Theta Deep Brain Stimulation for Cognitive Enhancement in Parkinson's Disease

NCT06518824 | Recruiting

• 1 other identifier: thetaDBS
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive impairment is common in Parkinson's disease. A recent study demonstrated 40% of people with PD suffer from mild cognitive impairment and \> 80% of patients develop dementia after a disease duration of 20 years. Cognitive impairment significantly impairs quality of life and has limited treatment options. While the pathophysiology of cognitive symptoms in PD is multifactorial, one contributing factor is dysfunction in subthalamic-cortical loops. The subthalamic nucleus (STN) receives input from distributed regions of the cortex, forming partially segregated parallel networks with sensorimotor regions, associative (cognitive) cortical regions, and limbic cortical regions. These subthalamic-cortical networks are thought to play a domain general role in inhibitory control, which is a fundamental mechanism underlying flexible behavior across motor, cognitive, and affective domains. Information processing in these subthalamic-cortical networks is expressed through oscillatory activity within distinct frequency bands. For example, communication between the STN and prefrontal regions involved in executive function is thought to occur through coherence in the theta (4-8 Hz) frequency band. As a result of these observations, stimulation of the STN at a theta frequency has been investigated as a method of modulating cognitive processes. Theta stimulation of the STN has been shown to enhance coherence in subthalamic-cortical networks, facilitating information processing and modulating behavior. For example, a recent study demonstrated that theta stimulation of the STN improved working memory performance in PD subjects, while no effect was seen for other frequency bands. The authors performed a post-hoc analysis and found that the effect may be mediated by connectivity between the stimulated STN region and the right dorsolateral prefrontal cortex (DLPFC). While these studies have demonstrated proof of principle, they are limited by small sample sizes and post-hoc analyses assessing the relationship between stimulation location and outcomes. Further research is needed to directly test the hypothesis that theta stimulation of the STN can improve executive control in PD patients by modulating associative STN circuitry.

Conditions

Parkinson Disease; Cognitive Impairment

Keywords

Theta Stimulation

Outcome Measures

Primary Outcomes (1)

• Change in working memory performance between conditions

  Working memory performance will be assessed through a modified Sternberg task. Subjects will undergo the task with and without stimulation. Measures the main effect of stimulation condition, with hypothesis that theta stimulation of associative STN will improve performance compared to no stimulation. Outcome measured through percent of correctly recalled sequences.

  Immediately after task performance

Secondary Outcomes (1)

• Interaction effect between groups and stimulation condition

  Immediately after task performance

Other Outcomes (1)

• Correlation between working memory performance and STN connectivity

  Immediately after task performance

Study Arms (4)

Stimulation off

SHAM COMPARATOR

The deep brain stimulation device will be turned off.

Device: DBS Off

Theta stimulation of associative STN region

EXPERIMENTAL

The deep brain stimulation device will be set to a frequency of 6 Hz and will stimulate the associative STN region. If differential activation of the associative and sensorimotor STN networks is not feasible, ventral stimulation is employed.

Device: DBS On

Theta stimulation of STN sensorimotor region

ACTIVE COMPARATOR

The deep brain stimulation device will be set to a frequency of 6 Hz and will stimulate the sensorimotor region, acting as an anatomical control. If differential activation of the associative and sensorimotor STN networks is not feasible, dorsal stimulation is employed.

Device: DBS On

High frequency stimulation of associative STN region

ACTIVE COMPARATOR

The deep brain stimulation device will be set to a frequency of 135 Hz and will stimulate the associative STN region, acting as a frequency control. If differential activation of the associative and sensorimotor STN networks is not feasible, ventral VTA is employed.

Device: DBS On

Interventions

DBS On DEVICE

The DBS device will be turned on while the patient undergoes the working memory task.

High frequency stimulation of associative STN region; Theta stimulation of STN sensorimotor region; Theta stimulation of associative STN region

DBS Off DEVICE

The DBS device will be turned off while the patient undergoes the working memory task.

Stimulation off

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Those with STN DBS devices
• Those with pre- and post-operative imaging
• Those that are at least 3 months post-operative

You may not qualify if:

• Those unable to complete the cognitive task (due to language barriers or dementia)
• Those with significant DBS complications

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

Leslie and Gordan Diamond Health Care Centre

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Stefan Lang, MD PhD FRCSC

CONTACT

604-875-5540; stefan.lang@vch.ca

Danielle Pietramala

CONTACT

604-875-4111; danielle.pietram@ubc.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD FRCSC

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: July 24, 2024
• Study Start: December 1, 2024
• Primary Completion: September 1, 2025
• Study Completion: October 1, 2025
• Last Updated: November 25, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)