Abnormal Pain Network In Patients With Functional Dyspepsia: A MRI Study

Functional dyspepsia(FD),a common functional gastrointestinal disorder,is characterized by postprandial epigastric pain,early fullness,heart burning,sour regurgitation,bloating,nausea,vomiting and abdominal discomfort.FD has significantly negative effect on health-related qualities of life and leads to high health-care costs.A world-based epidemiological study shows that about 11%-30% of the population suffer from FD.In the Chinese population the prevalence of FD was 23.5%.Studies have shown that the pathogenesis of FD is multifactorial,including altered gastrointestinal motility,Helicobacter pylori infection,visceral hypersensitivity,brain-gut axis dysregulation,and psychological factors.Accumulating evidence have suggested the crucial role of brain-gut interactions in the development and maintenance of FD.Brain imaging techniques have indicated the differences of brain activity and structure in FD patients compared to healthy controls(HCs).In the present thesis,we thereby aimed to explore brain functional and structural alterations in FD using resting-state functional and structural magnetic resonance imaging(MRI)respectively.Firstly,functional connectivity analysis was performed to investigate the periaqueductal gray(PAG)connectivity pattern differences between the FD patients and HCs.The result showed that compared to HCs,FD patients had increased PAG connectivity with the insula,and decreased PAG connectivity with the orbitofrontal cortex(OFC),dorsolateral prefrontal cortex(dl PFC)and hippocampus/parahippocampus(HIPP/para HIPP).There were positive correlations between disease duration and PAG connectivity with the putamen and supplementary motor area(SMA),and positive correlations between the Nepean Dyspepsia Index(NDI)and PAG connectivity with the insula.FD patients with high level of anxiety and depression had altered PAG connectivity with the anterior cingulate cortex(ACC),precuneus,dl PFC and caudate,compared to other patients.These findings indicate that abnormal intrinsic network of the PAG might be associated with abnormality of pain processing and disruption of emotion processing in FD patients.Secondly,we explored brain structural alterations including the cortical thickness and subcortical volumes in FD patients by cortical thickness analysis method.Our results showed that FD patients had decreased cortical thickness compared to HCs in the distributed brain regions including the(dl PFC),ventrolateral prefrontal cortex(vl PFC),medial prefrontal cortex(m PFC),anterior/posterior cingulate cortex(ACC/PCC),insula,superior parietal cortex(SPC),supramarginal gyrus and lingual gyrus.Significantly negative correlations were observed between the NDI and cortical thickness in the m PFC,second somatosensory cortex(SII),ACC and para HIPP.And significantly negative correlations were found between disease duration and the cortical thickness in the vl PFC,first somatosensory cortex(SI)and insula in FD patients.These findings suggest that FD patients have structural abnormalities in brain regions involved in sensory perception,sensorimotor integration,pain modulation,affective and cognitive controls.In summary,our findings provide further evidence of the brain activity and structural abnormalities in FD which might help to further improve our understanding of the neural mechanisms of FD and thereby improving the treatment of FD.