Multilayer brain network analysis in mice reveals ketamine-induced reorganization of brain- wide fluctuations and gut-brain axis
7 affiliations
- 1School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, China
- 2Bioland Laboratory, Guangzhou, China
- 3School of Medical Imaging, Tianjin Medical University, Tianjin, China
- 4Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China
- 5Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- 6School of Basic Medicine, Tianjin Medical University, Tianjin, China
- 7Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, China
Abstract
Depression involves dysregulation across distributed cortico-limbic circuits, and ketamine is notable for its rapid antidepressant effects. Although depression and ketamine treatment have been linked to altered brain network topology, how within-frequency and cross-frequency coupling are jointly reorganized at the brain-wide level remains unclear. Here, we developed a frequency-varying multilayer brain functional network (FMBFN) framework to analyze local field potential recordings from eight brain regions in male C57BL/6 mice. This framework integrates within- and cross-frequency coupling and extracts multi-scale network features to characterize brain network structure. Applying this approach in the chronic social defeat stress (CSDS) model, we found that CSDS was associated with frequency-specific hyperconnectivity and selective alterations in network integration during social interaction. Ketamine reversed social avoidance and induced the distinct reorganization of multilayer network topology, including region-specific nodal changes. Notably, the lateral habenula showed the response pattern opposite to that of the other recorded regions. As an exploratory cross-modal extension, we further examined gut microbial features and found that specific ketamine-associated microbial changes were linked to global network topology, suggesting candidate gut-brain association patterns. Together, these findings establish the FMBFN framework as a systems-level tool for characterizing brain-wide neural dynamics in psychiatric disorders and for linking network-level alterations to biological contexts.
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BibTeX
@article{he2026multilayer,
title = {{Multilayer brain network analysis in mice reveals ketamine-induced reorganization of brain- wide fluctuations and gut-brain axis}},
author = {Fengkai He and Xiaojun Xu and Yuqi Zhu and Jiahui Lu and Jie Liu and Dongyong Guo and Aili Liu and Wenwen Bai and Xuyuan Zheng and Baolin Guo and Tiaotiao Liu},
journal = {Communications Biology},
year = {2026},
month = jul,
doi = {10.1038/s42003-026-10606-0},
url = {https://doi.org/10.1038/s42003-026-10606-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multilayer brain network analysis in mice reveals ketamine-induced reorganization of brain- wide fluctuations and gut-brain axis
AU - Fengkai He
AU - Xiaojun Xu
AU - Yuqi Zhu
AU - Jiahui Lu
AU - Jie Liu
AU - Dongyong Guo
AU - Aili Liu
AU - Wenwen Bai
AU - Xuyuan Zheng
AU - Baolin Guo
AU - Tiaotiao Liu
PY - 2026
DA - 2026/07/03
JO - Communications Biology
DO - 10.1038/s42003-026-10606-0
UR - https://doi.org/10.1038/s42003-026-10606-0
AB - Depression involves dysregulation across distributed cortico-limbic circuits, and ketamine is notable for its rapid antidepressant effects. Although depression and ketamine treatment have been linked to altered brain network topology, how within-frequency and cross-frequency coupling are jointly reorganized at the brain-wide level remains unclear. Here, we developed a frequency-varying multilayer brain functional network (FMBFN) framework to analyze local field potential recordings from eight brain regions in male C57BL/6 mice. This framework integrates within- and cross-frequency coupling and extracts multi-scale network features to characterize brain network structure. Applying this approach in the chronic social defeat stress (CSDS) model, we found that CSDS was associated with frequency-specific hyperconnectivity and selective alterations in network integration during social interaction. Ketamine reversed social avoidance and induced the distinct reorganization of multilayer network topology, including region-specific nodal changes. Notably, the lateral habenula showed the response pattern opposite to that of the other recorded regions. As an exploratory cross-modal extension, we further examined gut microbial features and found that specific ketamine-associated microbial changes were linked to global network topology, suggesting candidate gut-brain association patterns. Together, these findings establish the FMBFN framework as a systems-level tool for characterizing brain-wide neural dynamics in psychiatric disorders and for linking network-level alterations to biological contexts.
SN - 2399-3642
ER -