Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Radiology, Stanford University School of Medicine, Stanford, California.
Biol Psychiatry. 2024 Sep 15;96(6):445-454. doi: 10.1016/j.biopsych.2024.02.1004. Epub 2024 Feb 22.
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.
未定带（ZI）是一个主要在啮齿动物中研究的皮质下结构，涉及从运动控制到与生存相关的活动等各种行为，部分原因是其整合到多个神经回路中。在目前的研究中，我们使用弥散磁共振成像轨迹技术对 178 名人类连接体计划参与者进行了扩散磁共振成像分析，以了解 ZI 在人类各种回路中的连接情况。
我们在 7T 弥散 MRI 上对 178 名人类连接体计划参与者进行了概率性轨迹追踪，以验证 ZI 的解剖细分及其各自的轨迹。K-均值聚类根据每个体素的连接分布对 ZI 进行分段。我们使用概率性轨迹追踪，以每个亚区为种子，进一步对每个 ZI 亚区的连接进行了特征描述。
我们确定了 2 个主要的聚类，将整个 ZI 分为头侧和尾侧亚区。尾侧 ZI 主要与运动区域相连，而头侧 ZI 从前额区域接收了一个投射的拓扑分布，特别是前扣带和内侧前额皮质。我们生成了一个概率性的 ZI 图谱，该图谱被注册到患者参与者的磁共振成像扫描中，以便放置立体脑电图导联，用于电生理学引导的深部脑刺激治疗他们的强迫症。头侧 ZI 刺激改善了患者的核心症状（平均改善 21%）。
我们使用来自 178 名健康参与者的高分辨率弥散磁共振成像，提出了一种基于轨迹追踪的头侧和尾侧 ZI 亚区图谱。我们的工作为探索头侧 ZI 作为深部脑刺激治疗难治性强迫症和其他与功能障碍性奖励回路相关障碍的新靶点提供了解剖学基础。
