Anxiety in Adolescents with ASD Modulates Neural Responses during Simulated Social Interactive Paradigm.

Background: Anxiety affects 40-50% of individuals with autism spectrum disorder (ASD) and potentiates the social difficulties experienced by these individuals. Prior work demonstrates atypical brain activity and patterns of attention to social stimuli in both individuals with ASD and anxiety. However, most research has relied on passive observation of static and dynamic stimuli, and there is little research investigating the relationship of anxiety and brain response in interactive contexts.

Objectives: We developed a novel interactive paradigm in which on-screen faces responded to participants’ looking patterns to assess: (1) brain and gaze response to faces that respond in a reciprocal manner between individuals with ASD and typically developing (TD) controls and (2) the moderating effect of anxiety on brain activity and looking patterns. We hypothesized that anxious symptomology would differentially impact the expression of temporally early social brain function in the context of social vulnerabilities in ASD.

Methods: EEG and eye-tracking were collected from adolescents with ASD (n=45, age=14.68 years, IQ=110.44) and age/IQ matched TD controls (n=43, age=13.68 years, IQ=109.52). Following an arrow cue, participants would look to the eyes or mouth of an on-screen face, which responded by opening its eyes or mouth. In this way, faces would display reciprocal (eye-to-eye; mouth-to-mouth) and nonreciprocal (eye-to-mouth; mouth-to-eye) facial movement. We examined temporally early brain responses at face sensitive ERP components, the P100 and N170, and measured their relationships to social and anxious symptomatology using parent-report on the Child Behavior Checklist (CBCL).

Results: Participants with ASD exhibited significantly greater parent-reported anxiety, as determined by the CBCL’s Anxiety Problems (F(1,58)=12.063, p=0.001), Social Problems (F(1,58)=25.678, p<0.000), and Anxious Depressed T-Scores (F(1,58)=9.954, p=0.003). A significant main effect of condition (eye-to-eye/mouth-to-mouth) for N170 peak amplitude (F(1, 86)=48.512, p<0.000) demonstrated that reciprocal eye-contact elicited the largest effect on N170 response across groups. Individuals with ASD, compared to TD controls, exhibited greater N170 amplitudes to reciprocal eye-contact in the right hemisphere (F(1, 86)=10.783, p<0.001) and this effect correlated with increased anxiety, such that greater levels of anxiety correlated with greater neural response to eye-contact (Anxiety Problems (r(28)=-0.369, p=0.053), Social Problems (r(28)=-0.346, p=0.072), and Anxious Depressed (r(28)=-0.482, p=0.009)). Furthermore, a diagnosis by condition interaction at the P100 amplitude revealed that, across both hemispheres, individuals with ASD exhibited greater P100s to mouth movements while controls exhibited greater P100s to reciprocal eye-contact (F(1, 86)=4.074, p=0.047), suggesting that participants with ASD exhibit atypical patterns of preparatory vigilance during reciprocal social interactions. Eye-tracking data analysis is ongoing.

Conclusions: Our findings show that anxiety modulates neural responses to social interaction simulations in participants with ASD and that these individuals exhibit both hypersensitivity to reciprocal eye-contact and atypical patterns of vigilance when viewing faces. Given the prevalence of anxiety in ASD and the differential neural responses to social interactions observed in these individuals, anxiety could serve not only as a treatment target for alleviating ASD symptomatology but also as a specific subtype of ASD. The particular neural responses seen in our participants with ASD may also act as a potential biomarker for ASD and anxiety.