MR imaging of the effects of methylphenidate on brain structure and function in attention-deficit/hyperactivity disorder.

Methylphenidate is the first-choice pharmacological intervention for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). The pharmacological and behavioral effects of methylphenidate are well described, but less is known about neurochemical brain changes induced by methylphenidate. This level of analysis may be informative on how the behavioral effects of methylphenidate are established. This paper reviews structural and functional MRI studies that have investigated effects of methylphenidate in children with ADHD. Structural MRI studies provide evidence that long-term stimulant treatment may normalize structural brain changes found in the white matter, the anterior cingulate cortex, the thalamus, and the cerebellum in ADHD. Moreover, preliminary evidence suggests that methylphenidate treatment may normalize the trajectory of cortical development in ADHD. Functional MRI has provided evidence that methylphenidate administration has acute effects on brain functioning, and even suggests that methylphenidate may normalize brain activation patterns as well as functional connectivity in children with ADHD during cognitive control, attention, and during rest. The effects of methylphenidate on the developing brain appear highly specific and dependent on numerous factors, including biological factors such as genetic predispositions, subject-related factors such as age and symptom severity, and task-related factors such as task difficulty. Future studies on structural and functional brain changes in ADHD may benefit from inclusion strategies guided by current medication status and medication history. Further studies on the effects of methylphenidate treatment on structural and functional MRI parameters are needed to address unresolved issues of the long-term effects of treatment, as well as the mechanism through which medication-induced brain changes bring about clinical improvement.