Cognition and mood in Parkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial

Abstract

Objective: Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease.

Methods: Fifty-two subjects were randomized to unilateral STN or GPi DBS. The co-primary outcome measures were the Visual Analog Mood Scale, and verbal fluency (semantic and letter) at 7 months post-DBS in the optimal setting compared to pre-DBS. At 7 months post-DBS, subjects were tested in four randomized/counterbalanced conditions (optimal, ventral, dorsal, and off DBS).

Results: Forty-five subjects (23 GPi, 22 STN) completed the protocol. The study revealed no difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes pre- to post-DBS in the optimal setting (Hotelling's T(2) test: p = 0.16 and 0.08 respectively). Subjects in both targets were less "happy", less "energetic" and more "confused" when stimulated ventrally. Comparison of the other 3 DBS conditions to pre-DBS showed a larger deterioration of letter verbal fluency in STN, especially when off DBS. There was no difference in UPDRS motor improvement between targets.

Interpretation: There were no significant differences in the co-primary outcome measures (mood and cognition) between STN and GPi in the optimal DBS state. Adverse mood effects occurred ventrally in both targets. A worsening of letter verbal fluency was seen in STN. The persistence of deterioration in verbal fluency in the off STN DBS state was suggestive of a surgical rather than a stimulation-induced effect. Similar motor improvement were observed with both STN and GPi DBS.

Figure 1A

reveals the flow chart for the study; and figure 1B a picture representation of the DBS testing procedures in the four blinded conditions examined in the general clinical research center (CRC).

Figure 1B

reveals four examples of field modeling of DBS during the four acute simulation conditions. The STN is shown in green, the contacts on the DBS lead in purple, and the field model in red. The top left panel reveals an example of dorsal stimulation, or stimulation one contact superior to the optimal contact utilized for DBS. The top right panel reveals an example of the stimulation field when moving the contact to a more ventral setting. The bottom left panel shows the DBS lead when the voltage is turned off. The panel on the right bottom reveals an example of stimulation at the optimal DBS contact. This figure reveals to the reader the types of changes that were made in each patient's DBS during the course of the study. Field models were generated using the Stim-Explorer software package were provided by the McIntyre laboratory (Cleveland Clinic).