Well, as Chris pointed out, I study the human brain, the functions and structure of the human

brain. And I just want you to think for a minute about what this entails. Here is this mass of
jelly, three-pound mass of jelly you can hold in the palm of your hand, and it can contemplate
the vastness of interstellar space. It can contemplate the meaning of infinity and it can
contemplate itself contemplating on the meaning of infinity. And this peculiar recursive
quality that we call self-awareness, which I think is the holy grail of neuroscience, of
neurology, and hopefully, someday, we'll understand how that happens.
OK, so how do you study this mysterious organ? I mean, you have 100 billion nerve cells,
little wisps of protoplasm, interacting with each other, and from this activity emerges the
whole spectrum of abilities that we call human nature and human consciousness. How does
this happen? Well, there are many ways of approaching the functions of the human brain.
One approach, the one we use mainly, is to look at patients with sustained damage to a
small region of the brain, where there's been a genetic change in a small region of the brain.
What then happens is not an across-the-board reduction in all your mental capacities, a sort
of blunting of your cognitive ability. What you get is a highly selective loss of one function,
with other functions being preserved intact, and this gives you some confidence in asserting
that that part of the brain is somehow involved in mediating that function. So you can then
map function onto structure, and then find out what the circuitry's doing to generate that
particular function. So that's what we're trying to do.
So let me give you a few striking examples of this. In fact, I'm giving you three examples, six
minutes each, during this talk. The first example is an extraordinary syndrome called
Capgras syndrome. If you look at the first slide there, that's the temporal lobes, frontal lobes,
parietal lobes, OK -- the lobes that constitute the brain. And if you look, tucked away inside
the inner surface of the temporal lobes -- you can't see it there -- is a little structure called
the fusiform gyrus. And that's been called the face area in the brain, because when it's
damaged, you can no longer recognize people's faces. You can still recognize them from
their voice and say, "Oh yeah, that's Joe," but you can't look at their face and know who it is,
right? You can't even recognize yourself in the mirror. I mean, you know it's you because
you wink and it winks, and you know it's a mirror, but you don't really recognize yourself as
yourself.
OK. Now that syndrome is well known as caused by damage to the fusiform gyrus. But
there's another rare syndrome, so rare, in fact, that very few physicians have heard about it,
not even neurologists. This is called the Capgras delusion, and that is a patient, who's
otherwise completely normal, has had a head injury, comes out of coma, otherwise
completely normal, he looks at his mother and says, "This looks exactly like my mother, this
woman, but she's an impostor. She's some other woman pretending to be my mother." Now,
why does this happen? Why would somebody -- and this person is perfectly lucid and
intelligent in all other respects, but when he sees his mother, his delusion kicks in and says,
it's not mother.
Now, the most common interpretation of this, which you find in all the psychiatry textbooks,
is a Freudian view, and that is that this chap -- and the same argument applies to women, by
the way, but I'll just talk about guys. When you're a little baby, a young baby, you had a
strong sexual attraction to your mother. This is the so-called Oedipus complex of Freud. I'm
not saying I believe this, but this is the standard Freudian view. And then, as you grow up,
the cortex develops, and inhibits these latent sexual urges towards your mother. Thank God,
or you would all be sexually aroused when you saw your mother. And then what happens is,
there's a blow to your head, damaging the cortex, allowing these latent sexual urges to
emerge, flaming to the surface, and suddenly and inexplicably you find yourself being
sexually aroused by your mother. And you say, "My God, if this is my mom, how come I'm
being sexually turned on? She's some other woman. She's an impostor." It's the only
interpretation that makes sense to your damaged brain.
This has never made much sense to me, this argument. It's very ingenious, as all Freudian
arguments are -- (Laughter) -- but didn't make much sense because I have seen the same
delusion, a patient having the same delusion, about his pet poodle. (Laughter) He'll say,
"Doctor, this is not Fifi. It looks exactly like Fifi, but it's some other dog." Right? Now, you try
using the Freudian explanation there. (Laughter) You'll start talking about the latent bestiality
in all humans, or some such thing, which is quite absurd, of course.
Now, what's really going on? So, to explain this curious disorder, we look at the structure
and functions of the normal visual pathways in the brain. Normally, visual signals come in,
into the eyeballs, go to the visual areas in the brain. There are, in fact, 30 areas in the back
of your brain concerned with just vision, and after processing all that, the message goes to a
small structure called the fusiform gyrus, where you perceive faces. There are neurons there
that are sensitive to faces. You can call it the face area of the brain, right? I talked about that
earlier. Now, when that area's damaged, you lose the ability to see faces, right?
But from that area, the message cascades into a structure called the amygdala in the limbic
system, the emotional core of the brain, and that structure, called the amygdala, gauges the
emotional significance of what you're looking at. Is it prey? Is it predator? Is it mate? Or is it
