Attentive brain states in infants with and without later autism

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

Understanding the nature of face processing in early autism: a prospective study

4AbstractDimensional approaches to psychopathology interrogate the core neurocognitive domains interactingat the individual level to shape diagnostic symptoms. Embedding this approach in prospective longitudinal studies couldtransform our understanding of the mechanisms underlying neurodevelopmental disorders. Such designs require us to move beyond traditional group comparisons and determine which domain-specific alterations apply at the level of the individual, and whether they vary across distinct phenotypic subgroups. As a proof of principle, this studyexamineshow the domain of face processingcontributes to the emergenceof Autism Spectrum Disorder (ASD). We used an event-related potentials (ERPs) task in a cohort of 8-month-oldinfants with (n=148) and without (n=68) an older sibling withASD, andcombined traditional case-control comparisonswith machine-learningtechniques for prediction of social traits and ASD diagnosisat 36 months,and Bayesian hierarchical clustering for stratification into subgroups. Abroad profile of alterations in the time-course of neural processing of faces in infancy was predictive oflaterASD, with a strong convergence in ERP features predicting social traits and diagnosis.We identified two main subgroups in ASD,defined by distinct patternsof neural responsestofaces,which differed on latersensory sensitivity. Taken together, our findings suggest that individual differences between infantscontribute to the diffuse pattern of alterations predictive of ASD in the first year of life. Moving from group-level comparisons to pattern recognition and stratification can help to understand and reduce heterogeneity in clinical cohorts, and improve our understanding of the mechanisms that lead to later neurodevelopmental outcomes

Latent trajectories of adaptive behaviour in infants at high and low familial risk for autism spectrum disorder

Background: Autism Spectrum Disorder (ASD) is characterized by persisting difficulties in everyday functioning. Adaptive behaviour is heterogeneous across individuals with ASD, and it is not clear to what extent early development of adaptive behaviour relates to ASD outcome in toddlerhood. This study aims to identify subgroups of infants based on early development of adaptive skills and investigate their association with later ASD outcome. Methods: Adaptive behaviour was assessed on infants at high (n=166) and low (n=74) familial risk for ASD between 8 and 36 months using the Vineland Adaptive Behavior Scales (VABS-II). The four domains of VABS-II were modelled in parallel using growth mixture modelling to identify distinct classes of infants based on adaptive behaviour. Then, we associated class membership with clinical outcome and ASD symptoms at 36 months, and longitudinal measures of cognitive development. Results: We observed three classes characterised by: decreasing trajectories below age-appropriate norms (8.3%); stable trajectories around age-appropriate norms (73.8%); increasing trajectories reaching average scores by age 2 (17.9%). Infants with declining adaptive behaviour had a higher risk [odd ratio, OR=4.40 (confidence interval, CI: 1.90; 12.98)] for ASD and higher parent-reported symptoms in the social, communication and repetitive behaviour domains at 36 months. Furthermore, there was a discrepancy between adaptive and cognitive functioning as the class with improving adaptive skills showed stable cognitive development around average scores. Conclusions: Findings confirm the heterogeneity of trajectories of adaptive functioning in infancy, with a higher risk for ASD in toddlerhood linked to a plateau in the development of adaptive functioning after the first year of life

The sensory-first account of autism

Recent data suggest that infants with later autism have striking differences in sensory processing. We recap these findings and discuss their implications for theories of autism emergence. Due to the primacy of sensory processing for developing cognitive systems, it is time to embrace a ‘sensory-first’ account of autism

Infant responses to direct gaze and associations to autism : A live eye-tracking study

Being looked at is an important communicative signal, and attenuated responses to such direct gaze have been suggested as an early sign of autism. Using live eye tracking, we examined whether direct gaze elicits different gaze responses in infants at ages 10, 14 and 18 months with and without later autism in real-life interaction. The sample consisted of 169 infants: 35 with elevated likelihood of autism and subsequent diagnosis, 94 without subsequent diagnosis and 40 with typical likelihood of autism. Infants in all groups tended to look more towards the adult’s face shortly after the direct gaze occurred. Neither how much nor how quickly the infants responded to the direct gaze differentiated the without elevated likelihood of autism and subsequent diagnosis and with elevated likelihood of autism and subsequent diagnosis groups. Infants in the typical likelihood group looked more at the face after the direct-gaze event than infants in the two elevated likelihood groups, but this result is tentative. In an exploratory analysis, infants in the elevated likelihood of autism and subsequent diagnosis group looked away quicker from faces with direct gaze than infants in the typical likelihood group, but this measure did not correlate with dimensional autism or differentiate between the two elevated likelihood groups. The current results suggest that attenuated behavioural responses to direct gaze in infancy are neither strong nor specific early markers of autism. Lay abstract When other people look directly towards us, we often respond by looking back at them, and such direct-gaze responses are important for establishing eye contact. Atypical eye contact is common in autism, but how and when this aspect of autism develops is not well understood. Here, we studied whether how much and how quickly infants respond to others’ direct gaze is associated with autism in toddlerhood. We did this by measuring direct-gaze responses in a playful social interaction using live eye tracking. The study included 169 infants, of whom 129 had an elevated likelihood of developing autism due to having a first-degree family member with the condition, and 40 with typical likelihood of autism. In the elevated likelihood group, 35 were diagnosed with autism spectrum disorder at 3 years of age, and 94 were not. The results showed that infants in all three groups tended to increase their looking towards the adult’s face after the adult looked directly at them. However, neither how much nor how quickly the infants responded to direct gaze by looking back at the adult reliably differentiated the infants with or without subsequent autism. While infants in the elevated likelihood of autism and subsequent diagnosis group tended to look away quicker from faces with direct gaze than infants in the typical likelihood group, this measure did not differentiate between the two elevated likelihood groups. We interpret the results as supporting the view that atypical direct-gaze responses are not early markers of autism

The latent structure of emerging cognitive abilities : An infant twin study

It is well known that genetic factors account for up to 70% of variability in cognition from childhood to adulthood. However, less is known about the first year of life. This study investigated the etiological factors influencing individual variability in different domains of emerging cognitive and motor abilities in early infancy, and to what extent genetic and environmental influences are unique or shared across different domains. We compared multivariate twin models built on scores from the five scales of the Mullen Scales of Early Learning (MSEL) in a community sample of monozygotic and dizygotic twins at 5 months of age (n=567). The results indicated a hierarchical etiological structure whereby a general genetic latent factor accounted for 54% of variance underlying the different domains of emerging cognitive and motor abilities (A=0.54, confidence interval CI=[0; 0.82]). We also found additional genetic influences that were specific to early motor and language development. Unlike previous findings on older children, we did not find significant influences of shared environment on the shared factor (C=0, CI=[0, 0.57]), or any specific scale. Furthermore, influences of unique environment, which include measurement error, were moderate and statistically significant (E=0.46, CI=0.18; 0.81]). This study provides strong evidence for a unitary hierarchical structure across different domains of emerging cognition. Evidence that a single common etiological factor, which we term infant g, contributes to a range of different abilities supports the view that in young infants, intrinsic and general neurodevelopmental processes are key drivers of observable behavioural differences in specific domains