High (130 Hz)- and mid (60 Hz)-frequency deep brain stimulation in the subthalamic nucleus differentially modulate response inhibition: A preliminary combined EEG and eye tracking study

Abstract

While deep brain stimulation (DBS) in the subthalamic nucleus (STN) improves motor functions in Parkinson's disease (PD), it may also increase impulsivity by interfering with the inhibition of reflexive responses. The aim of this study was to investigate if varying the pulse frequency of STN-DBS has a modulating effect on response inhibition and its neural correlates. For this purpose, 14 persons with PD repeated an antisaccade task in three stimulation settings (DBS off, high-frequency DBS (130 Hz), mid-frequency DBS (60 Hz)) in a randomized order, while eye movements and brain activity via high-density EEG were recorded. On a behavioral level, 130 Hz DBS stimulation had no effect on response inhibition measured as antisaccade error rate, while 60 Hz DBS induced a slight but significant reduction of directional errors compared with the DBS-off state and 130 Hz DBS. Further, stimulation with both frequencies decreased the onset latency of correct antisaccades, while increasing the latency of directional errors. Time-frequency domain analysis of the EEG data revealed that 60 Hz DBS was associated with an increase in preparatory theta power over a midfrontal region of interest compared with the off-DBS state which is generally regarded as a marker of increased cognitive control. While no significant differences in brain activity over mid- and lateral prefrontal regions of interest emerged between the 60 Hz and 130 Hz conditions, both stimulation frequencies were associated with a stronger midfrontal beta desynchronization during the mental preparation for correct antisaccades compared with DBS off-state which is discussed in the context of potentially enhanced proactive recruitment of the oculomotor network. Our preliminary findings suggest that mid-frequency STN-DBS may provide beneficial effects on response inhibition, while both 130 Hz- and 60 Hz STN-DBS may promote voluntary actions at the expense of slower reflexive responses.

Keywords: Antisaccade; Executive functions; Eye tracking; Movement disorders; Parkinson’s disease; Response inhibition.