Contingent conversations build more than language: How communicative interactions in toddlerhood relate to preschool executive function skills.

High-quality communicative interactions between caregivers and children provide a foundation for children's social and cognitive skills. Although most studies examining these types of interactions focus on child language outcomes, this paper takes another tack. It examines whether communicative, dyadic interactions might also relate to child executive function (EF) skills and whether child language might mediate this relation. Using a subset of data from the NICHD Study of Early Child Care and Youth Development, dyadic interactions between 2-year-olds and their mothers were coded for three behaviors: symbol-infused joint engagement, routines and rituals, and fluency and connectedness. Child language was assessed at age 3 and three facets of EF (self-regulation, sustained attention, and verbal working memory) were assessed at age 4.5. Structural equation modeling showed that dyadic interaction related to later child sustained attention and verbal working memory, indirectly through child language and directly related with child self-regulation. This suggests that communicative interactions with caregivers that include both verbal and non-verbal elements relate to child EF, in part through child language. Our findings have implications for the role of caregiver interactions in the development of language and cognitive skills more broadly. RESEARCH HIGHLIGHTS: Using structural equation modeling, we examined how communicative interactions between caregivers and toddlers relate to preschool executive function skills Communicative interactions relate to later language which in turn relates to sustained attention and verbal working memory in preschool Communicative interactions relate directly to self-regulation in preschool Associations between communicative interactions, language, and executive function vary across facets of executive function and may not be unidirectional.

Beyond talk: Contributions of quantity and quality of communication to language success across socioeconomic strata.

Infants from low-socioeconomic status (SES) households hear a projected 30 million fewer words than their higher-SES peers. In a recent study, Hirsh-Pasek et al. (Psychological Science, 2015; 26: 1071) found that in a low-income sample, fluency and connectedness in exchanges between caregivers and toddlers predicted child language a year later over and above quantity of talk (Hirsh-Pasek et al., Psychological Science, 2015; 26: 1071). Here, we expand upon this study by examining fluency and connectedness in two higher-SES samples. Using data from the NICHD Study of Early Child Care and Youth Development, we sampled 20 toddlers who had low, average, and high language outcomes at 36 months from each of 2 groups based on income-to-needs ratio (INR; middle and high) and applied new coding to the mother-toddler interaction at 24 months. In the high-INR group, the quality of mother-toddler interaction at 24 months accounted for more variability in language outcomes a year later than did quantity of talk, quality of talk, or sensitive parenting. These results could not be accounted for by child language ability at 24 months. These effects were not found in the middle-INR sample. Our findings suggest that when the quality of interaction, fluency and connectedness, predicts language outcomes, it is a robust relation, but it may not be universal.

The Importance of Temperament for Understanding Early Manifestations of Autism Spectrum Disorder in High-Risk Infants.

The present study investigated the relationship between infant temperament characteristics and autism spectrum disorder (ASD) risk status. Temperament was examined at 6, 12, and 24 months in 282 infants at high familial risk for ASD and 114 low-risk controls using the Infant Behavior Questionnaire-Revised and Early Childhood Behavior Questionnaire. Infants were divided into three groups at 24 months: High-Risk Positive-classified as ASD (HR Pos), High-Risk Negative (HR Neg), and Low-Risk Negative (LR Neg). At 6 and 12 months HR Pos infants exhibited lower Surgency and Regulatory Capacity than LR Neg infants. By 12 months they also demonstrated increased Negative Affect. Group differences remained, when early signs of ASD were controlled for, suggesting that temperament differences could be useful targets for understanding the development of ASD.

Autism spectrum disorder screening with the CBCL/1½-5: Findings for young children at high risk for autism spectrum disorder.

