Effective connectivity of default mode network in relapsing remitting multiple sclerosis: a resting-state functional MRI Granger causality analysis

Objective To explore the effective connectivity of default mode network (DMN) in relapsing-remitting multiple sclerosis (RRMS) patients using a resting-state functional MRI (rs-fMRI) Granger causality analysis (GCA).Methods Twenty four patients with RRMS,admitted to our hospital from June 2010 to December 2012,and 24 age-,and gender-matched healthy controls were examined by rs-fMRI and 3D-T1 on Trio 3.0T MRI.The preprocessing and processing rs-fMRI data were analyzed using Data Processing Assistant for rs-fMRI Advanced Edition based on Matlab 2012a; the posterior cingulate cortex (PCC) was selected as the seed,and a seed-based correlation analysis was used to construct the spatial patterns ofDMN; 6 principal components of DMN were selected as regions of interest; GCA method was used to compare the effective connectivity between the two groups.The specific correlations between effective connectivity changes of DMN and clinical parameters,as scores of clinical expanded disability scale (EDSS),synchronous auditory continuous additions test (PASAT) and modified fatigue impact scale (MFIS),brain parenchymal fraction (BPF) and lesion volume seen under T2,were further analyzed.Results As compared with healthy control group,RRMS group exhibited an altered signed-path coefficient and direction between the left and right inferior parietal lobules (IPLs,t=3.071,P=0.004),and the left inferior parietal lobule and the right middle temporal gyrus (MTG,t=2.053,P=0.046).Significant positive-relations were observed between EDSS scores and signed-path coefficient between left and right IPLs (t=0.410,P=0.045) and left IPL and right MTG (t=0.470,P=0.020),respectively.The correlations of altered signed-path coefficient with PASAT scores,BPF,MFIS scores and total white matter lesion loads were not observed (P＞0.05).Conclusions The abnormal effective connectivity between principal components of DMN in RRMS patients is an invalid compensation.This study adds an important observation for understanding the changed mechanism of pathophysiology in patients with RRMS. Key words: Relapsing remitting multiple sclerosis;  Granger causality analysis;  Functional MRI;  Resting state;  Default mode network;  Effective connectivity