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Brain overlapping system-level architecture influenced by external magnetic stimulation and internal gene expression in AD-spectrum patients

Molecular Psychiatry volume 30, pages 4110–4121 (2025) Cite this article

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Abstract

The brain overlapping system-level architecture is associated with functional information integration in the multiple roles of the same region, and it has been developed as an underlying novel biomarker of brain disease and may characterise the indicators for the treatment of Alzheimer’s disease (AD). However, it remains uncertain whether these changes are influenced by external magnetic stimulation and internal gene expression. A total of 73 AD-spectrum patients (52 with true stimulation and 21 with sham stimulation) were underwent four-week neuronavigated transcranial magnetic stimulation (rTMS). Shannon-entropy diversity coefficient analysis was used to explore the brain overlapping system of the neuroimaging data in these pre- and posttreatment patients. Transcription-neuroimaging association analysis was further performed via gene expression data from the Allen Human Brain Atlas. Compared with the rTMS_sham stimulation group, the rTMS_true stimulation group achieved the goal of cognitive improvement through the reconstruction of functional information integration in the multiple roles of 27 regions associated with the brain overlapping system, involving the attentional network, sensorimotor network, default mode network and limbic network. Furthermore, these overlapping regions were closely linked to gene expression on cellular homeostasis and immune inflammation, and support vector regression analysis revealed that the baseline diversity coefficients of the attentional and sensorimotor networks can effectively predict memory improvement after rTMS treatment. These findings highlight the brain overlapping system associated with cognitive improvement, and provide the first evidence that external magnetic stimulation and internal gene expression could influence these overlapping regions in AD-spectrum patients.

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Fig. 1: Study design and analysis pipeline schematic overview.
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Fig. 2: Schematic diagram of the brain networks.
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Fig. 3: Differences in the distribution of the Shannon-entropy diversity coefficient in 27 differential brain overlapping regions after four weeks of neuronavigated rTMS intervention (Bonferroni corrected, P < 0.05).
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Fig. 4
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Fig. 5: Functional enrichment of the differential brain overlapping system-related genes.
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Fig. 6: Specific expression of the differential brain overlapping system-related genes.
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Fig. 7: The differential brain overlapping system-related genes were used to construct the PPI network.
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Data availability

Data supporting the findings of this study are available from the corresponding author upon request. The data are not publicly available because they contain information that could compromise the privacy of the research participants.

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Acknowledgements

This study was supported partly by grants from the National Natural Science Foundation of China (No. 82371437), the Key Research and Development Program of Jiangsu Province (No. BE2023674), and Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (No. 2022-LCYG-MS-05).

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Authors and Affiliations

  1. Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China

    Weina Yao & JunJian Zhang

  2. Geriatric Medicine Center, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210046, China

    Weina Yao & Feng Bai

  3. Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China

    Weina Yao, Xinle Hou, Wenao Zheng, Xian Shi & Feng Bai

  4. Institute of Geriatric Medicine, Medical School of Nanjing University, Nanjing, 210046, China

    Weina Yao & Feng Bai

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  1. Weina Yao
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  3. Wenao Zheng
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  4. Xian Shi
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Contributions

WY and FB contributed to the conception and design of the study. WY, XH and WZ performed the analyses, obtained the findings and provided guidance on the interpretation of the results. WY, XH, WZ and XS were involved in the collection of the data. WY, FB and JZ wrote the manuscript and supervised the study.

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Correspondence to JunJian Zhang or Feng Bai.

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The study protocol was approved by the Ethics Committee of Drum Tower Hospital of Nanjing University. All participants submitted their written informed consent to participate before the recruitment.

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Yao, W., Hou, X., Zheng, W. et al. Brain overlapping system-level architecture influenced by external magnetic stimulation and internal gene expression in AD-spectrum patients. Mol Psychiatry 30, 4110–4121 (2025). https://doi.org/10.1038/s41380-025-02991-5

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