Aberrant functional connectome gradient and its neurotransmitter basis in Parkinson's disease
Patients with Parkinson's disease (PD) exhibit heterogenous clinical deficits not only in motor function, other deficits in both sensory and higher-order cognitive processing are also involved. Connectome studies have suggested a primary-to-transmodal gradient and a primary-to-primary gradient...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125000373 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832573255958921216 |
|---|---|
| author | Tao Guo Cheng Zhou Jiaqi Wen Jingjing Wu Yaping Yan Jianmei Qin Min Xuan Haoting Wu Chenqing Wu Jingwen Chen Sijia Tan Xiaojie Duanmu Baorong Zhang Xiaojun Xu Minming Zhang Xiaojun Guan |
| author_facet | Tao Guo Cheng Zhou Jiaqi Wen Jingjing Wu Yaping Yan Jianmei Qin Min Xuan Haoting Wu Chenqing Wu Jingwen Chen Sijia Tan Xiaojie Duanmu Baorong Zhang Xiaojun Xu Minming Zhang Xiaojun Guan |
| author_sort | Tao Guo |
| collection | DOAJ |
| description | Patients with Parkinson's disease (PD) exhibit heterogenous clinical deficits not only in motor function, other deficits in both sensory and higher-order cognitive processing are also involved. Connectome studies have suggested a primary-to-transmodal gradient and a primary-to-primary gradient in functional brain networks, supporting the spectrum from sensation to cognition. However, whether these gradients are altered in PD patients and how these alterations associate with neurotransmitter profiles remain unknown. By constructing functional network and calculating its gradient in 134 PD patients and 172 normal controls, we compared functional connectivity gradients between groups and performed spearman correlation to explore the association between neurotransmitter expression and functional network gradient-based alternations in PD. Decreased first gradients were detected mainly in association cortex, including frontal cortex, insula, cingulate, and parietal cortex, corresponding to the decrement of frontoparietal/ventral attention network observed in network-level analyses. Decreased second gradients were observed in primary motor and somatosensory cortex, meeting the decrement of somatomotor network at the network level. Besides, network-level comparisons revealed the increment of visual network in the first gradient and increment of ventral attention network in the second gradient. Transcription-neuroimaging association analyses showed that changes of the first gradient were mainly negatively correlated with nondopaminergic system, while alterations of the second gradient were positively correlated with both dopaminergic and nondopaminergic systems. These results highlight the connectome gradient dysfunction in PD and its linkage with neurotransmitter expression profiles, providing insight into the molecular mechanisms for functional alterations underlying PD. |
| format | Article |
| id | doaj-art-ebc59a03f12e4c03aa416b4d1f7e5ff7 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-ebc59a03f12e4c03aa416b4d1f7e5ff72025-02-02T05:26:49ZengElsevierNeurobiology of Disease1095-953X2025-03-01206106821Aberrant functional connectome gradient and its neurotransmitter basis in Parkinson's diseaseTao Guo0Cheng Zhou1Jiaqi Wen2Jingjing Wu3Yaping Yan4Jianmei Qin5Min Xuan6Haoting Wu7Chenqing Wu8Jingwen Chen9Sijia Tan10Xiaojie Duanmu11Baorong Zhang12Xiaojun Xu13Minming Zhang14Xiaojun Guan15Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Corresponding author at: Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou 310009, China.Patients with Parkinson's disease (PD) exhibit heterogenous clinical deficits not only in motor function, other deficits in both sensory and higher-order cognitive processing are also involved. Connectome studies have suggested a primary-to-transmodal gradient and a primary-to-primary gradient in functional brain networks, supporting the spectrum from sensation to cognition. However, whether these gradients are altered in PD patients and how these alterations associate with neurotransmitter profiles remain unknown. By constructing functional network and calculating its gradient in 134 PD patients and 172 normal controls, we compared functional connectivity gradients between groups and performed spearman correlation to explore the association between neurotransmitter expression and functional network gradient-based alternations in PD. Decreased first gradients were detected mainly in association cortex, including frontal cortex, insula, cingulate, and parietal cortex, corresponding to the decrement of frontoparietal/ventral attention network observed in network-level analyses. Decreased second gradients were observed in primary motor and somatosensory cortex, meeting the decrement of somatomotor network at the network level. Besides, network-level comparisons revealed the increment of visual network in the first gradient and increment of ventral attention network in the second gradient. Transcription-neuroimaging association analyses showed that changes of the first gradient were mainly negatively correlated with nondopaminergic system, while alterations of the second gradient were positively correlated with both dopaminergic and nondopaminergic systems. These results highlight the connectome gradient dysfunction in PD and its linkage with neurotransmitter expression profiles, providing insight into the molecular mechanisms for functional alterations underlying PD.http://www.sciencedirect.com/science/article/pii/S0969996125000373Parkinson's diseaseMagnetic resonance imagingConnectomeGradientNeurotransmitter |
| spellingShingle | Tao Guo Cheng Zhou Jiaqi Wen Jingjing Wu Yaping Yan Jianmei Qin Min Xuan Haoting Wu Chenqing Wu Jingwen Chen Sijia Tan Xiaojie Duanmu Baorong Zhang Xiaojun Xu Minming Zhang Xiaojun Guan Aberrant functional connectome gradient and its neurotransmitter basis in Parkinson's disease Neurobiology of Disease Parkinson's disease Magnetic resonance imaging Connectome Gradient Neurotransmitter |
| title | Aberrant functional connectome gradient and its neurotransmitter basis in Parkinson's disease |
| title_full | Aberrant functional connectome gradient and its neurotransmitter basis in Parkinson's disease |
| title_fullStr | Aberrant functional connectome gradient and its neurotransmitter basis in Parkinson's disease |
| title_full_unstemmed | Aberrant functional connectome gradient and its neurotransmitter basis in Parkinson's disease |
| title_short | Aberrant functional connectome gradient and its neurotransmitter basis in Parkinson's disease |
| title_sort | aberrant functional connectome gradient and its neurotransmitter basis in parkinson s disease |
| topic | Parkinson's disease Magnetic resonance imaging Connectome Gradient Neurotransmitter |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125000373 |
| work_keys_str_mv | AT taoguo aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT chengzhou aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT jiaqiwen aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT jingjingwu aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT yapingyan aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT jianmeiqin aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT minxuan aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT haotingwu aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT chenqingwu aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT jingwenchen aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT sijiatan aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT xiaojieduanmu aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT baorongzhang aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT xiaojunxu aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT minmingzhang aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease AT xiaojunguan aberrantfunctionalconnectomegradientanditsneurotransmitterbasisinparkinsonsdisease |