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The causes that individuals attribute to reading outcomes shape future behaviors, including engagement or persistence with learning tasks. Although previous reading motivation research has examined differences between typical and struggling readers, there may be unique dynamics related to varying levels of reading and attention skills. Using latent profile analysis, we found 4 groups informed by internal attributions to ability and effort. Reading skills, inattention, and hyperactivity/impulsivity were investigated as functional correlates of attribution profiles. Participants were 1,312 youth (8-15 years of age) of predominantly African American and Hispanic racial/ethnic heritage. More adaptive attribution profiles had greater reading performance and lower inattention. The reverse was found for the least adaptive profile with associations to greater reading and attention difficulties. Distinct attribution profiles also existed across similar-achieving groups. Understanding reading-related attributions may inform instructional efforts in reading. Promoting adaptive attributions may foster engagement with texts despite learning difficulties and, in turn, support reading achievement.

Anxiety is a risk factor for many adverse neuropsychiatric and socioeconomic outcomes, and has been linked to functional and structural changes in the ventromedial prefrontal cortex (VMPFC). However, the nature of these differences, as well as how they develop in children and adolescents, remains poorly understood. More effective interventions to minimize the negative consequences of anxiety require better understanding of its neurobiology in children. Recent research suggests that structural imaging studies may benefit from clearly delineating between cortical surface area and thickness when examining these associations, as these distinct cortical phenotypes are influenced by different cellular mechanisms and genetic factors. The present study examined relationships between cortical surface area and thickness of the VMPFC and a self-report measure of anxiety (SCARED-R) in 287 youths aged 7-20 years from the Pediatric Imaging, Neurocognition, and Genetics (PING) study. Age and gender interactions were examined for significant associations in order to test for developmental differences. Cortical surface area and thickness were also examined simultaneously to determine whether they contribute independently to the prediction of anxiety. Anxiety was negatively associated with relative cortical surface area of the VMPFC as well as with global cortical thickness, but these associations diminished with age. The two cortical phenotypes contributed additively to the prediction of anxiety. These findings suggest that higher anxiety in children may be characterized by both delayed expansion of the VMPFC and an altered trajectory of global cortical thinning. Further longitudinal studies will be needed to confirm these findings.

Dyslexia and language impairment (LI) are complex traits with substantial genetic components. We recently completed an association scan of the DYX2 locus, where we observed associations of markers in DCDC2, KIAA0319, ACOT13, and FAM65B with reading-, language-, and IQ-related traits. Additionally, the effects of reading-associated DYX3 markers were recently characterized using structural neuroimaging techniques. Here, we assessed the neuroimaging implications of associated DYX2 and DYX3 markers, using cortical volume, cortical thickness, and fractional anisotropy. To accomplish this, we examined eight DYX2 and three DYX3 markers in 332 subjects in the Pediatrics Imaging Neurocognition Genetics study. Imaging-genetic associations were examined by multiple linear regression, testing for influence of genotype on neuroimaging. Markers in DYX2 genes KIAA0319 and FAM65B were associated with cortical thickness in the left orbitofrontal region and global fractional anisotropy, respectively. KIAA0319 and ACOT13 were suggestively associated with overall fractional anisotropy and left pars opercularis cortical thickness, respectively. DYX3 markers showed suggestive associations with cortical thickness and volume measures in temporal regions. Notably, we did not replicate association of DYX3 markers with hippocampal measures. In summary, we performed a neuroimaging follow-up of reading-, language-, and IQ-associated DYX2 and DYX3 markers. DYX2 associations with cortical thickness may reflect variations in their role in neuronal migration. Furthermore, our findings complement gene expression and imaging studies implicating DYX3 markers in temporal regions. These studies offer insight into where and how DYX2 and DYX3 risk variants may influence neuroimaging traits. Future studies should further connect the pathways to risk variants associated with neuroimaging/neurocognitive outcomes.

