Brain responses to disorder-related visual threat in panic disorder

Abstract

Panic disorder (PD) patients show aberrant neural responses to threatening stimuli in an extended fear network, but results are only partially comparable, and studies implementing disorder-related visual scenes are lacking as stimuli. The neural responses and functional connectivity to a newly developed set of disorder-related, ecologically valid scenes as compared with matched neutral visual scenes, using event-related functional magnetic resonance imaging (fMRI) in 26 PD patients and 26 healthy controls (HC) were investigated. PD patients versus HC showed hyperactivation in an extended fear network comprising brainstem, insula, thalamus, anterior, and mid-cingulate cortex and (dorso-)medial prefrontal cortex for disorder-related versus neutral scenes. Amygdala differences between groups failed significance. Subjective levels of anxiety significantly correlated with brainstem activation in PD patients. Analysis of functional connectivity by means of beta series correlation revealed no emotion-specific alterations in connectivity in PD patients versus HC. The results suggest that subjective anxiety evoked by external stimuli is directly related to altered activation in the homeostatic alarm system in PD. With novel disorder-related stimuli, the study sheds new light on the neural underpinnings of pathological threat processing in PD. Hum Brain Mapp 37:4439-4453, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: brainstem; disorder-related scenes; fMRI; panic disorder.

Figure 1

Mean post‐scanning ratings for valence, arousal and anxiety according to disorder‐related and neutral scenes for panic disorder patients (PD) and healthy controls (HC). Ratings were given on 9‐point Likert scales as follows: valence, 1 = negative, 5 = neutral, 9 = positive; arousal, 1 = calm, 9 = intense; anxiety, 1 = low, 9 = high. * P < 0.025.

Figure 2

Differential brain activation for disorder‐related compared with neutral stimuli in panic disorder patients (PD) versus healthy controls (HC) in a priori defined ROIs (PD > HC, disorder‐related > neutral, all P < 0.005 uncorrected; P < 0.05 corrected). Black bars display parameter estimates for PD, white bars for HC. PD patients display an enhanced activation in brainstem, bilateral thalamus, bilateral insula, bilateral midcingulate cortex (MCC), right medial prefrontal cortex (MPFC), and dorsomedial prefrontal cortex/anterior cingulate cortex (ACC). All figures displayed at P < 0.005. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Correlation between brainstem beta values in panic disorder patients in the contrast Scene Type and individual anxiety ratings (disorder‐related minus neutral). [Color figure can be viewed at http://wileyonlinelibrary.com]