The stimulants methylphenidate and amphetamine are well known for their efficacy in treating symptoms of ADHD in both youth and adults. Although these medications have been used for several decade, relatively little is known about the mechanisms of action that lead to their therapeutic effect. New data about mechanism comes from a meta-analysis by Katya Rubia and colleagues. They analyzed 14 functional magnetic resonance imaging (fMRI) data sets comprising 212 youth with ADHD. Each of these data sets assessed the short term effects of stimulants on fMRI assessed brain activations. In the fMRI paradigm, ADHD and control participants are asked to do a neurocognitive task while the activity of their brains is being measured. Dr. Rubia and colleagues analyzed data from fMRI assessments of time discrimination, inhibition and working memory, each of which are known to be deficient in ADHD patients. The meta-analysis found that the most consistent brain activations were seen in a region comprising the right inferior frontal cortex (IFC) and insula, even when the analysis was limited to previously medication naïve patients. The implicated region of the brain is known to mediate cognitive control, time estimation and attention. Dr. Rubia also notes that other studies show that the IFC/Insula is needed for updating information and allocating attention to relevant stimuli. Another region implicate by the meta-analysis was the right putamen, a region that is rich in dopamine transporters. This finding is consistent with the fact that the dopamine transporter is the main target of stimulant medications. What are the potential clinical implication of these findings? As Dr. Rubia and colleagues note, it is possible that the fMRI anomalies they identified could be used as a biomarker for ADHD or a biomarker to select patients who should respond optimally to stimulant medication. Although fMRI cannot be used as a clinical tool at this time, research of this sort is opening up new horizons for how we understand the etiology of ADHD and the mechanisms whereby medications exert their effects.
Rubia, K., Alegria, A. A., Cubillo, A. I., Smith, A. B., Brammer, M. J. & Radua, J. (2014). Effects of stimulants on brain function in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Biol Psychiatry 76, 616-28.