Emily J.H. Jones

Autism spectrum disorder is a construct used to describe individuals with a specific combination of impairments in social communication and repetitive behaviours, highly restricted interests and/or sensory behaviours beginning early in life. The worldwide prevalence of autism is just under 1%, but estimates are higher in high-income countries. Although gross brain pathology is not characteristic of autism, subtle anatomical and functional differences have been observed in post-mortem, neuroimaging and electrophysiological studies. Initially, it was hoped that accurate measurement of behavioural phenotypes would lead to specific genetic subtypes, but genetic findings have mainly applied to heterogeneous groups that are not specific to autism. Psychosocial interventions in children can improve specific behaviours, such as joint attention, language and social engagement, that may affect further development and could reduce symptom severity. However, further research is necessary to identify the long-term needs of people with autism, and treatments and the mechanisms behind them that could result in improved independence and quality of life over time. Families are often the major source of support for people with autism throughout much of life and need to be considered, along with the perspectives of autistic individuals, in both research and practice.

Background Autism spectrum disorders ( ASD ) and attention deficit hyperactivity disorder ( ADHD ) are two of the most common neurodevelopmental disorders, with a high degree of co‐occurrence. Methods Prospective longitudinal studies of infants who later meet criteria for ASD or ADHD offer the opportunity to determine whether the two disorders share developmental pathways. Results Prospective studies of younger siblings of children with autism have revealed a range of infant behavioral and neural markers associated with later diagnosis of ASD . Research on infants with later ADHD is less developed, but emerging evidence reveals a number of relations between infant measures and later symptoms of inattention and hyperactivity. Conclusions We review this literature, highlighting points of convergence and divergence in the early pathways to ASD and ADHD .

The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed.

A fast growing field, the study of infants at risk because of having an older sibling with autism (i.e. infant sibs) aims to identify the earliest signs of this disorder, which would allow for earlier diagnosis and intervention. More importantly, we argue, these studies offer the opportunity to validate existing neuro-developmental models of autism against experimental evidence. Although autism is mainly seen as a disorder of social interaction and communication, emerging early markers do not exclusively reflect impairments of the "social brain". Evidence for atypical development of sensory and attentional systems highlight the need to move away from localized deficits to models suggesting brain-wide involvement in autism pathology. We discuss the implications infant sibs findings have for future work into the biology of autism and the development of interventions.

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.

Autism spectrum disorder (ASD) is accompanied by highly individualized neuroanatomical deviations that potentially map onto distinct genotypes and clinical phenotypes. This study aimed to link differences in brain anatomy to specific biological pathways to pave the way toward targeted therapeutic interventions.The authors examined neurodevelopmental differences in cortical thickness and their genomic underpinnings in a large and clinically diverse sample of 360 individuals with ASD and 279 typically developing control subjects (ages 6-30 years) within the EU-AIMS Longitudinal European Autism Project (LEAP). The authors also examined neurodevelopmental differences and their potential pathophysiological mechanisms between clinical ASD subgroups that differed in the severity and pattern of sensory features.In addition to significant between-group differences in "core" ASD brain regions (i.e., fronto-temporal and cingulate regions), individuals with ASD manifested as neuroanatomical outliers within the neurotypical cortical thickness range in a wider neural system, which was enriched for genes known to be implicated in ASD on the genetic and/or transcriptomic level. Within these regions, the individuals' total (i.e., accumulated) degree of neuroanatomical atypicality was significantly correlated with higher polygenic scores for ASD and other psychiatric conditions, and it scaled with measures of symptom severity. Differences in cortical thickness deviations were also associated with distinct sensory subgroups, especially in brain regions expressing genes involved in excitatory rather than inhibitory neurotransmission.The study findings corroborate the link between macroscopic differences in brain anatomy and the molecular mechanisms underpinning heterogeneity in ASD, and provide future targets for stratification and subtyping.

Brain function is a product of the balance between excitatory and inhibitory (E/I) brain activity. Variation in the regulation of this activity is thought to give rise to normal variation in human traits, and disruptions are thought to potentially underlie a spectrum of neuropsychiatric conditions (e.g., Autism, Schizophrenia, Downs' Syndrome, intellectual disability). Hypotheses related to E/I dysfunction have the potential to provide cross-diagnostic explanations and to combine genetic and neurological evidence that exists within and between psychiatric conditions. However, the hypothesis has been difficult to test because: (1) it lacks specificity-an E/I dysfunction could pertain to any level in the neural system- neurotransmitters, single neurons/receptors, local networks of neurons, or global brain balance - most researchers do not define the level at which they are examining E/I function; (2) We lack validated methods for assessing E/I function at any of these neural levels in humans. As a result, it has not been possible to reliably or robustly test the E/I hypothesis of psychiatric disorders in a large cohort or longitudinal patient studies. Currently available, in vivo markers of E/I in humans either carry significant risks (e.g., deep brain electrode recordings or using Positron Emission Tomography (PET) with radioactive tracers) and/or are highly restrictive (e.g., limited spatial extent for Transcranial Magnetic Stimulation (TMS) and Magnetic Resonance Spectroscopy (MRS). More recently, a range of novel Electroencephalography (EEG) features has been described, which could serve as proxy markers for E/I at a given level of inference. Thus, in this perspective review, we survey the theories and experimental evidence underlying 6 novel EEG markers and their biological underpinnings at a specific neural level. These cheap-to-record and scalable proxy markers may offer clinical utility for identifying subgroups within and between diagnostic categories, thus directing more tailored sub-grouping and, therefore, treatment strategies. However, we argue that studies in clinical populations are premature. To maximize the potential of prospective EEG markers, we first need to understand the link between underlying E/I mechanisms and measurement techniques.

Abstract For most neuroimaging questions the range of possible analytic choices makes it unclear how to evaluate conclusions from any single analytic method. One possible way to address this issue is to evaluate all possible analyses using a multiverse approach, however, this can be computationally challenging and sequential analyses on the same data can compromise predictive power. Here, we establish how active learning on a low-dimensional space capturing the inter-relationships between pipelines can efficiently approximate the full spectrum of analyses. This approach balances the benefits of a multiverse analysis without incurring the cost on computational and predictive power. We illustrate this approach with two functional MRI datasets (predicting brain age and autism diagnosis) demonstrating how a multiverse of analyses can be efficiently navigated and mapped out using active learning. Furthermore, our presented approach not only identifies the subset of analysis techniques that are best able to predict age or classify individuals with autism spectrum disorder and healthy controls, but it also allows the relationships between analyses to be quantified.

The excitatory/inhibitory (E/I) imbalance hypothesis posits that imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. We used innovative analysis methods-combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT) to investigate relationships between genetic variance, brain structure and autism symptomatology of participants from the AIMS-2-TRIALS LEAP cohort (autism = 359, male/female = 258/101; neurotypical control participants = 279, male/female = 178/101) aged 6-30 years. Using competitive gene-set analyses, we investigated whether aggregated genetic variation in glutamate and GABA gene-sets could be associated with behavioral measures of autism symptoms and brain structural variation. Further, using the same gene-sets, we corelated expression profiles throughout the cortex with differences in CT between autistic and neurotypical control participants, as well as in separate sensory subgroups. The glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group. In adolescents and adults, brain regions with greater gene-expression of glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants although in opposing directions. Additionally, the gene expression profiles were associated with CT profiles in separate sensory subgroups. Our results suggest complex relationships between E/I related genetics and autism symptom profiles as well as brain structure alterations, where there may be differential roles for glutamate and GABA.

Temporal coordination during infant-caregiver social interaction is thought to be crucial for supporting early language acquisition and cognitive development. Despite a growing prevalence of theories suggesting that increased inter-brain synchrony associates with many key aspects of social interactions such as mutual gaze, little is known about how this arises during development. Here, we investigated the role of mutual gaze onsets as a potential driver of inter-brain synchrony. We extracted dual EEG activity around naturally occurring gaze onsets during infant-caregiver social interactions in N = 55 dyads (mean age 12 months). We differentiated between two types of gaze onset, depending on each partners' role. 'Sender' gaze onsets were defined at a time when either the adult or the infant made a gaze shift towards their partner at a time when their partner was either already looking at them (mutual) or not looking at them (non-mutual). 'Receiver' gaze onsets were defined at a time when their partner made a gaze shift towards them at a time when either the adult or the infant was already looking at their partner (mutual) or not (non-mutual). Contrary to our hypothesis we found that, during a naturalistic interaction, both mutual and non-mutual gaze onsets were associated with changes in the sender, but not the receiver's brain activity and were not associated with increases in inter-brain synchrony above baseline. Further, we found that mutual, compared to non-mutual gaze onsets were not associated with increased inter brain synchrony. Overall, our results suggest that the effects of mutual gaze are strongest at the intra-brain level, in the 'sender' but not the 'receiver' of the mutual gaze.

Over the past decade, biomarker discovery has become a key goal in psychiatry to aid in the more reliable diagnosis and prognosis of heterogeneous psychiatric conditions and the development of tailored therapies. Nevertheless, the prevailing statistical approach is still the mean group comparison between "cases" and "controls," which tends to ignore within-group variability. In this educational article, we used empirical data simulations to investigate how effect size, sample size, and the shape of distributions impact the interpretation of mean group differences for biomarker discovery. We then applied these statistical criteria to evaluate biomarker discovery in one area of psychiatric research-autism research. Across the most influential areas of autism research, effect size estimates ranged from small (d = 0.21, anatomical structure) to medium (d = 0.36 electrophysiology, d = 0.5, eye-tracking) to large (d = 1.1 theory of mind). We show that in normal distributions, this translates to approximately 45% to 63% of cases performing within 1 standard deviation (SD) of the typical range, i.e., they do not have a deficit/atypicality in a statistical sense. For a measure to have diagnostic utility as defined by 80% sensitivity and 80% specificity, Cohen's d of 1.66 is required, with still 40% of cases falling within 1 SD. However, in both normal and nonnormal distributions, 1 (skewness) or 2 (platykurtic, bimodal) biologically plausible subgroups may exist despite small or even nonsignificant mean group differences. This conclusion drastically contrasts the way mean group differences are frequently reported. Over 95% of studies omitted the "on average" when summarising their findings in their abstracts ("autistic people have deficits in X"), which can be misleading as it implies that the group-level difference applies to all individuals in that group. We outline practical approaches and steps for researchers to explore mean group comparisons for the discovery of stratification biomarkers.

Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed.We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2-32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n = 212 ASD, n = 199 neurotypicals [NT], all with IQ > 75). We performed analyses in source-space using individual head models derived from the participants' MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%-30% split).In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p = .042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52-0.62, specificity 0.59-0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset.The statistical power to detect weak effects-of the magnitude of those found in the training dataset-in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset's effects.This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects.

Human faces are one of the most prominent stimuli in the visual environment of young infants and convey critical information for the development of social cognition. During the COVID-19 pandemic, mask wearing has become a common practice outside the home environment. With masks covering nose and mouth regions, the facial cues available to the infant are impoverished. The impact of these changes on development is unknown but is critical to debates around mask mandates in early childhood settings. As infants grow, they increasingly interact with a broader range of familiar and unfamiliar people outside the home; in these settings, mask wearing could possibly influence social development. In order to generate hypotheses about the effects of mask wearing on infant social development, in the present work, we systematically review N = 129 studies selected based on the most recent PRISMA guidelines providing a state-of-the-art framework of behavioral studies investigating face processing in early infancy. We focused on identifying sensitive periods during which being exposed to specific facial features or to the entire face configuration has been found to be important for the development of perceptive and socio-communicative skills. For perceptive skills, infants gradually learn to analyze the eyes or the gaze direction within the context of the entire face configuration. This contributes to identity recognition as well as emotional expression discrimination. For socio-communicative skills, direct gaze and emotional facial expressions are crucial for attention engagement while eye-gaze cuing is important for joint attention. Moreover, attention to the mouth is particularly relevant for speech learning. We discuss possible implications of the exposure to masked faces for developmental needs and functions. Providing groundwork for further research, we encourage the investigation of the consequences of mask wearing for infants' perceptive and socio-communicative development, suggesting new directions within the research field.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is associated with significant difficulties in adaptive behavior and variation in clinical outcomes across the life span. Some individuals with ASD improve, whereas others may not change significantly, or regress. Hence, the development of "personalized medicine" approaches is essential. However, this requires an understanding of the biological processes underpinning differences in clinical outcome, at both the individual and subgroup levels, across the lifespan.The authors conducted a longitudinal follow-up study of 483 individuals (204 with ASD and 279 neurotypical individuals, ages 6-30 years), with assessment time points separated by ∼12-24 months. Data collected included behavioral data (Vineland Adaptive Behavior Scale-II), neuroanatomical data (structural MRI), and genetic data (DNA). Individuals with ASD were grouped into clinically meaningful "increasers," "no-changers," and "decreasers" in adaptive behavior. First, the authors compared neuroanatomy between outcome groups. Next, they examined whether deviations from the neurotypical neuroanatomical profile were associated with outcome at the individual level. Finally, they explored the observed neuroanatomical differences' potential genetic underpinnings.Outcome groups differed in neuroanatomical features (cortical volume and thickness, surface area), including in "social brain" regions previously implicated in ASD. Also, deviations of neuroanatomical features from the neurotypical profile predicted outcome at the individual level. Moreover, neuroanatomical differences were associated with genetic processes relevant to neuroanatomical phenotypes (e.g., synaptic development).This study demonstrates, for the first time, that variation in clinical (adaptive) outcome is associated with both group- and individual-level variation in anatomy of brain regions enriched for genes relevant to ASD. This may facilitate the move toward better targeted/precision medicine approaches.

