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.

中文翻译：

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独立于Atlas的N-of-1组织激活模型以绘制丘脑深部脑刺激对帕金森病的最佳区域

背景

丘脑深部脑刺激（STN DBS）治疗帕金森病（PD）后的运动结果在患者之间差异很大，并且强烈取决于刺激的位置。这项回顾性研究的目的是使用不依赖图谱的完全个性化（N-of-1）组织激活建模方法绘制PD的最佳STN DBS区域，并评估患者水平组织激活治疗量之间的关系（VTA）和运动改善。

方法

使用有限元分析对40例接受双侧STN DBS治疗的PD患者的刺激诱发电场进行建模。为每个患者生成了神经刺激模型，其中包括他们各自的STN解剖结构，DBS导联位置和方向，各向异性组织电导率以及临床刺激设置。然后使用基于体素的VTA分析来绘制刺激的最佳位置。测量特定区域中相对于STN的刺激量，并比较最佳刺激的STN的数量，这些最佳刺激由其运动改善评分和VTA决定。然后使用相关分析评估VTA位置与运动结果之间的关系。还评估了患者在STN解剖，活动接触位置和VTA位置方面的变异性。

结果

组织激活模型将刺激的最佳位置映射到STN质心的内侧，后侧和背侧。这些区域超出了STN边界，朝着尾部不透明带（cZI）延伸。在STN之间，VTA的位置和活动的接触位置之间存在显着差异，在背腹和前后方向上的最佳刺激越来越少。治疗性刺激在背侧和后侧方向明显扩展，为cZI作为重要的DBS靶点提供了更多证据。通过VTA测得的背部刺激和后刺激的量与运动能力的改善之间存在显着的线性关系。这些关系比主动接触位置和运动改善之间的关系更牢固。STN解剖结构变化很大，患者之间的主动接触位置和VTA位置。球形VTA建模无法重现这些结果，并倾向于高估VTA的大小。

结论

需要准确表征刺激的扩散，以优化用于PD的STN DBS。患者之间神经解剖结构，刺激位置和运动能力的高度变异性凸显了对个性化建模技术的需求。本研究中提出的独立于图谱的N-of-1组织激活模型方法可用于开发和评估刺激策略，以改善个体临床疗效。