something absolutely trivial, like a piece of lint, or a piece of chalk, or a -- I don't want to
point to that, but -- or a shoe, or something like that? OK? Which you can completely ignore.
So if the amygdala is excited, and this is something important, the messages then cascade
into the autonomic nervous system. Your heart starts beating faster. You start sweating to
dissipate the heat that you're going to create from muscular exertion. And that's fortunate,
because we can put two electrodes on your palm and measure the change in skin resistance
produced by sweating. So I can determine, when you're looking at something, whether
you're excited or whether you're aroused, or not, OK? And I'll get to that in a minute.
So my idea was, when this chap looks at an object, when he looks at his -- any object for
that matter, it goes to the visual areas and, however, and it's processed in the fusiform
gyrus, and you recognize it as a pea plant, or a table, or your mother, for that matter, OK?
And then the message cascades into the amygdala, and then goes down the autonomic
nervous system. But maybe, in this chap, that wire that goes from the amygdala to the limbic
system, the emotional core of the brain, is cut by the accident. So because the fusiform is
intact, the chap can still recognize his mother, and says, "Oh yeah, this looks like my
mother." But because the wire is cut to the emotional centers, he says, "But how come, if it's
my mother, I don't experience a warmth?" Or terror, as the case may be? Right? (Laughter)
And therefore, he says, "How do I account for this inexplicable lack of emotions? This can't
be my mother. It's some strange woman pretending to be my mother."
How do you test this? Well, what you do is, if you take any one of you here, and put you in
front of a screen, and measure your galvanic skin response, and show pictures on the
screen, I can measure how you sweat when you see an object, like a table or an umbrella.
Of course, you don't sweat. If I show you a picture of a lion, or a tiger, or a pinup, you start
sweating, right? And, believe it or not, if I show you a picture of your mother -- I'm talking
about normal people -- you start sweating. You don't even have to be Jewish. (Laughter)
Now, what happens if you show this patient? You take the patient and show him pictures on
the screen and measure his galvanic skin response. Tables and chairs and lint, nothing
happens, as in normal people, but when you show him a picture of his mother, the galvanic
skin response is flat. There's no emotional reaction to his mother, because that wire going
from the visual areas to the emotional centers is cut. So his vision is normal because the
visual areas are normal, his emotions are normal -- he'll laugh, he'll cry, so on and so forth --
but the wire from vision to emotions is cut and therefore he has this delusion that his mother
is an impostor. It's a lovely example of the sort of thing we do: take a bizarre, seemingly
incomprehensible, neural psychiatric syndrome and say that the standard Freudian view is
wrong, that, in fact, you can come up with a precise explanation in terms of the known neural
anatomy of the brain.
By the way, if this patient then goes, and mother phones from an adjacent room -- phones
him -- and he picks up the phone, and he says, "Wow, mom, how are you? Where are you?"
There's no delusion through the phone. Then, she approaches him after an hour, he says,
"Who are you? You look just like my mother." OK? The reason is there's a separate pathway
going from the hearing centers in the brain to the emotional centers, and that's not been cut
by the accident. So this explains why through the phone he recognizes his mother, no
problem. When he sees her in person, he says it's an impostor.
OK, how is all this complex circuitry set up in the brain? Is it nature, genes, or is it nurture?
And we approach this problem by considering another curious syndrome called phantom
limb. And you all know what a phantom limb is. When an arm is amputated, or a leg is
amputated, for gangrene, or you lose it in war -- for example, in the Iraq war, it's now a
serious problem -- you continue to vividly feel the presence of that missing arm, and that's
called a phantom arm or a phantom leg. In fact, you can get a phantom with almost any part
of the body. Believe it or not, even with internal viscera. I've had patients with the uterus
removed -- hysterectomy -- who have a phantom uterus, including phantom menstrual
cramps at the appropriate time of the month. And in fact, one student asked me the other
day, "Do they get phantom PMS?" (Laughter) A subject ripe for scientific enquiry, but we
haven't pursued that.
OK, now the next question is, what can you learn about phantom limbs by doing
experiments? One of the things we've found was, about half the patients with phantom limbs
claim that they can move the phantom. It'll pat his brother on the shoulder, it'll answer the
phone when it rings, it'll wave goodbye. These are very compelling, vivid sensations. The
patient's not delusional. He knows that the arm is not there, but, nevertheless, it's a
compelling sensory experience for the patient. But however, about half the patients, this
doesn't happen. The phantom limb -- they'll say, "But doctor, the phantom limb is paralyzed.
It's fixed in a clenched spasm and it's excruciatingly painful. If only I could move it, maybe
the pain will be relieved."
Now, why would a phantom limb be paralyzed? It sounds like an oxymoron. But when we
were looking at the case sheets, what we found was, these people with the paralyzed
phantom limbs, the original arm was paralyzed because of the peripheral nerve injury. The
actual nerve supplying the arm was severed, was cut, by say, a motorcycle accident. So the
patient had an actual arm, which is painful, in a sling for a few months or a year, and then, in