Background Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD. Aims Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. Method Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age). Results Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD. Conclusions Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Neurodevelopmental conditions are characterised by differences in the way children interact with the people and environments around them. Despite extensive investigation, attempts to uncover the brain mechanisms that underpin neurodevelopmental conditions have yet to yield any translatable insights. We contend that one key reason is that psychologists and cognitive neuroscientists study brain function by taking children away from their environment, into a controlled lab setting. Here, we discuss recent research that has aimed to take a different approach, moving away from experimental control through isolation and stimulus manipulation, and towards approaches that embrace the measurement and targeted interrogation of naturalistic, user-defined and complex, multivariate datasets. We review three worked examples (of stress processing, early activity level in ADHD and social brain development in autism) to illustrate how these new approaches might lead to new conceptual and translatable insights into neurodevelopment.

There are well-documented links between structural racism and inequities in children's opportunities. Yet, when it comes to understanding the role of the built environment, a disproportionate focus on redlining obscures other historical policies and practices such as blockbusting, freeway displacement, and urban renewal that may impact contemporary child development. We hypothesized that historical structural racism in Allegheny County, Pennsylvania's, built environment would be associated with fewer contemporary educational, socioeconomic, and health opportunities. We also hypothesized that these measures would explain more collective variance in children's opportunities than redlining alone.We used geospatial data from the US Census, Mapping Inequality Project, and other archival sources to construct historical measures of redlining, blockbusting, freeway displacement, and urban renewal in ArcGIS at the census tract level. These were linked with data from the Child Opportunity Index 2.0 to measure children's opportunities across domains of education, socioeconomic status, and health. We ran spatial regression analyses in Stata 18.0 to examine individual and collective associations between structural racism and children's opportunities.Historical redlining, blockbusting, and urban renewal were largely associated with fewer contemporary educational, socioeconomic, and health opportunities, and explained up to 47.4% of the variance in children's opportunities. The measures collectively explained more variance in children's opportunities than redlining alone.In support of our hypotheses, novel measures of structural racism were related to present-day differences in children's opportunities. Findings lay the groundwork for future research focused on repairing longstanding harm perpetuated by structural racism.

Abstract Pea seeds are widely consumed in their immature form, known as garden peas and petit pois, mostly after preservation by freezing or canning. Mature dry peas are rich in iron in the form of ferritin, but little is known about the content, form or bioavailability of iron in immature stages of seed development. Using specific antibodies and in-gel iron staining, we show that ferritin loaded with iron accumulated gradually during seed development. Immunolocalization and high-resolution secondary ion mass spectrometry (NanoSIMS) revealed that iron-loaded ferritin was located at the surface of starch-containing plastids. Standard cooking procedures destabilized monomeric ferritin and the iron-loaded form. Iron uptake studies using Caco-2 cells showed that the iron in microwaved immature peas was more bioavailable than in boiled mature peas, despite similar levels of soluble iron in the digestates. By manipulating the levels of phytic acid in the digestates we demonstrate that phytic acid is the main inhibitor of iron uptake from mature peas in vitro . Taken together, our data show that immature peas and mature dry peas contain similar levels of ferritin-iron, which is destabilized during cooking. However, iron from immature peas is more bioavailable because of lower phytic acid levels compared to mature peas.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects social communication skills and flexible behaviour. Developing new treatment approaches for ASD requires early identification of the factors that influence later behavioural outcomes. One fruitful research paradigm has been the prospective study of infants with a first degree relative with ASD, who have around a 20% likelihood of developing ASD themselves. Early findings have identified a range of candidate neurocognitive markers for later ASD such as delayed attention shifting or neural responses to faces, but given the early stage of the field most sample sizes are small and replication attempts remain rare. The Eurosibs consortium is a European multisite neurocognitive study of infants with an older sibling with ASD conducted across nine sites in five European countries. In this manuscript, we describe the selection and standardization of our common neurocognitive testing protocol. We report data quality assessments across sites, showing that neurocognitive measures hold great promise for cross-site consistency in diverse populations. We discuss our approach to ensuring robust data analysis pipelines and boosting future reproducibility. Finally, we summarise challenges and opportunities for future multi-site research efforts.

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 in March–July 2020, pertaining to (1) access to COVID-19 tests; (2) provisions for treatment, hospitalisation and intensive care units (ICUs); and (3) changes to standard health and social care. In parallel, we analysed survey data on the lived experiences of 1301 autistic people and caregivers. Results Autistic people experienced significant barriers when accessing COVID-19 services. First, despite being at elevated risk of severe illness due to co-occurring health conditions, there was a lack of accessibility of COVID-19 testing. Second, many COVID-19 outpatient and inpatient treatment services were reported to be inaccessible, predominantly resulting from individual differences in communication needs. Third, ICU triage protocols in many European countries (directly or indirectly) resulted in discriminatory exclusion from lifesaving treatments. Finally, 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, probably contributing to disproportionate increases in morbidity and mortality, mental health and behavioural difficulties, and reduced quality of life. An urgent need exists for policies and guidelines on accessibility of COVID-19 services to be updated to prevent the widespread exclusion of autistic people from services, which represents a violation of international human rights law.

Abstract Background Interpersonal processes influence our physiological states and associated affect. Physiological arousal dysregulation, a core feature of anxiety disorders, has been identified in children of parents with elevated anxiety. However, little is understood about how parent–infant interpersonal regulatory processes differ when the dyad includes a more anxious parent. Methods We investigated moment-to-moment fluctuations in arousal within parent-infant dyads using miniaturised microphones and autonomic monitors. We continually recorded arousal and vocalisations in infants and parents in naturalistic home settings across day-long data segments. Results Our results indicated that physiological synchrony across the day was stronger in dyads including more rather than less anxious mothers. Across the whole recording epoch, less anxious mothers showed responsivity that was limited to ‘peak’ moments in their child's arousal. In contrast, more anxious mothers showed greater reactivity to small-scale fluctuations. Less anxious mothers also showed behaviours akin to ‘stress buffering’ – downregulating their arousal when the overall arousal level of the dyad was high. These behaviours were absent in more anxious mothers. Conclusion Our findings have implications for understanding the differential processes of physiological co-regulation in partnerships where a partner is anxious, and for the use of this understanding in informing intervention strategies for dyads needing support for elevated levels of anxiety.

Recent research suggests a link between autism spectrum disorder (ASD) and anorexia nervosa (AN). Individuals with AN show high scores on measures of ASD symptoms, relative to individuals without AN, however, there are currently no studies directly comparing women with AN to women with ASD. The aim of the current study was to examine profiles of ASD symptoms in young women in the acute and recovered stages of AN, women with ASD, and typically developing controls (TD), on both self-report and clinical interview measures.Four groups of participants aged 12-30 years were included (n = 218): AN, recovered AN (REC), ASD, and TD. Group differences on the Social Responsiveness Scale, 2nd edition (SRS-2), 10-item Autism Quotient (AQ-10), and the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) were examined. To explore similarities and differences in specific symptom profiles associated with AN and ASD, individual item endorsement on the ADOS-2 was also examined in AN, REC, and ASD.Across measures, women with ASD showed the highest scores, and TDs the lowest. Generally, individuals with AN and REC showed intermediate levels of ASD symptoms, scoring between the other two groups. However, AN and ASD did not differ on restricted interests and repetitive behaviour subscales. The ADOS-2 item 'quality of social response' adequately discriminated between ASD and non-ASD participants.A full diagnostic assessment for ASD was not provided for participants with AN/REC, nor were eating disorders assessed in the ASD group. Therefore, some diagnostic overlap between groups is possible. The cross-sectional design is another limitation.The results suggest similarities in scores on both self-report and clinical interview measures in AN and ASD. However, individual ADOS-2 item analyses also revealed subtle differences, particularly in reciprocal social interaction. ASD symptoms may be a combination of both state and trait features in AN.

Although many studies have explored atypicalities in gray matter (GM) and white matter (WM) morphology of autism, most of them relied on unimodal analyses that did not benefit from the likelihood that different imaging modalities may reflect common neurobiology. We aimed to establish brain patterns of modalities that differentiate between individuals with and without autism and explore associations between these brain patterns and clinical measures in the autism group.We studied 183 individuals with autism and 157 nonautistic individuals (age range, 6-30 years) in a large, deeply phenotyped autism dataset (EU-AIMS LEAP [European Autism Interventions-A Multicentre Study for Developing New Medications Longitudinal European Autism Project]). Linked independent component analysis was used to link all participants' GM volume and WM diffusion tensor images, and group comparisons of modality shared variances were examined. Subsequently, we performed univariate and multivariate brain-behavior correlation analyses to separately explore the relationships between brain patterns and clinical profiles.One multimodal pattern was significantly related to autism. This pattern was primarily associated with GM volume in bilateral insula and frontal, precentral and postcentral, cingulate, and caudate areas and co-occurred with altered WM features in the superior longitudinal fasciculus. The brain-behavior correlation analyses showed a significant multivariate association primarily between brain patterns that involved variation of WM and symptoms of restricted and repetitive behavior in the autism group.Our findings demonstrate the assets of integrated analyses of GM and WM alterations to study the brain mechanisms that underpin autism and show that the complex clinical autism phenotype can be interpreted by brain covariation patterns that are spread across the brain involving both cortical and subcortical areas.

Abstract 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.

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.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.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.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.

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.

Automated systems for identifying and removing non-neural ICA components are growing in popularity among EEG researchers of adult populations. Infant EEG data differs in many ways from adult EEG data, but there exists almost no specific system for automated classification of source components from paediatric populations. Here, we adapt one of the most popular systems for adult ICA component classification for use with infant EEG data. Our adapted classifier significantly outperformed the original adult classifier on samples of naturalistic free play EEG data recorded from 10 to 12-month-old infants, achieving agreement rates with the manual classification of over 75% across two validation studies (n = 44, n = 25). Additionally, we examined both classifiers' ability to remove stereotyped ocular artifact from a basic visual processing ERP dataset compared to manual ICA data cleaning. Here, the new classifier performed on level with expert manual cleaning and was again significantly better than the adult classifier at removing artifact whilst retaining a greater amount of genuine neural signal operationalised through comparing ERP activations in time and space. Our new system (iMARA) offers developmental EEG researchers a flexible tool for automatic identification and removal of artifactual ICA components.

Abstract Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals’ adaptive skills naturally improve or remain stable, while others’ decrease. To pave the way for ‘precision-medicine’ approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6–30 years), with two assessment time points separated by ~12–24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful “Increasers”, “No-changers”, and “Decreasers” in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup’s neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences’ potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.

Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97-99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry.

Externalizing and internalizing behavior problems can have deleterious psychosocial consequences for youth. Both sympathetic nervous system (SNS) and hypothalamic-pituitary adrenal (HPA) axis activity and reactivity may contribute to behavior problems but have largely been studied separately, with inconsistent findings. Because the SNS and HPA axis interact to carry out physiological processes (e.g., responding to stressors), considering SNS and HPA axis activity jointly may elucidate disparate findings. This review discusses studies that simultaneously assessed SNS and HPA axis (re)activity and youth behavior problems using measures of salivary alpha amylase (sAA) and salivary cortisol. Multiple patterns of SNS and HPA axis coordination were associated with problem behaviors, especially when considering individual differences and youth's psychosocial context. Importantly, many study findings may be artifacts of widespread methodological differences. The reviewed studies lay the foundation for future research on neuroendocrine coordination as a contributing factor to youth problem behaviors and some recommendations for future research are discussed.

Infant habitual sleep has been proposed as an important moderator of development in domains such as attention, memory or temperament. To test such hypotheses, we need to know how to accurately and consistently assess habitual sleep in infancy. Common assessment methods include easy to deploy but subjective parent-report measures (diary/sleep questionnaire); or more labour-intensive but objective motor movement measures (actigraphy). Understanding the degree to which these methods provide converging insights is important, but cross-method agreement has yet to be investigated longitudinally. Moreover, it is unclear whether concordance systematically varies with infant or maternal characteristics that could represent confounders in observational studies. This longitudinal study (up to 4 study visits/participant) investigated cross-method concordance on one objective (7-day actigraphy) and three commonly used subjective (7-day sleep diary, Brief Infant Sleep Questionnaire, Sleep & Settle Questionnaire) sleep measures in 76 typically developing infants (age: 4-14 months) and assessed the impact of maternal characteristics (stress, age, education) and infant characteristics (age) on cross-method concordance. In addition, associations between objective and subjective sleep measures and a measure of general developmental status (Ages & Stages Questionnaire) were investigated. A range of equivalence analyses (tests of equivalence, correlational analyses, Bland-Altman plots) showed mixed agreement between sleep measures. Most importantly, cross-method agreement was associated with maternal stress levels and infant age. Specifically, agreement between different measures of night waking was better for mothers experiencing higher stress levels and was higher for younger than older infants; the reverse pattern was true for day sleep duration. Interestingly, objective and subjective measures did not yield the same patterns of association with developmental domains, indicating that sleep method choice can influence which associations are found between sleep and cognitive development. However, results converged across day sleep and problem-solving skills, highlighting the importance of studying day sleep in future studies. We discuss implications of sleep method choice for investigating sleep in the context of studying infant development and behaviour.

