Evidence of functional abnormalities in the default mode network in bipolar depression: A coordinate-based activation likelihood estimation meta-analysis

J Affect Disord. 2023 Apr 1:326:96-104. doi: 10.1016/j.jad.2023.01.088. Epub 2023 Jan 27.


Background: The default mode network (DMN) is thought to be involved in the pathophysiology of bipolar depression (BD). However, the findings of prior studies on DMN alterations in BD are inconsistent. Thus, this study aimed to systematically investigate functional abnormalities of the DMN in BD patients.

Methods: We systematically searched PubMed, Ovid, and Web of Science for functional neuroimaging studies on regional homogeneity, amplitude of low frequency fluctuations (ALFF), and functional connectivity of the DMN in BD patients published before March 18, 2022. The stereotactic coordinates of the reported altered brain regions were extracted and incorporated into a brain map using the coordinate-based activation likelihood estimation approach.

Results: A total of 43 original research studies were included in the meta-analysis. BD patients showed specific changes in the DMN including decreased ALFF/fractional ALFF in the left cingulate gyrus (CG) and bilateral precuneus (PCUN); increased functional connectivity (FC) in the left CG, left posterior CG, left PCUN, bilateral medial frontal gyrus, and bilateral superior frontal gyrus; and decreased FC in the left CG, left PCUN, left inferior parietal lobule, and left postcentral gyrus.

Limitations: Conclusions are limited by the small number of studies, additional meta-analyses are needed to obtain more data in BD subgroup.

Conclusion: This meta-analysis supports specific changes in DMN activity and FC in BD patients, which may be powerful biomarkers for the diagnosis of BD. The CG and PCUN were the most affected regions and are thus potential targets for clinical interventions to delay BD progression.

Keywords: Activation likelihood estimation; Amplitude of low-frequency fluctuation; Bipolar depression; Default mode network; Functional connectivity.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bipolar Disorder* / diagnostic imaging
  • Brain / diagnostic imaging
  • Default Mode Network
  • Humans
  • Likelihood Functions
  • Magnetic Resonance Imaging / methods