The importance of decomposing periodic and aperiodic EEG signals for assessment of brain function in a global context.

Measures of early neuro-cognitive development that are suitable for use in low-resource settings are needed to enable studies of the effects of early adversity on the developing brain in a global context. These measures should have high acquisition rates and good face and construct validity. Here, we investigated the feasibility of a naturalistic electroencephalography (EEG) paradigm in a low-resource context during childhood. Additionally, we examined the sensitivity of periodic and aperiodic EEG metrics to social and non-social stimuli. We recorded simultaneous 20-channel EEG and eye-tracking in 72 children aged 4-12 years (45 females) while they watched videos of women singing nursery rhymes and moving toys, selected to represent familiar childhood experiences. These measures were part of a feasibility study that assessed the feasibility and acceptability of a follow-up data collection of the South African Safe Passage Study, which tracks environmental adversity and brain and cognitive development from before birth up until childhood. We examined whether data quantity and quality varied with child characteristics and the sensitivity of varying EEG metrics (canonical band power in the theta and alpha band and periodic and aperiodic features of the power spectra). We found that children who completed the EEG and eye-tracking assessment were, in general, representative of the full cohort. Data quantity was higher in children with greater visual attention to the stimuli. Out of the tested EEG metrics, periodic measures in the theta frequency range were most sensitive to condition differences, compared to alpha range measures and canonical and aperiodic EEG measures. Our results show that measuring EEG during ecologically valid social and non-social stimuli is feasible in low-resource settings, is feasible for most children, and produces robust indices of social brain function. This work provides preliminary support for testing longitudinal links between social brain function, environmental factors, and emerging behaviors.

Editorial Perspective: The paradox of precision health in early development - building large samples to yield individual-level measures.

Precision health refers to the use of individualised biomarkers or predictive models to provide more tailored information about an individual's likely prognosis. For child psychiatry and psychology, we argue that this approach requires a focus on neurocognitive measures collected in early life and at large scale. However, the large sample sizes necessary to uncover individual-level predictors are currently rare in studies of neurodevelopmental conditions in early childhood. We recommend two strategies going forward: first, including neurocognitive measures in new national cohort studies, and second, synergising measures and data across currently funded longitudinal studies.

Neuroadaptive Bayesian optimisation can allow integrative design spaces at the individual level in the social and behavioural sciences and beyond.

Almaatouq et al. propose an integrative experiment design space combined with large samples for scientific advancement. We argue recent innovative designs combining closed-loop experiment designs and Bayesian optimisation allow for integrative experiments at an individual level during a single session, circumventing the necessity for large samples. This method can be applied across disciplines, including developmental and clinical research.

The roles of sensory hyperreactivity and hyporeactivity in understanding infant fearfulness and emerging autistic traits.

BACKGROUND: Existing evidence indicates that atypical sensory reactivity is a core characteristic of autism, and has been linked to both anxiety (and its putative infant precursor of fearfulness) and repetitive behaviours. However, most work has used cross-sectional designs and not considered the differential roles of hyperreactivity and hyporeactivity to sensory inputs, and is thus limited in specificity. METHODS: 161 infants with and without an elevated likelihood of developing autism and attention-deficit hyperactivity disorder (ADHD) were followed from 10 to 36 months of age. Parents rated an infant precursor of later anxiety (fearfulness) using the Infant Behaviour Questionnaire at 10 and 14 months, and the Early Childhood Behavioural Questionnaire at 24 months, and sensory hyperreactivity and hyporeactivity at 10, 14 and 24 months using the Infant Toddler Sensory Profile. Domains of autistic traits (restrictive and repetitive behaviours; RRB, and social communication interaction, SCI) were assessed using the parent-rated Social Responsiveness Scale at 36 months. Cross-lagged models tested (a) paths between fearfulness and hyperreactivity at 10-24 months, and from fearfulness and hyperreactivity to later autism traits, (b) the specificity of hyperreactivity effects by including hyporeactivity as a correlated predictor. RESULTS: Hyperreactivity at 14 months was positively associated with fearfulness at 24 months, and hyperreactivity at 24 months was positively associated with SCI and RRB at 36 months. When hyporeactivity was included in the model, paths between hyperreactivity and fearfulness remained, but paths between hyperreactivity and autistic traits became nonsignificant. CONCLUSIONS: Our findings indicate that alterations in early sensory reactivity may increase the likelihood of showing fearfulness in infancy, and relate to later social interactions and repetitive behaviours, particularly in individuals with a family history of autism or ADHD.

