Impact of Frequency-specific Subthalamic Nucleus Subregion Stimulation on Inhibitory Control in Parkinson's Disease

Frequency-dependent Modulation of Inhibitory Control Via Subthalamic Nucleus Subregional Stimulation in Parkinson's Disease

The core symptoms of Parkinson's disease (PD) include both motor and non-motor symptoms. Cognitive impairment is one of the most common non-motor symptoms in PD patients, with approximately 30% of patients exhibiting cognitive dysfunction at diagnosis and up to 80% eventually progressing to dementia. Among these, impairment of inhibitory control is the most detrimental cognitive dysfunction, as patients with compromised inhibitory control have difficulty suppressing impulsive behaviors and maintaining attention, which severely reduces their quality of life.

The subthalamic nucleus (STN) plays an important role in the development and progression of PD. Along its longitudinal axis from posterior to anterior, it can be divided into three subregions: motor, associative, and limbic. The motor subregion receives extensive projections from the motor cortex and serves as a core node in the PD motor network, participating in the coordination and control of motor function. The associative subregion receives widespread projections from the prefrontal cortex and serves as a core node in the cognitive control network, regulating cognitive processes such as inhibitory control, set-shifting, and working memory.

High-frequency (>100Hz) deep brain stimulation of the STN (STN-DBS) is a well-established effective treatment for mid-to-late stage PD and can significantly improve motor symptoms. However, long-term high-frequency stimulation may exacerbate cognitive impairment. Recent studies have shown that low-frequency (4-10Hz) STN-DBS can improve cognitive functions such as working memory and verbal fluency in PD patients, but research on its effects in the domain of inhibitory control is lacking. Moreover, different STN subregions are involved in regulating distinct functions, yet previous studies have not differentiated the effects of stimulation targeting specific STN subregions.

Therefore, conducting in-depth research on the effects of different stimulation frequencies applied to distinct STN subregions on inhibitory control function in PD patients is of great significance for exploring ways to improve cognitive impairment in PD and enhance the clinical individualized therapeutic effects of STN-DBS. This study plans to perform high- and low-frequency electrical stimulation of different STN subregions in PD patients who have undergone routine bilateral STN-DBS surgery, collect behavioral indicators during inhibitory control tasks (Arrow Flanker and Stop-Signal) under different stimulation conditions, and through comparative analysis, identify the specific stimulation sites and frequencies that can effectively improve inhibitory control function in PD patients.

Inclusion Criteria:

1. Age 40-80 years old;
2. Diagnosed with idiopathic Parkinson's disease;
3. Meeting the indications for DBS surgery.

Exclusion Criteria:

1. Patient declined to participate in the study;
2. Presence of significant post-DBS complications (e.g., intracranial hemorrhage, cerebral edema, electrode misplacement);
3. Significant psychiatric disorders or dementia (MMSE score <20 for uneducated; <23 for 1-6 years education; <27 for ≥7 years education);
4. Visual or auditory impairment affecting cognitive task performance
5. History of conditions potentially impairing cognitive function.