Microstructural and functional abnormalities of the locus coeruleus in freezing of gait in Parkinson's disease
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-norepi...
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Elsevier
2025-05-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125000841 |
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| author | Huimin Sun Caiting Gan Xingyue Cao Yongsheng Yuan Heng Zhang Chenhui Wan Jiaxin Shi Xufeng Wang Youyong Kong Tao Feng Kezhong Zhang |
| author_facet | Huimin Sun Caiting Gan Xingyue Cao Yongsheng Yuan Heng Zhang Chenhui Wan Jiaxin Shi Xufeng Wang Youyong Kong Tao Feng Kezhong Zhang |
| author_sort | Huimin Sun |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e1214e2f85954cd09a24444a69f8cd28 |
| institution | OA Journals |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-e1214e2f85954cd09a24444a69f8cd282025-08-20T02:09:31ZengElsevierNeurobiology of Disease1095-953X2025-05-0120810686810.1016/j.nbd.2025.106868Microstructural and functional abnormalities of the locus coeruleus in freezing of gait in Parkinson's diseaseHuimin Sun0Caiting Gan1Xingyue Cao2Yongsheng Yuan3Heng Zhang4Chenhui Wan5Jiaxin Shi6Xufeng Wang7Youyong Kong8Tao Feng9Kezhong Zhang10Department of Neurology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, ChinaDepartment of Neurology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, ChinaDepartment of Neurology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, ChinaDepartment of Neurology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, ChinaDepartment of Neurology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, ChinaDepartment of Neurology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, ChinaDepartment of Neurology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, ChinaDepartment of Neurology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, ChinaLaboratory of Image Science and Technology, Key Laboratory of Computer Network and Information Integration, School of Computer Science and Engineering, Southeast University, Nanjing 210029, China.Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China.; Corresponding author at: Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing 100070, PR China.Department of Neurology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S0969996125000841Locus coeruleusFree-water imagingFreezing of gait |
| spellingShingle | Huimin Sun Caiting Gan Xingyue Cao Yongsheng Yuan Heng Zhang Chenhui Wan Jiaxin Shi Xufeng Wang Youyong Kong Tao Feng Kezhong Zhang Microstructural and functional abnormalities of the locus coeruleus in freezing of gait in Parkinson's disease Neurobiology of Disease Locus coeruleus Free-water imaging Freezing of gait |
| title | Microstructural and functional abnormalities of the locus coeruleus in freezing of gait in Parkinson's disease |
| title_full | Microstructural and functional abnormalities of the locus coeruleus in freezing of gait in Parkinson's disease |
| title_fullStr | Microstructural and functional abnormalities of the locus coeruleus in freezing of gait in Parkinson's disease |
| title_full_unstemmed | Microstructural and functional abnormalities of the locus coeruleus in freezing of gait in Parkinson's disease |
| title_short | Microstructural and functional abnormalities of the locus coeruleus in freezing of gait in Parkinson's disease |
| title_sort | microstructural and functional abnormalities of the locus coeruleus in freezing of gait in parkinson s disease |
| topic | Locus coeruleus Free-water imaging Freezing of gait |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125000841 |
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