The Predictive Value of Developmental Assessments at 1 and 2 for Intelligence Quotients at 6.

Intelligence is an important individual difference factor related to mental health, academic achievement, and life success, yet there is a lack of research into its early cognitive predictors. This study investigated the predictive value of infant developmental assessment scores for school-age intelligence in a large, heterogeneous sample of single- and twin-born subjects (N = 521). We found that Early Learning Composite (ELC) scores from the Mullen Scales of Early Learning have similar predictive power to that of other infant tests. ELC scores at age 2 were predictive of Stanford-Binet abbreviated intelligence (ABIQ) scores at age 6 (r = 0.46) even after controlling for sex, gestation number, and parental education. ELC scores at age 1 were less predictive of 6-year ABIQ scores (r = 0.17). When the sample was split to test robustness of findings, we found that results from the full sample replicated in a subset of children born at ≥32 weeks gestation without birth complications (n = 405), though infant cognitive scores did not predict IQ in a subset born very prematurely or with birth complications (n = 116). Scores at age 2 in twins and singletons showed similar predictive ability for scores at age 6, though twins had particularly high correlations between ELC at age 1 and ABIQ at age 6.

Development of thalamocortical connectivity during infancy and its cognitive correlations.

Although commonly viewed as a sensory information relay center, the thalamus has been increasingly recognized as an essential node in various higher-order cognitive circuits, and the underlying thalamocortical interaction mechanism has attracted increasing scientific interest. However, the development of thalamocortical connections and how such development relates to cognitive processes during the earliest stages of life remain largely unknown. Leveraging a large human pediatric sample (N = 143) with longitudinal resting-state fMRI scans and cognitive data collected during the first 2 years of life, we aimed to characterize the age-dependent development of thalamocortical connectivity patterns by examining the functional relationship between the thalamus and nine cortical functional networks and determine the correlation between thalamocortical connectivity and cognitive performance at ages 1 and 2 years. Our results revealed that the thalamus-sensorimotor and thalamus-salience connectivity networks were already present in neonates, whereas the thalamus-medial visual and thalamus-default mode network connectivity emerged later, at 1 year of age. More importantly, brain-behavior analyses based on the Mullen Early Learning Composite Score and visual-spatial working memory performance measured at 1 and 2 years of age highlighted significant correlations with the thalamus-salience network connectivity. These results provide new insights into the understudied early functional brain development process and shed light on the behavioral importance of the emerging thalamocortical connectivity during infancy.

Associations between white matter microstructure and infants' working memory.

Working memory emerges in infancy and plays a privileged role in subsequent adaptive cognitive development. The neural networks important for the development of working memory during infancy remain unknown. We used diffusion tensor imaging (DTI) and deterministic fiber tracking to characterize the microstructure of white matter fiber bundles hypothesized to support working memory in 12-month-old infants (n=73). Here we show robust associations between infants' visuospatial working memory performance and microstructural characteristics of widespread white matter. Significant associations were found for white matter tracts that connect brain regions known to support working memory in older children and adults (genu, anterior and superior thalamic radiations, anterior cingulum, arcuate fasciculus, and the temporal-parietal segment). Better working memory scores were associated with higher FA and lower RD values in these selected white matter tracts. These tract-specific brain-behavior relationships accounted for a significant amount of individual variation above and beyond infants' gestational age and developmental level, as measured with the Mullen Scales of Early Learning. Working memory was not associated with global measures of brain volume, as expected, and few associations were found between working memory and control white matter tracts. To our knowledge, this study is among the first demonstrations of brain-behavior associations in infants using quantitative tractography. The ability to characterize subtle individual differences in infant brain development associated with complex cognitive functions holds promise for improving our understanding of normative development, biomarkers of risk, experience-dependent learning and neuro-cognitive periods of developmental plasticity.

Infant word segmentation and childhood vocabulary development: a longitudinal analysis.

Infants begin to segment novel words from speech by 7.5 months, demonstrating an ability to track, encode and retrieve words in the context of larger units. Although it is presumed that word recognition at this stage is a prerequisite to constructing a vocabulary, the continuity between these stages of development has not yet been empirically demonstrated. The goal of the present study is to investigate whether infant word segmentation skills are indeed related to later lexical development. Two word segmentation tasks, varying in complexity, were administered in infancy and related to childhood outcome measures. Outcome measures consisted of age-normed productive vocabulary percentiles and a measure of cognitive development. Results demonstrated a strong degree of association between infant word segmentation abilities at 7 months and productive vocabulary size at 24 months. In addition, outcome groups, as defined by median vocabulary size and growth trajectories at 24 months, showed distinct word segmentation abilities as infants. These findings provide the first prospective evidence supporting the predictive validity of infant word segmentation tasks and suggest that they are indeed associated with mature word knowledge. A video abstract of this article can be viewed at http://www.youtube.com/watch?v=jxzLi5oLZQ8.

