Objective: To determine frequency and/or predictors of improvement or worsening of apathy, we evaluated this behavior among those who received bilateral subthalamic deep brain stimulation (STN-DBS) for the treatment of Parkinson’s Disease (PD), per inclusion as a study participant in the INTREPID randomized controlled trial (RCT).

Background: Motivational disturbances including apathy have been commonly reported following bilateral STN-DBS. Many studies have suggested that apathy can be associated with dopaminergic denervation and unmasked by drug withdrawal and by aggressive drug tapering following STN-DBS surgery. Additionally, it is suspected that stimulation of limbic-associative sub-regions of STN might serve as a catalyst, an independent cause, or possibly act synergistically with dopaminergic medication reduction.

Method: INTREPID (NCT01839396) is a multi-center, prospective, double-blinded RCT. Participants with advanced PD received bilateral STN-DBS and completed a neuropsychological battery at screening (prior to DBS) and at follow up (12-months). Apathy was assessed using the Starkstein Apathy Scale (SAS). Demographic and clinical data including age, gender, disease duration, disease severity, levodopa-equivalent daily dose (LEDD), and imaging correlates of DBS (including location and volume of tissue activation [VTA]) were analyzed.

Results: At 1-year follow-up, post-bilateral STN-DBS, 44 (27.5%) reported an improvement in apathy scores of at least 5-points, and 7 (4.4%) an improvement >10 points. Eighteen (11.3%) participants had worsening apathy scores >5 points, and 8 (5%) reported worsening >10 points. Aggregation of stimulation field models (VTAs) showed worsening in apathy by at least 5-points was associated by activation of limbic (30%) and associative (11%) regions, but only minimally with motor regions (0.7%). There was a weak association with LED change.

Conclusion: Improvement and worsening of apathy at 1-year follow-up was observed. Further analysis of dopamine agonist use and VTA is a promising approach to better understand apathy following STN-DBS surgery. Limbic and associative spread of DBS current may be important and frequently unaccounted for factors in post-DBS apathy.  Future applications using aggregate VTA maps and patient outcomes may help target lead-placement and guide programming strategies to avoid apathy as unintended outcome.

« Back to 2022 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/apathy-and-volume-of-tissue-activated-vta-following-bilateral-subthalamic-deep-brain-stimulation-for-parkinsons-disease-the-intrepid-cohort/