2026 ECNP Congress

PS03-3021

Electrocortical function at rest and during emotion processing in the 7.5% carbon dioxide model of anxiety

Joshua Hyde — N.J. Kelley, N.T.M. Huneke, D.S. Baldwin, M. Garner · University of Southampton, Centre for Innovation in Mental Health- School of Psychology- Faculty of Environmental and Life Sciences, Southampton, United Kingdom

2026 ECNP Congress

Generalised anxiety disorder (GAD), is characterised by worry, distractibility and cognitive biases that prioritise threatening information. Cognitive hyperactivity in anxiety is associated with increased autonomic arousal (e.g. heart rate). Experimental medicine models, such as the 7.5% carbon dioxide (CO2) inhalation challenge, can induce subjective, autonomic and cognitive characteristics of generalised anxiety [1]. Increased activity in neural threat-networks (at baseline) predicts anxiety and autonomic arousal during subsequent CO2 challenge [2], and recent evidence suggests CO2 challenge alters activity in prefrontal – limbic regions involved in threat processing [3]. However, the effect of CO2 challenge on electrocortical function at rest and during emotion processing is not clear. This study investigated the effect of 7.5% CO2 vs. air inhalation on electroencephalography activity at rest and during an emotional flanker attention task in healthy volunteers. Thirty-one university students underwent 20 minutes of normal air inhalation followed by 20 minutes of an air mixture with 7.5% CO2. Each inhalation period consisted of an 8-minute resting-state phase, followed by a 12-minute flanker task with emotional faces (EFT). Subjective anxiety, mood and heart rate were measured, and EEG was recorded via 32 electrodes arranged in a 10-20 montage. Resting-state EEG analysis included measures of spectral power, alpha lateral asymmetry and functional connectivity via a pairwise phase consistency (PPC) algorithm. EFT EEG analysis explored characteristics of the N2 and Late Positive Potential (LPP) components. Twenty minutes of 7.5% CO2 inhalation increased subjective anxiety (t(59.1) = 4.42, p = <.001), negative mood (t(59.5) = 3.40, p = .003) and heart rate (t(105) = 5.69, p = <.001). We observed large effects of inhalation condition on resting-state electrocortical activity – CO2 inhalation significantly increased frontocentral midline theta (p = .015*) and central and parietal gamma power (p = <.001*), and significantly reduced frontal, central and lateral left alpha (p = <.001*), and central beta power (p = <.001*), compared with normal air inhalation. Furthermore, functional connectivity analysis revealed increased connectivity between several frontolateral and central EEG channels in the theta band frequency during CO2 inhalation. Altered resting-state electrophysiological activity was reflected in cognitive functioning during the EFT via globally increased response times (t(9258) = 3.03, p = .002), and reduced LPP amplitudes (t(181) = 4.24, p = <.001). Our findings provide further validation for the 7.5% CO2 inhalation experimental model of generalised anxiety. Large elevations in anxiety and heart rate, and impaired task performance replicate previous findings in healthy volunteers [1, 2, 3]. Analyses of EEG spectral power and functional connectivity revealed strong effects that are consistent with evidence of increased gamma and theta band activity in anxiety and related disorders [4,5]. Future work should explore whether these electrophysiological markers might be treatment-responsive, which would potentially provide proof-of-concept for a translational biomarker for generalised anxiety.

Note. *p values reported after cluster-based permutation test.

References

  1. Garner, M., Attwood, A., Baldwin, D. S., James, A., & Munafo, M. R. (2011). Inhalation of 7.5% Carbon Dioxide Increases Threat Processing in Humans. Neuropsychopharmacology, 36(8), 1557-1562. doi:10.1038/npp.2011.15
  2. Huneke, N. T. M., Broulidakis, M. J., Darekar, A., Baldwin, D. S., & Garner, M. (2020). Brain Functional Connectivity Correlates of Response in the 7.5% CO2 Inhalational Model of Generalized Anxiety Disorder: A Pilot Study. Int J Neuropsychopharmacol, 23(4), 268-273. doi:10.1093/ijnp/pyaa019
  3. Graham, D., Mathew, S., Marsden, J., Smith, A. D., Smerdon, G., & Hall, S. D. (2024). Characterising the anxiogenic network from functional connectivity analysis of the CO(2) challenge model. Sci Rep, 14(1), 29294. doi:10.1038/s41598-024-80901-5
  4. Oathes, D. J., Ray, W. J., Yamasaki, A. S., Borkovec, T. D., Castonguay, L. G., Newman, M. G., & Nitschke, J. (2008). Worry, generalized anxiety disorder, and emotion: Evidence from the EEG gamma band. Biological psychology, 79(2), 165-170.
  5. Gerez, M., Suárez, E., Serrano, C., Castanedo, L., & Tello, A. (2016). The crossroads of anxiety: distinct neurophysiological maps for different symptomatic groups. Neuropsychiatric Disease and Treatment, 159-175.