Multimodal brain imaging of the neural effects of methylphenidate in patients with ADHD

There is continued interest to develop novel pharmacological treatments for attention deficit hyperactivity disorder (ADHD), in part because of its high prevalence in the community, and lack of optimal response to current medications, including intolerable side effects. Central nervous system (CNS) pharmacodynamic (PD) measures have not been well characterized in pediatric and adolescent populations, which is important for future drug development. Brain imaging tools are ideal CNS PD measures in children because they are non-invasive and reproducible. Our goal is to understand the neural correlates of treating ADHD with methylphenidate, specifically in children and adolescents. First, we propose to determine the dose-dependent changes in cognitive task-related neural activity after acute methylphenidate using functional magnetic resonance imaging (fMRI, Aim 1). Then we will identify the changes in brain glutamate and other brain metabolites after acute methylphenidate using high-field strength magnetic resonance spectroscopy (MRS), and determine if these changes in brain chemistry correlate with changes in brain function (Aim 2). Data from this study will shed light onto the pathophysiology of the cognitive symptoms of ADHD and the neural response to treatment with stimulants, which will guide future development of novel treatments and could serve as CNS PD measures in future treatment trials. Furthermore, we will determine the utility of these CNS PD measures in children and adolescents that will lay the groundwork for developing pediatric brain imaging measures for other drugs and other CNS disorders.