Long-Term Effects of Methylphenidate on Neural Networks Associated With Executive Attention in Children With ADHD: Results From a Longitudinal Functional MRI Study

Abstract

Little is known about the long-term effects of stimulants on the functional organization of the developing brain. Nonacute effects of stimulants on neural activity related to three aspects of attention (alerting, reorienting, and executive control) were examined in children with attention-deficit/hyperactivity disorder (ADHD) using a longitudinal functional magnetic resonance imaging approach. Nine boys with ADHD were scanned while drug naïve (t1) and after 1 year of methylphenidate treatment (t2). Eleven matched controls were also investigated twice. ADHD children stopped medication 1 week before t2. Although all of the children showed stable alerting and reorienting performance from t1 to t2, normal controls significantly improved their executive control performance at t2, whereas children with ADHD did not. Neurally, controls showed a larger increase in neural activity from t1 to t2 in regions critical to task performance (i.e., in the temporoparietal junction during reorienting of attention and in the anterior cingulate cortex during executive control) compared to the patient group. However, only children with ADHD showed a decrease in neural activity in the insula and putamen during reorienting, indicating a reduction in compensatory brain activation over time. These data suggest that 1 year of MPH treatment may be beneficial, albeit insufficient, to show enduring normalization of neural correlates of attention.