Prospective study of 27 PD patients found cognitive and affective Theory of Mind abilities largely unchanged one year after bilateral subthalamic deep brain stimulation, with ToM performance correlating with overall cognition and specific neuropsychological domains.

This supports the cognitive/ToM safety profile of STN-DBS and helps guide patient counseling and selection, but provides limited mechanistic or therapeutic-discovery insights for Parkinson's disease drug development.

BACKGROUND: Parkinson's disease (PD) is associated with specific cognitive deficits and dysfunctions in Theory of Mind (ToM), which can impact patients' quality of life. ToM refers to the ability to infer the mental and emotional state of one's counterpart and involves the prefrontal cortex and the basal ganglia in its function. While bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in PD significantly improves motor symptoms, little is known about its effects on ToM. METHODS: We prospectively applied an adapted version of the Yoni ToM paradigm, the Montréal Cognitive Assessment (MoCA), and an extensive tablet-based neurocognitive test set (CANTAB Connect™) before and 1 year after DBS surgery. Wilcoxon signed-rank tests were performed for comparisons of pre- and postoperative results, and Spearman's correlations assessed the association between parameters with consequent Bonferroni corrections for multiple comparisons. RESULTS: A total of 27 PD patients who received bilateral STN-DBS at Charité Universitätsmedizin Berlin between June 2019 and September 2021 were included in the study. Among these patients, 21 (77.8%) were men, with an average age of 58.7 ± 10.1 years and a disease duration averaging 10.2 ± 5.0 years. ToM abilities remained stable 1 year after DBS surgery and were associated with overall cognitive function and several specific neuropsychological domains, including reaction time, visual learning, and multitasking performance. CONCLUSION: Our findings suggest that specific ToM abilities and overall cognitive performance remain largely stable 1 year following STN-DBS. Performance on ToM tasks appears to be linked to individual cognitive profiles.