The overall goal of this project is to evaluate a new model for understanding the neurologic basis of Attention Deficit Hyperactivity Disorder (ADHD). Theories about neural mechanisms have recently focused on deficient response inhibition as one of the fundamental features driving the pathophysiology of ADHD; however, the nature of these deficits and their neurologic underpinnings remain unclear. Previous investigators have attempted to view response inhibition as a unitary phenomenon, theorizing that its neurologic basis could be localized to a specific frontal region (i.e., a specific frontal sub-cortical circuit), which, once recognized, could then be regarded as the brain basis for ADHD. Recent data from electrophysiology and imaging studies, however, support a multiple-domain model of response inhibition according to which the specific frontal-sub-cortical circuit crucial for response inhibition depends on the nature of the task skeletomotor, oculomotor, cognitive, socioemotional) being performed. In ADHD, there is evidence for impairment on tasks reflecting all four of these domains of response inhibition; furthermore, recent imaging findings suggest that frontal abnormalities in ADHD involve regions within both premotor and prefrontal cortices. Accordingly, we propose to use neurobehavioral testing, anatomic MRI, and functional MRI to investigate the hypothesis that deficient response inhibition associated with ADHD is not a unitary phenomenon localized to one specific frontal region. Rather, impairments across skeletomotor, oculomotor, cognitive, and socioemotional domains of response inhibition are each linked to abnormality within a specific frontal circuit: skeletomotor, oculomotor, dorsolateral prefrontal and orbitoficontal, respectively. The findings will not only contribute to increased understanding of the pathophysiology of ADHD, but could also lay the foundation for neurobiological sub-typing of ADHD and in doing so improve diagnosis and decisions regarding targeted interventions. The conduct of this research project will also provide opportunities to extend, in both scope and in level of depth, investigative work begun during the candidate's training grant and to collaborate with scientists in related fields of discipline, helping to establish the candidate as an independent investigator.
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