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Abstract Background Canonical babbling—producing syllables with a mature consonant, full vowel, and smooth transition—is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed. Methods Vocalizations produced at 6 and 12 months by infants (n = 267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome. Results No diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression. Limitations Small numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds. Conclusions Lower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own.

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.

Abstract Background Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS. Methods School-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n = 80) and ASD children (n = 29). ANOVAs were conducted to compare groups on cognitive and adaptive assessments. ANCOVAs (covarying for age, sex, and total cerebral volume; TCV) compared cortical brain volumes between groups. Correlations between behavioral metrics and cortical and cerebellar volumes (separately for gray (GM) and white matter (WM)) were conducted separately by group. Results As expected, children with DS had significantly lower cognitive skills compared to ASD and TD children. Daily Living adaptive skills were comparable between ASD children and children with DS, and both groups scored lower than TD children. Children with DS exhibited a smaller TCV compared to ASD and TD children. Additionally, when controlling for TCV, age, and sex, children with DS had significantly smaller total GM and tissue volumes. Cerebellum volumes were significantly correlated with Daily Living adaptive behaviors in the DS group only. Conclusions Despite children with DS exhibiting lower cognitive skills and smaller brain volume overall than children with ASD, their deficits in Socialization and Daily Living adaptive skills are comparable. Differences in lobar volumes (e.g., Right Frontal GM/WM, Left Frontal WM, and Left and Right Temporal WM) were observed above and beyond overall differences in total volume. The correlation between cerebellum volumes and Daily Living adaptive behaviors in the DS group provides a novel area to explore in future research.

Abstract Background Empirical evidence regarding the development of sensory responsivity in young children at high likelihood to develop autism spectrum disorder (ASD) remains relatively limited. It is unclear how sensory responsivity behaviors may change over time and impact later developmental outcomes. The goals of this study were to (a) characterize developmental trajectories of sensory responsivity across infancy (∼12 months), toddlerhood (∼24 months), and school age (6–11 years) in children at high and low familial likelihood for ASD; and (b) determine if sensory responsivity in infancy predicts adaptive and cognitive functioning at school age among children with ASD. Methods Generalized linear mixed effects models were used to examine scores from the Sensory Experiences Questionnaire in three groups of children including high‐likelihood children later diagnosed with ASD (HL‐ASD; n = 30), high‐likelihood children without ASD (HL‐Neg; n = 150), and low‐likelihood control children not meeting ASD diagnostic criteria (LL‐Neg; n = 94). Hierarchical linear regression was then used to examine the association between sensory responsivity scores in infancy and functional adaptive and cognitive outcomes at school age for children at high likelihood of ASD. Results Development of sensory responsivity from infancy to later childhood is best estimated by the effects of chronological age and Group for Sensory Seeking and Hypo responsivity and the additional effect of the interaction of Group and chronological age for Total and Hyper responsivity. Early elevated Hypo responsivity and Sensory Seeking scores are negatively associated with later adaptive behavior but not cognitive level. Conclusion Overall, higher degrees of Sensory Seeking and Hypo sensory responsivity are detectable in autistic children's behavioral repertoires by 12 months of age and associate with reduced adaptive functioning in middle childhood. These results point to the potential importance of early detection and treatment implications of early sensory behaviors.

Abstract Background Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings. Methods Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24 months using DSM-IV-TR criteria (n = 89 concordant for ASD; n = 296 discordant). We addressed two aims: (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24 months. Results Regarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ = 1.06; 95% CI = 1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains; proband scores explained 9–18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC = 0.50, p

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. [ABSTRACT FROM AUTHOR]

