Differing effects of methylphenidate on attention-related behavior and brain activity in medication-naive and non-naive ADHD adults.

Methylphenidate (MPH) is a widely used pharmacological treatment for attention deficit/hyperactivity disorder (ADHD), which increases the extracellular dopamine and noradrenaline level by inhibiting their reuptake. Despite reported improvements in cognitive functions, the influence of medication history on MPH efficacy and its impact on attentional brain regions remain unclear. We examined 36 adults with ADHD using a within-subject design. Participants completed a central cue version of the Posner task during functional magnetic resonance imaging scans before and after at least 8 weeks of MPH administration. Participants were classified into medication-naive and non-naive groups based on prior exposure to pharmacotherapy. Behavioral and neural responses were compared across conditions, and correlations with symptom changes were assessed using the Conners' Adult ADHD Rating Scales. Reaction times tended to be shorter after MPH administration across both groups, whereas accuracy did not change. With MPH, activation in the left frontal eye field (FEF) and right intraparietal sulcus (IPS) increased in the naive group but did not increase in the non-naive participants. Further, a moderate correlation was observed between increased FEF activation and symptom reduction in the naive group, although this did not survive correction for multiple comparison. These results suggest that the effects of MPH on the dorsal attention network differ by medication history, supporting the notion that MPH modulates attention through both transient and long-lasting mechanisms. They underscore the importance of considering medication history when evaluating treatment response in ADHD.