Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
10:00 AM
J. D. Rudie
,
Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA
Z. Shehzad
,
Department of Psychology, Yale, New Haven, CT
N. Colich
,
Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA
S. Y. Bookheimer
,
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA
M. Iacoboni
,
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA
M. Dapretto
,
Department of Psychiatry and Biobehavioral Sciences & Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA
Background: Converging evidence from neuroimaging and neurobiological studies of autism has led some to propose that autism spectrum disorders (ASDs) result from a failure of coordinated neural activity across long-range networks required for complex reciprocal social behavior (see Geschwind & Levitt, 2007, for review). In addition, dysfunction in the mirror neuron system (MNS), which rely on “long-range” fronto-parietal circuits subserving sensorimotor integration, has been linked to social communication deficits observed in ASD (see Oberman & Ramachandran, 2007, for review). We have previously shown that high-functioning children with ASD display less MNS activity in the right pars opercularis of the inferior frontal gyrus (IFG) compared to typically-developing (TD) controls while observing and imitating emotional expressions.Objectives: We sought to further test the hypothesis that individuals with ASD have diminished functional connectivity across long-range networks that underlie complex social behavior. Specifically, we were interested in examining functional connectivity within the MNS. In order to test this hypothesis, we used a seed based functional connectivity analysis to characterize differences in connectivity in the MNS between TD and ASD children.Methods: Twenty-three high-functioning children with ASDs and twenty-five typically developing children (matched by age, gender, IQ and head motion) passively observed faces displaying different emotions (angry, fearful, happy, sad, and neutral) while undergoing functional Magnetic Resonance Imaging (fMRI). Using an event-related design, each face was presented for two seconds according to an optimized random sequence. In order to minimize connectivity between regions simply due to task-related activity, we removed task effects by using the residuals from the general linear model that included the stimuli timings convolved with a double gamma-HRF. The right pars opercularis, as defined from the Harvard-Oxford probabilistic atlas (25% probability), was used as a seed region in our whole brain functional connectivity analysis.Results: Direct contrasts of whole-brain corrected connectivity maps showed that in TD children, activity in the right pars opercularis was more strongly correlated with other long-range mirror neuron regions, including contralateral IFG and bilateral inferior parietal lobule. Children with ASD showed stronger local connectivity with anterior cingulate and ventromedial prefrontal cortex. While we regressed out the task effects, these “pseudoresting state” networks may still reflect enhanced correlations in networks involved in processing facial expressions. Conclusions: Building on our previous findings of significant between-group differences in the frontal component of the MNS, the current results found during the observation of facial expressions provide supporting evidence of a relationship between deficits in ASD and the MNS. Additionally, increased connectivity with the anterior cingulate in participants with ASD is interesting in light of recent studies showing hyperactivity or the inability to deactivate the anterior cingulate cortex in individuals with ASD (Tesink 2009, Dichter 2009). The present findings highlight the importance of functional connectivity approaches in autism neuroimaging research and add to the literature implicating dysfunction in long-range networks in ASD etiology.
