Decades of research have highlighted the amygdala's influential role in fear. We found that inhalation of 35% CO2 evoked not only fear, but also panic attacks, in three rare patients with bilateral amygdala damage. These results indicate that the amygdala is not required for fear and panic, and make an important distinction between fear triggered by external threats from the environment versus fear triggered internally by CO2.
Why do these 'fearless' patients feel fear when CO2 levels in their blood are increased? The authors suggest:
...that all of these other stimuli were exteroceptive in nature, mainly processed through visual and auditory pathways that project to the amygdala. In contrast, CO2 acts internally at acid-activated chemoreceptors and causes an array of physiological changes. Thus, CO2 might engage interoceptive afferent sensory pathways that project to the brainstem, diencephalon and insular cortex. In addition, many brain areas outside the amygdala possess CO2 and pH-sensitive chemoreceptors, including acid-sensing ion channels. Thus, CO2 may directly activate extra-amygdalar brain structures that underlie fear and panic, which may help to explain the apparent discrepancy between these findings and previous work in mice. In either case, our results indicate that, in humans, the internal threat signaled by CO2 is detected and interpreted as fear and panic despite the absence of an intact amygdala.