Dynamic functional connectivity in bipolar disorder is associated with executive function and processing speed: A preliminary study

Abstract

Objective: Disturbances in functional connectivity have been suggested to contribute to cognitive and emotion processing deficits observed in bipolar disorder (BD). Functional connectivity between medial prefrontal cortex (mPFC) and other brain regions may be particularly abnormal. The goal of the present study was to characterize the temporal dynamics of the default mode network (DMN) connectivity in BD and examine its association with cognition.

Method: In a preliminary study, euthymic BD (n = 15) and healthy comparison (HC, n = 19) participants underwent resting-state functional MRI, using high-resolution sequences adapted from the Human Connectome Project, and completed neuropsychological measures of processing speed and executive function. A seed-based approach was used to measure DMN correlations in each participant, with regions of interest in the mPFC, posterior cingulate cortex (PCC), and lateral parietal cortex. Subsequently, to characterize temporal dynamics, correlational analyses between the mPFC and other DMN nodes were repeated using a sliding-window correlational analysis with subsets of the time series.

Results: When averaged across the entire scan, there were no group differences in overall connectivity strength between the mPFC and other regions of the DMN. However, dynamic connectivity between the mPFC and PCC was altered in BD, such that connectivity was less variable (i.e., more rigid) over time. Decreased connectivity variability was associated with slower processing speed and reduced cognitive set-shifting in BD patients.

Conclusions: Variability in resting-state functional connectivity may be an index of internetwork flexibility that is reduced in BD and a correlate of ongoing cognitive impairment during periods of euthymia. (PsycINFO Database Record

Figure 1

Static (A) and dynamic (B) resting-state functional connectivity between the mPFC and canonical DMN regions. (A) Scores represent the average connectivity strength of the mPFC with other DMN regions for the entire resting-state scan. BD and HC did not differ on average connectivity of the mPFC to the PCC or AG regions. (B) Scores are presented as the variance in correlation strength, across 19 sliding windows, between the mPFC and other DMN regions. mPFC connectivity strength with PCC was less variable over time in BD than in HC. *Bonferroni-corrected p ≤ .017 BD, bipolar disorder; HC, healthy control; AG, angular gyrus and inferior parietal lobule; mPFC, medial prefrontal cortex; L, left; PCC, posterior cingulate cortex; R, right

Figure 2

mPFC-PCC connectivity has reduced variability in BD compared to HC but not reduced average correlation strength. (A) Mask locations of the mPFC, PCC, and DMN ROIs. (B) Representative sliding-window correlation time courses between the mPFC and PCC for a HC and BD participant. BD, bipolar disorder; HC, healthy control; mPFC, medial prefrontal cortex; PCC, posterior cingulate cortex

Figure 3

Scatterplots depicting the significant interaction of Group (BD vs. HC) and mPFC-PCC connectivity variability on composite measures of (A) processing speed and (B) executive function. **p ≤ .01 BD, bipolar disorder; HC, healthy control; mPFC, medial prefrontal cortex; PCC, posterior cingulate cortex