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. 2014 Oct 22;34(43):14252-9.
doi: 10.1523/JNEUROSCI.1683-14.2014.

Sex and disease-related alterations of anterior insula functional connectivity in chronic abdominal pain

Jui-Yang Hong  1 , Lisa A Kilpatrick  2 , Jennifer S Labus  3 , Arpana Gupta  4 , David Katibian  5 , Cody Ashe-McNalley  2 , Jean Stains  4 , Nuwanthi Heendeniya  4 , Suzanne R Smith  4 , Kirsten Tillisch  2 , Bruce Naliboff  3 , Emeran A Mayer  6
Affiliations

Sex and disease-related alterations of anterior insula functional connectivity in chronic abdominal pain

Jui-Yang Hong et al. J Neurosci. .

Abstract

Resting-state functional magnetic resonance imaging has been used to investigate intrinsic brain connectivity in healthy subjects and patients with chronic pain. Sex-related differences in the frequency power distribution within the human insula (INS), a brain region involved in the integration of interoceptive, affective, and cognitive influences, have been reported. Here we aimed to test sex and disease-related alterations in the intrinsic functional connectivity of the dorsal anterior INS. The anterior INS is engaged during goal-directed tasks and modulates the default mode and executive control networks. By comparing functional connectivity of the dorsal anterior INS in age-matched female and male healthy subjects and patients with irritable bowel syndrome (IBS), a common chronic abdominal pain condition, we show evidence for sex and disease-related alterations in the functional connectivity of this region: (1) male patients compared with female patients had increased positive connectivity of the dorsal anterior INS bilaterally with the medial prefrontal cortex (PFC) and dorsal posterior INS; (2) female patients compared with male patients had greater negative connectivity of the left dorsal anterior INS with the left precuneus; (3) disease-related differences in the connectivity between the bilateral dorsal anterior INS and the dorsal medial PFC were observed in female subjects; and (4) clinical characteristics were significantly correlated to the insular connectivity with the dorsal medial PFC in male IBS subjects and with the precuneus in female IBS subjects. These findings are consistent with the INS playing an important role in modulating the intrinsic functional connectivity of major networks in the resting brain and show that this role is influenced by sex and diagnosis.

Keywords: IBS; fMRI; insula; pain; sex difference.

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Figures

Figure 1.
Figure 1.
Significant clusters connected to the dorsal anterior INS among all subjects. Regions showed positive functional connectivity to the left dorsal anterior INS (a) and the right dorsal anterior INS (b). Regions were negatively connected to the left dorsal anterior INS (c) and the right dorsal anterior INS (d). Images were thresholded at a voxelwise p value of 0.005 and clusterwise corrected for multiple comparisons using FWE correction at a p value <0.05.
Figure 2.
Figure 2.
Group differences in functional connectivity of the left dorsal anterior INS. a, Single-group connectivity maps of the left dorsal anterior INS. For display purposes only, all statistical results, thresholding at p < 0.005 uncorrected and cluster > 29 voxels, were overlapped on a MRIcron ch2better template. Red, Positive connectivity; blue, negative connectivity. b, Regions showed significant functional connectivity differences between groups (p < 0.05, corrected). c, Graph showed mean Z scores of significant regions connected with the left dorsal anterior INS for each group. * indicates significant difference after controlling for age, anxiety, and depression, p < 0.05, corrected. Error bars reflect SE. dmPFC, dorsal medial PFC; dpINS, dorsal posterior INS; HCF, HC females; HCM, HC males; IBSF, IBS female patients; IBSM, IBS male patients; L, left; mPFC, medial PFC.
Figure 3.
Figure 3.
Group differences in functional connectivity of the right dorsal anterior INS. a, Single-group positive and negative connectivity maps of the right dorsal anterior INS (all statistical results were overlapped on a MRIcron ch2better template). b, Regions showed significant functional connectivity differences between groups (p < 0.05, corrected). c, Graph showed average Z scores of significant regions connected with the right dorsal anterior INS for each group. * indicates significant difference after controlling for age, anxiety, and depression, p < 0.05, corrected for multiple comparison. dmPFC, dorsal medial PFC; dpINS, dorsal posterior INS; HCF, HC females; HCM, HC males; IBSF, IBS female patients; IBSM, IBS male patients; L, left; mPFC, medial PFC; R, right.
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