CORTICAL &SUBCORTICAL BRAIN MECHANISMS UNDERLYING ADHD

Hugo W. Moser Res Inst Kennedy Krieger, Baltimore MD

Investigators

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Abstract

DESCRIPTION (provided by applicant): This K08 Supplemental Award proposal is built upon the original three year K08 award that contained a plan to develop the candidate into an independent investigator in the area of developmental behavioral neurology. The original proposal provided for the candidate's development through formal course work, extensive mentorship in a collaborative research environment, and implementation of a study designed to be the first step towards a larger body of research aimed at understanding the neurobiological basis of Attention Deficit Hyperactivity Disorder (ADHD). As originally proposed, experimental neurobehavioral paradigms, structural MRI, and functional MRI (fMRI) have been used to investigate the hypothesis that ADHD is related to dysfunction within an anterior frontal network, comprised of the frontal lobes and interconnected subcortical structures including the basal ganglia and cerebellum. Progress since the award has included didactic instruction in statistics, research ethics, and principles of behavioral neurology, as well as mentored experience in study design and implementation and structural and functional MRI techniques. The original study design included 40 children with ADHD, ages 8 through 12 years, and 40 controls. Thus far, 37 children with ADHD and 23 controls have been recruited, most of whom have completed neurobehavioral testing and structural MRI; a smaller sample have completed an fMRl scan. Analyses of preliminary data provide support for the original hypothesis; in particular, the presence of deficits in motor response inhibition and motor persistence, as well as structural abnormalities in frontal, striatal, and cerebellar regions in ADHD. Therefore, for the current proposal, the overarching hypothesis remains unchanged, However, oculomotor studies have raised additional questions regarding the contribution of deficits in working memory to the clinical presentation of ADHD and the effect of stimulant medications on neurobehavioral findings associated with the syndrome. An additional two years of K08 supported training would allow for further training (particularly in fMR imaging), further analysis of neurobehavioral data (including correlations with findings from structural MRI), completion and analysis of proposed fMRI studies, and examination of additional questions regarding the contribution of working memory to the ADHD phenotype and the effect of stimulant medications. Primary mentorship will continue to be provided by Martha B. Denckla, M.D., Director of the candidate's department and a leading researcher in the field of developmental behavioral neurology. Research will be conducted in a multidisciplinary environment enhanced by the addition of the F M. Kirby Center for Functional Brain Imaging.