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Dynamic functional network connectivity impairment in bipolar disorder and its relationship with global functioning.

Daniele Olivo1, Alessandro Miola2, Francesco Folena Comini3

  • 1Department of Neuroscience (DNS), University of Padova, Padua, Italy; Padova Neuroscience Center, University of Padova, Padua, Italy; Padua University Hospital, UOC Psychiatry 3, Padua, Italy.

European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology
|December 14, 2025
PubMed
Summary

Bipolar disorder (BD) shows reduced dynamic functional network connectivity (dFNC), indicating less brain flexibility. This neural inflexibility is linked to poorer global functioning, especially in bipolar I disorder (BD1).

Keywords:
Bipolar disorderDynamic functional network connectivity (dFNC)Global functioning (GAF)Meta-state brain network dynamicsResting-state fMRI

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Computational Neuroscience

Background:

  • Abnormal functional connectivity (FC) is a hallmark of bipolar disorders (BD).
  • Traditional FC analyses assume static brain interactions, but connectivity is dynamic over time.
  • Understanding dynamic functional network connectivity (dFNC) alterations in BD is crucial for clinical insights.

Purpose of the Study:

  • To investigate dFNC alterations in bipolar disorder (BD) compared to healthy controls (HCs).
  • To examine the association of dFNC with symptom severity and global functioning in BD.
  • To explore potential differences in dFNC between bipolar I disorder (BD1) and bipolar II disorder (BD2).

Main Methods:

  • Case-control study involving 57 patients with BD (29 BD1, 28 BD2) and 43 HCs.
  • Resting-state fMRI data analyzed using spatially constrained independent component analysis and a sliding-window approach.
  • Meta-state metrics (number of meta-states, transitions, total distance, span) derived and compared across groups; correlations with clinical measures and GAF scores tested.

Main Results:

  • Patients with BD exhibited reduced dynamic metrics (number of meta-states, state transitions, total distance) compared to HCs.
  • The greatest reduction in dynamic metrics was observed in BD1, followed by BD2.
  • Higher Global Assessment of Functioning (GAF) scores in the BD sample were positively associated with greater dynamic fluidity, not symptom severity.

Conclusions:

  • Bipolar disorder is characterized by disrupted spatio-temporal dynamics of large-scale brain networks, with severity correlating with disorder type (BD1 > BD2).
  • Reduced neural flexibility, as measured by dFNC meta-state metrics, is linked to poorer global functioning in BD.
  • dFNC meta-state metrics may serve as clinically relevant biomarkers for assessing illness burden in bipolar disorder.