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The Woman Who Felt No Fear

43m 11s

The Woman Who Felt No Fear

This episode of Science Verses, hosted by Wendy Zuckerman with science journalist Joel Werner, examines the case of SM, a woman with a rare genetic mutation that calcified her amygdala—the brain region long considered the center of fear. SM’s condition made her exceptionally friendly and fearless in response to external dangers: she couldn’t recognize fear in others, showed no fear of snakes (even handling large ones), remained unflustered in a haunted house, and stayed calm during a knife attack and a gun threat. Researchers, including Dr. Justin Feinstein, spent years trying to scare her, but she never flinched at external stimuli. However, a breakthrough experiment involved having SM inhale a single breath of air with extremely high carbon dioxide levels. Within seconds, she panicked, gasped for air, and reported feeling fear for the first time. This response, known as interoceptive fear, arises from internal bodily signals—chemoreceptors detecting blood acidity—and appears to bypass the amygdala entirely. Tests on two other patients with similar amygdala damage confirmed the finding. This challenges decades of neuroscience, suggesting fear is not a single emotion localized in one brain area but involves multiple pathways. The discovery has significant implications for treating conditions like PTSD and anxiety, as it highlights that fear can emerge from diverse neural mechanisms. SM’s case also shows that while fear is often protective, its absence can put individuals in dangerous situations, yet her resilience and curiosity have provided invaluable insights into the human brain.

