Cortical Surface Anatomy in Adult Females with Autism

Background: It is well established that Autism Spectrum Disorder (ASD) is accompanied by neurodevelopmental differences in brain anatomy and connectivity.  The neurocognitive networks underlying ASD may involve the cerebellum, amygdala-hippocampal complex, frontotemporal regions and caudate nucleus (Amaral, Schumann, & Nordahl, 2008). However, most of the previous structural neuroimaging studies only examined measures of cortical volume (CV), which is a product of cortical thickness (CT) and surface area (SA). Thus, examining independent variations of these distinct anatomical features may provide additional important insights into the cortical neuropathology of ASD (Ecker et al., 2013). Further, most previous studies examined males and not females with ASD, and the neuroanatomy of ASD in females therefore remains currently underexplored (Lai et al., 2013).

Objectives: The present study aimed to establish the neuroanatomical correlates of ASD in adult females with the condition relative to typically developing adult female controls, using a spatially-unbiased surface-based approach.

Methods:  Structural T1-weighted MRI scans were collected on 49 females adults with ASD (mean age=28yrs (sd=7), mean FSIQ=119 (sd=16)) diagnosed with gold-standard diagnostic tools (i.e. ADOS, ADI-R), and 49 matched typically developing female controls. Participants were recruited with the support of the MRC AIMS (Autism Imaging Multi-Centre Study) Consortium, and scanned at two sites (London and Cambridge, UK). Surface reconstructions for all structural MRI scans were performed using FreeSurfer software (http://surfer.nmr.mgh.harvard.edu). A set of three volumetric features (CV, CT, SA) was obtained at each spatial location on the cortical surface. Between-group differences in these features were examined using a general linear model including group and site as categorical fixed effects factors, and age and IQ as continuous covariates. A random-field-based cluster-threshold (p<0.05) was used to correct for multiple comparisons.

Results:  Females with ASD differed from controls in all three surface-based features. Females with ASD had a significant increase in CV in right occipital lobe relative to controls.  We also found a significant increase in CT in the right superior frontal gyrus in ASD, and a decrease in CT in the left fusiform gyrus and right parahippocampal gyrus.  Finally, females with ASD showed a decreased SA of the right superior frontal gyrus relative to controls. However, neither CT nor SA contributed uniquely to the observed differences in CV.

Conclusions:  Adult females with ASD have significant neuroanatomical differences in a variety of surface-based cortical features relative to controls. It remains to be established, however, to what extent these differences overlap with the neuroanatomical differences observed in males with the conditions, and to what degree neuroanatomical differences between the sexes mediate differences in the respective symptom profiles that are typical for males and females with ASD.