Sex differences and autism: brain function during verbal fluency and mental rotation

Abstract

Autism spectrum conditions (ASC) affect more males than females. This suggests that the neurobiology of autism: 1) may overlap with mechanisms underlying typical sex-differentiation or 2) alternately reflect sex-specificity in how autism is expressed in males and females. Here we used functional magnetic resonance imaging (fMRI) to test these alternate hypotheses. Fifteen men and fourteen women with Asperger syndrome (AS), and sixteen typically developing men and sixteen typically developing women underwent fMRI during performance of mental rotation and verbal fluency tasks. All groups performed the tasks equally well. On the verbal fluency task, despite equivalent task-performance, both males and females with AS showed enhanced activation of left occipitoparietal and inferior prefrontal activity compared to controls. During mental rotation, there was a significant diagnosis-by-sex interaction across occipital, temporal, parietal, middle frontal regions, with greater activation in AS males and typical females compared to AS females and typical males. These findings suggest a complex relationship between autism and sex that is differentially expressed in verbal and visuospatial domains.

Figure 1. Mental rotation stimuli (a) and control condition (b).

Figure 2. Verbal fluency paradigm: A.

left: main effect of diagnosis (ASC > controls) within language network on the left hemisphere (middle occipital gyrus, inferior frontal gyrus, inferior parietal lobule); right: plot of effect size (parameter estimates of T contrasts) for the region showing the most statistically significant main effect of diagnosis (left middle occipital gyrus, BA 37); B. left and middle: main effect of sex (males> females) on left caudate and right parahippocampal gyrus; right: plot of effect size (parameter estimates of T contrasts) for the region showing the most statistically significant main effect of sex (left caudate tail). C. left: Cluster of activation in the left Superior Frontal gyrus showing an activity pattern based on the planned contrast: AS males>AS females ≥ typical males>typical females; right: plot of effect size (parameter estimates of the T contrast). Images of activation maps are thresholded at p = 0.005 uncorrected level for visualisation purpose and are overlaid on a standard template with MRICRON software (http://cnl.web.arizona.edu).

Figure 3. Mental rotation task:

A. left and middle: interaction effect on left middle occipital gyrus (BA 19), right inferior parietal lobule (BA 7), left inferior parietal cortex (BA 40); right: plot of effect size (parameter estimates of the interaction T contrast) B, C, D: Results of post hoc analyses showing the regions and the types of effects driving an apparent interaction with the corresponding plots of effect size (parameter estimates of T contrast). E. Cluster of activation in the left Lingual gyrus showing an activity pattern based on the planned contrast: AS males>AS females ≥ typical males>typical females; right: plot of effect size (parameter estimates of the T contrast). Images of activation maps are thresholded at p = 0.005 uncorrected level for visualisation purpose and are overlaid on a standard template with MRICRON software (http://cnl.web.arizona.edu). Legend: L = left; R = right.