The main objective of the multi-site Pediatric Imaging, Neurocognition, and Genetics (PING) study was to create a large repository of standardized measurements of behavioral and imaging phenotypes accompanied by whole genome genotyping acquired from typically-developing children varying widely in age (3 to 20 years). This cross-sectional study produced sharable data from 1493 children, and these data have been described in several publications focusing on brain and cognitive development. Researchers may gain access to these data by applying for an account on the PING portal and filing a data use agreement. Here we describe the recruiting and screening of the children and give a brief overview of the assessments performed, the imaging methods applied, the genetic data produced, and the numbers of cases for whom different data types are available. We also cite sources of more detailed information about the methods and data. Finally we describe the procedures for accessing the data and for using the PING data exploration portal.

Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. We investigated relationships between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1,099 typically developing individuals between 3 and 20 years of age. Income was logarithmically associated with brain surface area. Among children from lower income families, small differences in income were associated with relatively large differences in surface area, whereas, among children from higher income families, similar income increments were associated with smaller differences in surface area. These relationships were most prominent in regions supporting language, reading, executive functions and spatial skills; surface area mediated socioeconomic differences in certain neurocognitive abilities. These data imply that income relates most strongly to brain structure among the most disadvantaged children.

The present study investigated the relation among reading skills and attributions, naming speed, and phonological awareness across a wide range of reading skill. Participants were 1,105 school-age children and youths from two understudied populations: African Americans and Hispanic Americans. Individual assessments of children ranging in age from 8 to 15 years were conducted for reading outcomes, cognitive and linguistic predictors of reading, and attributions for success and failure in reading situations. Quantile regressions were formulated to estimate these relations across the full skill span of each outcome. Reading-related attributions predicted contextual word recognition, sight word and decoding fluency, and comprehension skills. Attributions to ability in success situations were positively related to each outcome across the full span. On three reading outcomes, this relation strengthened at higher skill levels. Attributions to effort in success situations were consistently and negatively related to all reading outcomes. The results provide evidence that the strength of the relation between reading and attributions varies according to reading skill levels, with the strongest evidence for ability-based attributions in situations of reading success.

ObjectiveThe NIH Toolbox Cognition Battery (NTCB) was designed to provide a brief, efficient computerized test of key neuropsychological functions appropriate for use in children as young as 3 years of age. This report describes the performance of a large group of typically developing children and adolescents and examines the impact of age and sociocultural variables on test performance.MethodThe NTCB was administered to a sample of 1,020 typically developing males and females ranging in age from 3 to 20 years, diverse in terms of socioeconomic status (SES) and race/ethnicity, as part of the new publicly accessible Pediatric Imaging, Neurocognition, and Genetics (PING) data resource, at 9 sites across the United States.ResultsGeneral additive models of nonlinear age-functions were estimated from age-differences in test performance on the 8 NTCB subtests while controlling for family SES and genetic ancestry factors (GAFs). Age accounted for the majority of the variance across all NTCB scores, with additional significant contributions of gender on some measures, and of SES and race/ethnicity (GAFs) on all. After adjusting for age and gender, SES and GAFs explained a substantial proportion of the remaining unexplained variance in Picture Vocabulary scores.ConclusionsThe results highlight the sensitivity to developmental effects and efficiency of this new computerized assessment battery for neurodevelopmental research. Limitations are observed in the form of some ceiling effects in older children, some floor effects, particularly on executive function tests in the youngest participants, and evidence for variable measurement sensitivity to cultural/socioeconomic factors.

