Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, 230031, China; Center for Biomedical Imaging, University of Science and Technology of China, Hefei, Anhui, 2300026, China; School of Medical Information Engineering, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, 230012, China.
Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, 230031, China; Key Laboratory of Xin'an Medicine of the Ministry of Education, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, 230031, China.
Neuroimage Clin. 2024;43:103618. doi: 10.1016/j.nicl.2024.103618. Epub 2024 May 11.
Extensive neuroimaging abnormalities in subcortical regions build the pathophysiological basis of Wilson's disease (WD). Yet, subcortical topographic organization fails to articulate, leaving a huge gap in understanding the neural mechanism of WD. Thus, how functional abnormalities of WD subcortical regions influence complex clinical symptoms and response to treatment remain unknown. Using resting-state functional MRI data from 232 participants (including 130 WD patients and 102 healthy controls), we applied a connectivity-based parcellation technique to develop a subcortical atlas for WD. The atlas was further used to investigate abnormalities in subcortical function (ASF) by exploring intrasubcortical functional connectivity (FC) and topographic organization of cortico-subcortical FC. We further used support vector machine (SVM) to integrate these functional abnormalities into the ASF score, which serves as a biomarker for characterizing individual subcortical dysfunction for WD. Finally, the baseline ASF score and one-year treatment data of the follow-up WD patients were used to assess treatment response. A group set of subcortical parcellations was evaluated, in which 26 bilateral regions well recapitulated the anatomical nuclei of the subcortical areas of WD. The results of cortico-subcortical FC and intrasubcortical FC reveal that dysfunction of the somatomotor networks-lenticular nucleus-thalamic pathways is involved in complex symptoms of WD. The ASF score was able to characterize disease progression and was significantly associated with treatment response of WD. Our findings provide a comprehensive elaboration of functional abnormalities of WD subcortical regions and reveal their association with clinical presentations, improving our understanding of the functional neural underpinnings in WD. Furthermore, abnormalities in subcortical function could serve as a potential biomarker for understanding the disease progression and evaluating treatment response of WD.
广泛的皮质下区域神经影像学异常为威尔逊病（WD）的病理生理学基础。然而，皮质下的拓扑组织未能阐明，这使得我们对 WD 的神经机制的理解存在巨大的空白。因此，WD 皮质下区域的功能异常如何影响复杂的临床症状和治疗反应仍然未知。本研究使用来自 232 名参与者（包括 130 名 WD 患者和 102 名健康对照者）的静息态功能磁共振成像数据，应用基于连接的分割技术，为 WD 建立皮质下图谱。该图谱进一步用于通过探索皮质下功能异常（ASF）来研究皮质下功能异常，通过探索皮质下功能连接（FC）和皮质下 FC 的拓扑组织。我们进一步使用支持向量机（SVM）将这些功能异常整合到 ASF 评分中，作为 WD 个体皮质下功能障碍的特征生物标志物。最后，使用 WD 患者的基线 ASF 评分和一年的随访数据来评估治疗反应。评估了一组皮质下分割，其中 26 个双侧区域很好地概括了 WD 皮质下区域的解剖核。皮质下 FC 和皮质下 FC 的结果表明，躯体运动网络-豆状核-丘脑通路的功能障碍与 WD 的复杂症状有关。ASF 评分能够描述疾病进展，并与 WD 的治疗反应显著相关。我们的研究结果全面阐述了 WD 皮质下区域的功能异常，并揭示了它们与临床表现的关联，提高了我们对 WD 中功能神经基础的理解。此外，皮质下功能异常可以作为理解疾病进展和评估 WD 治疗反应的潜在生物标志物。
