Attention Deficit Hyperactivity Disorder Clinical Trial
Official title:
Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach
The growing number of medications used to treat attention-deficit/hyperactivity disorder (ADHD) raises important questions about whether different medications have similar or different therapeutic mechanisms of action. We have recently shown that the stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) produce clinical improvement via a common mechanism in motor cortex, and distinct actions in frontostriatal and midline cingulate-precuneus regions. These exciting findings offer a window into the common and unique neurophysiological mechanisms of response to stimulant and non-stimulant treatments. However, the interpretation and clinical utility of these results would be greatly enhanced by in-depth investigation of the impact of the two treatments on relevant neural networks, and analyses which evaluate whether improvement is achieved via normalization or other adaptive changes in brain function.
The specific aims of this project are to use functional magnetic resonance imaging (fMRI) to
determine the significance of activation changes over treatment related to clinical
improvement, and the impact of treatment on neural connectivity within and between the
anti-correlated frontostriatal 'task-positive' circuit and cingulate-precuneus
'task-negative' network. Our central hypotheses are that clinical improvement is associated
with: (i) normalization of reduced connectivity of regions within the 'task-positive'
network, with resultant increased inhibition of motor cortex, and (ii) normalization of low
task-related connectivity in regions within the task-negative network for MPH and the
'task-positive' network for ATX.
This research proposes to test a model which posits a neurophysiological basis of mechanisms
of response to stimulant and non-stimulant medications, and fits with our long term
objectives of being able to match treatments to individual patients. Testing this model
requires large samples of youth scanned using fMRI before and after treatment, and matched
healthy controls also scanned twice. We will use an innovative network-based approach to
study the effects of treatment, building on results from our current fMRI treatment study,
and incorporating new theoretical approaches to understanding ADHD and its treatment.
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