Sex Differences in Biological Motion Perception Among Youth with ASD: An fMRI Investigation

Saturday, May 16, 2015: 11:30 AM-1:30 PM
Imperial Ballroom (Grand America Hotel)
A. Jack1, C. M. Keifer1, D. Gulliford2, C. Torgerson3, E. H. Aylward2, S. Y. Bookheimer4, M. Dapretto5, N. Gaab6, J. Van Horn3 and K. Pelphrey1, (1)Child Study Center, Yale University, New Haven, CT, (2)Seattle Children's Research Institute, Seattle, WA, (3)University of Southern California, Los Angeles, CA, (4)Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, (5)Ahmanson-Lovelace Brain Mapping Center, UCLA, Los Angeles, CA, (6)Dept. of Medicine, Division of Developmental Medicine, Harvard University, Boston, MA
Background: Males (♂) are more likely to carry a diagnosis of autism spectrum disorder (ASD) than females (♀), with the sex ratio estimated at ~4:1. This skewed ratio is not well understood, and research on sex-related differences in functional brain activity among individuals with ASD is particularly sparse.

Objectives: Investigation of the skewed sex ratio in ASD has previously been limited by small sample sizes of ♀ASD. To address this knowledge gap, we are oversampling ♀ASD by recruiting from multiple sites nationwide over a five year period. Here, we report on preliminary fMRI-assessed sex differences in brain response to biological motion, among youth with ASD as well as unaffected sibling (US) and typically developing comparison groups.

Methods: Participants, aged 8-18 years (M = 12.8 yr), are a subsample (N = 93) collected during this ongoing project. Exclusion criteria included root mean squared movement ≥ 4mm. Group membership was as follows: ♀ASD n = 19; ♂ASD n = 21; ♀US n = 15; ♂US n = 6; ♀TD n = 15; ♂TD n = 20. Participants viewed 12 interleaved blocks of point-light displays of biological motion, 6 coherent (BIO) and 6 scrambled (SCRAM). FMRI data were analyzed using tools from FSL implemented via LONI Pipeline. At the single-subject level, the contrast of interest was BIO > SCRAM with standard motion parameters and motion outliers included as covariates. Higher-level analysis was carried out at the whole-brain level with automatic outlier deweighting; images were thresholded at Z > 2.3 and a cluster-corrected p = 0.05. Variances were calculated separately for ASD, US, and TD groups, and age was entered as a covariate. The BIO > SCRAM mean was calculated for each group; additionally, BIO > SCRAM activity for ♀ASD  was compared to ♂ASD, ♀US, and ♀TD. Sex differences within the comparison groups were also tested.

Results: Clear functional differences exist between ♂ASD  and ♀ASD responses to biological motion stimuli, with ♀ASD demonstrating greater activity in temporo-occipital, prefrontal, striatal, amygdalar, and neocerebellar regions than ♂ASD. ♀ASD response to biological motion was also greater than ♀TD in amygdala, medial prefrontal cortex, precuneus, and paracingulate. Similar to ♀ASD, ♂TD had greater activity than ♀TD in ventromedial prefrontal cortex and precuneus. No significant differences were found between ♀ASD and ♀US. See figure for further detail.

Conclusions: Previously-drawn conclusions about atypicalities in social brain response among individuals with ASD may be male-specific. In particular, ♀ASD may not show the hypoactivation in temporal regions (e.g., posterior superior temporal sulcus and temporo-parietal junction) that has been repeatedly documented in predominantly ♂ASD  samples. Further, the differences in ♂ASD  and ♀ASD response are not completely attributable to an overlaying of typical sexually dimorphic brain responses onto this population; ♀ASD differed from ♀TD in ways that were highly similar to the ways in which ♂TD differed from ♀TD. These results are highly novel, and even in their preliminary form represent one of the largest samples in which ASD-related sex differences in functional brain response have been tested.