Exploring local and network effects of subthalamic stimulation on semantic verbal fluency in Parkinson’s disease

OBJECTIVE A decline in verbal fluency (VF) after subthalamic stimulation has been frequently reported; however, the reasons and mechanisms for this decline remain unclear. This study investigated the impact of subthalamic stimulation on semantic VF decline, analyzed the associated factors, and uncovered the relevant mechanisms by exploring local and network effects. METHODS Included in the study were 78 patients with Parkinson’s disease who were categorized into either the stable group (n = 32) or the decliner group (n = 46) based on whether semantic VF decreased after subthalamic stimulation. The baseline and follow-up clinical profiles were compared between the two groups. Local and network effect models were constructed based on volume of tissue activation (VTA). RESULTS Semantic VF decline was closely related to the Hoehn and Yahr stage (OR 3.38, p = 0.024), left standardized X-coordinate (OR 1.928, p = 0.025), and left standardized Y-coordinate (OR 0.534, p = 0.013). The VTA-covered motor subthalamic nucleus was negatively correlated with semantic VF. The probabilistic stimulation maps indicated that the stimulation site for semantic VF decline was closer to the optimal site for motor symptom improvement. Finally, fiber filtering and structural network analyses indicated that the decline in semantic VF was associated with a decrease in prefrontal cortex connectivity induced by stimulation, including the dorsolateral prefrontal cortex. CONCLUSIONS Subthalamic stimulation resulted in a decline in semantic VF. The semantic VF decline is related not only to the severity of postoperative disease but also to the effects of stimulation, and this effect is lateralized, especially in the left hemisphere.