First-Dose Methylphenidate–Induced Changes in Brain Functional Connectivity Are Correlated With 3-Month Attention-Deficit/Hyperactivity Disorder Symptom Response

Background: Attention-deficit/hyperactivity disorder (ADHD) symptoms are most commonly treated with stimulant medication such as methylphenidate (MPH); however, approximately 25% of patients show little or no symptomatic response. We examined the extent to which initial changes in brain functional connectivity (FC) associated with the first MPH dose in boys newly diagnosed with ADHD predict MPH-associated changes in ADHD inattentiveness and hyperactivity symptoms at 3 months. Methods: Brain FC was estimated using steady-state visual evoked potential partial coherence before and 90 minutes after the administration of the first MPH dose to 40 stimulant drug-naïve boys newly diagnosed with ADHD while they performed the AX version of the continuous performance task. The change in parent-rated inattention and hyperactivity scores over the first 3 months of MPH medication was correlated with the initial 90-minute MPH-mediated FC changes. Results: Hyperactivity improvements at 3 months were associated with first-dose MPH-mediated FC reductions restricted to frontal-prefrontal sites following the appearance of the "A" and at frontal and right temporal sites during the appearance of the "X." Corresponding 3-month inattention score improvement was associated with initial MPH-mediated FC reductions restricted to occipitoparietal sites following the appearance of the "A.". Conclusions: These findings are discussed in the context of MPH effects on the default mode network and the possible role of the default mode network in MPH-mediated improvements in inattention and hyperactivity symptom scores.