Dysfunction in sensorimotor and default mode networks in major depressive disorder with insights from global brain connectivity

Major depressive disorder (MDD) is recognized as a severe mental illness with imbalanced interactions among brain networks. However, the detailed mechanisms of large-scale network dysfunction and their clinical implications are not fully understood. To explore the neurological basis of altered connectivity within the brain, the current case-control study aimed to examine large-scale connectivity coherence in MDD using resting-state functional magnetic resonance imaging data from 1,148 individuals with MDD and 1,079 healthy volunteers across nine research centers. Global brain connectivity (GBC) was estimated and compared between groups. Compared with healthy volunteers, individuals with MDD had decreased GBC in sensorimotor/visual networks and increased GBC mainly in default mode networks (DMNs) (voxel-level P < 0.001, cluster-level P < 0.05). These main findings were consistent across different clinical states of MDD, indicating their independence from clinical factors (P < 0.05, FDR-corrected). Further seed connectivity revealed that individuals with MDD had heightened connectivity between DMNs and primary sensory cortices, but reduced connectivity within primary sensory cortices (voxel-level P < 0.001, cluster-level P < 0.05). The findings suggest a network imbalance toward the DMNs at the expense of the sensorimotor/visual networks in individuals with MDD experiencing a depressive episode. These alterations, involving both higher-order cognitive systems and low-level sensory systems, could provide insights into understanding the multifaceted clinical and cognitive deficits observed in MDD.