Differential cognitive and behavioral development from 6 to 24 months in autism and fragile X syndrome.

BACKGROUND: Specifying early developmental differences among neurodevelopmental disorders with distinct etiologies is critical to improving early identification and tailored intervention during the first years of life. Recent studies have uncovered important differences between infants with fragile X syndrome (FXS) and infants with familial history of autism spectrum disorder who go on to develop autism themselves (FH-ASD), including differences in brain development and behavior. Thus far, there have been no studies longitudinally investigating differential developmental skill profiles in FXS and FH-ASD infants. METHODS: The current study contrasted longitudinal trajectories of verbal (expressive and receptive language) and nonverbal (gross and fine motor, visual reception) skills in FXS and FH-ASD infants, compared to FH infants who did not develop ASD (FH-nonASD) and typically developing controls. RESULTS: Infants with FXS showed delays on a nonverbal composite compared to FH-ASD (as well as FH-nonASD and control) infants as early as 6 months of age. By 12 months an ordinal pattern of scores was established between groups on all domains tested, such that controls > FH-nonASD > FH-ASD > FXS. This pattern persisted through 24 months. Cognitive level differentially influenced developmental trajectories for FXS and FH-ASD. CONCLUSIONS: Our results demonstrate detectable group differences by 6 months between FXS and FH-ASD as well as differential trajectories on each domain throughout infancy. This work further highlights an earlier onset of global cognitive delays in FXS and, conversely, a protracted period of more slowly emerging delays in FH-ASD. Divergent neural and cognitive development in infancy between FXS and FH-ASD contributes to our understanding of important distinctions in the development and behavioral phenotype of these two groups.

Associations between early trajectories of amygdala development and later school-age anxiety in two longitudinal samples.

Amygdala function is implicated in the pathogenesis of autism spectrum disorder (ASD) and anxiety. We investigated associations between early trajectories of amygdala growth and anxiety and ASD outcomes at school age in two longitudinal studies: high- and low-familial likelihood for ASD, Infant Brain Imaging Study (IBIS, n = 257) and typically developing (TD) community sample, Early Brain Development Study (EBDS, n = 158). Infants underwent MRI scanning at up to 3 timepoints from neonate to 24 months. Anxiety was assessed at 6-12 years. Linear multilevel modeling tested whether amygdala volume growth was associated with anxiety symptoms at school age. In the IBIS sample, children with higher anxiety showed accelerated amygdala growth from 6 to 24 months. ASD diagnosis and ASD familial likelihood were not significant predictors. In the EBDS sample, amygdala growth from birth to 24 months was associated with anxiety. More anxious children had smaller amygdala volume and slower rates of amygdala growth. We explore reasons for the contrasting results between high-familial likelihood for ASD and TD samples, grounding results in the broader literature of variable associations between early amygdala volume and later anxiety. Results have the potential to identify mechanisms linking early amygdala growth to later anxiety in certain groups.

Enlarged Perivascular Spaces in Infancy and Autism Diagnosis, Cerebrospinal Fluid Volume, and Later Sleep Problems.

Importance: Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume. Objective: To examine whether enlarged PVS are more prevalent in infants who develop autism compared with controls and whether they are associated with trajectories of extra-axial CSF volume (EA-CSF) and sleep problems in later childhood. Design, Setting, and Participants: This prospective, longitudinal cohort study used data from the Infant Brain Imaging Study. Magnetic resonance images were acquired at ages 6, 12, and 24 months (2007-2017), with sleep questionnaires performed between ages 7 and 12 years (starting in 2018). Data were collected at 4 sites in North Carolina, Missouri, Pennsylvania, and Washington. Data were analyzed from March 2021 through August 2022. Exposure: PVS (ie, fluid-filled channels that surround blood vessels in the brain) that are enlarged (ie, visible on magnetic resonance imaging). Main Outcomes and Measures: Outcomes of interest were enlarged PVS and EA-CSF volume from 6 to 24 months, autism diagnosis at 24 months, sleep problems between ages 7 and 12 years. Results: A total of 311 infants (197 [63.3%] male) were included: 47 infants at high familial likelihood for autism (ie, having an older sibling with autism) who were diagnosed with autism at age 24 months, 180 high likelihood infants not diagnosed with autism, and 84 low likelihood control infants not diagnosed with autism. Sleep measures at school-age were available for 109 participants. Of infants who developed autism, 21 (44.7%) had enlarged PVS at 24 months compared with 48 infants (26.7%) in the high likelihood but no autism diagnosis group (P = .02) and 22 infants in the control group (26.2%) (P = .03). Across all groups, enlarged PVS at 24 months was associated with greater EA-CSF volume from ages 6 to 24 months (ß = 4.64; 95% CI, 0.58-8.72; P = .002) and more frequent night wakings at school-age (F = 7.76; η2 = 0.08; P = .006). Conclusions and Relevance: These findings suggest that enlarged PVS emerged between ages 12 and 24 months in infants who developed autism. These results add to a growing body of evidence that, along with excessive CSF volume and sleep dysfunction, the glymphatic system could be dysregulated in infants who develop autism.

