Deep brain stimulation (DBS) of the subthalamic nucleus (STN) was proposed as an effective way to improve the symptoms of Parkinson's disease (PD). We studied metabolic modulation in the brain by bilateral STN stimulation using FDG PET. Five PD patients (age 61.6 +/- 3.9 years) at advanced stage were scanned under OFF and ON conditions of stimulation. Network analysis was used to evaluate the effect of stimulation on the expression of an abnormal Parkinson's disease-related spatial covariance pattern (PDRP). In addition, statistical parametric mapping was used to assess the effect of this intervention on regional glucose metabolism. We found that bilateral STN DBS led to a significant reduction (P < 0.02) in the PDRP network activity on an individual subject basis between OFF and ON conditions, parallel to significant improvement (P < 0.002) of clinical symptoms in these patients. The treatment also decreased glucose metabolism in the right lentiform nucleus and cerebellum, and in the bilateral ventral thalamus and precuneus, but increased metabolism in the left midbrain and pons. This was consistent with the notion that clinical benefit in a PD patient was associated with the suppression of hyperactive motor circuitry following STN stimulation. These findings suggest that DBS is more likely to function by regulating the entire neural network rather than merely exciting or inhibiting certain nuclei.