NCT Number: NCT06518824
Official Title: Theta Deep Brain Stimulation for Cognitive Enhancement in Parkinson's Disease
Study Type: Interventional (Clinical Trial)
Status: Recruiting
Study Start Date: 2024
Estimated Completion: 2027
Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD), primarily targeting motor symptoms. Traditional high-frequency DBS (130-180 Hz) effectively reduces tremor, rigidity, and bradykinesia. However, cognitive dysfunction remains a significant challenge in PD patients, and conventional DBS approaches have limited effects on cognition.
Theta frequency stimulation (4-8 Hz) represents a novel approach that may differentially affect cognitive domains. Preliminary research suggests that theta DBS could modulate prefrontal cortical networks involved in executive function, working memory, and attention. This trial investigates whether theta frequency stimulation of traditional DBS targets (subthalamic nucleus or globus pallidus internus) can improve cognitive function in PD patients without exacerbating motor symptoms.
To evaluate the safety and efficacy of theta frequency deep brain stimulation on cognitive performance in Parkinson's disease patients.
This trial relates to:
Deep brain stimulation has revolutionized PD treatment since its FDA approval in 2002[1]. The standard approach uses high-frequency stimulation (130-180 Hz), which effectively reduces motor symptoms by:
However, high-frequency DBS has notable limitations[2]:
The frequency of stimulation critically determines the behavioral outcomes[3][@ baker2020]:
| Frequency | Effects |
|---|---|
| 130-180 Hz | Motor symptom improvement, possible cognitive side effects |
| 60-80 Hz | Improved gait, reduced dysarthria |
| 4-8 Hz (theta) | Potential cognitive enhancement, minimal motor effects |
Theta oscillations (4-8 Hz) are fundamental to cognitive processes[4]:
In PD, theta-band activity is often reduced in prefrontal cortex, correlating with executive dysfunction[5]. Theta DBS may restore this oscillatory activity.
Theta DBS may improve cognition through prefrontal cortex modulation[6]:
The basal ganglia participate in multiple motor and cognitive loops[7]:
Theta stimulation may differentially affect these loops, enhancing cognitive circuits while preserving motor benefits.
###Theta-Band Physiology
Theta oscillations in the basal ganglia[@hersberger2021]:
Supporting evidence for theta DBS in PD:
| Study | Frequency | Cognitive Outcome |
|---|---|---|
| Witt et al., 2013 | 130 Hz | Mild decline in verbal fluency |
| Vezina et al., 2017 | 130 Hz | Executive function stable |
| Castrioto et al., 2013 | Various | Cognitive trajectory unchanged |
This trial (NCT06518824) represents the first systematic investigation of theta DBS specifically for cognitive enhancement.
Potential targets for theta DBS[8]:
Protocol for theta frequency stimulation:
| Parameter | Value |
|---|---|
| Frequency | 4-8 Hz |
| Pulse width | 60-120 μs |
| Voltage | 1-4 V (individualized) |
| Mode | Monopolar or bipolar |
Comprehensive neuropsychological testing at:
Based on the mechanistic rationale and preliminary data:
Standard DBS surgical risks apply[9]:
Theta frequency may reduce certain side effects:
Future iterations may incorporate:
Cognitive biomarkers under investigation:
Trial information will be updated as results become available.
Benabid AL, et al. Deep brain stimulation for Parkinson's disease. 1998. ↩︎
Kalia SK, et al. Deep brain stimulation for Parkinson's disease. 2013. ↩︎
Volkmann J, et al. DBS frequency optimization in PD. 2014. ↩︎
Buzsaki G, et al. Theta oscillations in cognition. 2012. ↩︎
Horton J, et al. Theta-band oscillations in basal ganglia. 2020. ↩︎
Pavlides A, et al. Theta oscillations and memory consolidation. 2015. ↩︎
Krack P, et al. DBS mechanisms and limitations. 2010. ↩︎
Okun MS, et al. DBS for PD: what matters most. 2012. ↩︎
Bronstein JM, et al. Deep brain stimulation for essential tremor. 2011. ↩︎