The Emerging Mind: The Reith Lectures 2003

sense to his brain given the peculiar disconnection.

Now how do you test an outlandish idea like this? My student Bill Hirstein and I in La Jolla, and Haydn Ellis and Andrew Young here in England, did some very simple experiments measuring galvanic skin response which I'll talk about in detail in my last lecture, and we found - sure enough - there has been this disconnection between vision and emotion as predicted by our theory, just as we had thought. Now what's even more amazing is when David, this patient who when his mother said she's an imposter, an hour later his mother phones him and he picks up the phone and answers the phone and he says 'mum, how are you, where are you?' Instantly he recognises her. There is no delusion. An hour later the mother walks into the room and he says 'who are you? You look just like my mother but you're an imposter, you're not my mother'. Now why does this happen? Well it turns out there's a separate pathway going from the auditory cortex in the superior temporal gyrus to the amygdala, and that pathway perhaps is not cut by the accident. That's why when he listens to his mother on the phone, he says 'oh my god, this is my mum, where are you?' But when he sees her, the delusion kicks in immediately and he says 'who are you'?

Now, there are many other twists to this story which I'm going to tell you about in my last lecture on neuropsychiatry, but I thought I'd just mention it briefly today because it's a lovely example of the sort of thing we do, of cognitive neuroscience in action.

Now we have talked about visual response to visual images, your emotional response to visual images. Obviously this response is vital for your survival but the existence of connections between visual brain centres and the limbic system or emotional core of the brain also raises another interesting question, and that is what is art? How does the brain response to beauty? Given that these connections are between vision and emotion, and art involves an aesthetic emotional response to visual images, surely these connections must be involved, and this is a topic I'll take up my lecture in Birmingham.

Now we've been talking about all these intricate connections in the brain, in the limbic system, in the visual centres, in the amygdala. An obvious question is the question of nature versus nurture. In other words, are these connections laid down by the genome in the foetus, or are they acquired in early infancy as the infant interacts with the world, the so- called nature/nurture debate. This takes me to the next syndrome I'd like to talk to you about and that is phantom limbs.

Everyone here knows what a phantom limb is. A patient has an arm amputated because there's a tumour, malignant tumour on the arm or there's been a car accident and the arm has to be amputated, but the patient continues to vividly feel the presence of that arm. Some of you here, this being England, would now about Lord Nelson who vividly felt a phantom arm. I'll tell you about an experiment we did on these patients. So we have a patient with a phantom left arm. His arm had been amputated above the left elbow so I had him sitting in my office blindfolded and I took a Q tip and touched different parts of the body and asked him what do you feel? I touched his shoulder and he said oh you're touching my shoulder. I touched his belly and he said oh you're touching my belly. I touched his chest and he said you're touching my chest - not surprising. But the amazing thing is when I touched his face, the left side of his face - remember his left arm is amputated so he has a phantom on the left side - when I touched his cheek he said oh my god doctor, you're touching my left thumb, my missing phantom thumb and he seemed as surprised as I was. Then I touched him on the upper lip and he said oh my god you're touching my phantom index finger, and then on his lower jaw and he said you're touching my phantom pinkie, my little finger.

So why does this happen? There was a complete map, a systematic map of the missing phantom hand on his face, draped on his face. So you have a medical mystery of sorts, the sort of mystery we saw with David, the patient with the Capgras syndrome, the sort of mystery that would have intrigued Sherlock Holmes, Conan Doyle or Berton Rouché. So what's going on?

To answer this question, you have to look at the anatomy of the brain again. The entire skin surface, touch signals, all the skin surface on the left side of the brain is mapped on to the right cerebral hemisphere on a vertical strip of cortical tissue called the post-central gyrus. Actually there are several maps but I'll simplify them and pretend there's only one map called the post-central gyrus. Now this a faithful representation of the entire body surface. It's almost as though you have a little person draped on the surface of the brain. It's called the Penfield homunculus, and for the most part it's continuous which is what you mean by a map, but there is one peculiarity and that is the representation of the face on this map on the surface of the brain is right next to the representation of the hand on this map, instead of being near the neck where it should be, so it's dislocated. Now nobody knows why, something to do with the phylogeny or the way in which the brain develops in early foetal life or in early infancy, but that's the way the map is.

So I realised that what's going on here is when you amputate the arm, the part of the cortex of the brain corresponding to the hand is not receiving any signals because you've removed the hand. So it's hungry for sensory input. So what happens is the sensory input from the face skin now invades the vacated territory corresponding to the missing hand, and that then is misinterpreted by higher centres in the brain and arising from the missing phantom hand. And that's why the patient says, every time you touch his face he says oh that's my phantom thumb you're touching, that's my phantom index finger, that's my phantom pinkie. In fact you can even put an ice cube on the face and the patient will say oh my thumb is ice cold. You can put a drop of hot water, in fact you put a drop of hot water and the water started trickling down the face, the patient will trace the trickle on his phantom with his normal hand following its path. On one occasion we had the patient raise his phantom and he was amazed to feel the trickle going uphill which is against the law of physics.

