Characterizing the properties of brain networks across mood states seen in bipolar disorder (BP) can provide a deeper insight into the mechanisms involved in this type of affective disorder. In this study, graph theoretical methods were used to examine global, modular and nodal brain network topology in the resting state using functional magnetic resonance imaging data acquired from 95 participants, including those with bipolar depression (BPD; n = 30) and bipolar mania (BPM; n = 39) and healthy control (HC) subjects (n = 26). The threshold value of the individual subjects’ connectivity matrix varied from 0.15 to 0.30 with steps of 0.01. We found that: (1) at the global level, BP patients showed a significantly increased global efficiency and synchronization and a decreased path length; (2) at the nodal level, BP patients showed impaired nodal parameters, predominantly within the frontoparietal and limbic sub-network; (3) at the module level, BP patients were characterized by denser FCs (edges) between Module III (the front-parietal system) and Module V (limbic/paralimbic systems); (4) at the nodal level, the BPD and BPM groups showed state-specific differences in the orbital part of the left superior-frontal gyrus, right putamen, right parahippocampal gyrus and left fusiform gyrus. These results revealed abnormalities in topological organization in the whole brain, especially in the frontoparietal-limbic circuit in both BPD and BPM. These deficits may reflect the pathophysiological processes occurring in BP. In addition, state-specific regional nodal alterations in BP could potentially provide biomarkers of conversion across different mood states.
