Cognitive Decline Following Deep Brain Stimulation: A DBS-fMRI Study

A Neural Basis for Cognitive Decline Following Deep Brain Stimulation: A DBS-fMRI Study

The objective of this research study is to understand how Deep Brain Stimulation (DBS) targeting the subthalamic nucleus (STN) affects cognitive networks in the brain, potentially leading to cognitive decline in patients with Parkinson's Disease (PD). A total of 55 participants with PD who have undergone DBS surgery will be recruited from MUSC's Clinical DBS Program. Participants will attend two post-DBS visits: a 3-hour visit for consent, demographic, and cognitive assessments, and a 3-hour DBS-MRI visit to evaluate brain network connectivity with stimulation ON and OFF. These findings will help improve patient selection for surgery and optimize the selection of stimulation targets that minimize undesirable cognitive side effects.

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. This research seeks to identify how DBS-induced changes in neural connectivity contribute to cognitive decline and how brain microstructure influences these changes. Understanding how these factors has the potential to improve patient selection for surgery and optimize the selection of stimulation targets that minimize undesirable cognitive side effects.

Inclusion Criteria:

• Subjects above 18 years of age
• Individuals with a PD diagnosis as defined by the UK Brain Bank diagnostic criteria for Parkinson's disease (58) which have undergone a neurological and neuropsychological evaluation at MUSCs movement disorder center, and were selected to undergo 3T compatible unilateral or bilateral STN- DBS implants

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 that have a history of neurological disease (other than PD) including previous stroke, major head trauma, and epilepsy or seizures.
• 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.)