Fear and panic in humans with bilateral amygdala damage

Abstract

Decades of research have highlighted the amygdala's influential role in fear. We found that inhalation of 35% CO(2) 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 CO(2).

Figure 1

Panic attack rate and self-reported levels of fear and panic during the first CO₂ inhalation. (a) Panic attack rate (%) in amygdala-lesion patients (n=3) versus the neurologically-intact comparison participants (n=12). All of the amygdala-lesion patients had a panic attack, whereas only 3 of the 12 comparison participants panicked (*p<0.05; Fisher’s Exact Test). (b) Level of subjective fear and (c) level of subjective panic reported during CO₂ relative to baseline quantified with visual analog scales (VAS). Both the amygdala-lesion patients and the comparison participants who panicked reported significantly higher levels of fear and panic relative to the comparison participants who did not panic (*p<0.05; Mann-Whitney U-tests). There were no significant differences between the amygdala-lesion patients and the comparison panickers. Error bars represent the standard error of the mean.

Figure 2

CO₂–evoked physiological changes. (a) Change from baseline in maximum respiratory rate during the first CO₂ trial relative to the first air trial. Both the amygdala-lesion patients (n=3) and the comparison participants who panicked (n=3) demonstrated significantly higher increases in respiratory rate relative to the comparison participants who did not panic (n=9) (*p<0.05; Mann-Whitney U-tests). There was no significant difference between the amygdala-lesion patients and the comparison panickers. (b) Change from baseline in maximum heart rate during CO₂ relative to air trials. Both the amygdala-lesion patients (n=2) and the comparison participants who panicked (n=3) demonstrated higher increases in heart rate relative to the comparison participants who did not panic (n=9). (c) Change from baseline in maximum SCR during the first CO₂ trial relative to the first air trial. Patient AM demonstrated a significantly higher maximum SCR than the comparison participants who did not panic (*p<0.001; modified t-test). (d) Change from baseline in SCR during the first CO₂ trial relative to the first air trial graphed during the first minute post-inhalation. Error bars represent the standard error of the mean.

Figure 3

Anticipatory physiological responses prior to inhalation. (a) SCR graphed during the 10 seconds prior to inhalation and (b) the maximum evoked-SCR during the same time period. Patient AM showed no anticipatory SCR response on any trials. (c) Change in heart rate relative to baseline during the 40 seconds prior to inhalation and (d) the maximum change in heart rate during the same time period. The amygdala-lesion patients (n=2) had a significantly lower anticipatory heart rate response relative to the comparison participants (n=12) (*p<0.05; Mann-Whitney U-test). Error bars represent the standard error of the mean.