Large-scale dynamic causal modeling of major depressive disorder based on resting-state functional magnetic resonance imaging

Guoshi Li, Yujie Liu, Yanting Zheng, Danian Li, Xinyu Liang, Yaoping Chen, Ying Cui, Pew Thian Yap, Shijun Qiu, Han Zhang, Dinggang Shen

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


Major depressive disorder (MDD) is a serious mental illness characterized by dysfunctional connectivity among distributed brain regions. Previous connectome studies based on functional magnetic resonance imaging (fMRI) have focused primarily on undirected functional connectivity and existing directed effective connectivity (EC) studies concerned mostly task-based fMRI and incorporated only a few brain regions. To overcome these limitations and understand whether MDD is mediated by within-network or between-network connectivities, we applied spectral dynamic causal modeling to estimate EC of a large-scale network with 27 regions of interests from four distributed functional brain networks (default mode, executive control, salience, and limbic networks), based on large sample-size resting-state fMRI consisting of 100 healthy subjects and 100 individuals with first-episode drug-naive MDD. We applied a newly developed parametric empirical Bayes (PEB) framework to test specific hypotheses. We showed that MDD altered EC both within and between high-order functional networks. Specifically, MDD is associated with reduced excitatory connectivity mainly within the default mode network (DMN), and between the default mode and salience networks. In addition, the network-averaged inhibitory EC within the DMN was found to be significantly elevated in the MDD. The coexistence of the reduced excitatory but increased inhibitory causal connections within the DMNs may underlie disrupted self-recognition and emotional control in MDD. Overall, this study emphasizes that MDD could be associated with altered causal interactions among high-order brain functional networks.

Original languageEnglish
Pages (from-to)865-881
Number of pages17
JournalHuman Brain Mapping
Issue number4
Publication statusPublished - 2020 Mar 1


  • brain networks
  • drug-naive
  • dynamic causal modeling
  • effective connectivity
  • first-episode
  • major depressive disorder
  • parametric empirical Bayes
  • resting-state fMRI

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology


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