Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures

Yu-Jie Dai, Xin Zhang, Yang Yang, Hai-Yan Nan, Ying Yu, Qian Sun, Lin-Feng Yan, Bo Hu, Jin Zhang, Zi-Yu Qiu, Yi Gao, Guang-Bin Cui, Bi-Liang Chen, Wen Wang, Yu-Jie Dai, Xin Zhang, Yang Yang, Hai-Yan Nan, Ying Yu, Qian Sun, Lin-Feng Yan, Bo Hu, Jin Zhang, Zi-Yu Qiu, Yi Gao, Guang-Bin Cui, Bi-Liang Chen, Wen Wang

Abstract

Background: The incidence of pain disorders in women is higher than in men, making gender differences in pain a research focus. The human insular cortex is an important brain hub structure for pain processing and is divided into several subdivisions, serving different functions in pain perception. Here we aimed to examine the gender differences of the functional connectivities (FCs) between the twelve insular subdivisions and selected pain-related brain structures in healthy adults.

Methods: Twenty-six healthy males and 11 age-matched healthy females were recruited in this cross-sectional study. FCs between the 12 insular subdivisions (as 12 regions of interest (ROIs)) and the whole brain (ROI-whole brain level) or 64 selected pain-related brain regions (64 ROIs, ROI-ROI level) were measured between the males and females.

Results: Significant gender differences in the FCs of the insular subdivisions were revealed: (1) The FCs between the dorsal dysgranular insula (dId) and other brain regions were significantly increased in males using two different techniques (ROI-whole brain and ROI-ROI analyses); (2) Based on the ROI-whole brain analysis, the FC increases in 4 FC-pairs were observed in males, including the left dId - the right median cingulate and paracingulate/ right posterior cingulate gyrus/ right precuneus, the left dId - the right median cingulate and paracingulate, the left dId - the left angular as well as the left dId - the left middle frontal gyrus; (3) According to the ROI-ROI analysis, increased FC between the left dId and the right rostral anterior cingulate cortex was investigated in males.

Conclusion: In summary, the gender differences in the FCs of the insular subdivisions with pain-related brain regions were revealed in the current study, offering neuroimaging evidence for gender differences in pain processing.

Trial registration: ClinicalTrials.gov, NCT02820974 . Registered 28 June 2016.

Keywords: Functional connectivity; Gender differences; Insular subdivisions; Pain; Resting-state.

Conflict of interest statement

Ethics approval and consent to participate

This study conformed to the principles of the Declaration of Helsinki and was approved by the ethics committee of Tangdu Hospital of the Fourth Military Medical University.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
ROI-whole brain analysis of FCs between the 12 insular subdivisions and the whole brain (visualization of the clusters on the brain surface). The warm color in the statistical differences map indicated the increased FCs between the dId_L and the whole brain in males. dId, dorsal dysgranular insula; L, left; R, right; FCs, functional connectivities; ROI, region of interest
Fig. 2
Fig. 2
ROI-ROI analysis of FCs between the 12 insular subdivisions and 64 selected pain-related brain regions. The red ball represented the dId_L, the green ball represented the rACC_R, and the yellow rod represented the statistically increased FC in males. L, left; R, right; dId, dorsal dysgranular insula; rACC, rostral anterior cingulate cortex; ROI, region of interest; FCs, functional connectivities
Fig. 3
Fig. 3
Merging of ROI-whole brain and ROI-ROI analyses. The warm color in the statistical differences map exhibited the increased FCs between the dId_L and the whole brain in males (ROI-whole brain analysis). The red ball represented the dId_L, the green ball represented the rACC_R, and the yellow rod represented the statistically increased FC between the dId_L and the rACC_R in males (ROI-ROI analysis). L, left; R, right; dId, dorsal dysgranular insula; rACC, rostral anterior cingulate cortex; ROI, region of interest; FCs, functional connectivities

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