Vagus nerve stimulation as a modulator of feedforward and feedback neural transmission

TL;DR

This paper proposes a theoretical framework based on predictive coding to understand how vagus nerve stimulation modulates neural circuits, enhancing feedforward transmission and influencing plasticity and behavior across clinical conditions.

Contribution

It introduces a novel predictive coding-based model explaining VNS effects on neural circuits, integrating anatomical, physiological, and neuromodulatory data.

Findings

VNS shifts the balance between feedforward and feedback processing.

VNS enhances feedforward signal transmission.

VNS influences neural plasticity through neuromodulators.

Abstract

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. VNS 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 circuit-specific VNS effects and suggests new directions for investigating their therapeutic mechanisms.