Amelioration of lipid-induced insulin resistance in rat skeletal muscle by overexpression of Pgc-1ß involves reductions in long-chain acyl-CoA levels and oxidative stress.

AIMS/HYPOTHESIS: To determine if acute overexpression of peroxisome proliferator-activated receptor, gamma, coactivator 1 beta (Pgc-1ß [also known as Ppargc1b]) in skeletal muscle improves insulin action in a rodent model of diet-induced insulin resistance. METHODS: Rats were fed either a low-fat or high-fat diet (HFD) for 4 weeks. In vivo electroporation was used to overexpress Pgc-1ß in the tibialis cranialis (TC) and extensor digitorum longus (EDL) muscles. Downstream effects of Pgc-1ß on markers of mitochondrial oxidative capacity, oxidative stress and muscle lipid levels were characterised. Insulin action was examined ex vivo using intact muscle strips and in vivo via a hyperinsulinaemic-euglycaemic clamp. RESULTS: Pgc-1ß gene expression was increased >100% over basal levels. The levels of proteins involved in mitochondrial function, lipid metabolism and antioxidant defences, the activity of oxidative enzymes, and substrate oxidative capacity were all increased in muscles overexpressing Pgc-1ß. In rats fed a HFD, increasing the levels of Pgc-1ß partially ameliorated muscle insulin resistance, in association with decreased levels of long-chain acyl-CoAs (LCACoAs) and increased antioxidant defences. CONCLUSIONS: Our data show that an increase in Pgc-1ß expression in vivo activates a coordinated subset of genes that increase mitochondrial substrate oxidation, defend against oxidative stress and improve lipid-induced insulin resistance in skeletal muscle.

Infant Attentional behaviors Are Associated With ADHD Symptomatology and Executive Function in Early Childhood.

Objective: We explored associations between infant attentional behaviors as measured by the First Year Inventory (FYIv2.0) and dimensional ratings of ADHD symptomatology and executive function (EF) in early childhood. Methods: This study included parents (N = 229) who filled out the FYIv2.0 when their children were 12 months of age. When children were approximately 54 months (4.5 years) of age, parents completed reports of children's ADHD symptomatology and EF abilities. Correlation and regression analyses were conducted among measures. Results: We found significant associations among the variables of interest, both cross-sectionally and longitudinally, as well as gender differences. Notably, non-social sensory attention (NSA) was significantly related to 54-month ADHD symptom severity. All three 12-month attention variables were significantly related to 54-month EF. Conclusion: Results suggest that infant attentional behaviors predict later ADHD-related behaviors in early childhood. Future research should explore associations using laboratory-based measures and could inform early intervention efforts.

Measurement of Cognition for the National Children's Study.

The National Children's Study Cognitive Health Domain Team developed detailed plans for assessing cognition longitudinally from infancy to early adulthood. These plans identify high-priority aspects of cognition that can be measured efficiently and effectively, and we believe they can serve as a model for future large-scale longitudinal research. For infancy and toddlerhood, we proposed several paradigms that collectively allowed us to assess six broad cognitive constructs: (1) executive function skills, (2) episodic memory, (3) language, (4) processing speed, (5) spatial and numerical processing, and (6) social cognition. In some cases, different trial sequences within a paradigm allow for the simultaneous assessment of multiple cognitive skills (e.g., executive function skills and processing speed). We define each construct, summarize its significance for understanding developmental outcomes, discuss the feasibility of its assessment throughout development, and present our plan for measuring specific skills at different ages. Given the need for well-validated, direct behavioral measures of cognition that can be used in large-scale longitudinal studies, especially from birth to age 3 years, we also initiated three projects focused on the development of new measures.

Overexpression of the orphan receptor Nur77 alters glucose metabolism in rat muscle cells and rat muscle in vivo.

