Hyperactive frontolimbic and frontocentral resting-state gamma connectivity in major depressive disorder

•Elevated frontolimbic and frontocentral gamma connectivity was identified in major depressive disorder.•Virtual cortical resection revealed that the right amygdala was the key network controller accounting for aberrant cerebral connectivity patterns in major depressive disorder.•Frontocentral and frontolimbic gamma hyper-connectivity in major depressive disorder was positively correlated with depression severity. Major depressive disorder (MDD) is a system-level disorder affecting multiple functionally integrated cerebral networks. Nevertheless, their temporospatial organization and potential disturbance remain mostly unknown. The present report tested the hypothesis that deficient temporospatial network organization separates MDD and healthy controls (HC), and is linked to symptom severity of the disorder. Eyes-closed resting-state magnetoencephalographic (MEG) recordings were obtained from twenty-two MDD and twenty-two HC subjects. Beamforming source localization and functional connectivity analysis were applied to identify frequency-specific network interactions. Then, a novel virtual cortical resection approach was used to pinpoint putatively critical network controllers, accounting for aberrant cerebral connectivity patterns in MDD. We found significantly elevated frontolimbic and frontocentral connectivity mediated by gamma (30–48 Hz) activity in MDD versus HC, and the right amygdala was the key differential network controller accounting for aberrant cerebral connectivity patterns in MDD. Furthermore, this frontolimbic and frontocentral gamma-band hyper-connectivity was positively correlated with depression severity. The overall sample size was small, and we found significant effects in the deep limbic regions with resting-state MEG, the reliability of which was difficult to corroborate further. Overall, these findings support a notion that the right amygdala critically controls the exaggerated gamma-band frontolimbic and frontocentral connectivity in MDD during the resting-state condition, which potentially constitutes pre-established aberrant pathways during task processing and contributes to MDD pathology.