What do the fearless fear?

Patient S.M. is practically fearless! She suffers from Urbach-Wiethe disease which has caused a bilateral lesion in a part of the brain known as the amygdala, an almond-shaped structure located on the medial part of the temporal lobe. Much evidence suggests the amygdala plays an influential role in fear. Patient S.M., because of her lesion, hasn’t experienced fear since childhood. Researchers have tried to frighten her by exposing her to fear-provoking stimuli such as haunted houses, scary movies, and live snakes and spiders, but she showed no signs of fear at any point during these experiments, and when asked, she never reported being even the least bit frightened. On top of that, she fails to recognise fear in the faces of others, suggesting that her whole concept of the emotion might be missing. However, Justin Fernstein and colleagues, by accident, found a way to scare her…

A recent study suggested that the amygdala in mice directly detects increased CO₂ levels and induces fear-related behaviours as a response. Therefore, Fernstein and colleagues hypothesised that patients with bilateral amygdala lesions, such as S.M., would not experience fear when inhaling 35 % CO₂ , the way healthy people do. Inhalation of CO₂ usually causes shortness of breath and elicits fear. In patients with panic disorder, inhaling CO₂ can even trigger panic attacks.

Contrary to all predictions, patient S.M. and two other patients with similar amygdala lesions did not only experience fear when inhaling CO₂, but all suffered panic attacks. When asked to describe the experience, the patients reported fear of losing control, fear of dying, and fear of going crazy along with unpleasant physiological symptoms. The patients described the sensation as “panic” and all three exhibited similar panic responses of gasping for air, distressed facial expressions, and escape behaviours. These patients, who were thought to be fearless, suddenly experienced great fear (a sensation they described as “novel”) when exposed to an internal bodily threat rather than external threats. The authors therefore propose that we have separate fear systems in the brain: one for triggering fear of external threats and one for triggering fear of internal bodily threats. While the amygdala is necessary in order to experience the former type, the experiment clearly show that it is not needed to experience fear and exhibit fear-behaviours in response to the latter.

The responses of the three “thought-to-be-fearless” patients were compared to a control sample of 12 participants with intact brains. It was found that out of the 12 healthy participants, only three suffered panic attacks from inhaling CO₂. That is, the CO₂ actually triggered panic attacks in a greater proportion of the “fearless” patients than of the normal participants. The patients also showed signs of greater fear and reported greater panic than the participants with intact brains. The authors, trying to make sense of this finding, suggest that the amygdala may furthermore play a role in inhibiting panic behaviour.

The case of patient S.M. clearly shows how important a role the amygdala plays in triggering states of fear, an emotion S.M. had not experienced since childhood. However, Fernstein and colleagues demonstrated that amygdala activation is not necessary for experiencing fear, nor for eliciting fear-related behaviours. Further research is needed to define other areas of the brain that may be more specifically involved in triggering the experience of fear and fear-behaviours in response to bodily threats.

Reference: Fernstein, J.S., et al. (2013). Fear and panic in humans with bilateral amygdala damage. Nature Neuroscience, doi: 10.1038/nn.3323