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Hi, I'm Wendy Zuckerman and you're listening to Science Verses. Today on the show, we are opening up a case file. This is where we report on case reports, which are curious stories from the scientific nerd literature. Basically, in N of 1, a patient wears something weird as happened to them. To go on this adventure, we have science journalist at Fred of the show, Goldwater. Hello. Hello, I'm a curious nerd. This is perfect. Let's go. All right, Joel, to kick us off today, can you tell me that a time that you felt afraid? Very afraid. Look, it's a long list. My fear runs deep. Oh, really? Are you afraid? Yeah, absolutely. I think the last time I felt truly afraid was when I found out how many people listened to podcasts at double speed. What's wrong with you people? This is supposed to be a fun thing. You're supposed to relax. Don't rush through it. No, but seriously, growing up in Australia, I spend a lot of time in the ocean as a kid. And it's really easy for the ocean to go from being like an idyllic, beautiful day to being a near-death experience. And like, I have this one memory of being at a surf beach, and I had gone to the beach with some friends, and we'd sort of swam out beyond the first breakers, like the short break, where the first wave's crashed. And we're catching some waves, you know, frollicking in the water. It's like a soda commercial. And then, yes, suddenly get dumped by a wave, get thrown around underwater, stick my head up, take in a breath, and as I come up, there's another wave crashing on me straight away. And so it happens again. And then I think when the waves hit in a particular frequency, then you suddenly just like you, every gasp of air is a little bit shallower than the last one. And you start panicking a little bit. Is that what you were doing? Oh, definitely. Yeah, yeah, yeah. I was, I was, it went from feeling like, you know, I've been thrown around for one or two waves to being like, if this keeps going, if I don't get out of this, then there's a good chance that something bad could happen. Well, so what did you do? How did you get out? Well, I ended up being able to swim with the wave, so I kind of caught a wave through to that short break area. And then once you can stand, you can kind of like stand up and battle the surf with your legs as well. But I think it's that feeling when you're just floating in the ocean and getting pummeled by the waves. It's, yeah, it's pretty intimidating. Well, today on the show, we're telling you about someone who would be in that situation, and their heart might not even skip a beat. They wouldn't, they wouldn't be scared at all. Wow, someone who has nerves of still, like not not the Friday cat that I am. Someone the complete opposite. And it's all coming up after the break. Welcome back today on the show. We're bringing you a case file, strange reports, case reports, from the literature, and we're here with Joel winner. Hello, hello. Hello. All right, we're going to jump right in. This is a story about a woman who we're going to call SM. And years ago, she started getting these strange spells where she would smell a funny odor, and it was followed by this sensation of being detached or feeling like she was watching herself from above. And so she gets a referral to the University of Iowa for a checkup. See what's going on. She had there an in a paper about SM and kind of this moment, really. Doctors describe her as pleasant and cheerful, but also quick to become friendly with examiners and experimenters, which is exactly how Dr. Justin Feinstein, who worked at the University of Iowa, describes that. She's extremely friendly. She's very trusting. She starts speaking to you right away as if you have this long history, as if she's already your friend. The next thing you know, she's asking personal details about your life and she's telling you very personal details about her life. So she's a bit too much. We all know people like this. This isn't, you know, we don't need to study people who are just like don't know boundaries, don't understand social boundaries, right? But there's some other reasons we might want to study is it, right? So doctors start running tests to see what's going on with these spells. And they give her a CT scan, which uses a kind of x-ray on your brain and normally with a CT scan, you just want to see a little gray brain. That's how, you know, you don't want to see like white patches in there suggesting there's some bone somewhere in your brain, but here's what they saw when they looked at SM's brain. It's quite exquisite. What they saw was very much unprecedented at the time. It was these two bean shaped patterns, hyper intense bright white patterns. So weird. It's so weird looking at the CT scans. It's so specific. It's really bizarre. Even neurosurgeon said how, how his nature, you know, carving out this little almond shaped nucleus and leaving the rest of the brain mostly intact. So bright white patterns, like with an x-ray, does suggest there's something hard in your brain. Let me show you this CT scan. So you see those little. Oh yeah! Like they jump out at you. It's almost like two sort of eyes within the brain. Yeah. Little, little poke-down eyes. Yeah. Not meant to be that. For you and me, presumably, yeah, that should look great. So it turns out that SM has a genetic mutation that calcifies this very particular part of her brain. So the rest of her brain is fine. It's just these specific almond shaped bits get calcified. Yes, it's so weird. It's so weird. The condition is called Herbuck V-Tair disease. It does other things to your body, but in the brain, it's just really calcifying those two almond shaped bits. That's so