In addition to core symptoms, i.e., social interaction and communication difficulties and restricted and repetitive behaviors, autism is also characterized by aspects of superior perception 1. One ...well-replicated finding is that of superior performance in visual search tasks, in which participants have to indicate the presence of an odd-one-out element among a number of foils 2–5. Whether these aspects of superior perception contribute to the emergence of core autism symptoms remains debated 4, 6. Perceptual and social interaction atypicalities could reflect co-expressed but biologically independent pathologies, as suggested by a “fractionable” phenotype model of autism 7. A developmental test of this hypothesis is now made possible by longitudinal cohorts of infants at high risk, such as of younger siblings of children with autism spectrum disorder (ASD). Around 20% of younger siblings are diagnosed with autism themselves 8, and up to another 30% manifest elevated levels of autism symptoms 9. We used eye tracking to measure spontaneous orienting to letter targets (O, S, V, and +) presented among distractors (the letter X; Figure 1). At 9 and 15 months, emerging autism symptoms were assessed using the Autism Observation Scale for Infants (AOSI; 10), and at 2 years of age, they were assessed using the Autism Diagnostic Observation Schedule (ADOS; 11). Enhanced visual search performance at 9 months predicted a higher level of autism symptoms at 15 months and at 2 years. Infant perceptual atypicalities are thus intrinsically linked to the emerging autism phenotype.
•We measured visual search abilities in infants at familial risk for autism•Enhanced visual search at 9 months predicted a higher level of autism symptoms at 2 years•Atypical perception is intrinsically linked to the emerging autism phenotype
It remained unknown whether superior perception, a common feature of the autism phenotype, contributes to the emergence of core social interaction and communication symptoms. Gliga et al. show that superior performance in a visual search task in 9-month-old infants predicts a higher level of autism symptoms at 15 months and 2 years.
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.
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.
ObjectiveThis is a prospective population screening study for autism in toddlers aged 18–30 months old using the Quantitative Checklist for Autism in Toddlers (Q-CHAT), with follow-up at age ...4.DesignObservational study.SettingLuton, Bedfordshire and Cambridgeshire in the UK.Participants13 070 toddlers registered on the Child Health Surveillance Database between March 2008 and April 2009, with follow-up at age 4; 3770 (29%) were screened for autism at 18–30 months using the Q-CHAT and the Childhood Autism Spectrum Test (CAST) at follow-up at age 4.InterventionsA stratified sample across the Q-CHAT score distribution was invited for diagnostic assessment (phase 1). The 4-year follow-up included the CAST and the Checklist for Referral (CFR). All with CAST ≥15, phase 1 diagnostic assessment or with developmental concerns on the CFR were invited for diagnostic assessment (phase 2). Standardised diagnostic assessment at both time-points was conducted to establish the test accuracy of the Q-CHAT.Main outcome measuresConsensus diagnostic outcome at phase 1 and phase 2.ResultsAt phase 1, 3770 Q-CHATs were returned (29% response) and 121 undertook diagnostic assessment, of whom 11 met the criteria for autism. All 11 screened positive on the Q-CHAT. The positive predictive value (PPV) at a cut-point of 39 was 17% (95% CI 8% to 31%). At phase 2, 2005 of 3472 CASTs and CFRs were returned (58% response). 159 underwent diagnostic assessment, including 82 assessed in phase 1. All children meeting the criteria for autism identified via the Q-CHAT at phase 1 also met the criteria at phase 2. The PPV was 28% (95% CI 15% to 46%) after phase 1 and phase 2.ConclusionsThe Q-CHAT can be used at 18–30 months to identify autism and enable accelerated referral for diagnostic assessment. The low PPV suggests that for every true positive there would, however, be ~4–5 false positives. At follow-up, new cases were identified, illustrating the need for continued surveillance and rescreening at multiple time-points using developmentally sensitive instruments. Not all children who later receive a diagnosis of autism are detectable during the toddler period.
