Evidence map›Paper›PMID 40866988›Full record

ArticleClinical and translational medicine2025

Molecular architecture of language-related cortical areas revealed by integrative proteomic and connectome analyses.

Jinsong Wu, Zixian Wang, Fengjiao Li, Shuolei Bu, Lianglong Sun, Chen Zheng, Zhixin Bai, Luhao Yang, Fangyuan Gong, Jiali Chen and 21 more

Abstract read
In one paragraph

Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors.

Jinsong WuGlioma Surgery Division, Neurological Surgery Department of Huashan Hospital, Fudan University, Shanghai, China.
Zixian WangMOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences & Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Fengjiao LiDepartment of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Shuolei BuInstitutes of Biomedical Sciences, Fudan University, Shanghai, China.
Lianglong SunState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
Chen ZhengInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
Zhixin BaiDepartment of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Luhao YangGlioma Surgery Division, Neurological Surgery Department of Huashan Hospital, Fudan University, Shanghai, China.
Fangyuan GongGlioma Surgery Division, Neurological Surgery Department of Huashan Hospital, Fudan University, Shanghai, China.
Jiali ChenKey Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, China: Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, China.
Yien HuangKey Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, China: Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, China.
Wanjing LiKey Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, China: Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, China.
Guoquan YanInstitutes of Biomedical Sciences, Fudan University, Shanghai, China.
Weiwei XianDepartment of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Jiaxuan YangHanGene Biotech, Xiaoshan Innovation Polis, Hangzhou, China.
Shuai WuGlioma Surgery Division, Neurological Surgery Department of Huashan Hospital, Fudan University, Shanghai, China.ORCID 0000-0002-2776-1710
Kemin ZhuDepartment of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Wenke FanDepartment of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Qiong LiuDepartment of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Guomin ZhouDepartment of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Gong-Hong WeiMOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences & Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.ORCID 0000-0001-6546-9334
Wensheng LiDepartment of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Jing YanDepartment of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Jingliang ChengDepartment of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Russell G SnellApplied Translational Genetics Group, School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Maurice A CurtisCentre for Brain Research, Auckland University, Auckland, New Zealand.
Tianye JiaInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
Binke YuanKey Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, China: Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, China.
Yong HeState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
Weijiang ZhangInstitutes of Biomedical Sciences, Fudan University, Shanghai, China.
Linya YouDepartment of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.ORCID 0000-0002-2569-0269

Funding

Fudan University #JIF101017Fudan University JIF101047Fudan University SXF101012High-performance Computing Platform of Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical CollegeInnovation Program of Shanghai Municipal Education Commission #2023ZKZD13Major Project of National Social Science Fund 22 &ZD299Medical Science Data Center at Shanghai Medical College of Fudan University and High-performance Computing Platform of Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical CollegeMinistry of Science and Technology (MOST), ChinaNational Key Research and Development Program of China #2022YFC2703600National Key Research and Development Program of China #2022YFC2703604National Key Research and Development Program of China #2024YFF1206904National Natural Science Foundation of China #32100889National Natural Science Foundation of China #81801773National Natural Science Foundation of China #82021004National Natural Science Foundation of China #82070482National Natural Science Foundation of China #82203416National Natural Science Foundation of China #T2122005Science Innovation 2030-Brain Science and Brain-Inspired Intelligence Technology Major Project #2021ZD0201100Science Innovation 2030-Brain Science and Brain-Inspired Intelligence Technology Major Project #2021ZD0201104Shanghai Pujiang Project #18PJ1400900
6 · The paper itself

Abstract

backgroundProtein expression asymmetry between brain hemispheres is hypothesized to influence functional connectivity, yet its role in language-related networks remains poorly understood. Additionally, how such molecular differences relate to brain reorganization in glioma requires further exploration.

methodsWe performed label-free tandem mass spectrometry on 13 left-hemispheric language-related Brodmann areas (BAs) and their right-hemispheric counterparts from 10 donor brains, identifying protein signatures across 6 language-related functional modules. We then compared these proteomic profiles with resting-state structural and functional connectivity data from 26 BAs across 90 subjects from the Human Connectome Project (HCP). Finally, we examined functional compensation in 13 glioma patients with tumors in Wernicke's area, correlating gray matter volume in contralateral homologs with linguistic performance.

resultsProtein expression heterogeneity was greater within hemispheres than between homologous contralateral BAs. Hierarchical clustering revealed interactions between core language areas (Broca's, Wernicke's, Geschwind's) and auditory/motor regions. Functional connectivity strength correlated with protein expression similarity, particularly in symmetric BA4 (primary motor cortex). Excitatory/inhibitory (E/I) neuronal markers (GRIA1/GRIA4) showed a left-positive, right-negative correlation with connectivity, suggesting hemispheric differences in synaptic regulation. Glioma patients exhibited right-hemispheric compensation, with gray matter volume in Wernicke's homolog correlating with linguistic function.

conclusionOur findings support the hypothesis of a homophilic mixing effect between protein expression similarity and connectome architecture, and help explain brain rearrangement in glioma patients. KEY POINTS: Protein expression differs more within hemispheres than across homologous regions, with distinct signatures in language-related brain areas. Functional connectivity strength correlates with protein expression similarity, showing left-right asymmetry in excitatory/inhibitory synaptic regulation (GRIA1/GRIA4). Right-hemispheric homologs compensate for left-hemispheric language-area damage in glioma patients, linking molecular profiles to functional reorganization.

Indexed as

Cerebral CortexConnectomeLanguageProteomicsAdultFemaleGliomaHumansMaleMiddle Agedbilateralbrain reorganisationBrodmann areaconnectomehuman postmortem brainlanguageproteomics

Identifiers

PMID40866988
PMCPMC12390769

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.