Abstract Background 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. Method 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. Results 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. Limitations 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. Conclusions 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.

Attenuated social attention is a key marker of autism spectrum disorder (ASD). Recent neuroimaging findings also emphasize an altered processing of sensory salience in ASD. The locus coeruleus-norepinephrine system (LC-NE) has been established as a modulator of this sensory salience processing (SSP). We tested the hypothesis that altered LC-NE functioning contributes to different SSP and results in diverging social attention in ASD.We analyzed the baseline eye-tracking data of the EU-AIMS Longitudinal European Autism Project (LEAP) for subgroups of autistic participants (n = 166, age = 6-30 years, IQ = 61-138, gender [female/male] = 41/125) or neurotypical development (TD; n = 166, age = 6-30 years, IQ = 63-138, gender [female/male] = 49/117) that were matched for demographic variables and data quality. Participants watched brief movie scenes (k = 85) depicting humans in social situations (human) or without humans (non-human). SSP was estimated by gazes on physical and motion salience and a corresponding pupillary response that indexes phasic activity of the LC-NE. Social attention is estimated by gazes on faces via manual areas of interest definition. SSP is compared between groups and related to social attention by linear mixed models that consider temporal dynamics within scenes. Models are controlled for comorbid psychopathology, gaze behavior, and luminance.We found no group differences in gazes on salience, whereas pupillary responses were associated with altered gazes on physical and motion salience. In ASD compared to TD, we observed pupillary responses that were higher for non-human scenes and lower for human scenes. In ASD, we observed lower gazes on faces across the duration of the scenes. Crucially, this different social attention was influenced by gazes on physical salience and moderated by pupillary responses.The naturalistic study design precluded experimental manipulations and stimulus control, while effect sizes were small to moderate. Covariate effects of age and IQ indicate that the findings differ between age and developmental subgroups.Pupillary responses as a proxy of LC-NE phasic activity during visual attention are suggested to modulate sensory salience processing and contribute to attenuated social attention in ASD.

Psychosocial factors are related to immune, viral, and vaccination outcomes. Yet, this knowledge has been poorly represented in public health initiatives during the COVID-19 pandemic. This review provides an overview of biopsychosocial links relevant to COVID-19 outcomes by describing seminal evidence about these associations known prepandemic as well as contemporary research conducted during the pandemic. This focuses on the negative impact of the pandemic on psychosocial health and how this in turn has likely consequences for critically relevant viral and vaccination outcomes. We end by looking forward, highlighting the potential of psychosocial interventions that could be leveraged to support all people in navigating a postpandemic world and how a biopsychosocial approach to health could be incorporated into public health responses to future pandemics.

Background Social attention affords learning opportunities across development and may contribute to individual differences in developmental trajectories, such as between male and female individuals, and in neurodevelopmental conditions, such as autism. Methods Using eye‐tracking, we measured social attention in a large cohort of autistic ( n = 123) and nonautistic females ( n = 107), and autistic ( n = 330) and nonautistic males ( n = 204), aged 6–30 years. Using mixed Growth Curve Analysis, we modelled sex and diagnostic effects on the temporal dynamics of proportional looking time to three types of social stimuli (lean‐static, naturalistic‐static, and naturalistic‐dynamic) and examined the link between individual differences and dimensional social and nonsocial autistic traits in autistic females and males. Results In the lean‐static stimulus, average face‐looking was higher in females than in males of both autistic and nonautistic groups. Differences in the dynamic pattern of face‐looking were seen in autistic vs. nonautistic females, but not males, with face‐looking peaking later in the trial in autistic females. In the naturalistic‐dynamic stimulus, average face‐looking was higher in females than in males of both groups; changes in the dynamic pattern of face looking were seen in autistic vs. nonautistic males, but not in females, with a steeper peak in nonautistic males. Lower average face‐looking was associated with higher observer‐measured autistic characteristics in autistic females, but not in males. Conclusions Overall, we found stronger social attention in females to a similar degree in both autistic and nonautistic groups. Nonetheless, the dynamic profiles of social attention differed in different ways in autistic females and males compared to their nonautistic peers, and autistic traits predicted trends of average face‐looking in autistic females. These findings support the role of social attention in the emergence of sex‐related differences in autistic characteristics, suggesting an avenue to phenotypic stratification.

Abstract Autism and ADHD are characterised by atypical sensory responsivity, and this may be driven by alterations in the balance of cortical excitation to inhibition (E/I). Studies in early development are required to establish the primary of effects. We utilised data from a prospective longitudinal cohort of infants with and without a family history (FH) of autism and/or ADHD (N=151; 55% male, 83% white). We extracted electroencephalography (EEG) metrics of E/I balance at 5, 10 and 14 months; the aperiodic exponent of the slope of the power spectrum (‘1/f’). Models estimated correlated latent growth curves of parent-reported hyper and hypo-responsivity between 10 – 36 months. Analyses tested associations between developmental trajectories of sensory responsivity and FH, parent-rated neurodevelopmental traits at 3 years and E/I balance. Results showed that FH-autism was associated with steeper increases in parent-reported hyper-responsivity between 10 to 36 months, whereas FH-ADHD was associated with steeper increases in hypo-responsivity. Higher hypo-responsivity at 10-month baseline was associated with both autistic and ADHD traits at 3 years. A steeper slope of hypo-responsivity predicted ADHD traits at 3 years. Neither the baseline or slope of hyper-responsivity was associated with FH-ADHD, or autistic or ADHD traits at 3 years. Males displayed higher baseline hypo-responsivity. Aperiodic exponent values at 5 and 10, but not 14 months, were associated with hyper-responsivity. Results suggest that hypo-responsivity in infancy may be an indicator of later autism and ADHD outcomes. Alterations in E/I balance may contribute to early differences in sensory responsivity and thus could represent a useful target for intervention development.

BackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) is linked to strengths in creative problem-solving amongst school-aged children and adults. In contrast, autism (which frequently co-occurs with ADHD) is associated with lower generativity, and perseverative responses during problem-solving. Little is known about how ADHD and autism traits – or broader heritable autism and ADHD phenotypes – associate with problem-solving skills in early childhood.Methods129 UK 2- and 3-year-olds (exploratory dataset) and 74 Swedish 3-year-olds (confirmatory dataset) with and without a family history (FH) of ADHD and autism, completed a problem-solving task. Parents reported on their 3-year-olds’ ADHD and autism traits using the Child Behavior Checklist and Social Responsiveness Scale-2. FH group differences in problem-solving performance (success, generativity, perseveration, persistence) were tested using ANOVA in the exploratory dataset. A pre-registered t-test followed up FH-ADHD effects on problem-solving success in the confirmatory dataset. Linear regressions of problem-solving success on autism/ADHD traits were run in both samples.ResultsCompared with peers with no FH-ADHD, children with FH-ADHD showed higher problem-solving success at 2 (partial ω2=.106) and 3 years (partial ω2=.045) in the exploratory dataset. The hypothesized FH-ADHD effect was of a consistent direction and magnitude in the confirmatory dataset but success scores were only significantly higher for children with FH-ADHD when compared with children with no FH-ADHD-or-autism (gs =.977). Parent-reported ADHD (but not autism) traits were positively associated with problem-solving performance in the exploratory (β=.212, p=.031) and combined samples (β=.173, p=.024). Effects were of a consistent direction and magnitude but not significant in the confirmatory sample alone (β=.201, p=.103). ConclusionsConsidering a child’s family history alongside their neurodivergent traits may help to identify their likely strengths, and how to access them: Children with ADHD traits and/or a family history of ADHD are likely to have an aptitude for generative problem-solving when presented with highly-motivating, ecologically-valid challenges.

Abstract Background The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. Methods Eye-tracking data were collected from 486 6-to-30-year-old autistic ( N = 282) and non-autistic control ( N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). Results The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. Limitations The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. Conclusions Biological motion preference elicits small-to-medium-sized case–control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear.

Difficulties in social communication are a defining clinical feature of autism. However, the underlying neurobiological heterogeneity has impeded targeted therapies and requires new approaches to identifying clinically relevant bio-behavioural subgroups. In the largest autism cohort to date, we comprehensively examined difficulties in facial expression recognition, a key process in social communication, as a bio-behavioural stratification biomarker, and validated them against clinical features and neurofunctional responses.Between 255 and 488 participants aged 6-30 years with autism, typical development and/or mild intellectual disability completed the Karolinska Directed Emotional Faces task, the Reading the Mind in the Eyes Task and/or the Films Expression Task. We first examined mean-group differences on each test. Then, we used a novel intersection approach that compares two centroid and connectivity-based clustering methods to derive subgroups based on the combined performance across the three tasks. Measures and subgroups were then related to clinical features and neurofunctional differences measured using fMRI during a fearful face-matching task.We found significant mean-group differences on each expression recognition test. However, cluster analyses showed that these were driven by a low-performing autistic subgroup (~ 30% of autistic individuals who performed below 2SDs of the neurotypical mean on at least one test), while a larger subgroup (~ 70%) performed within 1SD on at least 2 tests. The low-performing subgroup also had on average significantly more social communication difficulties and lower activation in the amygdala and fusiform gyrus than the high-performing subgroup.Findings of autism expression recognition subgroups and their characteristics require independent replication. This is currently not possible, as there is no other existing dataset that includes all relevant measures. However, we demonstrated high internal robustness (91.6%) of findings between two clustering methods with fundamentally different assumptions, which is a critical pre-condition for independent replication.We identified a subgroup of autistic individuals with expression recognition difficulties and showed that this related to clinical and neurobiological characteristics. If replicated, expression recognition may serve as bio-behavioural stratification biomarker and aid in the development of targeted interventions for a subgroup of autistic individuals.

Perfectionism has a strong association with eating disorders. Research in non-clinical adults has suggested that perfectionism has both direct and indirect effects on eating disorder symptoms, and that compulsive exercise is a potential mediator. The aim of this study was to understand whether perfectionism is associated with eating disorder symptoms, both directly and indirectly through compulsive exercise in underweight adolescents with eating disorders. Participants were 149 female adolescents (M = 14.90 years, age range 13-17) with eating disorders from the Helping to Outline Paediatric Eating Disorders (HOPE) Project, an ongoing, registry study of individuals consecutively referred individuals to a statewide eating disorder service. The majority had a diagnosis of anorexia nervosa restricting type (66 %), followed by unspecified feeding or eating disorder (21 %), and anorexia nervosa binge-eating purging type (13 %). To test the model, path analyses with bootstrapping were conducted. All paths were statistically significant, including the indirect effect from perfectionism to eating disorder pathology via the mediator of compulsive exercise, and the direct effect of perfectionism on eating disorder pathology. Overall, this research provides further evidence that compulsive exercise may be one factor that can explain the relationship between perfectionism and eating disorder symptoms. Future research should seek to determine the relative efficacy of approaches for the treatment of eating disorders in adolescents which target perfectionism and compulsive exercise.

Purpose To examine whether emotional support moderates the association between college generation status and concurrent and prospective levels of systemic inflammation during the college transition among a sample of older U.S. adolescents. Methods At an undergraduate tertiary institution, 41 first-generation college students (first-gens) and 46 continuing-generation college students (continuing-gens) in their first semester of college reported on basic demographic information and perceived emotional support. They also had their blood drawn midway through both the first and second semester to measure C-reactive protein and interleukin-6. An inflammatory composite for each semester was created by averaging the standardized scores for log-transformed C-reactive protein and interleukin-6. Results Compared to continuing-gens, first-gens had greater systemic inflammation in the first semester regardless of their level of emotional support (B = 0.515, p = .003). However, emotional support moderated the association between college generation status and prospective systemic inflammation in the second semester (B = −0.525, p = .007) such that first-gens had greater systemic inflammation compared to continuing-gens, but only if they reported lower levels of emotional support (B = 0.826, p = .002). This moderation effect held after further adjusting for systemic inflammation in the first semester (B = −0.374, p = .022). Also discussed are results of secondary analyses examining sources of support. Discussion Compared to continuing-gens, first-gens had greater systemic inflammation in the first semester irrespective of emotional support, suggesting all first-gens may stand to benefit from college resources provided early in the college transition. Furthermore, first-gens who reported lower levels of emotional support may benefit from additional college resources provided beyond the first semester.

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.

