Emotional Facial Expressions Evoke Regionally-Specific Activation in the Amygdala in Children, Adolescents and Adults with Autism Spectrum Disorder Relative to Typically-Developing Individuals

Background: Direct eye gaze is essential for the identification of emotional expressions. Averted gaze is a common behavioural phenotype in children with autism spectrum disorder (ASD), which is thought to underlie social communication impairments seen in this population. While averted gaze is increasingly included in early diagnostic assessments for ASD, the neural mechanisms are poorly understood. Previous neuroimaging studies have reported conflicting reports on the neural activation and behavioural responses during viewing of emotional face stimuli in individuals with ASD, with some studies reporting hyperactivation in the amygdala and fusiform gyri, key regions for emotional face processing, while others have reported hypoactivation. Findings may reflect differences in saliency cues directed towards the eye region when viewing emotional face stimuli during the experimental tasks.

Objectives: Using meta-analytic methods, to determine whether individuals with ASD demonstrate differential activation in brain regions involved in processing emotional face stimuli, compared to typically developing (TD) individuals. Further, we aim to examine whether task differences (constrained or fixated gaze) affects regional activation in the brain, particularly in the amygdala.

Methods: A comprehensive literature search of electronic databases was conducted for peer-reviewed studies which included comparisons of functional magnetic resonance imaging (fMRI) data acquired during an emotional face viewing task between individuals with ASD and typically developing controls. BrainMap GingerALE v2.3 was used to conduct an Activation Likelihood Estimate (ALE) meta-analysis of all studies found which met the inclusion criteria. Data were corrected for multiple comparisons using the false discovery rate (FDR, p<0.05).

Results: A total of 22 studies were identified, encompassing data from 418 individuals diagnosed with ASD, and 476 TD participants (ages ranging from 8-44 years), which served as a comparison group. A further measure of constrained or fixated eye gaze to the eye region of the stimuli was identified in 8 of these studies (comprised of 184 individuals with ASD and 219 TD individuals), which were included in sub-analyses examining the likelihood of activation in the brain in response to constrained gaze during the emotional face processing tasks. Analyses of all studies, regardless of gaze constraints, confirmed significant bilateral amygdala activation in both typically developing (right: p=0.004; left: p=0.004) and ASD individuals (right: p=0.003; left: p=0.003). The fusiform gyrus was activated only in TD participants only (p=0.003). The analyses of the constrained eye gaze studies revealed that only ASD participants had increased activation of the left amygdala in compared to TD controls (p=.003).

Conclusions: ASD and TD participants employ different networks when processing emotional face stimuli. Findings from the constrained gaze analyses, suggest individuals with ASD are experiencing increased arousal reflected in an increased likelihood of evoking activation in the left amygdala when viewing the eye region of emotional stimuli. Desire to avoid this negative biological response to emotional stimuli, and eye regions specifically, may underlie atypical gaze patterns and emotional face processing in individuals with ASD.