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PERSPECTIVE article
Front. Neural Circuits
Volume 19 - 2025 | doi: 10.3389/fncir.2025.1568655
This article is part of the Research Topic Neuro-inspired computation View all 4 articles
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Vagus nerve stimulation (VNS) has emerged as a promising therapeutic intervention across various neurological and psychiatric conditions, including epilepsy, depression, and stroke rehabilitation; however, its mechanisms of action on neural circuits remain incompletely understood. Here, we present a novel theoretical framework based on predictive coding that conceptualizes VNS effects through differential modulation of feedforward and feedback neural circuits. Based on recent evidence, we propose that VNS shifts the balance between feedforward and feedback processing through multiple neuromodulatory systems, resulting in enhanced feedforward signal transmission. This framework integrates anatomical pathways, receptor distributions, and physiological responses to explain the influence of the VNS on neural dynamics across different spatial and temporal scales. Vagus nerve stimulation may facilitate neural plasticity and adaptive behavior through acetylcholine and noradrenaline (norepinephrine), which differentially modulate feedforward and feedback signaling. This mechanistic understanding serves as a basis for interpreting the cognitive and therapeutic outcomes across different clinical conditions. Our perspective provides a unified theoretical framework for understanding circuitspecific VNS effects and suggests new directions for investigating their therapeutic mechanisms.
Keywords: Vagus Nerve Stimulation, Acetylcholine, noradrenaline, plasticity, Cognitive Function, Epilepsy, Depression, stroke rehabilitation
Received: 30 Jan 2025; Accepted: 31 Mar 2025.
Copyright: © 2025 Kumagai, Shiramatsu, Kawai and Takahashi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hirokazu Takahashi, The University of Tokyo, Bunkyo, Japan
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