Vagus nerve stimulation: mechanisms and factors involved in memory enhancement

Abstract

Vagus nerve stimulation (VNS) has been recognized as a useful neuromodulation tool to target the central nervous system by electrical stimulation of peripheral nerves. Activation of the nucleus of the solitary tract (NTS) in the brainstem by vagal afferent nerve fibers allows for modulation of various higher order brain regions, including limbic and cerebral cortex structures. Along with neurological and psychiatric indications, clinical and preclinical studies suggest that VNS can improve memory. While the underlying mechanisms to improve memory with VNS involve brain areas, such as the prefrontal cortex and processes including alertness and arousal, here we focus on VNS-induced memory improvements related to the hippocampus, the main area implicated in memory acquisition. In addition, we detail research demonstrating that a targeted approach to VNS can modify memory outcomes and delve into the molecular mechanisms associated with these changes. These findings indicate that a greater understanding of VNS mechanisms while also considering stimulation parameters, administration site, timing in relation to training, and sex-specific factors, may allow for optimal VNS application to enhance memory.

Longitudinal EpiTrack assessment of executive functions following vagus nerve stimulation therapy in patients with drug‐resistant epilepsy

“…There is increasing data to support the direct neurobiological effects of VNS on cognition‐related brain functions. 12 , 24 VNS affects excitability in cognition‐associated pathways by altering brain neurotransmitters, such as gamma‐aminobutyric acid and glutamate as well as the neuromodulators serotonin, dopamine, and norepinephrine. 25 , 26 Activation of the nucleus of the solitary tract in the brainstem by vagal afferent nerve fibers allows for modulation of various higher‐order brain regions, e.g.…”

The gut-brain vagal axis scales hippocampal memory processes and plasticity

“…The vagus nerve has recently been pointed as a contributor of learning and memory processes (Olsen et al, 2023). By taking advantage of the subdiaphragmatic vagotomy model (SDV), here we investigated whether the gut-brain vagal axis plays a permissive role in shaping learning and memory events, notably recognition memories which strongly rely on the hippocampus formation (Broadbent et al, 2004; Gálvez-Márquez et al, 2022).…”

Transcutaneous vagus nerve stimulation: a new strategy for Alzheimer’s disease intervention through the brain-gut-microbiota axis?

“…The VN transmits signals through four nuclei in the CNS, namely the nucleus tractus solitarius (NTS), the spinal trigeminal nucleus, the solitary nucleus and the dorsomedial nucleus (DMN; Berthoud and Neuhuber, 2000 ). Notably, the NTS is closely associated with brain regions associated with neurodegenerative diseases, such as the blue patch and the hippocampus ( Olsen et al, 2023 ) and is believed to influence cognitive functions ( Humphrey et al, 2023 ). Therefore, the central connectivity of the VN with brain regions such as the hippocampus provides a neuronal basis for pathophysiological processes linking gut and brain as caused by AD.…”