RESUMO
Given the inconsistent results in the past, there is an ongoing debate whether and how deep brain stimulation in the subthalamic nucleus modifies cognitive control processes like response inhibition in persons with Parkinson's disease. In this study, we examined how the location of the stimulation volume within the subthalamic nucleus affects the performance in an antisaccade task but also how its structural connectivity is related to response inhibition. Antisaccade error rates and latencies were collected in 14 participants on and off deep brain stimulation in a randomized order. Stimulation volumes were computed based on patient-specific lead localizations using preoperative MRI and postoperative CT scans. Structural connectivity of the stimulation volumes with pre-defined cortical oculomotor control regions as well as whole-brain connectivity was estimated using a normative connectome. We showed that the detrimental effect of deep brain stimulation on response inhibition, measured as antisaccade error rate, depended upon the magnitude of the intersection of volumes of activated tissue with the non-motor subregion of the subthalamic nucleus and on its structural connectivity with regions of the prefrontal oculomotor network including bilateral frontal eye fields and right anterior cingulate cortex. Our results corroborate previous recommendations for avoidance of stimulation in the ventromedial non-motor subregion of the subthalamic nucleus which connects to the prefrontal cortex to prevent stimulation-induced impulsivity. Furthermore, antisaccades were initiated faster with deep brain stimulation when the stimulation volume was connected to fibres passing the subthalamic nucleus laterally and projecting onto the prefrontal cortex, indicating that improvement of voluntary saccade generation with deep brain stimulation may be an off-target effect driven by stimulation of corticotectal fibres directly projecting from the frontal and supplementary eye fields onto brainstem gaze control areas. Taken together, these findings could help implement individualized circuit-based deep brain stimulation strategies that avoid impulsive side effects while improving voluntary oculomotor control.
RESUMO
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.