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Associations between neuromelanin depletion and cortical rhythmic activity in Parkinson's disease.

作者信息

Wiesman Alex I, Madge Victoria, Fon Edward A, Dagher Alain, Collins D Louis, Baillet Sylvain

机构信息

Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.

Department of Biomedical Physiology & Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.

出版信息

Brain. 2025 Mar 6;148(3):875-885. doi: 10.1093/brain/awae295.


DOI:10.1093/brain/awae295
PMID:39282945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11884654/
Abstract

Parkinson's disease (PD) is marked by the death of neuromelanin-rich dopaminergic and noradrenergic cells in the substantia nigra (SN) and the locus coeruleus (LC), respectively, resulting in motor and cognitive impairments. Although SN dopamine dysfunction has clear neurophysiological effects, the association of reduced LC norepinephrine signalling with brain activity in PD remains to be established. We used neuromelanin-sensitive T1-weighted MRI (PD, n = 58; healthy control, n = 27) and task-free magnetoencephalography (PD, n = 58; healthy control, n = 65) to identify neuropathophysiological factors related to the degeneration of the LC and SN in patients with PD. We found pathological increases in rhythmic alpha-band (8-12 Hz) activity in patients with decreased LC neuromelanin, which were more strongly associated in patients with worse attentional impairments. This negative alpha-band-LC neuromelanin relationship is strongest in fronto-motor cortices, where alpha-band activity is inversely related to attention scores. Using neurochemical co-localization analyses with normative atlases of neurotransmitter transporters, we also show that this effect is more pronounced in regions with high densities of norepinephrine transporters. These observations support a noradrenergic association between LC integrity and alpha-band activity. Our data also show that rhythmic beta-band (15-29 Hz) activity in the left somatomotor cortex decreases with lower levels of SN neuromelanin; the same regions where beta activity reflects axial motor symptoms. Together, our findings clarify the association of well-documented alterations of rhythmic neurophysiology in PD with cortical and subcortical neurochemical systems. Specifically, attention-related alpha-band activity is related to dysfunction of the noradrenergic system, and beta activity with relevance to motor impairments reflects dopaminergic dysfunction.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3cb/11884654/43f60a37f523/awae295f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3cb/11884654/588c954d367a/awae295f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3cb/11884654/7fd4c33e62b1/awae295f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3cb/11884654/43f60a37f523/awae295f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3cb/11884654/588c954d367a/awae295f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3cb/11884654/7fd4c33e62b1/awae295f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3cb/11884654/43f60a37f523/awae295f3.jpg

相似文献

[1]
Associations between neuromelanin depletion and cortical rhythmic activity in Parkinson's disease.

Brain. 2025-3-6

[2]
Associations between neuromelanin depletion and cortical rhythmic activity in Parkinson's disease.

medRxiv. 2024-2-18

[3]
Neuromelanin-sensitive magnetic resonance imaging features of the substantia nigra and locus coeruleus in de novo Parkinson's disease and its phenotypes.

Eur J Neurol. 2018-4-11

[4]
Association of Locus Coeruleus and Substantia Nigra Pathology With Cognitive and Motor Functions in Patients With Parkinson Disease.

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[5]
Substantia nigra neuromelanin magnetic resonance imaging in de novo Parkinson's disease patients.

Eur J Neurol. 2015-3

[6]
An investigation of neuromelanin distribution in substantia nigra and locus coeruleus in patients with Parkinson's disease using neuromelanin-sensitive MRI.

BMC Neurol. 2023-8-14

[7]
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Neuroreport. 2006-7-31

[8]
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J Neurol. 2025-2-11

[9]
Neuromelanin related ultra-high field signal intensity of the locus coeruleus differs between Parkinson's disease and controls.

Neuroimage Clin. 2023

[10]
Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson's disease.

Brain. 2020-9-1

引用本文的文献

[1]
Unraveling the complexity of neurodegeneration: heterogeneous damage patterns of locus coeruleus and substantia nigra in Alzheimer's disease.

Alzheimers Dement. 2025-9

[2]
The PREVENT-AD cohort: accelerating Alzheimer's disease research and treatment in Canada and beyond.

medRxiv. 2025-7-23

[3]
Changes in sensorimotor network dynamics in resting-state recordings in Parkinson's disease.

Brain Commun. 2025-7-23

[4]
Cortical Effects of Dopamine Replacement Account for Clinical Response Variability in Parkinson's Disease.

Mov Disord. 2025-4-18

[5]
Catecholaminergic dysfunction drives postural and locomotor deficits in a mouse model of spinal muscular atrophy.

Cell Rep. 2025-1-28

[6]
Cortical effects of dopamine replacement account for clinical response variability in Parkinson's disease.

medRxiv. 2024-11-23

本文引用的文献

[1]
Neurochemical organization of cortical proteinopathy and neurophysiology along the Alzheimer's disease continuum.

Alzheimers Dement. 2024-9

[2]
The neurophysiological brain-fingerprint of Parkinson's disease.

EBioMedicine. 2024-7

[3]
Alterations of Cortical Structure and Neurophysiology in Parkinson's Disease Are Aligned with Neurochemical Systems.

Ann Neurol. 2024-4

[4]
Adverse and compensatory neurophysiological slowing in Parkinson's disease.

Prog Neurobiol. 2023-12

[5]
Cortex-wide topography of 1/f-exponent in Parkinson's disease.

NPJ Parkinsons Dis. 2023-7-13

[6]
A dataset of multi-contrast unbiased average MRI templates of a Parkinson's disease population.

Data Brief. 2023-4-12

[7]
Slowing of Frontal β Oscillations in Atypical Parkinsonism.

Mov Disord. 2023-5

[8]
Aberrant neurophysiological signaling associated with speech impairments in Parkinson's disease.

NPJ Parkinsons Dis. 2023-4-14

[9]
The aperiodic exponent of subthalamic field potentials reflects excitation/inhibition balance in Parkinsonism.

Elife. 2023-2-22

[10]
Long-Term Recording of Subthalamic Aperiodic Activities and Beta Bursts in Parkinson's Disease.

Mov Disord. 2023-2

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