Take my breath away: Neural activation at breath-hold differentiates individuals with panic disorder from healthy controls.

There is neuroanatomical evidence of an "extended fear network" of brain structures involved in the etiology of panic disorder (PD). Although ventilatory distrubance is a primary symptom of PD these sensations may also trigger onset of a panic attack (PA). Here, a voluntary breath-holding paradigm was used to mimic the hypercapnia state in order to compare blood oxygen level-dependent (BOLD) response, at the peak of a series of 18 s breath-holds, of 21 individuals with PD to 21 low anxiety matched controls. Compared to the rest condition, BOLD activity at the peak (12 - 18 s) of the breath-hold was greater for PD versus controls within a number of structures implicated in the extended fear network, including hippocampus, thalamus, and brainstem. Activation was also observed in cortical structures that are shown to be involved in interoceptive and self-referential processing, such as right insula, middle frontal gyrus, and precuneus/posterior cingulate. In lieu of amygdala activation, our findings show elevated activity throughout an extended network of cortical and subcortical structures involved in contextual, interoceptive and self-referential processing when individuals with PD engage in voluntary breath-holding.