Embodied Souls — Lessons from Neurology V.S. Ramachandran

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0:20 (upbeat music)- Thank you for coming this afternoon.

0:47 My name is Paula Varsano and I'm a professor of East

0:51 Asian languages and cultures and the chair of the Foerster Lectures Committee.

0:56 We, along with the graduate council, are very, very happy to present V.S.

1:03 Ramachandran, this year's speaker in the Foerster Lecture Series.

1:08 I'm also very pleased to tell you a bit about how the endowment

1:12 supporting the Foerster lectures on the immortality

1:15 of the soul came to UC Berkeley.

1:18 It's actually a story that really exemplifies the ways in which this campus

1:23 is linked to the history of California and in particular to the Bay Area.

1:28 In 1928, Miss Edith Zweybruck established the Foerster

1:33 Lectureship to honor the memory of Agnes A.

1:36 Foerster and her husband, Constantine E.

1:40 Foerster.

1:41 Edith was a public school teacher for many years in San Francisco.

1:45 And the teaching profession, in her eyes,

1:48 was the perfect opportunity to develop a true knowledge and love

1:52 of the spiritual values of life in the young minds entrusted to her care.

1:59 Edith's beloved sister, Agnes A.

2:01 Foerster shared her high ideals and her hopes,

2:04 as did Agnes' husband, Constantine.

2:08 A lawyer by profession,

2:10 he was a man of high intellectual achievements and of rare personal charm.

2:20 Although he passed away at the age of 37,

2:23 he had achieved an enviable place at the San

2:27 Francisco Bar as one of its most highly respected members.

2:31 For several years prior to his death,

2:34 Foerster was a law partner of none other than Alexander F.

2:37 Morrison, one of the most prominent of San Francisco attorneys,

2:41 for whom our Morrison Memorial Library is named.

2:47 In her last days, Miss Edith Zweybruck expressed

2:50 her deep and abiding interest in the spiritual

2:53 life by creating this lecture series

2:56 on the subject of the immortality of the soul.

3:00 She believed that through the medium of great

3:03 universities and the words of scholarly lecturers

3:06 she might shed new light upon a subject

3:08 that has interested the world for centuries.

3:11 So we have to thank Edith Zweybruck.

3:14 And now about our lecturer.

3:16 Sometimes the best way to characterize a person is to consider

3:20 what kinds of questions he or she likes to ask.

3:24 And here's a question that is always being asked in various ways by our speaker.

3:30 And I quote him here.

3:32 How can a three pound mass of jelly that you

3:36 can hold in the palm of your hand imagine angels,

3:40 contemplate the meaning of infinity,

3:42 and even question its own place in the cosmos?

3:47 Now, what kind of person can ask

3:49 this question in a way that doesn't sound rhetorical?

3:52 Poets can do that.

3:55 And Doctor V.S.

3:56 Ramachandran is, indeed, a poet of sorts.

3:59 Officially, however, he serves as the director of the Center for Brain

4:04 and Cognition and is a distinguished professor at the University of California,

4:08 San Diego, as well as an adjunct professor of biology at the Salk Institute.

4:16 He has also been called the Marco Polo of neuroscience by Richard Dawkins,

4:20 and the modern Paul Brokaw by Eric Kendau.

4:25 But as pithily impressive as these titles and these epithets may be,

4:30 they actually do very,

4:32 very little to reveal the mind-teasing pathway he has followed

4:36 and on which he leads us in the work that he does,

4:39 and in the contributions that he makes.

4:43 Doctor Ramachandran is renowned for his ongoing inquiry into the field

4:48 of cognitive neuroscience that is

4:51 the intersection of neurology and perceptual psychology.

4:55 To steal a few words from the title of one of his books,

4:58 he is actually a neuroscientist on a quest for what makes us human.

5:04 Building on his early work on visual perception,

5:07 Ramachandran has led pioneering experiments in behavioral neurology,

5:12 taking cues from malfunctions in perception,

5:15 including phantom limbs, synesthesia, and xenomelia,

5:19 to delve into the unique ways in which

5:23 the human brain forms and deforms the workings of mind.

5:28 Laypeople are perhaps most familiar with his controversial assertion of mirror

5:34 neurons as playing a central role in the unique evolution of humans.

5:40 His approach to neurology has been to revisit classic syndromes,

5:44 bring them to the lab, determine their broader significance,

5:47 and devise new treatments where possible.

5:51 Of course, Ramachandran, many of you know, is a very prolific author,

5:55 and he's published over 180 papers in scientific journals,

5:59 five of which were invited review articles for Scientific American.