Abstract Background Differences in face processing are commonly reported in case/control studies of autism. Their neural correlates have been explored extensively across single neuroimaging modalities within key regions of the face processing network, such as the fusiform gyrus (FFG). Nonetheless, it is poorly understood how different variation(s) in brain anatomy and function combine to impact face processing and social functioning. Extracting the shared information across different modalities is essential to better delineate the complex relationship between brain structure and function, leading to a more comprehensive understanding of the mechanisms underlying autism. Methods Here, we leveraged data from the large multimodal EU-AIMS Longitudinal European Autism Project (LEAP) to study the cross-modal signature of face processing within the FFG across structural magnetic resonance imaging (MRI), resting-state fMRI (rs-fMRI), task-fMRI (based on the Hariri emotional faces task) and electroencephalography (EEG; recorded when observing facial stimuli) in a sample of 99 autistic and 105 non-autistic individuals (NAI) aged 6-30 years. We combined two methodological innovations: (i) normative modelling was employed on each imaging modality separately to derive individual-level deviations from a predicted developmental trajectory and (ii) unimodal deviations were fused through Linked Independent Component (IC) Analysis to simultaneously decompose the imaging data into underlying modes that characterise multi-modal signatures across the cohort. Next, we tested whether ICs significantly differed between autistic and NAI and whether multimodal ICs would outperform unimodal ICs in discriminating autistic individuals from NAI using a support vector machine under 10-fold cross-validation. Finally, we tested the association between multimodal ICs and cognitive, clinical measures of social or non-social functioning in autism using canonical correlation analysis (CCA). Results In total, 50 independent components were derived. Among these one multimodal IC differed significantly between autistic and NAI ( t =3.5, p FDR =0.03). This IC was mostly driven by bilateral rs-fMRI, bilateral structure, right task-fMRI, and left EEG loadings and implicated both face-selective and retinotopic regions of the FFG. Furthermore, multimodal ICs performed significantly better at differentiating autistic from NAI than unimodal ICs ( p <0.001). Finally, there was a significant multivariate association between multimodal ICs and a set of cognitive and clinical features associated with social functioning ( r =0.65, p FDR =0.008); but not with non-social features. Discussion The FFG appears to be a central region differentially implicated in autistic and NAI across a range of inter-related imaging modalities and category-selective regions in both the left and right hemispheres. Elucidating more integrated, individual-level neural associations of core social functioning in autism will pave the way for further work on identifying more fine-grained stratification, mechanistic and prognostic biomarkers, and the development of more personalised support.

Abstract Differences in face processing are commonly reported in case/control studies of autism. Their neural correlates have been explored extensively across single neuroimaging modalities within key regions of the face processing network, such as the fusiform gyrus (FFG). Nonetheless, it is poorly understood how different variation(s) in brain anatomy and function combine to impact face processing and social functioning. Extracting the shared information across different modalities is essential to derive a more comprehensive understanding of the mechanisms underlying autism. Here, we leveraged a large multimodal sample to study the cross-modal signature of face processing within the FFG across four imaging modalities (structural MRI, resting-state fMRI [rs-fMRI], task-fMRI and EEG) in 204 individuals aged 7-30years comprising both autistic and non-autistic individuals (NAI). Combining two methodological innovations – normative modeling and linked independent component analysis – we integrated individual-level deviations across modalities to assess the efficacy of multimodal components in differentiating autistic from NAI and informing autism-associated social functioning. Autistic individuals differed significantly in a multimodal component, driven by bilateral rs-fMRI, bilateral structure, right task-fMRI, and left EEG loadings involving face-selective and retinotopic FFG regions. Multimodal components outperformed unimodal ones in differentiating autistic from NAI. Within the autism group, there was a significant multivariate association between multimodal components and a set of cognitive and clinical features associated with social functioning but not non-social features. These findings underscore the importance of elucidating individual-level, integrated neural associations of core social functioning in autism, offering potential for refined stratification and the identification of mechanistic and prognostic biomarkers.

Abstract Background There is a strong association between perfectionism and eating disorders. In a cognitive–behavioural model of compulsive exercise it has been suggested there are reciprocal associations between perfectionism, eating disorder pathology, and compulsive exercise. No study has examined if there is an indirect association between perfectionism and compulsive exercise through eating disorder pathology, which would inform a preliminary understanding of the cognitive–behavioural model of compulsive exercise. Methods The sample included 301 adolescent females diagnosed with eating disorders (age M = 14.89, SD = 0.85, range 13–17). We tested models of direct and indirect associations of compulsive exercise in the relationship between perfectionism and eating disorder pathology, and direct and indirect associations of eating disorder pathology in the relationship between compulsive exercise and perfectionism. Results Perfectionism was directly associated with eating disorder pathology and compulsive exercise. Perfectionism was indirectly associated with eating disorder pathology through compulsive exercise. Perfectionism also had an indirect association with compulsive exercise through eating disorder pathology. Discussion The findings suggest it would be useful for future prospective research to examine the cognitive–behavioural model of compulsive exercise in adolescents with eating disorders. Compulsive exercise and perfectionism may be useful targets for future research to improve eating disorder treatment. Level of evidence Level V: Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Childhood trauma may contribute to poor lifelong health in part through programming of the HPA-axis response to future life stressors. To date, empirical evidence shows an association of childhood trauma with dysregulation of the HPA-axis and blunted cortisol reactivity to acute stressors. Here, we conduct an initial examination of childhood trauma as a moderator of changes over time in perceived stress levels and HPA-axis response to a major chronic stressor in adulthood. Participants were 83 maternal caregivers of children newly diagnosed with cancer who completed the Childhood Trauma Questionnaire (CTQ), and who, over the year following their child's cancer diagnosis, had hair samples collected up to 7 times for the assessment of cortisol and completed monthly measures of perceived stress. CTQ scores were in the expected range for a community sample and associated with changes in perceived stress and cortisol concentration over time (γ =.003, p =.002; γ = -.0004, p =.008, respectively) independently of age, education, treatment intensity and randomization to stress management intervention. Maternal caregivers who endorsed lower childhood trauma showed a steeper decline in perceived stress and a larger increase in cortisol levels across the year than caregivers who recalled more childhood trauma. Findings extend animal models and studies that examine cortisol reactivity to acute stressors and suggest that childhood trauma may program a phenotype that is more psychologically reactive but shows a blunted HPA-axis response to chronic stress. While adaptive in the short-term, this early life programming may incur long-term costs for health. Further work is warranted to examine this possibility.

Purpose: Infants later diagnosed with autism typically have smaller vocabularies than their peers. The MacArthur-Bates Communicative Developmental Inventory (CDI) and the Mullen Scales of Early Learning (MSEL) are key tools for assessing infants' language abilities, but it remains unclear what the association is between these measures in infancy, and whether associations vary with group status (elevated likelihood of autism or not; confirmed diagnosis of autism or not).Methods: We analyzed data from 720 14-month-old infants in the Eurosibs consortium, looking at whether the correlation between CDI and MSEL was influenced by group status (elevated likelihood of autism or not; confirmed diagnosis or not) and native language. We also compared vocabulary sizes between the two likelihood groups, and then between the two diagnostic groups.Results: Moderate correlations between CDI and MSEL scores were found across most groups, rs = [.34, .58]. Infants with an elevated likelihood of autism showed a slightly higher correlation in expressive language scores than typically developing children. Diagnosed children had smaller vocabularies than their non-diagnosed counterparts on both CDI and MSEL. The elevated likelihood group had smaller vocabularies on MSEL but not on CDI when compared to typical likelihood peers.Conclusion: The moderate associations between CDI and MSEL suggest they may measure different aspects of language in infancy, as these associations are weaker than previously reported for older children. Vocabulary size differences were more pronounced in diagnostic groups than in likelihood groups. Further research is needed to understand why these associations are lower in infants. Keywords: Language assessment, Communicative Developmental Inventory, Mullen Scales of Early Learning, Autism, Infants

Clinical perfectionism, self-esteem, mood intolerance, and interpersonal difficulties are associated with eating disorder symptoms in clinical samples. The aim of the current study was to test a model including clinical perfectionism, self-esteem, mood intolerance, and interpersonal difficulties to understand eating disorder symptoms in an adolescent community sample. Adolescents (N = 446, M age = 16.25 years, SD = 1.64; 74.2% female) completed measures of clinical perfectionism, self-esteem, mood intolerance, interpersonal difficulties, and eating disorder symptoms. Path analysis indicated clinical perfectionism, self-esteem, mood intolerance, and interpersonal difficulties were all directly associated with symptoms of eating disorders, and that clinical perfectionism was indirectly associated with eating disorders through self-esteem, mood intolerance, and interpersonal difficulties. The results indicate the cognitive-behavioural model of eating disorders can be applied to adolescents in the community with symptoms of eating disorders. Directional causality between constructs should be established to understand whether increased clinical perfectionism, and reduced self-esteem, mood intolerance, and interpersonal difficulties are vulnerabilities to the development and maintenance of eating disorders.

BackgroundAcute otitis externa (AOE) is a common inflammatory condition affecting the external ear that occasionally presents with persistent, severe pain, which may be unresponsive to first-line therapy and require assessment and treatment in the hospital setting. AimsTo identify the microorganisms responsible for cases of otitis externa presenting to Wellington Hospital, New Zealand, over a five-year period between 2007 and 2011.We also aim to evaluate current management of this condition and to recommend future treatment options. MethodA five-year retrospective study, with data obtained from case notes and electronic records for all patients presenting with otitis externa to Wellington Hospital between 2007 and 2011. ResultsOf 347 cases identified, 144 were included in the study.Pseudomonas aeruginosa (P.aeruginosa) was the most common organism (46.5 per cent), while Staphylococcus aureus (S. aureus) was the second most common (31.9 per cent).Most patients received appropriate topical treatment.However, a significant number were treated with systemic antibiotics alone without adverse outcomes. ConclusionPseudomonas aeruginosa is the most common microbe causing acute otitis externa in patients that require hospital level management in Wellington, New Zealand.In most cases, patients received appropriate topical therapy; however, it appears a large number received systemic antibiotic therapy without topical treatment.We recommend broad-spectrum topical antimicrobial therapy in all patients with uncomplicated AOE and culture-sensitive topical treatment with consideration of systemic antimicrobials for severe AOE requiring hospital admission.

Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype.Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9- to 24-month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3-year ASD outcome, polygenic liability for ASD and dimensional 3-year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD ) were calculated for 190 infants.While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (β = -.16, 95% CI = -0.31, -0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative 'catch-up') between 14 and 24 months relative to those with other outcomes (typical: β = .54, 95% CI = 0.08, 0.99; other: β = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD-related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9- to 14-month amplitude was associated with higher SA (β = .08, 95% CI = 0.01, 0.14) and RRB (β = .05, 95% CI = 0.004, 0.11) traits.These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.

Co-regulation of physiological arousal within the caregiver-child dyad precedes later self-regulation within the individual. Despite the importance of unimpaired self-regulatory development for later adjustment outcomes, little is understood about how early co-regulatory processes can become dysregulated during early life. Aspects of caregiver behavior, such as patterns of anxious speech, may be one factor influencing infant arousal dysregulation. To address this, we made day-long, naturalistic biobehavioral recordings in home settings in caregiver-infant dyads using wearable autonomic devices and miniature microphones. We examined the association between arousal, vocalization intensity, and caregiver anxiety. We found that moments of high physiological arousal in infants were more likely to be accompanied by high caregiver arousal when caregivers had high self-reported trait anxiety. Anxious caregivers were also more likely to vocalize intensely at states of high arousal and produce intense vocalizations that occurred in clusters. High-intensity vocalizations were associated with more sustained increases in autonomic arousal for both anxious caregivers and their infants. Findings indicate that caregiver vocal behavior differs in anxious parents, cooccurs with dyadic arousal dysregulation, and could contribute to physiological arousal transmission. Implications for caregiver vocalization as an intervention target are discussed.

Neurofibromatosis type 1 (NF1) is a genetic disorder often associated with cognitive dysfunctions, including a high occurrence of deficits in visuoperceptual skills. The neural underpinnings of these visuoperceptual deficits are not fully understood. We used steady-state visual evoked potentials (SSVEPs) to investigate possible alterations in the synchronization of neural activity in the occipital cortex of children with NF1.SSVEPs were measured using electroencephalography and compared between children with NF1 (n = 28) and neurotypical controls (n = 28) aged between 4 and 13 years old. SSVEPs were recorded during visual stimulation with coloured icons flickering at three different frequencies (6 Hz, 10 Hz, and 15 Hz) and analyzed in terms of signal-to-noise ratios. A mixed design ANCOVA was performed to compare SSVEP responses between groups at the three stimulation frequencies. Pearson's correlations with levels of intellectual functioning as well as with symptoms of ADHD, ASD and emotional/behavioral problems were performed. The impact of psychostimulant medication on the SSVEP responses was analyzed in a subset of the NF1 group (n = 8) with paired t-tests.We observed reduced signal-to-noise ratios of the SSVEP responses in children with NF1. The SSVEP responses were negatively correlated with symptoms of inattention and with symptoms of emotional/behavioral problems in the NF1 group. The SSVEP response generated by the lowest stimulation frequency (i.e., 6 Hz) was rescued with the intake of psychostimulant medication.Impaired processing of rhythmic visual stimulation was evidenced in children with NF1 through measures of SSVEP responses. Those responses seem to be more reduced in children with NF1 who exhibit more symptoms of inattention and emotional/behavioral problems in their daily life. SSVEPs are potentially sensitive electrophysiological markers that could be included in future studies investigating the impact of medication on brain activity and cognitive functioning in children with NF1.