Differences in Intrinsic Gray Matter Connectivity and Their Genomic Underpinnings in Autism Spectrum Disorder.

BACKGROUND: Autism is a heterogeneous neurodevelopmental condition accompanied by differences in brain connectivity. Structural connectivity in autism has mainly been investigated within the white matter. However, many genetic variants associated with autism highlight genes related to synaptogenesis and axonal guidance, thus also implicating differences in intrinsic (i.e., gray matter) connections in autism. Intrinsic connections may be assessed in vivo via so-called intrinsic global and local wiring costs. METHODS: Here, we examined intrinsic global and local wiring costs in the brain of 359 individuals with autism and 279 healthy control participants ages 6 to 30 years from the EU-AIMS LEAP (Longitudinal European Autism Project). FreeSurfer was used to derive surface mesh representations to compute the estimated length of connections required to wire the brain within the gray matter. Vertexwise between-group differences were assessed using a general linear model. A gene expression decoding analysis based on the Allen Human Brain Atlas was performed to link neuroanatomical differences to putative underpinnings. RESULTS: Group differences in global and local wiring costs were predominantly observed in medial and lateral prefrontal brain regions, in inferior temporal regions, and at the left temporoparietal junction. The resulting neuroanatomical patterns were enriched for genes that had been previously implicated in the etiology of autism at genetic and transcriptomic levels. CONCLUSIONS: Based on intrinsic gray matter connectivity, the current study investigated the complex neuroanatomy of autism and linked between-group differences to putative genomic and/or molecular mechanisms to parse the heterogeneity of autism and provide targets for future subgrouping approaches.

Phenotypic and Genetic Associations Between Preschool Fine Motor Skills and Later Neurodevelopment, Psychopathology, and Educational Achievement.

BACKGROUND: Fine motor skills are heritable and comprise important milestones in development, and some evidence suggests that impairments in fine motor skills are associated with neurodevelopmental conditions, psychiatric disorders, and poor educational outcomes. METHODS: In a preregistered study of 9625 preschool children from TEDS (Twins Early Development Study), fine motor assessments (drawing, block building, folding, and questionnaires) were conducted at 2, 3, and 4 years of age. A cross-age fine motor score was derived using principal component analysis. Multivariate regression analysis was used to examine the relationships between the fine motor score and neurodevelopmental traits, psychopathology, and educational outcomes at 3 later ages (7/8, 12, and 16 years) and cross-age psychopathology composite scores. Polygenic scores (PGSs) were created for attention-deficit/hyperactivity disorder (ADHD), autism, schizophrenia, anxiety, major depressive disorder, obsessive-compulsive disorder, and years of education. We ran single-PGS models and a multi-PGS model. RESULTS: Fine motor skills were negatively associated with neurodevelopmental traits and psychopathology across childhood and adolescence and positively associated with educational achievement in adolescence (ß = 0.25, p < .001). Superior fine motor skills were associated with a higher years-of-education PGS (ß = 0.07, p < .001), a lower ADHD PGS (ß = -0.04, p = .011), and a higher anxiety PGS (ß = 0.03, p = .040). Similarly, the multi-PGS model retained the PGSs for years of education (ß = 0.07), ADHD (ß = -0.03), and anxiety (ß = 0.01). A non-preregistered analysis in an independent preschool sample replicated the ADHD PGS association, but not the years of education or anxiety PGS associations. CONCLUSIONS: Fine motor skills are linked genetically and phenotypically to later neurodevelopment, psychopathology, and educational outcomes. Future work should investigate the mechanisms that underlie the role of fine motor development in later outcomes.

Three year outcomes in infants with a family history of autism and/or attention deficit hyperactivity disorder.

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.

The neuroanatomical substrates of autism and ADHD and their link to putative genomic underpinnings.

BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental conditions accompanied by differences in brain development. Neuroanatomical differences in autism are variable across individuals and likely underpin distinct clinical phenotypes. To parse heterogeneity, it is essential to establish how the neurobiology of ASD is modulated by differences associated with co-occurring conditions, such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to (1) investigate between-group differences in autistic individuals with and without co-occurring ADHD, and to (2) link these variances to putative genomic underpinnings. METHODS: We examined differences in cortical thickness (CT) and surface area (SA) and their genomic associations in a sample of 533 individuals from the Longitudinal European Autism Project. Using a general linear model including main effects of autism and ADHD, and an ASD-by-ADHD interaction, we examined to which degree ADHD modulates the autism-related neuroanatomy. Further, leveraging the spatial gene expression data of the Allen Human Brain Atlas, we identified genes whose spatial expression patterns resemble our neuroimaging findings. RESULTS: In addition to significant main effects for ASD and ADHD in fronto-temporal, limbic, and occipital regions, we observed a significant ASD-by-ADHD interaction in the left precentral gyrus and the right frontal gyrus for measures of CT and SA, respectively. Moreover, individuals with ASD + ADHD differed in CT to those without. Both main effects and the interaction were enriched for ASD-but not for ADHD-related genes. LIMITATIONS: Although we employed a multicenter design to overcome single-site recruitment limitations, our sample size of N = 25 individuals in the ADHD only group is relatively small compared to the other subgroups, which limits the generalizability of the results. Also, we assigned subjects into ADHD positive groupings according to the DSM-5 rating scale. While this is sufficient for obtaining a research diagnosis of ADHD, our approach did not take into account for how long the symptoms have been present, which is typically considered when assessing ADHD in the clinical setting. CONCLUSION: Thus, our findings suggest that the neuroanatomy of ASD is significantly modulated by ADHD, and that autistic individuals with co-occurring ADHD may have specific neuroanatomical underpinnings potentially mediated by atypical gene expression.

Early development and epilepsy in tuberous sclerosis complex: A prospective longitudinal study.

AIM: To characterize early changes in developmental ability, language, and adaptive behaviour in infants diagnosed with tuberous sclerosis complex (TSC), and determine whether clinical features of epilepsy influence this pathway. METHOD: Prospective, longitudinal data were collected within the Early Development in Tuberous Sclerosis (EDiTS) Study to track development of infants with TSC (n = 32) and typically developing infants (n = 33) between 3 and 24 months of age. Questionnaire and observational measures were used at up to seven timepoints to assess infants' adaptive behaviour, developmental ability, language, and epilepsy. RESULTS: A significant group by age interaction effect showed that infants with TSC had lower adaptive functioning at 18 to 24 months old (intercept = 88.12, slope estimate = -0.82, p < 0.001) and lower developmental ability scores from 10 months old (intercept = 83.33, slope estimate = -1.44, p < 0.001) compared to typically developing infants. Early epilepsy severity was a significant predictor of these emerging developmental (R2 = 0.35, p = 0.004, 95% confidence interval [CI] -0.08 to -0.01) and adaptive behaviour delays (R2 = 0.34, p = 0.004, 95% CI -0.05 to -0.01]). Lower vocabulary production (intercept = -1.25, slope = -0.12, p < 0.001) and comprehension scores (intercept = 2.39, slope estimate = -0.05, p < 0.001) in infants with TSC at 24 months old were not associated with epilepsy severity. INTERPRETATION: Divergence of developmental ability and adaptive functioning skills occur in infants with TSC from 10 and 18 months, respectively. Associations between early epilepsy severity and impaired development supports the importance of early intervention to reduce seizure severity.

Cortical responses to social stimuli in infants at elevated likelihood of ASD and/or ADHD: A prospective cross-condition fNIRS study.

Autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) are highly prevalent neurodevelopmental conditions that often co-occur and present both common and distinct neurodevelopmental profiles. Studying the developmental pathways leading to the emergence of ASD and/or ADHD symptomatology is crucial in understanding neurodiversity and discovering the mechanisms that underpin it. This study used functional near-infrared spectroscopy (fNIRS) to investigate differences in cortical specialization to social stimuli between 4- to 6-month-old infants at typical and elevated likelihood of ASD and/or ADHD. Results showed that infants at both elevated likelihood of ASD and ADHD had reduced selectivity to vocal sounds in left middle and superior temporal gyrus. Furthermore, infants at elevated likelihood of ASD showed attenuated responses to visual social stimuli in several cortical regions compared to infants at typical likelihood. Individual brain responses to visual social stimuli were associated with later autism traits, but not ADHD traits. These outcomes support our previous observations showing atypical social brain responses in infants at elevated likelihood of ASD and align with later atypical brain responses to social stimuli observed in children and adults with ASD. These findings highlight the importance of characterizing antecedent biomarkers of atypicalities in processing socially relevant information that might contribute to both phenotypic overlap and divergence across ASD and ADHD conditions and their association with the later emergence of behavioural symptoms.