6:05 He's the co-author with Sandra Blakely of "Phantoms in the Brain,

6:10 1999," which has been translated into nine languages,

6:14 and formed the basis for a PBS special.

6:17 His BBC Reith lectures were published in 2003 in a volume titled

6:23 "The Emerging Mind," and were dubbed by the Nobel Laureate David Hubel as bold,

6:29 irreverent, original, and ingenious.

6:32 His latest book, a New York Times bestseller,

6:35 is "The Telltale Brain." After training

6:39 as a physician in Stanley Medical College in Madras,

6:42 India, Ramachandran attained a PhD from Trinity

6:46 College and the University of Cambridge.

6:48 He's an honorary fellow of the Royal College of Physicians,

6:51 London, and the recipient of two honorary doctorates.

6:55 Ramachandran has received many accolades throughout his career.

6:59 He was awarded the Henry Dale Medal in 2005 and was elected

7:05 to an honorary life membership to the Royal Institution of Great Britain.

7:10 The president of India conferred on him the highest honorific title in India,

7:17 Padma Bhushan, in 2007.

7:20 And besides the BBC Reith lectures he delivered in the UK,

7:24 he also gave the Gifford Lectures in Scotland.

7:28 Time Magazine named him one of the most influential

7:32 people in the world in their 2011 Time 100.

7:38 Finally, before I cede the stage to Doctor Ramachandran,

7:42 I would like to leave you with a few words by Ted Cruiser,

7:45 US Poet Laureate from 2004 to 2006, who also asks what makes us human.

7:54 He words it differently though, and much more mournfully than our speaker does.

8:00 Here we will not find the mind's brain

8:02 imagining angels or contemplating the meaning of infinity.

8:07 In the closing lines of Cruiser's poem "In the Hall of Bones," after cataloging

8:13 the array of skeletons that he found

8:15 in what seems to be a natural history museum,

8:18 he writes these words: "And then, here's man,

8:23 "all matchsticks, wooden spoons, "and tongue depressors, wired together.

8:29 "A rack supporting a leaky jug of lust and worry.

8:33 "Of all the skeletons assembled here,

8:36 "this is the only one in which once throbbed a heart "made sad

8:41 by brooding on its shadow." It's

8:45 my pleasure to welcome Doctor Ramachandran to Berkeley.

8:49 (audience applauding)- Well thank you for that amazing introduction.

9:03 I'm delighted to be here and honored to be

9:05 invited by the committee to do this lecture, Foerster Lecture.

9:09 When the committee first phoned me up about

9:11 this and said I was to talk about the soul, the immortality of the soul, I said,

9:14 "Well, that's easy, I'm happy to do it." (audience laughing) And then

9:19 I did a double take and I realized what I was getting into.

9:22 But then fortunately they reassured me that in fact,

9:24 it doesn't have to be anything directly related to the soul,

9:26 but so long as it's tangentially relevant,

9:29 which means essentially all phenomena in the universe.

9:33 So I'm gonna approach the problem of the soul not so much the soul but the self.

9:36 It's after all the immortality of the self that we're all concerned about.

9:40 We call it the soul.

9:41 And I'm gonna use two approaches.

9:44 Mainly one approach,

9:45 but I'm not gonna deal with the metaphysical question of soul,

9:48 which is extensively dealt with in Indian

9:51 philosophy and in Western philosophy as well...

9:56 But if you sort of pause and introspect on the self,

9:59 there are many attributes, it's kind of common sense,

10:01 but roughly speaking, there's embodiment.

10:04 One of the most obvious aspects of the self is,

10:05 it's you're anchored in one body.

10:07 I'm not anchored in Tony's body, I'm right here.

10:10 But we'll call that into question in a minute.

10:12 Then there's a sense of continuity in space and time.

10:15 You all have a calendar.

10:17 Sense of agency.

10:18 Sort of like the free will.

10:20 Sense of unity and coherence,

10:22 despite a diversity of sense impressions and memories over a lifetime.

10:26 You feel like one person.

10:27 I'm one guy, one name, one bank account, one spouse, so on and so forth.

10:33 And a sense of privacy and individuality.

10:37 And then finally, most mysterious of all, self awareness.

10:40 Self is not aware of its self.

10:41 Sort of like an oxymoron.

10:43 There's a curious, recursive quality to it which is hard to come to grips with.

10:48 I'm not gonna talk about all the attributes of the self.

10:50 That would take a whole week.

10:51 But let's talk about embodiment and partly about privacy.

10:56 And from the point of view, cognitive neuroscience and neurology.

