Gray and White Matter Metrics Demonstrate Distinct and Complementary Prediction of Differences in Cognitive Performance in Children: Findings from ABCD (N = 11,876).

Individual differences in cognitive performance in childhood are a key predictor of significant life outcomes such as educational attainment and mental health. Differences in cognitive ability are governed in part by variations in brain structure. However, studies commonly focus on either gray or white matter metrics in humans, leaving open the key question as to whether gray or white matter microstructure plays distinct or complementary roles supporting cognitive performance. To compare the role of gray and white matter in supporting cognitive performance, we used regularized structural equation models to predict cognitive performance with gray and white matter measures. Specifically, we compared how gray matter (volume, cortical thickness, and surface area) and white matter measures (volume, fractional anisotropy, and mean diffusivity) predicted individual differences in cognitive performance. The models were tested in 11,876 children (ABCD Study; 5,680 female, 6,196 male) at 10 years old. We found that gray and white matter metrics bring partly nonoverlapping information to predict cognitive performance. The models with only gray or white matter explained respectively 15.4 and 12.4% of the variance in cognitive performance, while the combined model explained 19.0%. Zooming in, we additionally found that different metrics within gray and white matter had different predictive power and that the tracts/regions that were most predictive of cognitive performance differed across metrics. These results show that studies focusing on a single metric in either gray or white matter to study the link between brain structure and cognitive performance are missing a key part of the equation.

Common Cause Versus Dynamic Mutualism: An Empirical Comparison of Two Theories of Psychopathology in Two Large Longitudinal Cohorts.

Mental disorders are among the leading causes of global disease burden. To respond effectively, a strong understanding of the structure of psychopathology is critical. We empirically compared two competing frameworks, dynamic-mutualism theory and common-cause theory, that vie to explain the development of psychopathology. We formalized these theories in statistical models and applied them to explain change in the general factor of psychopathology (p factor) from early to late adolescence (N = 1,482) and major depression in middle adulthood and old age (N = 6,443). Change in the p factor was better explained by mutualism according to model-fit indices. However, a core prediction of mutualism was not supported (i.e., predominantly positive causal interactions among distinct domains). The evidence for change in depression was more ambiguous. Our results support a multicausal approach to understanding psychopathology and showcase the value of translating theories into testable statistical models for understanding developmental processes in clinical sciences.

Protocol and preregistration for the CODEC project: measuring, modelling and mechanistically understanding the nature of cognitive variability in early childhood.

BACKGROUND: Children's cognitive performance fluctuates across multiple timescales. However, fluctuations have often been neglected in favour of research into average cognitive performance, limiting the unique insights into cognitive abilities and development that cognitive variability may afford. Preliminary evidence suggests that greater variability is associated with increased symptoms of neurodevelopmental disorders, and differences in behavioural and neural functioning. The relative dearth of empirical work on variability, historically limited due to a lack of suitable data and quantitative methodology, has left crucial questions unanswered, which the CODEC (COgnitive Dynamics in Early Childhood) study aims to address. METHOD: The CODEC cohort is an accelerated 3-year longitudinal study which encompasses 600 7-to-10-year-old children. Each year includes a 'burst' week (3 times per day, 5 days per week) of cognitive measurements on five cognitive domains (reasoning, working memory, processing speed, vocabulary, exploration), conducted both in classrooms and at home through experience sampling assessments. We also measure academic outcomes and external factors hypothesised to predict cognitive variability, including sleep, mood, motivation and background noise. A subset of 200 children (CODEC-MRI) are invited for two deep phenotyping sessions (in year 1 and year 3 of the study), including structural and functional magnetic resonance imaging, eye-tracking, parental measurements and questionnaire-based demographic and psychosocial measures. We will quantify developmental differences and changes in variability using Dynamic Structural Equation Modelling, allowing us to simultaneously capture variability and the multilevel structure of trials nested in sessions, days, children and classrooms. DISCUSSION: CODEC's unique design allows us to measure variability across a range of different cognitive domains, ages, and temporal resolutions. The deep-phenotyping arm allows us to test hypotheses concerning variability, including the role of mind wandering, strategy exploration, mood, sleep, and brain structure. Due to CODEC's longitudinal nature, we are able to quantify which measures of variability at baseline predict long-term outcomes. In summary, the CODEC study is a unique longitudinal study combining experience sampling, an accelerated longitudinal 'burst' design, deep phenotyping, and cutting-edge statistical methodologies to better understand the nature, causes, and consequences of cognitive variability in children. TRIAL REGISTRATION: ClinicalTrials.gov - NCT06330090.