Seminowicz DA, et al. proved that IBS was associated with decreased gray matter density in the medial prefrontal cortex, ventrolateral prefrontal cortex, posterior parietal cortex, ventral striatum and thalamus, and increased GMD in the pACC and the orbitofrontal cortex. These studies provided a new approach to exploring the pathogenesis of FGID. However, no study has been performed on the FD patients. We hypothesize that the persistent and recurrent dyspepsia experience and the significant cerebral functional abnormality might influence the brain structure of FD patients. By using structural fMRI, this study aimed to 1) compare the cerebral GMD difference between the meal-related FD patients and the HS with a relatively large and tightly screened sample; 2) explore the possible influence of the emotional state on regional GMD and 3) investigate the correlations of regional GMD changes with clinical variables. The HS were recruited by advertisement. Each HS was free from any gastrointestinal symptoms or signs, and underwent a basic evaluation, including a review of medical history, a physical examination, gastrointestinal endoscopy, upper abdominal ultrasound and electrocardiogram. The resulting greymatter partial volume images were then aligned to MNI152 standard space using the FMRIB’s linear image registration tool, followed by FMRIB’s nonlinear image registration tool which uses a b-spline representation of the registration warp field. The resulting images were averaged to create a study-specific template, to which the native gray matter images were then nonlinearly re-registered. In order to correct for local expansion or contraction, the registered partial volume images were modulated by dividing by the Jacobian of the warp field. An isotropic Gaussian kernel with a sigma of 3 mm was then used to smooth the modulated segmentated images. Finally, a voxelwise group-difference was assessed by using permutationbased non-parametric testing with the covariates: gender+age, gender+age+anxiety+depression. For multiple comparison corrections, the threshold-free cluster enhancement with the family-wise error AbMole Nortriptyline correction was employed. In order to assess the relationship between clinical variables and GMD, the mean value of the first ten continuous voxels around the local maximum of each cluster showing a significant group-difference was first extracted. Then the mean values’ correlations with symptom scores of the NDI and disease durations were calculated respectively by using a partial correlation analysis. Bonferroni correction was applied for multiple comparisons. The regions of interest were chosen mainly based on our previous study and the current VBM results. In 
our previous study, we found that the abnormal activities in the ACC, MCC, insula, thalamus and cerebellum were significantly associated with symptom severity of FD patients.