11:00 And the way we deal with this, the way we study this, is by looking at patients.

11:08 We can do brain imaging, it's one thing we do,

11:10 but mainly we do behavioral, old-fashioned, 19th century behavioral neurology.

11:15 We look at patients who have sustained an injury

11:17 or a change in a small part of the brain,

11:19 and then producing characteristic changes in their behavior

11:23 and trying to correlate structure and function,

11:25 trying to explain the changes in behavior in terms

11:26 of the anatomical organization of the normal human brain.

11:30 To give you some insight into the question

11:34 of what's mediating that particular function.

11:37 So let me begin with a bang and talk

11:39 about a syndrome which few people even heard of.

11:43 It's called xenomelia.

11:45 Xenomelia is the name we gave it,

11:47 but it's also known as apotemnophilia, unpronounceable name but apotemnophilia.

11:51 These are first patients...

11:53 I'll mention one example, second example of it,

11:55 dean of an engineering school who came to see me at the age of 70,

11:59 had just retired at 70 years old, and he had harbored, through his entire life,

12:03 he'd harbored a secret urge, as he described it,

12:06 to amputate his own healthy arm.

12:09 Going back as far back in childhood as he can remember.

12:12 He's a perfectly normal guy in every respect,

12:14 not obviously psychotic or depressed or mentally disturbed,

12:18 no neurological findings, completely normal, led a normal family life,

12:22 had friends, had a job as a dean.

12:25 Everything seemed normal,

12:25 except for this one particularity that he had this urge.

12:28 And by then I discovered that many of these people, it's not that rare.

12:31 It is rare, but not that rare.

12:34 And about one third of them to half of them go and get it amputated.

12:38 This is not some mild obsession these people have.

12:41 There's few serious clinical consequences, the loss of the limb.

12:45 So then I said, "Why did you come to see me?

12:47 "Do you want us to treat you or cure you?" He said,

12:51 "No, I enjoy it, I don't wanna be cured.

12:53 "I want you to remove the arm, give me a letter "so I can go get it removed.

12:56 "And I can't do it here in this country.

12:58 "I'll go to Mexico, across the border,

12:59 "it's legal to get a healthy limb amputated." I'm not making this up,

13:02 this is what he said.

13:03 Later I checked on this and it's true:

13:05 you can get it amputated in Mexico and in Canada, but you can't do it here.

13:08 So many patients travel north or south to get it amputated.

13:12 And what would cause this?

13:13 The first thing (mumbles) is,

13:14 one of the things you learn in clinical medicine is first talk to the guy.

13:18 You know, 90% of the time you figure out what's

13:19 going on in his brain by just talking to him.

13:22 You don't need to do brain imaging, you don't need to do even clinical testing.

13:25 I said, "Do you feel like this arm doesn't belong to you?" He said,

13:29 "No, no it's the opposite.

13:31 "It feels like it over belongs to me.

13:32 "It's intrusive.

13:33 "It's intruding itself on me.

13:35 "And I want it removed." I said, "Okay," and I started thinking about this.

13:41 And I said, maybe what's gone wrong is you look at the surface of the brain,

13:45 that's the somatosensory cortex, so there's one,

13:48 it's called the Penfield map of the body surface.

13:50 And the entire surface of the body,

13:53 the body skin surface is mapped onto the post sympathizer...

13:56 There's a vertical cleft going down the side

13:57 of the brain called the central surface.

13:59 Behind that cleft there's a vertical strip of cortex, it's shown in brown there.

14:04 So that'd be the left hemisphere, if you were going to touch my right side,

14:06 closer to that is on the left hemisphere.

14:09 There's a complete map of the body's surface on that post-central gyrus there.

14:13 That map is shown in the next slide.

14:15 Many of you may have seen this before.

14:18 It's got some peculiar features which I will come back to.

14:20 But I said, well maybe in this guy, it was a very naive,

14:23 phrenological hunch, maybe in this guy that part of the brain is missing.

14:27 The hand is not there.

14:29 You don't know how much of this map is present,

14:31 the scaffolding is present at birth, and how much of it is shaped by experience.

14:35 And I'm gonna talk about that in a few minutes.

14:37 But for now, let's assume it's hardwired, partly.

14:40 Maybe it's congenitally missing the arm,

14:43 and that's why he feels it's alien or it doesn't belong to him.

14:46 So we did the obvious experiment of galvanic skin response,

14:49 poked him with a needle, gently, in different parts of the body,

14:52 and obtained electrical skin conduction responses.

14:55 And we thought we would find no responses.

