Objective:To investigate the changes in gray matter volume of the subsystems as well as intra-subsystem and inter-subsystem functional connectivity in the default mode network (DMN) of relapsing-remitting multiple sclerosis (RRMS) patients with preserved cognitive function.Methods:In this prospective study, thirty-seven RRMS patients with preserved cognitive function who were admitted to Huashan Hospital of Fudan University from April 2020 to January 2021 (RRMS group) and 43 healthy volunteers (HC group) were recruited. Patients in the RRMS group received the cognitive assessment using a clinical cognitive functioning scale. Three-dimensional T 1WI and resting-state functional MRI were performed to obtain the brain structural and functional data. The DMN was divided into three subsystems: CORE, dorsal medial prefrontal cortex (DMPFC), and medial temporal lobe (MTL). The gray matter volume of the three subsystems were extracted from the gray matter volume map generated by spatial normalization; 24 regions of interest (ROIs) of the DMN were defined based on Yeo′s 17 networks, and their functional connectivity values were calculated to derive the mean intra-subsystem and inter-subsystem functional connectivity values. Differences in gray matter volume and functional connectivity between the RRMS and HC groups were compared using independent sample t-tests; Spearman′s partial correlation was used to analyze the correlation between subsystems′ gray matter volume and functional connectivity, as well as between subsystems′ functional connectivity and clinical scale scores. Results:Compared to the HC group, the gray matter volume of the three subsystems of the DMN were considerably reduced in the RRMS group ( P<0.05). The functional connectivity within and between the three subsystems were not statistically significantly different between the HC and RRMS groups ( P>0.05). Based on the ROI analysis, patients with RRMS the brain regions with significantly reduced DMN intra-subsystem functional connectivity values were mainly located in the left dorsomedial prefrontal cortex of the DMPFC, the right lateral temporal cortex of the DMPFC, and the left medial temporal cortex of the MTL, as compared with the HC group ( P<0.01). The gray matter volume of DMPFC was positively correlated with the functional connectivity within DMPFC in the control group ( r=0.326, P=0.040). In the RRMS group, the gray matter volume of CORE was positively correlated with the functional connectivity between CORE and DMPFC ( r=0.363, P=0.038), and the functional connectivity within CORE was positively correlated with scores on the memory and executive screening scale ( r=0.430, P=0.036). Conclusions:RRMS patients with preserved cognitive function exhibit gray matter atrophy in all three DMN subsystems. There is no correlation between the structure and function of the DMPFC subsystem. The functional connectivity within CORE subsystem may reflect memory and execution status; DMPFC and CORE may be critical encephalic regions for neurodegeneration and brain functional changes in RRMS patients with preserved cognitive function.