Why the study?
Vagus nerve stimulation is a promising therapeutic intervention across neurological and psychiatric conditions, but its mechanisms of action on neural circuits remain incompletely understood.
This perspective proposes that vagus nerve stimulation acts as a predictive coding modulator by enhancing feedforward over feedback neural transmission, facilitating neural plasticity.
Offers predictive coding framework for VNS; hypothesis-generating and requires empirical validation before clinical use.
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 circuit-specific VNS effects and suggests new directions for investigating their therapeutic mechanisms.
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Kumagai et al. (2025) studied this question.
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