• Youjin Zhao, Feifei Zhang, Wenjing Zhang, Lizhou Chen, Ziqi Chen, Su Lui, and Qiyong Gong.
• Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China.
• J Magn Reson Imaging. 2021 Mar 1; 53 (3): 742-752.

BackgroundMajor depressive disorder (MDD) has been increasingly conceptualized as a disconnection syndrome. However, most studies have only focused on functional connectivity (FC) alterations in gray matter (GM), and the functional alterations in white matter (WM) remain largely unknown in MDD.PurposeTo investigate WM functional alterations and the functional interaction between GM and WM networks in medication-naïve MDD.Study TypeProspective.SubjectsSixty-eight patients with MDD and 66 age- and sex-matched healthy controls (HCs).Field Strength/SequenceResting state-functional MRI (fMRI) using a gradient-echo imaging sequence and T1 -weighted images were acquired at 3.0T.AssessmentFunctional GM and WM networks, based on resting-state blood oxygenation level-dependent (BOLD) signals, were identified by the K-means clustering algorithm, and FC matrices were obtained for each subject.Statistical TestsTwo-sample t-tests, Pearson chi-square test, and Pearson correlation analysis.ResultsBoth the GM and WM of the visual network (GM1 and WM11) showed reduced FC with the sensorimotor network (WM5 and GM8), lateral temporal network (GM5 and WM6), cingulo-opercular network (GM9), and dorsal attention network (GM7) in MDD patients compared to controls (P < 0.05, false discovery rate [FDR]-corrected). Reduced FC between the anterior cingulum network (WM3) and the lateral temporal network (GM5 and WM6) and temporal pole network (GM13) and between GM13 and the medial temporal network (GM4) and medial prefrontal-subcortical network (GM10) were also observed in MDD patients (P < 0.05, FDR-corrected). In addition, the WM BOLD signal in the sensorimotor network was negatively correlated with illness duration (r = -0.286, P = 0.018).Data ConclusionDisconnectivity between the GM and WM networks in the perception-motor system may be the foundation of extensively disrupted connections in MDD. Furthermore, the observed decoupling between subsystems of the default mode network may help explain previous findings of persistent negative rumination and theory of mind deficits in depression.Level Of Evidence3.Technical EfficacyStage 3.© 2020 International Society for Magnetic Resonance in Medicine.

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