Living Without Fear

Doctors at University of Iowa have been studying a female patient they call "SM" for more than 20 years. SM has a damaged amygdala, a part of the brain. As a result, she doesn't experience fear. Daniel Tranel explains what doctors have learned from SM and how that information might be useful.

IRA FLATOW, host:

You're listening to SCIENCE FRIDAY. I'm Ira Flatow.

Up next, an unusual story of a woman who knows no fear, literally.

For decades now, doctors in Iowa have been studying a patient they call SM. SM first came to them as an adolescent. She was diagnosed with a rare condition that caused lesions on a certain area of her brain, the amygdala. And because of the damage to her amygdala, SM does not experience fear.

Doctors have shown her snakes and spiders. They've taken her to haunted houses. They've sat through with her what most of us would consider to be scary movies, and none of that seems to frighten her.

Joining me now to talk more about this unusual patient and what her brain condition might tell us about fear in other people is my guest, Daniel Tranel. He is professor of neurology and psychology at the University of Iowa in Iowa City.

Welcome to SCIENCE FRIDAY.

Professor DANIEL TRANEL (Neurology and Psychology, University of Iowa): Thank you, Ira. I'm glad to be here.

FLATOW: She must certainly be the most unusual patient you've had, I imagine.

Prof. TRANEL: Well, she ranks up there with some of our most interesting cases and some of the patients from whom we've learned a tremendous amount in terms of understanding how the brain works.

FLATOW: How did she come to your attention?

Prof. TRANEL: Well, she was actually referred to the Neurology Department here at the University of Iowa, to a colleague of mine - in fact, a co-author on this paper, Antonio Damasio - for neurological symptoms.

We - at that time - that was back in the era when CT scans were the primary mechanism to look at brain structure. And we gave her such a scan, and lo and behold, this revealed these very intriguing lesions in the amygdala that you mentioned in the lead-in.

FLATOW: Mm-hmm. And how are you sure that that's where and why that she has no fear?

Prof. TRANEL: Well, that's a good question. We've studying her for, well, for more than 20 years at this point and have done numerous experiments, leading to the basic conclusion that she doesn't experience fear.

The recent study in Current Biology that we just published perhaps is the most definitive in that regard, though, because these field experiments that you summarized, Ira, in terms of exposing her to snakes and spiders and going through haunted houses really provide the best evidence that I've seen to date, you know, of no fear in situations that should be triggering fear.

FLATOW: Mm-hmm. Let's talk about fear for a bit. Is there a difference between fear and worry? Does she worry about things?

Prof. TRANEL: There's a very fundamental difference between fear and worry, and she does worry. Worry is more in the domain of anxiety and has a lot to do with something we humans do a lot of, which is the future, spending time in the future.

Fear, by contrast, is more of an immediate emotion that's kind of in the moment.

FLATOW: And does she realize what fear is? In other words, can you describe it to her? It's hard - is it a concept she can relate to?

Prof. TRANEL: It is. And, in fact, I was listening to your opening, and she's actually not a person who knows no fear. She experiences no fear, but she, in fact, does know fear sort of in an intellectual way.

She has a concept of what fear is and what it, you know, the situations that ought to provoke it and what normal people would do when in such situations.

FLATOW: So if she is confronted by something that might be fearful to us - let's say a snake. She's in a pet shop. She's not afraid to go over and touch it because she has no fear of it?

Prof. TRANEL: Correct. That's - yeah, that stimulus doesn't induce a state of fear, and thus, she doesn't have the feeling of fear.

FLATOW: And if you tell her that she should be afraid of it, she would not know why she should be afraid of it?

Prof. TRANEL: Well, she would at the level of, you know, yes, lots of people are afraid of snakes, and snakes could bite you. I mean, she would articulate that intellectually. So it's really the feeling that's missing.

FLATOW: Has this lack of fear caused any problems for her?

Prof. TRANEL: Very much so. She has been repeatedly in situations that fear would have kept her out of, I mean, in a nutshell. She goes into unsafe situations, where a normal person would not even approach the situation. And, of course, she does this repeatedly and doesn't avoid those situations and puts herself in harm's way, as a consequence.

FLATOW: Mm-hmm. And what do you learn from her in terms of people like us, who have fear?

Prof. TRANEL: Great question. We learn that the amygdala is a critical brain structure for taking stimuli, sensory information coming from the world outside and relaying that information to critical brain stem nuclei, hypothalamus that are responsible for enacting a bodily pattern of fear-related signals.

Those are, in turn, interpreted, you know, consciously as a feeling of fear, and now we know that the amygdala is a critical part of that pathway. So when you take that out of the loop, you don't get the fear in the body, and you don't get the feeling of fear.

