Study On The Dynamic Functional Connectivity Of The Default Mode Network And Thalamocortical System In Relapsing-Remitting Multiple Sclerosis

Objective:(1)To explore the difference patterns of dynamic functional connectivity(dFC)variability in default mode network(DMN)of patients with relapsing-remitting multiple sclerosis(RRMS)in acute phase and remission phase and its relationship with spontaneous fluctuation time state.(2)To investigate the dFC variability and static functional connectivity(sFC)changes in the thalamocortical system in RRMS patients and study their relationship to clinical markers(such as cognitive impairment,fatigue,etc.).Methods:3.0 T magnetic resonance imaging was used to collect rs-fMRI data from the acute phase RRMS(n=18),the remission phase RRMS(n=26),and age-and sex-matched healthy controls(HC group,n=23).The fMRI data was preprocessed use Data Processing Assistant for Resting-State fMRI Advanced Edition(DPABI_V3.0)and dynamic brain connectome analysis toolbox(DynamicBC v2.1)based on Matlab R2012a.(1)The posterior cingulate cortex(PCC)(0,-53,26)was selected as the seed,combining the sliding time window and K-mean clustering analysis technique,the differences of dFC variability patterns in the DMN among the three groups are compared.Furthermore,we analyzed correlations between dFC variability coefficient of the differences regions and MRI-derived metrics(brain parenchymal fraction,T2 lesion load),as well as the expanded disability status scale,the paced auditory serial addition test,the modified fatigue effect scale(MFIS-5)score and disease duration of the disease.(2)Based on the a priori thalamic sub-region template,the sliding time window analysis method was used to capture the dFC variability pattern of the three groups of thalamocortical systems.We quantified dFC variability between seven paired thalamic connectivity-defined regions and exclusive cortical regions using their standard deviation and to identify correlations with clinical markers.Results:(1)The seed-based correlation analysis via functional connectivity of PCC showed that DMN including:bilateral precuneus/cingulate gyrus,bilateral superior/middle frontal gyrus,bilateral superior/middle temporal gyrus,left angular gyrus.Compared with HC and acute phase RRMS patients,the remission phase RRMS group showed excessive variability(increased dFC variability)in the left superior temporal gyrus(L.STG),the left medial superior frontal gyrus(L.MSFG)and the right middle temporal gyrus(R.MTG).By contrast,excessive stability(decreased dFC variability)was found in the L.STG,L.MSFG,rignt median cingulate and paracingulate gyri(R.MCPG)and the R.MTG in the acute phase RRMS patients when compared with the remission phase RRMS.We use k-means clustering to identify reoccurring short-term connectivity patterns(as functional connectivity states),the optimal number of DMN clusters is 2.In state 2,compared with HC,the FC of acute phase RRMS in the L.STG,L.MSFG and R.MTG is decreased,and the FC of the R.MCPG is increased;only the FC of the R.MTG is lower than HC.In state 1,only the FC of the L.MSFG of acute RRMS was less than HC.In addition,correlation analysis revealed that the excessive variability in the left SFG(0.14±0.02)of remission phase RRMS was related to the course of disease(r=0.582,P=0.003),while excessive stability in the right MTG(0.12±0.02)of the acute phase RRMS patients was positively correlation with the course of the disease(r = 0.509,P = 0.044).(2)Compared with HC and remitting MS,the acute MS patients exhibited:1)excessive variability(increased dFC variability)in the left calcarine and cuneus of occipital cortices,left middle frontal gyrus of prefrontal cortices,left superior temporal pole of temporal cortices.By contrast,excessive stability(decreased dFC variability)was found in the left postcentral gyrus of primary and secondary somatosensory cortices,right superior frontal gyrus of prefrontal cortices,left superior parietal lobule of posterior parietal cortices;2)significant decreased static functional connectivity values of the cuneus,left superior temporal pole and increased static functional connectivity values of the left superior parietal lobule.3)In addition,we also found significant correlations between increased dFC variability of right superior frontal gyrus and slowed cognitive processing(p=0.02,r=-0.361)or increased the impact of fatigue(Modified Fatigue Impact Scale-5,MFIS-5)(p=0.022,r=0.574)and also revealed that the excessive variability in the cuneus was related to MFIS-5(p=0.027,r=-0.461).Conclusion:(1)Abnormal changes dFC variability of the DMN in patients with acute and remission RRMS.The excessive increase of dFC variability in DMN in RRMS patients during remission is likely to be a limited compensatory mechanism to maintain stable DMN function,and the DMN of the RRMS in the acute phase increases in vulnerability and changes over time state.(2)Our finding show that an excessive variability and excessive stability thalamocortical patterns was vulnerable to acute onset of MS,and dFC may help to further understand the disease progress associated interaction of large-scale network.