Predicting self-injurious behavior at age three among infant siblings of children with autism.

Existing research suggests that self-injurious behavior (SIB) is a relatively common interfering behavior that can occur across the lifespan of individuals with autism spectrum disorder (ASD). We previously reported that SIB or proto-injurious SIB at 12 months was related to increased risk of SIB at 24 months among a preschool sample of children with a high familial likelihood for ASD (Dimian et al., 2017). In the present study, we extend these findings, examine SIB occurrence, and associated potential risk factors at 36 months. The present sample included 149 infants with an older sibling with ASD (65.8% male) who completed assessments at ages 12, 24, and 36 months. Descriptive analyses and binary logistic regression models were utilized. SIB was more prevalent among those children who received a diagnosis of ASD. Logistic regression indicated that presence of SIB, stereotypy, hyper- and hypo- sensory responsivity, and lower intellectual functioning at age 12 months significantly predicted the occurrence of SIB at 36 months. These findings have implications for understanding developmental processes culminating in persistent SIB and may inform prevention programming.

The prevalence and developmental course of auditory processing differences in autistic children.

Auditory processing differences, including hyper- or hyposensitivity to sound, aversions to sound, and difficulty listening under noisy, real-world conditions, are commonly reported in autistic individuals. However, the developmental course and functional impact of these auditory processing differences are unclear. In this study, we investigate the prevalence, developmental trajectory, and functional impact of auditory processing differences in autistic children throughout childhood using a longitudinal study design. Auditory processing differences were measured using the Short Sensory Profile, a caregiver questionnaire, in addition to adaptive behaviors and disruptive/concerning behaviors at 3, 6, and 9 years of age. Our results showed that auditory processing differences were reported in greater than 70% of the autistic children in our sample at all three timepoints, maintained a high prevalence through 9 years of age, and were associated with increased disruptive/concerning behaviors and difficulty with adaptive behaviors. Furthermore, in our sample of children, auditory processing differences at age 3 years predicted disruptive/concerning behaviors and difficulty with adaptive behaviors at age 9 years. These findings warrant further investigations of the potential benefit of incorporating measures of auditory processing during routine clinical evaluations as well as interventions targeting auditory processing differences in autistic children.

Donor perspectives on informed consent and use of biospecimens for brain organoid research.

Debates about the ethics of human brain organoids have proceeded without the input of individuals whose brains are being modeled. Interviews with donors of biospecimens for brain organoid research revealed overall enthusiasm for brain organoids as a tool for biomedical discovery, alongside a desire for ongoing engagement with research teams to learn the results of the research, to allow transfer of decision-making authority over time, and to ensure ethical boundaries are not crossed. Future work is needed to determine the most feasible and resource-efficient way to longitudinally engage donors participating in brain organoid research.

Association of Sex With Neurobehavioral Markers of Executive Function in 2-Year-Olds at High and Low Likelihood of Autism.

