Connor McCabe

Neuroanatomical assessment of biological maturity

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.

Multimodal imaging of the self-regulating developing brain

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.

Long-term influence of normal variation in neonatal characteristics on human brain development

It is now recognized that a number of cognitive, behavioral, and mental health outcomes across the lifespan can be traced to fetal development. Although the direct mediation is unknown, the substantial variance in fetal growth, most commonly indexed by birth weight, may affect lifespan brain development. We investigated effects of normal variance in birth weight on MRI-derived measures of brain development in 628 healthy children, adolescents, and young adults in the large-scale multicenter Pediatric Imaging, Neurocognition, and Genetics study. This heterogeneous sample was recruited through geographically dispersed sites in the United States. The influence of birth weight on cortical thickness, surface area, and striatal and total brain volumes was investigated, controlling for variance in age, sex, household income, and genetic ancestry factors. Birth weight was found to exert robust positive effects on regional cortical surface area in multiple regions as well as total brain and caudate volumes. These effects were continuous across birth weight ranges and ages and were not confined to subsets of the sample. The findings show that (i) aspects of later child and adolescent brain development are influenced at birth and (ii) relatively small differences in birth weight across groups and conditions typically compared in neuropsychiatric research (e.g., Attention Deficit Hyperactivity Disorder, schizophrenia, and personality disorders) may influence group differences observed in brain parameters of interest at a later stage in life. These findings should serve to increase our attention to early influences.

The Pediatric Imaging, Neurocognition, and Genetics (PING) Data Repository

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.

The NIH Toolbox Cognition Battery: Results from a Large Normative Developmental Sample (PING)

OBJECTIVE The 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. METHOD The 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. RESULTS General 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. CONCLUSIONS The 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.

Current methods and limitations for longitudinal fMRI analysis across development

The human brain is remarkably plastic. The brain changes dramatically across development, with ongoing functional development continuing well into the third decade of life and substantial changes occurring again in older age. Dynamic changes in brain function are thought to underlie the innumerable changes in cognition, emotion, and behavior that occur across development. The brain also changes in response to experience, which raises important questions about how the environment influences the developing brain. Longitudinal functional magnetic resonance imaging (fMRI) studies are an essential means of understanding these developmental changes and their cognitive, emotional, and behavioral correlates. This paper provides an overview of common statistical models of longitudinal change applicable to developmental cognitive neuroscience, and a review of the functionality provided by major software packages for longitudinal fMRI analysis. We demonstrate that there are important developmental questions that cannot be answered using available software. We propose alternative approaches for addressing problems that are commonly faced in modeling developmental change with fMRI data.

Longitudinal modeling in developmental neuroimaging research: Common challenges, and solutions from developmental psychology

Hypotheses about change over time are central to informing our understanding of development. Developmental neuroscience is at critical juncture: although the majority of longitudinal imaging studies have observations with two time points, researchers are increasingly obtaining three or more observations of the same individuals. The goals of the proposed manuscript are to draw upon the long history of methodological and applied literature on longitudinal statistical models to summarize common problems and issues that arise in their use. We also provide suggestions and solutions to improve the design, analysis and interpretation of longitudinal data, and discuss the importance of matching the theory of change with the appropriate statistical model used to test the theory. Researchers should articulate a clear theory of change and to design studies to capture that change and use appropriately sensitive measures to assess that change during development. Simulated data are used to demonstrate several common analytic approaches to longitudinal analyses. We provide the code for our simulations and figures in an online supplement to aid researchers in exploring and plotting their data. We provide brief examples of best practices for reporting such models. Finally, we clarify common misunderstandings in the application and interpretation of these analytic approaches.

Detecting random responders with infrequency scales using an error-balancing threshold

Infrequency scales are becoming a popular mode of data screening, due to their availability and ease of implementation. Recent research has indicated that the interpretation and functioning of infrequency items may not be as straightforward as had previously been thought (Curran & Hauser, 2015), yet there are no empirically based guidelines for implementing cutoffs using these items. In the present study, we compared two methods of detecting random responding with infrequency items: a zero-tolerance threshold versus a threshold that balances classification error rates. The results showed that a traditional zero-tolerance approach, on average, screens data that are less indicative of careless responding than those screened by the error-balancing approach. Thus, the de facto standard of applying a “zero-tolerance” approach when screening participants with infrequency scales may be too stringent, so that meaningful responses may also be removed from analyses. Recommendations and future directions are discussed.

Improving Present Practices in the Visual Display of Interactions

Interaction plots are used frequently in psychology research to make inferences about moderation hypotheses. A common method of analyzing and displaying interactions is to create simple-slopes or marginal-effects plots using standard software programs. However, these plots omit features that are essential to both graphic integrity and statistical inference. For example, they often do not display all quantities of interest, omit information about uncertainty, or do not show the observed data underlying an interaction, and failure to include these features undermines the strength of the inferences that may be drawn from such displays. Here, we review the strengths and limitations of present practices in analyzing and visualizing interaction effects in psychology. We provide simulated examples of the conditions under which visual displays may lead to inappropriate inferences and introduce open-source software that provides optimized utilities for analyzing and visualizing interactions.

Random responses inflate statistical estimates in heavily skewed addictions data

BACKGROUND Some respondents may respond at random to self-report surveys, rather than responding conscientiously (Meade and Craig, 2012), and this has only recently come to the attention of researchers in the addictions field (Godinho et al., 2016). Almost no research in the published addictions literature has reported screening for random responses. We illustrate how random responses can bias statistical estimates using simulated and real data, and how this is especially problematic in skewed data, as is common with substance use outcomes. METHOD We first tested the effects of varying amounts and types of random responses on covariance-based statistical estimates in distributions with varying amounts of skew. We replicated these findings in correlations from a real dataset (Add Health) by replacing varying amounts of real data with simulated random responses. RESULTS Skew and the proportion of random responses influenced the amount and direction of bias. When the data were not skewed, uniformly random responses deflated estimates, while long-string random responses inflated estimates. As the distributions became more skewed, all types of random responses began to inflate estimates, even at very small proportions. We observed similar effects in the Add Health data. CONCLUSIONS Failing to screen for random responses in survey data produces biased statistical estimates, and data with only 2.5% random responses can inflate covariance-based estimates (i.e., correlations, Cronbachs alpha, regression coefficients, factor loadings, etc.) when data are heavily skewed. Screening for random responses can substantially improve data quality, reliability and validity.