Increased hippocampal shape asymmetry and volumetric ventricular asymmetry in autism spectrum disorder

Abstract

Autism spectrum disorder (ASD) is a prevalent and fast-growing pervasive neurodevelopmental disorder worldwide. Despite the increasing prevalence of ASD and the breadth of research conducted on the disorder, a conclusive etiology has yet to be established and controversy still exists surrounding the anatomical abnormalities in ASD. In particular, structural asymmetries have seldom been investigated in ASD, especially in subcortical regions. Additionally, the majority of studies for identifying structural biomarkers associated with ASD have focused on small sample sizes. Therefore, the present study utilizes a large-scale, multi-site database to investigate asymmetries in the amygdala, hippocampus, and lateral ventricles, given the potential involvement of these regions in ASD. Contrary to prior work, we are not only computing volumetric asymmetries, but also shape asymmetries, using a new measure of asymmetry based on spectral shape descriptors. This measure represents the magnitude of the asymmetry and therefore captures both directional and undirectional asymmetry. The asymmetry analysis is conducted on 437 individuals with ASD and 511 healthy controls using T1-weighted MRI scans from the Autism Brain Imaging Data Exchange (ABIDE) database. Results reveal significant asymmetries in the hippocampus and the ventricles, but not in the amygdala, in individuals with ASD. We observe a significant increase in shape asymmetry in the hippocampus, as well as increased volumetric asymmetry in the lateral ventricles in individuals with ASD. Asymmetries in these regions have not previously been reported, likely due to the different characterization of neuroanatomical asymmetry and smaller sample sizes used in previous studies. Given that these results were demonstrated in a large cohort, such asymmetries may be worthy of consideration in the development of neurodiagnostic classification tools for ASD.

Keywords: Amygdala; Asymmetry; Autism; Hippocampus; MRI; Ventricles.

Fig. 1

Graphical overview of steps for computing the brain asymmetry with the BrainPrint. MRI scans are segmented with FreeSurfer and meshes for the lateralized structure of interest, here hippocampus, are created. The computation of the shapeDNA results in the spectral shape descriptor in BrainPrint. The Mahalanobis distance between shape vectors yields measure of shape asymmetry.

Fig. 2

Illustration of brain structures investigated in the present study. Coloring is according to significance of shape asymmetry with respect to diagnosis, where red indicates significant and blue indicates no significant group-related differences in asymmetry. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Mean amygdala asymmetry values by diagnosis and sex.

Fig. 4

Mean hippocampal asymmetry values by diagnosis and sex.

Fig. 5

Mean ventricular asymmetry values by diagnosis and sex.

Fig. 6

Visualization of the hippocampus mesh and the first three non-constant eigenfunctions of the Laplace-Beltrami operator calculated on the surface. Increasing positive values of the eigenfunctions are shown in the color gradient from red to yellow and decreasing negative values are shown from dark blue to light blue. Level sets are shown in green. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)