siblings and 60 unrelated control subjects. This study will enrich the comprehensive multidisciplinary data collection now underway in the Simons Simplex Collection and may uncover common neurobiological themes within the various genetic causes represented by simplex autism. The availability of full genetic and neuroimaging data on a common set of sibling pairs discordant for autism will constitute an unprecedented and lasting resource for the testing of current and future hypotheses that relate specific genetic pathways to specific patterns of brain dysfunction.

• Simons Simplex Collection Site

Institution

• Washington University in St. Louis