Hyper-focus, sticky attention, and springy attention in young autistic children: Associations with sensory behaviors and cognitive ability.

The autistic-developed monotropism account suggests that atypical, domain-general attentional hyper-focus on interests is a central aspect of autism, but domain-general attention differences in autism can manifest differently. Prior research suggests autistic children are often slow to disengage attention from stimuli-a pattern often called "sticky attention"-and that they can show reduced novelty preference. These attentional patterns could influence sensory experiences and learning. We used eye-tracking to investigate novelty preference and "sticky attention" in young autistic children; we also examined whether attentional patterns were related to cognitive abilities and caregiver-reported sensory responsiveness. A total of 46 autistic and 28 nonautistic participants, aged between 2 and 4 years, provided usable data. We found no evidence that autistic children exhibited greater "sticky attention" than nonautistics, but "sticky attention" in autism was associated with more caregiver-reported sensory hyper-responsiveness, seeking/interests, and enhanced perception. Autistic children also nonsignificantly trended toward exhibiting reduced novelty preference. Unexpectedly, the time-course of this trending novelty preference difference implied it was not driven by reduced orienting to novelty, but increased returning to already-familiarized stimuli: what we call "springy attention." Exploratory analyses of data from the attentional disengagement task suggest autistic participants may have exhibited greater "springy attention," though further research with paradigms optimized for measuring this construct should confirm this. Importantly, "springy attention" was robustly related to reduced cognitive abilities and greater caregiver-reported hypo-responsiveness. Thus, this study illuminates two distinct domain-general attentional patterns, each with distinct correlates in young autistic children, which could have important implications for understanding autistic children's learning, development, and experiences.

Sex differences in trajectories of cortical development in autistic children from 2-13 years of age.

Previous studies have reported alterations in cortical thickness in autism. However, few have included enough autistic females to determine if there are sex specific differences in cortical structure in autism. This longitudinal study aimed to investigate autistic sex differences in cortical thickness and trajectory of cortical thinning across childhood. Participants included 290 autistic (88 females) and 139 nonautistic (60 females) individuals assessed at up to 4 timepoints spanning ~2-13 years of age (918 total MRI timepoints). Estimates of cortical thickness in early and late childhood as well as the trajectory of cortical thinning were modeled using spatiotemporal linear mixed effects models of age-by-sex-by-diagnosis. Additionally, the spatial correspondence between cortical maps of sex-by-diagnosis differences and neurotypical sex differences were evaluated. Relative to their nonautistic peers, autistic females had more extensive cortical differences than autistic males. These differences involved multiple functional networks, and were mainly characterized by thicker cortex at ~3 years of age and faster cortical thinning in autistic females. Cortical regions in which autistic alterations were different between the sexes significantly overlapped with regions that differed by sex in neurotypical development. Autistic females and males demonstrated some shared differences in cortical thickness and rate of cortical thinning across childhood relative to their nonautistic peers, however these areas were relatively small compared to the widespread differences observed across the sexes. These results support evidence of sex-specific neurobiology in autism and suggest that processes that regulate sex differentiation in the neurotypical brain contribute to sex differences in the etiology of autism.

Improving autism identification and support for individuals assigned female at birth: clinical suggestions and research priorities.

Emerging evidence suggests that the higher prevalence of autism in individuals who are assigned male than assigned female at birth results from both biological factors and identification biases. Autistic individuals who are assigned female at birth (AFAB) and those who are gender diverse experience health disparities and clinical inequity, including late or missed diagnosis and inadequate support. In this Viewpoint, an international panel of clinicians, scientists, and community members with lived experiences of autism reviewed the challenges in identifying autism in individuals who are AFAB and proposed clinical and research directions to promote the health, development, and wellbeing of autistic AFAB individuals. The recognition challenges stem from the interplay between cognitive differences and nuanced or different presentations of autism in some AFAB individuals; expectancy, gender-related, and autism-related biases held by clinicians; and social determinants. We recommend that professional development for clinicians be supported by health-care systems, professional societies, and governing bodies to improve equitable access to assessment and earlier identification of autism in AFAB individuals. Autistic AFAB individuals should receive tailored support in education, identity development, health care, and social and professional sense of belonging.

