AIM: To examine the functional brain alterations in Parkinson's disease (PD) by measuring blood oxygenation level dependent (BOLD) functional MRI (fMRI) signals at rest while controlling for the structural atrophy. MATERIALS AND METHODS: Twenty-three PD patients and 20 age, gender, and education level matched normal controls (NC) were included in this study. Resting state fMRI and structural MRI data were acquired. The resting state brain activity was measured by the regional homogeneity (ReHo) method and the grey matter (GM) volume was attained by the voxel-based morphology (VBM) analysis. Two-sample t-test was then performed to detect the group differences with structural atrophy as a covariate. RESULTS: VBM analysis showed GM volume reductions in the left superior frontal gyrus, left paracentral lobule, and left middle frontal gyrus in PD patients as compared to NC. There were widespread ReHo differences between NC and PD patients. Compared to NC, PD patients showed significant alterations in the motor network, including decreased ReHo in the right primary sensory cortex (S1), while increased ReHo in the left premotor area (PMA) and left dorsolateral prefrontal cortex (DLPFC). In addition, a cluster in the left superior occipital gyrus (SOG) also showed increased ReHo in PD patients. CONCLUSION: The current findings indicate that significant changes of ReHo in the motor and non-motor cortices have been detected in PD patients, independent of age, gender, education level, and structural atrophy. The present study thus suggests ReHo abnormalities as a potential biomarker for the diagnosis of PD and further provides insights into the biological mechanism of the disease. (C) 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.