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.

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Brain functional connectivity correlates of response in the 7.5% CO2 inhalational model of generalized anxiety disorder: a pilot study

10.1101/823617 ◽

2019 ◽

Author(s):

Nathan T.M. Huneke ◽

M. John Broulidakis ◽

Angela Darekar ◽

David S. Baldwin ◽

Matthew Garner

Keyword(s):

Heart Rate ◽

Anxiety Disorder ◽

Pilot Study ◽

Functional Connectivity ◽

Healthy Volunteers ◽

Generalized Anxiety Disorder ◽

Regions Of Interest ◽

Generalized Anxiety ◽

Affective Valence ◽

Potential Threat

AbstractThe 7.5% CO2 inhalational model (‘CO2 challenge’) can be used to explore potential treatments for generalized anxiety disorder. However, it remains unknown how inter-individual variability in the functional architecture of negative affective valence systems might relate to the anxiogenic response to CO2 challenge. In this pilot study, we explored how connectivity in systems associated with processing potential threat (“anxiety”) correlated with behavioural measures of anxiety following prolonged CO2 inhalation.The negative affective valence system was identified using a passive emotional face perception task. Spherical regions of interest were created from peak voxels of significant brain activation when 100 young adult participants viewed emotional faces compared with black and white concentric circles during a functional MRI scan. Using these regions of interest, generalized psychophysiological interaction (gPPI) analysis was undertaken to explore task-evoked functional connectivity in a separate group of 13 healthy volunteers. Within 7 days of the scan, these participants underwent CO2 challenge and results from the gPPI analysis were correlated with CO2 outcome measures.Exposure to CO2 challenge significantly increased subjective anxiety, negative affect, systolic blood pressure and heart rate. Functional connectivity between the ventromedial prefrontal cortex and right amygdala was positively correlated with heart rate. Increased connectivity between the vmPFC and the right amygdala, and decreased connectivity between the midcingulate cortex (MCC) and the left amygdala, correlated with subjective anxiety during CO2 challenge.Response to CO2 challenge was related to task-evoked functional connectivity between regions known to be important in processing potential threat. Further studies are required to assess whether this translates into clinical populations. Measures of functional connectivity within emotional processing networks could be potential biomarkers to enable stratification of healthy volunteers, and to examine correlates of response, in trials using experimental medicine models.

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Anomalous neurovascular coupling in patients with generalized anxiety disorder evaluated by combining cerebral blood flow and functional connectivity strength

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2021.110379 ◽

2021 ◽

pp. 110379

Author(s):

Yuyan Chen ◽

Qian Cui ◽

Wei Sheng ◽

Qin Tang ◽

Fengmei Lu ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Anxiety Disorder ◽

Functional Connectivity ◽

Generalized Anxiety Disorder ◽

Neurovascular Coupling ◽

Generalized Anxiety ◽

Functional Connectivity Strength ◽

Connectivity Strength

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1122 RESTING STATE FUNCTIONAL CONNECTIVITY IN PRIMARY INSOMNIA, GENERALIZED ANXIETY DISORDER AND CONTROLS

SLEEP ◽

10.1093/sleepj/zsx050.1121 ◽

2017 ◽

Vol 40 (suppl_1) ◽

pp. A418-A418

Author(s):

EF Pace-Schott ◽

JP Zimmerman ◽

RM Bottary ◽

EG Lee ◽

MR Milad ◽

...

Keyword(s):

Anxiety Disorder ◽

Functional Connectivity ◽

Generalized Anxiety Disorder ◽

Resting State ◽

Primary Insomnia ◽

Generalized Anxiety ◽

Resting State Functional Connectivity

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Illness Severity Moderated Association Between Trait Anxiety and Amygdala-Based Functional Connectivity in Generalized Anxiety Disorder

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.637426 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yang Du ◽

Hailong Li ◽

Hongqi Xiao ◽

Mei Wang ◽

Wei Zhang ◽

...

Keyword(s):

Anxiety Disorder ◽

Functional Connectivity ◽

Generalized Anxiety Disorder ◽

Trait Anxiety ◽

Symptom Severity ◽

Inferior Frontal Gyrus ◽

Illness Severity ◽

Anterior Cingulate ◽

Generalized Anxiety ◽

Significant Group

Trait anxiety is considered a vulnerability factor for the development of generalized anxiety disorder (GAD). The amygdala is related to both trait anxiety and GAD. Thus, we investigated amygdala-based functional connectivity (FC) in drug-naive non-comorbid GAD patients and explored its associations with personality, symptoms, and illness severity. FC analyses using the bilateral amygdala as seeds were performed with resting-state functional MRI data from 38 GAD patients and 20 matched healthy controls (HCs). Clinical characteristics were correlated with FC Z-scores from regions showing significant group differences. Furthermore, moderation analyses were used to explore the conditional effect of illness severity measured by the Clinical Global Impression–Severity (CGI-S) scale on the relationship between FC and trait anxiety. Relative to HCs, GAD patients showed hypoconnectivity between the amygdala and the rostral anterior cingulate cortex (rACC), inferior frontal gyrus (IFG), parahippocampal gyrus, and cerebellum and hyperconnectivity between the amygdala and the superior temporal gyrus (STG), insula, and postcentral gyrus. In GAD patients, amygdala–rACC connectivity was negatively associated with symptom severity and trait anxiety, and amygdala–IFG connectivity was positively associated with symptom severity. Moreover, CGI-S scores moderated the negative correlation between trait anxiety and amygdala–rACC FC. We demonstrate that there is extensive amygdala-based network dysfunction in patients with GAD. More importantly, amygdala–rACC connectivity plays a key role in the neural pathology of trait anxiety. Finally, the more severe the illness, the stronger the negative association between trait anxiety and amygdala–rACC FC. Our results emphasize the importance of personalized intervention in GAD.

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