And if I can just go one more step, that has some immediate and very important treatment implications. You know, for example, we can target the amygdala with medications, with therapy that could, you know, down-regulate that structure in people where it was overactive - for example, people with psychiatric conditions, with post-traumatic stress disorder, with phobias.

FLATOW: Interesting - and try to counteract it, then.

Prof. TRANEL: Yes. If we could down-regulate the amygdala in, you know, for example, people with PTSD, that could be a very effective treatment for, you know, getting rid of their fear, which is, in that case, abnormal.

FLATOW: If she hears a loud noise, or somebody yells boo or something, does it startle her?

Prof. TRANEL: Well, she tends to have a basic startle response, but not to fear stimuli. She has a more robust startle response to surprise, you know, more positive types of startled.

FLATOW: So what's it like to do this kind of work with her? Do you find her, you know, as something that you can't relate to because you're fearful of many things she's not?

Prof. TRANEL: Well, that's a great question, Ira. It's always remarkable to - you know, and I've worked with human patients, neurological patients, for close to three decades with my colleagues Antonio Damasio and Justin Feinstein and Ralph Adolphs, who participated in this study, and it's always remarkable to, you know, have a patient come along and just be missing some really basic behavior that's such a basic part of our repertoire as humans.

FLATOW: Right.

Prof. TRANEL: And, you know, to relate that to a particular brain structure is, of course, very intriguing. And that's been the bedrock of our research program here at Iowa.

FLATOW: Right. You know, when we think of fear, we also think of pain. You know now to touch something hot, right? You're fearful of that. Does she understand those things, that something might be painful?

Prof. TRANEL: She has a normal concept and reaction to pain at a basic level, but not in the sense of pain that would be associated with or conditioned to another stimulus. In fact, with Antoine Bechara, we did an experiment several years ago where we did exactly that.

We tried to condition her to a - it was basically a blue patch of color that we presented, and we accompanied that with a sort of a loud, painful auditory stimulus. And she showed no conditioning in that situation, so kind of not learning that certain things can be painful.

FLATOW: Let's go to Leslie in Indiana. Hi, Leslie. Welcome to SCIENCE FRIDAY.

LESLIE (Caller): Hi, thanks. I was wondering how it affects her in, like, social situations. I think of fear as being - sometimes being afraid of the possible consequences. Does she not fear possible consequences? Like, is she willing to say inappropriate things to her boss or something like that, approach someone with a gun and not be worried about what could happen?

Prof. TRANEL: Yeah, great question. Yes. She is impaired in that kind of a situation. The amygdala is probably more specialized for basic fear, behavior, you know, things like kind of in the spiders and snakes category.

But, you know, as you work your way up the system, you - it's exactly what the question suggests. Do you fear the, you know, adverse consequences for a particular behavioral choice and make a decision now to avoid a path that's going to run you into those consequences?

FLATOW: Right.

Prof. TRANEL: And she does have that kind of a deficit.

FLATOW: Right. And you can see the problems, the social problems or the physical problems, you know, on a street in the wrong neighborhood where, you know, you might walk into an armed robbery or something and not even know that something's going on there.

Prof. TRANEL: Yeah.

FLATOW: Where to be afraid of. How about height? Is she afraid of heights? Does she have a concept of that?

Prof. TRANEL: She's not afraid of heights. She claims to enjoy rollercoasters, and maybe that could be her next field experiment, is to take her on some rollercoasters.

FLATOW: Huh. Is there any way to monitor her brain function in real time if you would, let's say, put her on a rollercoaster and see what kind of reaction she might have? Or is that something that you don't need to do?

Prof. TRANEL: Well, it will be ideal for scientists to be able to do that. In fact, you know, the best case scenario you can look at, you know, blood flowing in the brain and neurons firing and the whole nine yards. That's, of course, really not feasible for, you know, the rollercoaster. But we could, you know, we can monitor physiological responses and, of course, behavioral output...

FLATOW: Yeah.

Prof. TRANEL: ...which brings me - you know, one of the great advantages to working with a human patient is that they can tell you what's happening. This idea that fear and the amygdala are connected has been around for a long time, and there's a lot of animal work that brought us into this hypothesis. But to confirm this with a person is, you know, you have the access to the person's consciousness.

FLATOW: And this is something that's been going on for a long time with her.

Prof. TRANEL: Yes.

FLATOW: So she's been poked and prodded and looked at ever since she was an adolescent. And is - so does she find this as a normal part of her life now?

Prof. TRANEL: I would say she does. In fact, I was telling Justin the other day, if a couple of months goes by and we haven't called her, she starts to call us.

FLATOW: Hmm.

Prof. TRANEL: And wonders if a graduate student has some new experiments to try.

