Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jul 8:19:1595737.
doi: 10.3389/fnhum.2025.1595737. eCollection 2025.

A vagal route to memory: evidence from invasive and non-invasive electrical vagus nerve stimulation studies and areas for future clinical application

Christoph Szeska  1 , Carlos Ventura-Bort  1 , Manon Giraudier  1 , Mathias Weymar  1   2
Affiliations
Review

A vagal route to memory: evidence from invasive and non-invasive electrical vagus nerve stimulation studies and areas for future clinical application

Christoph Szeska et al. Front Hum Neurosci. .

Abstract

The ability to remember emotionally significant stimuli and stimulus associations is critical to survival, as it ensures that rewarding and threatening events can be recalled to guide future behavior. Consequently, events are consolidated more strongly into long-term memory as they are encoded under heightened emotional arousal. Such memory prioritization is partly driven by the release of peripheral adrenaline, which acts as a bodily signal emphasizing an event's emotional significance and enhances plasticity in the brain. Animal research suggest that the vagus nerve translates elevated peripheral adrenaline into central noradrenergic activation of memory-relevant brain areas via its projections to the brainstem locus coeruleus-the main source of noradrenaline in the brain. The possibility of vagus nerve stimulation (VNS), both invasively (iVNS) and non-invasively (i.e., transcutaneously; tVNS), has opened up new avenues to test a potential vagal route to memory in humans whilst circumventing the necessity of actual peripheral adrenergic release. Here, we briefly review recent research applying iVNS and tVNS in a variety of animal and human emotional episodic memory and Pavlovian conditioning and extinction learning experiments, supporting a critical role of the vagus nerve in modulating emotional memories. Based on this body of evidence, we highlight clinical areas where VNS may therefore serve as an adjunct to treatments for neurocognitive, anxiety- and trauma-related disorders, that aim at improving learning and memory consolidation. In fact, a brief review of (sub-) clinical studies shows that VNS alleviates symptoms in mild cognitive impairment, Alzheimer's disease as well as anxiety- and trauma-related disorders.

Keywords: Alzheimer’s disease; PTSD - Posttraumatic stress disorder; anxiety disorders; associative memory; emotional memory; fear extinction; mild cognitive impairment - MCI; vagus nerve stimulation.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

“Diagram illustrating the vagal afferent brain-body axis guiding emotional memory. It shows a pathway, by which emotional events, like encountering a threat (e.g., snake or gun), which trigger attentive processing, lead to activation of the adrenal glands releasing adrenaline and glucocorticoids. Peripheral vagal afferent fibers transmit this signal to the Amygdala (AMY), medial prefrontal cortex (mPFC), hippocampus (HIPP), locus coeruleus (LC), and nucleus of the solitary tract (NTS) in the brain. The auricular branch of the vagus nerve is shown linked to TAVNS stimulated via the ear.”
FIGURE 1
Schematic representation of interacting neural systems presumed to drive arousal-based memory enhancement, involving the adrenal glands, vagal afferent fibers and multiple brain regions, including the nucleus of the solitary tract (NTS), locus coeruleus (LC), amygdala (AMY), hippocampus (HIPP) and medial prefrontal cortex (mPFC). TAVNS, transcutaneous auricular vagus nerve stimulation.
Diagram showing potential clinical applications of episodic and associative memory enhancement using transcutaneous auricular vagus nerve stimulation (TAVNS). Applications include mild cognitive impairment, Alzheimer’s disease, trauma-related disorders, and anxiety disorders. The lower section illustrates the brain's regions impacted by TAVNS, connected by the auricular branch of the vagus nerve to stimulate specific areas.
FIGURE 2
Non-exhaustive overview of potential clinical areas where treatment might benefit from vagus nerve stimulation.
See this image and copyright information in PMC

References

    1. Abercrombie H. C., Kalin N. H., Thurow M. E., Rosenkranz M. A., Davidson R. J. (2003). Cortisol variation in humans affects memory for emotionally laden and neutral information. Behav. Neurosci. 117 505–516. 10.1037/0735-7044.117.3.505 - DOI - PubMed
    1. Adolphs R., Cahill L., Schul R., Babinsky R. (1997). Impaired declarative memory for emotional material following bilateral amygdala damage in humans. Learn. Mem. 4 291–300. 10.1101/lm.4.3.291 - DOI - PubMed
    1. Alvarez-Dieppa A. C., Griffin K., Cavalier S., Mcintyre C. K. (2016). Vagus nerve stimulation enhances extinction of conditioned fear in rats and modulates arc protein, CaMKII, and GluN2B-Containing NMDA receptors in the basolateral amygdala. Neural Plast. 2016:4273280. 10.1155/2016/4273280 - DOI - PMC - PubMed
    1. American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders. Washington, D.C: American Psychiatric Association. 10.1176/appi.books.9780890425596 - DOI
    1. Ben-Menachem E., Hamberger A., Hedner T., Hammond E. J., Uthman B. M., Slater J., et al. (1995). Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Res. 20 221–227. 10.1016/0920-1211(94)00083-9 - DOI - PubMed

LinkOut - more resources