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Background 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. Methods 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. Results 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. Conclusions 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.

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BackgroundSocial deficits are among the most important functional impairments in attention-deficit/hyperactivity disorder (ADHD). However, the relationship between social impairment and ADHD core symptoms as well as the underlying cerebral blood flow (CBF) characteristics remain unclear.MethodsA total of 62 ADHD subjects with social deficits (ADHD + SD), 100 ADHD subjects without social deficits (ADHD-SD) and 81 age-matched typically developing controls (TDC) were enrolled. We first examined the correlation between the Social Responsiveness Scale (SRS-1) and ADHD core symptoms (inattention, hyperactivity, and impulsion) and then explored categorical and dimensional ADHD-related regional CBF by arterial spin labeling (ASL). For the categorical analysis, a voxel-based comparison of CBF maps between the ADHD + SD, ADHD-SD, and TDC groups was performed. For the dimensional analysis, the whole-brain voxel-wise correlation between CBF and ADHD symptoms (inattention, hyperactivity/impulsivity, and total scores) was evaluated in three groups. Finally, correlations between the SRS-1 and ADHD-related regional CBF were investigated. We applied Gaussian random field (GRF) for the correction of multiple comparisons in imaging results (voxel-level P < 0.01, and cluster-level P < 0.05).ResultsThe clinical characteristics analysis showed that social deficits positively correlated with ADHD core symptoms, especially in social communication and autistic mannerisms domains. In the categorical analysis, we found that CBF in the left middle/inferior temporal gyrus in ADHD groups was higher than TDCs and was negatively correlated with the social motivation scores. Moreover, in dimensional analysis, we found that CBF in the left middle frontal gyrus was negatively correlated with the inattention scores, SRS total scores and autistic mannerisms scores in ADHD + SD subjects.ConclusionThe present study shows that inattention, hyperactivity, and impulsivity may be responsible for the occurrence of social deficits in ADHD, with autistic traits being another significant contributing factor. Additionally, CBF in the left middle/inferior temporal gyrus and the left middle frontal gyrus might represent the corresponding physiological mechanisms underlying social deficits in ADHD.

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