Previously, a phase II clinical trial demonstrated that delivery of glutamic acid decarboxylase (GAD) into the subthalamic nucleus (STN) via gene therapy led to functional improvements that lasted for 1 year in patients with Parkinson disease (PD). Researchers believed that the therapy worked by inducing an inhibitory phenotype in some neurons within the STN that prevented pathological overactivation of this area, but the exact mechanism was unknown. In a new study, the same team has performed metabolic network analysis on PET scans from 15 patients with PD who received the GAD gene therapy and 20 who had sham surgery. Patients treated with the gene therapy formed unconventional brain circuits that linked the STN to cortical motor regions. Presence of the new network pattern was associated with motor improvements. This rewiring might compensate for pathology in conventional motor circuits in PD. Formation of the new network might also be a useful biomarker in future clinical trials.