Objective: Resting-state brain activity in neuromyelitis optica (NMO) patients can give clues to the pathophysiology of the disorder, and may be helpful in diagnosis; however, it has been less explored using functional MRI (fMRI). In the current study, we used a regional homogeneity (ReHo) method to investigate NMO-related modulations of neural activity in the resting state. Methods: Resting-state fMRIs acquired in 17 NMO patients as well as in 17 age-and sex-matched normal controls were compared. Kendall's coefficient of concordance was used to measure the regional homogeneity. Correlative analyses were performed to explore the relationship between the expanded disability status scale (EDSS), disease duration and ReHo in regions with significant group differences. Results: Comparing the NMO group with the healthy controls, we found ReHo decreased in extensive brain regions, including the left anterior cingulate, left medial frontal gyrus, left posterior cingulate, right precuneus and right middle temporal gyrus; and increased in the right inferior frontal gyrus. Conclusions: These results demonstrate that neural activity in the resting state is changed in patients with NMO. Significance: The present study reveals clear abnormalities of NMO patients in the baseline activities that have not been well detected, and further improves our understanding of the neural substrates of cognitive impairment in NMO patients. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.