bizarre. And the bits that this disease is going after very interesting. It's the amygdala. Ah, okay. Jarl, you didn't. You didn't mean a dabbled in neuroscience in the past. Yes, but what does the amygdala mean to you? Well, given the story we were talking about before as well, which is like maybe a big clue. It sort of has something to do with the way that we process fear. Yes, yes, exactly. So the amygdala, we have two on each side of our brains, but for SM, she has none. And it's really. The amygdala is considered the fear center of the brain. It does other stuff, but as one paper put it in the minds of many scientists, the amygdala is synonymous with fear. And basically many researchers have thought that you need it to feel fear. So we use the amygdala to recognize fear, to feel fear when you look at pictures of threatening animals and threatening people. Your amygdala lights up. There have been studies into what happens if we mess up an animal's amygdala to rats who have lesions in there amygdala will go up to a cat. In fact, one of the rats in this very particular study nibbled on the cat's ear. Cat didn't like that? No, no, not a wise decision if you're a rat. No, no. So do they think that. So say when I'm out in the surf and I'm getting pounded by these waves and then I start to think on maybe I can't get out and that panic feeling overwhelms my brain. That's the neurons in my amygdala are firing off. Yeah, they're playing a big role in that whole reaction that you're feeling. Maybe if I have these calcified almonds in their place, then maybe I'm just like lovely day for a surf today. Well, the question was, how would she react? Particularly at this stage when doctors are just meeting her. And this is exactly what they wanted to know because she is so unique here in the world of like brain science. Justin said that at this University of Iowa, they basically collected patients with weird brain lesions and brain stuff going on. It's like a very specific type of Pokemon card. Like you got to collect them all. They had like thousands of people with different brain conditions and with SM. SM is one of the only living humans walking around this earth without an amygdala. So researchers wanted to study it and researchers like Justin to find out what does this mean? Does she really not feel fear? Would she really go into that water and how would she react? She's bunchy jumping every weekend, going skydiving. Well, great, great example because just to give you a bit of context about what's possible here, do you know who Alex Honald is? He's a climber who climbed El Capitan. Oh, the free solo guy. Yes, yes, yes, yes. Okay. So for those who don't know there was a documentary about him called free solo, he climbed this cliff, 3,000 feet up into the air without a harness, without a rope, just him on his own. I feel like my amygdala was like working over time just watching that documentary I was having sweaty palms like that. sinking, feeling in your stomach. - And so he has a functioning amygdala, but researchers have found that it's a little bit tapped down, so when they did some studies on him, they were like, they showed him images that with you and me, our amygdala would be like, "Bing, bing, bing, bing, bing." And he's was like, "Bong, bong, bong, bong." So that is what's possible. And yet he still has an amygdala. - Wow. - And I just do wanna say that the reason scientists wanted to get to the bottom of this, it's not just as a medical curiosity of what is SM capable of, but understanding what the amygdala does, understanding fear could help us with many different things, it could help us understand how we all understand fear, it could help us unravel treatments for PTSD and anxiety, which in some cases are thought to be where your fear responses is maybe a little different to other people. - So the researchers start doing experiments on SM and they start simple. Like at first they'll show her these photos of people's faces with different expressions on them. There's a very classic experiment. - Surprise and disgust and anger and happiness and fear. She clearly could see the pictures, she could tell if it's male or female, she could tell you all the description of what color hair they have, what color eyes they have. - She could recognize anger and happiness and disgust. - But then fear, she had this warping deficit. - Wow. - Yeah, she couldn't recognize when someone else was afraid. - It's not that she just can't recognize emotion generally in people that she's picking up all of these other emotions, but then fear nothing. - Yeah, the warping deficit, it's very strange, right? Next they wanted to know basically could we scare her? And they really wanted to do what's called condition this fear response into SM. So what they do is they show her slides with different colors. - And when a blue square would appear, the shape would be paired with a very loud boat horn. (laughing) - Wow. - Look, I had a boat horn and then forgot it at home. - So, I'm not gonna lie, I'm kind of thankful that I didn't get pranked by a blowhorn. This isn't like early 2000 reality TV. (laughing) This is serious science journalism here. (laughing) - It was really loud, I was. - I also feel like what else are they conditioning? - Well, the thing is, if you, for you and me, it wouldn't take that long to show us the blue square, pair it with the loud sound. And then as soon as we see the blue square, we'll be like, but for SM, never flinched. - What? - Never had any reaction, they could not condition her to feel fear. - Amazing. - All right, they ask her questions out in the real world. Have you ever been scared? And they get into specifics asking her questions about things that a lot of people are scared of. - What