Early developmental pathways to childhood symptoms of attention-deficit hyperactivity disorder, anxiety and autism spectrum disorder

Background Children with autism spectrum disorder (ASD) often have co-occurring symptoms of attention-deficit/hyperactivity disorder (ADHD) and/or anxiety. It is unclear whether these disorders arise from shared or distinct developmental pathways. We explored this question by testing the specificity of early-life (infant and toddler) predictors of mid-childhood ADHD and anxiety symptoms compared to ASD symptoms. Methods Infants (n = 104) at high and low familial risk for ASD took part in research assessments at 7, 14, 24 and 38 months, and 7 years of age. Symptoms of ASD, ADHD and anxiety were measured by parent report at age 7. Activity levels and inhibitory control, also measured by parent report, in infancy and toddlerhood were used as early-life predictors of ADHD symptoms. Fearfulness and shyness measured in infancy and toddlerhood were used as early-life predictors of anxiety symptoms. Correlations and path analysis models tested associations between early-life predictors and mid-childhood ADHD and anxiety symptoms compared to mid-childhood ASD symptoms, and the influence of controlling for ASD symptoms on those associations. Results Increased activity levels and poor inhibitory control were correlated with ADHD symptoms and not ASD or anxiety; these associations were unchanged in path models controlling for risk-group and ASD symptoms. Increased fearfulness and shyness were correlated with anxiety symptoms, but also ASD symptoms. When controlling for risk-group in path analysis, the association between shyness and anxiety became nonsignificant, and when further controlling for ASD symptoms the association between fearfulness and anxiety became marginal. Conclusions The specificity of early-life predictors to ADHD symptoms suggests early developmental pathways to ADHD might be distinct from ASD. The overlap in early-life predictors of anxiety and ASD suggests that these disorders are difficult to differentiate early in life, which could reflect the presence of common developmental pathways or convergence in early behavioural manifestations of these disorders

Modulation of EEG theta by naturalistic social content is not altered in infants with family history of autism

Theta oscillations (spectral power and connectivity) are sensitive to the social content of an experience in typically developing infants, providing a possible marker of early social brain development. Autism is a neurodevelopmental condition affecting early social behaviour, but links to underlying social brain function remain unclear. We explored whether modulations of theta spectral power and connectivity by naturalistic social content in infancy are related to family history for autism. Fourteen-month-old infants with (family history; FH; N = 75) and without (no family history; NFH; N = 26) a first-degree relative with autism watched social and non-social videos during EEG recording. We calculated theta (4–5 Hz) spectral power and connectivity modulations (social–non-social) and associated them with outcomes at 36 months. We replicated previous findings of increased theta power and connectivity during social compared to non-social videos. Theta modulations with social content were similar between groups, for both power and connectivity. Together, these findings suggest that neural responses to naturalistic social stimuli may not be strongly altered in 14-month-old infants with family history of autism

Probing the strength of infants' preference for helpers over hinderers: two replication attempts of Hamlin and Wynn (2011)

Several studies indicate that infants prefer individuals who act prosocially over those who act antisocially toward unrelated third parties. In the present study, we focused on a paradigm published by Kiley Hamlin and Karen Wynn in 2011. In this study, infants were habituated to a live puppet show in which a protagonist tried to open a box to retrieve a toy placed inside. The protagonist was either helped by a second puppet (the “Helper”), or hindered by a third puppet (the “Hinderer”). At test, infants were presented with the Helper and the Hinderer, and encouraged to reach for one of them. In the original study, 75% of 9-month-olds selected the Helper, arguably demonstrating a preference for prosocial over antisocial individuals. We conducted two studies with the aim of replicating this result. Each attempt was performed by a different group of experimenters. Study 1 followed the methods of the published study as faithfully as possible. Study 2 introduced slight modifications to the stimuli and the procedure following the guidelines generously provided by Kiley Hamlin and her collaborators. Yet, in our replication attempts, 9-month-olds’ preference for helpers over hinderers did not differ significantly from chance (62.5% and 50%, respectively, in Studies 1 and 2). Two types of factors could explain why our results differed from those of Hamlin and Wynn: minor methodological dissimilarities (in procedure, materials, or the population tested), or the effect size being smaller than originally assumed. We conclude that fine methodological details that are crucial to infants’ success in this task need to be identified to ensure the replicability of the original result