Shanna D. Ray, Jennifer D. Lockman, Emily J. Jones, and Melanie H. KellyOnline First Publication, September 22, 2014. http://dx.doi.org/10.1037/a0037884CITATIONRay, S. D., Lockman, J. D., Jones, E. J., & Kelly, M. H. (2014, September 22). Attributions toGod and Satan About Life-Altering Events. Psychology of Religion and Spirituality. Advanceonline publication. http://dx.doi.org/10.1037/a0037884

The aim of the study was to assess whether the association between chronic family stress and physiological measures is moderated by emotion regulation strategies in an adolescent sample.Chronic family stress was assessed via a semistructured interview and emotion regulation strategies (cognitive reappraisal and suppression) via questionnaire among 261 adolescents (14.57 (1.07) years). Several metabolic (waist-hip ratio, systolic and diastolic blood pressure) and inflammatory markers (basal and stimulated proinflammatory cytokine production in response to bacterial challenge) as well as glucocorticoid sensitivity were assessed.There were no main effects of chronic family stress, cognitive reappraisal, or suppression on physiological measures (all p's > .10). Emotion regulation moderated the association between chronic family stress and physiological measures. As chronic family stress increased, adolescents higher in cognitive reappraisal had smaller waist-hip ratios (B = -.003, SE = .001, p = .015) and lower systolic blood pressure (B = -.303, SE = .143, p = .035), although no moderation was found with respect to inflammatory markers and glucocorticoid sensitivity (all p's > .30). In addition, as chronic family stress increased, adolescents higher in suppression showed evidence of higher stimulated proinflammatory cytokine production (B = .046, SE = .020, p = .021) and lower glucocorticoid sensitivity (B = .051, SE = .021, p = .015), although basal inflammation and metabolic measures were not moderated by suppression (all p's > .50).This study suggests that the types of emotion regulation strategies used by adolescents may affect the extent to which chronic family stress affects important metabolic and immune processes.

Attention bias modification training (ABMT) and cognitive behavioral therapy (CBT) likely target different aspects of aberrant threat responses in anxiety disorders and may be combined to maximize therapeutic benefit. However, studies investigating the effect of ABMT in the context of CBT have yielded mixed results. Here, we propose an enhanced ABMT to target the attentional bias towards threat, in addition to classic CBT for anxiety disorders in youth. This enhanced ABMT integrates the modified dot-probe task used in previous studies, where a target is always presented at the previous location of the neutral and not the simultaneously presented threatening stimulus, with a visual search, where the targets are always presented distally of threatening distractors. These two training elements (modified dot-probe and visual search) are embedded in an engaging game to foster motivation and adherence. Our goal is to determine the efficacy of the enhanced ABMT in the context of CBT. Further, we aim to replicate two previous findings: (a) aberrant amygdala connectivity being the neurobiological correlate of the attentional bias towards threat at baseline; and (b) amygdala connectivity being a mediator of the ABMT effect. We will also explore moderators of treatment response (age, sex, depressive symptoms and irritability) on a behavioral and neuronal level. One hundred and twenty youth (8–17 years old) with a primary anxiety disorder diagnosis all receive CBT and are randomized to nine weeks of either active or control ABMT and symptom improvement will be compared between the two study arms. We will also recruit 60 healthy comparison youth, who along with eligible anxious youth, will be assessed with the dot-probe task during fMRI (anxious youth: before and after training; healthy volunteers: second measurement twelve weeks after initial assessment). The present study will contribute to the literature by (1) potentially replicating that aberrant amygdala connectivity mediates the attentional bias towards threat in anxious youth; (2) determining the efficacy of enhanced ABMT; and (3) advancing our understanding of the mechanisms underlying ABMT. Clinicaltrials.gov: NCT03283930 Trial registration date: September 14th 2017. The trial registration took place retrospectively. Data acquisition started February 1st 2017.

The validity of the transdiagnostic cognitive-behavioural model of eating disorders has been examined in adults, however there is limited examination in adolescents with eating disorders. The present study examined the direct and indirect relationships between eating disorder symptoms and the four maintaining processes: perfectionism, low core self-esteem, mood intolerance, and interpersonal difficulties. Using a correlational cross-sectional design, adolescents with eating disorders (N = 270; anorexia nervosa [restricting; 35.9%]; anorexia nervosa [binge purge; 8.1%]; bulimia nervosa [9.3%]; atypical anorexia nervosa [27.4%]; bulimia nervosa [of low frequency and/or limited duration; 3%]; purging [1.1%]; and unspecified feeding or eating disorders [15.2%]) completed measures of perfectionism, self-esteem, mood intolerance, interpersonal difficulties, and eating disorder symptoms as part of the intake assessment to an eating disorders program. Path analysis revealed that low self-esteem and mood intolerance were directly associated with eating disorder symptoms. Perfectionism was indirectly associated with eating disorder symptoms through self-esteem and mood intolerance. The findings provide partial support for the transdiagnostic model of eating disorders in an adolescent clinical sample. In particular, core low self-esteem and mood intolerance were found to be pertinent in adolescents with eating disorders. A limitation of the current study was the use of cross-sectional data. Future research should examine the transdiagnostic model with the use of longitudinal data. Furthermore, future research is required to examine potential differences in the way the maintaining mechanisms operate between adolescents and adults with eating disorders and the implications for treatment.

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 groups, including autistic people/ those with intellectual disability (ID), may become excluded from services. Methods: We reviewed policies from 15 European member states, published March-July 2020, pertaining to: 1) accessibility of COVID-19 testing; 2) provisions for treatment, hospitalisation and intensive care units (ICU); and 3) changes to standard health and social care. In parallel, we analysed survey data on the lived experiences of 1,301 autistic people and caregivers.Results: Autistic people/ those with ID experienced significant barriers accessing COVID-19 services. First, despite these groups being at elevated risk for severe illness due to co-morbid health conditions, there was a lack of access to COVID-19 testing. Second, many COVID-19 outpatient and inpatient treatment services were reported to be inaccessible - predominantly resulting from individual differences in communication needs. Third, ICU triage protocols (directly or indirectly) resulted in 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 emphasised healthcare inequalities for autistic people/ those with ID, likely contributing to disproportionate increases in morbidity and mortality in these groups. Current policies and guidelines regarding the accessibility of COVID-19 services require urgent revision to prevent the widespread exclusion of autistic people and those with ID from services, which represents a violation of international human rights law.

Abstract Automated systems for identifying and removing non-neural ICA components are growing in popularity among adult EEG researchers. Infant EEG data differs in many ways from adult EEG data, but there exists almost no specific system for automated classification of source components from paediatric populations. Here, we adapt one of the most popular systems for adult ICA component classification for use with infant EEG data. Our adapted classifier significantly outperformed the original adult classifier on samples of naturalistic free play EEG data recorded from 10 to 12-month-old infants, achieving agreement rates with the manual classification of over 75% across two validation studies (n=44, n=25). Additionally, we examined both classifiers ability to remove stereotyped ocular artifact from a basic visual processing ERP dataset, compared to manual ICA data cleaning. Here the new classifier performed on level with expert manual cleaning and was again significantly better than the adult classifier at removing artifact whilst retaining a greater amount of genuine neural signal, operationalised through comparing ERP activations in time and space. Our new system (iMARA) offers developmental EEG researchers a flexible tool for automatic identification and removal of artifactual ICA components.

This cohort study investigates whether N290 latency to faces vs nonfaces is associated with autism polygenic scores and cross-disorder polygenic scores in infants with and without a family history of autism.

Background: Autism Spectrum Disorder (ASD or autism) is characterized by difficulties in social communication and interaction, which negatively impact on individuals and their families' quality of life. Currently no pharmacological interventions have been shown to be effective for improving social communication in autism. Previous trials have indicated the potential of arbaclofen for improving social function among autistic children and adolescents with fluent speech. The AIMS2TRIALS-Clinical Trial 1 (AIMS-CT1) will examine whether arbaclofen is superior to placebo in improving social function and other secondary outcomes over 16 weeks, along with safety and tolerability profiles. Methods: AIMS-CT1 is an international, multi-site, double-blind, parallel group Phase II randomized clinical trial. It will include 130 males and females aged 5:0–17:11 years, with a diagnosis of ASD and fluent speech. Eligible participants will be randomized on a ratio of 1:1 for a 16-week treatment period. Medication will be titrated over 5 weeks. The primary outcome is the effect on social function from weeks 0 to 16 measured on the Socialization domain of the Vineland Adaptive Behavior Scales, 3rd edition TM . Secondary outcome measures include the CGI–S (Clinical Global Impression–Severity), CGI–I (Clinical Global Impression–Improvement), other areas of adaptive function, social communication and other autism symptoms, co-occurring behavior problems and health-related quality of life. Genetic and electrophysiological markers will be examined as potential stratifiers for treatment response. Exploratory novel digital technologies will also be used to measure change, examining simultaneously the validity of digital biomarkers in natural environments. The safety and tolerability of the drug will also be examined. Our protocol is very closely aligned with a parallel Canadian trial of 90 participants (ARBA Study, US NCT number: NCT03887676) to allow for secondary combined analyses. Outcomes will be compared using both an Intent-to-reat and Per Protocol approach. Discussion: The outcomes of this trial, combined with the parallel Canadian trial, will contribute to the evidence base for medications used to help social difficulties among young autistic individuals; demonstrate the capabilities of the AIMS-2-TRIALS network of academic centers to deliver clinical trials; and support future drug development. Clinical Trial Registration: EudraCT number: 2018-000942-21 and ClinicalTrials.gov registry number: NCT03682978. Currently under protocol v.7.2, dated 20.11.2020.

Abstract Electroencephalography (EEG) has substantial potential value for examining individual differences during early development. Current challenges in developmental EEG research include high dropout rates and low trial numbers, which may in part be due to passive stimulus presentation. Comparability is challenged by idiosyncratic processing pipelines. We present a novel toolbox (“ Braintools” ) that uses gaze‐contingent stimulus presentation and an automated processing pipeline suitable for measuring visual processing through low‐density EEG recordings in the field. We tested the feasibility of this toolbox in 61 2.5‐ to 4‐year olds, and computed test–retest reliability (1‐ to 2‐week interval) of event‐related potentials (ERP) associated with visual (P1) and face processing (N290, P400). Feasibility was good, with 52 toddlers providing some EEG data at the first session. Reliability values for ERP features were moderate when derived from 20 trials; this would allow inclusion of 79% of the 61 toddlers for the P1 and 82% for the N290 and P400. P1 amplitude/latency were more reliable across sessions than for the N290 and P400. Amplitudes were generally more reliable than latencies. Automated and standardized solutions to collection and analysis of event‐related EEG data would allow efficient application in large‐scale global health studies, opening significant potential for examining individual differences in development.

Abstract Low inhibitory control (IC) is sometimes associated with enhanced problem‐solving amongst adults, yet for young children high IC is primarily framed as inherently better than low IC. Here, we explore associations between IC and performance on a novel problem‐solving task, amongst 102 English 2‐ and 3‐year‐olds (Study 1) and 84 Swedish children, seen at 18‐months and 4‐years (Study 2). Generativity during problem‐solving was negatively associated with IC, as measured by prohibition‐compliance (Study 1, both ages, Study 2 longitudinally from 18‐months). High parent‐reported IC was associated with poorer overall problem‐solving success, and greater perseveration (Study 1, 3‐year‐olds only). Benefits of high parent‐reported IC on persistence could be accounted for by developmental level. No concurrent association was observed between problem‐solving performance and IC as measured with a Delay‐of‐Gratification task (Study 2, concurrent associations at 4‐years). We suggest that, for young children, high IC may confer burden on insight‐ and analytic‐aspects of problem‐solving.

Childhood trauma may confer risk for poorer adult health through changes in systemic inflammation. Emotion regulation may plausibly moderate associations between childhood trauma and adult psychological well-being, but it remains unclear whether moderation effects extend to differences in systemic inflammation. To examine whether childhood trauma and emotion regulation separately and interactively predict prospective changes in C-reactive protein (CRP) and interleukin-6 (IL-6) and whether biopsychosocial factors account for observed associations. Healthy midlife adults (N = 331) retrospectively reported on childhood trauma, current trait-level cognitive reappraisal and expressive suppression, and had their blood drawn. At baseline and then a median of 2.85 years later, 279 of the 331 participants had their blood drawn, body mass index calculated, and reported on health behaviours (smoking, sleep), psychological distress (perceived stress, depressive symptoms), and years of education. Childhood trauma predicted prospective increases in CRP (B = 0.004, p = 0.049), which were partially accounted for by differences in adiposity, psychological distress, and health behaviours. In contrast, cognitive reappraisal predicted prospective decreases in IL-6 (B = -0.007, p = 0.006), which were independent of biopsychosocial influences. Cognitive reappraisal further moderated the association between childhood trauma and prospective changes in IL-6 (B = -0.001, p = 0.012) such that childhood trauma predicted greater IL-6 increases but only among adults lower in cognitive reappraisal (B = 0.006, p = 0.007). There were no main or moderation effects of expressive suppression (ps > 0.05). Cognitive reappraisal may attenuate IL-6 changes over time and may moderate the prospective association between childhood trauma and systemic inflammation in midlife.

Abstract 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.