AIMS/HYPOTHESIS: A hallmark feature of the metabolic syndrome is abnormal glucose metabolism which can be improved by exercise. Recently the orphan nuclear receptor subfamily 4, group A, member 1 (NUR77) was found to be induced by exercise in muscle and was linked to transcriptional control of genes involved in lipid and glucose metabolism. Here we investigated if overexpression of Nur77 (also known as Nr4a1) in skeletal muscle has functional consequences for lipid and/or glucose metabolism. METHODS: L6 rat skeletal muscle myotubes were infected with a Nur77-coding adenovirus and lipid and glucose oxidation was measured. Nur77 was also overexpressed in skeletal muscle of chow- and fat-fed rats and the effects on glucose and lipid metabolism evaluated. RESULTS: Nur77 overexpression had no effect on lipid oxidation in L6 cells or rat muscle, but did increase glucose oxidation and glycogen synthesis in L6 cells. In chow- and high-fat-fed rats, Nur77 overexpression by electrotransfer significantly increased basal glucose uptake and glycogen synthesis, but no increase in insulin-stimulated glucose metabolism was observed. Nur77 electrotransfer was associated with increased production of GLUT4 and glycogenin and increased hexokinase and phosphofructokinase activity. Interestingly, Nur77 expression in muscle biopsies from obese men was significantly lower than in those from lean men and was closely correlated with body-fat content and insulin sensitivity. CONCLUSIONS/INTERPRETATION: Our data provide compelling evidence that NUR77 is a functional regulator of glucose metabolism in skeletal muscle in vivo. Importantly, the diminished content in muscle of obese insulin-resistant men suggests that it might be a potential therapeutic target for the treatment of dysregulated glucose metabolism.

Better working memory for non-social targets in infant siblings of children with Autism Spectrum Disorder.

We compared working memory (WM) for the location of social versus non-social targets in infant siblings of children with Autism Spectrum Disorders (sibs-ASD, n = 25) and of typically developing children (sibs-TD, n = 30) at 6.5 and 9 months of age. There was a significant interaction of risk group and target type on WM, in which the sibs-ASD had better WM for non-social targets as compared with controls. There was no group by stimulus interaction on two non-memory measures. The results suggest that the increased competency of sibs-ASD in WM (creating, updating and using transient representations) for non-social stimuli distinguishes them from sibs-TD by 9 months of age. This early emerging strength is discussed as a developmental pathway that may have implications for social attention and learning in children at risk for ASD.

Maternal responses to child frustration and requests for help in dyads with fragile X syndrome.

BACKGROUND: Variability in behaviour displayed by children with fragile X syndrome (FXS) may be partially attributable to environmental factors such as maternal responsivity. The purpose of this study was to explore variables associated with maternal behaviour during a task designed to elicit frustration in their children with FXS. METHODS: Forty-six mother-child dyads, in which the child had full-mutation FXS, were observed in their homes during a task designed to elicit frustration in the child. Each child was given a wrong set of keys and asked to open a box to retrieve a desired toy. Mothers were provided with the correct set of keys and instructed to intervene when they perceived their child was getting too frustrated. Child-expressed frustration and requests for help and maternal behaviours (comforting, negative control, and encouraging/directing) were observed and coded. Maternal variables (e.g. depression, stress, education levels), child variables (e.g. autistic behaviours, age, medication use) and child behaviours (frustration, requests for help) were explored as predictors of maternal behaviour. RESULTS: Almost all mothers intervened to help their children and most used encouraging/directing behaviours, whereas very few used comforting or negative control. Child age and child behaviours during the frustrating event were significant predictors of encouraging/directing behaviours in the mothers. Children whose mothers reported higher depressive symptomology used fewer requests for help, and mothers of children with more autistic behaviours used more negative control. CONCLUSIONS: The results of this study suggest that child age and immediate behaviours are more strongly related to maternal responsivity than maternal traits such as depression and stress.

Biological bases of childhood shyness.

The initial behavioral reaction to unfamiliar events is a distinctive source of intraspecific variation in humans and other animals. Two longitudinal studies of 2-year-old children who were extreme in the display of either behavioral restraint or spontaneity in unfamiliar contexts revealed that by 7 years of age a majority of the restrained group were quiet and socially avoidant with unfamiliar children and adults whereas a majority of the more spontaneous children were talkative and interactive. The group differences in peripheral physiological reactions suggest that inherited variation in the threshold of arousal in selected limbic sites may contribute to shyness in childhood and even extreme degrees of social avoidance in adults.

The Social Orienting Continuum and Response Scale (SOC-RS): a dimensional measure for preschool-aged children.

