Editorial: Embedding Functional Neuroimaging Within Clinical Trials for Mania: Toward Answering the Questions, Who, How, and When?

Neurocognitive deficits are common in bipolar disorder (BD) across the life span, and functional neuroimaging studies have elucidated anomalous neural circuitry underlying these deficits. Nonetheless, the literature regarding changes in neural circuitry in the context of clinical trials in BD remains sparse. In this issue, Li and Lei et al.1 report results of a randomized, double-blind, controlled trial comparing treatment effects of lithium and quetiapine on functional neural circuitry during a continuous performance task probing vigilance and working memory. Participants completed the continuous performance task while undergoing functional magnetic resonance imaging (MRI) to determine functional connectivity. This method uses functional MRI data to examine temporal synchrony in activation of spatially distinct brain regions' coordinated activation, which is thought to reflect flow of neural information between brain regions. At baseline, compared with controls, youth with BD experiencing a manic episode exhibited relative deficits in connectivity within regions relevant to sensory processing, affective reactivity, and cognitive control. After 1 week of treatment, functional connectivity among youth with BD treated with quetiapine, but not lithium, became similar to controls. After 6 weeks of treatment, functional connectivity deficits were normalized in both treatment groups, with no significant differences between treatment groups. Youth with the greatest changes in manic symptoms and functional connectivity were older, but similar in terms of other baseline clinical characteristics. This study underscores the benefits of including functional neuroimaging in clinical trials, offering unique insights into differential effects of antimanic treatments on key brain processes thought to underlie symptoms and symptomatic improvement in youth with BD.