Autism is proposed to be characterised by an atypical balance of cortical excitation and inhibition (E/I). However, most studies have examined E/I alterations in older autistic individuals, meaning ...that findings could in part reflect homeostatic compensation. To assess the directionality of effects, it is necessary to examine alterations in E/I balance early in the lifespan before symptom emergence. Recent explanatory frameworks have argued that it is also necessary to consider how early risk features interact with later developing modifier factors to predict autism outcomes.
We indexed E/I balance in early infancy by extracting the aperiodic exponent of the slope of the electroencephalogram (EEG) power spectrum ('1/f'). To validate our index of E/I balance, we tested for differences in the aperiodic exponent in 10-month-old infants with (n = 22) and without (n = 27) neurofibromatosis type 1 (NF1), a condition thought to be characterised by alterations to cortical inhibition. We then tested for E/I alterations in a larger heterogeneous longitudinal cohort of infants with and without a family history of neurodevelopmental conditions (n = 150) who had been followed to early childhood. We tested the relevance of alterations in E/I balance and our proposed modifier, executive attention, by assessing whether associations between 10-month aperiodic slope and 36-month neurodevelopmental traits were moderated by 24-month executive attention. Analyses adjusted for age at EEG assessment, sex and number of EEG trials.
Infants with NF1 were characterised by a higher aperiodic exponent, indicative of greater inhibition, supporting our infant measure of E/I. Longitudinal analyses showed a significant interaction between aperiodic slope and executive attention, such that higher aperiodic exponents predicted greater autistic traits in childhood, but only in infants who also had weaker executive functioning abilities.
The current study relied on parent report of infant executive functioning-type abilities; future work is required to replicate effects with objective measures of cognition.
Results suggest alterations in E/I balance are on the developmental pathway to autism outcomes, and that higher executive functioning abilities may buffer the impact of early cortical atypicalities, consistent with proposals that stronger executive functioning abilities may modify the impact of a wide range of risk factors.
The effects of selectively different experience of eye contact and gaze behaviour on the early development of five sighted infants of blind parents were investigated. Infants were assessed ...longitudinally at 6–10, 12–15 and 24–47 months. Face scanning and gaze following were assessed using eye tracking. In addition, established measures of autistic-like behaviours and standardized tests of cognitive, motor and linguistic development, as well as observations of naturalistic parent–child interaction were collected. These data were compared with those obtained from a larger group of sighted infants of sighted parents. Infants with blind parents did not show an overall decrease in eye contact or gaze following when they observed sighted adults on video or in live interactions, nor did they show any autistic-like behaviours. However, they directed their own eye gaze somewhat less frequently towards their blind mothers and also showed improved performance in visual memory and attention at younger ages. Being reared with significantly reduced experience of eye contact and gaze behaviour does not preclude sighted infants from developing typical gaze processing and other social-communication skills. Indeed, the need to switch between different types of communication strategy may actually enhance other skills during development.
Reduced executive functions (EF) are commonly associated with developmental conditions (e.g., autism spectrum disorder, ASD; attention deficit/hyperactivity disorder, ADHD), although EF seems to be ...typical in children with callous unemotional (CU) traits. Regulatory function (RF) is a proposed infant precursor that maps on onto factors driving later EF. Here, we first test whether RF is specifically and negatively associated with ASD and ADHD traits, but not CU traits. Second, we test whether RF can act as a protective factor, by moderating the association between infant markers and subsequent ASD and ADHD traits.
Participants were 79 infants at high (N = 42) and low (N = 37) familial risk for ASD. Data come from the 14-month infant visit (Autism Observational Scale for Infants; AOSI; activity level and RF from the Infant Behavior Questionnaire; IBQ) and the 7-year visit (ASD traits: Social Responsiveness Scale, SRS; ADHD traits: Conners 3, CU traits: Inventory of Callous Unemotional Traits).