Importance: Children with autism and their siblings exhibit executive function (EF) deficits early in development, but associations between EF and biological sex or early brain alterations in this population are largely unexplored. Objective: To investigate the interaction of sex, autism likelihood group, and structural magnetic resonance imaging alterations on EF in 2-year-old children at high familial likelihood (HL) and low familial likelihood (LL) of autism, based on having an older sibling with autism or no family history of autism in first-degree relatives. Design, Setting, and Participants: This prospective cohort study assessed 165 toddlers at HL (n = 110) and LL (n = 55) of autism at 4 university-based research centers. Data were collected from January 1, 2007, to December 31, 2013, and analyzed between August 2021 and June 2022 as part of the Infant Brain Imaging Study. Main Outcomes and Measures: Direct assessments of EF and acquired structural magnetic resonance imaging were performed to determine frontal lobe, parietal lobe, and total cerebral brain volume. Results: A total of 165 toddlers (mean [SD] age, 24.61 [0.95] months; 90 [54%] male, 137 [83%] White) at HL for autism (n = 110; 17 diagnosed with ASD) and LL for autism (n = 55) were studied. The toddlers at HL for autism scored lower than the toddlers at LL for autism on EF tests regardless of sex (mean [SE] B = -8.77 [4.21]; 95% CI, -17.09 to -0.45; η2p = 0.03). With the exclusion of toddlers with autism, no group (HL vs LL) difference in EF was found in boys (mean [SE] difference, -7.18 [4.26]; 95% CI, 1.24-15.59), but EF was lower in HL girls than LL girls (mean [SE] difference, -9.75 [4.34]; 95% CI, -18.32 to -1.18). Brain-behavior associations were examined, controlling for overall cerebral volume and developmental level. Sex differences in EF-frontal (B [SE] = 16.51 [7.43]; 95% CI, 1.36-31.67; η2p = 0.14) and EF-parietal (B [SE] = 17.68 [6.99]; 95% CI, 3.43-31.94; η2p = 0.17) associations were found in the LL group but not the HL group (EF-frontal: B [SE] = -1.36 [3.87]; 95% CI, -9.07 to 6.35; η2p = 0.00; EF-parietal: B [SE] = -2.81 [4.09]; 95% CI, -10.96 to 5.34; η2p = 0.01). Autism likelihood group differences in EF-frontal (B [SE] = -9.93 [4.88]; 95% CI, -19.73 to -0.12; η2p = 0.08) and EF-parietal (B [SE] = -15.44 [5.18]; 95% CI, -25.86 to -5.02; η2p = 0.16) associations were found in girls not boys (EF-frontal: B [SE] = 6.51 [5.88]; 95% CI, -5.26 to 18.27; η2p = 0.02; EF-parietal: B [SE] = 4.18 [5.48]; 95% CI, -6.78 to 15.15; η2p = 0.01). Conclusions and Relevance: This cohort study of toddlers at HL and LL of autism suggests that there is an association between sex and EF and that brain-behavior associations in EF may be altered in children at HL of autism. Furthermore, EF deficits may aggregate in families, particularly in girls.

Sensory Profiles in Relation to Later Adaptive Functioning Among Toddlers at High-Familial Likelihood for Autism.

This study investigated the extent to which sensory responsivity in infancy contributes to adaptive behavior development among toddlers at high-familial likelihood for autism. Prospective, longitudinal data were analyzed for 218 children, 58 of whom received an autism diagnosis. Results indicated that sensory profiles at age one year (hyperresponsivity, sensory seeking) were negatively associated with later adaptive behavior, particularly for socialization, at age 3 years regardless of diagnostic status. These results suggest that early differences in sensory responsivity may have downstream developmental consequences related to social development among young children with high-familial likelihood for autism.

Quantifying latent social motivation and its associations with joint attention and language in infants at high and low likelihood for autism spectrum disorder.

