Abnormal Intrinsic Functional Hubs in Relapsing- Remitting Multiple Sclerosis: Evidence from a Voxel-Wise Degree Centrality Analysis

Abstract

Objective: To explore the abnormal intrinsic functional hubs in relapsing-remitting multiple sclerosis (RRMS) using degree centrality approach and their relationships with clinical features. Methods: Total of 26 RRMS (13 males, 13 females; mean age, 35.38 ± 11.33 years) and 27 statusmatched healthy groups (HGs; 12 males, 15 females; mean age, 35.37 ± 11.67 years) were recruited. RRMS underwent a physical examination using Expanded Disability Status Scale (EDSS) by an experienced neurologist. Degree centrality and functional connectivity approach was used to assess the abnormal intrinsic functional hubs features. Partial correlation analysis was conducted to investigate the relationships between clinical features and abnormal functional hubs. Receiver operating characteristic (ROC) curve was applied to calculate the sensitivities and specificities of those altered functional hubs to distinguish RRMS from HGs. Results: Compared with HGs, RRMS exhibited significantly higher degree centrality values in multiple brain areas and lower degree centrality values in bilateral salience network and left cingulate gyrus. Decreased functional connectivity was found within left-right salience network, and between salience network and cingulate gyrus. Duration of disease and EDSS revealed negative correlations with degree centrality value in the salience network. ROC analysis showed good performances of these abnormal hubs in distinguishing RRMS from HGs with high degree of sensitivities and specificities. Conclusions: RRMS is associated with multiple specific abnormal functional hubs including relatively reduced and increased degree centrality value, which expands our understanding of the functional characteristics and may provide a new insight into understanding the pathophysiological mechanisms of RRMS.