A new study describes how “fearless” patients with damage to the brain’s amygdala or “fear centre” experienced terrifying panic in a suffocation experiment, suggesting other brain circuits that do not involve the amygdala can also produce a fear response in reaction to potential threats.

Justin Feinstein, of the Departments of Neurology and Psychology at the University of Iowa in the US, and colleagues, write about their findings in the 3 February online issue of Nature Neuroscience.

For years, SM, a 44-year-old woman, has been helping researchers study the emotion of fear. Dubbed the “woman with no fear”, she suffers from a rare genetic condition known as Urbach-Wiethe disease, which in late childhood destroyed both sides of her amygdala, two almond sized structures on either side of the brain.

The condition means she is not afraid of things that strike fear in most people, such as snakes, spiders, horror films, and being attacked at knife or gunpoint.

In December 2010, Feinstein and colleagues reported a study involving SM that they hope will lead to safe and non-invasive ways of diminishing amygdala activity to treat patients with post-traumatic stress disorder (PTSD).

Many studies on animals have shown that the amygdala is crucial for the fear response. Some human studies have also confirmed this.

This has led to the belief, together with the evidence from SM’s case, that the amygdala must be the only circuit in the brain that processes events and triggers that evoke fear responses.

One type of event that triggers fear and panic attacks via the amygdala brain circuit is when inhaled air has unusually high levels of carbon dioxide (CO2), a sign of possible suffocation. The brain picks this up because inhaling high levels of CO2, even at non-lethal concentrations, increases acidity of the blood.

So, if the amygdala is essential for processing events that lead to fear, then people with damaged amygdalas should not get afraid by inhaling CO2.

This was the idea that Feinstein and colleagues wanted to test: especially as inhaling CO2 is a different kind of trigger to sensing external events with eyes and ears.

But when SM underwent an experiment, where she wore a mask to breathe in air enriched with 35% CO2, she had a full blown panic attack. Her body went rigid, her skin was flushed and her eyes opened wide.

The researchers then repeated the experiment with two other female patients with Urbach-Wiethe disease, and 12 healthy controls.

The two brain-damaged patients had the same reaction as SM, and to the researchers’ surprise this was much stronger than the fear and panic experienced by the healthy volunteers.

When interviewed after the experiment, all three brain-damaged patients said they were afraid of suffocating and dying when they had the mask on. SM said it was the first time she had felt afraid since being a child.

Feinstein says in a report by Nature News:

“The patients experienced significantly more fear and panic than the controls.”

Previous studies clearly show that the amygdala plays an important role in processing external events, threats from the environment, and in the social aspect of emotion, such as recognizing the facial expressions of others.

But Feinstein and colleagues propose their findings reveal the amydgala may not be the only circuit for the fear response, or for all fear responses. There may be another circuit for processing events that arise within the body, they say.

Perhaps there is one circuit with the amygdala, for internal events, and another without the amygdala, for external events.

Joseph LeDoux, of New York University, author of “The Emotional Brain” and somewhat of an expert on the amygdala, was not involved in the research. According to Nature News he says:

“This study adds to a growing body of work showing that there are different systems for responses to different kinds of threats.”

“There is lots of evidence that the amygdala contributes to threat-evoked responses, but very little evidence that it generates the conscious experience of fear,”he adds.

Christian Jarrett, Editor of the Research Digest Blog for the British Psychological Society, says the study also raises some deep and almost philosophical questions:

“If the amgydala-damaged patients usually live a life that’s entirely fear-free, how did they know to describe their feelings during the inhalation as extreme fear or panic? Can we be sure they really felt fear the way that the rest of us do?”

Feinstein is now planning to look for possible non-amygdala brain circuits using brain scans. He anticipates they will find them in the brainstem and the insular cortex, a brain region known to play a part in bodily awareness.

Written by Catharine Paddock PhD