Association between functional alterations and specific transcriptional expression patterns in craniocervical dystonia

IF 3.4 3区医学 Q2 CLINICAL NEUROLOGY Parkinsonism & related disorders Pub Date : 2025-01-31 DOI:10.1016/j.parkreldis.2025.107315

Gang Liu , Jiana Zhang , Haoran Zhang , Qinxiu Cheng , Xiaodong Zhang , Jun Liu , Yuhan Luo , Linchang Zhong , Zhengkun Yang , Yue Zhang , Zilin Ou , Zhicong Yan , Weixi Zhang , Kangqiang Peng , Huiming Liu , Jinping Xu

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Abstract

Purpose

Craniocervical dystonia (CCD) is a large-scale network disorder that involves functional changes in multiple brain regions. However, the association between these functional changes and the underlying molecular mechanisms has not been explored.

Objective

We aimed to characterize the molecular changes associated with the imaging-defined functional architecture of the brain in CCD.

Methods

Resting-state functional magnetic resonance imaging (rs-fMRI) data were obtained from 146 patients with CCD and 137 healthy controls (HCs). Differences in the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were compared between groups. Transcriptomic data were obtained from the Allen Human Brain Atlas to identify the gene expression patterns underlying the affected functional architecture in CCD using partial least squares regression.

Results

Compared to HCs, patients with CCD showed common functional alterations, mainly in the left middle occipital gyrus, right middle occipital gyrus, right calcarine, right precentral gyrus, and left postcentral gyrus. These functional alteration patterns were positively associated with 1763 genes (including five risk genes for dystonia) enriched for synaptic signaling, regulation of trans-synaptic signaling, and neuronal systems, while they were negatively associated with 2318 genes (including eight risk genes for dystonia), which were enriched for monoatomic cation transport, DNA damage response and neurodevelopment.

Conclusions

Our study reveals a genetic pathological mechanism explaining CCD-related brain functional changes.

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颅颈肌张力障碍的功能改变与特定转录表达模式之间的关联

目的颅颈肌张力障碍（CCD）是一种涉及多脑区功能改变的大规模网络障碍。然而，这些功能变化与潜在的分子机制之间的联系尚未被探索。目的研究CCD患者脑成像功能结构的相关分子变化。方法对146例CCD患者和137例健康对照进行静息状态功能磁共振成像（rs-fMRI）分析。比较各组之间低频波动幅度（ALFF）、分数ALFF （fALFF）和区域均匀性（ReHo）的差异。转录组学数据来自Allen人脑图谱，利用偏最小二乘回归确定CCD中受影响功能结构的基因表达模式。结果与hc相比，CCD患者表现出常见的功能改变，主要发生在左侧枕中回、右侧枕中回、右侧钙脑回、右侧中央前回和左侧中央后回。这些功能改变模式与1763个基因（包括5个肌张力障碍风险基因）富集的突触信号、跨突触信号调节和神经元系统呈正相关，而与2318个基因（包括8个肌张力障碍风险基因）富集的单原子阳离子转运、DNA损伤反应和神经发育负相关。结论sour研究揭示了一种解释ccd相关脑功能改变的遗传病理机制。

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来源期刊

Parkinsonism & related disorders 医学-临床神经学

CiteScore

6.20

自引率

4.90%

发文量

292

审稿时长

39 days

期刊介绍： Parkinsonism & Related Disorders publishes the results of basic and clinical research contributing to the understanding, diagnosis and treatment of all neurodegenerative syndromes in which Parkinsonism, Essential Tremor or related movement disorders may be a feature. Regular features will include: Review Articles, Point of View articles, Full-length Articles, Short Communications, Case Reports and Letter to the Editor.