Theta Deep Brain Stimulation for Cognitive Enhancement in Parkinson's Disease
NCT Number: NCT06518824
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Parkinson Disease|Cognitive Impairment
Interventions: DEVICE: DBS On|DEVICE: DBS Off
Sponsor: University of British Columbia
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 27
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: SINGLE (PARTICIPANT)|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2025-10
Locations: Leslie and Gordan Diamond Health Care Centre, Vancouver, British Columbia, V5Z 1M9, Canada

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.

Primary Outcome Measures: 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 Outcome Measures: Correlation between working memory performance and STN connectivity, Connectivity of the stimulated STN region will be calculated with structural (streamline count and strength) and functional (Pearson Correlation) MRI data. The change in working memory performance will be correlated to the connectivity metrics with a linear regression. The hypothesis is that there will be a positive correlation between working memory change and connectivity strength of the STN to associative networks (higher connectivity will be related to higher working memory performance)., Immediately after task performance