Multimethod investigation of the neurobiological basis of ADHD symptomatology in children aged 9-10: baseline data from the ABCD study

Abstract Attention deficit/hyperactivity disorder is associated with numerous neurocognitive deficits, including poor working memory and difficulty inhibiting undesirable behaviors that cause academic and behavioral problems in children. Prior work has attempted to determine how these differences are instantiated in the structure and function of the brain, but much of that work has been done in small samples, focused on older adolescents or adults, and used statistical approaches that were not robust to model overfitting. The current study used cross-validated elastic net regression to predict a continuous measure of ADHD symptomatology using brain morphometry and activation during tasks of working memory, inhibitory control, and reward processing, with separate models for each MRI measure. The best model using activation during the working memory task to predict ADHD symptomatology had an out-of-sample R 2 = 2% and was robust to residualizing the effects of age, sex, race, parental income and education, handedness, pubertal status, and internalizing symptoms from ADHD symptomatology. This model used reduced activation in task positive regions and reduced deactivation in task negative regions to predict ADHD symptomatology. The best model with morphometry alone predicted ADHD symptomatology with an R 2 = 1% but this effect dissipated when including covariates. The inhibitory control and reward tasks did not yield generalizable models. In summary, these analyses show, with a large and well-characterized sample, that the brain correlates of ADHD symptomatology are modest in effect size and captured best by brain morphometry and activation during a working memory task.