Intrinsic Brain Connectivity Following Long-Term Treatment with Methylphenidate in Children with Attention-Deficit/Hyperactivity Disorder

Although widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD) across the life span, the effects of methylphenidate (MPH) on the brain are not completely understood. Functional neuroimaging techniques may help increase knowledge about the mechanisms of MPH action.To evaluate changes in functional connectivity patterns of the default mode network (DMN) in children with ADHD following long-term treatment with MPH.Twenty-three right-handed treatment-naïve boys with ADHD underwent a protocol of intrinsic functional connectivity before and after 6 months of treatment with MPH. Functional connectivity was analyzed using a region of interest (ROI) approach and independent component analysis (ICA).ROI analyses showed no significant changes in connectivity between regions of the DMN following treatment, with a relatively small increase in the anterior-posterior connectivity of the network. ICA revealed a significant increase in connectivity between the left putamen and the DMN (p 0.001, corrected). There was a correlation between the reduction of symptoms and the increased connectivity between the putamen and the DMN after treatment (rho = -0.65, p = 0.017).Dysfunctions in cortical-subcortical circuits have often been associated with the pathophysiology of ADHD. Our findings suggest that effective treatment with MPH in children with ADHD may affect brain functioning by increasing connectivity between the DMN and subcortical nuclei.