Subthalamic nucleus deep brain stimulation (STN-DBS) has been proven to improve health-related quality of life (HRQoL) in patients with Parkinson's disease (PD) presenting medically refractory motor complications and dyskinesia. However, some patients fail to benefit from STN-DBS despite rigorous preoperative selection. We postulated that they have a particular, clinically ineloquent, brain metabolism before surgery. We divided 40 stimulated PD patients into two groups (responders vs. nonresponders) depending on whether they reported or not a clinically significant improvement in their quality of life 1 year after surgery. We retrospectively compared their preoperative brain metabolism on the basis of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scans. We also analyzed their neuropsychological and psychiatric profiles before and after surgery. All 40 patients met the STN-DBS selection criteria, but only 50% of them had significantly improved 1 year after surgery. Preoperative PET scans showed that metabolism was higher in the left insula, both inferior frontal gyri and left precentral gyrus in nonresponders than in responders. Clinically, postoperative motor scores were similar in both groups, but a worsening of the depression score was observed among nonresponders. PET imaging revealed that nonresponders were characterized by distinctive brain functioning pre-surgery, in regions involved in associative and limbic circuits, as a result of PD-related degeneration. STN-DBS may have interfered with this already abnormal circuitry, leading to the occurrence of complex nonmotor symptoms reducing quality of life. Preoperative brain metabolism could be a useful biomarker for anticipating STN-DBS efficacy in terms of HRQoL in the context of advanced PD.