Although methylphenidate (MPH) and atomoxetine (ATX) can improve clinical symptoms and functional impairments in attention deficit/hyperactive disorder (ADHD), the underlying psychopharmacological mechanism have not been clearly elucidated. Therefore, we aimed to explore the shared and unique neurologic basis of these two medications in alleviating the clinical symptoms and functional impairments observed in ADHD.
Sixty-seven ADHD and 44 age-matched children with typical development were finally included and underwent resting-state functional magnetic resonance imaging (fMRI) scans at baseline. Then patients were assigned to MPH, ATX or untreated subgroups, based on the patients’ and their parents’ choice, for a 12-week follow-up, and underwent a second fMRI scan. The treatment effect on degree centrality (DC) was identified and correlated with clinical symptoms and functional impairments in the ADHD group.
Both of MPH and ATX normalised the DC value in extensive brain regions mainly involving fronto-cingulo-parieto-cerebellum circuits. However, ATX showed limited significant effects on the cerebellum compared to ADHD at baseline. The improvements in clinical symptoms were correlated with increased DC in the right inferior temporal gyrus in both MPH and ATX subgroups, but showed opposite effects. The alleviation of functional impairments in the school/learning domain negatively correlated with decreased DC in the bilateral cerebellum after MPH treatment, while the family functional domain positively correlated with decreased DC in the cerebellum and negatively correlated with decreased DC in the postcentral gyrus after ATX treatment.
Both MPH and ATX can normalise abnormal brain functions that mainly involve the fronto-cingulo-parieto-cerebellum circuit in ADHD. Furthermore, the two medications affected shared and unique effective brain regions to alleviate clinical symptoms and functional impairment.

© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.