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Our next guest, V.M.(ph) Ramachandran, is known for thinking about the mysteries of the human brain in creative ways. In his new book, for example, he seeks to understand why a man in the hospital with a brain injury could speak to his father on the telephone, but was unable to recognize him or speak when his father entered the room.

Ramachandran's research combines modern advances in neuroscience with low-tech, common-sense approaches, as you'll soon hear. His new book looks at unusual cases of brain dysfunction for clues about how the brain works, and he explores evolutionary explorations for the brain's complex wiring in what he calls a quest for what makes us human.

V.M. Ramachandran is the director of the Center for Brain and Cognition, and distinguished professor with the psychology department and neurosciences program at the University of California San Diego. He's the author of "Phantoms in the Brain." His new book is called "The Tell-Tale Brain."

Well, V.S. Ramachandran, welcome to FRESH AIR. Let's begin by talking about some of this amazing work you've done with mirror visual feedback, and this involves people who have had an amputation, but who feel a phantom limb. First of all, explain that phenomenon, what happens to people sometimes - when they're sometimes missing a limb and they feel these things.

Dr. V.S. RAMACHANDRAN (Author, "The Tell-Tale Brain"): Well, when an arm in amputated following a crash injury in a car accident, or there's a cancer or malignant tumor or a cancer in the arm, or there's a gangrene and the arm is amputated, typically for diabetes, and when that's done, 98 percent of the time the patient continues to vividly feel the presence of that missing arm. We call this a phantom limb.

So typically the patient goes under general anesthesia and you've already told him that you're going to amputate his arm, unfortunately. And then you proceed with the amputation and he comes out of anesthesia, and he's surprised initially because under the sheets he continues to feel the arm, and he says when are you going to do surgery?

Then you remove the sheets him and show him that the arm is gone, and he's often shocked to see this because he continues to feel the presence of the arm even upon seeing that it's not there.

This has been known for a couple of hundred years, but studied systematically over the last hundred years, and there have been dozens of case studies, but nobody really understood what was going on in the brain. Why would these people be haunted by these phantom appendages? And you get a phantom with almost any part of the body.

DAVIES: Yeah. And it was fascinating to read that some people will feel an itch in the palm of a hand that isn't there, or feel chronic pain, right?

Dr. RAMACHANDRAN: Yes. Chronic phantom pain is a serious clinical problem. About two-thirds of them, they have very severe pain. Sometimes so excruciating the patient becomes very depressed, sometimes - often loses his job. Sometimes even contemplates suicide.

DAVIES: Yeah. And before we talk about some of the work you did with mirrors to alleviate this, tell the story of the gentleman who you were able to discover regions of his face that would affect his sensory perceptions of his missing limb.

Dr. RAMACHANDRAN: Well, there are nerves which used to supply the fingers and hand which now supply the stump. But those nerves get irritated and misinform the brain that the hand is still there and surviving, and the nerves are painful. You get pain referred to the missing phantom hand. And based on this, therapies were devised where you remove the nerves or the terminals of the nerves which are curled up and painful. This often provides partial relief, but is usually notoriously ineffective.

What we did was a simple experiment based on an idea that there's a complete map of the body surface on the surface of the brain. So every point in the body surface has a corresponding point in the brain, and there's a systematic map.

Now, the curious thing about this map is, even though it's continuous, all parts are represented, the face area of the map is right next to the hand area. It's dislocated, instead of being near the neck where it should be, and nobody knows why. So our reasoning was, when the arm was amputated, the hand representation in the cortex is devoid of sensory input. It's deprived of sensory input. It becomes hungry for new sensory input.

So the sensory input from the face skin sprouts terminals or invades the territory corresponding to the missing hand. So when you now touch the face, the hand area of the brain is activated, not just the face area.

So the result of all this is very simple. You blindfold the patient so he doesn't know where you're touching him and you touch his leg and his abdomen and his chest and he accurately reports where you're touching him, obviously. But when you touch his face on the same side as the amputation, the patient says oh, I feel that in my phantom missing thumb, and expresses considerable surprise.