14:57 One of the things that clued us

14:58 in to this as being a neurological rather than a psychological disorder,

15:02 if you ask him where did he want it amputated, he'd take a felt pen,

15:05 and he would draw an exact line just above

15:07 the elbow or below the elbow or just above the hand.

15:10 Very precise line, often irregular line, sloping line,

15:14 and then if you let him go home, don't tell him you're gonna retest him,

15:16 but bring him back after six months, he'll draw exactly the same line.

15:19 Unless he's being deliberately deceptive, got it memorized.

15:22 It's very unlikely he's doing that.

15:23 So this suggests that...

15:25 Why would the precise line matter?

15:26 Some vague inclination to get the arm removed,

15:28 why would the precise line matter?

15:30 In fact there are many psychological theories of this.

15:32 One psychiatric theory holds that it's a cry for attention,

15:34 that's why they want their arm removed.

15:36 Why arm?

15:37 Why not remove the nose or the ear or something like that?

15:40 Why the arm always, or the leg, right?

15:44 Seems pretty drastic way of getting attention.

15:46 Another theory, believe it or not, the Freudian theory,

15:48 the guy wants his arm removed in order to create an amputation stump,

15:52 to resemble the giant penis.

15:55 I'm not making this up.

15:56 You can see this in the literature.

15:58 So we thought we'd come up with a neurological,

16:00 phrenological theory of what's going on.

16:02 Then we drew the line with the felt tip,

16:06 poked him with a needle in different parts of the body,

16:08 to see if the galvanic skin response is normal

16:11 below the line as opposed to above the line.

16:13 We expected a diminished galvanic skin response below the line,

16:16 because that part of the arm is not represented in the brain,

16:20 according to our theory.

16:22 Well we found the opposite.

16:24 As often happens in science.

16:25 We found below the line there's a huge galvanic skin response.

16:28 Above the line, is perfectly normal as you would expect.

16:30 Is that clear?

16:31 Okay if you poke somebody with a needle, unless it goes to S1 of course, and S2,

16:37 the somatic representation of the body,

16:39 but it also goes to an area called the insular cortex,

16:41 and from there it gets into the anterior singular

16:44 and from there messages cascade down the sympathetic nervous system,

16:47 producing sympathetic arousal to the pain.

16:49 And then this manifests as a change in sweating of the skin,

16:53 which in turn can be measured as a change in skin resistance.

16:56 You put two electrodes in the palm and I scare you

16:58 with a needle or I scare you with a lion, you start sweating.

17:02 This registers as a fall in skin resistance.

17:05 Base of lie detectors.

17:07 Any anxiety, any panic will produce resistance.

17:10 So clearly, he was registering a higher response to the alienated

17:15 part of the limb than to the normal part,

17:19 which is opposite of what we predicted.

17:21 But hang on a second.

17:22 So we said, well our basic, early theory was wrong, so what's going on here?

17:25 Then we resorted to brain imaging.

17:29 I don't have any pictures to show you,

17:30 but basically what we found was this map was normal,

17:36 the one I just showed you, S1 is normal.

17:37 S2, which represents joints, muscles, and light touch, that was also normal.

17:44 We said what's going on here?

17:46 Everything's normal.

17:46 Then we went to in superior parietal lobule, SPL, wherever four is,

17:52 superior parietal lobule is where you create

17:56 a polysensory representation of your body image.

17:59 You close your eyes,

18:00 your vivid impression of your own body, inhabiting your own body,

18:03 the movements of your arms and legs and all that, that sense

18:05 which was called body image by Henry Head and Lord Russell Brain,

18:09 two real neurologists, by the way, who called this the body image.

18:14 And that combined sensation from hearing, touch,

18:17 and vision is in the superior parietal lobule.

18:21 In that map, there is no response from the hand.

18:26 So that map was abnormal.

18:28 There's a hole, to put it crudely,

18:29 corresponding to the hand he wanted amputated.

18:33 So what's going on in this patient is, the messages from the hand and arm

18:37 are reaching the somatosensory cortex completely normal.

18:40 So the messages, sensory signals are normal,

18:42 sensory cortex is normal, S2 is normal, but they have nowhere to go to, 'cause

18:45 there's a hole in that region of the brain.

18:49 So this creates a discrepancy between the incoming sensory input and there's

18:53 no place for them to go to, and the brain aborts discrepancy,

18:56 that signal goes to the insular and possibly the amygdala,

18:59 generating a galvanic skin response.

19:00 (grunts) right?

19:03 So here we have an example of...