Changes in the severity of autism symptom domains are related to mental health challenges during middle childhood.

LAY ABSTRACT: For many autistic children, the severity of their autism symptoms changes during middle childhood. We studied whether these changes are associated with the emergence of other mental health challenges such as anxiety and attention-deficit hyperactivity disorder. Children who had increased social-communication challenges had more anxiety and attention-deficit hyperactivity disorder symptoms and disruptive behavior problems than other children. Children who decreased their restricted and repetitive behaviors, on the contrary, had more anxiety. We discuss why these changes in autism symptoms may lead to increases in other mental health concerns.

IQ trajectories in autistic children through preadolescence.

Background: We extended our study of trajectories of intellectual development of autistic individuals in early (mean age 3 years; T1), and middle childhood (mean age 5 years, 7 months; T2) into later middle childhood/preadolescence (mean age 11 years, 6 months; T3) in the longitudinal Autism Phenome Project cohort. Participants included 373 autistic children (115 females). Methods: Multivariate latent class growth analysis was used to identify distinct IQ trajectory subgroups. Baseline and developmental course group differences and predictors of trajectory membership were assessed using linear mixed effects models with repeated measures with pairwise testing, multinomial logistic regression models, and sensitivity analyses. Results: We isolated three IQ trajectories between T1 and T3 for autistic youth that were similar to those found in our prior work. These included a group with persistent intellectual disability (ID; 45%), a group with substantial increases in IQ (CHG; 39%), and a group with persistently average or above IQs (P-High; 16%). By T3, the groups did not differ in ADOS-2 calibrated severity scores (CSS), and there were no group differences between Vineland (VABS) communication scores in CHG and P-High. T1-T3 externalizing behaviors declined significantly for CHG, however, there were no significant T3 group differences between internalizing or externalizing symptoms. T1 correlates for CHG and P-High versus ID group membership included higher VABS communication and lower ADOS-2 CSS. A T1 to T2 increase in VABS communication scores and a decline in externalizing predicted CHG versus ID group membership at T3, while T1 to T2 improvement in VABS communication and reduction in ADOS-2 CSS predicted P-High versus ID group membership. Conclusions: Autistic youth exhibit consistent IQ developmental trajectories from early childhood through preadolescence. Factors associated with trajectory group membership may provide clues about prognosis, and the need for treatments that improve adaptive communication and externalizing symptoms.

Why do we need sex-balanced studies of autism?

Males are diagnosed with autism much more frequently than females, and most research study samples reflect this male predominance. The result is that autistic females are understudied. There is a critical need to increase our understanding of autistic females, both biologically and clinically. The only way to do this is to recruit sex-balanced cohorts in studies so that similarities and differences between males and females can be evaluated in all autism research studies. The purpose of this commentary is to (1) provide historical context about how females came to be under-represented in all research, not just in the field of autism and (2) learn from other areas of health and medicine about the potentially dire consequences of not studying both sexes, and (3) draw attention to the need to recruit sex-balanced cohorts in autism research, particularly in neuroimaging studies.

Video Game Use, Aggression, and Social Impairment in Adolescents with Autism Spectrum Disorder.

We used parent report data to investigate video game playing, aggression, and social impairment in adolescents with autism spectrum disorder. Parents of autistic adolescents were more likely to report that their child plays video games as a hobby compared to parents of adolescents with typical development and also reported that their children spent more time playing video games. For autistic participants, we found no differences in aggression levels or social impairment when comparing players versus non-players. However, playing video games "more than average," as compared to "average" was associated with greater aggression and greater social impairment on "awareness" and "mannerisms" subscales. Future studies should focus on how type of video game(s) played is associated with these clinically important variables.

Patterns of sensory processing in young children with autism: Differences in autism characteristics, adaptive skills, and attentional problems.

