David Charles

Objective This study was undertaken to describe relationships between electrode localization and motor outcomes from the subthalamic nucleus (STN) deep brain stimulation (DBS) in early stage Parkinson disease (PD) pilot clinical trial. Methods To determine anatomical and network correlates associated with motor outcomes for subjects randomized to early DBS (n = 14), voxelwise sweet spot mapping and structural connectivity analyses were carried out using outcomes of motor progression (Unified Parkinson Disease Rating Scale Part III [UPDRS‐III] 7‐day OFF scores [∆baseline➔24 months, MedOFF/StimOFF]) and symptomatic motor improvement (UPDRS‐III ON scores [%∆baseline➔24 months, MedON/StimON]). Results Sweet spot mapping revealed a location associated with slower motor progression in the dorsolateral STN (anterior/posterior commissure coordinates: 11.07 ± 0.82mm lateral, 1.83 ± 0.61mm posterior, 3.53 ± 0.38mm inferior to the midcommissural point; Montreal Neurological Institute coordinates: +11.25, −13.56, −7.44mm). Modulating fiber tracts from supplementary motor area (SMA) and primary motor cortex (M1) to the STN correlated with slower motor progression across STN DBS subjects, whereas fiber tracts originating from pre‐SMA and cerebellum were negatively associated with motor progression. Robustness of the 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. The sweet spot and fiber tracts associated with motor progression revealed strong similarities to symptomatic motor improvement sweet spot and connectivity in this early stage PD cohort. Interpretation These results suggest that stimulating the dorsolateral region of the STN receiving input from M1 and SMA (but not pre‐SMA) is associated with slower motor progression across subjects receiving STN DBS in early stage PD. This finding is hypothesis‐generating and must be prospectively tested in a larger study. ANN NEUROL 2023;94:271–284