Reduced Language Lateralization in Autism and the Broader Autism Phenotype as Assessed with Robust Individual‐Subjects Analyses

Abstract

One of the few replicated functional brain differences between individuals with autism spectrum disorders (ASD) and neurotypical (NT) controls is reduced language lateralization. However, most prior reports relied on comparisons of group-level activation maps or functional markers that had not been validated at the individual-subject level, and/or used tasks that do not isolate language processing from other cognitive processes, complicating interpretation. Furthermore, few prior studies have examined functional responses in other brain networks, as needed to determine the spatial selectivity of the effect. Using functional magnetic resonance imaging (fMRI), we compared language lateralization between 28 adult ASD participants and carefully pairwise-matched controls, with the language regions defined individually using a well-validated language "localizer" task. Across two language comprehension paradigms, ASD participants showed less lateralized responses due to stronger right hemisphere activity. Furthermore, this effect did not stem from a ubiquitous reduction in lateralization of function across the brain: ASD participants did not differ from controls in the lateralization of two other large-scale networks-the Theory of Mind network and the Multiple Demand network. Finally, in an exploratory study, we tested whether reduced language lateralization may also be present in NT individuals with high autismlike traits. Indeed, autistic trait load in a large set of NT participants (n = 189) was associated with less lateralized language responses. These results suggest that reduced language lateralization is robustly associated with autism and, to some extent, with autism-like traits in the general population, and this lateralization reduction appears to be restricted to the language system.

Differences in subcortico-cortical interactions identified from connectome and microcircuit models in autism

“…Notably, connectome manifold distortions in autism showed more marked effects in the right hemisphere for idiotypic areas, and more marked effects in the left hemisphere in heteromodal areas. Several prior studies suggested asymmetric findings in autism at the level of cortical morphology as well as functional organization [87][88][89][90][91][92][93] . Our results may contribute to these prior findings by suggesting a differential susceptibility for structural reorganization in autism for left and right hemispheres for unimodal versus heteromodal regions, respectively.…”

Evidence for normal extra-axial cerebrospinal fluid volume in autistic males from middle childhood to adulthood

“…Remarkably, the latter finding was even observed by Leo Kanner in 1943 when he noted that five of his 11 cases, “had relatively large heads” (p. 248). Additional findings include abnormal lateralization of the brain with a lack of left lateralization in the structure and function of regions involved with language ( Jouravlev et al, 2020 ; Lindell and Hudry, 2013 ; Nielsen et al, 2014 ), and hypoconnectivity within the default mode network ( Di Martino et al, 2014 ). Furthermore, it has been found that the amygdala initially enlarges but fails to undergo the age-related increase found in typically developing (TD) children, with a larger amygdala predicting more severe symptomatology ( Schumann et al, 2004 ).…”

Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium

“…ASD was most notably associated with widespread alterations of cortical thickness asymmetry, involving the medial frontal, posterior cingulate and inferior temporal cortex. These regions overlapped with those showing altered functional lateralization for language and social cognitive tasks in ASD 11, 12 .…”

“…4 ), which included working memory and other executive function-related annotations in common across the networks, but also language-related, reading-related, and sensorimotor annotations. Language delay is a common feature of ASD 5, 6 , and the disorder is also associated with reduced left-hemisphere language dominance 11 . Numerous reports based on behavioral, neurophysiological, neuroimaging or histopathological data have also reported atypical motor system development in ASD 65 .…”

“…For example, roughly 90% of the adult population has left-hemispheric dominance for word generation tasks, which particularly elicit activation of inferior frontal and temporal cortex 8, 9 , while theory-of-mind tasks typically elicit rightward asymmetrical activation around the temporo-parietal junction 10 . Moreover, increased autism symptom severity has been associated with reduced laterality of activation during language and social cognition tasks 11, 12 . At the structural level, too, studies have reported altered asymmetries of regions of the cortex important for language and/or social cognition, including temporal regions and the fusiform gyrus 13–15 .…”