Objective: Predictive testing for familial disorders can guide healthcare and reproductive decisions. Familial disorders with onset in childhood (e.g., autism spectrum disorder [ASD]) are promising targets for presymptomatic prediction; however, little is known about parent perceptions of risk to their children in the presymptomatic period. The current study examined risk perceptions in parents of infants at high familial risk for ASD enrolled in a longitudinal study of brain and behavior development.Methods: Semistructured interviews were conducted with 37 parents of high-risk infants during the presymptomatic window (3-15 months) that precedes an ASD diagnosis. Infants were identified as high familial risk due to having an older sibling with ASD. Parent interview responses were coded and interpreted to distill emerging themes.Results: The majority of parents were aware of the increased risk of ASD for their infants, and risk perceptions were influenced by comparisons to their older child with ASD. Parents reported a variety of negative emotions in response to perceived risk, including worry, fear, and sadness, and described impacts of perceived risk on their behavior: increased vigilance to emerging symptoms, altered reproductive and healthcare decisions, and seeking ongoing assessment through research.Conclusions: Parents of children at high familial risk for childhood-onset disorders like ASD face a period of challenging uncertainty during early development. In anticipation of a future in which presymptomatic testing for ASD is made available, it is important to understand how parents react to and cope with the elevated-but still highly uncertain-risk conveyed by family history. [ABSTRACT FROM AUTHOR]

Background: Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings. Methods: Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24 months using DSM-IV-TR criteria (n = 89 concordant for ASD; n = 296 discordant). We addressed two aims: (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24 months. Results: Regarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ = 1.06; 95% CI = 1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains; proband scores explained 9–18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC = 0.50, p < 0.001). Conclusions: Proband ASD symptomology, indexed by the SCQ, is a predictor of familial ASD recurrence risk. While quantitative variation in social communication and restricted and repetitive behavior were not associated among sibling pairs, standardized ratings of proband language and communication explained significant variation in the same domains in the sibling at 24 months, especially among toddlers with an ASD diagnosis. These data suggest that proband characteristics can alert clinicians to areas of developmental concern for young children with familial risk for ASD. [ABSTRACT FROM AUTHOR]

Importance: Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder and the most common inherited cause of intellectual disability in males. However, there are no published data on brain development in children with FXS during infancy.Objective: To characterize the development of white matter at ages 6, 12, and 24 months in infants with FXS compared with that of typically developing controls.Design, Setting, and Participants: Longitudinal behavioral and brain imaging data were collected at 1 or more time points from 27 infants with FXS and 73 typically developing controls between August 1, 2008, and June 14, 2016, at 2 academic medical centers. Infants in the control group had no first- or second-degree relatives with intellectual or psychiatric disorders, including FXS and autism spectrum disorder.Main Outcomes and Measures: Nineteen major white matter pathways were defined in common atlas space based on anatomically informed methods. Diffusion parameters, including fractional anisotropy, were compared between groups using linear mixed effects modeling. Fiber pathways showing group differences were subsequently examined in association with direct measures of verbal and nonverbal development.Results: There were significant differences in the development of 12 of 19 fiber tracts between the 27 infants with FXS (22 boys and 5 girls) and the 73 infants in the control group (46 boys and 27 girls), with lower fractional anisotropy in bilateral subcortical-frontal, occipital-temporal, temporal-frontal, and cerebellar-thalamic pathways, as well as 4 of 6 subdivisions of the corpus callosum. For all 12 of these pathways, there were significant main effects between groups but not for the interaction of age × group, indicating that lower fractional anisotropy was present and stable from age 6 months in infants with FXS. Lower fractional anisotropy values in the uncinate fasciculi were correlated with lower nonverbal developmental quotient in the FXS group (left uncinate, F = 10.06; false discovery rate-corrected P = .03; right uncinate, F = 21.8; P = .004).Conclusions and Relevance: The results substantiate in human infants the essential role of fragile X gene expression in the early development of white matter. The findings also suggest that the neurodevelopmental effects of FXS are well established at 6 months of age. [ABSTRACT FROM AUTHOR]

