Functional constipation (FCon) is one of the common functional gastrointestinal disorders (FGID) (Alame and Bahna 2012; De Giorgio et al. 2015; Koppen et al. 2015) with an average female-male ratio of 2.1:1 (Mugie et al. 2010) and a prevalence ranging from 0.7–79% in clinical practice (Alame and Bahna 2012; Koppen et al. 2015; Mugie et al. 2010). FCon features infrequent bowel movements, difficulty of defecation, large and/or hard stools, excessive straining, and is usually associated with abdominal distension/pain (Alame and Bahna 2012; De Giorgio et al. 2015; Koppen et al. 2015). These symptoms have imposed a huge burden on families and society because of impaired quality of life (Bongers et al. 2009) and emotional status (Jones et al. 2006).
In recent years, neuroimaging has been gradually employed to assess brain structural and functional changes in patients with FCon (Li et al. 2021; Blankstein et al. 2010; Hu et al. 2020; Jin et al. 2019; Mayer et al. 2009; Tillisch et al. 2011). Previous resting-state functional magnetic resonance imaging (RS-fMRI) report showed FCon related brain functional abnormalities were in areas associated with emotional modulation including anterior insula-aINS, hippocampal gyrus-HIPP, orbital frontal cortex-OFC, and dorsal anterior cingulate cortex-dACC (Zhu et al. 2016). Another RS-fMRI report was designed to examine gender-related differences in resting-state brain activity and functional connectivity in FCon patients, and results showed lower basal brain activities (i.e., insula-INS, precentral gyrus-PreCen, thalamus, and OFC) in female FCon patients than in males and INS/OFC had a negative correlation with FCon symptoms (Jin et al. 2019). One study combining graph theory with RS-fMRI showed that FCon had small-worldness and a low normalized clustering coefficient, indicating reduced brain functional connectivity, which were predominately related to the rostral anterior cingulate cortex (emotional processing), SMA (motor-control), and thalamus (somatic/sensory) (Liu et al. 2021). One newly published study reported FCon showed decreased activity in fractional amplitude of low-frequency fluctuation in the perigenual anterior cingulate cortex, dorsomedial prefrontal cortex and precuneus (Li et al. 2021).
Growing evidence have showed that brain functional abnormalities might be associated with structural changes (Hao et al. 2013; Hubbard et al. 2016; Wang et al. 2020). Previous MRI study reported cortical morphometric alterations in brain areas involved with emotional processing (middle frontal cortex-MFG, dACC, and OFC), self-referential processing (precuneus/posterior cingulate cortex), and somatic/motor-control (SMA) in FCon group (Hu et al. 2020). Cortical morphological abnormalities may be related to changes in diffusion parameters (Tamnes et al. 2010). Another recent study showed that FCon was related to changes in thalamo-limbic/parietal structural connectivity (SC) (Zhang et al. 2020). However, few studies have been performed to examine the alterations in gray matter (GM) volume and associated SC in patients with FCon.
In addition, one structural MRI study reported that IBS patients displayed significant alterations in GM volumes in the middle frontal gyrus (MFG), anterior cingulate cortex (ACC), INS, and HIPP (Zhao et al. 2018). Diffusion tensor imaging (DTI) detected abnormalities in SC between INS and ACC in IBS patients (Chen et al. 2011). Female IBS patients had decreased GM volumes in the INS, MFG, ACC, and HIPP (Labus et al. 2014). These previous brain imaging studies on IBS consistently recorded changes in brain regions implicated in emotional processing and modulation, especially in the aINS and ACC, which are key nodes of the salience network (SN) (Chang et al. 2013; Garcia-Larrea 2012; Mayer et al. 2015). The SN, which includes INS, ACC, and MFG, is responsible for integrating all kinds of sensory information and directing specific brain regions to respond appropriately (Peters et al. 2016). However, whether FCon is implicated in structural abnormalities in the SN has not been investigated yet.
The current study was designed to explore the brain structural changes in FCon patients. Thus, voxel-based morphometry (VBM) was first employed to explore differences in GM volumes between 48 FCon patients and 52 healthy controls (HC), and regions showing significant differences were then selected as seed regions for probabilistic tractography to feature regional SC as quantified by fractional anisotropy (FA), mean- (MD), axial- (AD), and radial diffusivity (RD). The study aimed to test whether: (a) FCon would be associated with abnormality in GM volumes in brain regions within the SN, which are implicated in interoception and emotional processing. (b) FCon would be associated with alterations in SC of brain regions within the SN.