Atypically rightward cerebral asymmetry in male adults with autism stratifies individuals with and without language delay

Abstract

In humans, both language and fine motor skills are associated with left-hemisphere specialization, whereas visuospatial skills are associated with right-hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right-handed adults with ASC and 69 age- and IQ-matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel-based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl's gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC.

Keywords: autism; cortical asymmetry; language delay; lateralization; volumetric MRI.

Figure 1

Anatomical and Functional Regions of Interest. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

(a) Significant cluster (ASC vs. controls). Sagittal slices of the MNI stereotactic atlas with superimposed significant between‐group differences in LI covering perisylvian regions. Red: IPL cluster; Blue: Auditory cluster. (b) Means and standard deviations of laterality indices extracted from the auditory cluster and the IPL cluster. Positive values indicate rightward asymmetry, and negative values indicate leftward asymmetry (with arbitrary unit). Controls (NT) show leftward asymmetry in both clusters, whereas individuals with ASC show reduced leftward asymmetry in the auditory cluster and reversed rightward asymmetry in the IPL cluster. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 3

Group differences in left and right IPL and Auditory cluster volume. Means and SD of volume (in mm³) extracted from left and right auditory and IPL clusters. Differences in the IPL cluster were driven by larger rightward and smaller leftward volumes, whereas only by larger rightward volume in the auditory cluster in individuals with ASC. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 4

Group differences in peak voxels for non‐significant ROIs. Abbreviations: A Motor: anatomical motor ROI; A PT: anatomical auditory ROI (planum temporale); A Broca: anatomical language ROI; F Motor: functional motor ROI; F Language: functional language ROI; F Visuospatial: functional visuospatial ROI.

Figure 5

Relationship between Auditory LI and symptom severity. Positive values indicate rightward asymmetry, and negative values indicate leftward asymmetry (arbitrary unit). There was a positive correlation between abnormal social reciprocity scores on the ADI‐R and asymmetry of the auditory cluster, indicating more childhood symptoms with reduced leftward / stronger rightward asymmetry.

Figure 6

(a) Significant cluster (ASC with LD vs. controls). Sagittal slices of the MNI stereotactic atlas with superimposed significant between‐group differences in the auditory LI showing the overlap between significant clusters. Blue: Auditory cluster (all ASC‐controls); Green: Auditory cluster (ASC with LD‐controls). (b) Group differences in Auditory LI between individuals with ASC with and without LD and controls. Abbreviations: NT: neurotypicals (controls); NoLD: individuals with ASC without language delay; LD: individuals with ASC with language delay means and standard deviations of laterality indices extracted from the auditory cluster (ASC with LD vs. controls). Positive values indicate rightward asymmetry, and negative values indicate leftward asymmetry (with arbitrary unit). Individuals without language delay (NoLD) show an intermediate position between individuals with language delay (LD) and controls (NT) for the values extracted from the auditory cluster. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 7

Differential association between the Auditory LI and social symptoms in individuals with ASC with and without LD. Positive values indicate rightward asymmetry, and negative values indicate leftward asymmetry (arbitrary unit). There was a positive correlation between abnormal social reciprocity scores on the ADI‐R and asymmetry of the auditory cluster, indicating greater childhood symptoms with reduced leftward / stronger rightward asymmetry in ASC individuals with LD, but not in those without LD. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 8a

Non‐thresholded, descriptive t‐maps. Unthresholded t‐map of the ASC‐Control contrasts. Regions where ASC has larger LI values are shown in red, whereas regions where controls have larger LI values than ASC are shown in blue. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 8b

Unthresholded t‐maps within each anatomical and structural ROI. Unthresholded t‐map of the ASC‐Control contrasts. Regions where ASC has larger LI values are shown in red, whereas regions where controls have larger LI values than ASC are shown in blue. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]