DAVIES: Right. So this person might feel an itch in his palm which he could scratch by touching the right spot on his face. And I guess one of the things this tells us is that the brain is growing new tissue as even - it doesn't just happen in embryo. I mean, it's - new things are happening, the brain is sort of remapping itself a bit as we grow older?

Dr. RAMACHANDRAN: Yes. I mean, what we were all taught as medical students say a decade or two ago was that connections in the fetal brain, or an infant brain, are fixed during infancy or fetal life by the genome - by genes. And then as you grow into adulthood, the maps crystallize and are there permanently. And you can't do anything but change these - alter these maps. And if there's injury to the brain, the injury is permanent and there's very little recovery or function after tissue damage to the brain.

So we - our findings suggest that this is not true. The map - even the basic sensory map in the brain gets completely reorganized in a matter of weeks. And more recently we have shown that if this happens in just a couple of days, you get some reorganization taking place. This challenges the dogma that all medical students are raised with, and all neurologists are raised with, that no new connections or new pathways can emerge in the adult brain. That was news 10 or 15 years ago. Now, it's widely accepted.

DAVIES: OK. Let's talk about this remarkable treatment that you developed for people who have had amputations and may have terrible pain in their phantom limb, and a treatment that you did with a simple mirror. Explain what you had your subject do.

Dr. RAMACHANDRAN: Well, in simple terms, the patient has a phantom limb, and very often, for reasons that are not entirely clear, the phantom is clenched in an excruciating position, like the fingers are clenched into the fist with the nails digging into the palm - the phantom nails digging into the phantom palm.

And they will often say things like well, if I could only open my phantom hand or move my phantom arm, it might relieve this cramping sensation. But I can't do that, my phantom is paralyzed. I should backtrack a little bit and say that many patients with a phantom can move the phantom. They'll say it's waving goodbye, it's patting my little brother on the shoulder, it's reaching out for the phone when the phone rings.

These are very vivid sensory impressions for the patient. But in about a third to half the cases, the phantom is paralyzed as I just said. It sounds like an oxymoron. How can a phantom be paralyzed?

What we found when we looked at the case history, many of these people had a real paralysis of the arm where the arm was intact. For example, nerves going from the spinal cord into the arm were yanked off the spinal cord in a motorcycle accident so the entire arm is paralyzed and lying in a sling and excruciatingly painful and paralyzed for years.

And then, in a misguided attempt to get rid of the pain, sometimes the arm is amputated. And the irony is the patient is then left with a phantom arm in a phantom sling when the pain persists with a vengeance in the phantom. And we call this phenomenon learned pain or learned paralysis. The question is can you unlearn the learned pain or learned paralysis by allowing the brain to send a command to the phantom and have the phantom move in response to the command or appear to move. How do you do that? The guy doesn't have an arm so how do you make his phantom appear to move?

DAVIES: You have to trick the brain, in a way?

Dr. RAMACHANDRAN: To trick the brain. How do you trick the brain? So then I hit on a technique of just using a five-dollar mirror which you prop up on the table in front of you, put some bricks or take a cardboard box and remove the top of the box and remove the front of the box, prop up a vertical mirror. And then, the mirror is sort of parallel to your nose and sitting in front of you on the table. Sorry, I should say standing up in front of you on the table. Then, the patient puts his phantom limb, let's say his phantom left arm, on the left side of the mirror, which is the non-reflecting side, puts the normal right arm on the right side of the mirror, which is the reflecting side, and looks into the mirror at the reflection of the normal hand.

Now, if he then starts moving his two hands, well, he can't move his phantom. He can pretend it's moving. Clapping his hand or conducting an orchestra or waving goodbye, while looking in the mirror, he's going see the mirror reflection of the right hand super-imposed on the phantom, moving in command -moving in perfect synchrony with the command sent to the left hand, to the command sent to the phantom arm. So you give the visual illusion that the phantom, in fact, is obeying the command.

DAVIES: When you've done that, do patients say, oh, my God, I can actually see my phantom limb now?

