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. Post-hoc 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.

Neural network of bipolar disorder: Toward integration of neuroimaging and neurocircuit-based treatment strategies.

Bipolar disorder (BD) is a complex psychiatric disorder characterized by dysfunctions in three domains including emotional processing, cognitive processing, and psychomotor dimensions. However, the neural underpinnings underlying these clinical profiles are not well understood. Based on the reported data, we hypothesized that (i) the core neuropathology in BD is damage in fronto-limbic network, which is associated with emotional dysfunction; (ii) changes in intrinsic brain network, such as sensorimotor network, salience network, default-mode network, central executive network are associated with impaired cognition function; and (iii) beyond the dopaminergic-driven basal ganglia-thalamo-cortical motor circuit modulated by other neurotransmitter systems, such as serotonin (subcortical-cortical modulation), the sensorimotor network and related motor function modulated by other non-motor networks such as the default-mode network are involved in psychomotor function. In this review, we propose a neurocircuit-based clinical characteristics and taxonomy to guide the treatment of BD. We draw on findings from neuropsychological and neuroimaging studies in BD and link variations in these clinical profiles to underlying neurocircuit dysfunctions. We consider pharmacological, psychotherapy, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions in BD. Finally, it is suggested that the methods of testing the neurocircuit-based taxonomy and important limitations to this approach should be considered in future.