LAY ABSTRACT: Research has found differences in responding to various sensory stimuli among autistic individuals, which are associated with social and adaptive skills. However, our understanding of sensory profiles in autism has been complicated due to the variable presentation of sensory symptoms. One way to better understand variability in sensory symptoms is to use advanced statistical approaches, such as latent profile analysis, that allow for the identification of more similar sensory classes in otherwise variable groups. We used the Short Sensory Profile to identify homogeneous classes of sensory reactivity in autistic children based on both severity and modality and examined whether sensory classes differed in terms of autism characteristics, adaptive skills, and attention-deficit/hyperactivity disorder symptoms. Based on the pattern of both severity and modality, four sensory classes emerged and were named Moderate/Mixed (35.5%; probable-to-definite differences in all modalities except in movement sensitivity and low energy/weakness), Severe/Mixed (8.5%; definite sensory differences in all modalities except in low energy/weakness), Moderate/Broad (14.6%; probable-to-definite differences in all modalities), and Low/Mixed (41.1%; typical scores in most modalities with probable differences in taste/smell sensitivity, under-responsive/seeks sensation, and auditory filtering). The Severe/Mixed class exhibited greater problems in a variety of areas such as social, adaptive, and attention-deficit/hyperactivity disorder symptoms, whereas the Low/Mixed class showed overall fewer problems. This may provide insight for clinicians and researchers aiming to understand whether autistic children who exhibit distinct sensory patterns are more or less likely to also experience social, adaptive, and/or attention/behavior-related difficulties.

Default mode and fronto-parietal network associations with IQ development across childhood in autism.

BACKGROUND: Intellectual disability affects approximately one third of individuals with autism spectrum disorder (autism). Yet, a major unresolved neurobiological question is what differentiates autistic individuals with and without intellectual disability. Intelligence quotients (IQs) are highly variable during childhood. We previously identified three subgroups of autistic children with different trajectories of intellectual development from early (2-3½ years) to middle childhood (9-12 years): (a) persistently high: individuals whose IQs remained in the normal range; (b) persistently low: individuals whose IQs remained in the range of intellectual disability (IQ < 70); and (c) changers: individuals whose IQs began in the range of intellectual disability but increased to the normal IQ range. The frontoparietal (FPN) and default mode (DMN) networks have established links to intellectual functioning. Here, we tested whether brain regions within the FPN and DMN differed volumetrically between these IQ trajectory groups in early childhood. METHODS: We conducted multivariate distance matrix regression to examine the brain regions within the FPN (11 regions x 2 hemispheres) and the DMN (12 regions x 2 hemispheres) in 48 persistently high (18 female), 108 persistently low (32 female), and 109 changers (39 female) using structural MRI acquired at baseline. FPN and DMN regions were defined using networks identified in Smith et al. (Proc Natl Acad Sci U S A 106:13040-5, 2009). IQ trajectory groups were defined by IQ measurements from up to three time points spanning early to middle childhood (mean age time 1: 3.2 years; time 2: 5.4 years; time 3: 11.3 years). RESULTS: The changers group exhibited volumetric differences in the DMN compared to both the persistently low and persistently high groups at time 1. However, the persistently high group did not differ from the persistently low group, suggesting that DMN structure may be an early predictor for change in IQ trajectory. In contrast, the persistently high group exhibited differences in the FPN compared to both the persistently low and changers groups, suggesting differences related more to concurrent IQ and the absence of intellectual disability. CONCLUSIONS: Within autism, volumetric differences of brain regions within the DMN in early childhood may differentiate individuals with persistently low IQ from those with low IQ that improves through childhood. Structural differences in brain networks between these three IQ-based subgroups highlight distinct neural underpinnings of these autism sub-phenotypes.

Altered Development of Amygdala-Connected Brain Regions in Males and Females with Autism.

