Acute effects of nitrous oxide on visual processing: a connectome study in healthy adults

Nitrous oxide (N₂O) produces perceptual alterations and changes in large-scale brain network organization, yet its effects on task-specific visual processing remain unclear. Given the prominence of visual alterations during psychedelic exposure, we investigated how subanesthetic N₂O modulates functional connectivity during visual stimulation.

Thirteen healthy adults completed a placebo-controlled, crossover fMRI study acquired before and during subanesthetic N₂O administration (35% in oxygen). Participants viewed a flashing annulus checkerboard and rated evoked subjective visual intensity and unpleasantness. Task-modulated connectivity was assessed using generalized psychophysiological interaction (gPPI) analyses, alongside graph-theoretical measures of modularity and hierarchical clustering to characterize multiscale network organization.

gPPI analyses revealed that increased unpleasantness under N₂O was associated with reduced connectivity between the right anterior insula (rAI) and clusters in the anterior cingulate cortex (ACC) and right lateral occipital cortex (LOC). Network-level analyses showed redistribution of sensorimotor connectivity toward salience and associative networks, accompanied by reduced modularity and a collapse of hierarchical network organization during visual stimulation under N₂O.

These findings suggest that visual processing under N₂O is associated with altered salience attribution and increased cross-network communication. Decoupling of rAI from ACC and LOC implicates a mechanism by which affective appraisal of sensory input is modulated, while reduced modularity and hierarchical differentiation indicate diminished stability of canonical functional networks. Together, these preliminary findings indicate that altered visual experience under N₂O arises from large-scale network reconfiguration and disrupted salience integration rather than changes in early sensory processing.