Brain Functional Connectivity Correlates of Response in the 7.5% CO2 Inhalational Model of Generalized Anxiety Disorder: A Pilot Study

Abstract

Background: The 7.5% CO2 inhalational model can be used to explore potential treatments for generalized anxiety disorder. However, it is unknown how inter-individual variability in the functional architecture of negative affective valence systems might relate to anxiogenic response in this model.

Methods: A total of 13 healthy volunteers underwent functional magnetic resonance imaging during a passive emotional face perception task. We explored task-evoked functional connectivity in the potential threat system through generalized psychophysiological interaction analysis. Within 7 days, these participants underwent prolonged 7.5% CO2 inhalation, and results from the generalized psychophysiological interaction analysis were correlated with CO2 outcome measures.

Results: Functional connectivity between ventromedial prefrontal cortex and right amygdala positively correlated with heart rate and subjective anxiety, while connectivity between midcingulate cortex and left amygdala negatively correlated with anxiety during CO2 challenge.

Conclusions: Response to CO2 challenge correlated with task-evoked functional connectivity in the potential threat system. Further studies should assess whether this translates into clinical populations.

Keywords: Anxiety; CO2 challenge; experimental medicine; fMRI; functional connectivity.

Figure 1.

Significant activation seen on whole-brain analysis of the contrast all faces >control in the passive emotional face perception task; all Zs are >5.91, all voxelwise corrected P < .0005. Color bar represents Z value.

Figure 2.

(A) Task-evoked functional connectivity (contrast angry >happy) between right amygdala and ventromedial prefrontal cortex (vmPFC) and between left amygdala and midcingulate cortex (MCC) correlated with CO₂ outcome measures. These connectivity results were visualized with the BrainNet Viewer (http://www.nitrc.org/projects/bnv/). B and C are scatter plots showing the association of functional connectivity in these regions of interest with heart rate and peak subjective anxiety during CO₂ challenge. bpm, beats per minute; GAD, generalized anxiety disorder screener.