杏吧原创

Read more: 鈥�Extraordinary minds: Peculiar brain powers鈥�

FOR the first six years that he knew her, Justin Feinstein could find nothing to scare the woman known as 鈥淪M鈥�. It wasn鈥檛 for lack of trying. He showed her films like The Blair Witch Project, Arachnophobia, The Shining and Silence 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, 鈥淭his is so cool!鈥� 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 in Louisville, Kentucky 鈥� a haunted house tourist attraction billed as 鈥渙ne of the scariest places on Earth鈥�. 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 鈥渕onsters鈥� when she reached out to touch its head 鈥� just to find out what it felt like, she later explained.

Feinstein鈥檚 mission to scare SM might sound like the pranks of a mischievous sibling, but it has a serious purpose. He is a 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鈥檚 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鈥檚 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鈥檚 case, the disease destroyed the almond-shaped amygdala region of each brain hemisphere (see diagram).

鈥淭o have a lesion that鈥檚 so localised is rare,鈥� says , a neuroscientist at Indiana University in Bloomington. 鈥淪he鈥檚 one of only a couple dozen known cases.鈥� Seeing such restricted damage, Tranel realised that SM鈥檚 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 鈥渨hat those studies can鈥檛 tell you is whether it is absolutely necessary for the experience鈥�, says , a neurobiologist at the University of Wisconsin-Madison. It鈥檚 possible, he says, that the amygdala activity is a result of processes in other brain structures, without being essential to the feeling.

SM鈥檚 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 鈥�Snapshots of fearless living鈥�). What鈥檚 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. 鈥淪he鈥檚 not unemotional in any way,鈥� says Feinstein.

Indeed, her lively personality reveals a more nuanced picture of the amygdala鈥檚 responsibilities in our daily lives. Some of these insights come from her relationships with other people. 鈥淪he鈥檚 very social, and you might even put her in the category of a slight sensation seeker,鈥� says Feinstein. , 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鈥檛 read the subtle cues that would cause most of us to feel reticent. This is particularly true when dealing with shady characters. 鈥淧eople that you and I would identify as untrustworthy, she would identify as more trustworthy,鈥� Kennedy says. 鈥淪he has a bias towards trusting people and wanting to approach them.鈥� 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鈥檚 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 (). 鈥淵ou have this physiological reaction when someone comes too close and invades your personal space, and your amygdala helps to create that,鈥� says Kennedy. 鈥淚t鈥檚 almost like a car鈥檚 brakes 鈥� it helps to protect us by giving us the ability to regulate our distance.鈥�

Further clues to the amygdala鈥檚 function come from SM鈥檚 inability to read the subtle cues in certain facial expressions. Again, the deficit is very selective 鈥� 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鈥檚 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 鈥� 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 ().

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鈥檛 naturally look into someone鈥檚 eyes, which offer the surest signs of fear. 鈥淭hey get wide, and you get a lot of white in the eyes 鈥� it鈥檚 a very clear way to distinguish fear,鈥� he says. When the experiment was rigged so that her gaze went straight to the eyes, her performance improved dramatically ().

Such differences suggest that the amygdala has a more advanced job than that of a simple 鈥渄anger detector鈥� 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 鈥� in this case, the eyes 鈥� and assess the danger at hand.

This evaluative step may be essential to the ability to experience fear. Without it, SM鈥檚 brain misinterprets the non-conscious cues signalling danger 鈥� they may still elicit a feeling of arousal, but without the amygdala鈥檚 assessment of the situation, it creates a sense of excitement rather than terror. This could explain SM鈥檚 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鈥檚 how it seemed until Feinstein鈥檚 latest breakthrough, when he finally managed to scare SM. She was joined in the study by 鈥淎M鈥� and 鈥淏G鈥�, 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. 鈥淭he majority of healthy people who do this feel an immediate change in their physiology,鈥� 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.

鈥淪he called out 鈥榟elp me鈥� and raised her hands. It was the first time she had felt scared as an adult鈥�

To Feinstein鈥檚 surprise, all three subjects with amygdala damage experienced a dramatic panic attack (New 杏吧原创, 9 February, p 19). SM called out, 鈥淗elp me!鈥� and put her hands to the mask, gesturing for the researchers to remove it. When asked what she was feeling she responded: 鈥淧anic mostly, because I didn鈥檛 know what the hell was going on.鈥� 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 鈥渁 strong fear of suffocation鈥� and said it was the strongest fear she had ever experienced 鈥� 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 鈥渢otally new鈥�.

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

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. 鈥淚t鈥檚 a primal layer, a very basic form of fear,鈥� he says. This makes sense, given that high levels of CO₂ change the blood鈥檚 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.

鈥淚t makes a lot of sense that something like CO₂ could activate some other circuit downstream of the amygdala,鈥� says 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 鈥渇earless鈥� volunteers may have reacted so strongly to the CO₂ experiment 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鈥檛 let that happen, damping down their sense of panic. Without the amygdala to weigh up those external cues, however, SM, AM and BG couldn鈥檛 calibrate the internal sensations with the signs of safety around them, and so found no comfort to ease their terror.

Anticipating threat

The amygdala鈥檚 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 鈥� 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.

鈥淲e know the amygdala is often overactive in people with fear and anxiety disorders,鈥� 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. 鈥淭his is an active, ongoing area of research,鈥� he says. The hope is that researchers might develop drugs or other tools to alter the amygdala鈥檚 response and reduce the symptoms of these conditions.

Even so, the researchers will have to tread carefully, says Feinstein 鈥� 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: 鈥淚 wouldn鈥檛 wish it upon anyone.鈥�

This article appeared in print under the headline 鈥淭he curious lives of the people who feel no fear鈥