Using multi-modal neuroimaging to characterise social brain specialisation in infants.

The specialised regional functionality of the mature human cortex partly emerges through experience-dependent specialisation during early development. Our existing understanding of functional specialisation in the infant brain is based on evidence from unitary imaging modalities and has thus focused on isolated estimates of spatial or temporal selectivity of neural or haemodynamic activation, giving an incomplete picture. We speculate that functional specialisation will be underpinned by better coordinated haemodynamic and metabolic changes in a broadly orchestrated physiological response. To enable researchers to track this process through development, we develop new tools that allow the simultaneous measurement of coordinated neural activity (EEG), metabolic rate, and oxygenated blood supply (broadband near-infrared spectroscopy) in the awake infant. In 4- to 7-month-old infants, we use these new tools to show that social processing is accompanied by spatially and temporally specific increases in coupled activation in the temporal-parietal junction, a core hub region of the adult social brain. During non-social processing, coupled activation decreased in the same region, indicating specificity to social processing. Coupling was strongest with high-frequency brain activity (beta and gamma), consistent with the greater energetic requirements and more localised action of high-frequency brain activity. The development of simultaneous multimodal neural measures will enable future researchers to open new vistas in understanding functional specialisation of the brain.

Variation in spatial dependencies across the cortical mantle discriminates the functional behaviour of primary and association cortex.

Recent theories of cortical organisation suggest features of function emerge from the spatial arrangement of brain regions. For example, association cortex is located furthest from systems involved in action and perception. Association cortex is also 'interdigitated' with adjacent regions having different patterns of functional connectivity. It is assumed that topographic properties, such as distance between regions, constrains their functions, however, we lack a formal description of how this occurs. Here we use variograms, a quantification of spatial autocorrelation, to profile how function changes with the distance between cortical regions. We find function changes with distance more gradually within sensory-motor cortex than association cortex. Importantly, systems within the same type of cortex (e.g., fronto-parietal and default mode networks) have similar profiles. Primary and association cortex, therefore, are differentiated by how function changes over space, emphasising the value of topographical features of a region when estimating its contribution to cognition and behaviour.

Delineating early developmental pathways to ADHD: Setting an international research agenda.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent, impairing, and highly heritable condition typically diagnosed in middle childhood. However, it is now recognized that symptoms emerge much earlier in development. Research focused on understanding-using multiple units of analysis-the cascade of early-life (i.e., prenatal-infant-toddler) developmental changes that will later emerge as ADHD has the potential to transform early identification, prevention, and intervention. To this end, we introduce the recently established Early ADHD Consortium, an international network of investigators engaged in prospective, longitudinal studies of risk for ADHD beginning early in life, conducted within a developmental framework, and which incorporate multimethod approaches. This network seeks to harmonize measures and methodological approaches to increase the potential for data sharing and subsequent impact. Methods: This perspective paper highlights the importance of investigating pre-diagnostic markers of ADHD, and potential models and mechanisms of ADHD risk and development, with the long-term objective of facilitating development of preemptive interventions that will minimize the impact of ADHD symptoms on everyday functioning and maximize health and developmental outcomes. Results: We selectively describe key challenges and questions for this field related to theoretical models and developmental mechanisms in ADHD and recommend next steps for the science, including methodological, measurement, and study design considerations. We then describe potential implications for preemptive intervention development. We conclude by considering other issues including ethical concerns and the critical value of incorporating stakeholder input. Conclusions: It is hoped that this perspective puts forth a research agenda that will enhance collaborative efforts and accelerate progress in understanding developmental mechanisms and the early ADHD phenotype, with implications for early intervention enhancement of healthy development for infants, young children, and their families.

Developing customized NIRS-EEG for infant sleep research: methodological considerations.

