本文作者：小红猪小分队

Some people really are not scared of anything. Understanding why reveals the way the rest of us process terror

Read more: "Extraordinary minds: Peculiar brain powers"

FOR the first six years that he knew her, Justin Feinstein could find nothing to scare the woman known as "SM". It wasn't for lack of trying. He showed her films like The Blair Witch Project, Arachnophobia, The Shining andSilence of the Lambs, but none elicited even a hint of fear. He then took her to an exotic pet store where, without provocation, she approached a terrarium of snakes and reached in to hold one. She even touched its flicking tongue and declared, "This is so cool!" SM approached the animals with so little caution that a shop assistant had to intervene to stop her petting a tarantula.

Next, Feinstein took her to Waverly Hills Sanatorium in Louisville, Kentucky – a haunted house tourist attraction billed as "one of the scariest places on Earth". Once again, nothing rattled her. While others taking the tour startled or screamed at the strange noises, creepy music and eerie scenes featuring actors dressed as murderers, monsters and ghosts, SM smiled and laughed. In an ironic twist, she managed to frighten one of the "monsters" when she reached out to touch its head – just to find out what it felt like, she later explained.

Feinstein's mission to scare SM might sound like the pranks of a mischievous sibling, but it has a serious purpose. He is a clinical neuropsychologist at the California Institute of Technology in Pasadena, and he believes that studying SM, and a handful of people with a similar lack of fear, could pave the way for a better understanding of how the brain processes terror. Strangely, Feinstein's theory only fell into place once he had finally managed to scare SM. In the future, this work might lead to treatments for post-traumatic stress disorder.

SM first attracted the attention of scientists when she arrived in Daniel Tranel's neurology lab at the University of Iowa in the mid-1980s. She had just been diagnosed with Urbach-Wiethe disease, a genetic condition so rare that fewer than 300 cases have ever been identified. Its symptoms include skin lesions and a build up of calcium deposits in the brain. In SM's case, the disease destroyed the almond-shaped amygdala region of each brain hemisphere (see diagram).

"To have a lesion that's so localised is rare," says Daniel Kennedy, a neuroscientist at Indiana University in Bloomington. "She's one of only a couple dozen known cases." Seeing such restricted damage, Tranel realised that SM's condition could provide a unique opportunity to understand what this region of the brain does.

The amygdala has long been thought to play an important part in the processing of emotions, particularly fear, though its exact role was unknown. Brain imaging studies show amygdala activity during fear, but "what those studies can't tell you is whether it is absolutely necessary for the experience", says Mike Koenigs, a neurobiologist at the University of Wisconsin-Madison. It's possible, he says, that the amygdala activity is a result of processes in other brain structures, without being essential to the feeling.

SM's experience would seem to rule out this possibility, since the feeling of fear vanished from her life soon after the onset of her brain damage (see "Snapshots of fearless living"). What's more, the rest of her emotional palette remains intact, which suggests that the amygdala is not the centre of all our emotions, as some had proposed. "She's not unemotional in any way," says Feinstein.

Indeed, her lively personality reveals a more nuanced picture of the amygdala's responsibilities in our daily lives. Some of these insights come from her relationships with other people. "She's very social, and you might even put her in the category of a slight sensation seeker," says Feinstein.Naotsugu Tsuchiya, a neuroscientist at Monash University in Melbourne, Australia, agrees. He recalls once taking SM to a restaurant while he was working at Caltech. She enjoyed chatting with the waiter during their brief encounter and the next day she wanted to eat at the same place. When they returned, she became visibly happy when she saw the waiter and was extremely genial towards him.

Applying the brakes

Such openness may seem a virtue, but in other situations it suggests that SM can't read the subtle cues that would cause most of us to feel reticent. This is particularly true when dealing with shady characters. "People that you and I would identify as untrustworthy, she would identify as more trustworthy," Kennedy says. "She has a bias towards trusting people and wanting to approach them." All of which would suggest that the amygdala deals not just with immediate threats to our life, but also the smaller signs that might curb our social behaviour.

Kennedy recently tested SM's openness in the lab by examining her sense of personal space. He asked a woman to slowly approach SM, who had to signal the distance at which she felt most at ease. Her preferred distance from the other person was 0.34 metres, almost half the distance chosen by other volunteers (Nature Neuroscience, vol 12, p 1226). "You have this physiological reaction when someone comes too close and invades your personal space, and your amygdala helps to create that," says Kennedy. "It's almost like a car's brakes – it helps to protect us by giving us the ability to regulate our distance."

