The zona incerta (ZI) is a subcortical structure primarily investigated in rodents that is implicated in various behaviors, ranging from motor control to survival-associated activities, partly due to its integration in multiple neural circuits. In the current study, we used diffusion magnetic resonance imaging tractography to segment the ZI and gain insight into its connectivity in various circuits in humans. We performed probabilistic tractography in 7T diffusion MRI on 178 participants from the Human Connectome Project to validate the ZI’s anatomical subdivisions and their respective tracts. K-means clustering segmented the ZI based on each voxel’s connectivity profile. We further characterized the connections of each ZI subregion using probabilistic tractography with each subregion as a seed. We identified 2 dominant clusters that delineated the whole ZI into rostral and caudal subregions. The caudal ZI primarily connected with motor regions, while the rostral ZI received a topographic distribution of projections from prefrontal areas, notably the anterior cingulate and medial prefrontal cortices. We generated a probabilistic ZI atlas that was registered to a patient-participant’s magnetic resonance imaging scan for placement of stereoencephalographic leads for electrophysiology-guided deep brain stimulation to treat their obsessive-compulsive disorder. Rostral ZI stimulation improved the patient’s core symptoms (mean improvement 21%). We present a tractography-based atlas of the rostral and caudal ZI subregions constructed using high-resolution diffusion magnetic resonance imaging from 178 healthy participants. Our work provides an anatomical foundation to explore the rostral ZI as a novel target for deep brain stimulation to treat refractory obsessive-compulsive disorder and other disorders associated with dysfunctional reward circuitry.

中文翻译：

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扩散磁共振成像纤维束成像指导未定带的研究：深部脑刺激的新目标

未定带 (ZI) 是一种主要在啮齿类动物中研究的皮层下结构，与从运动控制到生存相关活动等各种行为有关，部分原因是其在多个神经回路中的整合。在当前的研究中，我们使用扩散磁共振成像纤维束成像技术来分割 ZI，并深入了解其在人体各种回路中的连接性。我们对人类连接组项目的 178 名参与者进行了 7T 扩散 MRI 概率纤维束成像，以验证 ZI 的解剖细分及其各自的纤维束。 K 均值聚类根据每个体素的连通性配置文件对 ZI 进行分段。我们进一步使用概率纤维束成像技术以每个子区域作为种子来表征每个 ZI 子区域的连接。我们确定了 2 个主要簇，将整个 ZI 划分为吻侧和尾侧亚区域。尾部 ZI 主要与运动区域连接，而喙部 ZI 接收来自前额叶区域的投影的地形分布，特别是前扣带皮层和内侧前额叶皮质。我们生成了一个概率 ZI 图集，该图集被注册到患者参与者的磁共振成像扫描中，用于放置立体脑描记导线，用于电生理学引导的深部脑刺激，以治疗他们的强迫症。头侧 ZI 刺激改善了患者的核心症状（平均改善 21%）。我们提出了基于纤维束成像的头侧和尾侧 ZI 亚区域图谱，该图谱是使用 178 名健康参与者的高分辨率扩散磁共振成像构建的。我们的工作为探索头侧 ZI 作为深部脑刺激的新靶点提供了解剖学基础，以治疗难治性强迫症和与奖赏回路功能失调相关的其他疾病。