Atypical Cerebral Lateralization of Language and Motor-Related Regions in High-Functioning Male Adults with Autism
One potential neuroanatomical marker of autism spectrum conditions (ASC) is atypical cerebral lateralization. The “left hemisphere dysfunction theory” is based on the notion that individuals with ASC exhibit deficits in functions ascribed to the left hemisphere such as language, communication and motor skills whilst appearing relatively unaffected in cognitive functions mainly supported by the right-hemisphere.
To investigate in individuals with autism (1) whether atypical structural cerebral lateralization is present in regions integral to language and motor processing and (2) whether atypical lateralization is related to autistic characteristics and language and motor functioning.
Participants comprised 67 adult males with autism (26 with high-functioning autism [HFA]; 41 with Asperger Syndrome [AS]) and 69 typically developing (TD) males, all aged 18-43 years and the two groups were not significantly different in age and IQ. All participants were right-handed based on the Edinburgh Handedness Inventory. Simulated T1-weighted IR images generated from DESPOT1 MRI scans (at 3T) were preprocessed in SPM8 using the VBM8 toolbox. Region-of-interest analyses were conducted by deriving the mean volume of selected motor (Precentral Gyrus [PG], Supplementary Motor Area [SMA]) and posterior language regions (Superior Temporal Gyrus [STG], Planum Temporale [PT], Angular Gyrus [AG], Supramargninal Gyrus [SG]) using the Harvard-Oxford atlas (Kennedy et al., 1998). Laterality indices of grey matter volumes were defined as: [(right – left) / (right + left)] × 100. Autistic characteristics were assessed using subdomain algorithm scores of the ADI-R and ADOS-G. Language performance was assessed using the Non-Word-Repetition task (Gathercole et al., 1994) and motor performance by the Purdue PegBoard Test (Tiffin et al.1948).
Among language regions, both the PT (p=0.012) and the AG (p=0.013) showed stronger rightward lateralization in males with ASC compared to TD males. Rightward asymmetry of the PT was associated with poorer performance on the Non-Word-Repetition Task in males with ASC (Pearson’s r=-0.429; p<0.001).
Among the motor regions, the PG showed stronger rightward lateralization in males with ASC compared to TD males (p=0.009). This was not associated with performance on the PegBoard Task, but with higher scores on current autistic communicative, social interaction and imagination difficulties (ADOS-A, r=0.427; p=0.037; ADOS-B, r=0.411, p=0.046; ADOS-C, r=0.430, p=0.036) but only in individuals with HFA and not those with AS. For both PT and PG asymmetries, males with AS were intermediate between those with HFA and TD males.
Atypical cerebral rightward lateralization is present in male adults with ASC in regions associated with language and motor functions. Specifically, atypical lateralizationin the motor cortex is associated with social-communicative deficits in autism, corresponding to theories suggesting that early motor deficits might underlie the core cognitive symptoms in autism (Mostofsky et al., 2000). Reversal of typical asymmetry in the PT in autism has been consistently reported in previous literature, and here we additionally found a gradation between individuals with and without language delay. This stepwise pattern between diagnostic subgroups also applies to a non-linguistic primary motor region, suggesting the possibility of common underlying neurodevelopmental mechanisms contributing to motor, social and language deficits in autism.