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Background: sensory modulation difficulties are common in children with conditions such as Autism Spectrum Disorder (ASD), and could contribute to other social and non-social symptoms. Positing a causal role for sensory processing differences requires observing atypicalsensory reactivity prior to the emergence of other symptoms, which can be achieved through prospective studies. Methods: in this longitudinalstudy, we examined auditory repetition suppression and change detection at 5 and 10-months ininfants with and without Neurofibromatosis Type 1 (NF1), a condition associated with higher likelihood of developing ASD. Results: in typically developing infants, suppression to vowel repetition and enhancedresponses to vowel/pitchchangedecreased with ageoverposterior regions, becoming more frontally-specific; age-related change was diminished in the NF1group. Whilst both groups detected changes in vowel and pitch, the NF1group were largely slower to show a differentiated neural response. Auditory responses did not relate to later language but were related to later ASD traits. Conclusions: these findings represent the first demonstration of atypical brain responses to soundsin infants with NF1, and suggests they may relate to the likelihood of later ASD.

Background: The global COVID-19 pandemic has had an unprecedented impact on European health and social care systems, with demands on testing, hospital and intensive care capacity exceeding available resources in many regions. This has led to concerns that some vulnerable groups,including autistic people, may be excluded from services. Methods: We reviewed policies from 15 European member states, published March-July 2020,pertaining to: 1) access to COVID-19 tests; 2) provisions for treatment, hospitalisation and intensive careunits(ICU); and 3) changes to standard health and social care. In parallel, we analysed surveydata onthelived experiences of 1,301 autistic people and caregivers. Results: Autistic peopleexperienced significant barriers accessing COVID-19services. First, despite being at elevated risk for severe illness due to co-occurring health conditions, there was a lack of accessibility ofCOVID-19 testing. Second, many COVID-19 outpatient and inpatient treatment serviceswere reported to be inaccessible -predominantly resulting from individual differences in communication needs. Third, ICU triage protocols in many European countries (directly or indirectly)resultedin discriminatory exclusion from lifesaving treatments. Last, interruptions to standard health and social care left over 70% of autistic people without everyday support. Conclusions: The COVID-19 pandemic has further exacerbated existing healthcare inequalities for autistic people, likely contributing to disproportionate increases in morbidity and mortality,mental health/behavioural difficulties and reduced qualityoflife. Current policies and guidelines regarding the accessibility of COVID-19 services require urgent update to prevent the widespread exclusion of autistic peoplefrom services, which represents a violation of international human rights law.

Autism spectrum disorder (ASD) likely emerges from a complex interaction between pre-existing neurodevelopmental vulnerabilities and the environment. The interaction with parents forms a key aspect of an infant’s social environment, but few prospective studies of infants at elevated likelihood (EL) for ASD (who have an older sibling with ASD) have examined parent-child interactions in the first year of life. As part of a European multisite network, parent-child dyads of free play were observed at 5 months (62 EL infants, 47 infants at typical likelihood (TL)) and 10 months (101 EL siblings, 77 TL siblings). The newly-developed Parent-Infant/Toddler Coding of Interaction (PInTCI) scheme was used, focusing on global characteristics of infant and parent behaviors. Coders were blind to participant information. Linear mixed model analyses showed no significant group differences in infant or parent behaviors at 5 or 10 months of age (all ps≥0.09, d≤0.36), controlling for infant’s sex and age, and parental educational level. However, without adjustments, EL infants showed fewer and less clear initiations at 10 months than TL infants (p = 0.02, d = 0.44), but statistical significance was lost after controlling for parental education (p = 0.09, d = 0.36), which tended to be lower in the EL group. Consistent with previous literature focusing on parent-infant dyads, our findings suggest that differences between EL and TL dyads may only be subtle during the first year of life. We discuss possible explanations and implications for future developmental studies.

