Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, ...are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6-12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.
By definition, autism spectrum disorder (ASD) is a neurodevelopmental disorder that emerges during early childhood. It is during this time that infants and toddlers transition from appearing typical ...across multiple domains to exhibiting the behavioral phenotype of ASD. Neuroimaging studies focused on this period of development have provided crucial knowledge pertaining to this process, including possible mechanisms underlying pathogenesis of the disorder and offering the possibility of prodromal or presymptomatic prediction of risk. In this paper, we review findings from structural and functional brain imaging studies of ASD focused on the first years of life and discuss implications for next steps in research and clinical applications.
Specific differences in visual orienting, critical in social-cognitive development, are associated with differences in white matter microstructure of the splenium.
ObjectiveThe authors sought to ...determine whether specific patterns of oculomotor functioning and visual orienting characterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors.MethodData were collected from 97 infants, of whom 16 were high-familial-risk infants later classified as having an ASD, 40 were high-familial-risk infants who did not later meet ASD criteria (high-risk negative), and 41 were low-risk infants. All infants underwent an eye-tracking task at a mean age of 7 months and a clinical assessment at a mean age of 25 months. Diffusion-weighted imaging data were acquired for 84 of the infants at 7 months. Primary outcome measures included average saccadic reaction time in a visually guided saccade procedure and radial diffusivity (an index of white matter organization) in fiber tracts that included corticospinal pathways and the splenium and genu of the corpus callosum.ResultsVisual orienting latencies were longer in 7-month-old infants who expressed ASD symptoms at 25 months compared with both high-risk negative infants and low-risk infants. Visual orienting latencies were uniquely associated with the microstructural organization of the splenium of the corpus callosum in low-risk infants, but this association was not apparent in infants later classified as having an ASD.ConclusionsFlexibly and efficiently orienting to salient information in the environment is critical for subsequent cognitive and social-cognitive development. Atypical visual orienting may represent an early prodromal feature of an ASD, and abnormal functional specialization of posterior cortical circuits directly informs a novel model of ASD pathogenesis.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors that typically emerge by 24 months of age. To develop effective early ...interventions that can potentially ameliorate the defining deficits of ASD and improve long-term outcomes, early detection is essential. Using prospective neuroimaging of 59 6-month-old infants with a high familial risk for ASD, we show that functional connectivity magnetic resonance imaging correctly identified which individual children would receive a research clinical best-estimate diagnosis of ASD at 24 months of age. Functional brain connections were defined in 6-month-old infants that correlated with 24-month scores on measures of social behavior, language, motor development, and repetitive behavior, which are all features common to the diagnosis of ASD. A fully cross-validated machine learning algorithm applied at age 6 months had a positive predictive value of 100% 95% confidence interval (CI), 62.9 to 100, correctly predicting 9 of 11 infants who received a diagnosis of ASD at 24 months (sensitivity, 81.8%; 95% CI, 47.8 to 96.8). All 48 6-month-old infants who were not diagnosed with ASD were correctly classified specificity, 100% (95% CI, 90.8 to 100); negative predictive value, 96.0% (95% CI, 85.1 to 99.3). These findings have clinical implications for early risk assessment and the feasibility of developing early preventative interventions for ASD.
Increased prevalence of autism spectrum disorder (ASD) has underscored the need for early intervention services. Early Intensive Behavioral Intervention (EIBI) is among the most common evidence-based ...approaches, however, stakeholders report significant waitlists. The effects of these delays to intervention are unknown. The purpose of this study was to evaluate the effects of delay to EIBI for preschool aged children with ASD on later educational outcomes. Medicaid records from Minnesota (2008–2010) were used to evaluate a cohort diagnosed with ASD and their later educational outcomes from 2010 to 2014 (
n
= 667) using generalized estimating equations. Approximately 70% of children experienced a delay to EIBI and children that experienced less delay and started EIBI at a younger age had better educational outcomes.
Background
Atypical sensory responsivity and sensory interests are now included in the DSM 5 diagnostic criteria for autism spectrum disorder (ASD) under the broad domain of restricted and repetitive ...behavior (RRB). However, relatively little is known about the emergence of sensory‐related features and their relation to conventionally defined RRB in the first years of life.
