Functional disconnection between subsystems of the default mode network in bipolar disorder

Disruption in connectivity between default mode network (DMN) regions has previously been reported in bipolar disorder (BD). The current study aimed to investigate the dysfunction of the DMN subsystem in patients with BD during manic and depressive episodes and to explore its relationship with the symptoms of BD. Fifty-two patients with bipolar disorder and 39 healthy controls were recruited. Eleven seed points were selected from three DMN subsystems. We performed seed-based resting-state functional connectivity (FC) analysis and obtained individual DMN FC matrices by computing the spatial correlations between pairs of FC maps. The strength of the connections within and between the three DMN subsystems, including the core subsystem, dorsal medial prefrontal cortex subsystem, and medial temporal lobe (MTL) subsystem, was used for group analyses. Compared with healthy controls, reduced FC between the core and MTL subsystem was observed in BD patients, especially in those with depressive episodes, but not in those with manic episodes. There were significant differences in core-MTL connectivity strength between the two patient groups during manic and depressive episodes. Moreover, core-MTL subsystem connectivity was negatively correlated with the depression scale. The FC within the core subsystem was negatively correlated with anxiety and negatively correlated with depression. This study provides evidence for an abnormal default network subsystem connection in bipolar disorder during manic and depressive episodes, revealing the neuropathological mechanism of the disease from the perspective of brain functional connectivity.