Altered intra- and interregional synchronization in relapsing-remitting multiple sclerosis: a resting-state fMRI study

Background and purpose: Neuroimaging studies of relapsing-remitting multiple sclerosis (RRMS) have found structural disconnection and large-scale neural network dysfunction. However, few studies have explored the local brain activity of RRMS patients in the resting state. Patients and methods: In this study, regional homogeneity (ReHo) and resting-state functional connectivity (FC) were used to investigate intra-and interregional synchronized activity in 22 patients with RRMS and 22 matched healthy controls (HCs). Results: Compared with HCs, patients with RRMS showed significantly decreased ReHo in the left insula and right caudate. Through further seed-based FC analysis, we found decreased FC between the left insula and left precentral gyrus in patients with RRMS compared with HCs, as well as increased FC between the right caudate and right dorsolateral prefrontal cortex. Pearson's correlation analysis showed that a decreased ReHo value in the left insula was associated with an increased total white matter lesion loads (TWMLL) score (r=-0.594, P=0.004) or a worsened paced auditory serial addition test score (r=0.536, P=0.010). No other significant correlations were observed between the FC value (left insula - left precentral gyrus) and clinical scores (P=0.246-0.982). The ReHo value of the right caudate was negatively correlated with disease duration (r=-0.526, P=0.012) and with the TWMLL score (r=-0.596, P=0.003). Moreover, a positive correlation was observed between the FC value (right caudate - right dorsolateral prefrontal cortex) and the TWMLL score (r=0.523, P=0.012) or the modified fatigue impact scale-5 score (r=0.608, P=0.003). Conclusion: Together, these findings suggest that the insula with regional dysfunction involves disconnection with sensorimotor regions, and demyelinating lesion-related intra-and interregional dysfunction in the caudate is associated with the impact of fatigue on cognitive control functions. Abnormal synchronization of intra-and interregional activity in the insula and caudate may play important roles in the pathology of RRMS.