Now that's just a hypothesis but to test this idea, we used the brain imaging technique called MEG or magnetoencephalography which allows you to see which parts of the brain light up when you touch different parts of the body, and sure enough what we found was in this patient, Victor, unlike the normal brain when you touch his face, it activated not only the face area in the brain but also activated the hand region of the Penfield map in the brain. So there has obviously been this cross-wiring in the brain of this patient. And this is important because it allows you to link changes in brain anatomy, changes in brain maps, in the sensory map, with phenomenology, allows you to link physiology and psychology which is one of the goals of cognitive neuroscience, this discipline we're talking about.

The discovery also has broader implications. One of the things we were all taught as medical students is that connections in the brain are laid down in the foetus or in early infancy, and once they are laid down, there is nothing much you can do to change these connections in the adult and that's why when there's damage to the nervous system as in a stroke, there is such little recovery of function and why neurological ailments are so notoriously difficult to treat. What I am saying is that's wrong. In fact there's a tremendous amount of plasticity or malleability even in the adult brain, and you can demonstrate this in a five minute experiment in a patient with a phantom limb. Now how you go about harnessing this ability in the clinic may be to help patients recover from stroke or indeed from phantom limb pain is a question that we don't have time to go into but we can take up during discussions.

OK so we have seen that after our arm amputation, the patient's brain gets cross-wired. The face input now innervates the hand region of the brain. Now that happens because of amputation. It turns out that the same thing can happen because of a mutation, if there is something wrong with your genes. Instead of the brain modules remaining segregated, you get this accidental cross-wiring and then you get a curious condition called synesthesia, which we have now been studying. This is going to be a topic of my lecture in Oxford. Briefly it was described by Francis Galton or clearly documented by him in the 19th century. He pointed out that some people who are perfectly normal in other respects have one peculiar symptom, if you want to call it a symptom, and that is these people who are otherwise completely normal, they get their senses mixed up and that is every time they hear a particular tone they see a particular colour. So C sharp is red, F sharp is blue. Another tone might be indigo, OK? And this phenomenon, this mingling of senses is synesthesia. Galton pointed out also that it runs in families. We and others have confirmed this, including Simon Baron-Cohen.

Now, another aspect of this syndrome is whenever you hear a particular tone you see a particular colour. Some of these people also when they see numbers in black and white, like the number five or the number six or the number seven, what we call Arabic numerals - Indian numerals strictly speaking - when you see these numbers, every time you see a number it evokes a particular colour so 5 is always red, 6 is always green. It's always tinged green. 7 is always indigo, 8 is always yellow, so this again is another example of synesthesia and it's very common. We find it's about one in two hundred people have this so it's not as rare as people have thought it to be in the past.

Now why does this happen? Why does this mixing of signals occur? Well we, a student of mine, Ed Hubbard and I were looking at brain atlases, brain maps and we were struck by the fact that if you look at the fusiform gyrus, that's where the colour information is analysed. But amazingly the number area of the brain which represents visual graphemes of numbers, 5 6 7 8 and all of that, is right next to it also in the fusiform gyrus, almost touching it. So we said this can't be a coincidence. Maybe in some people there is some accidental cross-wiring. Just as after amputation we get cross-wiring between the face and the hand, in these people maybe there's a cross-wiring between the number and colour area in the fusiform gyrus. Of course the key difference is in the case of phantom limbs, it's the amputation that causes the reorganisation whereas in synesthesia given that it runs in families, we think it's caused by a gene or a set of genes which causes abnormal connections between adjacent brain regions, in this case between numbers and colours so every time he sees a specific number it evokes a particular colour.

First of all many neurologists, neuroscientists in the past, even though the phenomenon was described by Galton a hundred years ago, it's been regarded mainly as a curiosity. It sounds crazy. They're just crazy or they're just faking it to draw attention to themselves, or maybe it's childhood memories. You played with refrigerator magnets, 5 was red, 6 was blue, 7 was green. Now it never made much sense to me because why does it then run in families? You have to say maybe the same magnets were passed round. So first thing we wanted to show this is a real phenomenon, it's the person genuinely sees red when he sees 5. It's not just imagination or memory. How do you show that?

So we devised a simple display on the computer screen, a number of 5s scattered on the screen, black 5s, just black and white. Embedded among those 5s are a number of 2s and these 2s form a shape like a triangle, a hidden shape, a triangle or a square. Now when all of us here, any one of us normals or less gifted individuals, looks at this pattern, you see nothing. But when a synesthete looks at it, who sees numbers as colour, he sees the 5s as red and the 2s as green so he looks at it and he says my god, instantly the 2s pop out and he says oh they're forming a triangle, they're forming a square. And they are much better at doing this than normal people so it's a clinical test for discovering synesthetes.

Now, the fact that synesthetes are actually better at this than normal people suggests that they can't be crazy. If they're crazy, how come they're better at it? So this shows this is a genuine sensory phenomenon. It also shows that it can't be memory association or something cognitive or a metaphor because - if that were true, how come he's able to see the triangle or the square pop out from the background? OK we have shown that this phenomenon is real, we in La Joya and as well as Jeffrey Gray and Mike Morgan and others here in London have done experiments to test the idea there's actual cross-wiring in the brain and have shown that in fact there's activation of the fusiform gyrus in the colour area just showing numbers to these people.

But then the next question is OK, here are some people with some quirk in the brain. They see numbers as colours so what's the big deal, why should I care? Well