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Psychedelic concentrations of nitrous oxide reduce functional differentiation in frontoparietal and somatomotor cortical networks.

ABSTRACT: Despite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. We measure the brain's functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns) using human resting-state functional magnetic resonance imaging data acquired before and during administration of 35% nitrous oxide. Both analyses demonstrate that nitrous oxide reduces functional differentiation in frontoparietal and somatomotor networks. Importantly, the subjective psychedelic experience induced by nitrous oxide is inversely correlated with the degree of functional differentiation. Thus, like classical psychedelics acting on serotonin receptors, nitrous oxide flattens the functional geometry of the cortex and disrupts temporal dynamics in association with psychoactive effects.

SUBMITTER: Dai R

PROVIDER: S-EPMC10730842 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Psychedelic concentrations of nitrous oxide reduce functional differentiation in frontoparietal and somatomotor cortical networks.

Dai Rui R Huang Zirui Z Larkin Tony E TE Tarnal Vijay V Picton Paul P Vlisides Phillip E PE Janke Ellen E McKinney Amy A Hudetz Anthony G AG Harris Richard E RE Mashour George A GA

Communications biology 20231219 1

Despite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. We measure the brain's functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns) using human resting-state functional magnetic resonance imaging data acquired before and during administration of 35% nitrous oxide. Both ana ...[more]

PMID: 38114805

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Project description:Parietal networks are hypothesised to play a central role in the cortical information synthesis that supports conscious experience and behavior. Significant reductions in parietal level functional connectivity have been shown to occur during general anesthesia with propofol and a range of other GABAergic general anesthetic agents. Using two analysis approaches (1) a graph theoretic analysis based on surrogate-corrected zero-lag correlations of scalp EEG, and (2) a global coherence analysis based on the EEG cross-spectrum, we reveal that sedation with the NMDA receptor antagonist nitrous oxide (N2O), an agent that has quite different electroencephalographic effects compared to the inductive general anesthetics, also causes significant alterations in parietal level functional networks, as well as changes in full brain and frontal level networks. A total of 20 subjects underwent N2O inhalation at either 20%, 40% or 60% peak N2O/O2 gas concentration levels. N2O-induced reductions in parietal network level functional connectivity (on the order of 50%) were exclusively detected by utilising a surface Laplacian derivation, suggesting that superficial, smaller spatial scale, cortical networks were most affected. In contrast reductions in frontal network functional connectivity were optimally discriminated using a common-reference derivation (reductions on the order of 10%), indicating that the NMDA antagonist N2O induces spatially coherent and widespread perturbations in frontal activity. Our findings not only give important weight to the idea of agent invariant final network changes underlying drug-induced reductions in consciousness, but also provide significant impetus for the application and development of multiscale functional analyses to systematically characterise the network level cortical effects of NMDA receptor related hypofunction. Future work at the source space level will be needed to verify the consistency between cortical network changes seen at the source level and those presented here at the EEG sensor space level.

Project description:BackgroundNeurophysiologic complexity has been shown to decrease during states characterized by a depressed level of consciousness, such as sleep or anesthesia. Conversely, neurophysiologic complexity is increased during exposure to serotonergic psychedelics or subanesthetic doses of dissociative anesthetics. However, the neurochemical substrates underlying changes in neurophysiologic complexity are poorly characterized. Cortical acetylcholine appears to relate to cortical activation and changes in states of consciousness, but the relationship between cortical acetylcholine and complexity has not been formally studied. We addressed this gap by analyzing simultaneous changes in cortical acetylcholine (prefrontal and parietal) and neurophysiologic complexity before, during, and after subanesthetic ketamine (10 mg/kg/h) or 50% nitrous oxide.MethodsUnder isoflurane anesthesia, adult Sprague Dawley rats (n = 24, 12 male and 12 female) were implanted with stainless-steel electrodes across the cortex to record monopolar electroencephalogram (0.5-175 Hz; 30 channels) and guide canulae in prefrontal and parietal cortices for local microdialysis quantification of acetylcholine levels. One subgroup of these rats was instrumented with a chronic catheter in jugular vein for ketamine infusion (n = 12, 6 male and 6 female). The electroencephalographic data were analyzed to determine subanesthetic ketamine or nitrous oxide-induced changes in Lempel-Ziv complexity and directed frontoparietal connectivity. Changes in complexity and connectivity were analyzed for correlation with concurrent changes in prefrontal and parietal acetylcholine.ResultsSubanesthetic ketamine produced sustained increases in normalized Lempel-Ziv complexity (0.5-175 Hz; P < .001) and high gamma frontoparietal connectivity (125-175 Hz; P < .001). This was accompanied by progressive increases in prefrontal (104%; P < .001) and parietal (159%; P < .001) acetylcholine levels that peaked after 50 minutes of infusion. Nitrous oxide induction produced a transient increase in complexity (P < .05) and high gamma connectivity (P < .001), which was accompanied by increases (P < .001) in prefrontal (56%) and parietal (43%) acetylcholine levels. In contrast, the final 50 minutes of nitrous oxide administration were characterized by a decrease in prefrontal (38%; P < .001) and parietal (45%; P < .001) acetylcholine levels, reduced complexity (P < .001), and comparatively weaker frontoparietal high gamma connectivity (P < .001). Cortical acetylcholine and complexity were correlated with both subanesthetic ketamine (prefrontal: cluster-weighted marginal correlation [CW r] [144] = 0.42, P < .001; parietal: CW r[144] = 0.42, P < .001) and nitrous oxide (prefrontal: CW r[156] = 0.46, P < .001; parietal: CW r[156] = 0.56, P < .001) cohorts.ConclusionsThese data bridge changes in cortical acetylcholine with concurrent changes in neurophysiologic complexity, frontoparietal connectivity, and the level of consciousness.

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Psychedelic concentrations of nitrous oxide reduce functional differentiation in frontoparietal and somatomotor cortical networks.

Publications

Psychedelic concentrations of nitrous oxide reduce functional differentiation in frontoparietal and somatomotor cortical networks.

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