Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Abstract

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen’s d = −0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer’s Disease

“…The implication that thickness asymmetry is important for healthy brain function agrees with a recent metaanalysis confirming that subtly reduced asymmetry is a feature of neurodevelopmental disorders 16 . However, our results also indicate that individual differences in regional asymmetry-change had little predictive value upon longitudinal cognitive scores across cognitively healthy adult life (neither memory nor fluid reasoning ability).…”

“…Despite being a global organizing property of the cortex 7,8 with plausible relevance for hemispheric specialization 9 , cortical thickness asymmetry has been mostly overlooked in studies examining cortical aging. Yet an asymmetrically organized cortex gives rise to efficient functional network organization [10][11][12][13] and thus may support cognition [14][15][16] . Hence, as the cortex thins over time 17 , cortical thickness asymmetry may also change, which may be informative for declining brain function.…”

Analysis of structural brain asymmetries in Attention-Deficit/Hyperactivity Disorder in 39 datasets

“…In a recent ENIGMA consortium study of autism spectrum disorder (ASD), medial orbitofrontal cortex surface area asymmetry was altered in the same direction, and to a similar extent, as in the present study (31). ADHD and ASD often co-occur (42) and are known to share genetic influences (43,44), such that the two diagnostic labels are likely to capture a partly overlapping spectrum of related disorders (45,46).…”

“…Douglas et al (14) performed the largest study of brain anatomical asymmetry in ADHD to date, including 192 cases with ADHD with a history of pharmacotherapy, 149 medication-naïve cases with ADHD, and 508 typically developing controls (ages 6-21 years), from eight separate datasets. They calculated per-subject Asymmetry Indexes (AI) for various regional grey matter volumes, AI=(Left-Right)/((Left+Right)/2) (a widely used approach in studies of brain asymmetry (28)(29)(30)(31)), but did not find any significant alterations of AIs in ADHD (14). However, in a subset of their dataset (56 cases and 48 controls), Douglas et al (14) analyzed diffusion tensor imaging (DTI) data, including fractional anisotropy and mean diffusivity measures, and reported alterations in the asymmetry of six white matter tracts, again not specifically driven by alterations in the right hemisphere.…”

Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number, independent of microglial inflammatory signaling

“…Within the neural networks supporting social behavior, the anterior cingulate cortex (ACC) is a subdivision of the pre-frontal cortex (PFC) that represents a critical node, across species (Bicks et al, 2015;Guo et al, 2020;Apps et al, 2016). Importantly, both the structure and functional connectivity of the ACC are altered in individuals with ASD (Postema et al, 2019;Guo et al, 2020;Laidi et al, 2019;Zhou et al, 2016). Somatostatin (SST) interneurons are important for maintaining and regulating excitatory/inhibitory balance and this cell population within the ACC has recently been implicated in the modulation of a variety of social behaviors including social interaction (Perez et al, 2019;Sun et al, 2020;van Heukelum et al, 2019), social affective discrimination (Scheggia et al, 2020), socio-sexual behavior (Nakajima et al, 2014), and social fear learning (Xu et al, 2019) in animal models.…”