The screening power of the CBCL/1½-5's Withdrawn and Diagnostic and Statistical Manual of Mental Disorders-Pervasive Developmental Problems (DSM-PDP) scales to identify children diagnosed with autism spectrum disorder at 24 months was tested in a longitudinal, familial high-risk study. Participants were 56 children at high risk for autism spectrum disorder due to an affected older sibling (high-risk group) and 26 low-risk children with a typically developing older sibling (low-risk group). At 24 months, 13 of the 56 high-risk children were diagnosed with autism spectrum disorder, whereas the other 43 were not. The high-risk children diagnosed with autism spectrum disorder group had significantly higher scores on the CBCL/1½-5's Diagnostic and Statistical Manual of Mental Disorders-Pervasive Developmental Problems and Withdrawn scales than children in the low-risk and high-risk children not diagnosed with autism spectrum disorder groups (ηp2>0.50). Receiver operating characteristic analyses yielded very high area under the curve values (0.91 and 0.89), and a cut point of T ⩾ 60 yielded sensitivity of 77% and specificity of 97% to 99% between the high-risk children diagnosed with autism spectrum disorder and the combination of low-risk and high-risk children not diagnosed with autism spectrum disorder. Consistent with several previous studies, the CBCL/1½-5's Diagnostic and Statistical Manual of Mental Disorders-Pervasive Developmental Problems scale and the Withdrawn syndrome differentiated well between children diagnosed with autism spectrum disorder and those not diagnosed.

Restricted and Repetitive Behavior and Brain Functional Connectivity in Infants at Risk for Developing Autism Spectrum Disorder.

BACKGROUND: Restricted and repetitive behaviors (RRBs), detectable by 12 months in many infants in whom autism spectrum disorder (ASD) is later diagnosed, may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown. METHODS: Behavioral and resting-state functional connectivity (fc) magnetic resonance imaging data were collected from 167 children at high and low familial risk for ASD at 12 and 24 months (n = 38 at both time points). Twenty infants met criteria for ASD at 24 months. We divided RRBs into four subcategories (restricted, stereotyped, ritualistic/sameness, self-injurious) and used a data-driven approach to identify functional brain networks associated with the development of each RRB subcategory. RESULTS: Higher scores for ritualistic/sameness behavior were associated with less positive fc between visual and control networks at 12 and 24 months. Ritualistic/sameness and stereotyped behaviors were associated with less positive fc between visual and default mode networks at 12 months. At 24 months, stereotyped and restricted behaviors were associated with more positive fc between default mode and control networks. Additionally, at 24 months, stereotyped behavior was associated with more positive fc between dorsal attention and subcortical networks, whereas restricted behavior was associated with more positive fc between default mode and dorsal attention networks. No significant network-level associations were observed for self-injurious behavior. CONCLUSIONS: These observations mark the earliest known description of functional brain systems underlying RRBs, reinforce the construct validity of RRB subcategories in infants, and implicate specific neural substrates for future interventions targeting RRBs.

Walking, Gross Motor Development, and Brain Functional Connectivity in Infants and Toddlers.

Infant gross motor development is vital to adaptive function and predictive of both cognitive outcomes and neurodevelopmental disorders. However, little is known about neural systems underlying the emergence of walking and general gross motor abilities. Using resting state fcMRI, we identified functional brain networks associated with walking and gross motor scores in a mixed cross-sectional and longitudinal cohort of infants at high and low risk for autism spectrum disorder, who represent a dimensionally distributed range of motor function. At age 12 months, functional connectivity of motor and default mode networks was correlated with walking, whereas dorsal attention and posterior cingulo-opercular networks were implicated at age 24 months. Analyses of general gross motor function also revealed involvement of motor and default mode networks at 12 and 24 months, with dorsal attention, cingulo-opercular, frontoparietal, and subcortical networks additionally implicated at 24 months. These findings suggest that changes in network-level brain-behavior relationships underlie the emergence and consolidation of walking and gross motor abilities in the toddler period. This initial description of network substrates of early gross motor development may inform hypotheses regarding neural systems contributing to typical and atypical motor outcomes, as well as neurodevelopmental disorders associated with motor dysfunction.

Resting-state fMRI in sleeping infants more closely resembles adult sleep than adult wakefulness.

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.

Joint Attention and Brain Functional Connectivity in Infants and Toddlers.

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.

Emerging Executive Functioning and Motor Development in Infants at High and Low Risk for Autism Spectrum Disorder.

