High-and Low-Frequency Deep Brain Stimulation in the Subthalamic Nucleus differentially modulate Response Inhibition and Action Selection in Parkinson's Disease

Waldthaler, J.; Sperlich, A.; König, A.; Stüssel, C.; Bremmer, F.; Timmermann, L.; Pedrosa, D. J.

doi:10.1101/2022.05.13.491771

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bioRxiv · 10.1101/2022.05.13.491771

High-and Low-Frequency Deep Brain Stimulation in the Subthalamic Nucleus differentially modulate Response Inhibition and Action Selection in Parkinson's Disease

Waldthaler, J.·Sperlich, A.·König, A.·Stüssel, C.·Bremmer, F.·Timmermann, L.·Pedrosa, D. J.

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Abstract

BackgroundWhile deep brain stimulation (DBS) in the subthalamic nucleus (STN) improves motor functions in Parkinsons disease (PD), it has also been associated with increased impulsivity. MethodsA combined approach of eye-tracking and high-density EEG was used to investigate how high- and low-frequency DBS impact impulsive actions in the antisaccade task in a cohort of ten persons with PD. Computational modelling of the behavioral outcomes allowed a nuanced insight into the effect of DBS on response inhibition and action selection processes. Results: Against our expectations, both 130 Hz- and 60 Hz-DBS improved response inhibition as both resulted in a reduced rate of early reflexive errors. Correspondingly, DBS with both frequencies led to increased desynchronization of beta power during the preparatory period which may be a correlate of anticipatory activation in the oculomotor network. Low-frequency DBS additionally was associated with increased midfrontal theta power, an established marker of cognitive control. While higher midfrontal theta power predicted longer antisaccade latencies in off-DBS state on a trial-by-trial basis, 130 Hz-DBS reversed this relationship. As informed by the computational model, 130 Hz-DBS further led to a shift in the speed-accuracy trade-off causing an acceleration and error-proneness of actions later in the trial. ConclusionsOur results disentangle the impact of DBS on early and late impulsive actions. Only 130 Hz-DBS may disrupt theta-mediated cognitive control mechanisms via medial frontal - STN pathways that are involved in delaying action selection. 60 Hz-DBS may provide beneficial effects on response inhibition without the detrimental effect on action selection seen with 130 Hz-DBS. FundingThis study was supported by the SUCCESS program of Philipps-University Marburg (JW), the Hessian Ministry of Sciences and the Arts, clusterproject: The Adaptive Mind - TAM (FB / AK) and the German Research Foundation (DFG). International Research Training Group 1901 (FB / AK)

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Waldthaler, J., Sperlich, A., König, A., Stüssel, C., Bremmer, F., Timmermann, L., Pedrosa, D. J.. 2022-05-16. High-and Low-Frequency Deep Brain Stimulation in the Subthalamic Nucleus differentially modulate Response Inhibition and Action Selection in Parkinson's Disease. https://doi.org/10.1101/2022.05.13.491771

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