Significance: Studies using simultaneous functional near-infrared spectroscopy (fNIRS)-electroencephalography (EEG) during natural sleep in infancy are rare. Developments for combined fNIRS-EEG for sleep research that ensure optimal comfort as well as good coupling and data quality are needed. Aim: We describe the steps toward developing a comfortable, wearable NIRS-EEG headgear adapted specifically for sleeping infants ages 5 to 9 months and present the experimental procedures and data quality to conduct infant sleep research using combined fNIRS-EEG. Approach: N=49 5- to 9-month-old infants participated. In phase 1, N=26 (10 = slept) participated using the non-wearable version of the NIRS-EEG headgear with 13-channel-wearable EEG and 39-channel fiber-based NIRS. In phase 2, N=23 infants (21 = slept) participated with the wireless version of the headgear with 20-channel-wearable EEG and 47-channel wearable NIRS. We used QT-NIRS to assess the NIRS data quality based on the good time window percentage, included channels, nap duration, and valid EEG percentage. Results: The infant nap rate during phase 1 was ∼40% (45% valid EEG data) and increased to 90% during phase 2 (100% valid EEG data). Infants slept significantly longer with the wearable system than the non-wearable system. However, there were more included good channels based on QT-NIRS in study phase 1 (61%) than phase 2 (50%), though this difference was not statistically significant. Conclusions: We demonstrated the usability of an integrated NIRS-EEG headgear during natural infant sleep with both non-wearable and wearable NIRS systems. The wearable NIRS-EEG headgear represents a good compromise between data quality, opportunities of applications (home visits and toddlers), and experiment success (infants' comfort, longer sleep duration, and opportunities for caregiver-child interaction).

Real-time monitoring of infant theta power during naturalistic social experiences.

Infant-directed speech and direct gaze are important social cues that shape infant's attention to their parents. Traditional methods for probing their effect on infant attention involve a small number of pre-selected screen-based stimuli, which do not capture the complexity of real-world interactions. Here, we used neuroadaptive Bayesian Optimization (NBO) to search a large 'space' of different naturalistic social experiences that systematically varied in their visual (gaze direct to averted) and auditory properties (infant directed speech to nonvocal sounds). We measured oscillatory brain responses (relative theta power) during episodes of naturalistic social experiences in 57 typically developing 6- to 12-month-old infants. Relative theta power was used as input to the NBO algorithm to identify the naturalistic social context that maximally elicited attention in each individual infant. Results showed that individual infants were heterogeneous in the stimulus that elicited maximal theta with no overall stronger attention for direct gaze or infant-directed speech; however, individual differences in attention towards averted gaze were related to interpersonal skills and greater likelihood of preferring speech and direct gaze was observed in infants whose parents showed more positive affect. Our work indicates NBO may be a fruitful method for probing the role of distinct social cues in eliciting attention in naturalistic social contexts at the individual level.

Associations between early language, motor abilities, and later autism traits in infants with typical and elevated likelihood of autism.

Slower acquisition of language and motor milestones are common in infants with later autism and studies have indicated that motor skills predict the rate of language development, suggesting these domains of development may be interlinked. However, the inter-relationships between the two domains over development and emerging autistic traits are not fully established. We studied language and motor development using standardized observational and parent-report measures in infants with (n = 271) and without (n = 137) a family history of autism across four waves of data collection from 10 to 36 months. We used Random Intercept Cross-Lagged Panel Models to examine contemporaneous and longitudinal associations between language and motor developments in both elevated and typical likelihood groups. We estimated paths between language and motor abilities at 10, 14, 24, and 36 months and autism trait scores at 36 months, to test whether the domains were interrelated and how they related to emerging autism traits. Results revealed consistent bidirectional Expressive Language (EL) and Fine Motor (FM) cross-lagged effects from 10 to 24 and a unidirectional EL to FM effect from 24 to 36 months as well as significantly correlated random intercepts between Gross motor (GM) and Receptive language (RL), indicating stable concurrent associations over time. However, only the associations between GM and RL were associated with later autism traits. Early motor and language are linked, but only gross motor and receptive language are jointly associated with autistic traits in infants with an autism family history.

Bridge-building between communities: Imagining the future of biomedical autism research.

A paradigm shift in research culture is required to ease perceived tensions between autistic people and the biomedical research community. As a group of autistic and non-autistic scientists and stakeholders, we contend that through participatory research, we can reject a deficit-based conceptualization of autism while building a shared vision for a neurodiversity-affirmative biomedical research paradigm.

