Imaging Study On Abnormal Topological Properties Of The Brain Functional Network In Patients With Functional Constipation And Its Subtypes Based On Graph Theory

In recent years,the changes in people’s dietary structure and living habits,increased stress caused by style of living and work,and reduced physical activity have led to an increase in the prevalence of functional constipation.Patients with long-term severe constipation symptoms suffer from further psychological disorders such as anxiety and depression,which seriously impact the patient’s health-related quality of life.Neuroimaging studies found that functional constipation was associated with abnormal brain function and structure,reflecting abnormal brain-gut interactions in patients.In addition,severe psychological disorders will participate in brain-gut interactions and impact the development of functional constipation.However,previous studies had paid more attention to the abnormalities in individual brain regions in patients with functional constipation and lacked investigations of the abnormal central mechanism of the brain from the perspective of brain networks.Therefore,the current study combined the resting-state functional magnetic resonance imaging and graph-theory approach to further explore the abnormal topological properties of the brain functional network in patients with functional constipation(FCon),FCon patients without anxiety/depression status(FCNAD)and FCon patients with anxiety/depression status(FCAD).These studies can provide imaging evidence for revealing the central mechanism of functional constipation from the perspective of the brain network.First,the study of the brain functional networks in patients with functional constipation was executed by applying the graph theory approach.This study included 42 FCon patients and 41 healthy controls.Permutation test was applied to investigate the abnormalities in the brain functional network from a global scale,regional scale and modular scale.Results showed that the patients and healthy controls had typical "small-worldness".Moreover,the normalized clustering coefficient and "small-worldness" of patients with FCon were lower than healthy controls.Regions showed abnormal nodal degree/efficiency located in the thalamus(THA),rostral anterior cingulate gyrus(r ACC)and supplementary motor area(SMA)(also including the precentral gyrus-Pre Cen,anterior insula-a INS,amygdala-AMY,superior parietal lobe-SPL and inferior parietal lobe-IPL).The nodal degree of the THA was significantly negatively correlated with the difficulty of defecation and the nodal degree of the r ACC was significantly negatively correlated with sensation of incomplete evacuation.In addition,the regions involved in somatic/sensory processing(THA),emotional processing(r ACC)and motor-control(SMA)showed abnormal within-module nodal degree/efficiency.Thalamus-related network had an abnormal interaction with limbic networks(mainly include AMY and hippocampus).These findings suggested that functional constipation was associated with abnormalities in the thalamus-cortical network.Second,we expanded the sample size on the basis of the previous study.Then,FCon patients were classified into 41 FCAD and 42 FCNAD using a hierarchical-clustering algorithm based on neuropsychological assessment(anxiety,depression,state-trait anxiety).One-way ANOVA analysis was used to determine the significant difference among FCAD,FCNAD and HC group.Results showed that there were abnormalities in normalized cluster coefficients and "small-worldness".The abnormal node degree/efficiency of FCAD and FCNAD were located in the r ACC,Pre Cen,THA,SMA and SPL.The abnormal normalized within-module nodal degree in the r ACC highlighted the abnormal information integration of the r ACC in the network in patients with functional constipation subtypes(FCAD and FCNAD).Meanwhile,the current study also found significant group effects in inter-module connectivity between the salience network and the frontal-parietal network.In the FCNAD group,functional connectivity(left a INS-left r ACC)was only associated with symptoms of constipation.However,in the FCAD group,functional connectivity(DMPFC-left r ACC and right Pre Cen-right a INS)was not only associated with constipation symptoms but was also associated with mental status,suggesting that there were different intestinal-brain interactions between FCAD and FCNAD.In addition,the results of the network-based statistical analysis(NBS)highlighted the importance of the r ACC in the whole-brain network of patients.These findings reflected that the brain functional networks of FCAD and FCNAD were abnormal in varying degrees and mental factors played an important role in the development of functional constipation.Finally,we selected the effective features from the topological parameters of the functional brain network and the functional connectivity of the local network(the union of the salience network and limbic network)in patients with functional constipation subtypes.Subjects were the same as the samples of FCAD and FCNAD in the last chapter.Support vector machine(SVM)was used to construct a classification model of the patient’s mental state by identifying these selected features.Results showed that the classification accuracy rate was 75.90%,the sensitivity rate was 80.95%,and the specificity rate was 70.73%,suggesting that the topological parameters of the brain functional network and functional connectivity of the local network have potential as biomarkers that can distinguish the mental state of patients with functional constipation.In this study,we investigated the abnormal topological properties of the functional network in patients with functional constipation(FCon)and its subtypes(FCAD and FCNAD)from a system-level perspective by using the graph-theory approach,providing new findings for the abnormal central mechanism induced by functional constipation.In addition,the classification study of functional constipation subtypes could provide clues for clinicians to diagnose patients’ mental state,which would facilitate personalized treatment.