Attentive brain states in infants with and without later autism

Anna Gui,Greg Pasco,Emily J H Jones,Mark H Johnson,Giorgia Bussu,Mayada Elsabbagh,Tony Charman,Charlotte Tye

doi:10.1038/s41398-021-01315-9

Abstract

Early difficulties in engaging attentive brain states in social settings could affect learning and have cascading effects on social development. We investigated this possibility using multichannel electroencephalography during a face/non-face paradigm in 8-month-old infants with (FH, n = 91) and without (noFH, n = 40) a family history of autism spectrum disorder (ASD). An event-related potential component reflecting attention engagement, the Nc, was compared between FH infants who received a diagnosis of ASD at 3 years of age (FH-ASD; n = 19), FH infants who did not (FH-noASD; n = 72) and noFH infants (who also did not, hereafter noFH-noASD; n = 40). ‘Prototypical’ microstates during social attention were extracted from the noFH-noASD group and examined in relation to later categorical and dimensional outcome. Machine-learning was used to identify the microstate features that best predicted ASD and social adaptive skills at three years. Results suggested that whilst measures of brain state timing were related to categorical ASD outcome, brain state strength was related to dimensional measures of social functioning. Specifically, the FH-ASD group showed shorter Nc latency relative to other groups, and duration of the attentive microstate responses to faces was informative for categorical outcome prediction. Reduced Nc amplitude difference between faces with direct gaze and a non-social control stimulus and strength of the attentive microstate to faces contributed to the prediction of dimensional variation in social skills. Taken together, this provides consistent evidence that atypical attention engagement precedes the emergence of difficulties in socialization and indicates that using the spatio-temporal characteristics of whole-brain activation to define brain states in infancy provides an important new approach to understanding of the neurodevelopmental mechanisms that lead to ASD.

Highlights

Autism spectrum disorder (ASD) affects between 1 and2% of the population in Western countries[1,2,3] but little is known about common mechanisms leading to symptomatology[4]
We looked at whether the early brain measures were associated with (1) autism spectrum disorder (ASD) liability, examining group differences based on ASD family history and clinical outcome defined at three years of age, and (2) dimensional variation in social skills, i.e., later social behaviour as assessed using the VABS Socialization standard scores at 3 years of age
Based on a previous study[15], smaller amplitudes and shorter latencies when attending to static faces with direct gaze than to Noise were expected in the FH-ASD infants, suggesting that neural correlates of reduced social attention engagement to features that are important during social interaction precede the development of difficulties in socialization

Summary

Introduction

Autism spectrum disorder (ASD) affects between 1 and2% of the population in Western countries[1,2,3] but little is known about common mechanisms leading to symptomatology[4]. Perspective longitudinal studies of infants with a family history of ASD ( called high-risk or elevated-likelihood infants) show that behavioural differences in social attention emerge over the first two years of life. Ozonoff and colleagues describe a declining trajectory of looking to faces between 6 months and 3 years in infants with emerging ASD13. In a temporally-resolved eye-tracking analysis, 10-month-old infants with a family history of ASD tend to look less towards faces from 300 ms after the adult initiated direct gaze during naturalistic interactions; relation to later ASD outcome was not tested[18]. It appears that attention to important features of social interaction (like faces with direct gaze) may be altered in the emergence of ASD

Methods

Results

Conclusion