kind of animals do you not like? Is there anything that maybe you're afraid of or you just don't find very pleasant and she goes, well, I'm not really afraid of any animals, but I just don't like snakes. She kept saying that. - Snakes. - Fair. - Now, it's interesting here because Justin and his colleagues think that SM's brain wasn't always, like the amygdala wasn't always calcified in that way and that it actually started in her adolescence. And maybe when she was younger, she had an amygdala because she had stories that when she was little, she did feel fear. And she told this story that when she was on a hike with her dad, she actually fell into this pit of baby snakes. - And she remembers at that time being extremely scared and yelling for her father to come get her out of it. - But Justin figures, well, fast forward. Let's see how she reacts to snakes now. So he takes her to a exotic pet store, picture it. I don't know, 50 or so cages of different snakes. They had small ones, very tiny slithering snakes. They had really large ones that probably were almost eight to 10 feet. - Did she share any sign of fear? - She did not. It was so fascinating. In fact, it was the exact opposite. She was extremely curious. You know, I'll never forget her holding one of the snakes and touching its flicking tongue and looking right into its eyes and going almost nose to nose. - Wait, so she intellectually understood that she should have some kind of fear of snakes based on this early childhood experience that she actually didn't feel the fear when confronted with this eight foot snake. - Yeah, even though she had said, I don't like them. She showed no sign of that and, in fact, at one point, the employee at the store had to tell her, like, stop trying to touch the snakes because we think you're going to get bitten. Some of these snakes are actually quite dangerous. - Wow. - And just in thought, maybe there was something about being in the pet store that made her kind of blaze about snakes, like maybe, you know, she felt like a safe environment. And so he asked her son, one of her sons. Has she ever showed, you know, this kind of fear in the real world and her son actually told this story of a time where he and his other brother were playing in the yard and they see this really big snake and they say, oh my god. And again, SM just grabs the snake, just throws it onto the grass, gets it away. And the sun said she seemed sort of feel this. - Wow. There's like some steve and levels snake handling here. It's like, let's just get it out of here. - I know. Justin takes it up a notch and takes her to a very scary spot. I can't believe you took it to a haunted house as part of a study. - You know, and it wasn't just any haunted house. It was Waverly Hills Sanitarium, which is considered one of the most haunted places in the world. - Okay, so Waverly Hills Sanatorium in Kentucky used to be a hospital for tuberculosis patients and a lot of people died there, a lot of people died. And it closed down decades ago, was abandoned, but now you can go on tours there. The Sanitarium even has a TikTok account. So Joel, I want you to describe this video. It is scary. I mean, I'm not into haunted houses, but this looks like a scary place. What are you seeing? - Okay, so there's like, it's a very gothic looking building. There's gargoyles on the top. Are we going down some creepy stairs? - Yeah, ooh, what's that on the walls? - Yeah, okay, I'm out already. Like, if I'm there, I'm just like-- - It looks really scary, right? - It looks pretty weird, yeah. I gotta say though, it's kind of weird hearing a scientist talk about like one of the most haunted places in America. It's like, buddy, come on. - What's even fun here, yeah? Is that other papers have sighted this paper with quite seriousness and been like, look, they even took her to a haunted house, guys. So-- - It was rating a nine on the haunted scale as deeply haunted. - But it's a freaky place, yeah. - It's a creepy place. And when Justin took SM, it was actually Halloween. When the owners of the Sanitarium really got a town and they create this very intense experience. It was extremely creepy. - Imagine, you know, going in through very dark corridors into rooms that you can't really tell what's on the other side, really loud bangs and startling sounds going off. Chainsaws coming out, the strobing lights, the people hiding in weird corners. It was managing to scare me, but there was SM leading us into battle saying, this way, guys, follow me, go through this hallway. Now let's go through this. - She was having a blast. - Amazing. She's just like, cocktail hour. (laughing) - Exactly. - Can we get that chain saw on some lines? I wanna make a hitter. (laughing) - She never screamed, never jumped backwards, never flinched. Justin wrote, she would gaze with amusement at the monstrous creatures smiling or laughing at them in one instance, even scaring an actor. - She's given a back. - She's just like, I'm here to party. - And I have to say that at this point, reading about SM, I was a little bit jealous about what it would be like to have no immediately, to live like, just to think of all the things that I haven't done in my life because I've been afraid. And she feels no fear. How are you feeling? - I don't know. I feel like fear, and correct me if I'm wrong, but I feel like fear plays an important part in our survival. It's good to be afraid of things. - That is exactly what Justin said. Justin was like, you know, we need that spidey sense, telling us, don't jump into that water, don't eat those poisonous berries. - Don't believe the myth of trickle-down economics. (laughing) - Yeah, don't go down that street, don't approach that person or that snake. He's