International Meeting for Autism Research: Long-Range Fronto-Parietal Connectivity Is Related to Language Abilities in Children with and without Autism Spectrum Disorders
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Long-Range Fronto-Parietal Connectivity Is Related to Language Abilities in Children with and without Autism Spectrum Disorders

Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
10:00 AM
A. A. Scott , Scripps Genomic Medicine, Scripps Translational Science Institute, La Jolla, CA
B. S. Abrahams , Department of Neurology, University of California, Los Angeles
A. I. Alvarez-Retuerto , Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles
L. Sonnenblick , Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
D. Ghahremani , Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
J. Mumford , Department of Psychology, University of California, Los Angeles
R. A. Poldrack , Department of Psychology, University of California, Los Angeles
M. Dapretto , Department of Psychiatry and Biobehavioral Sciences & Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA
D. H. Geschwind , Department of Neurology, University of California, Los Angeles
S. Y. Bookheimer , Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA
Background: Autism is a neurodevelopmental disorder characterized by impairments in language and social communication, and accompanied by restricted interests and stereotyped behaviors. A growing body of evidence implicates disruption of frontal cortical connectivity in autism spectrum disorders (ASD). Recently we found that an autism risk gene, CNTNAP2, modulates frontal functional connectivity in children with and without an ASD. This risk gene has been linked with language ability in both autism, and specific language impairment (SLI). Together, these findings suggest that variation in CNTNAP2 may confer disease risk by biasing the brain towards different patterns of connectivity. These findings prompted us to test the hypothesis that variation in frontal functional connectivity is associated with language abilities in children with and without autism spectrum disorders.

Objectives: The aim of this investigation was to determine whether patterns of functional connectivity with the medial prefrontal cortex (mPFC) are related to verbal ability (verbal IQ and receptive language) across children with and without an ASD.

Methods: We conducted task-independent functional connectivity analysis on functional magnetic resonance imaging (fMRI) scans collected from sixteen typically-developing (TD) boys (12.3 ± 1.76; FSIQ: 119.0 ± 8.41) and 16 age- and IQ-matched high-functioning boys with ASD (12.4 ± 2.14; FISQ: 112.3 ± 13.6). Briefly, a nuisance model including prewhitening with task as an explanatory variable, white matter average timeseries, cerebrospinal fluid average timeseries and motion included as covariates was run and residuals computed. The average timeseries from the seed ROI (mPFC) was extracted from the residual image. Both the extracted timeseries and residual image were normalized and entered into subject-wise correlations to create mPFC functional connectivity maps for each subject. Whole-brain regressions on the functional connectivity maps using verbal IQ (VIQ) and receptive language scores from the Peabody Picture Vocabulary Test (PPVT-III) were conducted.

Results: A whole-brain regression on mPFC functional connectivity with verbal IQ scores revealed a positive correlation in posterior cingulate cortex (MNIx,y,z= -10, 41, 48; Z = 4.23), bilateral angular gyri (Right MNIx,y,z= 52, -54, 30; Z = 4.34; Left MNIx,y,z= -52, -56, 24; Z= 3.13), and right superior cerebellum (MNIx,y,z = 40, 076, -34; Z=4.52). An additional whole-brain regression on mPFC functional connectivity with receptive language scores from the PPVT demonstrated a positive correlation with right angular gyrus (MNIx,y,z = 46, -66, 40; Z = 3.81) and right superior cerebellum (MNIx,y,z = 44, -70, -34; Z = 4.18).

Conclusions: These results indicate that children with higher verbal IQ scores had increased anterior-posterior functional connectivity between medial prefrontal cortex and posterior heteromodal speech, language and attention areas. Similar to the positive correlation observed with VIQ, which taps expressive language ability, we found that children with better receptive language abilities, as measured by the PPVT, also demonstrate stronger long-range connectivity between the mPFC and parietal cortices. These findings support the contribution of long-range frontoparietal networks to verbal abilities and reflect the importance of these connections for language development and autism pathogenesis.

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