Subanesthetic nitrous oxide alters large-scale network organization and insula connectivity during visual stimulation

Abstract

Pharmacological agents that alter consciousness, including classic psychedelics and non-classic agents such as nitrous oxide, are known to affect multiple domains of conscious experience, including visual perception. While most neuroimaging studies rely on resting-state data to characterize altered states of consciousness, task-based approaches enable investigation of specific perceptual domains. Here, we examine the visual domain using task-based functional magnetic resonance imaging in healthy adults before and during administration of subanesthetic nitrous oxide (35% in oxygen). Participants viewed a flashing annulus checkerboard and rated its sensory attributes, including perceived intensity and unpleasantness. Functional connectivity and large-scale network analyses show that nitrous oxide reduces network modularity and disrupts the hierarchical organization of large-scale brain networks, with the strongest effects in higher-order integrative systems and relative preservation of visual networks. Reduced coupling between the anterior insula and anterior cingulate and lateral occipital cortices is associated with greater subjective unpleasantness. These findings indicate that altered visual experience under nitrous oxide reflects reorganization of large-scale integrative brain networks and disrupted salience integration rather than changes within visual networks themselves. Subanesthetic nitrous oxide alters large-scale brain networks during visual stimulation, reducing modularity, disrupting hierarchical organization, decoupling the insula from the cingulate and occipital cortices; this decoupling was linked to subjective unpleasantness.