Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment in a subgroup of medically refractory patients with Parkinson's disease (PD). Here, we compared resting-state (18)F-fluorodeoxyglucose (FDG) positron emission tomography images in the stimulator off (DBS_OFF) and on (DBS_ON) conditions in eight PD patients in an unmedicated state, on average 2 years after bilateral electrode implantation. Global standardized uptake value (SUV) significantly increased by ∼11% in response to STN-DBS. To avoid any bias in the voxel-based analysis comparing DBS_ON and DBS_OFF conditions, individual scan intensity was scaled to a region where FDG-SUV did not differ significantly between conditions. The resulting FDG-SUV ratio (FDG-SUVR) was found to increase in many regions in response to STN-DBS including the target area of surgery, caudate nuclei, primary sensorimotor, and associative cortices. Contrary to previous studies, we could not find any regional decrease in FDG-SUVR. These findings were indirectly supported by comparing the extent of areas with depressed FDG-SUVR in DBS_OFF and DBS_ON relatively to 10 normal controls. Altogether, these novel results support the prediction that the effect of STN-DBS on brain activity in PD is unidirectional and consists in an increase in many subcortical and cortical regions.