Methods
Prospective, longitudinal parent‐report data using the Sensory Experiences Questionnaire (SEQ) were collected for 331 high‐risk toddlers (74 of whom met diagnostic criteria for ASD at age 2) and 135 low‐risk controls. Longitudinal profiles for SEQ scores were compared between groups across ages 12–24 months. Associations between SEQ measures and measures of RRB subtypes (based on the Repetitive Behavior Scale, Revised) were also examined.
Results
Longitudinal profiles for all SEQ scores significantly differed between groups. SEQ scores were elevated for the ASD group from age 12 months, with differences becoming more pronounced across the 12–24 month interval. At both 12 and 24 months, most measures derived from the SEQ were significantly associated with all subtypes of RRB.
Conclusions
These findings suggest that differences in sensory responsivity may be evident in high‐risk infants later diagnosed with ASD in early toddlerhood, and that the magnitude of these differences increases over the second year of life. The high degree of association between SEQ scores and RRB supports the conceptual alignment of these features but also raises questions as to explanatory mechanisms.
Restricted and repetitive behavior (RRB) is a core diagnostic feature of autism spectrum disorder (ASD). Previous research shows that RRB is prevalent early in life and observed in neurotypical ...development as well. Less is known, however, about early RRB patterns, developmental trajectories, and the relation to outcomes for autistic children. The purpose of this systematic review was to synthesize findings from studies examining RRB in autistic children from birth through age 3. A detailed protocol was designed
based on PRISMA guidelines for systematic reviews. From the published literature, 41 peer reviewed journal articles were identified and included in this review. Our synthesis of the literature suggests that differences in RRB are evident prior to age 2 in children with or who go onto be diagnosed with autism. These differences were evident for both frequency and intensity of RRB across multiple topographies. There were mixed results regarding functional outcomes associated with early RRB, such as cognitive and adaptive behavior, though relations appeared to become stronger as children aged beyond toddlerhood. Notably, level of RRB appears unrelated to autism severity in young autistic children. A wide range of RRB have been reported to be elevated in autistic children during the first years of life, including repetitive motor behaviors, atypical sensory behaviors, insistence on sameness (IS), and self-injurious behaviors (SIBs). In contrast to studies of older children, RRB in very young autistic children do not appear to be associated with functional outcomes but may be valuable to include in early screening efforts.
https://osf.io/huzf3, unique identifier: doi: 10.17605/OSF.IO/HUZF3.
Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning ...related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development.
Objective:Previous research has demonstrated that the amygdala is enlarged in children with autism spectrum disorder (ASD). However, the precise onset of this enlargement during infancy, how it ...relates to later diagnostic behaviors, whether the timing of enlargement in infancy is specific to the amygdala, and whether it is specific to ASD (or present in other neurodevelopmental disorders, such as fragile X syndrome) are all unknown.Methods:Longitudinal MRIs were acquired at 6–24 months of age in 29 infants with fragile X syndrome, 58 infants at high likelihood for ASD who were later diagnosed with ASD, 212 high-likelihood infants not diagnosed with ASD, and 109 control infants (1,099 total scans).Results:Infants who developed ASD had typically sized amygdala volumes at 6 months, but exhibited significantly faster amygdala growth between 6 and 24 months, such that by 12 months the ASD group had significantly larger amygdala volume (Cohen’s d=0.56) compared with all other groups. Amygdala growth rate between 6 and 12 months was significantly associated with greater social deficits at 24 months when the infants were diagnosed with ASD. Infants with fragile X syndrome had a persistent and significantly enlarged caudate volume at all ages between 6 and 24 months (d=2.12), compared with all other groups, which was significantly associated with greater repetitive behaviors.Conclusions:This is the first MRI study comparing fragile X syndrome and ASD in infancy, demonstrating strikingly different patterns of brain and behavior development. Fragile X syndrome–related changes were present from 6 months of age, whereas ASD-related changes unfolded over the first 2 years of life, starting with no detectable group differences at 6 months. Increased amygdala growth rate between 6 and 12 months occurs prior to social deficits and well before diagnosis. This gradual onset of brain and behavior changes in ASD, but not fragile X syndrome, suggests an age- and disorder-specific pattern of cascading brain changes preceding autism diagnosis.
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