Executive function profiles of preschool children with autism spectrum disorder and attention-deficit/hyperactivity disorder: A systematic review.

Background: Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are both associated with differences in Executive Functioning (EF). There is lack of clarity around the specificity or overlap of EF differences in early childhood when both disorders are first emerging. Method: This systematic review aims to delineate preschool EF profiles by examining studies comparing the EF profiles of children with and without ASD or ADHD. Five electronic databases were systematically searched (last search in May 2022) to identify published, quantitative studies of global and specific EF (Inhibition, Shifting, Working Memory (WM), Planning and Attentional Control), comparing children aged 2-6 with a diagnosis of ASD or ADHD to peers without ASD or ADHD. Results: Thirty-one empirical studies (10 ADHD and 21 ASD studies) met criteria for inclusion. EF profiles in preschool ASD were characterised by consistent Shifting, and, in most cases, Inhibition impairments. ADHD studies consistently reported impairments in Inhibition and Planning, and in most cases WM. Findings with regards to sustained Attention and Shifting in ADHD and WM and Planning in ASD were mixed. Conclusions: Overall, current evidence indicates overlap but also some specificity in EF impairments in preschool ASD and ADHD. There were differences in the degree to which individual domains were impaired, with Shifting more consistently impaired in ASD, and Inhibition, WM and Planning in ADHD. Methodological issues and differences in methods of outcome measurement could potentially underlie mixed findings, as informant-based measures revealed more robust EF impairments than laboratory-based tasks.

The typical and atypical development of empathy: How big is the gap from lab to field?

Background: Empathy-understanding and sharing someone else's feelings-is crucial for social bonds. Studies on empathy development are limited and mainly performed with behavioural assessments. This is in contrast to the extensive literature on cognitive and affective empathy in adults. However, understanding the mechanisms behind empathy development is critical to developing early interventions to support children with limited empathy. This is particularly key in toddlerhood, as children transition from highly scaffolded interactions with their parents and towards interactions with their peers. However, we know little about toddlers' empathy, in part due to the methodological constraints of testing this population in traditional lab settings. Methods: Here, we combine naturalistic observations with a targeted review of the literature to provide an assessment of our current understanding of the development of empathy in toddlerhood as it is expressed in real-world settings. We went into toddlers' typical habitat, a nursery, and we performed 21 h of naturalistic observations of 2-to-4-year-olds. We then reviewed the literature to evaluate our current understanding of the mechanisms that underpin observed behaviours. Results: We observed that (i) emotional contagion, possibly a primitive form of empathy, was observed at the nursery, but rarely; (ii) older toddlers often stared when someone cried, but there was no clear evidence of shared feelings; (iii) teacher and parent scaffolding might be paramount for empathy development; (iv) as some atypical empathic reactions can be observed from toddlerhood, early interventions could be developed. Several competing theoretical frameworks could account for current findings. Conclusions: Targeted studies of toddlers and their interaction partners in both controlled and naturalistic contexts are required to distinguish different mechanistic explanations for empathic behaviour in toddlerhood. We recommend the use of new cutting-edge methodologies to embed neurocognitively-informed frameworks into toddlers' natural social world.

Using the Infant Sibling-Design to Explore Associations Between Autism and ADHD Traits in Probands and Temperament in the Younger Siblings.

The purpose of the current study was to use the infant sibling design to explore whether proband traits of autism and ADHD could provide information about their infant sibling's temperament. This could help us to gain information about the extent to which infant temperament traits are differentially associated with autism and ADHD traits. We used parent-ratings of autistic traits and ADHD traits (CRS-3) in older siblings diagnosed with autism (age range 4 to 19 years), and their infant siblings' temperament traits (IBQ) at 9 months of age in 216 sibling pairs from two sites (BASIS, UK, and EASE, Sweden) to examine associations across siblings. We found specific, but modest, associations across siblings after controlling for sex, age, developmental level and site. Proband autistic traits were specifically related to low levels of approach in the infant siblings, with infant developmental level explaining part of the variance in infant approach. Proband ADHD traits were specifically related to high levels of infant activity even after controlling for covariates. Our findings suggest that proband traits of autism and ADHD carry information for infant sibling's temperament, indicating that inherited liability may influence early emerging behaviours in infant siblings. The impact of sex, age, developmental level and site are discussed.