Altered structural brain asymmetry in autism spectrum disorder: large-scale analysis via the ENIGMA Consortium

Abstract

Word count abstract: 249Word count main text: 5,660 Number of figures: 1 Number of tables: 1Supplemental information: yes 5 Abstract Background: Left-right asymmetry is an important organizing feature of the healthy brain.Various studies have reported altered structural brain asymmetry in autism spectrum disorder (ASD). However, findings have been inconsistent, likely due to limited sample sizes and low statistical power. Methods:We investigated 1,774 subjects with ASD and 1,809 controls, from 54 datasets, for differences in the asymmetry of thickness and surface area of 34 cerebral cortical regions. We also examined global hemispheric measures of cortical thickness and area asymmetry, and volumetric asymmetries of subcortical structures. Data were obtained via the ASD Working Group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas.Results: ASD was significantly associated with reduced leftward asymmetry of total hemispheric average cortical thickness, compared to controls. Eight regional thickness asymmetries, distributed over the cortex, also showed significant associations with diagnosis after correction for multiple comparisons, for which asymmetry was again generally lower in ASD versus controls. In addition, the medial orbitofrontal surface area was less rightward asymmetric in ASD than controls, and the putamen volume was more leftward asymmetric in ASD than controls. The largest effect size had Cohen's d = 0.15. Most effects did not depend on age, sex, IQ, or disorder severity.

Atypical brain asymmetry in autism – a candidate for clinically meaningful stratification

“…This lateralized pattern of deficits and strengths in autism has given rise to theories trying to reconcile its complex clinical profile with atypical structural hemispheric specialization (11). In the largest autism cohort to date comprising over 3000 subjects individuals with autism presented with widespread leftward cortical reductions (12). Smaller studies are in line with this showing either a reduction or even reversal of typical leftward asymmetries in language-and motor-related regions (13)(14)(15)(16)(17)(18)(19)(20).…”

Efficient optimization of network metrics in large uncertain graphs

“…We show the 3-clique MPDSs for both G T D and G ASD in Figures 4. brain regions and over-connectivity between closer ones [55,157], and that the hemispheres of ASD-affected brains are more symmetrical than those of typically developed ones [167]. Our consistent findings underline the importance of finding MPDSs in uncertain brain networks that can differentiate healthy and autistic brains.…”

“…Moreover, children with ASD have brains that are overly connected compared to typically developed children [79,186,118]. In addition, the hemispheres in ASD group are more symmetrical than those of the TD group [167]. We highlight this in Figure 3.15: the MPSPs in the left Remark: Despite its usefulness, this case study does have the limitation of being done on a dataset where the edge probabilities, are not available beforehand and are hence modelled by hand.…”

Neurological Symmetry Analysis Applications in Flair MRI

“…The analysis of structural asymmetries is also useful in identification of neuroanatomical disorders, presumed to be caused by abnormal brain development, such as dyslexia, autism and schizophrenia [48] [49] [50]. The goal of such studies is to show that abnormal brain development results in atypical structural asymmetries, which in turn are related to abnormal functional organization.…”