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

Methods 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. Results 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 N ₂ O. Discussion 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.