Objective: To describe the relationship between stimulation location and motor progression for the deep brain stimulation (DBS) in early-stage Parkinson’s disease (PD) pilot trial cohort [1].

Background: Subthalamic nucleus (STN) DBS is an effective adjunctive therapy for mid- and advanced-stage PD; however, individual motor improvement is variable, with electrode localization being a key determinant of efficacy. While DBS symptomatic effects are well-established, it is currently unclear how DBS influences motor progression.

Method: To determine anatomical and network correlates associated with motor progression in the early DBS cohort (n=14), voxel-wise sweet spot mapping and normative structural connectivity analysis were carried out using the outcome of two-year motor progression [Unified Parkinson Disease Rating Scale Part-III 7-day OFF therapy (MedOFF/StimOFF); change from baseline to 24 months].

Results: Sweet spot mapping revealed an early-stage PD optimal location associated with slower motor progression in the dorsolateral STN (AC/PC coordinates: 11.07±0.82 mm lateral, 1.83±0.61 mm posterior, 3.53±0.38 mm inferior to the midcommissural point; MNI coordinates: +11.25, -13.56, -7.44 mm). Modulating fiber tracts originating from supplementary motor area (SMA) and primary motor cortex (M1) to the STN correlated positively with slower motor progression, whereas fiber tracts originating from pre-SMA and cerebellum were negatively associated with motor progression. Robustness of the motor progression fiber tract model was demonstrated in leave-one-patient-out (R=0.56, P=0.02), 5-fold (R=0.50, P=0.03), and 10-fold (R=0.53, P=0.03) cross-validation paradigms.

Conclusion: This study suggests that stimulating the dorsolateral region of the STN in early-stage PD, specifically areas receiving input from SMA and M1 while avoiding input from pre-SMA, is associated with slower motor progression. This result is hypothesis-generating and must be prospectively tested in larger prospective study.

This study was previously presented at the XXVIII World Congress on Parkinson’s Disease and Related Disorders.

References: [1] Charles et al., 2014; 10.1016/j.parkreldis.2014.03.019

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MDS Abstracts - https://www.mdsabstracts.org/abstract/connectivity-profile-for-deep-brain-stimulation-in-early-stage-parkinsons-disease/