NOVEL CORTICAL LIMBIC ANALYSIS IN TWINS DISCORDANT FOR ADHD

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DESCRIPTION (provided by applicant): Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable neurodevelopmental disorder hypothesized to have very early developmental origins. A number of functional and structural neuroimaging studies suggest that there are relatively diffuse widespread cortical and subcortical differences with heightened focal differences occurring in frontal, striatal and parietal regions. This R21 proposal aims to utilize two new image analysis methods to characterize the cortex in adolescents and young adults with inattentive ADHD in an existing, unique multi-national pilot imaging data set of twins discordant for inattentive ADHD. We propose to characterize differences in sulcal/gyral folding patterns associated with inattentive ADHD across the whole cerebral cortex using surface based analysis methods, to derive sulcal depth maps, recently developed and implemented by Van Essen and colleagues. Concurrently we will use methods established by Miller and colleagues to quantify local cortical distance metrics (LCDM) in the cingulate cortex, a region which is hypothesized to be disrupted in ADHD. Results from surface sulcal depth analyses will be used to identify, in an integrated fashion, additional regions of interest to investigate via LCDM. Thus this application proposes several unique, cutting-edge image analysis techniques which have never been previously combined for the study of any disorder. We hypothesize this combination has a strong potential to substantially further our knowledge of the underlying pathophysiology of ADHD. However since these methods have not been applied previously to the investigation of ADHD or used concurrently in any investigation, this project is considered too preliminary for an R01 application. We seek to achieve the following three primary Aims: 1) characterize differences associated with inattentive ADHD in sulcal depth measures across the whole cortex; 2) quantify differences in LCDM of the cingulate cortex associated with inattentive ADHD; and 3) characterize regional cortical morphology by LCDM in regions of identified differences by sulcal metrics in this same population. Achieving these Aims with these combined methods will demonstrate the feasibility and utility of jointly applying these techniques in ADHD in order to eventually pursue a larger more definitive R01 study. If funded this project will be the first to examine and characterize cortical folding abnormalities in ADHD and the first to combine sulcal depth mapping with local cortical metric characterization in any disorder. We hypothesize that the combined use of these two unique image analysis approaches will provide a powerful mechanism to characterize cortical characteristics and will significantly advance our understanding of the underlying pathophysiology of ADHD and psychiatric disorders. PUBLIC HEALTH RELEVANCE ADHD is estimated to affect 5-12% of the population worldwide and because of its associated functional impairment and morbidity has significant public health impact. The prevalence of ADHD and its pervasive influence on individual and family functioning make it a significant public health concern. The underlying neurobiology of ADHD is incompletely understood and this project seeks to understand cortical folding characteristics of ADHD.