Altered amygdala development is implicated in the neurobiology of autism, but little is known about the coordinated development of the brain regions directly connected with the amygdala. Here we investigated the volumetric development of an amygdala-connected network, defined as the set of brain regions with monosynaptic connections with the amygdala, in autism from early to middle childhood. A total of 950 longitudinal structural MRI scans were acquired from 282 children (93 female) with autism and 128 children with typical development (61 female) at up to four time points (mean ages: 39, 52, 64, and 137 months, respectively). Volumes from 32 amygdala-connected brain regions were examined using mixed effects multivariate distance matrix regression. The Social Responsiveness Scale-2 was administered to assess degree of autistic traits and social impairments. The amygdala-connected network exhibited persistent diagnostic differences (p values ≤ 0.03) that increased over time (p values ≤ 0.02). These differences were most prominent in autistics with more impacted social functioning at baseline. This pattern was not observed across regions without monosynaptic amygdala connection. We observed qualitative sex differences. In males, the bilateral subgenual anterior cingulate cortices were most affected, while in females the left fusiform and superior temporal gyri were most affected. In conclusion, (1) autism is associated with widespread alterations to the development of brain regions connected with the amygdala, which were associated with autistic social behaviors; and (2) autistic males and females exhibited different patterns of alterations, adding to a growing body of evidence of sex differences in the neurobiology of autism.SIGNIFICANCE STATEMENT Global patterns of development across brain regions with monosynaptic connection to the amygdala differentiate autism from typical development, and are modulated by social functioning in early childhood. Alterations to brain regions within the amygdala-connected network differed in males and females with autism. Results also indicate larger volumetric differences in regions having monosynaptic connection with the amygdala than in regions without monosynaptic connection.

Sex-dependent structure of socioemotional salience, executive control, and default mode networks in preschool-aged children with autism.

The structure of large-scale intrinsic connectivity networks is atypical in adolescents diagnosed with autism spectrum disorder (ASD or autism). However, the degree to which alterations occur in younger children, and whether these differences vary by sex, is unknown. We utilized structural magnetic resonance imaging (MRI) data from a sex- and age- matched sample of 122 autistic and 122 typically developing (TD) children (2-4 years old) to investigate differences in underlying network structure in preschool-aged autistic children within three large scale intrinsic connectivity networks implicated in ASD: the Socioemotional Salience, Executive Control, and Default Mode Networks. Utilizing structural covariance MRI (scMRI), we report network-level differences in autistic versus TD children, and further report preliminary findings of sex-dependent differences within network topology.

Association of Amygdala Development With Different Forms of Anxiety in Autism Spectrum Disorder.

BACKGROUND: The amygdala is widely implicated in both anxiety and autism spectrum disorder. However, no studies have investigated the relationship between co-occurring anxiety and longitudinal amygdala development in autism. Here, the authors characterize amygdala development across childhood in autistic children with and without traditional DSM forms of anxiety and anxieties distinctly related to autism. METHODS: Longitudinal magnetic resonance imaging scans were acquired at up to four time points for 71 autistic and 55 typically developing (TD) children (∼2.5-12 years, 411 time points). Traditional DSM anxiety and anxieties distinctly related to autism were assessed at study time 4 (∼8-12 years) using a diagnostic interview tailored to autism: the Anxiety Disorders Interview Schedule-IV with the Autism Spectrum Addendum. Mixed-effects models were used to test group differences at study time 1 (3.18 years) and time 4 (11.36 years) and developmental differences (age-by-group interactions) in right and left amygdala volume between autistic children with and without DSM or autism-distinct anxieties and TD children. RESULTS: Autistic children with DSM anxiety had significantly larger right amygdala volumes than TD children at both study time 1 (5.10% increase) and time 4 (6.11% increase). Autistic children with autism-distinct anxieties had significantly slower right amygdala growth than TD, autism-no anxiety, and autism-DSM anxiety groups and smaller right amygdala volumes at time 4 than the autism-no anxiety (-8.13% decrease) and autism-DSM anxiety (-12.05% decrease) groups. CONCLUSIONS: Disparate amygdala volumes and developmental trajectories between DSM and autism-distinct forms of anxiety suggest different biological underpinnings for these common, co-occurring conditions in autism.

Charting brain growth and aging at high spatial precision.

Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and used normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision-making.

Identifying autism symptom severity trajectories across childhood.