just it again. - The whole point of fear is to. teach you something, right? So the amygdala's role is really to keep you alive and to keep you away from the things that can kill you. - And not having a functioning amygdala at times for SM, it has been rough. - Her life has actually been at risk quite a few times. - So researchers like Justin who study SM have protected her privacy very carefully and no journalists have ever been able to talk to her. But several years ago when Alex Spiegel was co-hosting the MPR podcast in Visibility, she was able to send a short list of questions to one of the neuroscientists who's been studying SM for the last few decades, his name is Daniel Trinnell. And SM told him this story. So it's night time. She's walking through a park near a church. - I was walking through the store and I saw this man on the park bench. - He said, "Come here please." So I went over to him. I said, "What do you need?" He said, "Me." "Why did hurt any how the knife to my throat?" And told him he was gonna cut me. I told him I said, "Go ahead and cut me." And I said, "I'll be coming back in a hunter ass." Oops, am I supposed to say that, I'm sorry. - That's okay, so it's an intense situation. - How did you feel when that happened? - I wasn't afraid. And I just put some reason he let me go. And I went home. - Probably. - No. - What an intense story. She said I got a knife held to her throat by a man in a dark park and still doesn't feel fear. - Yes, and she told Justin this story too. And she even took him to the park where it happened. The way she describes it as she wasn't panicked, she could hear the church choir in the background actually practicing. And it sounds like the guy may have been a little freaked out by how calm she was and he let her go and she walked home. - Wow. - Isn't that, I'd say, it's so, and the fact that she walked home, Justin said he didn't run. She's walked. - And I guess this is what we're talking about before when fear is very useful because for most of us, if we're in that situation, we're not even approaching the creepy guy on the bench. We're clocking him and just getting out of there as soon as we can. - Yeah, and it's not just this incident with the knife. At another time, a stranger put a gun to her head, yelled at the top of his lungs, bam, before running away. That didn't scare her. - SM said she found the whole experience strange. - So are there situations where anyone with a functioning amygdala would be out of there? Would have sort of sensed the fear in the moment and would have sort of extracted themselves from that situation, but for her, because she doesn't have that ability, her brain just doesn't experience that fear. She just stays in the situation until it's too late, essentially, and people are pulling knives and pulling guns. Is that sort of what they think is happening? - That why, I mean, she also lives in an area that's not super safe. There is a lot of violence. There's a lot of drug violence where she lives. And in that instance with the gun, how it happened is that her kid had found some drugs in the yard and she suspected who was in the neighborhood who was dealing and went to the police and just said that's that person. And as a result, was getting a bunch of threatening letters, including a gun being pointed at her. But it's the sort of thing that if you live in that neighborhood, I don't, and you've got kids. I don't think I would be going to the cops. - You keep your head down, right? - Keep your head down. And whereas she doesn't have that level of fear, so she just was like, well, I don't want drugs in my neighborhood. - Wow. - Yeah. And like the other really sort of curious thing about these times is if any of this stuff happened to you and me, it would stay with us. We would, you know, for weeks, you know, months maybe, maybe years we would be thinking over this time about how terrible it was, you know, because the amygdala plays such an important role in like capturing those memories. But maybe it's not so surprising that with SM. - The traumatic events do not seem to stick. It doesn't seem to have an imprint on her long term. - So when you would ask her about these horrible events, how would she react? - She would tell you very matter of factly what had happened. And in some cases, she would actually tell you it with a bit of pride, like, look what, you know, I've had to overcome in life. - So by this point, when it comes to sort of Justin's journey of trying to scare SM and doing all these experiments over years, I mean, he's really thinking, this woman just cannot feel afraid. - She seemed fearless. - After the break, forget snakes and haunted houses. Justin is going to try something completely different that may just change the way we think about fear. (intense music) - Okay, welcome back. Here's where we're at. Scientists have basically been trying to scare a woman who can apparently feel no fear, a part of her brain, the amygdala, that we think is critical for feeling fear does not work in her brain. So this mission is feeling a little bit frivolous. And as a reminder, scientists aren't just doing this for kicks. They're doing this to help us all understand how we feel fear. But I wanted to know, that's why scientists are interested in this. Why is, what about SM? So I asked Justin, why was she up for this? Like, she's been studied for decades. Why does she let herself do this? - You know, I think for her, she's actually quite curious as well about her condition. She knows that she's different. She knows that she obviously has this brain injury. Before this study, she didn't really fully understand how deep her lack of fear went. - But then Justin starts thinking, maybe I need to take a totally