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Brain Advance Access originally published online on January 29, 2008
Brain 2008 131(4):1000-1012; doi:10.1093/brain/awm334
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© The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Abnormal functional connectivity in autism spectrum disorders during face processing

Natalia M. Kleinhans1, Todd Richards1, Lindsey Sterling3, Keith C. Stegbauer1, Roderick Mahurin1, L. Clark Johnson2, Jessica Greenson4, Geraldine Dawson3 and Elizabeth Aylward1

1Department of Radiology, 2Department of Psychosocial & Community Health, 3Department of Psychology and 4Center on Human Development and Disability, University of Washington, Seattle, WA, USA

Correspondence to: Natalia M. Kleinhans, PhD, Department of Radiology, University of Washington, Box 357115, Seattle, WA 98195, USA E-mail: nkleinha{at}u.washington.edu

Abnormalities in the interactions between functionally linked brain regions have been suggested to be associated with the clinical impairments observed in autism spectrum disorders (ASD). We investigated functional connectivity within the limbic system during face identification; a primary component of social cognition, in 19 high-functioning adults with ASD and 21 age-and IQ-matched control adults. Activation during identification of previously viewed faces and houses using a one-back paradigm was compared. The fusiform face area (FFA) was individually localized in each participant and used as the seed point for functional connectivity analyses. The degree of correlation between FFA and the extended neural circuitry involved in face identification was tested. A whole brain analysis was also conducted in order to determine whether connectivity from the FFA to aberrant brain locations was present in the ASD group. Measures of clinical severity (ADOS social score and ADI-R social score) were included as independent variables into the functional connectivity analyses. Significant FFA-amygdala and FFA-superior temporal sulcus functional connectivity was found in both the ASD and control participants. However, the control group had significantly increased connectivity to the left amygdala and the posterior cingulate compared to ASD. Post hoc analyses additionally found increased connectivity to the thalamus in the controls. A significant relationship between abnormal functional connectivity and clinical severity in the ASD group was observed. Specifically, greater social impairment was associated with reduced FFA-amygdala connectivity and increased FFA-right inferior frontal connectivity. These results suggest that abnormal neural connections within the limbic system may contribute to the social impairments observed in ASD.

Key Words: autism; Asperger's disorder; functional connectivity; face processing; brain imaging

Abbreviations: ASD, autism spectrum disorders; FFA, fusiform face area; RFFA, right fusiform face area; fMRIB, centre for functional MRI of the brain; ROI, region of interest

Received May 30, 2007. Revised December 12, 2007. Accepted December 18, 2007.


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