Competent reading requires various skills beyond those for basic word reading (i.e., core language skills, rapid naming, phonological processing). Contributing "higher-level" or domain-general processes include information processing speed and executive functions (working memory, strategic problem solving, attentional switching). Research in this area has relied on largely Caucasian samples, with limited representation of children from racial or ethnic minority groups. This study examined contributions of executive skills to reading competence in 761 children of minority backgrounds. Hierarchical linear regressions examined unique contributions of executive functions (EF) to word reading, fluency, and comprehension. EF contributed uniquely to reading performance, over and above reading-related language skills; working memory contributed uniquely to all components of reading; while attentional switching, but not problem solving, contributed to isolated and contextual word reading and reading fluency. Problem solving uniquely predicted comprehension, suggesting that this skill may be especially important for reading comprehension in minority youth. Attentional switching may play a unique role in development of reading fluency in minority youth, perhaps as a result of the increased demand for switching between spoken versus written dialects. Findings have implications for educational and clinical practice with regard to reading instruction, remedial reading intervention, and assessment of individuals with reading difficulty.

Self-regulation refers to the ability to control behavior, cognition, and emotions, and self-regulation failure is related to a range of neuropsychiatric problems. It is poorly understood how structural maturation of the brain brings about the gradual improvement in self-regulation during childhood. In a large-scale multicenter effort, 735 children (4-21 y) underwent structural MRI for quantification of cortical thickness and surface area and diffusion tensor imaging for quantification of the quality of major fiber connections. Brain development was related to a standardized measure of cognitive control (the flanker task from the National Institutes of Health Toolbox), a critical component of self-regulation. Ability to inhibit responses and impose cognitive control increased rapidly during preteen years. Surface area of the anterior cingulate cortex accounted for a significant proportion of the variance in cognitive performance. This finding is intriguing, because characteristics of the anterior cingulum are shown to be related to impulse, attention, and executive problems in neurodevelopmental disorders, indicating a neural foundation for self-regulation abilities along a continuum from normality to pathology. The relationship was strongest in the younger children. Properties of large-fiber connections added to the picture by explaining additional variance in cognitive control. Although cognitive control was related to surface area of the anterior cingulate independently of basic processes of mental speed, the relationship between white matter quality and cognitive control could be fully accounted for by speed. The results underscore the need for integration of different aspects of brain maturation to understand the foundations of cognitive development.

Structural MRI allows unparalleled in vivo study of the anatomy of the developing human brain. For more than two decades, MRI research has revealed many new aspects of this multifaceted maturation process, significantly augmenting scientific knowledge gathered from postmortem studies. Postnatal brain development is notably protracted and involves considerable changes in cerebral cortical, subcortical, and cerebellar structures, as well as significant architectural changes in white matter fiber tracts (see [12]). Although much work has described isolated features of neuroanatomical development, it remains a critical challenge to characterize the multidimensional nature of brain anatomy, capturing different phases of development among individuals. Capitalizing on key advances in multisite, multimodal MRI, and using cross-validated nonlinear modeling, we demonstrate that developmental brain phase can be assessed with much greater precision than has been possible using other biological measures, accounting for more than 92% of the variance in age. Further, our composite metric of morphology, diffusivity, and signal intensity shows that the average difference in phase among children of the same age is only about 1 year, revealing for the first time a latent phenotype in the human brain for which maturation timing is tightly controlled.

Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.

Within the human genome, genetic mapping studies have identified 10 regions of different chromosomes, known as DYX loci, in genetic linkage with dyslexia, and two, known as SLI loci, in genetic linkage with Specific Language Impairment (SLI). Further genetic studies have identified four dyslexia genes within the DYX loci: "DYX1C1" on 15q, "KIAA0319" and "DCDC2" on 6p22, and "ROBO1" on 13q. "FOXP2" on 7q has been implicated in the development of Speech-Language Disorder. No genes for Specific Language Impairment have yet been identified within the two SLI loci. Functional studies have shown that all four dyslexia genes play roles in brain development, and ongoing molecular studies are attempting to elucidate how these genes exert their effects at a subcellular level. Taken together, these genes and loci likely represent only a fraction of the human lexinome, a term we introduce here to refer to the collection of all the genetic and protein elements involved in the development of human language, expression, and reading. Learning outcomes: The reader will become familiar with (i) methods for identifying genes for complex diseases, (ii) the application of these methods in the elucidation of genes underlying disorders of language and reading, and (iii) the cellular pathways through which polymorphisms in these genes may contribute to the development of the disorders.