different approach here. - For years, actually decades, all of the things we had done to probe SM's fear had been external threats, sounds, sight. But what if, in the words of Zeus, we need to look inside ourselves? Because there is this fear response that we have that has nothing to do with what we can see or hear, but it comes from within. And it's called interoceptive fear. - I'm talking about the brain's ability to sense the inside of your body, the viscera of the body. So like the heart, the gut, your whole respiratory system, for example. So is this like an awareness of your internal like system, like you're hearing your heart beat, you're like sensing the sort of breath going into your lungs? Is it exactly exactly? And so when things go wrong inside our body, sometimes it can make us feel afraid. And so the best example of this, I think, is when it comes to breathing. - From the moment we wake up, until the moment we go to sleep, and even while we're sleeping, we're just breathing, right? We take it for granted. - We breathe in oxygen, we breathe out carbon dioxide, it's this beautiful, delicate dance, our body is happy. But here's what happens if you screw up that dance for just a moment. So there's this experiment that Justin likes to do. Joel, will you do it with me? - Oh, absolutely, yep. - So let's do this experiment. - Just breathe normally. And then I want you to exhale all the air out of your lungs. Every last drop, nice and slowly go ahead. Take as big of an inhale as you can through the mouth all the way 'til you have no room left. And hold it, and then let go. And that's it. That's all it is, is you do that. - Okay, except there is one very important difference between what we just did and the actual experiment. Instead of breathing in regular air, which is actually quite nice, you breathe in a bag of air that has 870 times more carbon dioxide in it than regular air. - Yeah. - So there's quite a lot of CO2. And when people do this experiment, they can get really scared and think that they're going to die. And that's because normally if your CO2 levels go through the roof and your oxygen levels die, it's super dangerous. Now this experiment is safe because you're just taking in one big breath of carbon dioxide and you can sort of balance things out quite quickly when you breathe out air. You can kind of get rid of that carbon dioxide quickly. Also your oxygen levels are fine throughout the experiment, but still your brain, your body gets confused and people panic. - Did you, you must have tried it on yourself, right? - Oh yes, definitely. I started noticing that I'm hyperventilating and it was automatic. I'm just going (exhaling) and like all of a sudden the periphery of the world feels like getting a little darker. And then in my mind, the only thing I could think about at the time was if this continues, I'm going to suffocate. So when I was thinking about these events that have happened in the surf where I've been really afraid, I've thought that the one thing that was driving my fear reaction was the lack of oxygen. It was like I wasn't getting enough air into my lungs, I wasn't getting enough oxygen into my body and I always felt that if I could just get a really big breath in, then I would feel a lot better. And this sounds like this is what this experiment is as well. Yeah, exactly. It was probably both the situation around you, but then this interoceptive fear probably played a role in it as well. Exactly. Interesting. And so now let's go back to SF because Justin and his colleagues wanted to know how would she react to this. What did you think would happen with SM going into that day? Keep in mind the context that I had just spent, you know, the past five years trying my best to find a way to scare SM. And so my expectation is that her response was going to be blunt. What do you mean by blunt, like she'd breathe it in and what would you see on her face? You would not see fear, you would not see this extreme hyperventilation response. Basically, he's suspected and she might have some low-key reaction, but just like with the snakes and the haunted house, it was going to be a bust. And when SM walked into the lab that day, she didn't say more today now. She was from normal self. We're hooking her up to all these different sensors to measure different things. We're putting this breathing mask on her. No sense of fear or anticipatory anxiety. She seems very calm, talking to us, chitchatting and whatnot. She just takes a single breath of a bag of air that contains carbon dioxide. One breath, that's all it is. And this is where things get interesting. Within about a few seconds, she starts waving her hand, saying, "Help me, help me." And then she starts trying to tear off her face mask. When you look at her eyes, her eyes were wide open like a deer and headlights. Never seen that before in SM. And then afterwards, when we talked to her, it took several minutes for her to calm down from this experience. We asked her, "What happened?" And her response was, "I have never felt anything like that before. I felt fear." Wow. That must have been so intense for her. Yeah. Yeah. I mean, I think so. I think she remembered it later when Justin would talk to her, she'd say, "I never want to do that experiment again." Wow. So, do they think that this interceptive fear is like modulated by a different part of the brain? Yeah. Different system going on. Okay. What's happening? Yeah. Okay. Well, so first, he tested it with two other people. It was twin sisters who also had lesions in both of their amygdala's because of the same disease that SM has. Both of them got really scared too, gasping for air, looking very distressed, wanting to rip off the inhalation mask. It was all quite