Pedunculopontine and Subthalamic Nucleus Stimulation Effect on Saccades in Parkinson Disease

Abstract

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been explored as a target to treat axial motor symptoms of advanced Parkinson disease (PD). The aim of this study was to consider relative effects of bilateral subthalamic nucleus (STN) and PPN DBS on both initiation and inhibition of saccades in advanced PD. Five patients with advanced PD performed 2 different oculomotor tasks off stimulation, with bilateral STN DBS, with bilateral PPN DBS, and with simultaneous bilateral STN and PPN DBS. The first task involved visually guided saccades, and the second task involved antisaccades (ASs). Saccadic latency, accuracy, and velocity were recorded for both the visually guided saccade and AS tasks, and prosaccades were measured for the AS task alone. Control subjects included patients with advanced PD without DBS, age-matched healthy subjects, and young healthy subjects (n= 12 in each group). Simultaneous bilateral STN and PPN DBS produced the greatest improvement in mean latencies, velocities, and accuracies for visually guided saccades and ASs compared with DBS off (P < 0.001). Bilateral STN and PPN DBS caused a significant additional improvement compared with STN DBS alone by reducing the number of prosaccades (P < 0.01). It is known that the frontal lobe is involved in saccadic inhibition during AS tasks. Hence, our novel finding of an improvement in the AS task suggests an ascending, frontally mediated effect of PPN DBS. This implies that there may be PPN-to-frontal lobe connections that may partly explain the benefits of PPN DBS in axial motor function.