Children with autism show deficits in social referencing, joint attention, orienting to their names, and social smiling as early as the first year of life. The present study describes the development of the Social Orienting Continuum and Response Scale (SOC-RS), a quantitative scale assessing each of these behaviors during the course of video-recorded Autism Diagnostic Observation Schedule (ADOS) sessions. The SOC-RS was shown to be reliable and valid, and when applied to a longitudinal sample of children studied at 2 and 4 years of age, was shown to be sensitive to decreased levels of social referencing, joint attention, orienting to name, and social smiling in autism. The implications of these findings and potential applications of the SOC-RS are discussed.

Trajectories and predictors of the development of very young boys with fragile X syndrome.

OBJECTIVE: To describe the development of young boys with fragile X syndrome (FXS). METHODS: Fifty-five boys (aged 8-48 months at study entry) with the full mutation FXS received multiple developmental assessments. RESULTS: As expected, the boys' rate of development was significantly lower than chronological age expectations. No evidence of slowing in the rate of development was found. Autistic behavior was negatively associated with development, but maternal IQ was not. Developmental delays were evident in some domains as early as 9 months; however, initial detection of delays is complicated by measures and criteria used. Developmental age scores at 31 months of age were related to scores obtained at 61 months of age only in the global composite and visual reception domain. CONCLUSIONS: Developmental delays are evident in some infants with FXS as young as 9 months of age. Pediatric psychologists need to be informed about the developmental profiles in young children with FXS to accurately diagnose, treat, and support these children and their families.

Understanding the role of nutrition in the brain and behavioral development of toddlers and preschool children: identifying and addressing methodological barriers.

The preschool years (i.e. 1-5 years of age) is a time of rapid and dramatic postnatal brain development (i.e. neural plasticity), and of fundamental acquisition of cognitive development (i.e. working memory, attention and inhibitory control). Also, it is a time of transition from a direct maternal mediation/selection of diet-based nutrition to food selection that is more based on self-selection and self-gratification. However, there have been fewer published studies in preschool children than in infants or school-aged children that examined the role of nutrition in brain/mental development (125 studies versus 232 and 303 studies, respectively during the last 28 years). This may arise because of age-related variability, in terms of individual differences in temperament, linguistic ability, and patterns of neural activity that may affect assessment of neural and cognitive development in pre-school children. In this review, we suggest several approaches for assessing brain function in children that can be refined. It would be desirable if the discipline developed some common elements to be included in future studies of diet and brain function, with the idea that they would complement more targeted measures based on time of exposure and understanding of data from animal models. Underlining this approach is the concept of 'window of sensitivity' during which nutrients may affect postnatal neural development: investigators and expert panels need to look specifically for region-specific changes and do so with understanding of the likely time window during which the nutrient was, or was not available.

The effects of socioeconomic status, race, and parenting on language development in early childhood.

The authors examined the associations between socioeconomic status (SES), race, maternal sensitivity, and maternal negative-intrusive behaviors and language development in a sample selected to reduce the typical confound between race and SES (n = 146). Mother-child interactions were observed at 12 and 24 months (coded by randomly assigned African American and European American coders); language abilities were assessed at 18, 24, 30, and 36 months. For receptive language, race was associated with ability level, and maternal sensitivity and negative-intrusive parenting were related to rate of growth. For expressive communication, race, SES, and maternal sensitivity were associated with rate of growth; race moderated the association between negative-intrusive parenting and rate of growth such that the relation was weaker for African American than for European American children. The results highlight the importance of sensitive parenting and suggest that the association between negative-intrusive parenting and language development may depend upon family context. Future work is needed concerning the race differences found, including examining associations with other demographic factors and variations in language input experienced by children, using culturally and racially validated indices of language development.

The Performance of the First Year Inventory (FYI) Screening on a Sample of High-Risk 12-Month-Olds Diagnosed with Autism Spectrum Disorder (ASD) at 36 Months.

This study examined the performance of the First Year Inventory (FYI; version 2.0), a community-normed parent-reported screening instrument, in a high-risk (HR) sample of 12-month-olds with older siblings diagnosed with autism spectrum disorder (ASD). The FYI 2.0 was completed by parents of 86 HR infants and 35 low-risk control infants at age 12 months, followed by clinical diagnosis at 36 months. HR infants later diagnosed with ASD had significantly higher FYI 2.0 risk scores in both the social-communication and sensory-regulatory domains than typically developing infants. New FYI 2.0 cutoff scores for HR sample were explored by evaluating various cutoff options after considering tradeoffs between sensitivity and specificity and sample characteristics.

Early temperament and negative reactivity in boys with fragile X syndrome.

