Developing ERP biomarkers of social cognition: The journey from task design to treatment outcome measures

• In Event: Poster Session 13
  In Poster Session: PS 13 Topic - Social Cognition

Abstract

Background: Successful development of effective treatments targeting social cognition in children with autism spectrum disorder (ASD) depends in part on the availability of objective outcome measures. Multidimensional approaches combining traditional behavioral assessments with psychophysiological measures yield more detailed information about treatment effects than standardized tests alone.

Objective: The purpose of this series of studies was to develop and validate the nonverbal measure of social interest (incidental face memory) as a brain-based marker of social cognition suitable for use as a treatment outcome measure in children with autism.

Methods: Brain responses associated with spontaneous face perception and memory were evaluated using visual event-related potentials (ERPs) in a pre-post design in four groups of children with ASD (age 7-16 years, total n=90), including three treatment cohorts (peer-implemented social skills program). Additional data from typical controls (n=37) and children with Prader-Willi syndrome (PWS) who demonstrate social deficits overlapping with ASD (age 7-16 years, n=28) were used to further validate the proposed ERPs as a measure of social interest. All subjects viewed a series of 51 color photographs depicting unfamiliar smiling young adults or house facades. Unbeknown to the participants, one image of each type was randomly selected and repeated 50 times throughout the test session while the rest were shown only once. The children were instructed to press a button each time they saw an emoji (task-irrelevant attention probe). Social interest was quantified as the increased parietal ERP amplitude (300-500 ms) to repeated faces vs. those seen once. Behavioral measures of social cognition included NEPSY Memory for Faces test, caregiver reports (Social Communication Questionnaire, Social Responsiveness Scale), and coded observations of playground behaviors with peers.

Results: All participants demonstrated perceptual discrimination of faces vs. houses as reflected in the larger N170 responses to the former. Increased parietal ERP responses to the repeated faces indicative of incidental memory were present in typical controls and in children with PWS with more typical social functioning, but not in children with ASD prior to treatment or in children with PWS with greater ASD-related symptomatology. Following the social skills intervention, children with ASD in the treatment group demonstrated increased ERP amplitudes to repeated faces compared to the baseline assessment, while the waitlist control group showed no change. This pattern of results was replicated in each of the treatment cohorts. The ERP index of incidental face memory but not the N170 correlated with behavioral measures of social skills and behavior.

Conclusion: Our findings demonstrate that measures of higher order social cognitive processes (i.e., face memory) rather than face perception responses (i.e., N170) may be particularly informative about social skills in children with typical and atypical development. The ERP marker of incidental face memory fits the biomarker definition as an objective and reproducible measure of neural activity differentiating typical and atypical social information processing. Its sensitivity to treatment effects, good test-retest stability, correlations with behavioral endpoints, and reduced susceptibility to the placebo effects due to the passive nature of the task further support its value as an outcome measure.

Authors

• Alexandra Key, Vanderbilt University Medical Center
  Presenting Author

• Blythe Corbett, Vanderbilt University Medical Center
  Non-Presenting Author

• Dorita Jones, Vanderbilt University Medical Center
  Non-Presenting Author