Reduced language lateralization in autism and the broader autism phenotype as assessed with robust individual-subjects analyses

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 functional networks, as needed to determine the selectivity of the effect. Using fMRI, we compared language lateralization between 28 ASD participants and carefully pairwise-matched controls, with the language regions defined individually with a well-validated language localizer. ASD participants showed less lateralized responses due to stronger right hemisphere activations. Further, this effect did not stem from a ubiquitous reduction in lateralization 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 autistic trait load. Indeed, autistic trait load in a large set of NT participants (n=189) was associated with less lateralized language activations. These results suggest that reduced language lateralization is a robust and spatially selective neural marker of autism, present in individuals with ASD, but also in NT individuals with higher genetic liability for ASD, in line with a continuum model of underlying genetic risk.