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As adjuvant therapy for enhancing the effects of stimulants and thereby minimizing medication doses, we hypothesized that aerobic exercise might be an effective adjunctive therapy for enhancing the effects of methylphenidate on the clinical symptoms, cognitive function, and brain activity of adolescents with attention deficit hyperactivity disorder (ADHD).Thirty-five adolescents with ADHD were randomly assigned to one of two groups in a 1/1 ratio; methylphenidate treatment + 6-wk exercise (sports-ADHD) or methylphenidate treatment + 6-wk education (edu-ADHD). At baseline and after 6 wk of treatment, symptoms of ADHD, cognitive function, and brain activity were evaluated using the Dupaul attention deficit hyperactivity disorder rating scale--Korean version (K-ARS), the Wisconsin Card Sorting Test, and 3-T functional magnetic resonance imaging, respectively.The K-ARS total score and perseverative errors in the sports-ADHD group decreased compared with those in the edu-ADHD group. After the 6-wk treatment period, the mean β value of the right frontal lobe in the sports-ADHD group increased compared with that in the edu-ADHD group. The mean β value of the right temporal lobe in the sports-ADHD group decreased. However, the mean β value of the right temporal lobe in the edu-ADHD group did not change. The change in activity within the right prefrontal cortex in all adolescents with ADHD was negatively correlated with the change in K-ARS scores and perseverative errors.The current results indicate that aerobic exercise increased the effectiveness of methylphenidate on clinical symptoms, perseverative errors, and brain activity within the right frontal and temporal cortices in response to the Wisconsin card sorting test stimulation.