Neural circuit disruptions of eye gaze processing in autism spectrum disorder and schizophrenia: An activation likelihood estimation meta-analysis

Abstract

Background: 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 in 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.

Methods: Activation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates across the whole brain to identify spatial convergence. Functional coactivation with regions emerging as significant was assessed using meta-analytic connectivity modeling. Functional decoding was also conducted.

Results: Fifty-six experiments (n = 30 with schizophrenia and n = 26 with ASD) from 36 articles met inclusion criteria, which comprised 354 participants with ASD, 275 with schizophrenia and 613 healthy controls (1242 participants in total). In ASD, aberrant activation was found in the left amygdala relative to unaffected controls during gaze processing. In schizophrenia, aberrant activation was found in the right inferior frontal gyrus and supplementary motor area. Across ASD and schizophrenia, aberrant activation was found in the right inferior frontal gyrus and right fusiform gyrus during gaze processing. Functional decoding mapped the left amygdala to domains related to emotion processing and cognition, the right inferior frontal gyrus 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 and frontotemporal circuitry.

Conclusion: Alterations in frontoparietal and frontotemporal circuitry emerged as neural markers of gaze impairments in ASD and schizophrenia. These findings have implications for advancing transdiagnostic biomarkers to inform targeted treatments for ASD and schizophrenia.

Keywords: Amygdala; Autism spectrum disorder; Cognitive control; Eye gaze; Lateral prefrontal cortex; Schizophrenia.