Dr. RAMACHANDRAN: Yes, absolutely. They get spooked out by it or they get intrigued. They'll say, my God, my phantom. I see my phantom. Of course, I know it's not there. Some people will look behind the mirror and chuckle. I know it's not there, but it feels like it's there. It not only looks like it's there, it feels like it's there. And when I move my normal hand, the phantom arm looks like it's moving. When I open the normal fist of the right hand, the phantom limb, whose fist I could not open for months, now suddenly feels like the fist is opening as a result of the visual feedback and the painful cramp goes away. So this is a striking example of modulation of pain signals by vision.

DAVIES: You know, one of the fascinating things about the story that you just told is that modern medicine involves so many advances in sophisticated high-tech tests and treatments, and you're using a $5 mirror. And I have to note that you have quite a varied intellectual background. You think of these problems differently, don't you?

Dr. RAMACHANDRAN: Well, that is correct. I mean, I think that - I was raised in India and I was raised in Thailand, but the emphasis was on low-tech by necessity. And I think that emphasis actually is beneficial because it makes you think more creatively and it makes you more resourceful and rely on your ingenuity, so to speak. And this spills over into your research, this attitude and this technophobia.

But I want to emphasize that often, you know, we're not Luddites. We don't shun technology, but the initial experiments are often very simple and the simplicity of the experiment is often deceptive and often, in spite of being simple, the results can be quite stunning.

But more recently we've studied an extraordinary syndrome where a patient says he - we were just talking about phantom limbs earlier. But even more extraordinary and much more rare is a syndrome where a patient, who is otherwise completely normal - in fact, you can't even call them patients, in normal people out there - who want their arm amputated at a specific level.

DAVIES: Right. This is apotemophilia(ph), right? This is somebody who...

Dr. RAMACHANDRAN: Apotemnophilia.

DAVIES: OK. They think that a part of their own body is foreign to them, right?

Dr. RAMACHANDRAN: Well, not exactly. No, it's very interesting. Because in clinical medicine, it's very important to talk really carefully to the patient and often you can clinch the diagnosis 90 percent of the time, figure out what's going on by just talking to the guy, which is not fashionable these days.

So for example, this patient says, my arm - I want my arm removed. That's why he's there. I want my arm removed. I know I'll be happier if it's removed. And he takes a felt pen and draws a line along which he wants the amputation, maybe just above the elbow, just below the elbow. It's different for different patients. Or below the knee, right? And then, he says, I want it amputated and about a third of them will get it amputated.

DAVIES: Seriously? People will do that?

Dr. RAMACHANDRAN: Oh, absolutely. They will get it amputated and they feel much happier. Their depression goes away and they feel like more of a complete person, paradoxically. Well, they say, it's not like I don't - it's not like the arm doesn't belong to me. I know it belongs to me. It's not like it feels like it doesn't belong to me. In fact, it feels like it belongs too much to me. It feels intrusive, right, which is slightly different from saying, it doesn't belong to me. Now, why the difference?

DAVIES: Yeah, what's going on?

Dr. RAMACHANDRAN: OK. You see, there are two stages. First of all, the signals from the arm, skin, muscles, tendons and all of that go first to the sensory area in the brain, the vertical strip I told you about earlier when talking about phantom limbs. So there's a complete map of the skin surface and the muscles and all of that just on the side of the brain. That's where all the sensory processing occurs. And then, the signals are relayed around to the body image center, which then gets signals from vision and from your inner ear and all of that. So there is a more abstract representation of your body in the body image center, which is more dynamic.

So there are two stages. The sensation is processed from the skin and ligaments and tendons and muscle and then, after that, it's sent to the superior parietal lobule where you construct the body image, OK? So the sensory input going from the skin of the hand, from the muscles, from the tendons, goes to the sensory area and it's processed normally. That's not damaged because there's no stroke. But in his superior parietal lobule, in the body image center, the arm is congenitally missing so there is no place in the brain for the signals to be relayed to. And it gets there and there is an acute discrepancy between his body image and what the sensory signals are telling him.

DAVIES: And what might cause that? Is that a - would that be a congenital defect or...