Typically developing (TD) infants adapt to the social world in part by shifting the focus of their processing resources to the relevant aspects of a visual scene. Any impairment in visual orienting may therefore constrain learning and development in domains such as language. However, although something is known about visual orienting in infants at risk of autism, very little is known about it in infants/toddlers with other neurodevelopmental disorders. This is partly because previous studies focused on older children and rarely compared the children to both chronological- and mental-age matched TD controls. Yet, if visual orienting is important for learning and development, then it is imperative to investigate it early in development and ascertain whether it relates to higher-level cognitive functions such as language. We used eye tracking technology to directly compare visual orienting in infants/toddlers with one of three neurodevelopmental disorders—Down syndrome (DS), fragile X syndrome (FXS), and Williams syndrome (WS)—matched on chronological- or mental-age to TD controls (~15 months). We also measured language ability using the Mullen Scales of Early Learning. We found that the ability to disengage attention from a visual stimulus in order to shift it to another visual stimulus is related to language ability in infants/toddlers irrespective of group affiliation. We also found that, contrary to the literature, infants and toddlers with DS (but not WS) are slow at disengaging attention. Our data suggest that orienting attention constrains language development and is impaired in DS.

Background: Alexithymia (difficulties identifying and describing emotion) is a transdiagnostic trait implicated in social-emotional and mental health problems in the general population. Many autistic individuals experience significant social-communication difficulties and elevated anxiety/ depression and alexithymia. Nevertheless, the role of alexithymia in explaining individual variability in the quality/ severity of social-communication difficulties and/ or anxiety and depression symptoms in autism remains poorly understood. \ud Methods: 337 adolescents and adults (autism N=179) were assessed for alexithymia on the Toronto Alexithymia Scale and for social-communication difficulties, anxiety and depression symptoms. 135 individuals (autism N=76) were followed up 12-24-months later. We used regression models to establish cross-sectional and longitudinal associations between alexithymia, social-communication difficulties, anxiety and depression symptoms. \ud Results: Autistic individuals reported significantly higher alexithymia than comparison individuals (p

Identifying developmental endophenotypes on the pathway between genetics and behaviour is critical to uncovering the mechanisms underlying neurodevelopmental conditions. In this proof-of-principle study, we explored whether early disruptions in visual attention are a unique or shared candidate endophenotype of Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). We calculated the duration of the longest look (i.e., peak look) to faces in an array-based eye-tracking task for 335 14-month-old infants with and without first-degree relatives with ASD and/or ADHD. We leveraged parent-report and genotype data available for a proportion of these infants to evaluate the relation of looking behaviour to familial (n=285) and genetic liability (using polygenic scores, n=185) as well as ASD and ADHD-relevant temperament traits at 2 (shyness and inhibitory control, respectively, n=272) and ASD and ADHD clinical traits at 6 years of age (n=94). \ud Results showed that longer peak looks at the face were associated with elevated polygenic scores for ADHD (=0.078, p=0.023), but not ASD ( =0.002, p=0.944), and with elevated ADHD traits in mid-childhood (F(1,88)=6.401, p=0.013, η_p^2=0.068; ASD F (1,88)=3.218, p=0.076), but not in toddlerhood (ps > 0.2). This pattern of results did not emerge when considering mean peak look duration across face and non-face stimuli. Thus, alterations in attention to faces during spontaneous visual exploration may be more consistent with a developmental endophenotype of ADHD than ASD. Our work shows that dissecting paths to neurodevelopmental conditions requires longitudinal data incorporating polygenic contribution, early neurocognitive function and clinical phenotypic variation.

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. Electronic supplementary material The online version of this article (10.1186/s13229-019-0264-6) contains supplementary material, which is available to authorized users.

