Effects of deep brain stimulation frequency on eye movements and cognitive control

Abstract Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment option for Parkinson's disease (PD). Recent work has shown that using low- and high-frequency DBS can have a different effect on axial and distal limb functions suggesting that the frequency might affect pathways differently. The STN is also a critical node in the oculomotor and associative networks, which can lead to collateral visual and cognitive side effects. The role of frequency of stimulation on these networks remains unknown. The objective of this study was to investigate the effects of low- vs. high-frequency STN-DBS on eye movements and executive control. Twenty-one STN-DBS PD patients with 130Hz vs. 80Hz stimulation were compared with a healthy control group (n=16). All participants were tested twice in a double-blind manner. We examined prosaccades (latency and gain) and antisaccades (latency of the correct antisaccades, latency of the incorrect antisaccades, error rate and gain of the correct antisaccades). Non-oculomotor executive functions were tested with the Stroop task. The motor condition was assessed using Unified Parkinson’s Disease Rating Scale part III. The antisaccadic error rate was higher in patients (p=0.0113), and it was higher in patients on 80Hz compared to 130Hz (p=0.001). The differences between patients and controls and between different frequency of stimulation for all other eye-movements or cognitive measures were statistically non-significant. We show that 80Hz STN-DBS in PD reduces the ability to maintain stable fixation but does not alter inhibition, resulting in a higher antisaccade error rate due to less efficient fixation, without altering the motor state of the patients. This is also clinically important because it means that lowering the stimulation frequency from 130Hz to 80Hz can alter eye movement performance without affecting motor symptoms. This provides a wider range of stimulation parameters that can reduce specific DBS-related side effects without affecting motor outcomes.