Characterising the anxiogenic network from functional connectivity analysis of the CO2 challenge model

Abstract The CO2 challenge model (CCM) is a gas inhalation paradigm that provides precisely controlled anxiety induction in experimental settings. Despite its potential as an experimental model of anxiety, our understanding of the neural effects of the CCM is incomplete. This study employs resting-s...

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Main Authors: Daniel Graham, Santra Mathew, Jonathan Marsden, Alastair D. Smith, Gary Smerdon, Stephen D. Hall
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-80901-5
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author Daniel Graham
Santra Mathew
Jonathan Marsden
Alastair D. Smith
Gary Smerdon
Stephen D. Hall
author_facet Daniel Graham
Santra Mathew
Jonathan Marsden
Alastair D. Smith
Gary Smerdon
Stephen D. Hall
author_sort Daniel Graham
collection DOAJ
description Abstract The CO2 challenge model (CCM) is a gas inhalation paradigm that provides precisely controlled anxiety induction in experimental settings. Despite its potential as an experimental model of anxiety, our understanding of the neural effects of the CCM is incomplete. This study employs resting-state functional magnetic resonance imaging (rs-fMRI) to explore functional connectivity (FC) changes underlying the CCM. Following a preliminary CO2 tolerance assessment, participants completed an MRI session that included three rs-fMRI scans: during inhalation of control air (pre and post), and during a 6% CCM exposure. Here, we confirm that 6% CCM is a tolerable anxiogenic model in the MRI setting. We demonstrate that a transient CCM-induced increase in subjective anxiety is associated with an increase in FC within limbic and anxiety-related regions, with the insula emerging as a central node in this altered connectivity pattern. Further analysis revealed a significant correlation between the levels of subjective anxiety and enhanced FC between the brainstem and medial frontal cortex, highlighting the dynamic role of the brainstem in response to CO2-induced anxiety. These findings underscore the value of combining CCM and rs-fMRI to characterise the neural mechanisms of anxiety, with important implications for evaluating potential therapeutic interventions.
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spelling doaj-art-d6c3055320d74d0f9b48bbfff4d5dde82024-12-01T12:17:42ZengNature PortfolioScientific Reports2045-23222024-11-0114111010.1038/s41598-024-80901-5Characterising the anxiogenic network from functional connectivity analysis of the CO2 challenge modelDaniel Graham0Santra Mathew1Jonathan Marsden2Alastair D. Smith3Gary Smerdon4Stephen D. Hall5University of PlymouthUniversity of PlymouthUniversity of PlymouthUniversity of PlymouthDDRC HealthcareUniversity of PlymouthAbstract The CO2 challenge model (CCM) is a gas inhalation paradigm that provides precisely controlled anxiety induction in experimental settings. Despite its potential as an experimental model of anxiety, our understanding of the neural effects of the CCM is incomplete. This study employs resting-state functional magnetic resonance imaging (rs-fMRI) to explore functional connectivity (FC) changes underlying the CCM. Following a preliminary CO2 tolerance assessment, participants completed an MRI session that included three rs-fMRI scans: during inhalation of control air (pre and post), and during a 6% CCM exposure. Here, we confirm that 6% CCM is a tolerable anxiogenic model in the MRI setting. We demonstrate that a transient CCM-induced increase in subjective anxiety is associated with an increase in FC within limbic and anxiety-related regions, with the insula emerging as a central node in this altered connectivity pattern. Further analysis revealed a significant correlation between the levels of subjective anxiety and enhanced FC between the brainstem and medial frontal cortex, highlighting the dynamic role of the brainstem in response to CO2-induced anxiety. These findings underscore the value of combining CCM and rs-fMRI to characterise the neural mechanisms of anxiety, with important implications for evaluating potential therapeutic interventions.https://doi.org/10.1038/s41598-024-80901-5
spellingShingle Daniel Graham
Santra Mathew
Jonathan Marsden
Alastair D. Smith
Gary Smerdon
Stephen D. Hall
Characterising the anxiogenic network from functional connectivity analysis of the CO2 challenge model
Scientific Reports
title Characterising the anxiogenic network from functional connectivity analysis of the CO2 challenge model
title_full Characterising the anxiogenic network from functional connectivity analysis of the CO2 challenge model
title_fullStr Characterising the anxiogenic network from functional connectivity analysis of the CO2 challenge model
title_full_unstemmed Characterising the anxiogenic network from functional connectivity analysis of the CO2 challenge model
title_short Characterising the anxiogenic network from functional connectivity analysis of the CO2 challenge model
title_sort characterising the anxiogenic network from functional connectivity analysis of the co2 challenge model
url https://doi.org/10.1038/s41598-024-80901-5
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