Sex Differences in Amygdala Resting State Connectivity in Young Children with Autism Spectrum Disorder

Background: Sex differences in neuropathology and neural phenotypes of autism spectrum disorder (ASD) are currently poorly understood. While prior research in pre-school aged males with ASD implicated atypical amygdala resting-state functional magnetic imaging (rfMRI) connectivity, these differences in functional connectivity have yet to be examined in a female cohort of young children.

Objectives: The current research examines sex-differences in resting state amygdala functional connectivity in preschool aged children with ASD.

Methods: The sample included 105 children with ASD (76 male, 29 female) and 51 age-matched typically developing (TD) controls (30 male, 21 female) (mean age 3.76 years). Diagnostic assessments for ASD were carried out by expert clinicians using the ADOS and ADI-R. Structural and resting state EPI BOLD images were acquired during natural nocturnal sleep. Resting state images were preprocessed using tools from AFNI, FSL, and ANTS in the Configurable Pipeline for the Analysis of Connectomes (C-PAC) using identical preprocessing parameters as reported in Shen et al., (2016). In brief, EPI images were time-shifted, motion corrected, and band-pass filtered (.008 < f < .08 Hz). Volumes with frame-wise displacement greater than 0.25mm were scrubbed. EPIs were then co-registered to the participant’s structural T1-weighted image and then to MNI space, and smoothed at 6 mm FWHM. Seed-based connectivity analyses compared sex, diagnosis, and sex by diagnosis group differences in functional connectivity between amygdala and the rest of the brain. Cluster based correction for multiple comparisons was carried out using Gaussian Random Field theory using FSL (Z >2.3, p_GRF <.05).

Results: Preliminary results revealed atypical amygdala functional connectivity in both boys and girls with ASD. Investigation of sex by diagnosis interactions revealed multiple clusters in frontal, temporal and cingulate cortices. In general, sex differences that were observed in typically developing males and females were attenuated in children with ASD. These results suggest that the neural phenotype of ASD in young children is differentially presented in males and females compared to their respective typically developing peers.

Conclusions: These preliminary data suggest that females and males with ASD have at least partially dissimilar patterns of functional connectivity with the amygdala.