Social motivation-the psychobiological predisposition for social orienting, seeking social contact, and maintaining social interaction-manifests in early infancy and is hypothesized to be foundational for social communication development in typical and atypical populations. However, the lack of infant social-motivation measures has hindered delineation of associations between infant social motivation, other early-arising social abilities such as joint attention, and language outcomes. To investigate how infant social motivation contributes to joint attention and language, this study utilizes a mixed longitudinal sample of 741 infants at high (HL = 515) and low (LL = 226) likelihood for ASD. Using moderated nonlinear factor analysis (MNLFA), we incorporated items from parent-report measures to establish a novel latent factor model of infant social motivation that exhibits measurement invariance by age, sex, and familial ASD likelihood. We then examined developmental associations between 6- and 12-month social motivation, joint attention at 12-15 months, and language at 24 months of age. On average, greater social-motivation growth from 6-12 months was associated with greater initiating joint attention (IJA) and trend-level increases in sophistication of responding to joint attention (RJA). IJA and RJA were both positively associated with 24-month language abilities. There were no additional associations between social motivation and future language in our path model. These findings substantiate a novel, theoretically driven approach to modeling social motivation and suggest a developmental cascade through which social motivation impacts other foundational skills. These findings have implications for the timing and nature of intervention targets to support social communication development in infancy. HIGHLIGHTS: We describe a novel, theoretically based model of infant social motivation wherein multiple parent-reported indicators contribute to a unitary latent social-motivation factor. Analyses revealed social-motivation factor scores exhibited measurement invariance for a longitudinal sample of infants at high and low familial ASD likelihood. Social-motivation growth from ages 6-12 months is associated with better 12-15-month joint attention abilities, which in turn are associated with greater 24-month language skills. Findings inform timing and targets of potential interventions to support healthy social communication in the first year of life.

Relationship of Impairments in Associative Learning With Intellectual Disability and Cerebellar Hypoplasia in Autistic Children.

BACKGROUND AND OBJECTIVES: The severity of autism spectrum disorder (ASD) varies widely and is associated with intellectual disability (ID) and brain dysmorphology. We tested the hypothesis that the heterogeneity of ASD can be accounted for, in part, by altered associative learning measured by eye-blink conditioning (EBC) paradigms, used to test for forebrain and cerebellar dysfunction across the full range of ASD severity and intellectual ability. METHODS: Children in this cohort study were diagnosed with ASD or typical development (TD); most children were recruited from a 10-year longitudinal study. Outcome measures were the percentage and timing of conditioned eye-blink responses (CRs) acquired to a tone, recorded photometrically and related to measures of ASD severity, IQ, and age 2 brain morphometry by MRI. A sequence of trace and delay EBC was used. Analysis of variance, t test, and logistic regression (LR) were used. RESULTS: Sixty-two children were studied at school age. Nine children with ASD with ID since age 2 (ASD + ID; IQ = 49 ± 6; 11.9 ± 0.2 years old [±SD]) learned more slowly than 30 children with TD (IQ = 120 ± 16; 10.5 ± 1.5 years old [±SD]) during trace EBC and showed atypically early-onset CRs (1.4 SD pre-TD) related to hypoplasia of the cerebellum at age 2 but not of the amygdala, hippocampus, or cerebral cortex. Conversely, 16 children with ASD with robust intellectual development since age 2 (IQ = 100 ± 3; 12.0 ± 0.4 years old [±SD]) learned typically but showed early-onset CRs only during long-delay EBC (0.8 SD pre-TD) unrelated to hypoplasia of any measured brain area. Using 16 EBC measures, binary LR classified ASD and TD with 80% accuracy (95% CI = 72-88%), 81% sensitivity (95% CI = 69-92%), and 79% specificity (95% CI = 68-91%); multinomial LR more accurately classified children based on ID (94% accuracy, 95% CI = 89-100%) than ASD severity (85% accuracy, 95% CI = 77-93%). Separate analyses of 39 children with MRI (2.1 ± 0.3 years old [±SD]) indicated that cerebellar hypoplasia did not predict ASD + ID over ages 2-4 (Cohen d = 0.3) compared with early-onset CRs during age 11 trace EBC (Cohen d = -1.3). DISCUSSION: Trace EBC reveals the relationship between cerebellar hypoplasia and ASD + ID likely by engaging cerebrocerebellar circuits involved in intellectual ability and implicit timing. Follow-up prospective studies using associative learning can determine whether ID can be predicted in children with early ASD diagnoses.

IcoConv : Explainable brain cortical surface analysis for ASD classification.

