The purpose of this application is to elucidate the brain systems that underlie the deficiencies in attentional control, most notably in the area of executive control and inhibitory processes, in individuals with attention deficit hyperactivity disorder (ADHD). Although considered core deficits (e.g., Nigg, 1999), relatively little is known about the specific neural substrates that might underlie such deficits. Using a combination of behavioral and brain mapping techniques, we propose to address these issues by investigating the hypothesis that these core attentional difficulties manifest in ADHD are a result of dysfunction of specific regions of dorsolateral and medial prefrontal cortex. Furthermore, we will examine the degree to which these neurocognitive difficulties manifest in both adolescent and adult forms of ADHD, and the degree to which they may indicate a genetic vulnerability rather than a marker for the disorder. [unreadable] [unreadable] The team investigating these issues is multi-disciplinary, consisting of a cognitive neuroscientist with a special expertise in attentional control and brain imaging methods, a clinician with expertise in classification and diagnostic issues in ADHD as well as behavioral and molecular genetic techniques, a developmental neuropsychologist with expertise in learning disabilities, and a physicist with expertise in brain imaging. The proposal builds upon the principal investigator's neural model of the brain mechanisms involved in executive aspects of attention, and integrates it with the co-investigator's state-of-the-art model of the clinical manifestations of ADHD. Moreover it employs two well-characterized clinical samples: an adult sample of college-aged individuals with ADHD, and a sample of adolescent and adult dizygotic twins discordant for ADHD, allowing us to validate our findings by testing them across distinct populations. [unreadable] [unreadable] The proposed research has the potential to shed important new light on the nature of ADHD. Elucidating which brain regions are dysfunctional has the potential 1) to increase the ability to specifically diagnose ADHD itself, as well as, providing criteria for differentiating subtypes, 2) to facilitate the development of pharmacological treatments targeting the affected regions, 3) to determine the degree to which the manifestation of ADHD is continuous from childhood through adulthood. [unreadable] [unreadable]