BACKGROUND: The phenotype of children and adults with fragile X syndrome (FXS) includes a number of problem behaviours such as inattention, social anxiety and aggressive outbursts. However, very little work has been conducted with young children with FXS less than 5 years of age to examine the developmental pathway of problem behaviours in this population and to determine if later occurring problem behaviours may be rooted in early appearing temperament profiles. METHODS: Parent ratings and laboratory-based behavioural observations of negative reactivity were examined in 25 3-year-old boys with FXS and compared with 64 typically developing boys matched on age. RESULTS: Compared with the typically developing group, boys with FXS were rated by their parents as exhibiting less anger and sadness on the Child Behaviour Questionnaire (CBQ), and they showed less facial sadness on the Laboratory Temperament Assessment Battery (Lab-TAB). No group differences were found on the Lab-TAB measures of distress vocalisations, bodily struggle, and facial anger; and anger peaked in the middle of the arm restraint episode for both groups. For boys with FXS, mental age was moderately positively correlated, and autistic behaviour was moderately negatively correlated, with sadness scores from the CBQ. CONCLUSIONS: Our results show different behavioural profiles in very young children with FXS than reported in older-aged children with FXS which implies that temperamental differences and elevated problem behaviours reported in older-aged children with FXS may not be rooted in early temperament. This information is important to develop the phenotype of early development in FXS to facilitate early identification and treatment.

Infant quantitative risk for autism spectrum disorder predicts executive function in early childhood.

Much of the current research concerning autism spectrum disorder (ASD) focuses on early identification of behaviors that may indicate future deficits or higher risk for a later diagnosis. Additionally, there exists a strong claim regarding the dimensional nature of ASD, such that even among non-diagnosed individuals, a continuous distribution of symptom severity can be observed. Executive function (EF) has been widely studied in children, adolescents, and adults with ASD, with a robust body of research supporting widespread EF deficits in diagnosed individuals. However, it remains unclear how the degree of ASD symptomatology, outside of the presence of a diagnosis, affects EF abilities in a community sample. The First Year Inventory 2.0 (FYI 2.0), a parent-report measure, was designed to identify infants at 12 months who are at risk for an eventual ASD diagnosis. In the current study, a continuous scoring scale was used to examine risk (overall, Social-Communication, and Sensory-Regulatory) from a dimensional perspective. Parents also completed the Behavior Rating Inventory of Executive Function-Preschool Version and the Social Responsiveness Scale-2nd edition when their children were 42 months (3.5 years) old. Each FYI 2.0 risk variable significantly predicted scores on an overall EF composite and specific EF subscales. When controlling for general ASD symptomatology, Sensory-Regulatory risk still significantly predicted EF deficits. This research provides additional support for a quantitative consideration of risk for ASD and presents novel findings regarding the relation between infant behaviors indicative of ASD risk and EF in early childhood. Autism Research 2018, 11: 1532-1541. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Children with autism spectrum disorder (ASD) often have difficulty with executive function (EF) tasks that require a set of mental processes involved in goal-directed behaviors. Studying children without ASD who may have symptoms affecting EF is also important. This study demonstrates that certain infant behaviors related to ASD are linked to early childhood EF difficulties. These results support looking at a range of ASD symptoms to better understand children who struggle with EF and potentially design tools to help them.

Verbal and nonverbal predictors of executive function in early childhood.

The study of executive function (EF) has become increasingly popular in multiple areas of research. A wealth of evidence has supported the value of EF in shaping notable outcomes across typical and atypical development; however, little evidence has supported the cognitive contributors to early EF development. The current study used data from a large longitudinal sample of healthy children to investigate the differential influence of verbal and nonverbal cognition on later EF. Participants were assessed at 2 years of age using the Mullen Scales of Early Learning, and Mullen scores were used to calculate nonverbal and verbal developmental quotients. Executive function was measured at 6 years using assessments from the Stanford-Binet, Cambridge Neuropsychological Test Automated Battery, and the Behavior Rating Inventory of Executive Function. Results suggested that early nonverbal cognition was a better predictor of 6-year EF as measured by task-based laboratory assessments, whereas verbal cognition was a better predictor of parent-reported EF. Findings are discussed in regard to EF development and characteristics of EF measurement.

The broad autism phenotype questionnaire.

The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the BAP in adults, the Broad Autism Phenotype Questionnaire (BAPQ), was administered to 86 parents of autistic individuals and 64 community control parents. Sensitivity and specificity of the BAPQ for detecting the BAP were high (>70%). Parents of children with autism had significantly higher scores on all three subscales: aloof personality, rigid personality, and pragmatic language. This instrument provides a valid and efficient measure for characterizing the BAP.