STN-DBS activates the target area in Parkinson disease - An FDG-PET study

Objective: The immediate effects of deep brain stimulation (DBS) on subcortical neurons of its target region are controversial. Methods: We measured the regional normalized resting cerebral metabolic rate of glucose (nCMRGlc) with 18-fluorodeoxyglucose (FDG) and PET in 12 patients with Parkinson disease (PD) and bilateral DBS of the subthalamic nucleus (STN) compared to 10 age-matched controls. PET was performed before surgery and 6 months after electrode implantation in DBS off- and on-conditions. Stereotactic coordinates of active STN electrode poles were determined with intraoperative skull x-ray and transferred to preoperative MR images. Subsequently, volumes of interest (VOIs) were placed around active electrode contacts, in the STN and in the globus pallidus. DBS induced changes of nCMRGlc values were determined in each VOI after PET and MRI coregistration. Results: Electrode placement without stimulation led to significant FDG uptake reduction in the electrode region and in the STN (microlesional effect). Under active DBS, the local nCMRGlc significantly increased in all VOIs under investigation. Conclusions: The data demonstrate that deep brain stimulation (DBS) induced metabolic activation of the subthalamic region and the directly connected globus pallidus which is in line with local and remote excitation of neurons by high frequency stimulation. These PET findings most likely reflect tonic driving of the DBS target area and its projection sites via ortho-and antidromic fiber conduction. We conclude that subthalamic nucleus DBS has predominant excitatory properties and does, therefore, fundamentally differ from lesional neurosurgery.