An Anatomical MRI Investigation of Asymmetries in Frontal and Temporal Language Association Cortex in Children with Autism Disorder

Background: Recent MRI investigations of volumetric-based hemispheric asymmetries in high functioning children and adolescents with autistic disorder (AD) have provided evidence for abnormal patterns of cortical asymmetry. We used MRI to assess hemispheric asymmetries in frontal and temporal lobe cortical language regions in a large sample of relatively low functioning children with AD to determine if similar patterns of asymmetry are found in younger, lower functioning children.

Objectives: We conducted quantitative morphometric analyses of perisylvian and frontal regions in children with AD to elucidate the relationship between brain structure and language function. Objectives were to (i) assess hemispheric asymmetries in temporal and frontal language association cortex, (ii) determine the correspondence, if any, to neuropsychological measures of language function, and (iii) evaluate the concordance of these measures in three sets of monozygotic (MZ) twins to examine the role of epigenetic factors.

Methods: Sample: 53 children (44 male), ages 2-14yrs, who met ADOS and ADI-R research criteria, including three pairs of MZ twins (one of each pair was randomly excluded from the larger sample). Segmentation and cortical parcellation was performed on anatomical MRI images as previously described (Filipek et al., 1994). Regions of interest (ROIs) were planum temporale (PT) and posterior Superior Temporal Gyrus (pSTG), corresponding to the functional region Wernicke’s area, and pars triangularis (F3t) and pars opercularis (F3o), corresponding to the functional region Broca’s area.  Comparisons of volume were calculated and expressed using a symmetry index (SI=(2*(L-R))/(L+R)), positive numbers indicate a leftward preponderance. Neuropsychological measures (verbal IQ [vIQ], PPVT) were collected to determine their correspondence to lateralization in cortical language areas.

Results: Full sample (n=50): rightward asymmetry in temporal regions: pSTG (mean SI=-.0114, p<.01), PT showed a rightward, non significant, trend (mean SI=-.061, p=.08). PT and pSTG SIs were positively correlated (r=.444, p<.01).  Frontal regions: no significant asymmetries observed. When we constrained the sample to right-handed boys (n=30), direction of asymmetry results did not change. Temporal regions: pSTG (mean SI=-.145, p<.01), PT (mean SI=-.094, p<.05).  SIs for PT and pSTG were positively correlated (r=.404, p<.05). Frontal regions: no significant asymmetries observed. SIs for F3t and F3o were positively correlated (r=.414, p<.05). The full sample F3t SI showed a weak positive correlation with vIQ, that was significant when the sample was constrained to right-handed boys (r=.418, p<.05). PT asymmetry was age dependent, with greater rightward asymmetry as a function of age. We also report lack of concordance for asymmetry in frontal and temporal language association cortex in a cohort of MZ twins.

Conclusions: Findings of atypical rightward asymmetries in PT and pSTG, suggest a relationship in the maturational path of these two temporal lobe language regions. Variability between subjects contributed to non-significant asymmetries in the two frontal lobe regions; however they were significantly correlated within subject, providing further evidence for similar developmental paths. The correlation pattern reflecting higher vIQ scores associated with more typical, leftward asymmetry in F3t demonstrates a tentative link between anomalous brain structure and functional impairment.  MZ twin results indicate epigenetic factors are involved in the development of cortical language association regions.