Less locus coeruleus degeneration and its enhanced influence on neural circuit in Parkinson's tremor

Objectives: The involvement of the locus coeruleus in Parkinson's tremor remains unclear. We aimed to decode the role of locus coeruleus in Parkinson's tremor. Methods: We used MRI to examine 120 Parkinson's disease, including 48 tremor-dominant (TD) and 72 postural instability/gait d...

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Main Authors: Junyan Sun, Lili Chen, Liang Li, Tao Wu, Tao Feng
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Neurobiology of Disease
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Online Access:http://www.sciencedirect.com/science/article/pii/S0969996125001767
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author Junyan Sun
Lili Chen
Liang Li
Tao Wu
Tao Feng
author_facet Junyan Sun
Lili Chen
Liang Li
Tao Wu
Tao Feng
author_sort Junyan Sun
collection DOAJ
description Objectives: The involvement of the locus coeruleus in Parkinson's tremor remains unclear. We aimed to decode the role of locus coeruleus in Parkinson's tremor. Methods: We used MRI to examine 120 Parkinson's disease, including 48 tremor-dominant (TD) and 72 postural instability/gait disorder (PIGD), as well as 83 healthy controls. Neuromelanin-sensitive MRI accessed the contrast-to-noise ratio of locus coeruleus. Spectral dynamic causal modeling based on resting-state functional MRI accessed the effective connectivity from locus coeruleus to the cerebello-thalamo-cortical circuit. The pivotal nodes of cerebello-thalamo-cortical circuit included ventral intermediate nucleus, motor cortex, and cerebellum. Results: Both TD and PIGD patients exhibited lower bilateral contrast-to-noise ratio of locus coeruleus than healthy controls. But TD patients had higher contrast-to-noise ratio of locus coeruleus than PIGD, accompanied by increased effective connectivity from locus coeruleus to cerebello-thalamo-cortical circuit than healthy controls and PIGD patients on the more-affected side (P < 0.003125, one-way analysis of covariance). The contrast-to-noise ratio of locus coeruleus and effective connectivity (e.g. locus coeruleus→motor cortex) positively correlated with rest tremor in TD patients (R = 0.47, P = 0.002; R = 0.427, P = 0.003, respectively). Conclusions: TD patients exhibited less locus coeruleus degeneration than PIGD patients, alongside increased influence from locus coeruleus to the cerebello-thalamo-cortical circuit than healthy controls and PIGD patients. The structural/functional alterations of locus coeruleus are closely associated with rest tremor, suggesting the potential for tremor treatment targeting the locus coeruleus noradrenergic system.
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spelling doaj-art-39af052f7fa04ffdb07d7d65d27e16b62025-07-25T04:18:04ZengElsevierNeurobiology of Disease1095-953X2025-09-01213106960Less locus coeruleus degeneration and its enhanced influence on neural circuit in Parkinson's tremorJunyan Sun0Lili Chen1Liang Li2Tao Wu3Tao Feng4Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaCenter for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBrain Science Center, Beijing Institute of Basic Medical Sciences, China; Corresponding authors.Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Corresponding authors.Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Corresponding authors.Objectives: The involvement of the locus coeruleus in Parkinson's tremor remains unclear. We aimed to decode the role of locus coeruleus in Parkinson's tremor. Methods: We used MRI to examine 120 Parkinson's disease, including 48 tremor-dominant (TD) and 72 postural instability/gait disorder (PIGD), as well as 83 healthy controls. Neuromelanin-sensitive MRI accessed the contrast-to-noise ratio of locus coeruleus. Spectral dynamic causal modeling based on resting-state functional MRI accessed the effective connectivity from locus coeruleus to the cerebello-thalamo-cortical circuit. The pivotal nodes of cerebello-thalamo-cortical circuit included ventral intermediate nucleus, motor cortex, and cerebellum. Results: Both TD and PIGD patients exhibited lower bilateral contrast-to-noise ratio of locus coeruleus than healthy controls. But TD patients had higher contrast-to-noise ratio of locus coeruleus than PIGD, accompanied by increased effective connectivity from locus coeruleus to cerebello-thalamo-cortical circuit than healthy controls and PIGD patients on the more-affected side (P < 0.003125, one-way analysis of covariance). The contrast-to-noise ratio of locus coeruleus and effective connectivity (e.g. locus coeruleus→motor cortex) positively correlated with rest tremor in TD patients (R = 0.47, P = 0.002; R = 0.427, P = 0.003, respectively). Conclusions: TD patients exhibited less locus coeruleus degeneration than PIGD patients, alongside increased influence from locus coeruleus to the cerebello-thalamo-cortical circuit than healthy controls and PIGD patients. The structural/functional alterations of locus coeruleus are closely associated with rest tremor, suggesting the potential for tremor treatment targeting the locus coeruleus noradrenergic system.http://www.sciencedirect.com/science/article/pii/S0969996125001767Locus coeruleusTremorCerebello-thalamo-cortical circuitContrast-to-noise ratioEffective connectivity
spellingShingle Junyan Sun
Lili Chen
Liang Li
Tao Wu
Tao Feng
Less locus coeruleus degeneration and its enhanced influence on neural circuit in Parkinson's tremor
Neurobiology of Disease
Locus coeruleus
Tremor
Cerebello-thalamo-cortical circuit
Contrast-to-noise ratio
Effective connectivity
title Less locus coeruleus degeneration and its enhanced influence on neural circuit in Parkinson's tremor
title_full Less locus coeruleus degeneration and its enhanced influence on neural circuit in Parkinson's tremor
title_fullStr Less locus coeruleus degeneration and its enhanced influence on neural circuit in Parkinson's tremor
title_full_unstemmed Less locus coeruleus degeneration and its enhanced influence on neural circuit in Parkinson's tremor
title_short Less locus coeruleus degeneration and its enhanced influence on neural circuit in Parkinson's tremor
title_sort less locus coeruleus degeneration and its enhanced influence on neural circuit in parkinson s tremor
topic Locus coeruleus
Tremor
Cerebello-thalamo-cortical circuit
Contrast-to-noise ratio
Effective connectivity
url http://www.sciencedirect.com/science/article/pii/S0969996125001767
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