Autism diagnosis differentiates neurophysiological responses to faces in adults with tuberous sclerosis complex

- Background: Autism spectrum disorder (ASD) is a common and highly heritable neurodevelopmental disorder that is likely to be the outcome of complex aetiological mechanisms. One strategy to provide insight is to study ASD within tuberous sclerosis complex (TSC), a rare disorder with a high incidence of ASD, but for which the genetic cause is determined. Individuals with ASD consistently demonstrate face processing impairments, but these have not been examined in adults with TSC using event-related potentials (ERPs) that are able to capture distinct temporal stages of processing. - Methods: For adults with TSC (n = 14), 6 of which had a diagnosis of ASD, and control adults (n = 13) passively viewed upright and inverted human faces with direct or averted gaze, with concurrent EEG recording. Amplitude and latency of the P1 and N170 ERPs were measured. - Results: Individuals with TSC + ASD exhibited longer N170 latencies to faces compared to typical adults. Typical adults and adults with TSC-only exhibited longer N170 latency to inverted versus upright faces, whereas individuals with TSC + ASD did not show latency differences according to face orientation. In addition, individuals with TSC + ASD showed increased N170 latency to averted compared to direct gaze, which was not demonstrated in typical adults. A reduced lateralization was shown for the TSC + ASD groups on P1 and N170 amplitude. - Conclusions: The findings suggest that individuals with TSC + ASD may have similar electrophysiological abnormalities to idiopathic ASD and are suggestive of developmental delay. Identifying brain-based markers of ASD that are similar in TSC and idiopathic cases is likely to help elucidate the risk pathways to ASD

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

Background: Autism 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. 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%), 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. 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

Prediction of Autism at 3 Years from Behavioural and Developmental Measures in High-Risk Infants: A Longitudinal Cross-Domain Classifier Analysis.

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

Basic-level category discriminations by 7- and 9-month-olds in an object examination task

This study examines 7- and 9-month-olds’ ability to categorize cats as separate from dogs, and dogs as separate from cats in an object examination task. In Experiment 1, 7- and 9-month-olds (N=30) familiarized with toy cat replicas were found to form a category of cat that included novel cats but excluded a dog and an eagle. In Experiment 2, 7- and 9-month-olds (N=30) familiarized with toy dog replicas were found to form a category of dog that included a novel dogs and a novel cat but excluded an eagle. These results mirror those of 3- to 4-month-olds tested with visual preference methods and stand in contrast to previously reported object examination results. Analyses of the distribution of features in the exemplars used to familiarize infants suggest that, like the 3- to 4-month-olds, the 7- and 9-month-olds in these studies form categories within the task, and on the basis of feature distributions

Cortical development and saccade planning: the ontogeny of the spike potential

The spike potential is a sharply timed positivity which precedes eye movements in adults, and is thought to indicate cortical planning of saccades. While the spike potential is observed under most conditions in adults, it has not been reported in young infants. In the present study we shed light on the ontogeny of the spike potential by demonstrating for the first time its existence in a group of older infants (12 months). This result is consistent with a relatively delayed onset of cortical control over saccades during development

Near infrared spectroscopy reveals neural activation during face perception in infants and adults

We used near infrared spectroscopy to measure changes in cerebral oxygenation in both human infants and adults as they viewed images of faces or control "visual noise" stimuli. At an occipital site, adults showed a significant increase in oxyhaemoglobin and a contrasting pattern of results was observed in infants. While the same general difference between the processing of the two stimuli was observed, a larger decrease in oxyhemoglobin concentration in response to faces than to visual noise was found in infants. These results demonstrate that near infrared spectroscopy can detect differences in stimulus processing induced by a complex visual stimulus in both infants and adults