OBJECTIVES. The goals were to isolate and to estimate the genetic susceptibility to retinopathy of prematurity. METHODS. A retrospective study (1994-2004) from 3 centers was performed with zygosity data for premature twins who were born at a gestational age of [less than or equal to] 32 weeks and survived beyond a postmenstrual age of 36 weeks. Retinopathy of prematurity was diagnosed and staged by pediatric ophthalmologists at each center. Data analyses were performed with mixed-effects logistic regression analysis and latent variable probit modeling. RESULTS. A total of 63 monozygotic and 137 dizygotic twin pairs were identified and analyzed. Data on gestational age, birth weight, gender, respiratory distress syndrome, retinopathy of prematurity, bronchopulmonary dysplasia, duration of ventilation and supplemental oxygen use, and length of stay were comparable between monozygotic and dizygotic twins. In the mixed-effects logistic regression analysis for retinopathy of prematurity, gestational age and duration of supplemental oxygen use were significant covariates. After controlling for known and unknown nongenetic factors, genetic factors accounted for 70.1% of the variance in liability for retinopathy of prematurity. CONCLUSION. In addition to prematurity and environmental factors, there is a strong genetic predisposition to retinopathy of prematurity. Key Words neonate, retinopathy of prematurity, twins, genetic Abbreviations ROP--retinopathy of prematurity RDS--respiratory distress syndrome BPD--broncbopulmonary dysplasia MELR--mixed-effects logistic regression GA--gestational age BW--birth weight OR--odds ratio CI--confidence interval, RETINOPATHY OF PREMATURITY (ROP) is a disease process that results from disruption of the normal vascularization of the developing retina. The retinal blood supply is derived from both the choroidal [...]

BACKGROUND. Intraventricular hemorrhage, necrotizing enterocolitis, and broncho-pulmonary dysplasia remain significant causes of morbidity and mortality in preterm newborns. OBJECTIVES. Our goal was to assess the familial and genetic susceptibility to intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia. METHODS. Mixed-effects logistic-regression and latent variable probit model analysis were used to assess the contribution of several covariates in a multicenter retrospective study of 450 twin pairs born at [less than or equal to] 32 weeks of gestation. To determine the genetic contribution, concordance rates in a subset of 252 monozygotic and dizygotic twin pairs were compared. RESULTS. The study population had a mean gestational age of 29 weeks and birth weight of 1286 g. After controlling for effects of covariates, the twin data showed that 41.3%, 51.9%, and 65.2%, respectively, of the variances in liability for intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia could be accounted for by genetic and shared environmental factors. Among the 63 monozygotic twin pairs, the observed concordance for bronchopulmonary dysplasia was significantly higher than the expected concordance; 12 of 18 monozygotic twin pairs with [greater than or equal to] 1 affected member had both members affected versus 3.69 expected. After controlling for covariates, genetic factors accounted for 53% of the variance in liability for bronchopulmonary dysplasia. CONCLUSIONS. Twin analyses show that intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia are familial in origin. These data demonstrate, for the first time, the significant genetic susceptibility for bronchopulmonary dysplasia in preterm infants. Key Words premature newborn, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, logistic regression, zygosity Abbreviations IVH--intraventricular hemorrhage NEC--necrotizing enterocolitis BPD--- bronchopulmonary dysplasia BW--birth weight GA--gestational age RDS--respiratory distress syndrome INST--treating institution OR--odds ratio CI--confidence interval TNF--tumor necrosis factor IL--interleukin, DESPITE SIGNIFICANT CLINICAL advances in neonatal care over the last 2 decades, intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD) continue to account for most of the morbidity [...]