CART ACE II - Project 4: Neuroimaging signatures of autism: Linking brain function to genes and behavior

Project summary

Overview: The longitudinal stuides conducted under ACE II Project 4 will lead to a better characterization of functional brain networks in individuals with Autism Spectrum Disorder (ASD) that may ultimately be useful for earlier diagnosis as well as for informing the development of targeted behavioral and pharmacological interventions and/or evaluating their effectiveness.

Project 4 Summary: Autism is characterized by tremendous phenotypic heterogeneity likely due to its complex genetic and neural underpinnings. Research from our lab and others have provided mounting evidence of decreased responsivity to social stimuli and altered patterns of brain connectivity in individuals with ASD. Moreover, we have recently shown that aberrant functional and structural connectivity is significantly related to genetic vulnerability to the disorder. Despite these significant strides, critical questions remain unanswered with regard to:

i) the underlying mechanisms that may give rise to the reduced mirroring and reward-related responses to social stimuli we have previously characterized;

ii) the relationship between the functioning of these circuits and aberrant connectivity;

iii) the extent to which the latter reflects the cause or the effect of altered developmental trajectories in ASD and, more broadly,

iv) how know genetic risk factors for ASD impact brain circuitry subserving complex social behaviors.

The current studies are designed to address these issues, while seeking to build synergy amongst competing neurobiological accounts of ASD. Given our previously characterized cohorts, we will systematically chart longitudinal changes in brain activity and connectivity in children with and without ASD and relate the observed developmental trajectories to both behavioral phenotypes and autism risk genes.

More specifically, using a cross-lagged longitudinal design, we will perform functional magnetic resonance imaging (fMRI), resting state MRI and diffusion tensor imaging (DTI) at two timepoints (3 years apart) in two previously characterized age cohorts (6-9 and 12-14 years of age at first assessment) and relate these data to behavioral phenotypes and ASD risk poplymorphisms. This integrated research will identify the earliest departures from typical development and delineate the complex interactions among genes, brain, and behavior that drive and constrain the atypical development of the social brain in ASD.

Primary Investigator: 
Mirella Dapretto, Ph.D.
Susan Bookheimer, Ph.D.