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Nothing to fear but suffocation

People with a rare brain disorder don’t get scared — except when they breathe carbon dioxide

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4:03pm, February 3, 2013
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Not all fear is the same. A woman who laughs at horror movies, grabs dangerous snakes and calmly deals with knife-wielding men nonetheless surrenders to terror at a single puff of suffocating carbon dioxide.

This woman, known as SM, has a disease that damaged her amygdala, a brain structure implicated in fear. But the new results involving her and two others with the same disease, published online February 3 in Nature Neuroscience, show that a certain kind of danger signal can bypass the amygdala, hitting the panic button in other parts of the brain.

The need to breathe is one of the most fundamental requirements for survival. Clinical neuropsychologist Justin Feinstein of the University of Iowa in Iowa City believes that the instinct to get air might tap into a brain system that’s more primal than the amygdala.

Feinstein and colleagues work with SM and other patients who suffer from a rare genetic disorder called Urbach-Wiethe disease. In late childhood, this disease destroys the amygdala, a pair of almond-shaped structures deep in the brain. SM shows no fear when confronted with haunted houses, ominous spiders and scary movies (SN: 1/15/11, p. 14). Now, the scientists have found something that does scare her.

A breath of gas that is 35 percent carbon dioxide can immediately provoke a strong, panicky fear. (By contrast, normal air is less than one percent carbon dioxide.) When the gas hits the body, specialized proteins sense that something is amiss and send an urgent “must have air, now” message to the brain.

"It’s automatic,” says Feinstein, who has subjected himself to the procedure multiple times. “Your body’s alarms are firing like crazy within the first 10 seconds.”

A recent study using mice showed that the amygdala detects carbon dioxide and helps produce fearlike behavior. So the researchers thought that SM and the two other women in the study might likewise show a blunted response to the gas.

But the scientists were wrong. SM’s reaction to the gas was swift and unequivocal — she was afraid. She immediately started gasping and waving her hand frantically. Fourteen seconds after she inhaled the gas, she cried out for help. Her eyes flew open wide, her nostrils flared and her face flushed. She later said that she had felt panic. When a researcher asked if she was surprised by her reaction, she said, “I was, ‘cause usually nothing happens to me.”

The researchers were equally stunned. “It was a complete surprise to us all,” Feinstein says. “We’ve been studying her for a long time and we’d never witnessed a reaction like that.”

The other two volunteers responded similarly, both showing strong fear in response to the carbon dioxide, and both expressing surprise at the sensation, which they had never experienced before.

It was very striking,” Feinstein says. “You’re dealing with people here who have spent most of their adult lives without fear.”

When the researchers tested 12 healthy volunteers, carbon dioxide elicited panic attacks in only three. The exaggerated responses of the women suggest that the amygdala’s usual role in panic is to shut down a response that starts somewhere else.

"This study adds to a growing body of work showing that there are different systems for responses to different kinds of threats," says neuroscientist Joseph LeDoux of New York University. But he cautions that the amygdala's role in the emotion of fear is still far from clear. It's very difficult to tie a brain region to a particular emotion, particularly when much research on the subject is performed in animals.

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