In this study, we introduce a novel approach for the analysis and interpretation of 3D shapes, particularly applied in the context of neuroscientific research. Our method captures 2D perspectives from various vantage points of a 3D object. These perspectives are subsequently analyzed using 2D Convolutional Neural Networks (CNNs), uniquely modified with custom pooling mechanisms. We sought to assess the efficacy of our approach through a binary classification task involving subjects at high risk for Autism Spectrum Disorder (ASD). The task entailed differentiating between high-risk positive and high-risk negative ASD cases. To do this, we employed brain attributes like cortical thickness, surface area, and extra-axial cerebral spinal measurements. We then mapped these measurements onto the surface of a sphere and subsequently analyzed them via our bespoke method. One distinguishing feature of our method is the pooling of data from diverse views using our icosahedron convolution operator. This operator facilitates the efficient sharing of information between neighboring views. A significant contribution of our method is the generation of gradient-based explainability maps, which can be visualized on the brain surface. The insights derived from these explainability images align with prior research findings, particularly those detailing the brain regions typically impacted by ASD. Our innovative approach thereby substantiates the known understanding of this disorder while potentially unveiling novel areas of study.

Social motivation in infancy is associated with familial recurrence of ASD.

Pre-diagnostic deficits in social motivation are hypothesized to contribute to autism spectrum disorder (ASD), a heritable neurodevelopmental condition. We evaluated psychometric properties of a social motivation index (SMI) using parent-report item-level data from 597 participants in a prospective cohort of infant siblings at high and low familial risk for ASD. We tested whether lower SMI scores at 6, 12, and 24 months were associated with a 24-month ASD diagnosis and whether social motivation's course differed relative to familial ASD liability. The SMI displayed good internal consistency and temporal stability. Children diagnosed with ASD displayed lower mean SMI T-scores at all ages and a decrease in mean T-scores across age. Lower group-level 6-month scores corresponded with higher familial ASD liability. Among high-risk infants, strong decline in SMI T-scores was associated with 10-fold odds of diagnosis. Infant social motivation is quantifiable by parental report, differentiates children with versus without later ASD by age 6 months, and tracks with familial ASD liability, consistent with a diagnostic and susceptibility marker of ASD. Early decrements and decline in social motivation indicate increased likelihood of ASD, highlighting social motivation's importance to risk assessment and clarification of the ontogeny of ASD.

A Data-Driven Approach in an Unbiased Sample Reveals Equivalent Sex Ratio of Autism Spectrum Disorder-Associated Impairment in Early Childhood.

BACKGROUND: Sex differences in the prevalence of neurodevelopmental disorders are particularly evident in autism spectrum disorder (ASD). Heterogeneous symptom presentation and the potential of measurement bias hinder early ASD detection in females and may contribute to discrepant prevalence estimates. We examined trajectories of social communication (SC) and restricted and repetitive behaviors (RRBs) in a sample of infant siblings of children with ASD, adjusting for age- and sex-based measurement bias. We hypothesized that leveraging a prospective elevated familial likelihood sample, deriving data-driven behavioral constructs, and accounting for measurement bias would reveal less discrepant sex ratios than are typically seen in ASD. METHODS: We conducted direct assessments of ASD symptoms at 6 to 9, 12 to 15, 24, and 36 to 60 months of age (total nobservations = 1254) with infant siblings of children with ASD (n = 377) and a lower ASD-familial-likelihood comparison group (n = 168; nobservations = 527). We established measurement invariance across age and sex for separate models of SC and RRB. We then conducted latent class growth mixture modeling with the longitudinal data and evaluated for sex differences in trajectory membership. RESULTS: We identified 2 latent classes in the SC and RRB models with equal sex ratios in the high-concern cluster for both SC and RRB. Sex differences were also observed in the SC high-concern cluster, indicating that girls classified as having elevated social concerns demonstrated milder symptoms than boys in this group. CONCLUSIONS: This novel approach for characterizing ASD symptom progression highlights the utility of assessing and adjusting for sex-related measurement bias and identifying sex-specific patterns of symptom emergence.

