Objective: Prospective tractography-guided DBS targeting of the left STN-vmPFC and primary motor pathway to improve apathy alongside motor symptoms in PD.

Background: While STN DBS is a well-established treatment for motor symptoms in PD, its efficacy in addressing non-motor symptoms, such as apathy, remains controversial. Patients frequently experience apathy post-DBS, which has been linked to reduced dopamine medication without compensatory stimulation of limbic fronto-subthalamic network connections.^1-7 Recent findings suggest that co-stimulating these non-motor pathways, in particular left STN-vmPFC connections, alongside the primary motor pathway may help mitigate DBS-related apathy.⁸ However, the prospective selection of patients with medication-responsive apathy and the use of tractography-guided targeting to engage both motor and left-sided vmPFC connections have not been tested.

Method: We used probabilistic tractography to model the left STN-vmPFC and primary motor pathways pre-surgery to define the optimal surgical STN DBS target at their intersection. DBS parameter programming followed standard clinical protocol. After 6 months of therapeutic DBS, we assessed the therapeutic response. The patient was a 51-year-old male with 14 years of PD. His pre-surgical levodopa response was a reduction of 24 points on the MDS-UPDRS III (29 OFF med to 5 ON med, -83%) and a 7-point reduction on the SAS apathy scale (21 OFF med to 14 ON med, -33%).

Results: We were able to plan a surgical target at the intersection of the motor and vmPFC pathway, Fig 1. Post-surgical assessment of the electrode placement showed that the initial target was stimulated with the current therapeutic settings (Fig 2B). The patient reported a substantial reduction in apathy symptoms, along with an 81% decrease in medication use with these settings (ON med, ON stim). At the 6-month follow-up, there was a 6-point reduction in the SAS (from 21 OFF med to 15 OFF med/ON stim, -29%) and a 20-point improvement on the MDS-UPDRS III (29 OFF med to 9 OFF med/ON stim, -69%).

Conclusion: This case report demonstrates that prospective targeting of the left STN-vmPFC pathway can effectively alleviate apathy in PD patients with levodopa-responsive apathy. This individualized targeting approach offers a promising strategy to address both motor and non-motor symptoms with STN DBS in PD.

Fig 1.

Fig 2.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prospective-tractography-guided-stn-dbs-targeting-with-optimized-vmpfc-connectivity-for-apathy-in-pd-a-case-report/