Phasic changes in eye’s pupil diameter have been repeatedly observed during cognitive, emotional and behavioral activity in mammals. Although pupil diameter is known to be associated with noradrenergic firing in the pontine Locus Coeruleus (LC), thus far the causal chain coupling spontaneous pupil dynamics to specific cortical brain networks remains unknown. In the present study, we acquired steady-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data combined with eye-tracking pupillometry from fifteen healthy subjects that were trained to maintain a constant attentional load. Regression analysis revealed widespread visual and sensorimotor BOLD-fMRI deactivations correlated with pupil diameter. Furthermore, we found BOLD-fMRI activations correlated with pupil diameter change rate within a set of brain regions known to be implicated in selective attention, salience, error-detection and decision-making. These regions included LC, thalamus, posterior cingulate cortex (PCC), dorsal anterior cingulate and paracingulate cortex (dACC/PaCC), orbitofrontal cortex (OFC), and right anterior insular cortex (rAIC). Granger-causality analysis performed on these regions yielded a complex pattern of interdependence, wherein LC and pupil dynamics were far apart in the network and separated by several cortical stages. Functional connectivity (FC) analysis revealed the ubiquitous presence of the superior frontal gyrus (SFG) in the networks identified by the brain regions correlated to the pupil diameter change rate. No significant correlations were observed between pupil dynamics, regional activation and behavioral performance. Based on the involved brain regions, we speculate that pupil dynamics reflects brain processing implicated in changes between self- and environment-directed awareness.

We integrated multiple behavioural and developmental measures from multiple time-points using machine learning to improve early prediction of individual Autism Spectrum Disorder (ASD) outcome. We examined Mullen Scales of Early Learning, Vineland Adaptive Behavior Scales, and early ASD symptoms between 8 and 36 months in high-risk siblings (HR; n = 161) and low-risk controls (LR; n = 71). Longitudinally, LR and HR-Typical showed higher developmental level and functioning, and fewer ASD symptoms than HR-Atypical and HR-ASD. At 8 months, machine learning classified HR-ASD at chance level, and broader atypical development with 69.2% Area Under the Curve (AUC). At 14 months, ASD and broader atypical development were classified with approximately 71% AUC. Thus, prediction of ASD was only possible with moderate accuracy at 14 months.Electronic supplementary materialThe online version of this article (10.1007/s10803-018-3509-x) contains supplementary material, which is available to authorized users.

To investigate temperament as an early risk marker for autism spectrum disorder (ASD), we examined parent-reported temperament for high-risk (HR, n=170) and low-risk (LR, n=77) siblings at 8, 14, and 24 months. Diagnostic assessment was performed at 36 months. Group-based analyses showed linear risk gradients, with more atypical temperament for HR-ASD, followed by HR-Atypical, HR-Typical, and LR siblings. Temperament differed significantly between outcome groups (0.34≥ η p 2 ≥0.03). Machine learning analyses showed that, at an individual level, HR-ASD siblings could not be identified accurately, whereas HR infants without ASD could.Our results emphasize the discrepancy between group-based and individual-based predictions and suggest that while temperament does not facilitate early identification of ASD individually, it may help identify HR infants who do not develop ASD.

BackgroundAutism spectrum disorder (ASD) is characterised 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.MethodsAdaptive 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.ResultsWe observed three classes characterised by decreasing trajectories below age-appropriate norms (8.3%), stable trajectories around age-appropriate norms (73.8%), and increasing trajectories reaching average scores by age 2 (17.9%). Infants with declining adaptive behaviour had a higher risk (odds 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.ConclusionsFindings 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.Electronic supplementary materialThe online version of this article (10.1186/s13229-019-0264-6) contains supplementary material, which is available to authorized users.

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.