Sex-related differences in resting-state brain activity and connectivity in the orbital frontal cortex and insula in patients with functional constipation

Functional magnetic resonance imaging (fMRI) has been used to investigate sex-related differences in brain abnormalities in patients with irritable bowel syndrome (IBS). Like IBS, women with functional constipation (FC) are 2.1 times as many as men. No study has been performed yet to examine sex-related differences in brain activity and connectivity in patients with FC. Here, we employed resting-state fMRI with amplitude of low-frequency fluctuation (ALFF) to investigate brain functional differences in 51 patients with FC (34 females) and 52 healthy controls (34 females). Results showed abdominal pain and abdominal distension correlated with trait (TAI) and state (SAI) anxiety ratings in the female FC group, and abdominal distension correlated with sensation of incomplete evacuation in the male FC group. Two-way ANOVA revealed sex effects on ALFF in precentral gyrus, thalamus, insula (INS), and orbital frontal cortex (OFC, P-FWE < 0.05). Post hoc test showed that the female FC group had lower ALFF than males in these brain regions (P < 0.01), and ALFF in INS and OFC was correlated with abdominal pain and difficulty of defecation, respectively. Seed voxel correlation analysis showed that the female FC group had weaker connectivity than males between INS and lateral OFC (lOFC). INS-lOFC connectivity was negatively correlated with the anxiety score in the female FC group and was negatively correlated with abdominal distension in the male FC group. These findings provide the first insight into sex-related differences in patients with FC and highlight that INS and OFC play an important role in modulating the intrinsic functional connectivity of the resting brain network showing that this role is influenced by sex.