Subjective social status (SSS) refers to a person's perception of their social rank relative to others and is cross-sectionally linked to systemic inflammation independently of objective socioeconomic status.We test the extent to which SSS relates to multiyear changes in inflammation, or if associations differ by race or sex.Healthy adults (N = 331; 30-51 years) completed a baseline visit and 278 participants returned for a second visit 2.85 years later. At both visits, participants underwent a fasting blood draw and completed community (SSSC) and US (SSSUS) versions of the MacArthur Scale. Multiple linear regression analyses examined change in interleukin-6 (IL-6) and C-reactive protein (CRP) predicted by each type of SSS, adjusting for time between visits, sex, race, age, body mass index, smoking, baseline inflammation, and objective socioeconomic status. Additional analyses further adjusted for hopelessness and depressive symptoms. Interactions examined moderations by sex and race.Lower SSSC was longitudinally associated with greater IL-6 independently of all covariates, including education and income (β = -0.06), hopelessness (β = -0.06), and depressive symptoms (β = -0.06). Lower SSSUS was longitudinally associated with greater IL-6 independently of demographic covariates including education and income (β = -0.06), but was slightly attenuated after adjusting for hopelessness (β = -0.06) and depressive symptoms (β = -0.06). There were no associations for CRP or moderation by race or sex.Lower SSS may be associated with greater circulating markers of inflammation over time as suggested by increases in IL-6.Subjective social status (SSS) refers to how people perceive their social rank compared with others and has been linked to meaningful differences in physical health. Increases in inflammation may contribute to associations between lower SSS and poorer physical health. In a sample of healthy adults, we examined whether SSS was associated with prospective, multiyear changes in markers of systemic inflammation and if this differed by sex or race. We found that adults who perceived their social status as lower than peers in their community exhibited an accelerated increase in interleukin-6, a marker of systemic inflammation, over a 3-year period. When participants were asked to compare themselves to people in the broader USA, the pattern was similar but less robust. Results were independent of individual differences in sociodemographic characteristics including family-adjusted income and education. Findings did not differ by sex or race and were not explained by differences in adiposity and symptoms of depression and hopelessness. Effects for C-reactive protein, a second marker of inflammation, were generally nonsignificant. Although preliminary, findings suggest an immune pathway by which perceived social status may relate to chronic diseases of aging.

Neuroimaging analyses of brain structure and function in autism have typically been conducted in isolation, missing the sensitivity gains of linking data across modalities. Here we focus on the integration of structural and functional organisational properties of brain regions. We aim to identify novel brain-organisation phenotypes of autism. We utilised multimodal MRI (T1-, diffusion-weighted and resting state functional), behavioural and clinical data from the EU AIMS Longitudinal European Autism Project (LEAP) from autistic (n = 206) and non-autistic (n = 196) participants. Of these, 97 had data from 2 timepoints resulting in a total scan number of 466. Grey matter density maps, probabilistic tractography connectivity matrices and connectopic maps were extracted from respective MRI modalities and were then integrated with Linked Independent Component Analysis. Linear mixed-effects models were used to evaluate the relationship between components and group while accounting for covariates and non-independence of participants with longitudinal data. Additional models were run to investigate associations with dimensional measures of behaviour. We identified one component that differed significantly between groups (coefficient = 0.33, padj = 0.02). This was driven (99%) by variance of the right fusiform gyrus connectopic map 2. While there were multiple nominal (uncorrected p < 0.05) associations with behavioural measures, none were significant following multiple comparison correction. Our analysis considered the relative contributions of both structural and functional brain phenotypes simultaneously, finding that functional phenotypes drive associations with autism. These findings expanded on previous unimodal studies by revealing the topographic organisation of functional connectivity patterns specific to autism and warrant further investigation.

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.

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.

Abstract 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.

<ns3:p><ns3:bold>Background</ns3:bold>: Measurement of social and cognitive brain development using electroencephalography (EEG) offers the potential for early identification of children with elevated risk of developmental delay. However, there have been no published reports of how acceptable EEG technology is to parents and children within communities, especially in low-resource contexts such as in low and middle income countries (LMICs), which is an important question for the potential scalability of these assessments. We use a mixed-methods approach to examine whether EEG assessments are acceptable to children and their caregivers in a low resource community setting in India. <ns3:bold>Methods</ns3:bold>: We assessed the acceptability of neurophysiology research and <ns3:italic>Braintools</ns3:italic> (a novel neurodevelopmental assessment toolkit using concurrent EEG and eye-tracking technology) using: 1) a child engagement measure, 2) interviews with caregivers (n=8); 3) survey about caregiver’s experience (n=36). Framework analysis was used to analyse interview data. <ns3:bold>Results</ns3:bold>: A high level of child engagement in EEG tasks was demonstrated, with children’s gaze at the screen during the task averaging at 85.4% (±12.06%) of the task time. External distractions and noise during the tasks were measured, but not found to significantly effect child’s attention to the screen during EEG tasks. Key topics were examined using the framework analysis: 1) parental experience of the assessment; and 2) the acceptability of research. From topic 1, four sub-themes were identified: i) caregivers’ experience of the assessment, ii) caregivers’ perception of child's experience of assessment, iii) logistical barriers and facilitators to participation, and iv) recommendations for improvement. Results from interviews and the survey indicated acceptability for gaze-controlled EEG research for parents and children. From topic 2, three themes were identified: i) caregivers' understanding of the research, ii) barriers to participation, and iii) facilitators to participation. Barriers to participation mainly included logistical challenges, such as geographic location and time, whereas involvement of the wider family in decision making was highlighted as an important facilitator to partake in the research. <ns3:bold>Conclusions</ns3:bold>: We demonstrate for the first time the acceptability of conducting neurodevelopmental assessments using concurrent EEG and eye-tracking in preschool children in uncontrolled community LMIC settings. This kind of research appears to be acceptable to the community and we identify potential barriers and facilitators of this research, thus allowing for future large scale research projects to be conducted investigating neurodevelopment and risk factors for suboptimal development in LMICs.</ns3:p>

Background It is unclear how adverse childhood family environments differentially impact adult health outcomes among men and women. This brief communication reports on the independent and joint effects of adverse childhood family environments and sex on indicators of health in adulthood. Methods & Results 213 18-55-year olds reported on their childhood family environment (Risky Families Questionnaire (RFQ); Family Environment Scale (FEStotal)) and their current perceived stress and depressive and anxious affect. Resting systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) were taken during a laboratory visit, and total cortisol output was measured in saliva samples collected at home. Exposure to childhood adversity did not vary by sex. Women had lower SBP, DBP, and total cortisol output, but higher HR, than men (ps < .05). Sex moderated the association between childhood family environment and SBP (RFQ: B = -.316; SE = .120; p = .009; FEStotal: B = -.274; SE = .117; p = .021) and DBP (FEStotal: B = -.193; SE = .094; p = .041), such that exposure to greater childhood adversity was linked to lower BP in women only. Results were largely unchanged after adjusting for concurrent perceived stress and depressive and anxious affect. Separate effects of individual FES subscales are also discussed. Conclusions Contrary to expectations, exposure to adverse childhood family environments was associated with lower resting BP among women, perhaps indicative of basal cardiovascular hypoactivation, whereas early adversity was not linked to BP among men.

Visual attention plays a key role in infants’ interaction with the environment, and shapes their behavioral and brain development. As such, early problems with flexibly switching gaze from one stimulus to another (visual disengagement) have been hypothesized to lead to developmental difficulties (e.g. joint attention and social skills) over time. This study aimed to identify cross-sectional associations between performance in the Gap task (gaze shift latencies and visual attention disengagement) and measures of development and adaptive behavior in conjunction to any sex or socioeconomic status effects in infancy. We measured visual attention disengagement in 436 5-month-old infants and calculated its association with cognitive developmental level, adaptive behaviours, socioeconomic status (SES) and biological sex. In the Gap task, participants must redirect their gaze from a central stimulus to an appearing peripheral stimulus. The three experimental conditions of the task (Gap, Baseline and Overlap) differ on the timepoint when the central stimuli disappears in relation to the appearance of the peripheral stimulus: 200 ms before the peripheral stimulus appears (Gap), simultaneously to its appearance (Baseline), or with peripheral stimulus offset (Overlap). The data from the experimental conditions showed the expected pattern, with average latencies being the shortest in the Gap and longest in the Overlap condition. Females were faster (p = .004) than males in the Gap condition, which could indicate that arousal-related effects differ as a function of biological sex. Infants from higher SES were slower (p = .031) in the Overlap condition compared to lower SES infants. This suggests that basic visual attention may differ by socio-cultural background, and should be considered when studying visual attention and its developmental correlates. We observed no significant association to concurrent developmental level or adaptive function. Given its large sample size, this study provides a useful reference for future studies of visual disengagement in early infancy.

Human faces are one of the most prominent stimuli infants in the visual environment of young infants and convey critical information for the development of social cognition. During the COVID-19 pandemic, mask wearing has become a common practice outside the home environment. With masks covering nose and mouth regions, the facial cues available to the infant are impoverished. The impact of these changes on development is unknown, but is critical to debates around mask mandates in early childhood settings. As infants grow, they increasingly interact with a broader range of familiar and unfamiliar people outside the home; in these settings, mask wearing could possibly influence social development. In order to generate hypotheses about the effects of mask wearing on infant social development, in the present work we systematically review N=129 studies selected based on the most recent PRISMA guidelines providing a state-of-the-art framework of behavioural studies investigating face processing in early infancy. We focused on identifying sensitive periods during which being exposed to specific facial features or to the entire face configuration has been found to be important for the development of perceptive and socio-communicative skills. For perceptive skills, infants gradually learn to analyze the eyes or the gaze direction within the context of the entire face configuration. This contributes to identity recognition as well as emotional expression discrimination. For socio-communicative skills, direct gaze and emotional facial expressions are crucial for attention engagement while eye-gaze cuing is important for joint attention. Moreover, attention to the mouth is particularly relevant for speech learning. We discuss possible implications of the exposure to masked faces for developmental needs and functions. Providing groundwork for further research, we encourage the investigation of the consequences of mask-wearing for infants’ perceptive and socio-communicative development, suggesting new directions within the research field.

Metabolic pathways underlying brain function remain largely unexplored during neurodevelopment, predominantly due to the lack of feasible techniques for use with awake infants. Broadband near-infrared spectroscopy (bNIRS) provides the opportunity to explore the relationship between cerebral energy metabolism and blood oxygenation/haemodynamics through the measurement of changes in the oxidation state of mitochondrial respiratory chain enzyme cytochrome-c-oxidase (ΔoxCCO) alongside haemodynamic changes. We used a bNIRS system to measure ΔoxCCO and haemodynamics during functional activation in a group of 42 typically developing infants aged between 4 and 7 months. bNIRS measurements were made over the right hemisphere over temporal, parietal and central cortical regions, in response to social and non-social visual and auditory stimuli. Both ΔoxCCO and Δ[HbO 2 ] displayed larger activation for the social condition in comparison to the non-social condition. Integration of haemodynamic and metabolic signals revealed networks of stimulus-selective cortical regions that were not apparent from analysis of the individual bNIRS signals. These results provide the first spatially resolved measures of cerebral metabolic activity alongside haemodynamics during functional activation in infants. Measuring synchronised changes in metabolism and haemodynamics have the potential for uncovering the development of cortical specialisation in early infancy.

Abstract Background First-generation college students (“first-gens”) are often at a disadvantage socially and academically; whether they are at risk physiologically is unknown despite the well-established link between greater education and better long-term health. Purpose To examine whether first-gens have higher levels of cardiovascular disease (CVD) risk markers relative to continuing-generation college students (“continuing-gens”). Methods A panel of CVD risk markers was assessed among 87 emerging adults (41 first-gens) twice over their first year of college. Results Compared to continuing-gens, first-gens had greater systemic inflammation (composite of averaged z-scores for C-reactive protein and interleukin-6; B = 0.515, SE = 0.171, p = .003) during the fall but not spring semester (p &amp;gt; .05). Associations were independent of family home ownership and childhood adversity, even though first-gens were more likely to live in rental homes and reported riskier home environments. Lower childhood subjective social status (SSS) accounted for greater systemic inflammation among first-gens as evidenced by an indirect effect of college generation status on systemic inflammation through childhood SSS (a1b1 = 0.261, bootstrapped SE = 0.103, 95% boot CI [0.078, 0.482]). There were no differences in metabolic risk and latent virus regulation by college generation status in either semester (p &amp;gt; .10). Conclusions This is the first study to find that first-gens have higher levels of systemic inflammation than continuing-gens following the college transition and that childhood SSS may be one explanatory pathway. First-gens may benefit from university resources that address social class differences, which should be provided early on so that first-gens can reap the health-relevant benefits of higher education, at least in the short term.

Abstract Temporal coordination during infant-caregiver social interaction is thought to be crucial for supporting early language acquisition and cognitive development. Despite a growing prevalence of theories suggesting that increased inter-brain synchrony associates with many key aspects of social interactions such as mutual gaze, little is known about how this arises during development. Here, we investigated the role of mutual gaze onsets as a potential driver of inter-brain synchrony. We extracted dual EEG activity around naturally occurring gaze onsets during infant-caregiver social interactions in N=55 dyads (mean age 12 months). We differentiated between two types of gaze onset, depending on each partners’ role. ‘Sender’ gaze onsets were defined at a time when either the adult or the infant made a gaze shift towards their partner at a time when their partner was either already looking at them (mutual) or not looking at them (non-mutual). ‘Receiver’ gaze onsets were defined at a time when their partner made a gaze shift towards them at a time when either the adult or the infant was already looking at their partner (mutual) or not (non-mutual). Contrary to our hypothesis we found that, during a naturalistic interaction, both mutual and non-mutual gaze onsets were associated with changes in the sender, but not the receiver’s brain activity and were not associated with increases in inter-brain synchrony above baseline. Further, we found that mutual, compared to non-mutual gaze onsets were not associated with increased inter brain synchrony. Overall, our results suggest that the effects of mutual gaze are strongest at the intra-brain level, in the ‘sender’ but not the ‘receiver’ of the mutual gaze.

