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NCT Number: NCT07022522

Impact of Frequency-specific Subthalamic Nucleus Subregion Stimulation on Inhibitory Control 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.

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Key information

Age range

40 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

Location status: Recruiting

Location contact

Jianguo Zhang

CONTACT

[email protected]

+86 13601294613

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

5Hz stimulation on the STN motor subregion

Device

In this experimental arm, Parkinson's disease patients will undergo deep brain stimulation targeting the motor subregion of the subthalamic nucleus at a low frequency of 5Hz, with the primary objective of evaluating its specific effects on cognitive and behavioral outcomes such as inhibitory control and reaction time. The intervention involves precise postoperative programming of DBS electrodes localized to the motor subregion using neuroimaging verification.

5Hz stimulation on the STN associative subregion

Device

In this experimental arm, Parkinson's disease patients will undergo deep brain stimulation targeting the associative subregion of the subthalamic nucleus at a low frequency of 5Hz, with the primary objective of evaluating its specific effects on cognitive and behavioral outcomes such as inhibitory control and reaction time. The intervention involves precise postoperative programming of DBS electrodes localized to the associative subregion using neuroimaging verification.

130Hz stimulation on the STN motor subregion

Device

In this experimental arm, Parkinson's disease patients will undergo deep brain stimulation targeting the motor subregion of the subthalamic nucleus at a high frequency of 130Hz, with the primary objective of evaluating its specific effects on cognitive and behavioral outcomes such as inhibitory control and reaction time. The intervention involves precise postoperative programming of DBS electrodes localized to the motor subregion using neuroimaging verification.

130Hz stimulation on the STN associative subregion

Device

In this experimental arm, Parkinson's disease patients will undergo deep brain stimulation targeting the associative subregion of the subthalamic nucleus at a high frequency of 130Hz, with the primary objective of evaluating its specific effects on cognitive and behavioral outcomes such as inhibitory control and reaction time. The intervention involves precise postoperative programming of DBS electrodes localized to the associative subregion using neuroimaging verification.

No stimulation

Device

In this control arm, Parkinson's disease patients will not receive active deep brain stimulation, with the DBS system maintained in an "off" state throughout the testing period.

Primary outcomes

  1. Behavioral paradigm results

    Time frame: Outcome measures were assessed starting at 5 minutes after each stimulation condition

    • Arrow Flanker Task : Reaction time for congruent and incongruent trials.

Secondary outcomes

  1. Behavioral paradigm results

    Time frame: Outcome measures were assessed starting at 5 minutes after each stimulation condition

    Stop-Signal Task: Stop-signal reaction time (SSRT).

  2. Motor score

    Time frame: Outcome measures were assessed starting at 5 minutes after each stimulation condition

    MDS-UPDRS III score: The Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) is a standardized clinical assessment tool for evaluating motor symptoms in Parkinson's disease (PD). The total score ranges from 0 to 132, with higher scores indicating more severe motor dysfunction, including increased rigidity, bradykinesia (slowed movement), tremor, and postural instability. Conversely, lower scores reflect milder or absent motor impairments, suggesting better motor function and symptom control.

Study contacts

Contact information is provided by the study sponsor or research team.

Sponsors and collaborators

Lead sponsor

Beijing Tiantan Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Jun 15, 2025
Registry last updated
Jun 15, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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