a misguided attempt to get rid of the pain in the arm, the surgeon amputates the arm, and
then you get a phantom arm with the same pains, right? And this is a serious clinical
problem. Patients become depressed. Some of them are driven to suicide, OK?
So, how do you treat this syndrome? Now, why do you get a paralyzed phantom limb? When
I looked at the case sheet, I found that they had an actual arm, and the nerves supplying the
arm had been cut, and the actual arm had been paralyzed, and lying in a sling for several
months before the amputation, and this pain then gets carried over into the phantom itself.
Why does this happen? When the arm was intact, but paralyzed, the brain sends commands
to the arm, the front of the brain, saying, "Move," but it's getting visual feedback saying, "No."
Move. No. Move. No. Move. No. And this gets wired into the circuitry of the brain, and we
call this learned paralysis, OK? The brain learns, because of this Hebbian, associative link,
that the mere command to move the arm creates a sensation of a paralyzed arm. And then,
when you've amputated the arm, this learned paralysis carries over into your body image
and into your phantom, OK?
Now, how do you help these patients? How do you unlearn the learned paralysis, so you can
relieve him of this excruciating, clenching spasm of the phantom arm? Well, we said, what if
you now send the command to the phantom, but give him visual feedback that it's obeying
his command, right? Maybe you can relieve the phantom pain, the phantom cramp. How do
you do that? Well, virtual reality. But that costs millions of dollars. So, I hit on a way of doing
this for three dollars, but don't tell my funding agencies. (Laughter)
OK? What you do is you create what I call a mirror box. You have a cardboard box with a
mirror in the middle, and then you put the phantom -- so my first patient, Derek, came in. He
had his arm amputated 10 years ago. He had a brachial avulsion, so the nerves were cut
and the arm was paralyzed, lying in a sling for a year, and then the arm was amputated. He
had a phantom arm, excruciatingly painful, and he couldn't move it. It was a paralyzed
phantom arm.
So he came there, and I gave him a mirror like that, in a box, which I call a mirror box, right?
And the patient puts his phantom left arm, which is clenched and in spasm, on the left side of
the mirror, and the normal hand on the right side of the mirror, and makes the same posture,
the clenched posture, and looks inside the mirror. And what does he experience? He looks
at the phantom being resurrected, because he's looking at the reflection of the normal arm in
the mirror, and it looks like this phantom has been resurrected. "Now," I said, "now, look,
wiggle your phantom -- your real fingers, or move your real fingers while looking in the
mirror." He's going to get the visual impression that the phantom is moving, right? That's
obvious, but the astonishing thing is, the patient then says, "Oh my God, my phantom is
moving again, and the pain, the clenching spasm, is relieved."
And remember, my first patient who came in -- (Applause) -- thank you. (Applause) My first
patient came in, and he looked in the mirror, and I said, "Look at your reflection of your
phantom." And he started giggling, he says, "I can see my phantom." But he's not stupid. He
knows it's not real. He knows it's a mirror reflection, but it's a vivid sensory experience. Now,
I said, "Move your normal hand and phantom." He said, "Oh, I can't move my phantom. You
know that. It's painful." I said, "Move your normal hand." And he says, "Oh my God, my
phantom is moving again. I don't believe this! And my pain is being relieved." OK? And then I
said, "Close your eyes." He closes his eyes. "And move your normal hand." "Oh, nothing. It's
clenched again." "OK, open your eyes." "Oh my God, oh my God, it's moving again!" So, he
was like a kid in a candy store.
So, I said, OK, this proves my theory about learned paralysis and the critical role of visual
input, but I'm not going to get a Nobel Prize for getting somebody to move his phantom limb.
(Laughter) (Applause) It's a completely useless ability, if you think about it. (Laughter) But
then I started realizing, maybe other kinds of paralysis that you see in neurology, like stroke,
focal dystonias -- there may be a learned component to this, which you can overcome with
the simple device of using a mirror.
So, I said, "Look, Derek" -- well, first of all, the guy can't just go around carrying a mirror to
alleviate his pain -- I said, "Look, Derek, take it home and practice with it for a week or two.
Maybe, after a period of practice, you can dispense with the mirror, unlearn the paralysis,
and start moving your paralyzed arm, and then, relieve yourself of pain." So he said OK, and
he took it home. I said, "Look, it's, after all, two dollars. Take it home."
So, he took it home, and after two weeks, he phones me, and he said, "Doctor, you're not
going to believe this." I said, "What?" He said, "It's gone." I said, "What's gone?" I thought
maybe the mirror box was gone. (Laughter) He said, "No, no, no, you know this phantom I've
had for the last 10 years? It's disappeared." And I said -- I got worried, I said, my God, I
mean I've changed this guy's body image, what about human subjects, ethics and all of that?
And I said, "Derek, does this bother you?" He said, "No, last three days, I've not had a
phantom arm and therefore no phantom elbow pain, no clenching, no phantom forearm pain,
all those pains are gone away. But the problem is I still have my phantom fingers dangling
from the shoulder, and your box doesn't reach." (Laughter) "So, can you change the design
and put it on my forehead, so I can, you know, do this and eliminate my phantom fingers?"
He thought I was some kind of magician.