Interest in autonomic arousal in autism spectrum disorder (ASD) is increasing; however, reliability of these measures in ASD is unknown, and previously reported associations with social and cognitive abilities are inconsistent. This study assesses heart rate (HR) and HR variability (HRV) in preschoolers with ASD or typical development (TD) while they passively watched naturalistic videos. Measurement reliability, group differences, and the relationship with social and cognitive abilities were evaluated. Seventy one ASD and 66 TD children (2–4 years) provided cardiac data from two sessions. Test–retest intraclass correlations of HR and HRV over a 3‐week period were moderate to good in both groups. Groups did not differ in mean level of HR or HRV. Intra‐individual variability of HR between video segments within a session was higher in the ASD group, but intraclass correlations of this metric were low. Higher HR related to better language skills in TD children, but not after accounting for age and nonverbal ability. Higher HRV related to better expressive and receptive language in ASD children after controlling for age and nonverbal ability. HR/HRV were not related to social or executive functioning skills and did not explain any additional variance in abilities at a 12‐month follow‐up visit. In summary, variation in language abilities is associated with HR in the TD group and HRV in the ASD group. While preliminary, these results are promising for consideration of autonomic control as a biomarker for individual differences in ASD and may help us understand the mechanisms that contribute to communication skills.

Autism Spectrum Disorder (ASD) is a common, highly heritable, developmental disorder, and later-born siblings of diagnosed children are at higher risk for developing ASD than the general population. Although the emergence of behavioural symptoms of ASD in toddlerhood is well characterised, far less is known about development during the first months of life of infants at familial risk. In a prospective longitudinal study of infants at familial risk followed to 36 months, we measured functional near infrared spectroscopy (fNIRS) brain responses to social videos of people (i.e. peek-a-boo) compared to non-social images (vehicles) and human vocalisations compared to non-vocal sounds. At 4 to 6 months, infants who went on to develop ASD at 3 years (N = 5) evidenced reduced activation to visual social stimuli relative to low risk infants (N = 16) across inferior frontal (IFG) and posterior temporal (pSTS-TPJ) regions of the cortex. Furthermore, these infants also showed reduced activation to vocal sounds and enhanced activation to non-vocal sounds within left lateralised temporal (MTG-STG) regions compared with low risk infants and high risk infants who did not develop ASD (N = 15). The degree of activation to both the visual and auditory stimuli correlated with parent reported ASD symptomology in toddlerhood. These preliminary findings are consistent with later atypical social brain responses seen in children and adults with ASD, and highlight the need for further work interrogating atypical processing in early infancy and how it may relate to later social interaction and communication difficulties characteristic of ASD.

Prospective longitudinal studies of infants with older siblings with autism spectrum disorder (ASD) have indicated that differences in the neurocognitive systems underlying social attention may emerge prior to the child meeting ASD diagnostic criteria. Thus, targeting social attention with early intervention might have the potential to alter developmental trajectories for infants at high risk for ASD. \ud Electrophysiological and habituation measures of social attention were collected at 6, 12 and 18 months in a group of high-risk infant siblings of children with ASD (N=33). Between 9-11 months of age, infant siblings received a parent-delivered intervention, Promoting First Relationships, (n=19) or on-going assessment without intervention (n=14). PFR has been previously shown to increase parental responsivity to infant social communicative cues and infant contingent responding. \ud Compared to infants who only received assessment and monitoring, infants who received the intervention showed improvements in neurocognitive metrics of social attention, as reflected in a greater reduction in habituation times to face versus object stimuli between 6 and 12 months, maintained at 18 months; a greater increase in frontal EEG theta power between 6 and 12 months; and a more comparable P400 response to faces and objects at 12 months. The high-risk infants who received the intervention showed a pattern of responses that appeared closer to the normative responses of two groups of age-matched low-risk control participants. \ud Though replication is necessary, these results suggest that early parent-mediated intervention has the potential to impact the brain systems underpinning social attention in infants at familial risk for ASD.

