The relationship between dlPFC activity during unpredictable threat and CO2-induced panic symptoms

Nicholas L Balderston,Christian Grillon,Monique Ernst,Jeffrey Liu,Roxann Roberson-Nay

doi:10.1038/s41398-017-0006-5

Nicholas L Balderston, Christian Grillon + Show 3 more

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https://doi.org/10.1038/s41398-017-0006-5

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Abstract

Panic disorder is characterized by sudden, repeated, and unexpected attacks of intense fear and overwhelming anxiety about when another attack may strike. Patients with panic disorder and healthy individuals with a history of panic attacks show a hypersensitivity to unpredictable threats, suggesting a possible link between panic and sustained anxiety. The purpose of this study was to determine the degree to which induced symptoms of panic relate to fear and anxiety, as well as activity in the neural systems that mediate and regulate these affective states. Psychological and physiological symptoms of panic were assessed during an 8-min 7.5% CO2 challenge task. Psychological, physiological, and neural symptoms of fear and anxiety were measured during two sessions (one psychophysiology and one functional magnetic resonance imaging where subjects experienced several blocks of no threat (N), predictable shock (P), and unpredictable shock (U; NPU threat task). We used a principle component analysis to characterize panic susceptibility (PS), and found that PS significantly predicted dorsolateral prefrontal cortex (dlPFC) activity to the unpredictable cue during the NPU threat task. When examining the weighted beta coefficients from this analysis, we observed that self-reported fear/anxiety during the CO2 challenge negatively loaded onto dlPFC activity during the NPU task. Consistent with this observation, dlPFC activity during the unpredictable cue was also negatively correlated with anxiety during the NPU sessions. Together, these results suggest that panic symptoms and anxiety are regulated by the same prefrontal cognitive control system.

Highlights

Panic disorder is characterized by sudden, repeated, and unexpected attacks of intense fear and anxiety[1]
NPU laboratory To determine the effectiveness of the laboratory session of the NPU threat task, we analyzed the online ratings and startle magnitudes for the N, P, and U blocks using 3 (Block: N, P, U) × 2 (Interval: Cue vs. ITI) repeatedmeasures ANOVA (See Fig. 2)
We subtracted the rating (i.e., APR) and startle (i.e., anxietypotentiated startle (APS)) magnitude during the unpredictable blocks from the neutral blocks during both the cue and ITI. Both ratings and startle increased during the predictable cue compared to the predictable ITI, indicating an acute increase in fear brought on by the predictable cue (FPR: t(62) = 7.36; p < 0.001; d = 0.93, fear-potentiated startle (FPS): t(62) = 10.3; p < 0.001; d = 1.3). Both ratings and startle increased during the unpredictable cue (APR-CUE: t(62) = 11; p < 0.001, d = 1.39; APS-CUE: t(62) = 7.78; p < 0.001; d = 0.98) and ITI periods (APR-ITI: t(62) = 11.1; p < 0.001; d = 1.4, APS-ITI: t(62) = 8.37; p < 0.001; d = 1.05), indicating a sustained increase in anxiety that was present for the entire unpredictable blocks

Summary

Introduction

Panic disorder is characterized by sudden, repeated, and unexpected attacks of intense fear and anxiety[1]. Do individuals with panic disorder suffer from these paralyzing attacks, but they express intense worry and overwhelming anxiety about when another attack may strike[1] This disorder may profoundly impact the quality of life of the affected individuals, we know little about the etiology of this disorder, or the neural and cognitive systems that maintain and regulate panic symptoms[2]. Researchers have developed a CO2 challenge to experimentally induce panic symptoms. During this challenge, enriched air (5–7.5% CO2) is inhaled for up to 20 min, resulting in elevated symptoms of anxiety and panic, especially in those susceptible to panic disorder[3,4,5,6,7]. Effective for identifying panic susceptibility (i.e., elevated psychophysiological arousal and intense feelings of fear/anxiety in response to the CO2 administration), little is known about how CO2-induced panic symptoms relate to fear and anxiety

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