The overall objective of this project is to develop a system-level model of brain-behavior relationships in ADHD. This proposal builds on previous findings of the P1 and CoPIs using a combination of event-related potentials (ERP), behavioral tasks, anatomical magnetic resonance imaging (MRI) and neuropsychology assessments in ADHD children. In the proposed project, we will use a within-subject, multi-methodological approach to clarify the relationship between anatomical and functional imaging abnormalities in ADHD. We will obtain ERP, event-related functional MRI (ER-fMRI), and anatomical MRI at baseline in four cohorts of subjects: ADHD subjects with no history of psychopharmacological treatment, ADHD subjects who have been chronically treated with stimulant medication, subjects with Reading Disorders (RD) who have no history of ADHD or psychopharmacological treatment, and control subjects. Subjects will perform both the ERP and the Stroop task during the ERP and ER-fMRI studies. After baseline studies, ADHD subjects will undergo a 5-week double blind placebo controlled trial of methylphenidate to establish if a child is a responder or non-responder to methyiphenidate and to determine, for the responders, which is the optimal dose. Subjects with ADHD will then undergo ERP and er-fMRI twice more, once on placebo and once on the best dose of stimulant, again performing the Stroop and Stop Signal Task. Our hypotheses are: 1) Relative to controls and RD subjects, ADHD children will show decreased right frontal and anterior cingulate volume as well as decreased caudate volume. 2) On ERP, ADHD subjects will show decreased N200 and P3a responses to the stop signal on ERP and decreased anterior medial negativity to Incongruent vs. Congruent stimuli on the Stroop. 3) On er-fMRI, they will show decreased activity in the anterior cingulate during the Stroop task, and decreased right inferior prefrontal cortex (PFC) activity in response to the stop signal. 4) ERP and er-fMRI differences in ADHD children will be attenuated on methyiphenidate relative to placebo. The magnitude of these changes will correlate with clinical response of ADHD symptoms to methylphenidate. 5) We will control for effects of gender and age, in particular girls with ADHD may not show the same neurobiological mechanisms as boys.
