Functional Connectivity Between Anterior Insula and Key Nodes of Frontoparietal Executive Control and Salience Networks Distinguish Bipolar Depression From Unipolar Depression and Healthy Control Subjects

Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 May;3(5):473-484. doi: 10.1016/j.bpsc.2018.01.013. Epub 2018 Feb 7.


Background: Patients with bipolar depression are characterized by dysregulation across the full spectrum of mood, differentiating them from patients with unipolar depression. The ability to switch neural resources among the default mode network, salience network, and executive control network (ECN) has been proposed as a key mechanism for adaptive mood regulation. The anterior insula is implicated in the modulation of functional network switching. Differential connectivity between anterior insula and functional networks may provide insights into pathophysiological differences between bipolar and unipolar mood disorders, with implications for diagnosis and treatment.

Methods: Resting-state functional magnetic resonance imaging data were collected from 98 subjects (35 unipolar, 24 bipolar, and 39 healthy control subjects). Pearson correlations were computed between bilateral insula seed regions and a priori defined target regions from the default mode network, salience network, and ECN. After r-to-z transformation, a one-way multivariate analysis of covariance was conducted to identify significant differences in connectivity between groups. Post hoc pairwise comparisons were conducted and Bonferroni corrections were applied. Receiver-operating characteristics were computed to assess diagnostic sensitivity.

Results: Patients with bipolar depression evidenced significantly altered right anterior insula functional connectivity with the inferior parietal lobule of the ECN relative to patients with unipolar depression and control subjects. Right anterior insula-inferior parietal lobule connectivity significantly discriminated patients with bipolar depression.

Conclusions: Impaired functional connectivity between the anterior insula and the inferior parietal lobule of the ECN distinguishes patients with bipolar depression from those with unipolar depression and healthy control subjects. This finding highlights a pathophysiological mechanism with potential as a therapeutic target and a clinical biomarker for bipolar disorder, exhibiting reasonable sensitivity and specificity.

Keywords: Bipolar depression; Frontoparietal; Functional network connectivity; Insula; Salience; Unipolar depression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / physiopathology*
  • Brain Mapping / methods
  • Cerebral Cortex / physiopathology*
  • Depressive Disorder, Major / physiopathology*
  • Executive Function / physiology*
  • Female
  • Healthy Volunteers*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Parietal Lobe / physiopathology
  • Rest / physiology