White Matter Development from Birth to 6 Years of Age: A Longitudinal Study.

Human white matter development in the first years of life is rapid, setting the foundation for later development. Microstructural properties of white matter are linked to many behavioral and psychiatric outcomes; however, little is known about when in development individual differences in white matter microstructure are established. The aim of the current study is to characterize longitudinal development of white matter microstructure from birth through 6 years to determine when in development individual differences are established. Two hundred and twenty-four children underwent diffusion-weighted imaging after birth and at 1, 2, 4, and 6 years. Diffusion tensor imaging data were computed for 20 white matter tracts (9 left-right corresponding tracts and 2 commissural tracts), with tract-based measures of fractional anisotropy and axial and radial diffusivity. Microstructural maturation between birth and 1 year are much greater than subsequent changes. Further, by 1 year, individual differences in tract average values are consistently predictive of the respective 6-year values, explaining, on average, 40% of the variance in 6-year microstructure. Results provide further evidence of the importance of the first year of life with regard to white matter development, with potential implications for informing early intervention efforts that target specific sensitive periods.

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.

Sex differences in brain-behavior relationships in the first two years of life.

Background: Evidence for sex differences in cognition in childhood is established, but less is known about the underlying neural mechanisms for these differences. Recent findings suggest the existence of brain-behavior relationship heterogeneities during infancy; however, it remains unclear whether sex underlies these heterogeneities during this critical period when sex-related behavioral differences arise. Methods: A sample of 316 infants was included with resting-state functional magnetic resonance imaging scans at neonate (3 weeks), 1, and 2 years of age. We used multiple linear regression to test interactions between sex and resting-state functional connectivity on behavioral scores of working memory, inhibitory self-control, intelligence, and anxiety collected at 4 years of age. Results: We found six age-specific, intra-hemispheric connections showing significant and robust sex differences in functional connectivity-behavior relationships. All connections are either with the prefrontal cortex or the temporal pole, which has direct anatomical pathways to the prefrontal cortex. Sex differences in functional connectivity only emerge when associated with behavior, and not in functional connectivity alone. Furthermore, at neonate and 2 years of age, these age-specific connections displayed greater connectivity in males and lower connectivity in females in association with better behavioral scores. Conclusions: Taken together, we critically capture robust and conserved brain mechanisms that are distinct to sex and are defined by their relationship to behavioral outcomes. Our results establish brain-behavior mechanisms as an important feature in the search for sex differences during development.

Early Childhood Development of Node Centrality in the White Matter Connectome and Its Relationship to IQ at Age 6 Years.

BACKGROUND: The white matter (WM) connectome is important for cognitive development and intelligence and is altered in neuropsychiatric illnesses. Little is known about how the WM connectome develops or its relationship to IQ in early childhood. METHODS: The development of node centrality in the WM connectome was studied in a longitudinal cohort of 226 (123 female) children from the University of North Carolina Early Brain Development Study. Structural and diffusion-weighted images were acquired after birth and at 1, 2, 4, and 6 years, and IQ was assessed at 6 years. Eigenvector centrality, betweenness centrality, and the global graph metrics of global efficiency, small worldness, and modularity were determined at each age. RESULTS: The greatest developmental change in eigenvector centrality and betweenness centrality occurred during the first year of life, with relative stability between ages 1 and 6 years. Most of the high-centrality hubs at age 6 were also high-centrality hubs at 1 year, and many were already high-centrality hubs at birth. There were generally small but significant changes in global efficiency and modularity from birth to 6 years, while small worldness increased between 2 and 4 years. Individual node centrality was not significantly correlated with IQ at 6 years. CONCLUSIONS: Node centrality in the WM connectome is established very early in childhood and is relatively stable from age 1 to 6 years. Many high-centrality hubs are established before birth, and most are present by age 1.

Sex differences in resting state functional connectivity across the first two years of life.

Sex differences in behavior have been reported from infancy through adulthood, but little is known about sex effects on functional circuitry in early infancy. Moreover, the relationship between early sex effects on the functional architecture of the brain and later behavioral performance remains to be elucidated. In this study, we used resting-state fMRI and a novel heatmap analysis to examine sex differences in functional connectivity with cross-sectional and longitudinal mixed models in a large cohort of infants (n = 319 neonates, 1-, and 2-year-olds). An adult dataset (n = 92) was also included for comparison. We investigated the relationship between sex differences in functional circuitry and later measures of language (collected in 1- and 2-year-olds) as well as indices of anxiety, executive function, and intelligence (collected in 4-year-olds). Brain areas showing the most significant sex differences were age-specific across infancy, with two temporal regions demonstrating consistent differences. Measures of functional connectivity showing sex differences in infancy were significantly associated with subsequent behavioral scores of language, executive function, and intelligence. Our findings provide insights into the effects of sex on dynamic neurodevelopmental trajectories during infancy and lay an important foundation for understanding the mechanisms underlying sex differences in health and disease.