shocking because it showed that contrary to what science thought that the amygdala is essential for fear, I mean, all of a sudden it wasn't. So he's Justin. I mean, if you could have been a fly in the wall in the laboratory that day, our eyes were wide open, our jaw was agape. We were all dumbfounded because this was the exact opposite of what we had expected to happen. You know, for the better part of a half a century, it was always presumed that the amygdala was required to feel fear, to feel panic. And for the first time, we have a human who is lacking this structure in their brain, no longer has the amygdala, yet still felt fear and panic. Where is this happening in the brain? How is this happening in the brain? These were the types of questions spiraling through my head. So ever since this fateful day, I've been racking my brain to try to understand how is this happening? Amazing. So, generally speaking, the reason that all of us can get panicky when we have too much carbon dioxide is because we have these chemical sensors in our blood and throughout our body that detect if the blood is getting too acidic. Cells that are exquisitely sensitive to even small changes in carbon dioxide. And that's because we really need to know if there is too much carbon dioxide in our body, if it happens, it makes our blood more acidic, if our blood gets too acidic, organs can fail. So when these sensors detect, oh, CO2 levels are too high, they emit suffocation alarms or as Justin wrote in a paper, quote, "A proverbial primal scream aimed at alerting the nervous system of impending demise." That's right. You struck the red wine before riding that line, no doubt. Well, keep this in mind. It sounds a little hyperbolic, but it turns out it's absolutely true. If you breathe that level of CO2 for even one to two minutes, it could kill you. This panic response, this alarm is a real alarm. It's trying to alert you essentially that the pH of your blood is dropping. It's becoming acidic. And so these sensors then emit that suffocation alarm and that message ultimately gets sent into your brain. And now your brain is saying, "My goodness, where is all this CO2 coming from?" And that ultimately creates this feeling of fear and panic and, "Oh my gosh, I'm going to die." And so to go back to why did SM have this feeling, well, like the rest of us, she has those sensors that detect carbon dioxide levels. So when the CO2 hit the chemo receptors of SM, those chemo receptors fired like it was a firework show, right? And then those messages got sent to the brain and they must have generated that fear response bypassing any amygdala. Perhaps we don't even need the amygdala for this particular kind of fear response. So basically they're saying that for decades we've thought that the amygdala is necessary for the experience of fear and now they're saying that fear can be experienced in other parts of the brain. Exactly. And in fact, this study of SM with the carbon dioxide, it's since been cited hundreds of times as evidence for this exact thing that you can experience fear without an amygdala. And there's other research, it's not just this, that's showing this kind of thing. And when there's no carbon dioxide around, we are seeing people experiencing fear not involving the amygdala. So for example, there's another patient that had damaged to both of his amygdala, also had that same disease, a buckavita disease. And all of a sudden with him, he just developed these really nasty panic attacks where he'd get heart palpitations and have a fear of dying. And in that case, there was no CO2, it just sort of happened spontaneously. And there are other studies in folks with fully functioning amygdala that have found that other areas of the brain are lighting up in this kind of fear network. And maybe the amygdala isn't this fear center that we thought it was. Maybe it's, I mean, it is really making us think of fear in this totally new way. Obviously, the amygdala is still important for fear because SM did all of these things. Yeah, it's the idea that there are maybe different types of fear as well. But we've been labeling this whole sort of gamut of emotions with the label fear. But like something like, you know, if you're afraid of a snake, there's a sort of intellectualized component to that, right? Like you have to learn to some point that snakes are bad. Whereas this, it sort of seems like a more kind of physiological process where it's like, you've got the extra carbon dioxide in your blood, there are these biological senses that are kind of detecting it. It feels very low brain. Very little brain. Well, you know, that idea, that's kind of how like Justin sings it as well. I think one of the important lessons that SM has taught the scientific world about the neuroscience of fear is that there's probably not one type of fear that is all encompassing and is in one specific brain area. Got it. And just to cap us off, it's been about 10 years since that study that Justin did with SM has been published. And these days, Justin doesn't really study SM, but they are still in touch. And she actually called me the other day and she was quite alarmed with what's happening in the world. And when a patient with bilateral amygdala lesions tells you they're quite alarmed by something you listen, wow, that the world is such a dumpster fire that even the woman who cannot experience fear is afraid of what's going on. That's science vastness. Thank you so much, Joel. Being a pleasure. Thanks, Wendy. Don't know how many citations written this week's episode. Always. 51. Very solid. Thanks, and if people want to see them, they can go to our show notes. And there's a link to the transcript. Thanks. Bye. (upbeat music) (upbeat music)

