Frequency-specific alteration of functional connectivity density in bipolar disorder depression

Functional dysconnectivity has been widely reported in bipolar disorder during depressive episodes (BDD). However, the frequency-specific alterations of functional connectivity (FC) in BDD remain poorly understood. To address this issue, the FC patterns across slow-5 (0.01-0.027 Hz) and slow-4 (0.027-0.073 Hz) bands were computed using resting-state functional magnetic resonance imaging data from 37 BDD patients and 56 healthy controls (HCs). Short-range (local) FC density (lfcd) and long-range FC density (lrfcd) were calculated, and two-way analysis of variance was performed to ascertain the main effect of diagnosis and interaction effects between diagnosis and frequency. The BDD patients showed increased lfcd in the midline cerebelum. Meanwhile, the BDD patients showed increased lrfcd in the left supplementary motor cortex and right striatum and decreased lrfcd in the bilateral inferior temporal gyrus and left angular gyrus (AG) compared with the HCs. A significant frequency-by-diagnosis interaction was observed. In the slow-4 band, the BDD patients showed increased lfcd in the left pre-/postcentral gyrus and left fusiform gyrus (FG) and increased lrfcd in the left lingual gyrus (LG). In the slow-5 band, the BDD patients showed decreased lrfcd in the left LG. Moreover, the increased lfcd in the left FG in the slow-4 band was correlated with clinical progression and decreased lrfcd in the left AG was correlated with depressive severity. These results suggest that the presence of aberrant communication in the default mode network, sensory network, and subcortical and limbic modulating regions (striatum and midline cerebelum), which may offer a new framework for the understanding of the pathophysiological mechanisms of BDD.