Brain-clinical signatures of basal ganglia-related dysfunctional reorganisation in Parkinson's disease.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-09-11 DOI:10.1016/j.ebiom.2025.105917

Lili Chen, Lianglong Sun, Junyan Sun, Junling Wang, Dongling Zhang, Mingrui Xia, Tao Wu

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引用次数: 0

Abstract

Background: The hierarchical organisation of functional networks is crucial for integration and segregation, and its dysregulation is implicated in neurodegenerative progression. The basal ganglia (BG) is the communication hub of the BG-thalamo-cortical circuit, and its dysfunction drives the progression of clinical symptoms in Parkinson's disease (PD). However, network-level functional reorganisation of BG disruption remains unclear.

Methods: In this cross-sectional study, we applied functional gradient analysis based on a diffusion map embedding algorithm to delineate macroscale functional architectures of BG in 102 PD patients and 88 healthy controls (HCs). Partial least squares correlation analysis was employed to investigate the relationship between gradient alterations and clinical symptoms in PD.

Findings: The first functional gradient of BG extended from caudate nucleus to putamen, whereas second gradient was anchored at dorsal and ventral caudate nucleus. In PD patients, the first gradient showed significant global compression with the progression from unilateral to bilateral motor symptoms. The second gradient exhibited local disruptions in nucleus accumbens and putamen, driven by reduced connectivity with multiple functional systems. Gradient scores of these two nuclei displayed significant lateralisation in PD, regardless of motor deficit dominance. Dysfunctional gradients in PD are associated with motor deficits and emotional symptoms.

Interpretation: Our findings reveal that functional gradient reorganisation is a network-level signature of early-stage PD, linking functional reorganisation in BG circuit to clinical symptoms. The hemispheric asymmetry of gradient patterns may inform ongoing research on PD lateralisation.

Funding: National Natural Science Foundation of China (Nos. 82071423 and 82021004) and Beijing Natural Science Foundation (No. JQ23033).

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帕金森病基底神经节相关功能失调重组的脑临床特征

背景：功能网络的分层组织对于整合和分离至关重要，其失调与神经退行性进展有关。基底神经节（basal ganglia， BG）是脑-丘脑-皮层回路的通讯中枢，其功能障碍驱动帕金森病（PD）临床症状的进展。然而，BG中断的网络级功能重组仍不清楚。方法：在这项横断面研究中，我们应用基于扩散图嵌入算法的功能梯度分析来描绘102名PD患者和88名健康对照（hc）的BG宏观功能结构。采用偏最小二乘相关分析探讨梯度改变与帕金森病临床症状的关系。结果：BG的第一个功能梯度从尾状核延伸到壳核，而第二个梯度锚定在尾状核的背侧和腹侧。在PD患者中，随着从单侧到双侧运动症状的进展，第一个梯度显示出明显的全局压缩。第二个梯度表现出伏隔核和壳核的局部中断，这是由于与多个功能系统的连接减少所致。在PD中，这两个核的梯度评分显示出明显的偏侧，与运动缺陷无关。PD的功能障碍梯度与运动缺陷和情绪症状有关。解释：我们的研究结果表明，功能梯度重组是早期PD的网络水平特征，将BG回路的功能重组与临床症状联系起来。梯度模式的半球不对称可能为正在进行的PD侧化研究提供信息。国家自然科学基金（No. 82071423和82021004）；北京市自然科学基金（No. 82071423）；JQ23033)。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.