Children's early language environments are related to later development. Little is known about this association in siblings of children with autism spectrum disorder (ASD), who often experience language delays or have ASD. Fifty-nine 9-month-old infants at high or low familial risk for ASD contributed full-day in-home language recordings. High-risk infants produced more vocalizations than low-risk peers; conversational turns and adult words did not differ by group. Vocalization differences were driven by a subgroup of "hypervocal" infants. Despite more vocalizations overall, these infants engaged in less social babbling during a standardized clinic assessment, and they experienced fewer conversational turns relative to their rate of vocalizations. Two ways in which these individual and environmental differences may relate to subsequent development are discussed. [ABSTRACT FROM AUTHOR]

OBJECTIVE The 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. METHOD Data 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. RESULTS Visual 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. CONCLUSIONS Flexibly 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. [ABSTRACT FROM AUTHOR]

Objective: Individuals with autism as young as 2 years have been observed to have larger brains than healthy comparison subjects. Studies using head circumference suggest that brain enlargement is a postnatal event that occurs around the latter part of the first year. To the authors' knowledge, no previous brain imaging studies have systematically examined the period prior to age 2. In this study they used magnetic resonance imaging (MRI) to measure brain volume in 6-month-olds at high familial risk for autism.Method: The Infant Brain Imaging Study (IBIS) is a longitudinal imaging study of infants at high risk for autism. This cross-sectional analysis compared brain volumes at 6 months of age in high-risk infants (N=98) and infants without family members with autism (N=36). MRI scans were also examined for radiologic abnormalitiesResults: No group differences were observed for intracranial, cerebrum, cerebellum, or lateral ventricle volume or for head circumference.Conclusions: The authors did not observe significant group differences for head circumference, brain volume, or abnormalities in radiologic findings from a group of 6-month-old infants at high risk for autism. The authors are unable to conclude that these abnormalities are not present in infants who later go on to receive a diagnosis of autism; rather, abnormalities were not detected in a large group at high familial risk. Future longitudinal studies of the IBIS study group will examine whether brain volume differs in infants who go on to develop autism. [ABSTRACT FROM AUTHOR]

Objective: Evidence from prospective studies of high-risk infants suggests that early symptoms of autism usually emerge late in the first or early in the second year of life after a period of relatively typical development. The authors prospectively examined white matter fiber tract organization from 6 to 24 months in high-risk infants who developed autism spectrum disorders (ASDs) by 24 months.Method: The participants were 92 high-risk infant siblings from an ongoing imaging study of autism. All participants had diffusion tensor imaging at 6 months and behavioral assessments at 24 months; a majority contributed additional imaging data at 12 and/or 24 months. At 24 months, 28 infants met criteria for ASDs and 64 infants did not. Microstructural properties of white matter fiber tracts reported to be associated with ASDs or related behaviors were characterized by fractional anisotropy and radial and axial diffusivity.Results: The fractional anisotropy trajectories for 12 of 15 fiber tracts differed significantly between the infants who developed ASDs and those who did not. Development for most fiber tracts in the infants with ASDs was characterized by higher fractional anisotropy values at 6 months followed by slower change over time relative to infants without ASDs. Thus, by 24 months of age, those with ASDs had lower values.Conclusions: These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life. Longitudinal data are critical to characterizing the dynamic age-related brain and behavior changes underlying this neurodevelopmental disorder. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Resting state functional magnetic resonance imaging (rs-fMRI) in infants enables important studies of functional brain organization early in human development. However, rs-fMRI in infants has universally been obtained during sleep to reduce participant motion artifact, raising the question of whether differences in functional organization between awake adults and sleeping infants that are commonly attributed to development may instead derive, at least in part, from sleep. This question is especially important as rs-fMRI differences in adult wake vs. sleep are well documented. To investigate this question, we compared functional connectivity and BOLD signal propagation patterns in 6, 12, and 24 month old sleeping infants with patterns in adult wakefulness and non-REM sleep. We find that important functional connectivity features seen during infant sleep closely resemble those seen during adult sleep, including reduced default mode network functional connectivity. However, we also find differences between infant and adult sleep, especially in thalamic BOLD signal propagation patterns. These findings highlight the importance of considering sleep state when drawing developmental inferences in infant rs-fMRI.