Diffusion Tensor Based White Matter Tract Atlases for Pediatric Populations.

Diffusion Tensor Imaging (DTI) is a non-invasive neuroimaging method that has become the most widely employed MRI modality for investigations of white matter fiber pathways. DTI has proven especially valuable for improving our understanding of normative white matter maturation across the life span and has also been used to index clinical pathology and cognitive function. Despite its increasing popularity, especially in pediatric research, the majority of existing studies examining infant white matter maturation depend on regional or white matter skeleton-based approaches. These methods generally lack the sensitivity and spatial specificity of more advanced functional analysis options that provide information about microstructural properties of white matter along fiber bundles. DTI studies of early postnatal brain development show that profound microstructural and maturational changes take place during the first two years of life. The pattern and rate of these changes vary greatly throughout the brain during this time compared to the rest of the life span. For this reason, appropriate image processing of infant MR imaging requires the use of age-specific reference atlases. This article provides an overview of the pre-processing, atlas building, and the fiber tractography procedures used to generate two atlas resources, one for neonates and one for 1- to 2-year-old populations. Via the UNC-NAMIC DTI Fiber Analysis Framework, our pediatric atlases provide the computational templates necessary for the fully automatic analysis of infant DTI data. To the best of our knowledge, these atlases are the first comprehensive population diffusion fiber atlases in early pediatric ages that are publicly available.

Parent-Child Mindfulness-Based Training: A Feasibility and Acceptability Study.

Stress in young children can interfere with academic achievement. To help address stress and aid in developing beneficial lifelong coping skills, educational systems are more widely incorporating programs that teach social and emotional regulation, such as mindfulness-based programs. The effects of these programs may be strengthened through parental support in the home environment. This study examined the feasibility and acceptability of a new Parent-Child Mindfulness-Based Training (PC-MBT) program, which delivered mindfulness-based training to parents and children simultaneously in the home environment. This study also implemented a working memory training after PC-MBT to assess the feasibility of completing two trainings sequentially. Healthy children, ages 8-10 (n = 14), and their parents participated in the PC-MBT program. They met with an instructor at home and online each week for 6 weeks and were provided resources including books, worksheets, audio recordings, and daily practices to reinforce mindfulness skills. A control group (n = 8) participated in the working memory training only. All PC-MBT and control children, except one, participated in the working memory training. All PC-MBT assigned families completed the PC-MBT program, and a majority utilized all types of the mindfulness training materials. A majority of participants also reported high levels of enjoyment and understanding of the PC-MBT program. This study establishes the feasibility and acceptability of the PC-MBT program and lays the foundation for future studies to assess program efficacy in healthy and clinical populations as well as the utility of PC-MBT to improve engagement and outcomes of other cognitive training programs.

Canonical correlation analysis for elliptical copulas.

Canonical correlation analysis (CCA) is a common method used to estimate the associations between two different sets of variables by maximizing the Pearson correlation between linear combinations of the two sets of variables. We propose a version of CCA for transelliptical distributions with an elliptical copula using pairwise Kendall's tau to estimate a latent scatter matrix. Because Kendall's tau relies only on the ranks of the data this method does not make any assumptions about the marginal distributions of the variables, and is valid when moments do not exist. We establish consistency and asymptotic normality for canonical directions and correlations estimated using Kendall's tau. Simulations indicate that this estimator outperforms standard CCA for data generated from heavy tailed elliptical distributions. Our method also identifies more meaningful relationships when the marginal distributions are skewed. We also propose a method for testing for non-zero canonical correlations using bootstrap methods. This testing procedure does not require any assumptions on the joint distribution of the variables and works for all elliptical copulas. This is in contrast to permutation tests which are only valid when data are generated from a distribution with a Gaussian copula. This method's practical utility is shown in an analysis of the association between radial diffusivity in white matter tracts and cognitive tests scores for six-year-old children from the Early Brain Development Study at UNC-Chapel Hill. An R package implementing this method is available at github.com/blangworthy/transCCA.

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.

Individual differences in neonatal white matter are associated with executive function at 3 years of age.

