The purpose of this study is to investigate whether spontaneous brain activity amplitude alteration occurs in RRMS by comparing appropriately processed fMRI data from subjects with RRMS and healthy controls. Resting-state fMRIs collected from thirty-five RRMS patients and thirty-five ageand sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration. T2 lesion volume were further explored. Our results showed that RRMS patients showed no regions with decreased ALFF, while showed significantly increased ALFF in the bilateral thalami, right insula (BA 13)/ right superior temporal gyrus (BA 22). The correlation between the EDSS and ALFF in the right insula/right superior temporal gyrus was significant From this study, we demonstrate that increased resting state amplitudes occur in the brain of patients with RRMS, specifically in areas with extensive cortical connections. We hypothesize that this is an adaptive phenomenon, reflecting either ongoing cortical plasticity in the resting-state, or increased neuronal activity related to coordination of remapped cortical functions. (C) 2011 Elsevier B.V. All rights reserved.