Neural Circuit Disruptions of Eye Gaze Processing in Autism Spectrum Disorder and Schizophrenia: An Activation Likelihood Estimation Meta-Analysis

Abstract

Abstract Impairment in social cognition, particularly eye gaze processing, is a shared feature common to autism spectrum disorder (ASD) and schizophrenia. However, it is unclear if a convergent neural mechanism also underlies gaze dysfunction across these conditions. The present study examined whether this shared eye gaze phenotype is reflected in a profile of convergent neurobiological dysfunction in ASD and schizophrenia. All fMRI experiments were published between January 1990 and December 2021. Experiments were selected comparing brain responses across domains of gaze processing for ASD or schizophrenia vs healthy controls and reporting whole-brain findings. Fifty-nine experiments from 36 articles met inclusion criteria. Activation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates to identify spatial convergence across disorders. Functional coactivation was conducted with regions emerging as significant using meta-analytic connectivity modeling. Functional decoding was also conducted. The 59 experiments from 36 articles included 629 patients (ASD, schizophrenia) and 613 healthy controls (1242 participants). Across disorders, aberrant activation was found in the right inferior frontal gyrus and right fusiform gyrus during gaze processing. Functional decoding mapped the right inferior frontal gyrus to domains related to cognition and perception, and the right fusiform gyrus to visual perception, spatial cognition, and emotion perception. These regions also showed meta-analytic connectivity to frontoparietal circuitry. Aberrant activation in frontotemporal and frontoparietal circuitry emerged as convergent neural markers in ASD and schizophrenia across domains of gaze processing. These findings have implications for advancing transdiagnostic brain biomarkers to inform diagnosis and targeted treatments for ASD and schizophrenia.