Now, why does this happen? It's because the brain is faced with tremendous sensory
conflict. It's getting messages from vision saying the phantom is back. On the other hand,
there's no proprioception, muscle signals saying that there is no arm, right? And your motor
command saying there is an arm, and, because of this conflict, the brain says, to hell with it,
there is no phantom, there is no arm, right? It goes into a sort of denial -- it gates the signals.
And when the arm disappears, the bonus is, the pain disappears because you can't have
disembodied pain floating out there, in space. So, that's the bonus.

Now, this technique has been tried on dozens of patients by other groups in Helsinki, so it
may prove to be valuable as a treatment for phantom pain, and indeed, people have tried it
for stroke rehabilitation. Stroke you normally think of as damage to the fibers, nothing you
can do about it. But, it turns out some component of stroke paralysis is also learned
paralysis, and maybe that component can be overcome using mirrors. This has also gone
through clinical trials, helping lots and lots of patients.
OK, let me switch gears now to the third part of my talk, which is about another curious
phenomenon called synesthesia. This was discovered by Francis Galton in the nineteenth
century. He was a cousin of Charles Darwin. He pointed out that certain people in the
population, who are otherwise completely normal, had the following peculiarity: every time
they see a number, it's colored. Five is blue, seven is yellow, eight is chartreuse, nine is
indigo, OK? Bear in mind, these people are completely normal in other respects. Or C sharp
-- sometimes, tones evoke color. C sharp is blue, F sharp is green, another tone might be
yellow, right?
Why does this happen? This is called synesthesia. Galton called it synesthesia, a mingling of
the senses. In us, all the senses are distinct. These people muddle up their senses. Why
does this happen? One of the two aspects of this problem are very intriguing. Synesthesia
runs in families, so Galton said this is a hereditary basis, a genetic basis. Secondly,
synesthesia is about -- and this is what gets me to my point about the main theme of this
lecture, which is about creativity -- synesthesia is eight times more common among artists,
poets, novelists and other creative people than in the general population. Why would that
be? I'm going to answer that question. It's never been answered before.

