Functional neuroanatomy of CCK-4 induced panic attacks in healthy volunteers

Objective: Experimental panic induction with cholecystokinin tetrapeptide (CCK-4) is considered as a suitable model to investigate the pathophysiology of panic attacks. While only few studies investigated the brain activation patterns following CCK-4 administration in humans, no data are available on the putative involvement of the amygdala in the CCK-4 elicited anxiety response. Methods: Sixteen healthy male volunteers underwent challenge with CCK-4 compared to placebo in a single blind design with simultaneous fMRI recording. Results: CCK-4 elicited a statistically significant increase in panic rating scores. During anticipatory anxiety a weak activation was observed in some brain regions such as the dorsal part of the anterior cingulate cortex (ACC). In contrast, CCK-4 induced anxiety was accompanied by a strong and robust activation in the ventral ACC, precuneus, cuneus, medial frontal gyrus, inferior frontal gyrus/insula, lingual gyrus, caudate head and cerebellum. Overall functional responses did not differ between panickers and nonpanickers following CCK-4. Although we did not detect activation of the amygdala in the group analysis ROI analysis of the amygdala pointed towards higher scores in fear items in subjects showing high amygdala activation. Discussion: In conclusion, while overall brain activation patterns are not related to the subjective anxiety response to CCK-4, amygdala activation may be involved in the subjective perception of CCK-4 induced anxiety.