When doctors at the University of Iowa prepared a patient to inhale a panic-inducing dose of carbon dioxide, she was fearless. But within seconds of breathing in the mixture, she cried for help, overwhelmed by the sensation that she was suffocating.
The patient, a woman in her 40s known as SM, has an extremely rare condition called Urbach-Wiethe disease that has caused extensive damage to the amygdala, an almond-shaped area in the brain long known for its role in fear. She had not felt terror since getting the disease when she was an adolescent.
In a paper published online Feb. 3 in the journal Nature Neuroscience, the UI team provides proof that the amygdala is not the only gatekeeper of fear in the human mind. Other regions-such as the brainstem, diencephalon, or insular cortex-could sense the body's most primal inner signals of danger when basic survival is threatened.
"This research says panic, or intense fear, is induced somewhere outside of the amygdala," says John Wemmie, associate professor of psychiatry at the UI and senior author on the paper. "This could be a fundamental part of explaining why people have panic attacks."
If true, the newly discovered pathways could become targets for treating panic attacks, post-traumatic stress syndrome, and other anxiety-related conditions caused by a swirl of internal emotional triggers.
"Our findings can shed light on how a normal response can lead to a disorder, and also on potential treatment mechanisms," says Daniel Tranel, professor of neurology and psychology at the UI and a corresponding author on the paper.
Decades of research have shown the amygdala plays a central role in generating fear in response to external threats. Indeed, UI researchers have worked for years with SM, and noted her absence of fear when she was confronted with snakes, spiders, horror movies, haunted houses, and other external threats, including an incident where she was held up at knife point. But her response to internal threats had never been explored.
The UI team decided to test SM and two other amygdala-damaged patients with a well-known internally generated threat. In this case, they asked the participants, all females, to inhale a gas mixture containing 35 percent carbon dioxide, one of the most commonly used experiments in the laboratory for inducing a brief bout of panic that lasts for about 30 seconds to a minute. The patients took one deep breath of the gas, and quickly had the classic panic-stricken response expected from those without brain damage: They gasped for air, their heart rate shot up, they became distressed, and they tried to rip off their inhalation masks. Afterward, they recounted sensations that to them were completely novel, describing them as "panic."