RES E A R C H A R T I C L E Open Access
Gender differences in functional
connectivities between insular subdivisions
and selective pain-related brain structures
, Xin Zhang
, Yang Yang
, Hai-Yan Nan
, Ying Yu
, Qian Sun
, Lin-Feng Yan
, Jin Zhang
, Yi Gao
, Guang-Bin Cui
, Bi-Liang Chen
and Wen Wang
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: Gender differences, Insular subdivisions, Pain, Functional connectivity, Resting-state
* Correspondence: email@example.com; firstname.lastname@example.org;
Yu-Jie Dai, Xin Zhang and Yang Yang contributed equally to this work.
Department of Radiology & Functional and Molecular Imaging Key Lab of
Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA
Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi’an, Shaanxi
Province 710038, China
Department of Obstetrics and Gynecology, Xijing Hospital, the Military
Medical University of PLA Airforce (Fourth Military Medical University), 15
West Changle Road, Xi’an, Shaanxi Province 710032, China
Full list of author information is available at the end of the article
The Journal of Headache
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made.
Dai et al. The Journal of Headache and Pain (2018) 19:24