Dr. RAMACHANDRAN: It's a congenital defect, is what we think. And we've filmed this using brain imaging techniques, where these people have a congenital defect in that region of the brain. And we're still not 100 percent sure of this, but we're 90 percent sure that that's what's going on. And therefore, the signals come in from the arm, sensory representation is normal, but there is nowhere for the signal to go and the brain is faced with a discrepancy. And the brain abhors discrepancy.

It's constantly trying to produce a sort of coherency of information to produce stability of behavior. And when there is a discrepancy, the discrepancy is picked up by another region of the brain called the insular, which then generates the fight/flight response, generates acute anxiety and the patient says I want the arm removed. It feels over-present and he senses the discrepancy. So that is what's going on.

DAVIES: V.S. Ramachandran's book is called "The Tell-Tale Brain." More after a short break. This is Fresh Air.

(Soundbite of music)

If you're just joining us, we're speaking with V.S. Ramachandran. He is a behavioral neurologist and author of the new book "The Tell-Tale Brain: A Neural Scientist's Quest for What Makes Us Human."

You write a lot about mirror neurons and the role that they played on our evolution. You want to just tell us a little bit about that?

Dr. RAMACHANDRAN: Well, mirror neurons were not discovered by us, obviously. They were discovered by Giacomo Rizzolatti in Parma, Italy, and his colleagues. And what they refer to is in the front of the brain, the motor and pre-motor cortex, there are neurons that issue commands to your hands and other parts of your body to perform specific actions, semi-skilled actions, skilled actions or even non-skilled actions. So these are motor-command neurons which orchestrate specific sequence of muscle twitches for you to reach out and grab a peanut, for example, or put it in your mouth.

What Rizzolatti and his colleagues found was some of these neurons, as many as 20 percent or 30 percent, will fire not only when - let's say I'm measuring mirror neuron activity in your brain. So when you reach for a peanut, these neurons fire. But the astonishing thing is these neurons will also fire when you watch me reaching for a peanut so these are promptly dubbed mirror neurons for obvious reasons. So it's as though your brain is performing a virtual reality simulation of what's going on in my brain, saying, hey, the same neuron is firing now when he's doing that as would fire when I reach out and grab a peanut, therefore, that's what that guy's up to.

He's about to reach out and grab a peanut. So it's a mind-reading neuron. It's essential for you seeing other people as intentional beings who are about to perform certain specific intended actions.

DAVIES: And that might have helped us learn from one another and thereby advanced culturally far beyond our...

Dr. RAMACHANDRAN: That's correct. That's the stuff - that's kind of an obvious behind-site, but that's the claim I made, oh, about 10 years ago in a website run by Brockman called "Edge." And what I pointed out was - and others have pointed this out, too, is that mirror neurons obviously are required for imitation and emulation. So if I want to do something complicated that you're doing and I want to imitate it, I have to put myself in your shoes and view the world from your standpoint. And this is extremely important.

It seems like something trivial, you know, mimicry, but it's not. It's extremely important because imitation is vital for certain types of learning, rudimentary types of learning. These days you learn from books and other things, but in the early, early days when hominids were evolving, we learned largely from imitation. And there's a tremendous acceleration of evolution illusionary process. What I'm saying is maybe there are some outliers in the population who are especially smart simply because of genetic variation, who have stumbled, say, accidentally on an invention, like fire or skinning a bear.

Without the mirror neuron system being sophisticated, it would have died out, fizzled out immediately. But with a sophisticated mirror neuron system, your offsprings can learn that technique by imitation so it spreads like wild fire horizontally across a population and vertically across generations. And that's the dawn of what we call culture and therefore, of civilization.

DAVIES: Well, V.S. Ramachandran, it's been really interesting. Thanks so much for speaking with us.

Dr. RAMACHANDRAN: Thank you. Enjoyed that.

DAVIES: V.S. Ramachandran is director of The Center for Brain And Cognition at the University of California, San Diego. His new book is called "The Tell-Tale Brain." You can join us on Facebook and follow us on Twitter @nprfreshair. And you can download podcasts of our show @freshair.npr.org.

For Terry Gross, I'm Dave Davies.

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