Spatiotemporal, metabolic, and therapeutic characterization of altered functional connectivity in major depressive disorder

Abstract

Although imbalanced functional integration has been increasingly reported in major depressive disorder (MDD), there still lacks a general framework to characterize common characteristic and origin shared by the integrative disturbances. Here we examined spatial selectivity, temporal uniqueness, metabolic basis, and therapeutic response of altered functional connectivity (FC) in MDD by analyzing both cross-sectional and longitudinal multimodal functional magnetic resonance imaging data from 35 patients and 34 demographically matched healthy controls. First, based on a voxel-wise, data-driven, graph-based degree centrality approach, the bilateral anterior cingulate gyri, middle frontal gyri and superior frontal gyri, and the right parahippocampal gyrus were robustly identified to show decreased FC in MDD. Further spatiotemporal analyses revealed that these regions exhibited hub-like features and were selectively located in limbic and default mode networks spatially and, relative to other areas in the brain, exhibited unique, frequency-dependent oscillation power (stronger within 0.01-0.027 Hz and weaker within 0.027-0.073 Hz) and less dynamical variability of whole-brain FC profiles temporally. Moreover, a cross-modality fusion analysis showed that all MDD-related FC impairments were associated with reduced cerebral blood flow (CBF); however, there existed multiple regions that showed reduced CBF but had intact FC in the patients, which resulted in a decreased FC-CBF coupling and implied an earlier emergence of reduced CBF than impaired FC in MDD. Finally, the disrupted FC in MDD gradually recovered over the course of drug treatment (2 and 12 weeks). Altogether, these findings could help establish a general framework to provide mechanistic insights into integrative dysfunctions in MDD.

Disrupted Structural Brain Network Organization Behind Depressive Symptoms in Major Depressive Disorder

“…SFG is part of the DMN and is related to emotional disorder and higher cognitive function ( 40 , 41 ). Past study using a voxel-wise, data-driven, graph-based approach showed significantly reduced regional connections in SFG of MDD patients ( 30 ), which is in accordance with our findings. Du et al ( 42 ) have confirmed the involvement of the SFG in the neural network dedicated to working memory.…”

“…Recently, there has been greater focus on the mechanism behind the emotion disturbance in MDD patients. Studies on the emotion of MDD have centered on abnormal anatomical and functional connectivity ( 29 , 30 ). From the perspective of network topological architectures, imbalanced functional integration has been increasingly reported in MDD ( 31 , 32 ), and we are among the firsts to use graph theoretical analysis to explore the mood disturbance and cognitive function in MDD in this study.…”

Common and Specific Alterations of Amygdala Subregions in Major Depressive Disorder With and Without Anxiety: A Combined Structural and Resting-State Functional MRI Study

“…All patients were free of psychotropic medications for at least 4 weeks before the MRI scan and had a Hamilton depression rating (HAMD) score ≥ 14. We chose a HAMD ≥ 14 instead of 18 as in our previous studies (Shen et al, 2015 ; Sheng et al, 2018 ) to maximize the sample size of the current study. Out of the 49 patients, 26 were categorized as having AMDD in terms a HAMD anxiety/somatization factor score ≥ 7 (Fava et al, 2008 ).…”

Aberrant Effective Connectivity of the Right Anterior Insula in Primary Insomnia

“…Neuroimaging techniques provided a new avenue to study the pathophysiological mechanisms underlying many psychiatric disorders ( 7 – 12 ). With regard to PI, PET, functional, and structural MR imaging have shown abnormal glucose metabolism ( 13 ), activation ( 14 , 15 ), spontaneous activity ( 16 – 18 ), functional or structural connectivity ( 19 – 25 ), or atrophic structure ( 26 – 28 ) related to the cognitive system, especially the salience network (SN) ( 11 , 21 ), executive control network (ECN), and default mode network (DMN) ( 22 , 29 ).…”