Existing evidence suggests executive functioning (EF) deficits may be present in children with autism spectrum disorder (ASD) by 3 years of age. It is less clear when, prior to 3 years, EF deficits may emerge and how EF unfold over time. The contribution of motor skill difficulties to poorer EF in children with ASD has not been systematically studied. We investigated the developmental trajectory of EF in infants at high and low familial risk for ASD (HR and LR) and the potential associations between motor skills, diagnostic group, and EF performance. Participants included 186 HR and 76 LR infants. EF (A-not-B), motor skills (Fine and Gross Motor), and cognitive ability were directly assessed at 12 months and 24 months of age. Participants were directly evaluated for ASD at 24 months using DSM-IV-TR criteria and categorized as HR-ASD, HR-Negative, and LR-Negative. HR-ASD and HR-Negative siblings demonstrated less improvement in EF over time compared to the LR-Negative group. Motor skills were associated with group and EF performance at 12 months. No group differences were found at 12 months, but at 24 months, the HR-ASD and HR-Negative groups performed worse than the LR-Negative group overall after controlling for visual reception and maternal education. On reversal trials, the HR-ASD group performed worse than the LR-Negative group. Motor skills were associated with group and EF performance on reversal trials at 24 months. Findings suggest that HR siblings demonstrate altered EF development and that motor skills may play an important role in this process.

A mutation in COL4A2 causes autosomal dominant porencephaly with cataracts.

Mutations in COL4A1 are well described and result in brain abnormalities manifesting with severe neurological deficits including cerebral palsy, intellectual disability, and focal epilepsy. Families with mutations in COL4A2 are now emerging with a similar phenotype. We describe a family with an autosomal dominant disorder comprising porencephaly, focal epilepsy, and lens opacities, which was negative for mutations in COL4A1. Using whole exome sequencing of three affected individuals from three generations, we identified a rare variant in COL4A2. This COL4A2 (c.2399G>A, p.G800E, CCDS41907.1) variant was predicted to be damaging by multiple bioinformatics tools and affects an invariable glycine residue that is essential for the formation of collagen IV heterotrimers. The cataracts identified in this family expand the phenotypic spectrum associated with mutations in COL4A2 and highlight the increasing overlap with phenotypes associated with COL4A1 mutations.

Repetitive behavior in 12-month-olds later classified with autism spectrum disorder.

OBJECTIVE: As compared to the utility of early emerging social communicative risk markers for predicting a later diagnosis of autism spectrum disorder (ASD), less is known about the relevance of early patterns of restricted and repetitive behaviors. We examined patterns of stereotyped motor mannerisms and repetitive manipulation of objects in 12-month-olds at high and low risk for developing ASD, all of whom were assessed for ASD at 24 months. METHOD: Observational coding of repetitive object manipulation and stereotyped motor behaviors in digital recordings of the Communication and Symbolic Behavior Scales was conducted using the Repetitive and Stereotyped Movement Scales for 3 groups of 12-month-olds: low-risk infants (LR, n = 53); high-familial-risk infants who did not meet diagnostic criteria for ASD at 24 months (HR-negative, n = 75); and high-familial-risk infants who met diagnostic criteria for ASD at 24 months (HR-ASD, n = 30). RESULTS: The HR-ASD group showed significantly more stereotyped motor mannerisms than both the HR-negative group (p = .025) and the LR group (p = .001). The HR-ASD and HR-negative groups demonstrated statistically equivalent repetitive object manipulation scores (p = .431), and both groups showed significantly more repetitive object manipulation than the LR group (p < .040). Combining the motor and object stereotypy scores into a Repetitive and Stereotyped Movement Scales (RSMS) composite yielded a disorder-continuum effect such that each group was significantly different from one another (LR < HR-negative < HR-ASD). CONCLUSION: These results suggest that targeted assessment of repetitive behavior during infancy may augment early ASD identification efforts.

Longitudinal patterns of repetitive behavior in toddlers with autism.

BACKGROUND: Recent evidence suggests that restricted and repetitive behaviors may differentiate children who develop autism spectrum disorder (ASD) by late infancy. How these core symptoms manifest early in life, particularly among infants at high risk for the disorder, is not well characterized. METHODS: Prospective, longitudinal parent-report data (Repetitive Behavior Scales-Revised) were collected for 190 high-risk toddlers and 60 low-risk controls from 12 to 24 months of age. Forty-one high-risk children were classified with ASD at age 2. Profiles of repetitive behavior were compared between groups using generalized estimating equations. RESULTS: Longitudinal profiles for children diagnosed with ASD differed significantly from high- and low-risk children without the disorder on all measures of repetitive behavior. High-risk toddlers without ASD were intermediate to low risk and ASD positive counterparts. Toddlers with ASD showed significantly higher rates of repetitive behavior across subtypes at the 12-month time point. Repetitive behaviors were significantly correlated with adaptive behavior and socialization scores among children with ASD at 24 months of age, but were largely unrelated to measures of general cognitive ability. CONCLUSIONS: These findings suggest that as early as 12 months of age, a broad range of repetitive behaviors are highly elevated in children who go on to develop ASD. While some degree of repetitive behavior is elemental to typical early development, the extent of these behaviors among children who develop ASD appears highly atypical.

