Limitations
PD, impulsivity, pre-mature
RECRUITMENT
A major limitation of our study is its small sample size which may constrain generalizability of our results requiring confirmation in larger studies in the future. However, recruitment of eligible participants with PD and STN-DBS without any exclusion criteria is inherently very limited. Additionally, the study protocol was challenging to complete for this population as supported by the high proportion of pre-mature withdrawals of 44 % despite careful screening of potential participants.Since we did not include a healthy control group, we cannot state that response inhibition was overall impaired in the PD group. However, the mean antisaccade error rate of 47.3 % in off DBS-state is within the range of comparable studies in PD and considerable higher than in healthy age-matched controls (Participants completed the study in off-medication state. While this is a clear advantage of the study since it excludes effects of dopaminergic medication on the results to a large extent (long lasting effects >12 h cannot be entirely excluded), dopamine replacement therapy and DBS may interact in their effects on impulsivity in PD in real life scenarios. For instance, Bakhtari and colleagues showed that dopamine replacement therapy partly restored the detrimental effect of STN-DBS on antisaccade error rates (Participants were stimulated with their individual optimal DBS program and amplitude, impulse width, and DBS contacts were not changed for the study. Thus, DBS settings were not standardized between participants. On the other hand, standardization of DBS settings would have carried a high risk for side effects since therapeutic and side effects of DBS vary widely between patients and optimal settings are the result of highly individualized programming procedures. Further, additional factors such as individual deviations from optimal lead placement could have not been standardized anyway. By keeping the individualized optimal DBS settings instead (other than frequency), we aimed to avoid side effects and to resemble the DBS effect achieved in daily life with chronic stimulation.Since all conditions were recorded on the same day, carry-over effects of DBS cannot be completely excluded. However, any risk of systematic bias caused by carry-over effects was counteracted through randomizing the order of conditions.TEED was not kept constant between the DBS settings used in the study. TEED is expected to be lower with 60 Hz than with 130 Hz stimulation when stimulation amplitude is kept constant. As a recent study showed that changing DBS amplitude influences antisaccade performance (The small trial numbers impeded the inclusion of error trials as a control condition in the analysis of the EEG data. Thus, we cannot be certain that the increasing effect of 60 Hz-DBS on preparatory midfrontal theta power was limited to trials in which the inhibition of an impulsive response succeeded later in the trial. Given the low numbers of participants and of trials per participant, the results of this study should be considered preliminary requiring replication in larger samples.