To examine the trajectories of cognitive, motor and behavioural development in infants with NF1 compared to infants without a family history of neurodevelopmental difficulties.Infants with NF1 and low-risk controls were recruited from 5 months of age and followed longitudinally. Data from standardised tests was gathered at 5, 10 and 14 months and developmental trajectories of motor, language, behaviour, sleep, social development and parent-infant interaction were examined. Linear mixed modelling was used to estimate group differences in cognitive and behavioural measures over time.No group differences were observed on Mullen Scale of Early Learning, overall adaptive functioning, temperament or behavioural measures. There were no group differences observed on measures of social communication or parent-infant interaction. Over the course of development, the NF1 group slept less and took more time to settle to sleep as compared to the control group. Maternal education was significantly associated with cognitive and behavioural developmental outcomes in both groups.Cognitive, social and behavioural impairments are a cause of significant functional morbidity in children with NF1. This report is the first study to investigate the trajectories of cognitive, motor and behavioural development in infancy in NF1. Our results demonstrate that overall cognitive and behavioural developmental trajectories of the NF1 group in the infancy period are similar to controls. Given previous reports of delayed development in the NF1 cohort by 40 months, early clinical interventions strategies to promote sleep hygiene may be beneficial to optimise developmental outcomes.

Objective: It remains unclear whether an anxiety diagnosis is associated with children's emotional recognition. We considered children's age and types of primary anxiety diagnosis, which have been neglected, to elucidate this relationship. Methods: Sixty-three referred children with anxiety disorder(s) and 59 volunteer children without anxiety disorder(s), aged between 6 and 11 years, were presented with animated characters, displaying a range of simple and complex emotions, for identification. Statistical analyses examined identification accuracy based on presence or absence of anxiety disorder, age, and types of primary diagnoses. Results: Children with anxiety disorder(s) as a group performed comparably to children without anxiety disorder(s) in identifying emotions ( z = −0.72, P = 0.47). In both groups, accuracy for disgust increased significantly each year of age ([anxiety group] OR 2.6; 95% CI 1.6 to 4.3, P &lt; 0.001, [control group] OR 2.1; 95% CI 1.3 to 3.3, P = 0.002). When primary anxiety types were considered, while controlling for age, children with separation anxiety disorder (SAD) showed deficits in overall emotional recognition, compared with children with other subtypes or without anxiety ( P = 0.004). Further regression analyses showed that children with generalized anxiety disorder (GAD) presented significantly lower accuracy than children without anxiety disorder(s) at a young age, but the deficit disappeared with increased age. Conclusion: Children with anxiety disorder(s) as a group may not appear to be impaired in emotional recognition. However, when age and subtypes are considered, children with SAD and young children with GAD appear to have difficulty, compared with children without anxiety disorder(s).

We sought to evaluate a translation of anxiety-focused cognitive behavioral therapy (CBT) to a First Nations children's mental health provider in rural Ontario and to enhance our understanding of CBT challenges and adaptations unique to the First Nations context.The study was conceptualized as a mixed methods sequential explanatory approach using a quasi-experimental (before and after) design with quantitative and qualitative components. Data were produced in two ways: questionnaires completed by therapists, parents and clients pre- and post-training, and through a focus group with therapists working with First Nations clients. Participants of this study were a subset of a larger knowledge translation study involving ten agencies, and comprised nine therapists (two males and seven females), and seven children (six males and one female) from a single First Nations agency. The mean age of children was 11.8 years (±2.71), comparable to children in other agencies.First Nations therapists' scores on a child CBT knowledge questionnaire post-training did not differ from those of therapists in other agencies when controlling for initial values, suggesting comparable training benefit. Children did not differ between groups on any key measures, and all key measures showed improvement from pre- to post-training. Four key themes emerged from therapist focus groups: client challenges, value of supervision, practice challenges, and Northern/rural/remote challenges.The study highlights the importance of delivering a culturally appropriate CBT program to First Nations populations in Northern Ontario, and provides preliminary evidence of its effectiveness.Nous avons cherché à évaluer une adaptation de la thérapie cognitivo-comportementale (TCC) axée sur l’anxiété pour un prestataire de soins de santé mentale aux enfants des Premières nations en région rurale de l’Ontario, et à accroître notre compréhension des problèmes et des adaptations de la TCC propres au contexte des Premières nations.L’étude a été conceptualisée comme une approche de méthodes mixtes séquentielles explicatives à l’aide d’un devis quasi-expérimental (avant et après) avec des composantes quantitatives et qualitatives. Les données ont été produites de deux manières: des questionnaires remplis par les thérapeutes, les parents et les clients avant et après la formation, et à l’aide d’un groupe de discussion formé des thérapeutes travaillant avec les clients des Première nations. Les participants à cette étude étaient un sous-ensemble d’une étude plus vaste du transfert des connaissances comportant dix organismes et composée de neuf thérapeutes (deux masculins et sept féminins), et sept enfants (six garçons et une fille) d’un seul organisme des Premières nations. L’âge moyen des enfants était de 11,8 ans (±2,71), comparable aux enfants d’autres organismes.Les scores des thérapeutes des Premières nations à un questionnaire sur les connaissances de la TCC après la formation ne différaient pas de ceux des thérapeutes d’autres organismes, après contrôle des valeurs initiales, ce qui suggère des avantages comparables de la formation. Les enfants ne différaient pas entre les groupes à aucune des mesures clés, et toutes les mesures clés montraient une amélioration entre avant et après la formation. Quatre thèmes principaux se sont dégagés des groupes de discussion des thérapeutes: les problèmes des clients, la valeur de la supervision, les problèmes organisationnels, et les problèmes des régions nordiques/rurales/ éloignées.L’étude souligne l’importance d’exécuter un programme de TCC culturellement adapté aux populations des Premières nations du nord de l’Ontario, et fournit des données probantes préliminaires de son efficacité.

Objective: To examine prospective associations between physical and mental self-rated health (SRH), college generation status and college adjustment among first-year college students. Participants and methods: Eighty-seven first-year college students (41 first-generation college students) reported their SRH when starting college, and then, reported on psychosocial and academic adjustment and health behaviors midway through each semester. Results: Better physical and mental SRH were associated with better psychosocial adjustment in both semesters and academic adjustment in the fall but were generally not predictive of health behaviors. Specifically, better physical SRH was associated with less loneliness (fall: B = -.192, p = .048; spring: B = -.233, p = .008) and fewer anxiety symptoms in both semesters (fall: B = -.236, p = .011; spring: B = -.210, p = .014) and fewer depressive symptoms (fall: B = -.134, p = .016) and more fall semester credits (B = .965, p = .002). Better mental SRH was associated with greater sense of belonging (fall: B = .317, p < .001; spring: B = .242, p = .009), less loneliness (fall: -.210, p = .008; spring: B = -.181, p = .012), and fewer anxiety symptoms (fall: -.193, p = .011; spring: -.195, p = .006) in both semesters and higher fall semester grade point average (B = .129, p = .032). Independent effects of physical and mental SRH are also discussed. Largely, college generation status did not matter for college adjustment within this sample. Conclusions: Physical and mental SRH when starting college may be important indicators of psychosocial adjustment over the first year and academic adjustment in the fall.

Data from 213 adults were analysed to test the stress accumulation and stress sensitization models as they relate to daily mood, health behaviours and social interactions. Adults reported on childhood adversity, past year adversity, and daily experiences on 14 evenings. Results largely supported the stress accumulation and not stress sensitization model such that childhood and past year adversity had independent but not synergistic effects on daily experiences. Both adversity measures were independently associated with greater daily negative affect and negative affect variability. Childhood adversity independently associated with greater mean variability in daily positive affect. Past year adversity was associated with more daily social activities, greater odds of reporting interpersonal tension at least once, and daily tension. Although childhood adversity was associated with greater odds of sharing about one's day at least once, past year adversity was associated with more daily sharing and childhood adversity with less. Both measures were unrelated to daily health behaviours except childhood adversity was associated with lower odds of being a current drinker. The only support for the stress sensitization model was number of daily cigarettes among smokers. Our findings suggest childhood and recent adversity independently relate to adults' daily experiences and should be considered jointly.

It remains unclear whether an anxiety diagnosis is associated with children's emotional recognition. We considered children's age and types of primary anxiety diagnosis, which have been neglected, to elucidate this relationship.Sixty-three referred children with anxiety disorder(s) and 59 volunteer children without anxiety disorder(s), aged between 6 and 11 years, were presented with animated characters, displaying a range of simple and complex emotions, for identification. Statistical analyses examined identification accuracy based on presence or absence of anxiety disorder, age, and types of primary diagnoses.Children with anxiety disorder(s) as a group performed comparably to children without anxiety disorder(s) in identifying emotions (z = -0.72, P = 0.47). In both groups, accuracy for disgust increased significantly each year of age ([anxiety group] OR 2.6; 95% CI 1.6 to 4.3, P < 0.001, [control group] OR 2.1; 95% CI 1.3 to 3.3, P = 0.002). When primary anxiety types were considered, while controlling for age, children with separation anxiety disorder (SAD) showed deficits in overall emotional recognition, compared with children with other subtypes or without anxiety (P = 0.004). Further regression analyses showed that children with generalized anxiety disorder (GAD) presented significantly lower accuracy than children without anxiety disorder(s) at a young age, but the deficit disappeared with increased age.Children with anxiety disorder(s) as a group may not appear to be impaired in emotional recognition. However, when age and subtypes are considered, children with SAD and young children with GAD appear to have difficulty, compared with children without anxiety disorder(s).Objectif : Il n’est pas encore déterminé si un diagnostic d’anxiété est associé à la reconnaissance émotionnelle des enfants. Nous avons pris en compte l’âge des enfants et les types des diagnostics d’anxiété primaires, qui ont été négligés pour éclaircir cette relation. Méthodes : Soixante-trois enfants référés souffrant de trouble(s) anxieux et 59 enfants volontaires sans trouble(s) anxieux, âgés entre 6 et 11 ans, se sont fait présenter des personnages animés, qui affichaient une gradation d’émotions simples et complexes, aux fins d’identification. Des analyses statistiques ont examiné l’exactitude de l’identification d’après la présence ou l’absence de trouble anxieux, l’âge, et les types des diagnostics primaires. Résultats : Comme groupe, les enfants souffrant de trouble(s) anxieux ont eu un rendement comparable à celui des enfants sans trouble(s) anxieux pour identifier les émotions (z = –0,72; P = 0,47). Dans les deux groupes, l’exactitude de l’identification du dégoût augmentait significativement à chaque âge ([groupe anxieux] RC 2,6; IC à 95 % 1,6 à 4,3; P < 0,001, [groupe témoin] RC 2,1; IC à 95 % 1,3 à 3,3; P = 0,002). Lorsque les types d’anxiété primaires étaient examinés, en contrôlant l’âge, les enfants souffrant du trouble d’anxiété de séparation (TAS) présentaient des déficits de reconnaissance émotionnelle générale, comparativement aux enfants souffrant d’autres sous-types ou sans anxiété (P = 0,004). Des analyses de régression ont indiqué, les enfants souffrant du trouble d’anxiété généralisée (TAG) présentaient une exactitude significativement plus faible que les enfants sans trouble(s) anxieux à un jeune âge, mais le déficit s’estompait avec l’âge. Conclusion : Comme groupe, les enfants souffrant de trouble(s) anxieux peuvent ne pas sembler être déficients en matière de reconnaissance émotionnelle. Cependant, lorsque l’âge et les sous-types sont pris en compte, les enfants souffrant de TAS et les jeunes enfants souffrant de TAG semblent éprouver des difficultés, comparativement aux enfants sans trouble(s) anxieux.

<ns3:p><ns3:bold>Background</ns3:bold>: Measurement of social and cognitive brain development using electroencephalography (EEG) offers the potential for early identification of children with elevated risk of developmental delay. However, there have been no published reports of how acceptable EEG technology is to parents and children within communities, especially in low-resource contexts such as in low and middle income countries (LMICs), which is an important question for the potential scalability of these assessments. We use a mixed-methods approach to examine whether EEG assessments are acceptable to children and their caregivers in a low resource community setting in India.</ns3:p><ns3:p> <ns3:bold>Methods</ns3:bold>: We assessed the acceptability of neurophysiology research and <ns3:italic>Braintools</ns3:italic> (a novel neurodevelopmental assessment toolkit using concurrent EEG and eye-tracking technology) using: 1) a child engagement measure, 2) interviews with caregivers (n=8); 3) survey about caregiver’s experience (n=36). Framework analysis was used to analyse interview data.</ns3:p><ns3:p> <ns3:bold>Results</ns3:bold>: Key topics were examined using the framework analysis: 1) parental experience of the assessment; and 2) the acceptability of research. From topic 1, four sub-themes were identified: i) caregivers’ experience of the assessment, ii) caregivers’ perception of child's experience of assessment, iii) logistical barriers and facilitators to participation, and iv) recommendations for improvement. From topic 2, three themes were identified: i) caregivers' understanding of the research, ii) barriers to participation, and iii) facilitators to participation.</ns3:p><ns3:p> <ns3:bold>Conclusions</ns3:bold>: We demonstrate for the first time the acceptability of conducting neurodevelopmental assessments using concurrent EEG and eye-tracking in preschool children in uncontrolled community LMIC settings. This kind of research appears to be acceptable to the community and we identify potential barriers and facilitators of this research, thus allowing for future large scale research projects to be conducted investigating neurodevelopment and risk factors for suboptimal development in LMICs.</ns3:p>

Sleep problems in Autism Spectrum Disorder (ASD) emerge early in development, yet the origin remains unclear. Here, we characterise developmental trajectories in sleep onset latency (SOL) and night awakenings in infants at elevated likelihood (EL) for ASD (who have an older sibling with ASD) and infants at typical likelihood (TL) for ASD. Further, we test whether the ability to gate tactile input, using an EEG tactile suppression index (TSI), associates with variation in SOL and night awakenings. Parent-reported night awakenings and SOL from 124 infants (97 at EL for ASD) at 5, 10 and 14 months were analyzed using generalized estimating equations. Compared to TL infants, infants at EL had significantly more awakenings and longer SOL at 10 and 14 months. The TSI predicted SOL concurrently at 10 months, independent of ASD likelihood status, but not longitudinally at 14 months. The TSI did not predict night awakenings concurrently or longitudinally. These results imply that infants at EL for ASD wake up more frequently during the night and take longer to fall asleep from 10 months of age. At 10 months, sensory gating predicts SOL, but not night awakenings, suggesting sensory gating differentially affects neural mechanisms of sleep initiation and maintenance.

