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Characterization of Neural Disconnectivity in Autism: A Large-Sample Diffusion Tensor Imaging Study Using Tract-Based Spatial Statistics

Saturday, 4 May 2013: 11:45
Meeting Room 1-2 (Kursaal Centre)
J. K. Leung1,2, C. Cordeaux2, S. K. Mitchell2, I. Y. Murphy2, K. A. Pelphrey2 and R. J. Jou2, (1)Department of Pediatrics, Yale School of Medicine, New Haven, CT, (2)Child Neuroscience Lab, Child Study Center, Yale School of Medicine, New Haven, CT
Background: Mounting evidence from structural and functional MRI and diffusion tensor imaging (DTI) suggests that the brain phenotype in autism spectrum disorder (ASD) includes deficiencies in long-range neural connections; however, the specific pattern of disconnectivity in ASD is not yet known.  Preliminary evidence from our group has implicated the inferior fronto-occipital fasciculus (IFOF) in the pathobiology of ASD, suggesting a potential mechanism for known impairments recognizing emotions in faces.

Objectives: Characterize IFOF and other fiber tract aberrations by comparing a large sample of ASD children to typically developing controls.

Methods: Neuroimaging and behavioral data were collected on 84 participants: 52 children with ASD (age = 8.5 ±3.5 years) and 32 controls (age = 9.88 ±3.48 years).  Subjects with psychiatric and neurologic disorders associated with ASD were excluded from both groups, and subjects with a history of ASD in first- or second-degree relatives were excluded from the control group.  ASD participants had confirmed DSM-IV diagnoses based on expert evaluation using the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule.  To match for cognitive functioning, all subjects completed the Differential Abilities Scale.  The Social Responsiveness Scale (SRS) was collected on all subjects to characterize the severity of social disability.  Diffusion-weighted MRI (directions = 30 and b0 = 5) were acquired using a 3-Tesla scanner.  Fractional anisotropy (FA) was used as the primary measure of fiber tract integrity, which ranges from 0 (low integrity) to 1 (high integrity).  Data were analyzed using FMRIB Software Library (FSL).  After motion correction, FA maps for all participants were created.  Tract-Based Spatial Statistics was used to compare group-averaged FA maps where p < 0.05.  Affected voxels were labeled using an integrated white matter tractography atlas.  Post-hoc correlation analyses were conducted between mean fiber tract FA and SRS scores.

Results: Of the 84 participants, 17 were excluded due to motion artifact leaving a final sample of 67 (29 controls and 38 ASD).  When compared to controls, the ASD group had significant bilateral reductions in FA involving both association and commissure tracts.  The most severely affected association tracts included the IFOF and uncinate fasciculus.  The most severely affected commissural fibers included the forceps minor.  There were neither areas of increased FA in the ASD group nor decreased FA in the control group.  There were no significant group differences in intracranial volume, age, race, handedness, and cognitive functioning.  All post-hoc correlation analyses involving SRS measures did not reach statistical significance.

Conclusions: This large sample DTI study supports our preliminary data implicating the IFOF in the pathobiology of ASD.  In addition, it is consistent with many other studies in the research literature documenting abnormalities in the corpus callosum and uncinate fasciculus.  Determining the specific neural phenotype in ASD has implications for more objective diagnosis, targeted intervention, and better understanding of the etiology of ASD.

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