19496
Atypically Rightward Cortical Asymmetry in Both Children and Male Adults with Autism
One potential contributing neuroanatomical substrate for the functional characteristics of autism spectrum conditions (henceforth ‘autism’) is atypical cerebral asymmetry. Individuals with autism exhibit deficits in left hemisphere-specialized functions such as language, communication and motor control/praxis whilst appearing relatively unaffected in right hemisphere-specialized functions such as visuospatial abilities.
Objectives:
To investigate in two independent samples of individuals with autism whether (1) atypical structural asymmetry is present in regions integral to language, motor and visuospatial processing and (2) this relates to autistic characteristics and language, sensorimotor and visuospatial functioning.
Methods:
Sample 1 comprised 84 right-handed, high-functioning adult males with autism and 84 neurotypical males aged 18-43 years. Autistic symptoms were assessed by the ADI-R and ADOS. Language was assessed by the Non-Word-Repetition task, the word generativity F-A-S task and verbal IQ, motor performance by the Purdue PegBoard Test and visuospatial abilities by the Embedded Figures Task.
Sample 2 comprised 47 right-handed, high-functioning children with autism (8girls; 39boys) and 87 neurotypical children (61boys; 26girls) aged 8-12 years. Autistic symptoms were assessed by the ADI-R, ADOS and SRS. Motor performance was assessed by the Physical and Neurological Examination for Subtle Signs.
The two samples were analysed separately using SPM8. Simulated T1-weighted IR images generated from DESPOT1 MRI scans at 3T (sample1) and T1- MPRAGE scans at 3T (sample2) were flipped, segmented and registered to separate symmetrical DARTEL templates. Laterality indices of grey matter volumes were defined as: 2*[(right–left)/(right+left)]. Two analyses of volumetric asymmetry were conducted: (1) a voxel-wise ROI analysis within three functionally defined regions of interest; (2) a follow-up whole brain volumetric analysis. Functional ROIs were generated using the online database NeuroSynth by deriving meta-analytic co-activation patterns for regions functionally related to language, motor and visuospatial functions.
Results:
Voxel-wise analysis of volumetric asymmetry within the language ROI revealed significant reductions from typical leftward asymmetry in both adults with autism (cluster-level FDR-corrected q=0.021) and children with autism (cluster-level FDR-corrected q=0.010). There were no significant deviation from typical asymmetry for the motor and visuospatial ROI in either sample. The voxel-wise whole brain analyses revealed reductions in leftward asymmetry in perisylvian temporal and parietal regions and posterior ventrolateral frontal cortex in both adults (cluster-level q=0.01) and children with autism (cluster1: q=0.035; cluster2: q= 0.002; cluster3: q<0.001; cluster4; q=0.026). Correlations with symptom severity or cognitive-behavioural performance measures were not significant in either group.
Conclusions:
Atypical cerebral asymmetry is present in both children and adults with autism and is most pronounced in posterior regions related to language processing. Future studies should examine behavioural correlations with such cerebral asymmetry. Given that cerebral asymmetries are very subtle at the neuroanatomical level, future studies should take into account lateralization at a functional level to fully reveal the nature of atypical lateralization in autism. Finally, given the postulated role of prenatal sex hormones in creating cerebral laterality, and the recent finding of elevated prenatal sex steroids in autism, this mechanism should be explored in cohorts where fetal steroids, measures of autistic traits, and MRI data are available.