Altered dynamic functional connectivity of insular subdivisions among male cigarette smokers

Abstract

Background: Insular subdivisions show distinct patterns of resting state functional connectivity with specific brain regions, each with different functional significance in chronic cigarette smokers. This study aimed to explore the altered dynamic functional connectivity (dFC) of distinct insular subdivisions in smokers.

Methods: Resting-state BOLD data of 31 smokers with nicotine dependence and 27 age-matched non-smokers were collected. Three bilateral insular regions of interest (dorsal, ventral, and posterior) were set as seeds for analyses. Sliding windows method was used to acquire the dFC metrics of different insular seeds. Support vector machine based on abnormal insular dFC was applied to classify smokers from non-smokers.

Results: We found that smokers showed lower dFC variance between the left ventral anterior insula and both the right superior parietal cortex and the left inferior parietal cortex, as well as greater dFC variance the right ventral anterior insula with the right middle cingulum cortex relative to non-smokers. Moreover, compared to non-smokers, it is found that smokers demonstrated altered dFC variance of the right dorsal insula and the right middle temporal gyrus. Correlation analysis showed the higher dFC between the right dorsal insula and the right middle temporal gyrus was associated with longer years of smoking. The altered insular subdivision dFC can classify smokers from non-smokers with an accuracy of 89.66%, a sensitivity of 96.30% and a specify of 83.87%.

Conclusions: Our findings highlighted the abnormal patterns of fluctuating connectivity of insular subdivision circuits in smokers and suggested that these abnormalities may play a significant role in the mechanisms underlying nicotine addiction and could potentially serve as a neural biomarker for addiction treatment.

Keywords: dynamic functional connectivity (dFC); fMRI; insula; nicotine; subdivisions.

Figure 1

The group difference in dFC variance of insular subregions (voxel p < 0.005, cluster p < 0.05, Gaussian random field corrected). L, left; R, right; vAI, ventral anterior insula; dAI, dorsal anterior insula.

Figure 2

Relationship between years of smoking and dFC variance between the right dAI and right MTG. dFC, dynamic functional connectivity; dAI, dorsal anterior insula; MTG, middle temporal gyrus.

Figure 3

The performance of the classification model. (A) The area under the curve and (B) the permutation test results.