Disrupted Functional Connectivity In Major Depressive Disorder:Spatiotemporal Characteristics And Metabolic Basis

Major depressive disorder(MDD)is a worldwide emotional disorder,and is associated with disrupted intrinsic functional connectivity as revealed by increasing studies,however,the disruptions are far from fully understood,particularly with respect to their spatiotemporal characteristics and metabolic substrates.To address these questions,we collected resting-state BOLD and ASL functional MRI data from 35 MDD patients and 34 gender-,age-,and education-matched healthy controls(HCs).Based on a wholebrain voxel-wise degree centrality approach,significant decreases were found in the bilateral anterior cingulate gyri,middle frontal gyri and superior frontal gyri and the right parahippocampal gyrus for the MDD patients compared with the HCs.These results were largely independent on different choices during the network analytical scheme such as network types(binary/weighted),anatomical distance(long/short),and correlation threshold(0.1/0.15/0.2/0.25/0.3/0.35/0.4).Further analysis revealed that the MDD-related regions,relative to other areas in the brain,exhibited frequencydependent oscillation power(stronger within 0.01-0.027 Hz and lower within 0.027-0.073 Hz),and were more inclined to hub-like regions and selectively located in the limbic and default mode networks spatially.Interestingly,all the regions showing MDD-related centrality decreases were associated with lower CBF in the patients.Both regional and whole-brain across-modality correlation analysis revealed significantly positive correlations between degree centrality and CBF but only the whole-brain coupling was decreased in the patients.Finally,a co-analysis of multi-modal MRI data revealed that there existed widespread cortical and subcortical brain sites that only exhibited lower CBF in the patients with the degree centrality relatively spared.Taken together,our findings have important implications for understanding the characteristics and origin of disrupted functional connectivity in MDD and suggest that MDD-related alterations may happen earlier in CBF than functional connectivity MDD.