Rolle CE, Fonzo GA, Wu W, et al. - Researchers assessed data from a placebo-controlled, double-blinded randomized clinical trial, the Establishing moderators and biosignatures of antidepressant response in-clinic care study, in order to discover whether electroencephalography (EEG) connectivity could show neural moderators of antidepressant treatment. Of the participants recruited, 9 were removed following the first dose owing to reported adverse effects, and 221 participants who undergone EEG recordings and had high-quality pretreatment EEG data. Connectome-wide analyses revealed moderation by connections within and between widespread cortical regions—most prominently parietal—for both the antidepressant and placebo groups following correction for multiple comparisons. Better placebo outcomes and worse antidepressant outcomes were predicted with greater alpha-band and lower gamma-band connectivity. Lower connectivity levels in these moderating connections were correlated with higher levels of anhedonia. Connectivity characteristics that moderate treatment response variably by treatment group were different from connectivity characteristics that change from baseline to 1 week into treatment. These findings suggest the utility of EEG-based network functional connectivity analyses for differentiating between responses to an antidepressant vs placebo.