Influence of subthalamic deep brain stimulation versus levodopa on motor perseverations in Parkinson's disease

Abstract

Patients with Parkinson's disease (PD) show impairment in generating random motor sequences reflecting a higher order motor deficit in set-shifting and suppression of perseverative behavior. The impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on motor perseverations has not yet been elucidated. In 35 patients with PD, we evaluated the effect of STN-DBS and levodopa on motor perseverations using the Vienna perseveration task. The task was performed 6 months after implantation of stimulation electrodes in the following three conditions: Stimulation off/medication off (Stim OFF/Med OFF), Stim ON/Med OFF, and Stim OFF/Med ON. Perseverations were measured by redundancy of second order (R(2)) with higher values indicating more severe perseverations. ANCOVA analysis revealed that influence of STN-DBS on R(2) significantly depended on R(2) severity during Stim OFF/Med OFF (F = 4.69, P = 0.035). Accordingly, we classified patients with PD into two groups based on the R(2) value during off treatment. In patients with mild perseveration (R(2) < 35) neither STN-DBS nor levodopa changed perseverations. By contrast, in patients with severe perseveration (R(2) > 35), STN-DBS significantly reduced R(2) by 9.7 +/- 2.6 (P < 0.001) whereas levodopa had no impact (R(2) reduction 3.7 +/- 1.6, P = 0.081). This demonstrates that STN-DBS, by reducing motor perseveration, influences higher order aspects of motor behavior of patients with PD.