The Utility of ERP Measures as Putative Intermediate Phenotypes in Infancy

Background: Increasingly, researchers have advocated the use of dimensional intermediate phenotypes, viewed as more closely aligned to the genotype than complex clinical characterization. Specifically, measures of quantitative traits associated with ASD are though to be better candidates for gene mapping relative to diagnostic classification. The assumption here is that diagnosed forms of ASD, which are themselves highly variable, are extremes of what is otherwise typical individual variation. While this research has overwhelmingly focused on stable behavioral characteristics of children and adults, such intermediate phenotypes may not be static in early development, the period when dynamic gene-environment interactions are still unfolding. As such, studying infants at-risk for ASD, where manifestations of risk may be observed particularly in early brain functions, provides the opportunity for developing and validating intermediate phenotypes within the infancy period.

Objectives: The aim of the study was to examine the utility and feasibility of event-related potentials (ERP) within the first year of life as prospective measures of quantitative autism characteristics in toddlers followed longitudinally at 2-years of age. We focused on the neural correlates of gaze processing as the hypothesized developmental precursors to a wide range of emerging social and communicative skills.

Methods: Participants were from the British Autism Study of Infant Siblings (BASIS). One hundred infants (51 high-risk sibs and 50 low-risk controls) were included in the analysis. When aged between 6 and 10 months, ERPs were recorded while the infants viewed dynamic images of females shifting their gaze towards (directed) or away from (averted) the infant. At a 24-month follow-up visit, caregivers completed the Quantitative CHecklist for Autism in Toddlers (Q-CHAT), a measure of autistic traits that is normally distributed in the general population.

Results: Relative to the control group, the high-risk siblings group showed both similarities and differences in the amplitude and latency of components related to gaze processing. Variation in individual infant’s ERP response characteristics was correlated with Q-CHAT scores at 24-months. Dimensional associations between the infant ERP and later emerging behavioral characteristics included ERP components that distinguished the group of siblings at high-risk of ASD from low-risk controls, but also encompass components where the groups did not differ in infancy.

Conclusions: As a group, infants at-risk for ASD show differences in certain neural components related to the processing of eye gaze. Moreover, individual differences in the infant ERP could be mapped onto behavioral characteristics of the same infants at 2-years of age, as measured by parent-report. These findings emphasize the utility and feasibility of developing individually-sensitive and dimensional brain functioning measures as intermediate phenotypes within the infancy period.
* The BASIS Team in alphabetical order: R. Bedford^a, S. Chandler^a, H. Garwood^b,  T. Gliga^b, L. Tucker^b, A. Volein^b

^a Institute of Education, ^b Birkbeck, University of London