OK, what is synesthesia? What causes it? Well, there are many theories. One theory is
they're just crazy. Now, that's not really a scientific theory, so we can forget about it. Another
theory is they are acid junkies and potheads, right? Now, there may be some truth to this,
because it's much more common here in the Bay Area than in San Diego. (Laughter) OK.
Now, the third theory is that -- well, let's ask ourselves what's really going on in synesthesia.
All right?

So, we found that the color area and the number area are right next to each other in the
brain, in the fusiform gyrus. So we said, there's some accidental cross wiring between color
and numbers in the brain. So, every time you see a number, you see a corresponding color,
and that's why you get synesthesia. Now remember -- why does this happen? Why would
there be crossed wires in some people? Remember I said it runs in families? That gives you
the clue. And that is, there is an abnormal gene, a mutation in the gene that causes this
abnormal cross wiring.

In all of us, it turns out we are born with everything wired to everything else. So, every brain
region is wired to every other region, and these are trimmed down to create the
characteristic modular architecture of the adult brain. So, if there's a gene causing this
trimming and if that gene mutates, then you get deficient trimming between adjacent brain
areas. And if it's between number and color, you get number-color synesthesia. If it's
between tone and color, you get tone-color synesthesia. So far, so good.

Now, what if this gene is expressed everywhere in the brain, so everything is cross-
connected? Well, think about what artists, novelists and poets have in common, the ability to
engage in metaphorical thinking, linking seemingly unrelated ideas, such as, "It is the east,
and Juliet is the Sun." Well, you don't say, Juliet is the sun, does that mean she's a glowing
ball of fire? I mean, schizophrenics do that, but it's a different story, right? Normal people
say, she's warm like the sun, she's radiant like the sun, she's nurturing like the sun. Instantly,
you've found the links.

Now, if you assume that this greater cross wiring and concepts are also in different parts of
the brain, then it's going to create a greater propensity towards metaphorical thinking and
creativity in people with synesthesia. And, hence, the eight times more common incidence of
synesthesia among poets, artists and novelists. OK, it's a very phrenological view of
synesthesia. The last demonstration -- can I take one minute? (Applause)

OK. I'm going to show you that you're all synesthetes, but you're in denial about it. Here's
what I call Martian alphabet. Just like your alphabet, A is A, B is B, C is C. Different shapes
for different phonemes, right? Here, you've got Martian alphabet. One of them is Kiki, one of
them is Bouba. Which one is Kiki and which one is Bouba? How many of you think that's Kiki
and that's Bouba? Raise your hands. Well, it's one or two mutants. (Laughter) How many of
you think that's Bouba, that's Kiki? Raise your hands. Ninety-nine percent of you.

Now, none of you is a Martian. How did you do that? It's because you're all doing a cross-
model synesthetic abstraction, meaning you're saying that that sharp inflection -- ki-ki, in
your auditory cortex, the hair cells being excited -- Kiki, mimics the visual inflection, sudden
inflection of that jagged shape. Now, this is very important, because what it's telling you is
your brain is engaging in a primitive -- it's just -- it looks like a silly illusion, but these photons
in your eye are doing this shape, and hair cells in your ear are exciting the auditory pattern,
but the brain is able to extract the common denominator. It's a primitive form of abstraction,
and we now know this happens in the fusiform gyrus of the brain, because when that's
damaged, these people lose the ability to engage in Bouba Kiki, but they also lose the ability
to engage in metaphor.
If you ask this guy, what -- "all that glitters is not gold," what does that mean?" The patient
says, "Well, if it's metallic and shiny, it doesn't mean it's gold. You have to measure its
specific gravity, OK?" So, they completely miss the metaphorical meaning. So, this area is
about eight times the size in higher -- especially in humans -- as in lower primates.
Something very interesting is going on here in the angular gyrus, because it's the crossroads
between hearing, vision and touch, and it became enormous in humans. And something very
interesting is going on. And I think it's a basis of many uniquely human abilities like
abstraction, metaphor and creativity. All of these questions that philosophers have been
studying for millennia, we scientists can begin to explore by doing brain imaging, and by
studying patients and asking the right questions.