Malleability of Neural Activity in Response to Treatment: Examining fMRI Biomarkers of Social Behavior and Anxiety Among Autistic Adolescents across the PEERS® Intervention

Background: Autistic adolescents frequently experience clinical levels of anxiety that exacerbate social difficulties (van Steensel, Bögels, & Perrin, 2011). Improvements in both social behavior (Gates, Kang, & Lerner, 2017) and anxiety (e.g., Corbett, Blain, Ioannou, & Balser, 2017; Lei, Sukhodolsky, Abdullahi, Braconnier, & Ventola, 2017; McVey et al., 2016; Schohl et al., 2014) have been previously documented after receiving a social skills intervention. Recent literature highlights the importance of using neurobiological markers to assess for intervention response (Stavropoulos, 2017). No study to date, however, has examined changes in neural activity via fMRI and links with social behavior and anxiety across a well-validated social behavioral intervention for autistic adolescents.

Objectives: The present study will begin to address this gap by evaluating changes in neural activity (fMRI), 1) social behavior, 2) amygdala activity relative to anxiety subsequent to an evidence-based social skills intervention, the Program for the Education and Enrichment of Relational Skills (PEERS^®).

Methods: Sixty-one adolescents (48 autistic, 13 typically developing) ages 11-16 were recruited for the present study. In this randomized controlled trial, autistic adolescents were randomly assigned to an experimental or a waitlist control group. All adolescents underwent fMRI at two timepoints – before and after the PEERS^® intervention for the experimental group. Self- and caregiver-report measures of social behavior (Social Skills Improvement System, SSIS; Social Responsiveness Scale, SRS; and Test of Adolescent Social Skills Knowledge, TASSK) and anxiety were collected before and after intervention. Measures of anxiety (Child Behavior Checklist, CBCL and NIMH Diagnostic Interview Schedule for Children, Social Phobia, DISC) will be used to further classify the autistic groups as having or not having clinically-significant anxiety and social anxiety.

Results: Although the groups differed in their Ethnic identity (Table 1), neural differences are not expected based on this variable. Nonetheless, analyses will be conducted to examine potential effects based on Ethnicity due to the group difference. No other demographic differences were found (see Table 1). Preliminary results indicated that the intervention functioned as expected (paired sample t test of TASSK for the experimental group: t(21) = -10.85, p < .001; waitlist and typical group showed no change over time p > .05). Data analyses to be conducted include: two mixed model ANCOVAs to examine changes in amygdala activity over time and the moderating role of anxiety (Group*Time*Anxiety; Group*Time*Social Anxiety).

Conclusions: It is hypothesized that autistic adolescents in the experimental group with high levels of anxiety and social anxiety prior to the intervention will show decreased amygdala activity in response to the intervention, coinciding with improvements in social behavior and secondary effects on anxiety. Those with low levels of anxiety to start, on the other hand, will show increased amygdala activity, coinciding with improvements in social behavior (and no change in anxiety). The waitlist control and typically developing groups are expected to show no significant changes in neural amygdala activity over time. This study will be the first of its kind to examine effects of PEERS^® on brain function via fMRI among autistic adolescents.