Initial and sustained brain responses to threat anticipation in blood-injection-injury phobia

Abstract

Blood-injection-injury (BII) phobia differs from other subtypes of specific phobia in that it is associated with elevated disgust-sensitivity as well as specific autonomic and brain responses during processing of phobia-relevant stimuli. To what extent these features play a role already during threat anticipation is unclear. In the current fMRI experiment, 16 female BII phobics and 16 female healthy controls anticipated the presentation of phobia-specific and neutral pictures. On the behavioral level, anxiety dominated the anticipatory period in BII phobics relative to controls, while both anxiety and disgust were elevated during picture presentation. By applying two different models for the analysis of brain responses to anticipation of phobia-specific versus neutral stimuli, we found initial and sustained increases of activation in anterior cingulate cortex (ACC), insula, lateral and medial prefrontal cortex (PFC), thalamus and visual areas, as well as initial activation in the amygdala for BII phobics as compared to healthy controls. These results suggest that BII phobia is characterized by activation of a typical neural defense network during threat anticipation, with anxiety as the predominant emotion.

Keywords: Amygdala; Anterior cingulate cortex; Bed nucleus of the stria terminalis (BNST); Insula; fMRI.

Fig. 1

Ratings for anxiety (1 = “not anxious at all” to 9 = “very anxious”) and disgust (1 = “not disgusting at all” to 9 = “very disgusting”) in phobic and control subjects for the anticipatory period (a) and picture presentation (b). *p < 0.001.

Fig. 2

Change in heart rate (beats per minute) for phobic and control subjects over the anticipatory period (a) and picture presentation (b).

Fig. 3

Phobic subjects showed increased sustained activation during anticipation of phobia-specific in contrast to neutral pictures in dorsal anterior cingulate cortex (dACC), insula and dorsolateral prefrontal cortex (dlPFC) as well as decreased activation in orbitofrontal cortex (OFC) as compared to healthy control subjects. Statistical parametric maps are overlaid on an averaged T1 scan (radiological convention: left = right). Graphs display contrasts of parameter estimates (phobia-specific vs. neutral picture anticipation; mean ± standard error for activation cluster).

Fig. 4

Phobic subjects showed increased initial activation during anticipation of phobia-specific in contrast to neutral pictures in left amygdala, right and left anterior insula and a cluster of increased activation extending from the ventromedial prefrontal cortex (vmPFC) to the rostral anterior cingulate cortex (rACC). Statistical parametric maps are overlaid on an averaged T1 scan (radiological convention: left = right). Graphs display contrasts of parameter estimates (phobia-specific vs. neutral picture anticipation; mean ± standard error for activation cluster).

Fig. 5

Standardized differences in parameter estimates (anticipation of phobia-specific – neutral stimuli; mean ± standard error) resulting from the initial and sustained model within clusters of activation in dorsal anterior cingulate cortex (ACC), posterior insula, amygdala, rostral ACC and anterior insula.