Podcast Summary

Key Points:

  1. The episode explores a case report of a woman (SM) with a rare genetic condition (Urbach-Wiethe disease) that calcified her amygdala, leaving her unable to experience fear from external threats.
  2. SM could not recognize fear in others, showed no reaction to snakes or a haunted house, and remained calm during life-threatening events like a knife attack.
  3. Researchers initially believed the amygdala was essential for fear, but SM’s lack of response to external stimuli challenged this idea.
  4. In a key experiment, SM inhaled high levels of carbon dioxide and experienced intense fear, proving that interoceptive fear (internal bodily signals) can bypass the amygdala.
  5. This finding suggests fear is not a single emotion controlled by one brain region, but involves multiple pathways, including chemical sensors that detect blood acidity.
  6. SM’s story has implications for understanding and treating anxiety and PTSD, as it reveals alternative fear mechanisms in the brain.

Summary:

This episode of Science Verses, hosted by Wendy Zuckerman with science journalist Joel Werner, examines the case of SM, a woman with a rare genetic mutation that calcified her amygdala—the brain region long considered the center of fear. SM’s condition made her exceptionally friendly and fearless in response to external dangers: she couldn’t recognize fear in others, showed no fear of snakes (even handling large ones), remained unflustered in a haunted house, and stayed calm during a knife attack and a gun threat. Researchers, including Dr.

Justin Feinstein, spent years trying to scare her, but she never flinched at external stimuli. However, a breakthrough experiment involved having SM inhale a single breath of air with extremely high carbon dioxide levels. Within seconds, she panicked, gasped for air, and reported feeling fear for the first time.

This response, known as interoceptive fear, arises from internal bodily signals—chemoreceptors detecting blood acidity—and appears to bypass the amygdala entirely. Tests on two other patients with similar amygdala damage confirmed the finding. This challenges decades of neuroscience, suggesting fear is not a single emotion localized in one brain area but involves multiple pathways.

The discovery has significant implications for treating conditions like PTSD and anxiety, as it highlights that fear can emerge from diverse neural mechanisms. SM’s case also shows that while fear is often protective, its absence can put individuals in dangerous situations, yet her resilience and curiosity have provided invaluable insights into the human brain.

FAQs

SM has Urbach-Wiethe disease, a genetic condition that calcifies the amygdala, leaving the rest of her brain mostly intact. This means she lacks functioning amygdalae, which are typically considered the brain's fear center.

SM showed no fear in these situations. She was curious and amused by snakes, even touching them, and in a haunted house, she led the researchers through, smiling and laughing, never flinching or screaming.

SM felt fear when she inhaled a single breath of air with high carbon dioxide levels. She panicked, gasped for air, and tried to tear off the mask, saying she had never felt anything like that before.

It suggests that the amygdala is not essential for all types of fear. SM experienced fear through interoceptive signals, bypassing the amygdala, indicating that fear can be generated in other brain areas.

SM encountered a man with a knife at her throat and another with a gun, but felt no fear. She stayed in these situations, and her lack of fear also led her to report drug activity to police, risking retaliation.

Interoceptive fear comes from sensing internal body states, like blood CO2 levels, triggering panic. Unlike external threats (e.g., snakes), it bypasses the amygdala and involves chemical sensors that send suffocation alarms to the brain.

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