| Summary: | Background: Motor outcomes after subthalamic deep brain stimulation (STN DBS) for Parkinson disease (PD) vary considerably among patients and strongly depend on stimulation location. The objective of this retrospective study was to map the regions of optimal STN DBS for PD using an atlas-independent, fully individualized (N-of-1) tissue activation modeling approach and to assess the relationship between patient-level therapeutic volumes of tissue activation (VTAs) and motor improvement. Methods: The stimulation-induced electric field for 40 PD patients treated with bilateral STN DBS was modeled using finite element analysis. Neurostimulation models were generated for each patient, incorporating their individual STN anatomy, DBS lead position and orientation, anisotropic tissue conductivity, and clinical stimulation settings. A voxel-based analysis of the VTAs was then used to map the optimal location of stimulation. The amount of stimulation in specific regions relative to the STN was measured and compared between STNs with more and less optimal stimulation, as determined by their motor improvement scores and VTA. The relationship between VTA location and motor outcome was then assessed using correlation analysis. Patient variability in terms of STN anatomy, active contact position, and VTA location were also evaluated. Results from the N-of-1 model were compared to those from a simplified VTA model. Results: Tissue activation modeling mapped the optimal location of stimulation to regions medial, posterior, and dorsal to the STN centroid. These regions extended beyond the STN boundary towards the caudal zona incerta (cZI). The location of the VTA and active contact position differed significantly between STNs with more and less optimal stimulation in the dorsal-ventral and anterior-posterior directions. Therapeutic stimulation spread noticeably more in the dorsal and posterior directions, providing additional evidence for cZI as an important DBS target. There were significant linear relationships between the amount of dorsal and posterior stimulation, as measured by the VTA, and motor improvement. These relationships were more robust than those between active contact position and motor improvement. There was high variability in STN anatomy, active contact position, and VTA location among patients. Spherical VTA modeling was unable to reproduce these results and tended to overestimate the size of the VTA. Conclusion: Accurate characterization of the spread of stimulation is needed to optimize STN DBS for PD. High variability in neuroanatomy, stimulation location, and motor improvement among patients highlights the need for individualized modeling techniques. The atlas-independent, N-of-1 tissue activation modeling approach presented in this study can be used to develop and evaluate stimulation strategies to improve clinical outcomes on an individual basis.
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