The development of executive function (EF) in early childhood contributes to social and academic aspects of school readiness and facilitates emerging self-regulatory competence. Numerous efforts are underway to identify aspects of early brain development that contribute to emerging EF. Existing research supports the importance of multiple white matter tracts for EF in older children and adults. However, this research has not been extended to young children. In this study, we consider neonatal white matter microstructure in relation to children's performance on a battery of EF tasks three years later. We obtained diffusion tensor imaging data from a sample of neonates (N = 27) shortly after birth. At 3 years of age, children completed a computerized battery of EF tasks. The primary data analyses involved regression models estimated for each white matter tract. Multiple demographic and measure-related covariates were included in each model. A follow-up analysis of tracts determined to be associated with EF examined individual data points along those fibers. Among the white matter tracts analyzed, the cingulum was significantly associated with EF at 3 years of age. Specifically, lower axial diffusivity values along the cingulum were associated with increased performance on the EF battery. Results are discussed as providing initial evidence that individual differences in neonatal brain structure may facilitate the acquisition of EF abilities in early childhood. These findings are consistent with previous research that supports the value of the cingulum for higher-order cognitive abilities. Cautions and implications of these results are considered.

Development of Amygdala Functional Connectivity During Infancy and Its Relationship With 4-Year Behavioral Outcomes.

BACKGROUND: The amygdala represents a core node in the human brain's emotional signal processing circuitry. Given its critical role, both the typical and atypical functional connectivity patterns of the amygdala have been extensively studied in adults. However, the development of amygdala functional connectivity during infancy is less well studied; thus, our understanding of the normal growth trajectory of key emotion-related brain circuits during a critical period is limited. METHODS: In this study, we used resting-state functional magnetic resonance imaging (N = 233 subjects with 334 datasets) to delineate the spatiotemporal dynamics of amygdala functional connectivity development during the first 2 years of life. Their relationships with 4-year emotional (i.e., anxiety and inhibitory self-control parent report measures) and cognitive (i.e., IQ) behavioral outcomes were also assessed using multivariate modeling. RESULTS: Our results revealed nonlinear growth of amygdala functional connectivity during the first 2 years of life, featuring dramatic synchronization during the first year followed by moderate growth or fine tuning during the second year. Importantly, functional connectivity growth during the second year had significant behavioral implications exemplified by multiple significant predictions of 4-year emotional and cognitive developmental outcomes. CONCLUSIONS: The delineation of the spatiotemporal dynamics of amygdala functional connectivity development during infancy and their associations with 4-year behavioral outcomes may provide new references on the early emergence of both typical and atypical emotion processing capabilities.

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 development and validation of attention constructs from the First Year Inventory.

Individual differences in early attention are associated with later social, cognitive, and emotional development, and attentional deficits in the first year are associated with risk for developmental disorders such as Autism Spectrum Disorder (ASD). The First Year Inventory (FYI; Baranek, Watson, Crais, & Reznick, 2003) was developed to identify 12-month-olds at risk for an ASD diagnosis. The current study identifies FYI items that reflect aspects of early attention that might predict future typical and atypical social, cognitive, and emotional development. Using a series of theoretical and statistical methods, we developed 3 attention-based constructs from the FYI: Responding to Social Attention (RSA), Initiating Social Attention (ISA), and Nonsocial Sensory Attention (NSA). A database with completed FYIs was analyzed using these constructs to determine the strength of relations among items. Cronbach's alpha analyses indicated good internal consistency, and item distribution was further supported using a confirmatory factor analysis. Data analyses showed statistically significant relations between the scores on these domains at 12 months and subsequent social responsiveness scores at 3 years. Analyses demonstrating the statistical and predictive validity of these 3 FYI attention constructs support their use for innovative explorations of infant behavioral patterns that can be used to predict typical and atypical individual trajectories in the development of later social, cognitive, and emotional skills. (PsycINFO Database Record

Maternal depressive symptomatology: 16-month follow-up of infant and maternal health-related quality of life.

PURPOSE: The purpose of this study was to document risk factors for depressive symptoms during the postpartum period among working mothers and to determine longitudinal effects of depressive symptoms on maternal health-related quality of life and infant health and development. METHODS: Mother-infant dyads from a community-based cohort study of working mothers were recruited when infants were 4 months old and were interviewed every 4 months until infants were 16 months old. Depressive symptoms and health-related quality of life were assessed using the Center for Epidemiologic Studies Depression Scale and the Short Form-12 Health Survey, respectively. Infant development and health-related quality of life were measured with the Ages and Stages Questionnaire and the Infant-Toddler Quality of Life Questionnaire, respectively. RESULTS: Depressive symptoms were elevated among mothers who were younger, less educated, African American, unmarried, and impoverished. Mothers with significant depressive symptoms had significantly poorer physical and mental health-related quality of life, reported greater pain for their infant, and had more health-related concerns about their child. Maternal depressive symptoms at 4 months predicted infant poorer health-related quality of life at 8, 12, and 16 months. CONCLUSIONS: Several characteristics, including age, education level, race, marital status, and poverty, can help primary care physicians identify working mothers at risk for depressive symptoms. Identification of these symptoms is important; they are correlated with poorer maternal health-related quality of life and they predict poorer children's health-related quality of life.