The vagus nerve drives cognitive function through the default mode network
Musashi Yamakawa, 博之 吉留, Haruki Kawagoe, Shiratori Reina, Fumiya Fukushima, Takuya Urushihata, Ziyan Xie, Tasuku Kayama, Goro Ikeda, Wenfeng Xue, Tuo Xiaoying, Shinpei Kawaoka, Wang Hongbo, Motoko Maekawa, Yuji Owada, Kaoru Seiriki, Hitoshi Hashimoto, Ayumu Konno, Hirokazu Hirai, Yousuke Tsuneoka, Akiko Satoh, Hiroyuki Igarashi, Yusaku Iwasaki, Nariko Arimura, Nahoko Kuga, Takuya Sasaki
bioRxiv (Cold Spring Harbor Laboratory) October 15, 2026 preprint DOI: 10.64898/2026.10.08.757463 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study (mouse, brain-wide spatiotemporal neuronal activity analyses with selective activation/silencing manipulations) |
|---|---|
| Population | Mice |
| Intervention | Vagus nerve stimulation |
| Topics | Default mode network |
| Key points | Vagus nerve stimulation activated default mode network (DMN) neuronal ensembles across the mouse brain, an association mediated by locus coeruleus subpopulations, whereas vagal-independent mechanisms mainly affected the salience network. Activating vagal-responsive DMN ensembles reproduced VNS-induced gains in cognitive and progressive problem-solving behaviors, and silencing them abolished those gains. The authors propose this as a framework linking vagal signaling to cognition via the DMN. |
Abstract
The afferent vagus nerve transmits interoceptive signals to the brain but a systematic understanding of how vagal signals affect brain-wide neuronal dynamics remains elusive. Here, comprehensive spatiotemporal analyses across the entire mouse brain revealed that vagus nerve stimulation activated neuronal ensembles within the default mode network (DMN). In contrast, vagal-independent mechanisms predominantly affected the salience network. The vagal-DMN association was mediated by locus coeruleus neuronal subpopulations. Selective activation or silencing of vagal-responsive DMN neuronal ensembles replicated or abolished VNS-induced enhancement of cognitive behaviors and progressive problem-solving behaviors. These findings establish a unifying framework for how the vagus nerve drives cognitive functions by engaging the DMN.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Vagus nerve stimulation activated DMN neuronal ensembles via locus coeruleus subpopulations, and activating or silencing these ensembles replicated or abolished VNS-induced cognitive enhancement.
Synthesized
Comparable studies
Other preclinical and animal studies on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rat brains also have a default mode network Rats | 2012 | Observational study | |
| Large-scale topology and the default mode network in the mouse connectome Mouse brain | 2014 | Observational study | |
| Hippocampal Sharp-Wave Ripples Influence Selective Activation of the Default Mode Network Anesthetized monkeys | 2016 | Observational study | |
| Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats Healthy rats and a rat model of alcohol relapse | 2023 | Randomized, placebo-controlled crossover pharmaco-fMRI study | |
| Altered functional connectivity within the default mode network in two animal models with opposing episodic memories Rats (control, LPS-challenged, and footshock-exposed groups) | 2018 | Animal model study |