Structural and Functional Biomarkers of Attention-Deficit/Hyperactivity Disorder

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Abstract ADHD is one of the most highly prevalent (5-10%) child-onset neurodevelopmental disorders worldwide with an economic burden to society estimated to be in the tens of billions per year. Behaviorally, ADHD is characterized by problems with sustained attention and hyperactivity/impulsivity that often impair academic, social, and occupational abilities. The negative consequences of diminished social functioning put children with ADHD at greater risk for behavioral/emotional problems including anxiety and depression, and untreated adolescents with ADHD are at greater risk for drug use, nicotine dependency, and automobile accidents. Understanding the neural correlates of this disorder is of high importance for this population, as improved models of the disease could in turn inform individualized targeted therapies for optimal behavioral and cognitive benefit. Our recent work suggests that brain asymmetries in structural and functional MRI measures may be more valuable as descriptors for quantifying developmental differences in the ADHD brain than lateralized (left/right) measures alone. Building on this work, we will now examine how these asymmetries are altered over the course of treatment with stimulant medications. We hypothesize that hemispheric asymmetry differences may resolve to some extent after successful response to pharmaceutical therapy. Next, we will track brain white matter changes (and asymmetries) using DTI imaging before and after medication treatment to determine their potential in predicting a beneficial behavioral response to pharmacotherapy in ADHD-affected youth. It is then reasonable to ask - how are structural asymmetry differences linked to functional differences in the ADHD brain? We will address this question by connecting structural and functional MRI features with clinical assessment scores using an innovative approach to data clustering. We expect that this integrative approach will provide a link between the behavioral traits and quantitative brain biomarkers of ADHD. This project advances the Candidate's training by building on background strengths in neuroimaging and computational neuroscience while providing new training in translational research, data collection in childhood populations, coursework in the phenomenology and etiology of pediatric neurodevelopmental disorders, and clinical shadowing of intake and assessments of children suspected to have ADHD. The growth provided will make the candidate more specialized in translational research and neurodevelopmental disorders, making the candidate well suited for success as an independent investigator.