Cognitive and emotional effects of Deep Brain Stimulation of the Subthalamic Nucleus in patients with Parkinson's disease

Abstract

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective and secure option for treatment of Parkinson´s disease (PD). Its effect on improving motor impairments following dopaminergic depletion in the substantia nigra has been variously shown. The influence of STN-DBS on concomitant non-motor symptoms has also reached more and more of attention, since these may have the potential to affect subjectively perceived quality of life in patients. Behavioral, affective and cognitive changes in patients after STN-DBS have thus been considerably studied in recent years. The present thesis aimed to investigate STN-DBS modulations on different cognitive and emotional functions in PD patients. The STN is supposed to hold a crucial role in action selection and reward processing as well as in perceptual decision-making. The first thesis project investigated whether stimulation of the STN influences the patients´ selective ability to act for anticipated reward or loss, or whether DBS changes action selection independent from motivational valence. Behavioral results demonstrate the impact of STN-DBS on motivational action control in PD by selectively improving action execution when rewards are anticipated. Thus, STN-DBS establishes a reliable congruency between action and reward anticipation. The second project investigated whether STN-DBS in PD patients influences decision-making under difficult, high-risk decisions. Results show that stimulation of the STN affected perceptual decision-making depending on the difficulty of decisions and as a function of baseline impulsivity in patients. DBS of the STN selectively affected the tendency to stick with a default option on difficult decisions and increased accuracy of responses. Finally, I conducted an experimental setting to assess STN-DBS impact on implicit and explicit processing of emotional semantic and facial stimuli in an affective priming paradigm. I found that even reduced facial information is sufficient to induce automatic implicit emotional processing and can lead to classical and inverse priming effects in healthy control participants, but also in non-stimulated PD patients. In these patients, specific altered processing of the emotions happiness and disgust was detected. The experimental setting was finally applied in stimulation-treated PD patients. STN-DBS affected explicit more than implicit processing, indicating basal ganglia-thalamocortical regulations on explicit, and only attenuated on implicit emotion processing. Profound diminishing effects on response accuracy for disgust-connoted stimulus material, but also an ameliorating effect on fear stimuli could be demonstrated under stimulation. Taken together, this PhD thesis demonstrates that STN-DBS improved action selection under reward anticipation, facilitated decision-making under difficult decisions, and finally, influenced particularly explicit, but also implicit emotional processing. The results provide causal evidence for the potential of STN-DBS to influence cognitive and emotional aspects in patients and to have considerable impacts on quality of life besides improved motor functioning.