Multilayer brain network analysis in mice reveals ketamine-induced reorganization of brain- wide fluctuations and gut-brain axis
Communications Biology July 3, 2026 Fengkai He, Xiaojun Xu, Y Y Zhu et al.
Depression involves disrupted communication across brain circuits, and ketamine can rapidly alleviate depressive symptoms. A new analytical framework, the frequency-varying multilayer brain functional network (FMBFN), was developed to examine how brain regions coordinate activity both within and across different frequency bands. Using local field potential recordings from eight brain regions in male mice subjected to chronic social defeat stress (a model of depression), the framework revealed that stress led to frequency-specific hyperconnectivity and altered network integration during social interaction. Ketamine reversed social avoidance and reorganized the multilayer network topology, with the lateral habenula showing a response pattern opposite to other regions. Exploratory analysis also linked ketamine-associated gut microbial changes to global network topology, suggesting possible gut-brain associations.