The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Hum Brain Mapp. 2022 Feb 15;43(3):1145-1156. doi: 10.1002/hbm.25715. Epub 2021 Nov 18.
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by both motor and non-motor symptoms. A convergent pathophysiological hallmark of PD is an early selective vulnerability within the basal ganglia circuit. However, the causal interactions between basal ganglia atrophy and progressive structural network alterations in PD remain unaddressed. Here, we adopted voxel-based morphometry method to measure gray matter (GM) volume for each participant (n = 84 PD patients and n = 70 matched healthy controls). Patients were first divided into three stages according to the Hoehn and Yahr (H&Y) and the Part III of Unified Parkinson's Disease Rating Scale scores respectively to analyze the stage-specific GM atrophy patterns. Then, the modulation of early caudate atrophy over other brain structures was evaluated using the whole-brain voxel-wise and region-of-interest-wise causal structural covariance network approaches. We found that GM atrophy progressively expands from the basal ganglia to the angular gyrus, temporal areas, and eventually spreads through the subcortical-cortical networks as PD progresses. Notably, we identified a shared caudate-associated degeneration network including the basal ganglia, thalamus, cerebellum, sensorimotor cortex, and cortical association areas with the PD progressive factors. These findings suggest that the early structural vulnerability of basal ganglia in PD may play a pivotal role in the modulation of motor and non-motor circuits at the structural level. Our work provides evidence for a novel mechanism of network degeneration that underlies the pathology of PD and may have potential clinical applications in the development of early predictors of PD onset and progress.
帕金森病（PD）是一种进行性神经退行性疾病，其特征既有运动症状也有非运动症状。PD 的一个集中的病理生理学标志是基底神经节回路的早期选择性脆弱性。然而，基底神经节萎缩与 PD 进行性结构网络改变之间的因果相互作用仍未得到解决。在这里，我们采用基于体素的形态计量学方法测量每个参与者的灰质（GM）体积（n=84 名 PD 患者和 n=70 名匹配的健康对照者）。首先根据 Hoehn 和 Yahr（H&Y）评分和统一帕金森病评定量表第三部分评分将患者分为三个阶段，以分析特定阶段的 GM 萎缩模式。然后，使用全脑体素和感兴趣区的因果结构协方差网络方法评估早期尾状核萎缩对其他脑结构的调制作用。我们发现，随着 PD 的进展，GM 萎缩从基底神经节逐渐扩展到角回、颞叶区域，最终通过皮质下-皮质网络扩散。值得注意的是，我们确定了一个共享的尾状核相关退化网络，包括基底神经节、丘脑、小脑、感觉运动皮质和皮质联合区，这些区域与 PD 的进展因素有关。这些发现表明，PD 中基底神经节的早期结构脆弱性可能在运动和非运动回路的结构水平调节中发挥关键作用。我们的工作为 PD 病理学提供了一个新的网络退化机制的证据，并可能在开发 PD 发病和进展的早期预测因子方面具有潜在的临床应用价值。
