NCT Number: NCT07022522
Official Title: Impact of Frequency-specific Subthalamic Nucleus Subregion Stimulation on Inhibitory Control in Parkinson's Disease
Study Type: Interventional (Clinical Trial)
Status: Recruiting
Study Start Date: January 2025
Estimated Completion: December 2027
¶ Background and Rationale
Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established treatment for advanced Parkinson's disease, demonstrating efficacy for motor symptoms including tremor, rigidity, and bradykinesia. However, the effects of STN-DBS on cognitive functions, particularly inhibitory control and impulse control disorders, remain incompletely understood.
Traditional STN-DBS uses high-frequency stimulation (130-180 Hz), which effectively treats motor symptoms but may have differential effects on various cognitive domains. Recent advances in DBS technology enable frequency-specific targeting of distinct STN subregions, potentially allowing optimization of both motor and cognitive outcomes.
This study investigates whether frequency-specific stimulation of different STN subregions can differentially affect inhibitory control—the ability to suppress inappropriate or impulsive responses—in patients with Parkinson's disease.
To evaluate the effect of frequency-specific STN subregion stimulation on inhibitory control in patients with Parkinson's disease, as measured by Go/No-Go task performance.
- Compare motor symptom control across different stimulation frequencies
- Assess quality of life and neuropsychological outcomes
- Identify optimal frequency parameters for combined motor and cognitive benefit
- Characterize the relationship between STN subregion anatomy and stimulation response
- Design: Randomized, double-blind, cross-over study
- Participants: Patients with idiopathic PD who are candidates for STN-DBS (n≈40)
- Phases:
- Pre-operative baseline assessment (off medication)
- Post-operative programming and optimization (4 weeks)
- Double-blind frequency comparison (12 weeks, cross-over)
- Long-term follow-up (6 months)
- Age 40-75 years
- Diagnosis of idiopathic Parkinson's disease (UK Brain Bank criteria)
- H&Y stage II-IV
- Motor complications refractory to optimal medication
- Candidates for bilateral STN-DBS
- Stable cognitive function (MoCA ≥24)
- No history of psychiatric illness (except stable depression)
- Atypical parkinsonism (PSP, MSA, CBS)
- Severe cognitive impairment (MoCA <24)
- Major depression or psychiatric comorbidities
- Previous brain surgery (except thalamotomy)
- Metallic implants incompatible with MRI
- Active enrollment in other clinical trials
| Frequency |
Target Region |
Hypothesized Effect |
| 60-80 Hz (Low) |
Posterior STN |
May improve inhibitory control |
| 130-180 Hz (Standard) |
Central STN |
Standard motor benefit |
| >200 Hz (High) |
Anterior STN |
May worsen inhibitory control |
Primary:
- Go/No-Go Task performance (correct rejections, false alarms)
- Stroop Test inhibitory control score
Secondary:
- UPDRS Part III (motor examination)
- PDQ-39 (quality of life)
- Barratt Impulsiveness Scale (BIS-11)
- Iowa Gambling Task (decision-making)
- Neuropsychological battery
Safety:
- Adverse event monitoring
- Programming parameters documentation
- Lead Site: Movement Disorder Center, Academic Medical Center, Netherlands
- Collaborating Sites: 3 European movement disorder centers
- Frequency-dependent effects: Identification of optimal stimulation frequency for inhibitory control
- Subregion mapping: Anatomical-functional mapping of STN subregions
- Clinical guidelines: Evidence-based recommendations for DBS programming
- Patient selection: Identification of patients most likely to benefit from specific frequency settings
Impulse control disorders (ICDs) affect 10-30% of Parkinson's disease patients, particularly those on dopaminergic therapy. STN-DBS can either improve or worsen impulse control depending on stimulation parameters. This study will provide crucial data for:
- Optimizing DBS programming to minimize ICD risk
- Understanding STN subregion anatomy and function
- Developing personalized DBS approaches for cognitive outcomes
- Improving overall quality of life in PD patients undergoing DBS
This trial builds on prior work: