Imaging the impact of deep brain stimulation on transmitter activity and energy metabolism of basal ganglia networks in advanced Parkinson's disease

Functional brain imaging with PET provides a sensitive tool for detecting effects of medical and surgical therapies in patients with Parkinson's disease (PD) by means of metabolism, blood flow and receptor binding. Therefore, monitoring of the pathophysiological basis of effective treatment strategies and their possible impact on neuronal networks and on PD progression becomes available. PET measurements with the reversible dopamine-D2/3-receptorligand 11C-racloprid in the stimulator on- and off-condition showed that the strong antiparkinsonian effect of STN-DBS is independent from alterations of endogenous dopamine release at the striatal synapses. 15H2O-PET studies demonstrated an increased movement-related rCBF in SMA, lateral premotor cortex and DLPFC under effective STN-DBS, whereas a decreased motor cortex activation was found. With PD patients at rest in the PET scanner and 18-fluorodeoxyglucose (18FDG) as radiotracer, we found a reversible increase of the regional cerebral metabolic rate of glucose (rCMRGlc) in both subthalamic areas and in frontal limbic and associative cortical basal ganglia projection sites under bilateral STN stimulation. The data suggest an activating effect of DBS on its target sites and a central role of the STN in motor as well as associative and limbic basal ganglia circuits. Comparing preoperative 18FDG scans with the STN-off condition after surgery, we could not demonstrate any long-term microlesional effect of electrode insertion on the brains metabolic network. In contrast, significant thalamic, pallidal, midbrain and pontine FDG uptake reductions were proven in PD patients treated with unilateral subthalamotomy.