Dysfunction in Sensorimotor and Default Mode Networks: Elucidating the Neural Correlates of Major Depressive Disorder

Abstract

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 study aims to examine large-scale connectivity coherence in MDD. A total resting-state functional magnetic resonance image data of 1148 MDD patients and 1079 healthy volunteers (HV) was collected from nine research centers. The global brain connectivity (GBC) offering an objective and comprehensive perspective on changes in functional connectivity (FC) was estimated and compared between groups. The regions with notably altered GBC in MDD patients were identified as the seeds for calculating the brain FC. Compared to HV, MDD patients had decreased GBC in sensorimotor/visual networks, including bilateral pre-/postcentral, fusiform gyrus, and inferior occipital gyrus, and increased GBC mainly in default mode networks (DMN), including bilateral precuneus, posterior cingulate cortex, superior frontal gyrus, and left angular gyrus. These GBC alterations were closely linked with meta-analytic terms associated with sensory and higher-order cognitive processing. Further seed-based analyses revealed that MDD patients had heightened FC between DMN and primary sensory cortices, but reduced FC within primary sensory cortices themselves. Our findings suggest that the aberrant intrinsic functional hubs identified in both higher-order cognitive systems and low-level sensory systems may signify a disruption in information exchange from primary to higher-order systems, which may contribute to the multifaceted clinical and cognitive deficits observed in MDD.