Evoking fear in the fearless reveals new ways to panic

"AM" thought she was dying. Moments after taking a deep breath through the mask that had been voluntarily placed over her nose and mouth she lifted her arms in panic and clenched her hand into a fist. She was 37 years old and it was the first time in her life she had felt fear.

This came as quite a shock to Justin Feinstein, now at the California Institute of Technology in Pasadena, who carried out the experiment. That's because AM has a rare genetic condition called Urbach?Wiethe disease that has, until now, made her fearless due to the destruction of a region of her brain called the amygdala. Her experience challenges the widely held belief that the amygdala is essential for fear.

Feinstein managed to scare AM by exposing her to carbon dioxide levels of 35 per cent via the mask, a protocol that can produce breathlessness, a rapid heartbeat and dizziness lasting about 30 seconds. It usually induces a sense of fear in about 25 per cent of people who try it.

The technique also provoked intense fear in two other volunteers with the genetic disorder. Feinstein had previously subjected one of them to every other scare tactic imaginable ? snakes, scary films, haunted houses ? but couldn't frighten her.

Anticipating fear

Interestingly, the amygdala-impaired volunteers still didn't react in the same way as healthy volunteers. Unlike most people, whose heart and perspiration rates rise immediately prior to a repeat of the carbon dioxide experiment, AM and her cohorts never developed an anticipatory response. They could feel fear, but they couldn't anticipate it.

Carbon dioxide changes blood acidity, activating acid-activated chemo receptors in the brain. This study hints that internal threats, like carbon dioxide, are processed differently by the brain than external ones, says Feinstein.

"This study shows there are other ways to get fear besides through the amygdala," says Cornelius Gross, a molecular biologist at the European Molecular Biology Laboratory in Monterotondo, Italy. He hypothesises that the hypothalamus might be involved, since it can mediate fear response in healthy people.

Journal reference: Nature Neuroscience, DOI: 10.1038/nn.3323

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