Neuronal activation patterns of PD patients with deep brain stimulation depend on the location of active electrode poles in relation to the subthalamic nucleus

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to activate energy metabolism in the target region and directly connected basal ganglia (BG) output nuclei in Parkinson's disease (PD).1 Active electrode poles for maximal clinical benefit in STN-DBS were located to the upper and lateral border of the STN in the near of fiber tracks passing through the zona incerta. In this study, we intended to investigate effects of acute DBS on BG activity in patients with intra- and extranuclear electrode location using 18-FDG positron emission tomography (PET).

Methods: The resting cerebral metabolic rate of glucose (rCMRGlc) was measured with 18- FDG PET in 12 advanced PD patients 6 months after STN stimulation in DBS off- and on-conditions. 3D-MRI datasets were co-registered to PET and the rCMRGlc was determined in the following volumes-of-interest: STN, electrode region, pallidum, putamen, caudate and thalamus. The stereotactic coordinates of active electrode poles were transferred from intraoperative x-ray to preoperative treatment-planning MR images.

Results: Extranuclear electrode positions were found in 5/12 patients in the right and 3/12 in the left hemisphere. Individuals with poles outside of the STN had significantly higher rCMRGlc increases in the right putamen, pallidum and STN itself (each p<0.05, Mann-Whitney U test). A higher y coordinate (more anterior pole location) correlated with rCMRGlc increases in the pallidum on the right side (p<0.05, Spearman rank correlation). No significant differences in epidemiological data and clinical outcome were found between patients with extra- and intranuclear electrode positions.

Discussion: These PET data show that the pattern of metabolic BG activation under STN DBS depends on active electrode pole position in relation to the target nucleus. Stimulation by active poles outside the STN was associated with increased energy metabolism in the STN itself and the directly connected pallidum. This finding is presumably explained by the proximity of the electrical field to axons and nerve fibers surrounding the STN which are tonically excited by high frequent electrical stimuli. While clinical efficacy of STN DBS on PD motor symptom reduction did not directly differ between extra and intra STN electrode locations, possible differences in remote cortical activity changes under DBS remain to be elucidated.

1 Hilker et al., Neurology 2008; 71(10):708–13.