An in‐depth clinical evaluation of ten anorexia nervosa patients and their families is reported. Structural and process pathology found in common within all ten family systems is analysed according to “systems” criteria. A model is constructed in which anorexia nervosa is seen as a compromise solution for three primary, conflicting pathological processes which are identified as “the idealised family myth”, “an enmeshed family dyad” and “a process barrier within the patient”. It is the view of the authors that this model may have significant implications both for diagnosis and therapy.

Binge eating and purging profiles may vary in adolescents with eating disorders and this may potentially be a function of a range of cognitive and behavioural constructs. The aim was to determine whether cognitive and behavioural symptoms differed among purging profiles in 229 adolescent females (M age = 15.45). Differences were examined in three binge/purge profiles; (i) regular objective binge eating and purging (OBEP, n = 63), (ii) regular subjective binge eating and purging (SBEP, n = 41), and (iii) purging in the absence of any binge eating (P-noBE, n = 110). Adolescents with objective or subjective binge eating had significantly higher global eating disorder scores and eating, shape, and weight concerns than those without binge eating, but not more frequent compensatory behaviours. There were no significant differences on dietary restraint. The group with objective binge eating (OBEP) had significantly higher eating concerns and self-induced vomiting than adolescents with subjective binge eating (SBEP). Future research is required to understand the reasons for elevated symptoms in the OBE-P group, since the size of binge episodes is not thought to be a salient factor in binge eating. In contrast to the literature, we did not find support for a special relevance of dietary restraint to the purging only presentation (P-noBE), rather it was a universal characteristic of all binge/purge presentations. Eating concerns may be an important target in adolescents with objective binge symptoms. Future research should examine if treatment targeted at different binge/purge profiles improves efficacy of treatment in adolescents.

Abstract Background. There is considerable evidence reporting an excitatory/inhibitory (E/I) cortical imbalance in autism spectrum disorders (ASD). However, previous findings on the direction of this imbalance and its relationship to ASD symptomatology are heterogeneous. Some factors contributing to these mixed results might be the methodological differences between studies assessing the E/I ratio and the intrinsic variability within the autistic spectrum. Studying the evolution of ASD symptoms and the factors that modulate it might help to explain and reduce this variability. Here we present a study protocol to explore the longitudinal role of E/I imbalance in ASD symptoms, combining different approaches to measure the E/I ratio and using the trajectories of symptom severity as a framework. Methods. This observational two time-point prospective study assesses the E/I ratio and the evolution of the behavioural symptoms in a sample of at least 98 participants with ASD. Participants are enrolled at 12 to 72 months of age and followed from 18 to 48 months after. A comprehensive battery of tests is applied to evaluate ASD clinical symptoms. The E/I ratio is approached from electrophysiology, magnetic resonance, and genetics. We will calculate the individual change for the main ASD symptoms and, based on that, we will define the trajectories of symptom severity. Then, we will investigate the correlation between measures of excitation/inhibition balance and autistic symptomatology cross-sectionally, as well as the ability of these measurements to predict changes in symptoms over time. Discussion. This study presents a robust multisystemic approach to the E/I imbalance theory in autism and its relation to divergent symptom trajectories. That setting will allow us to relate and compare the neurobiological information coming from different sources and its impact on behavioural symptoms while accounting for the high variability in ASD. The findings derived from this study could contribute to the ASD biomarkers research and might provide valuable evidence for the development of more personalized treatments in ASD.

Abstract Background There is considerable evidence reporting an excitatory/inhibitory (E/I) cortical imbalance in autism spectrum disorders (ASD). However, previous findings on the direction of this imbalance and its relationship to ASD symptomatology are heterogeneous. Some factors contributing to these mixed results might be the methodological differences between studies assessing the E/I ratio and the intrinsic variability within the autistic spectrum. Studying the evolution of ASD symptoms and the factors that modulate it might help to explain and reduce this variability. Here we present a study protocol to explore the longitudinal role of E/I imbalance in ASD symptoms, combining different approaches to measure the E/I ratio and using the trajectories of symptom severity as a framework. Methods This observational two time-point prospective study assesses the E/I ratio and the evolution of the behavioural symptoms in a sample of at least 98 participants with ASD. Participants are enrolled at 12 to 72 months of age and followed from 18 to 48 months after. A comprehensive battery of tests is applied to evaluate ASD clinical symptoms. The E/I ratio is approached from electrophysiology, magnetic resonance, and genetics. We will calculate the individual change for the main ASD symptoms and, based on that, we will define the trajectories of symptom severity. Then, we will investigate the correlation between measures of excitation/inhibition balance and autistic symptomatology cross-sectionally, as well as the ability of these measurements to predict changes in symptoms over time. Discussion This study presents a robust multisystemic approach to the E/I imbalance theory in autism and its relation to divergent symptom trajectories. That setting will allow us to relate and compare the neurobiological information coming from different sources and its impact on behavioural symptoms while accounting for the high variability in ASD. The findings derived from this study could contribute to the ASD biomarkers research and might provide valuable evidence for the development of more personalized treatments in ASD.

The capacity to pay attention underpins all subsequent cognitive development. However, we understand little about how attention control is instantiated in the developing brain in real-world settings. We recorded naturalistic attention patterns, together with autonomic arousal and brain activity, in 5- and 10-month-old infants during free play. We examined whether changes in autonomic arousal and brain activity associate with changes in moment-by-moment attentional engagement, and whether they anticipate attention changes, or follow on from them. Early in infancy, slow-varying fluctuations in autonomic arousal forward-predicted attentional behaviours. Later in infancy, fluctuations in fronto-central theta power after but not before an attentional shift associated with changes in infants’ attentiveness, predicted the length of infants’ attention durations and modulated changes in arousal. Together, our results suggest that the modulation of real-world attention involves both arousal-based and cortical processes and what changes with developmental time is how these lower- and higher-order endogenous factors modulate real-world attention. As attentional systems mature, stronger associations emerge between attentional behaviour, cortical activity, and autonomic arousal.

The transition to parenthood is a common yet stressful experience faced by many young and midlife adults, and the risk of cardiometabolic conditions also begins to rise at this time. Consequently, parenthood represents an opportune time to intervene with adults to support their psychological and physical health. We examined whether the benefits of the Family Foundations program, a perinatal preventative intervention promoting positive coparenting, extend beyond documented mental health and family relationship outcomes to better cardiometabolic risk factors among parents. We analyzed data from 183 couples (n = 366 participants) who, eight years prior, were randomly assigned to the 9-session perinatal preventative intervention program or a control condition. We collected dried blood spots to measure C-reactive protein (CRP), interleukin-6 (IL-6), and cholesterol; parents also reported on their self-rated health. Randomization to the intervention condition was associated with lower cholesterol (B=−.081, p = .049). Among parents who demonstrated more negative communication styles at pretest (during pregnancy), the intervention was further associated with better self-rated health (B=.181, p = .018). Participation in the intervention program was also marginally associated with lower CRP (B=−.261, p = .077), particularly among mothers (B=−.428, p = .076). These findings indicate that coparenting-focused interventions, such as Family Foundations, can lead to benefits beyond psychosocial and behavioral outcomes, and suggest that Family Foundations may improve parents’ longer-term physical health, with potentially more benefits among couples who demonstrated more negative communication styles during pregnancy.

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 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 to 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 behaviours.

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.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.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.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.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).

Abstract Objective This prospective cohort study examines the cognitive, behavioural, ADHD trait and autism symptom development in infant and pre-school children with Neurofibromatosis 1 (NF1) compared with typically developing (TD) children without a family history of neurodevelopmental conditions. Methods Data from standardised tests was gathered at 5, 10, 14, 24 and 36 months of age (NF1 n=35, TD n=29). Developmental trajectories of cognitive and adaptive behavioural development from 5 to 36 months were analysed using linear mixed modelling. Measures of ADHD and autism traits were assessed at 24 and 36 months. Results The developmental trajectory of cognitive skills (all domains of the Mullen Scales of Early Learning -MSEL) and behavioural skills (four domains of the Vineland Adaptive Behaviour Scale -VABS) differed significantly between NF1 and TD groups. Post-hoc tests demonstrated that the NF1 participants scored significantly lower than TD participants at 24 months on all MSEL and VABS domains. The NF1 cohort demonstrated higher mean autism and ADHD traits at 24 months and 14% of the NF1 cohort met a research diagnostic classification for autism at 36 months. Conclusion By 24 months of age, the NF1 cohort show lower cognitive skills and adaptive behaviour and higher levels of autism and ADHD traits as compared to TD children.

The capacity to pay attention underpins all subsequent cognitive development. However, we understand little about how attention control is instantiated in the developing brain in real-world settings. We recorded naturalistic attention patterns, together with autonomic arousal and brain activity, in 5- and 10-month-old infants during free play. We examined whether changes in autonomic arousal and brain activity associate with changes in moment-by-moment attentional engagement, and whether they anticipate attention changes, or follow on from them. Early in infancy, slow-varying fluctuations in autonomic arousal forward-predicted attentional behaviours. Later in infancy, fluctuations in fronto-central theta power after but not before an attentional shift associated with changes in infants’ attentiveness, predicted the length of infants’ attention durations and modulated changes in arousal. Together, our results suggest that the modulation of real-world attention involves both arousal-based and cortical processes and what changes with developmental time is how these lower- and higher-order endogenous factors modulate real-world attention. As attentional systems mature, stronger associations emerge between attentional behaviour, cortical activity, and autonomic arousal.

The capacity to pay attention underpins all subsequent cognitive development. However, we understand little about how attention control is instantiated in the developing brain in real-world settings. We recorded naturalistic attention patterns, together with autonomic arousal and brain activity, in 5- and 10-month-old infants during free play. We examined whether changes in autonomic arousal and brain activity associate with changes in moment-by-moment attentional engagement, and whether they anticipate attention changes, or follow on from them. Early in infancy, slow-varying fluctuations in autonomic arousal forward-predicted attentional behaviours. Later in infancy, fluctuations in fronto-central theta power after but not before an attentional shift associated with changes in infants’ attentiveness, predicted the length of infants’ attention durations and modulated changes in arousal. Together, our results suggest that the modulation of real-world attention involves both arousal-based and cortical processes and what changes with developmental time is how these lower- and higher-order endogenous factors modulate real-world attention. As attentional systems mature, stronger associations emerge between attentional behaviour, cortical activity, and autonomic arousal.

Cognitive ability is a key factor that contributes to individual differences in life trajectories. Identifying early neural indicators of later cognitive ability may enable us to better elucidate the mechanisms that shape individual differences, eventually aiding identification of infants with an elevated likelihood of less optimal outcomes. A previous study associated a measure of neural activity (theta EEG) recorded at 12-months with nonverbal cognitive ability at ages two, three and seven in individuals with older siblings with autism (Jones et al., under review). In a pre-registered study (https://osf.io/v5xrw/), we replicate and extend this finding in a younger, low-risk infant sample. EEG was recorded during presentation of a non-social video to a cohort of 6-month-old infants and behavioural data was collected at 6- and 9-months-old. Initial analyses replicated the finding that frontal theta power increases over the course of video viewing, extending this to 6-month-olds. Further, individual differences in the magnitude of this change significantly predicted non-verbal cognitive ability measured at 9-months, but not early executive function. EEG theta change at 6-months-old may therefore be an early indicator of later cognitive ability. This could have important implications for identification of, and interventions for, children at risk of poor cognitive outcomes.

Abstract The implications of the substantial individual differences in infant sleep for early brain development remain unclear. Here, we examined whether night sleep quality relates to daytime brain activity, operationalized through measures of EEG theta power and its dynamic modulation, which have been previously linked to later cognitive development. For this longitudinal study, 76 typically developing infants were studied (age: 4–14 months, 166 individual study visits) over the course of 6 months with one, two, three, or four lab visits. Habitual sleep was measured with a 7‐day sleep diary and actigraphy, and the Brief Infant Sleep Questionnaire. Twenty‐channel EEG was recorded while infants watched multiple rounds of videos of women singing nursery rhymes; oscillatory power in the theta band was extracted. Key metrics were average theta across stimuli and the slope of change in theta within the first novel movie. Both objective and subjective sleep assessment methods showed a relationship between more night waking and higher overall theta power and reduced dynamic modulation of theta over the course of the novel video stimuli. These results may indicate altered learning and consolidation in infants with more disrupted night sleep, which may have implications for cognitive development.