Further clues to the amygdala's function come from SM's inability to read the subtle cues in certain facial expressions. Again, the deficit is very selective – she can recognise joy or sadness, but struggles to identify fear. Initially, the researchers thought her ability to recognise the emotion was completely lost, but Tsuchiya's recent experiments show that she does retain a short-lived, non-conscious reaction. He presented SM with a string of fearful or angry faces, or threatening scenes next to a neutral stimuli, showing each for just 40 milliseconds – too fast to consciously process. Each time, SM was asked to push a button as fast as she could to choose which face showed more fear or anger or which scene was most threatening. Surprisingly, her performance was completely normal, and it was only when she was given unlimited time to decide that her performance plummeted (Nature Neuroscience, vol 12, p 1224).

Digging deeper, Kennedy has found that the problems lie in the way her brain directs her gaze. When left to her own devices, SM doesn't naturally look into someone's eyes, which offer the surest signs of fear. "They get wide, and you get a lot of white in the eyes – it's a very clear way to distinguish fear," he says. When the experiment was rigged so that her gaze went straight to the eyes, her performance improved dramatically (Neuropsychologia, vol 48, p 3392).

Such differences suggest that the amygdala has a more advanced job than that of a simple "danger detector" as some theories had it. Instead, that initial recognition seems to happen in other regions, below our conscious radar, and it is only once we have registered the threat in our non-conscious that the amygdala orients our attention to gather the critical information – in this case, the eyes – and assess the danger at hand.

This evaluative step may be essential to the ability to experience fear. Without it, SM's brain misinterprets the non-conscious cues signalling danger – they may still elicit a feeling of arousal, but without the amygdala's assessment of the situation, it creates a sense of excitement rather than terror. This could explain SM's curiosity on her trips to the haunted house and exotic pet shops. Rather than behaving indifferently, she was fascinated by sights that terrify most people.

At least, that's how it seemed until Feinstein's latest breakthrough, when he finally managed to scare SM. She was joined in the study by "AM" and "BG", a pair of identical twins who had the same medical condition and similar amygdala damage. Turning to an established method of studying panic, Feinstein asked the group to don a mask that delivers a short burst of air containing 35 per cent carbon dioxide. "The majority of healthy people who do this feel an immediate change in their physiology," Feinstein says. Commonly reported symptoms include breathlessness, a racing heart, sweat on the skin and light-headedness. It can be an unsettling experience and about a quarter of people react with feelings of panic.

To Feinstein's surprise, all three subjects with amygdala damage experienced a dramatic panic attack (New Scientist, 9 February, p 19). SM called out, "Help me!" and put her hands to the mask, gesturing for the researchers to remove it. When asked what she was feeling she responded: "Panic mostly, because I didn't know what the hell was going on." It was the first time she had experienced fear since the onset of her disease.

Two kinds of fear

The other two amygdala-impaired volunteers had similar reactions. AM grimaced and her left hand clenched into a fist as she tried to escape from the mask. She reported feeling "a strong fear of suffocation" and said it was the strongest fear she had ever experienced – she thought she might be dying. BG, meanwhile, gasped for air and ripped the mask off her face. She also told the researchers that she thought she might die if the experiment continued, and said the panic she had felt was "totally new".

Initially, the results seemed to contradict everything that Feinstein thought he knew about amygdala function. How could someone without the structure suddenly feel fear? "It threw me for a bit of a loop," he says. "So much of our research over the past several decades has been focused on the amygdala as the quintessential structure for fear."

After a bit of careful thought, however, he began to see how the findings could fit with his previous theories. Feinstein suggests that the brain processes internal threats, such as an asthma or heart attack, differently from external ones. "It's a primal layer, a very basic form of fear," he says. This makes sense, given that high levels of CO2 change the blood's acidity, which triggers a cascade of reactions across the brain. The resulting neural activity is so widespread that it can create a feeling of panic without the amygdala, whose primary job seems to be to assess threats in our surroundings and direct our behaviour accordingly.

"It makes a lot of sense that something like CO2 could activate some other circuit downstream of the amygdala," says Cornelius Gross at the European Molecular Biology Laboratory in Monterotondo, Italy. He points to parts of the hypothalamus and the periaqueductal grey (PAG) region of the brain as probable candidates.