Investigation into the earliest signs of autism in infants has become a significant sub-field of autism research. This work invokes specific ethical concerns such as: use of ‘at-risk’ language; communicating study findings to parents; and the future perspective of enrolled infants when they reach adulthood. The current study aimed to ground this research field in an understanding of the perspectives of members of the autism community. Following focus groups to identify topics, an online survey was distributed to autistic adults, parents of children with autism, and practitioners in health and education settings across eleven European countries. Survey respondents (n=2317) were positively disposed towards early autism research and there was significant overlap in their priorities for the field, and preferred language to describe infant research participants. However there were also differences including overall less favourable endorsement of early autism research by autistic adults relative to other groups and a dislike of the phrase ‘at-risk’ to describe infant participants, in all groups except healthcare practitioners. The findings overall indicate that the autism community in Europe is supportive of early autism research. Researchers should endeavour to maintain this by continuing to take community perspectives into account.

The case for investment in early intervention for neurodevelopmental disorders.

Both autism spectrum (ASD) and anxiety disorders are associated with atypical neural and attentional responses to emotional faces, differing in affective face processing from typically developing peers. Within a longitudinal study of children with ASD (23 male, 3 female), we hypothesized that early ERPs to emotional faces would predict concurrent and later ASD and anxiety symptoms. Greater response amplitude to fearful faces corresponded to greater social communication difficulties at age 3, and less improvement by age 14. Faster ERPs to neutral faces predicted greater ASD symptom improvement over time, lower ASD severity in adolescence, and lower anxiety in adolescence. Early individual differences in processing of emotional stimuli likely reflect a unique predictive contribution from social brain circuitry early in life.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of the population, and close to 20% of prospectively studied infants with an older sibling with ASD. Although significant progress has been made in characterizing the emergence of behavioral symptoms of ASD, far less is known about the underlying disruptions to early learning. Recent models suggest that core aspects of the causal path to ASD may only be apparent in early infancy. Here, we investigated social attention in 6- and 12-month-old infants who did and did not meet criteria for ASD at 24 months using both cognitive and electrophysiological methods. We hypothesized that a reduction in attention engagement to faces would be associated with later ASD. Methods: In a prospective longitudinal design, we used measures of both visual attention (habituation) and brain function (event-related potentials to faces and objects) at 6 and 12 months, and investigated the relationship to ASD outcome at 24 months. Results: High-risk infants who met criteria for ASD at 24 months showed shorter epochs of visual attention, faster but less prolonged neural activation to faces, and delayed sensitization responses (increases in looking) to faces at 6 months; these differences were less apparent at 12 months. These findings are consistent with disrupted engagement of sustained attention to social stimuli. Conclusions: These findings suggest that there may be fundamental early disruptions to attention engagement that may have cascading consequences for later social functioning.

Between 6 and 12 months, typically developing infants undergo a socio-cognitive ‘revolution’. The Interactive Specialization (IS) theory of brain development predicts that these behavioral changes will be underpinned by developmental increases in the power and topographic extent of socially selective cortical responses. To test this hypothesis, we used EEG to examine developmental changes in cortical selectivity for ecologically valid dynamic social versus non-social stimuli in a large cohort of 6- and 12-month-old infants. Consistent with the Interactive Specialization model, results showed that differences in EEG theta activity between social and non-social stimuli became more pronounced and widespread with age. Differences in EEG activity were most clearly elicited by a live naturalistic interaction, suggesting that measuring brain activity in ecologically valid contexts is central to mapping social brain development in infancy.

Little is known about how spontaneous attentional deployment differs on a millisecond-level scale in the early development of autism spectrum disorders (ASD). We measured fine-grained eye movement patterns in 6-to 9-month-old infants at high or low familial risk (HR/LR) of ASD while they viewed static images. We observed shorter fixation durations (i.e. the time interval between saccades) in HR than LR infants. Preliminary analyses indicate that these results were replicated in a second cohort of infants. Fixation durations were shortest in those infants who went on to receive an ASD diagnosis at 36 months. While these findings demonstrate early-developing atypicality in fine-grained measures of attentional deployment early in the etiology of ASD, the specificity of these effects to ASD remains to be determined.