We live, survive, and develop in a society. Sophisticated social interaction skills are essential for adapting to society and realizing self-worth. Successful social interaction requires us to accurately infer the mental states of others, including their thoughts, intentions, and emotions, to understand and predict their behaviors. This human high cognitive function is empathy, also referred to as ToM. ToM encompasses cognitive components (inferring thoughts, thinking as they do) and affective components (inferring emotions, feeling as they feel). Patients with neurodegenerative diseases (e.g., Parkinson’s disease, PD) and neuropsychiatric disorders (e.g., autism spectrum disorder) often struggle to understand others' thoughts or emotions accurately in social interactions, which leads to difficulties understanding others' behaviors and reactions, and living and working normally. 

 

Previous studies mainly focused on the role of the frontal cortex in ToM. It remains unclear how deep brain structures like the STN are engaged in ToM. To fill this gap, this study measured the ToM performance of 34 PD patients with DBS ON and OFF. The study combined magnetic resonance imaging (MRI), computed tomography (CT), and biophysical modeling techniques to reconstruct the stimulation site and estimate the volumes of tissue activated. The study revealed that the associative STN plays a causal role in ToM. Stimulation of the associative STN impaired the cognitive component of ToM, without changing the affective component of ToM. Patients with greater associative STN stimulation in the DBS ON state tended to infer others' thoughts more slowly, especially in patients with mild cognitive decline. 

 

This study, for the first time, mapped ToM to the associative STN, demonstrating the role of the associative STN in understanding others' thoughts. This study not only opens a new window to the research of human social cognitive functions like empathy but also provides clinical insights for patient treatment and management.

 

This work, entitled “Subthalamic Nucleus Stimulation Modulates Cognitive Theory of Mind in Parkinson’s Disease”, has been published online in Movement Disorders on May 2rd, 2024. Ms. Haoyun Xiao at the Institute of Neuroscience, Center for Excellence in Brain Sciences and Intelligence Technology of the Chinese Academy of Sciences, and Dr. Liqin Lang at Huashan Hospital are co-first authors. Dr. Ye Zheng at the Institute of Neuroscience, Center for Excellence in Brain Sciences and Intelligence Technology of the Chinese Academy of Sciences, and Prof. Jianjun Wu at Huashan Hospital are co-corresponding authors. This work was supported by the Ministry of Science and Technology of China, the National Natural Science Foundation of China, and the National Health Commission of China.

Figure 1: The subthalamic nucleus (STN) is critical in the Theory of Mind (ToM). Deep brain stimulation (DBS) of the associative STN adversely affects cognitive ToM in Parkinson's disease. Patients with mild cognitive impairment were susceptible to the negative effect of associative STN stimulation and, therefore, need attention in patient treatment and management.

Original article: https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29830

 

Keywords: Parkinson’s disease, theory of mind, deep brain stimulation, subthalamic nucleus.