Indeed, the "fearless" volunteers may have reacted so strongly to the CO2experiment precisely because they lacked the ability to interpret the context of the situation. Although other participants felt the unpleasant sensations that signal the onset of suffocation, their other senses told them that the researchers wouldn't let that happen, damping down their sense of panic. Without the amygdala to weigh up those external cues, however, SM, AM and BG couldn't calibrate the internal sensations with the signs of safety around them, and so found no comfort to ease their terror.

Anticipating threat

The amygdala's role in risk assessment could shed some light on another puzzling finding from the same experiment. Healthy participants usually develop an anticipatory response before a repeat trial – minute changes in their sweat patterns and a slight increase in heart rate. By contrast, the volunteers diagnosed with Urbach-Wiethe disease showed no signs of anticipation as they approached the apparatus for the second time, even though they could clearly remember the panic they experienced on their previous visit. So it seems the amygdala is necessary to draw on memories of fear when assessing a current situation.

Besides advancing our understanding of this mysterious brain region, these results may one day help people who feel an inordinate amount of anxiety. Koenigs has studied veterans of the Vietnam war who were wounded during heavy combat. In a sample of 200 veterans with brain injuries, half had experienced post-traumatic stress disorder. However, none of those with damage to their amygdala had developed the condition.

"We know the amygdala is often overactive in people with fear and anxiety disorders," Koenigs says. His research implies that a functional amygdala may be required to develop post-traumatic stress disorder, though he cautions that it is too soon to know for sure. "This is an active, ongoing area of research," he says. The hope is that researchers might develop drugs or other tools to alter the amygdala's response and reduce the symptoms of these conditions.

Even so, the researchers will have to tread carefully, says Feinstein – knocking out the amygdala would not be a solution, as SM illustrates. Her lack of a sense of risk has made her vulnerable to muggers, and the difficulty she has in reading social signals means she struggles to develop long-term relationships.

A life without fear might seem like bliss, but when Feinstein asked SM what she would say to someone who wanted to be like her, her opinion was definite: "I wouldn't wish it upon anyone."

This article appeared in print under the headline "The curious lives of the people who feel no fear"

Snapshots of Fearless Living

SM has lived most of her life without the ability to feel scared, but she has a few distant memories of receiving a fright as a child, before her inherited condition destroyed her amygdala and with it the emotion. On one occasion, she was walking through a cemetery when her brother jumped out at her from behind a tree and she ran away screaming. On another occasion, a Dobermann belonging to a family friend cornered SM and growled at her viciously. "I can remember my gut tightening up. I was afraid to move," she says. "That's the only time I really felt scared. Like gut-wrenching scared."

Even so, it took researchers years to find any instances of SM experiencing fear as an adult (see main story). Indeed, her grown-up son cannot recall a single occasion on which SM seemed fearful. He remembers a time when an enormous snake had stretched itself across the one-lane road in front of their house. Without flinching, SM grabbed the animal with her bare hands and placed it on the grass where it could safely slink away. Surprisingly, she appears to have had little insight into her own extraordinary behaviour. "She would always tell me how she was scared of snakes and stuff like that, but then, all of a sudden, she's fearless of them. I thought that was kind of weird," her son told a team of researchers that included Justin Feinstein at the California Institute of Technology.

People have sometimes taken advantage of this fearless nature, which has put her life in danger on more than one occasion. One night when SM was 30, she was walking home, alone, through a park where a man she would later describe as looking "drugged out" was sitting on a bench. The man called out and gestured for her to come over. Without hesitation, she walked over to him and when she reached striking distance, the stranger stood up, grabbed her shirt and held a knife to her throat, threatening to cut her. SM didn't flinch. Fearlessly, she told him, "If you're going to kill me, you're gonna have to go through my God's angels first." The man released his hold and SM calmly walked away. The next day, she strolled the same route without a trace of anxiety.

That's not to say that SM isn't aware of everyday dangers and how to avoid them. "She's able to do rule-based fear learning," Feinstein. This is particularly true for routine risk avoidance – she never steps into the street without looking both ways first, for example.

Besides struggling to detect direct threats to her life, SM also fails to perceive risks in social situations, which makes her an easy target for internet scammers and she has had few long-term friendships.

In such precarious circumstances, her frequent lab visits provide an anchor of stability. "The one relationship that hasn't disappointed her has been her relationship with our research laboratory," Feinstein says. "It's something that weighs on me quite a bit." He feels a sense of responsibility to SM after all she has done to further his research. "I view it as, I'm the student and she's the teacher," he says.

Christie Aschwanden is a writer based in Colorado