(Soundbite of laughter)

FLATOW: 1-800-989-8255 is our number. We're talking about, well, fear in - and do you know of any other people who have this similar kind of condition or is she unique?

Prof. TRANEL: There are other people with this condition. It's very hard to make a guess, but maybe hundreds, the world over. It's a very rare genetic disorder. And, in fact, in only about half the cases that have the disorder, do you get this brain manifestation. So the cases are very rare. There are others in the world.

FLATOW: Well, let me just have - just put an idea in here just so we can talk a little bit more.

I'm Ira Flatow. This is SCIENCE FRIDAY from NPR.

Talking with Daniel Tranel. And this is what makes me think that could there be people - you know, you look at people who say, oh, that person is fearless. Could they be having a smaller functioning, you know, in the amygdala than most people have...

Prof. TRANEL: Absolutely.

FLATOW: ...and still be in the normal range, you know?

Prof. TRANEL: Absolutely. Absolutely. Most biological phenomena are distributed, you know, kind of in a bell curve. And you have people at the high end and at the low end and, you know, most of the people in the middle somewhere.

FLATOW: Right.

Prof. TRANEL: So, you know, lack of fear can be a good thing in some situations. You know, it can be constructive in some niches, not too many.

FLATOW: Hmm. Let's see if I can get a quick call in here. Paul in Louisville. Hi, Paul.

PAUL (Caller): Yeah, hi. Thanks for taking my call. I have a question about just, like, adventurism and fun. I mean, I've done some skydiving and bungee jumping, those kind of things. And you mentioned rollercoasters, earlier. I mean, part of the fun of that is the fear of it. I mean, that you - that the adrenaline rush and getting over this, like, terror of what it is you're about to do. Does she have that sense?

Prof. TRANEL: Well, no. She doesn't have that sense. And that's kind of a - you know, you're absolutely right. We deliberately put ourselves in situations that have a certain degree of fear because they're also thrilling and arousing, and there's a positive reinforcement from that. And she lacks a lot of that.

FLATOW: Hmm. A tweet from Tim Beauchamp says is there an opposite of fear? And if so, does she experience that?

Prof. TRANEL: Is there an opposite of fear?

FLATOW: Mm-hmm.

Prof. TRANEL: Well, she is the opposite of fear, in the sense, not having it.

FLATOW: Right.

Prof. TRANEL: And there are too much of it, and you have PTSD, you have a severe phobia that incapacitates you, et cetera.

FLATOW: Let's see if I can get another quick call from Brian in Columbus. Hi, Brian.

BRIAN (Caller): Hi. Thanks for picking up, Ira. Happy holidays.

FLATOW: You, too.

BRIAN: Hey, I'm fearful - no pun intended - that if a group of people with bad intentions were to learn the details of these findings, Dr. Tranel, could they perhaps, say terrorists, utilize this amygdala malfunction for their benefit?

Prof. TRANEL: Well, I suppose that's possible. Not to, you know, not to provide any recipes in a public forum, but, you know, let's say you were running an army and, you know, gave everybody in the army bilateral amygdala lesions, you know, maybe you'd have soldiers who would do anything. And I guess you could imagine that that could be a good thing somehow. But that's a - sounds like a disaster in the final analysis.

FLATOW: So where do you - where would you go from here? What would you like to know now and how would you proceed?

Prof. TRANEL: Well - so one interesting question, Ira, is, you know - so we have this connection with the amygdala in the middle of the circuit for stimuli coming from the outside. What about stimuli coming from the inside? What about the pain associated with a heart attack? What about the sensation of choking? What pathway would such signals use? So - and so a really interesting question to ask is whether that pathway might be different and not need the amygdala. There's a little evidence for that already, and that's an interesting question that we would like to pursue.

FLATOW: You're not going to choke or cause a heart attack or anything like that, just so we get that clear for our listeners who might be mishearing that.

Prof. TRANEL: I don't think we'll - we won't choke or give a heart attack to a subject who's arguably been a goldmine for...

(Soundbite of laughter)

Prof. TRANEL: ...the investigators in our group for a long time. But there are ways to induce those sensations experimentally, so you can kind of get that process - sort of an as-if process - started.

FLATOW: All right. This is fascinating. Thank you very much for taking the time to be with us.

Prof. TRANEL: I - thank you for having me on the show, Ira. It's always a pleasure and great to talk with everyone.

FLATOW: Thank you. Have a happy holiday.

Prof. TRANEL: Happy holiday to you, too.

FLATOW: Daniel Tranel is professor of neurology and psychology, University of Iowa in Iowa City. We're going to take a break and come back and talk more about putting a storm door under your tree. Yeah. Think about that. We'll be right back.

I'm Ira Flatow. This is SCIENCE FRIDAY from NPR.

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