Cognitive Decline Following Deep Brain Stimulation

Study Overview
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Brief Summary
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This research study aims to identify MRI-based brain biomarkers that predict an individual's response to Deep Brain Stimulation (DBS). In particular, this study will focus on changes in cognition associated with DBS. A total of 55 participants with Parkinson's Disease planning to undergo DBS will be recruited from MUSCs Clinical DBS Program. Participants will undergo four visits, including a 1-hour screening visit, a 1.5-hour pre-DBS MRI scanning visit, and a 3.5-hour post-DBS cognitive assessment visit.

Detailed Description
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Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) is a well-established surgical intervention to treat Parkinson's Disease (PD) patients with disabling motor fluctuations and dyskinesias. Although this therapy is effective for motor complications, a subset of patients will go on to experience cognitive decline, which can overshadow improvements in the quality of life provided by STN-DBS. This accelerated decline in cognition occurs in patients despite rigorous evaluation of their neuropsychological status prior to surgery. While the factors contributing to cognitive decline following DBS remain unclear, there is evidence this may be the result of 1) limited cognitive reserve prior to DBS surgery, 2) stimulation that interferes with cognitive networks, and/or 3) a microlesion effect due to placement of the lead. Understanding how these factors contribute to DBS-induced cognitive decline has the potential to improve patient selection for surgery and optimize the selection of stimulation targets that minimize undesirable cognitive side effects.

Official Title
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A Neural Basis for Cognitive Decline Following Deep Brain Stimulation

Conditions
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Parkinson Disease, Movement Disorders

Intervention / Treatment
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* Procedure: Deep Brain Stimulation Surgical Procedures as Part of Routine Clinical Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects above 18 years of age Subjects who will undergo DBS surgery as part of their clinical care for PD Exclusion Criteria: Uncorrected visual or hearing impairments, as indicated by self-report Individuals who are pregnant or expect to become pregnant during the course of the study Individuals with claustrophobia, or the inability to lie supine position in the MRI scanner COPD with oxygen dependence Non-MRI compatible metal implants (surgical clips or staples, cardiac pacemakers etc.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Parkinson's Disease undergoing DBS<br>This study will recruit patients with Parkinson disease (PD) participants who will undergo DBS surgery and and are scheduled for a pre-DBS neuropsychological evaluation at MUSC. | Procedure: Deep Brain Stimulation Surgical Procedures as Part of Routine Clinical Care<br>* Participants in this study will already be undergoing a DBS intervention, however, this is part of their standard clinical care. Pre-surgical DBS candidates that enroll in this study will consent to participate in 1) pre-operative neuroimaging including a high-resolution MRI scan, 2) collection of pre-operative neurocognitive data via chart review and 3) a 1-year postoperative neurocognitive assessment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cognition | Change in cognitive performance using a comprehensive neuropsychological battery (e.g., language, executive control, memory, and attention) | From the DBS candidacy evaluation stage (approximately one month prior to deep brain stimulation) until 1 year post surgery | 
| Brain Microstructure (DKI) | Nucleus Basalis of Meynert (NBM) and striatal microstructural integrity using diffusion kurtosis imaging (mean kurtosis; MK) | Within the DBS candidacy evaluation stage (approximately one month prior to deep brain stimulation (DBS)) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain Functional Connectivity | Functional connectivity in cognitive networks including the Nucleus Basalis of Meynert (NBM) and the striatum | Within the DBS candidacy evaluation stage (approximately one month prior to deep brain stimulation (DBS)) | 
| Brain Microstructure (DTI) | Nucleus Basalis of Meynert (NBM) and striatal microstructural integrity using diffusion tensor imaging (mean diffusivity; MD) | Within the DBS candidacy evaluation stage (approximately one month prior to deep brain stimulation (DBS)) |