An individual's autism symptom severity level can change across childhood. The prevalence and direction of change, however, are still not well understood. Nor are the characteristics of children that experience change. Symptom severity trajectories were evaluated from early to middle childhood (approximately ages 3-11) for 182 autistic children. Symptom severity change was evaluated using individual change scores and the Reliable Change Index. Fifty-one percent of participants experienced symptom severity change: 27% of children decreased in severity, 24% increased and 49% were stable. Symptom severity decreases were more common during early childhood. Severity increases occurred at both early and middle childhood but increase in social affect severity was especially prominent during middle childhood. Most children experienced significant change during only one period and remained stable during the other. Girls decreased more and increased less in symptom severity than boys. Children that increased in severity decreased in adaptive functioning across childhood. Exploratory analyses indicated that a decrease in severity was associated with higher parental education level and older parental age at the time of the child's birth. Conversely, increase in autism severity was associated with lower parental education level and younger parental age at the child's birth. These findings extend recent observations that symptom severity change is more likely than previously appreciated. An understanding of the role of both biological and sociodemographic factors in determining a child's symptom trajectory may factor into future decisions on allocation and type of interventions distributed to young autistic children. LAY SUMMARY: We studied whether a child's autism severity changed from initial diagnosis until middle childhood (ages 3-11). We found that 27% of the children decreased in severity, 24% increased and the rest stayed the same. Symptom severity decreases were more common during early childhood while severity increases were more prominent during middle childhood. We also found that girls were more likely to decrease than boys. Whether a child decreased or increased is related, in part, to parental characteristics.

Examining Associations Between Amygdala Volumes and Anxiety Symptoms in Autism Spectrum Disorder.

BACKGROUND: Anxiety is one of the most common co-occurring conditions in people with autism spectrum disorder. The amygdala has been identified as being associated with anxiety in populations with and without autism, yet associations in autism were based on relatively small or developmentally constrained samples, leaving questions as to whether these results hold at different developmental ages and in a larger, more robust sample. METHODS: Structural neuroimaging and parent report of anxiety symptoms of children ages 5-13 years with (n = 123) and without (n = 171) a diagnosis of autism were collected from the University of Maryland and three sites from the Autism Brain Imaging Data Exchange. Standardized residuals for bilateral amygdala volumes were computed adjusting for site, hemispheric volumes, and covariates (age, sex, Full Scale IQ). RESULTS: Clinically significant anxiety symptoms did not differentiate amygdala volumes between groups (i.e., autism and anxiety, autism without anxiety, without autism or anxiety). No significant association between left or right amygdala volumes and anxiety scores was observed among the sample of individuals with autism. Meta-analytic and Bayes factor estimations provided additional support for the null hypothesis. Age, sex, and autism severity did not moderate associations between anxiety and amygdala volumes. CONCLUSIONS: No relation between amygdala volumes and anxiety symptoms in children with autism was observed in the largest sample to investigate this question. We discuss directions for future research to determine whether additional factors including age or method of assessment may contribute to this lack of association.

Activation for newly learned words in left medial-temporal lobe during toddlers' sleep is associated with memory for words.

Little is known about the neural substrates underlying early memory functioning. To gain more insight, we examined how toddlers remember newly learned words. Hippocampal and anterior medial-temporal lobe (MTL) processes have been hypothesized to support forming and retaining the association between novel words and their referents, but direct evidence of this connection in early childhood is lacking. We assessed 2-year-olds (n = 38) for their memory of newly learned pseudowords associated with novel objects and puppets. We tested memory for these associations during the same session as learning and after a 1-week delay. We then played these pseudowords, previously known words, and completely novel pseudowords during natural nocturnal sleep, while collecting functional magnetic resonance imaging data. Activation in the left hippocampus and the left anterior MTL for newly learned compared to novel words was associated with same-session memory for these newly learned words only when they were learned as puppet names. Activation for known words was associated with memory for puppet names at the 1-week delay. Activation for newly learned words was also associated with overall productive vocabulary. These results underscore an early developing link between memory mechanisms and word learning in the medial temporal lobe.

Altered Gray-White Matter Boundary Contrast in Toddlers at Risk for Autism Relates to Later Diagnosis of Autism Spectrum Disorder.

BACKGROUND: Recent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the contrast of the gray-white matter boundary is decreased in adults with ASD. To determine how gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index of gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD. MATERIALS AND METHODS: We used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n = 20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at 3 years of age for diagnostic outcome. Three outcome groups were defined (ASD, n = 9; typical development, n = 8; non-typical development, n = 3). RESULTS: ASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e., prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network. LIMITATIONS: Our study is the first to measure maturational changes in GWC in toddlers who developed autism, but given the limited size of our sample results should be considered exploratory and warrant further replication in independent and larger samples. CONCLUSION: These preliminary results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread brain regions. Early onset of ASD diagnosis constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.