Toward a neurocircuit-based sequential transcranial magnetic stimulation treatment of pediatric bipolar II disorder

Background: Abnormalities in large-scale neuronal networks-the frontoparietal central executive network (CEN)-are consistent findings in bipolar disorder and potential therapeutic targets for transcranial magnetic stimulation (TMS). Objective: The present study aimed to assess the effects of CEN neurocircuit-based sequential TMS on the clinical symptoms and cognitive functions of adolescents with bipolar II disorder. Methods: The study was a single-blinded, randomized, placebo-control trial. Participants with DSM-5-defined bipolar disorder II were recruited and randomized to receive either a sham treatment (n = 20) or an active TMS treatment (n = 22). The active group patients were taking medication, with intermittent theta burst stimulation (iTBS) treatment provided as adjunctive treatment targeting the left DLPFC, the left ITG, and the left PPC nodes consecutively. Patients completed the measurements of HAMD and the Das-Naglieri Cognition Assessment System at baseline and 3 weeks after the intervention. Results: A significant group-by-time interaction was observed in the HAMD, total cognition, and planning. Posthoc analysis revealed that patients in the active group significantly improved HAMD scores following neurostimulation. Moreover, within-subject analysis indicated that the active group significantly improved in scores of total cognition and planning, while the sham group did not. No significant differences were seen in the other cognitive measures. Conclusion: The neurocircuit-based sequential TMS protocol targeting three CEN nodes, in conjunction with medication, safely and effectively improved depressive symptoms and cognitive function in adolescents with bipolar II disorder.