In the past few years, scientists have learned a lot about fear from a woman who could not experience it. A rare illness had damaged a part of her brain known as the amygdala and left her eerily unafraid.
Both in experiments and in life, the woman, known as SM, showed no fear of scary movies, snakes, spiders, or very real domestic assaults, death threats and robberies at knife and gunpoint.
Although she lived in an area "replete with crime, drugs, and danger," according to an earlier study, without a functioning amygdala, an evolutionarily ancient part of the brain long known to process fear, nothing scared her.
But recently SM had a panic attack. And the simple fact that she was able to know fear without a working amygdala, experts say, illuminates some of the brain's most fundamental processes and may have practical value in the study of panic attacks.
SM's moments of fear occurred during an experiment that involved inhaling carbon dioxide through a mask in amounts that are not harmful but create a momentary feeling of suffocation.
Not only SM, but two other women, identified as AM and BG, identical twins with amygdala damage similar to SM's, showed all the physical symptoms of panic, and reported that, to their surprise, they felt intense fear.
The researchers, who report on the experiment in the current issue of Nature Neuroscience, had hypothesized that SM would not panic. John Wemmie, a neuroscientist at the University of Iowa and the senior author of the paper, said, "We saw the exact opposite."
Antonio Damasio, of the University of Southern California, who had worked with SM and some of the researchers involved in this study on previous papers, but did not participate in this research, said the results confirmed his own thinking that while the amygdala was central to fear generated by external threats, there was a different brain path that produced the feeling of fear generated by internal bodily experiences like a heart attack. This idea was put forth in a 2011 paper about SM on which he was a co-author.
"I think it's a very interesting and important result," he said.
SM scores in the normal range on IQ and other tests, and voluntarily participated in this and earlier studies, all of which showed her lacking in any sort of fear response until now.
So what was so unusual about carbon dioxide?
The answer seems to lie in the way the brain monitors disturbances in the world outside the body -- snakes and robbers -- compared to the way it monitors trouble inside the body -- hunger, heart attacks, the feeling of not being able to breathe. External threats clearly are processed by the amygdala. But she had never been tested for internal signals of trouble.
In the experiment SM and others participated in, they took one deep breath with plenty of oxygen but much more carbon dioxide than air usually contains. Humans are actually not sensitive to how much oxygen they are breathing, but to how much carbon dioxide is accumulating in the body, since it builds up quickly when one cannot breathe. The sensation is familiar to anyone who has tried to hold their breath.
The researchers suggest that excess carbon dioxide produces signals that may be picked up in the brainstem and elsewhere, activating a fear-generating system in the brain that a venomous snake or a mugger with a gun would not trigger.
One puzzling aspect of the results is that SM and the two other women all reacted so strongly. Among people with normal brains, only those with panic disorder are reliably terrified in carbon dioxide experiments. Most people are not so susceptible, suggesting, said Colin Buzza, a co-author of the study and a medical student at the University of Iowa's Carver College of Medicine, that perhaps the amygdala is not functioning properly in people with panic disorder.