Microstructural and functional abnormalities of the locus coeruleus in freezing of gait in Parkinson's disease

IF 5.6 2区医学 Q1 NEUROSCIENCES Neurobiology of Disease Pub Date : 2025-03-09 DOI:10.1016/j.nbd.2025.106868

Huimin Sun , Caiting Gan , Xingyue Cao , Yongsheng Yuan , Heng Zhang , Chenhui Wan , Jiaxin Shi , Xufeng Wang , Youyong Kong , Tao Feng , Kezhong Zhang

{"title":"Microstructural and functional abnormalities of the locus coeruleus in freezing of gait in Parkinson's disease","authors":"Huimin Sun , Caiting Gan , Xingyue Cao , Yongsheng Yuan , Heng Zhang , Chenhui Wan , Jiaxin Shi , Xufeng Wang , Youyong Kong , Tao Feng , Kezhong Zhang","doi":"10.1016/j.nbd.2025.106868","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>The loss of locus coeruleus (LC)-norepinephrine system may contribute to freezing of gait (FOG) in Parkinson's disease (PD), but free-water (FW) imaging has not been applied to investigate LC microstructural degeneration in FOG. This study was to investigate the role of the LC-norepinephrine system in FOG pathophysiology using FW imaging and resting-state functional magnetic resonance imaging.</div></div><div><h3>Methods</h3><div>FW metrics of LC were analyzed in 52 healthy controls, 79 PD patients without FOG (Non-FOG), and 110 PD patients with FOG (48 “Off-period” FOG and 62 “Levodopa unresponsive” FOG). Correlation between LC FW metrics and clinical scales were assessed. Functional connectivity analysis with LC as the region of interest was performed across groups during medication withdrawal. Structural and functional differences in LC between FOG subgroups and the effects of dopaminergic medication were also explored.</div></div><div><h3>Results</h3><div>FOG patients had increased FW value, FW-corrected mean diffusivity, axial diffusivity, and radial diffusivity in LC, and decreased FW-corrected fractional anisotropy compared to Non-FOG patients and healthy controls. In FOG patients, FW value and FW-corrected mean axial diffusivity were positively correlated with the new FOG questionnaire scores. LC functional connectivity with occipital regions was reduced in FOG patients. No significant differences in LC microstructure or functional connectivity were observed between FOG subgroups during their “OFF” state. In contrast to “Levodopa-unresponsive” FOG patients, oral medication significantly improved LC functional connectivity with occipital regions in “Off-period” FOG patients.</div></div><div><h3>Conclusions</h3><div>LC degeneration may disrupt motor and compensatory network integration, especially in visual-motor pathways, contributing to FOG.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"208 ","pages":"Article 106868"},"PeriodicalIF":5.6000,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Disease","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0969996125000841","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

The loss of locus coeruleus (LC)-norepinephrine system may contribute to freezing of gait (FOG) in Parkinson's disease (PD), but free-water (FW) imaging has not been applied to investigate LC microstructural degeneration in FOG. This study was to investigate the role of the LC-norepinephrine system in FOG pathophysiology using FW imaging and resting-state functional magnetic resonance imaging.

Methods

FW metrics of LC were analyzed in 52 healthy controls, 79 PD patients without FOG (Non-FOG), and 110 PD patients with FOG (48 “Off-period” FOG and 62 “Levodopa unresponsive” FOG). Correlation between LC FW metrics and clinical scales were assessed. Functional connectivity analysis with LC as the region of interest was performed across groups during medication withdrawal. Structural and functional differences in LC between FOG subgroups and the effects of dopaminergic medication were also explored.

Results

FOG patients had increased FW value, FW-corrected mean diffusivity, axial diffusivity, and radial diffusivity in LC, and decreased FW-corrected fractional anisotropy compared to Non-FOG patients and healthy controls. In FOG patients, FW value and FW-corrected mean axial diffusivity were positively correlated with the new FOG questionnaire scores. LC functional connectivity with occipital regions was reduced in FOG patients. No significant differences in LC microstructure or functional connectivity were observed between FOG subgroups during their “OFF” state. In contrast to “Levodopa-unresponsive” FOG patients, oral medication significantly improved LC functional connectivity with occipital regions in “Off-period” FOG patients.

Conclusions

LC degeneration may disrupt motor and compensatory network integration, especially in visual-motor pathways, contributing to FOG.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

帕金森病步态冻结时蓝斑座的显微结构和功能异常。

目的：蓝斑座(LC)-去甲肾上腺素系统的缺失可能导致帕金森病（PD）的步态冻结（FOG），但自由水成像（FW）尚未应用于研究步态冻结（FOG）的LC微结构变性。本研究采用FW成像和静息状态功能磁共振成像，探讨lc -去甲肾上腺素系统在FOG病理生理中的作用。方法：对52例健康对照、79例无FOG的PD患者（Non-FOG）和110例有FOG的PD患者（Off-period FOG 48例、左旋多巴无反应FOG 62例）进行LC的FW指标分析。评估LC FW指标与临床量表的相关性。在停药期间，跨组进行以LC为感兴趣区域的功能连通性分析。我们还探讨了FOG亚组间LC的结构和功能差异以及多巴胺能药物的影响。结果：与非FOG患者和健康对照相比，FOG患者LC的FW值、FW校正的平均弥散度、轴向弥散度和径向弥散度均增加，FW校正的分数各向异性降低。在FOG患者中，FW值和FW校正后的平均轴向弥散度与新的FOG问卷得分呈正相关。在FOG患者中，LC与枕区功能连通性降低。在“关闭”状态下，FOG亚组之间的LC微观结构和功能连通性没有显著差异。与“左旋多巴无反应”型FOG患者相比，口服药物可显著改善“非经期”型FOG患者与枕部的LC功能连接。结论：LC变性可能破坏运动和代偿网络的整合，特别是视觉-运动通路，导致FOG。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.