Infant RF was negatively associated with later traits of ASD (B = - 0.5, p = 0.01) and ADHD inattention (B = - 0.24, p = 0.02) but not hyperactivity (B = - 0.25, p = 0.10) or CU traits (B = 0.02, p = 0.86). RF moderated the association between infant AOSI score and ASD traits, with a significant effect in those with low RF (B = 0.10, p = 0.006), not high RF (B = 0.01, p = 0.78). Similarly, for ADHD, infant activity level was associated with later ADHD inattention in those with low (B = 0.17, p = 0.04) but not high RF (B = 0.07, p = 0.48). For ADHD hyperactivity symptoms, activity level was predictive at both high and low levels of RF.
Strong RF may allow children to compensate for other atypicalities, thus attenuating the association between infant markers and later disorder traits. Whilst infant RF was associated with both ASD and ADHD inattention traits, there was no association with ADHD hyperactivity or CU traits. This suggests that any protective effect may not be universal and emphasises the need for a better understanding of the underlying moderating mechanisms.
Background
Most research on early outcomes in infants with a family history (FH) of autism has focussed on categorically defined autism, although some have language and developmental delays. Less is ...known about outcomes in infants with a FH of attention deficit hyperactivity disorder (ADHD).
Methods
Infants with and without a FH of autism and/or ADHD, due to a first‐degree relative with either or both conditions, were recruited at 5 or 10 months. Three year outcomes were characterised using latent profile analysis (LPA) across measures of cognitive ability, adaptive functioning and autism, ADHD and anxiety traits (n = 131). We additionally ran an LPA using only autism and ADHD measures, and the broader LPA in an independent cohort (n = 139) and in both cohorts combined (n = 270).
Results
A Low Developmental Level + High Behavioural Concerns class had elevated autism, ADHD and anxiety scores, low cognitive and adaptive function, and included all but one child with autism. A Low Developmental Level + Typical Behaviour class had average cognitive ability and typical behaviour but low adaptive function. A Typical Developmental Level + Some Behavioural Concerns class had average cognitive and adaptive function but slightly elevated behaviour scores. A High Developmental Level + Typical Behaviour class had above average cognitive ability and typical behaviour. All four LPAs identified classes characterised by combinations of either, or both, Low Development Level and elevated behaviour scores, as well as a typically developing class. No classes had elevated autism or ADHD traits in isolation.
Conclusions
Some infants with a FH of autism or ADHD have atypical developmental and behavioural outcomes, but do not show strong autism or ADHD traits in isolation. The field needs to recalibrate aims and methods to embrace the broader transdiagnostic pattern of outcomes seen in these infants.
We used a broad range of outcome measures to identify the ‘natural categories’ of early atypical outcome in infants with family history of autism or ADHD. Some infants with a family history of autism or ADHD have neurodevelopmental profiles characterised by combinations of either, or both, low developmental level and atypical behaviour but not elevated autism or ADHD traits in isolation. The field needs to adopt a transdiagnostic approach in the study of early development in autism and ADHD in order to develop fit‐for‐purpose developmental models and translational opportunities.
Mapping infant neurocognitive differences that precede later ADHD-related behaviours is critical for designing early interventions. In this study, we investigated (1) group differences in a battery ...of measures assessing aspects of attention and activity level in infants with and without a family history of ADHD or related conditions (ASD), and (2) longitudinal associations between the infant measures and preschool ADHD traits at 3 years. Participants (
= 151) were infants with or without an elevated likelihood for ADHD (due to a family history of ADHD and/or ASD). A multi-method assessment protocol was used to assess infant attention and activity level at 10 months of age that included behavioural, cognitive, physiological and neural measures. Preschool ADHD traits were measured at 3 years of age using the Child Behaviour Checklist (CBCL) and the Child Behaviour Questionnaire (CBQ). Across a broad range of measures, we found no significant group differences in attention or activity level at 10 months between infants with and without a family history of ADHD or ASD. However, parent and observer ratings of infant activity level at 10 months were positively associated with later preschool ADHD traits at 3 years. Observable behavioural differences in activity level (but not attention) may be apparent from infancy in children who later develop elevated preschool ADHD traits.
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