Infant Visual Brain Development and Inherited Genetic Liability in Autism.

OBJECTIVE: Autism spectrum disorder (ASD) is heritable, and younger siblings of ASD probands are at higher likelihood of developing ASD themselves. Prospective MRI studies of siblings report that atypical brain development precedes ASD diagnosis, although the link between brain maturation and genetic factors is unclear. Given that familial recurrence of ASD is predicted by higher levels of ASD traits in the proband, the authors investigated associations between proband ASD traits and brain development among younger siblings. METHODS: In a sample of 384 proband-sibling pairs (89 pairs concordant for ASD), the authors examined associations between proband ASD traits and sibling brain development at 6, 12, and 24 months in key MRI phenotypes: total cerebral volume, cortical surface area, extra-axial cerebrospinal fluid, occipital cortical surface area, and splenium white matter microstructure. Results from primary analyses led the authors to implement a data-driven approach using functional connectivity MRI at 6 months. RESULTS: Greater levels of proband ASD traits were associated with larger total cerebral volume and surface area and larger surface area and reduced white matter integrity in components of the visual system in siblings who developed ASD. This aligned with weaker functional connectivity between several networks and the visual system among all siblings during infancy. CONCLUSIONS: The findings provide evidence that specific early brain MRI phenotypes of ASD reflect quantitative variation in familial ASD traits. Multimodal anatomical and functional convergence on cortical regions, fiber pathways, and functional networks involved in visual processing suggest that inherited liability has a role in shaping the prodromal development of visual circuitry in ASD.

Examining the factor structure and discriminative utility of the Infant Behavior Questionnaire-Revised in infant siblings of autistic children.

Using the Infant Behavior Questionnaire-Revised in a longitudinal sample of infant siblings of autistic children (HR; n = 427, 171 female, 83.4% White) and a comparison group of low-risk controls (LR, n = 200, 86 female, 81.5% White), collected between 2007 and 2017, this study identified an invariant factor structure of temperament traits across groups at 6 and 12 months. Second, after partitioning the groups by familial risk and diagnostic outcome at 24 months, results reveal an endophenotypic pattern of Positive Emotionality at both 6 and 12 months, (HR-autism spectrum disorder [ASD] < HR-no-ASD < LR). Third, increased 'Duration of Orienting' at 12 months was associated with lower scores on the 24-month developmental outcomes in HR infants. These findings may augment efforts for early identification of ASD.

Subcortical Brain Development in Autism and Fragile X Syndrome: Evidence for Dynamic, Age- and Disorder-Specific Trajectories in Infancy.

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.

Are early social communication skills a harbinger for language development in infants later diagnosed autistic?-A longitudinal study using a standardized social communication assessment.

The early emergence of social communication challenges and their impact on language in infants later diagnosed with autism has sparked many early intervention programs that target social communication skills. While research has consistently shown lower scores on social communication assessments in the first year of life, there is limited research at 12-months exploring associations between different dimensions of social communication and later language. Understanding associations between early social communication skills and language would enhance our ability to choose high priority intervention goals that will impact downstream language skills. The current study used a standardized assessment to profile social communication skills across 516 infants with a high (HL) or low likelihood (LL-Neg) for autism (84% White, 60% Male), based on the presence of a sibling with autism in the family. The primary aim of the study was to profile social communication skill development in the second year of life and to evaluate associations between social communication skills and later language. HL infants who met criteria for autism (HL-ASD, N = 81) demonstrated widespread reductions in social communication skills at 12-months compared to HL infants who did not meet criteria for autism (HL-Neg, N = 277) and LL-Neg (N = 158) infants. Across all infants in the study, those with better social communication skills at 12-months had better language at 24-months. However, within group analyses indicated that infants who met criteria for autism did not show this developmental coupling until 24-months-of-age at which point social communication was positively associated with downstream language skills. The cascading pattern of reduced social communication skills as well as overall significant positive associations with later language provide further evidence for the need to support developing social communication skills prior to formal autism diagnosis, a goal that could possibly be reached through pre-emptive interventions.

Relations of Restricted and Repetitive Behaviors to Social Skills in Toddlers with Autism.

