Persistent Brain Connectivity Changes in Healthy Volunteers Following Nitrous Oxide Inhalation.
Ben Julian A Palanca, Charles R Conway, Thomas Zeffiro, Britt M Gott, Thomas Nguyen, Alvin Janski, Nisha Jain, Helga Komen, Broc A Burke, Charles F Zorumski, Peter Nagele
Biological Psychiatry Global Open Science October 1, 2023 DOI: 10.1016/j.bpsgos.2023.01.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind crossover study Randomized Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Healthy volunteers |
| Intervention | Nitrous oxide |
| Dose | 50% nitrous oxide/oxygen |
| Duration | 1-hour inhalation, with scans at 2 and 24 hours postinhalation |
| Topics | Depression Ketamine |
| Keywords | Functional connectivity Nmda receptor Nitrous oxide |
| Key points | Nitrous oxide inhalation produced persistent increases in global connectivity between regions of primary visual cortex and dorsal attention network for at least 24 hours. |
Abstract
Nitrous oxide holds promise in the treatment of major depressive disorder. Its psychotropic effects and NMDA receptor antagonism have led to comparisons with ketamine. Despite longstanding use, persistent effects of nitrous oxide on the brain have not been characterized. Sixteen healthy volunteers were recruited in a double-blind crossover study. In randomized order, individuals underwent a 1-hour inhalation of either 50% nitrous oxide/oxygen or air/oxygen mixtures. At least two 7.5-minute echo-planar resting-state functional magnetic resonance imaging scans were obtained before and at 2 and 24 hours after each inhalation (average 130 min/participant). Using the time series of preprocessed, motion artifact-scrubbed, and nuisance covariate-regressed imaging data, interregional signal correlations were measured and converted to T scores. Hierarchical clustering and linear mixed-effects models were employed. Nitrous oxide inhalation produced changes in global brain connectivity that persisted in the occipital cortex at 2 and 24 hours postinhalation (p < .05, false discovery rate-corrected). Analysis of resting-state networks demonstrated robust strengthening of connectivity between regions of the visual network and those of the dorsal attention network, across 2 and 24 hours after inhalation (p < .05, false discovery rate-corrected). Weaker changes in connectivity were found between the visual cortex and regions of the frontoparietal and default mode networks. Parallel analyses following air/oxygen inhalation yielded no significant changes in functional connectivity. Nitrous oxide inhalation in healthy volunteers revealed persistent increases in global connectivity between regions of primary visual cortex and dorsal attention network. These findings suggest that nitrous oxide inhalation induces neurophysiological cortical changes that persist for at least 24 hours.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.