Seizure semiology in autosomal dominant epilepsy with auditory features, due to novel LGI1 mutations.

Mutations in LGI1 are found in 50% of families with autosomal dominant epilepsy with auditory features (ADEAF). In ADEAF, family members have predominantly lateral temporal lobe seizures but mesial temporal lobe semiology may also occur. We report here three families with novel LGI1 mutations (p.Ile82Thr, p.Glu225*, c.432-2_436del). Seven affected individuals reported an auditory aura and one a visual aura. A 10-year old boy described a cephalic aura followed by an unpleasant taste and oral automatisms without auditory, visual or psychic features.

White matter microstructure and atypical visual orienting in 7-month-olds at risk for autism.

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.

Frontolimbic neural circuitry at 6 months predicts individual differences in joint attention at 9 months.

Elucidating the neural basis of joint attention in infancy promises to yield important insights into the development of language and social cognition, and directly informs developmental models of autism. We describe a new method for evaluating responding to joint attention performance in infancy that highlights the 9- to 10-month period as a time interval of maximal individual differences. We then demonstrate that fractional anisotropy in the right uncinate fasciculus, a white matter fiber bundle connecting the amygdala to the ventral-medial prefrontal cortex and anterior temporal pole, measured in 6-month-olds predicts individual differences in responding to joint attention at 9 months of age. The white matter microstructure of the right uncinate was not related to receptive language ability at 9 months. These findings suggest that the development of core nonverbal social communication skills in infancy is largely supported by preceding developments within right lateralized frontotemporal brain systems.

Brain volume findings in 6-month-old infants at high familial risk for autism.

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 abnormalities RESULTS: 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.

Differences in white matter fiber tract development present from 6 to 24 months in infants with autism.

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.

Neurodevelopmental and behavioral issues in Williams syndrome.

Much existing research on Williams syndrome (WS) has focused on the individuals' unusual cognitive profile, with less emphasis placed on the developmental and neural underpinnings of the disorder. We review recent findings from brain imaging and begin to discuss links from these data to the behavioral phenotype. Overall brain size is significantly reduced in individuals with WS, as it is in many mental retardation syndromes. However, the specific profile of deficits in WS, particularly the visuospatial deficits, appears to be linked to parietal lobe abnormalities. Results from both genetic and brain imaging studies have provided useful insights into WS neurobiology. However, future work needs to remediate the lack of studies investigating developmental processes.

Links between abnormal brain structure and cognition in holoprosencephaly.

Converging information on medical issues, motor ability, and cognitive outcomes is essential when addressing long-term clinical management in children with holoprosencephaly. This study considered whether adding more informative structural indices to classic holoprosencephaly categories would increase prediction of cognitive outcomes. Forty-two children with holoprosencephaly were examined to determine the association of deep gray nuclei abnormalities with cognitive abilities and the effect of motor skill deficits on cognitive performance. Additionally, a cognitive profile was described using the Carter Neurocognitive Assessment, an experimental diagnostic instrument designed specifically for young children with severe neurodevelopmental dysfunction. Findings indicated that nonseparation of the deep gray nuclei was significantly associated with the cognitive construct of vocal communication, but not with the cognitive constructs of social awareness, visual attention, or auditory comprehension. Importantly, motor skill deficits did not significantly affect performance on the Carter Neurocognitive Assessment. This study is the first investigation to provide a descriptive overview of specific cognitive skills in this group of children. The results also strongly suggest that this feature of the brain's structure does not predict all aspects of neurodevelopmental function. These findings contribute a critical component to the growing body of knowledge regarding the medical and clinical outcomes of children with holoprosencephaly.