We examined the relations of restricted and repetitive behaviors (RRB; insistence on sameness, repetitive sensory-motor, self-injurious behavior) to social skills overall and aspects that comprise social skills as measured by the VABS-II (coping skills, play/leisure time, interpersonal relationships) in 24- (n = 63) and 36-month old (n = 35), high-familial-risk toddlers with ASD. Hierarchical linear regression results indicated that repetitive sensory-motor was the best predictor of social skills overall. Secondary results indicated that all three RRB subtypes were associated with each subdomain of social skills; however, repetitive sensory-motor was the strongest and most consistent among these effects. While our results suggests a general negative relation of subtypes of RRB to aspects of adaptive social function, repetitive sensory-motor behaviors may be of particular relevance to the development of social skills during toddlerhood.

Variability in Responding to Joint Attention Cues in the First Year is Associated With Autism Outcome.

OBJECTIVE: With development, infants become increasingly responsive to the many attention-sharing cues of adults; however, little work has examined how this ability emerges in typical development or in the context of early autism spectrum disorder (ASD). This study characterized variation in the type of cue needed to elicit a response to joint attention (RJA) using the Dimensional Joint Attention Assessment (DJAA) during naturalistic play. METHOD: We measured the average redundancy of cue type required for infants to follow RJA bids from an experimenter, as well as their response consistency, in 268 infants at high (HR, n = 68) and low (LR, N = 200) familial risk for ASD. Infants were assessed between 8 and 18 months of age and followed up with developmental and clinical assessments at 24 or 36 months. Our sample consisted of LR infants, as well as HR infants who did (HR-ASD) and did not (HR-neg) develop ASD at 24 months. RESULTS: We found that HR and LR infants developed abilities to respond to less redundant (more sophisticated) RJA cues at different rates, and that HR-ASD infants displayed delayed abilities, identifiable as early as 9 months, compared to both HR-neg and LR infants. Interestingly, results suggest that HR-neg infants may exhibit a propensity to respond to less redundant (more sophisticated) RJA cues relative to both HR-ASD and LR infants. CONCLUSION: Using an approach to characterize variable performance of RJA cue-reading abilities, findings from this study enhance our understanding of both typical and ASD-related proficiencies and deficits in RJA development.

Longitudinal Prediction of Infant MR Images With Multi-Contrast Perceptual Adversarial Learning.

The infant brain undergoes a remarkable period of neural development that is crucial for the development of cognitive and behavioral capacities (Hasegawa et al., 2018). Longitudinal magnetic resonance imaging (MRI) is able to characterize the developmental trajectories and is critical in neuroimaging studies of early brain development. However, missing data at different time points is an unavoidable occurrence in longitudinal studies owing to participant attrition and scan failure. Compared to dropping incomplete data, data imputation is considered a better solution to address such missing data in order to preserve all available samples. In this paper, we adapt generative adversarial networks (GAN) to a new application: longitudinal image prediction of structural MRI in the first year of life. In contrast to existing medical image-to-image translation applications of GANs, where inputs and outputs share a very close anatomical structure, our task is more challenging as brain size, shape and tissue contrast vary significantly between the input data and the predicted data. Several improvements over existing GAN approaches are proposed to address these challenges in our task. To enhance the realism, crispness, and accuracy of the predicted images, we incorporate both a traditional voxel-wise reconstruction loss as well as a perceptual loss term into the adversarial learning scheme. As the differing contrast changes in T1w and T2w MR images in the first year of life, we incorporate multi-contrast images leading to our proposed 3D multi-contrast perceptual adversarial network (MPGAN). Extensive evaluations are performed to assess the qualityand fidelity of the predicted images, including qualitative and quantitative assessments of the image appearance, as well as quantitative assessment on two segmentation tasks. Our experimental results show that our MPGAN is an effective solution for longitudinal MR image data imputation in the infant brain. We further apply our predicted/imputed images to two practical tasks, a regression task and a classification task, in order to highlight the enhanced task-related performance following image imputation. The results show that the model performance in both tasks is improved by including the additional imputed data, demonstrating the usability of the predicted images generated from our approach.