19:05 We've taken the Freudian theory and discarded it.

19:08 By and large, that would be completely wrong,

19:10 and then replaced it with an anatomical theory,

19:13 which we can test in a few hours using a GSR machine,

19:17 and then do more sophisticated brain imaging

19:20 and show that we're on the right track.

19:21 This shows the power of this approach, cognitive neuroscience.

19:24 We can take a bizarre, seemingly incomprehensible neurological disorder,

19:28 a person wanting his arm removed,

19:30 and reject the traditional explanation in favor of an anatomical explanation

19:35 based on the known neuroanatomy of the sensory pathways in the brain.

19:41 Now, can you cure the disorder?

19:43 We haven't found a way of treating it yet.

19:44 In fact, they don't wanna be cured, as I said before.

19:48 But the next topic I'm gonna deal with...

19:51 So this is typical of what we do.

19:53 We take syndromes that have been known for a long time,

19:55 either rare ones or common ones, like synesthesia is very common.

19:57 I'm gonna talk about that later today.

20:00 Phantom limbs are quite common, I'll talk about that as well.

20:03 Our rare ones, and bring them from the clinic

20:05 to the laboratory and then do systematic experiments,

20:08 to find out what's going on, and sometimes

20:10 we're actually able to help the patient.

20:12 Now this at the start it doesn't always work, looking for anomalies.

20:16 Because every now and then...

20:17 You only hear of the success stories.

20:19 Nine out of 10 times it's a wild goose chase.

20:22 Anomalies in neurology.

20:23 Neurology and psychiatry are full of anomalous syndromes.

20:27 Nine out 10 times a wild goose chase.

20:28 You only hear of the success stories.

20:30 I'll give you three examples of wild goose chases.

20:33 Very briefly.

20:34 There's a syndrome called De Clerambault Syndrome.

20:38 How many of you know about De Clerambault Syndrome?

20:41 Nobody.

20:42 See?

20:42 Pretty obscure.

20:43 Even most neuro and psychiatrists haven't heard of it.

20:46 It refers to a syndrome that's

20:47 defined as, it's accepted in psychiatry textbooks,

20:50 a young woman, typically young woman,

20:52 who develops the delusion that an old, rich,

20:56 famous man is madly in love with her but is in denial about it.

21:00 (audience laughing) Funnily enough,

21:03 the converse of the syndrome has not been described,

21:05 where an older gentleman develops a delusion

21:07 that a young hottie is sexually interested in him, but is in denial about it.

21:12 This is much more common, I can assure you.

21:14 (audience laughing) Another bogus syndrome is chronic underachievement syndrome.

21:21 This is actually found in textbooks.

21:22 Chronic underachievement syndrome.

21:24 My day it used to be called stupidity.

21:26 (audience laughing) The third syndrome,

21:29 my favorite, is oppositional defiant disorder, ODD.

21:34 This young spirited youngster daring to challenge the establishment.

21:37 The psychiatrist challenged her parent...

21:42 The man who invented the syndrome is genius,

21:43 because any attempt by the patient to disprove the syndrome,

21:46 the pretend syndrome, can be construed as additional evidence for the diagnosis.

21:52 Leaving that aside, every now and then you

21:54 stumble on legitimate syndromes that give you key insights.

21:56 So for example, apotemnophilia.

21:59 Now I'm gonna talk about something else, this you heard before,

22:00 many of you, but I'm gonna repeat it, the gist of it.

22:04 Phantom limbs.

22:05 An arm or leg were amputated and you continue

22:07 to feel its presence is called a phantom limb.

22:10 Some years ago, nearly 15 years ago we had a patient with a left arm amputated

22:13 and we made a specific prediction based on work

22:16 on monkeys run by Mike Merzenich and others.

22:19 So nobody had tested it on humans, so we had a patient sitting in my lab,

22:23 whose left arm had been amputated, we blindfolded him and simply took a Q-tip

22:27 and touched different parts of his body,

22:29 and asked him, "What do you feel?" He said, "It's my right shoulder,

22:31 and my chest." So here's a patient sitting in the chair,

22:34 blindfolded, took a Q-tip, touched different parts of his body,

22:37 did a routine sensory neurological exam.

22:39 "What's that?" "That's a Q-tip." "What are you touching?"

22:41 "Right chest." "That's my right shoulder, my left shoulder.

22:47 "Left upper arm.

22:50 "Oh my god you're touching my left phantom thumb.

22:54 "And my phantom pinky, and my phantom index finger." We found there's

22:58 a complete map of the missing arm on the face,

23:01 and you can actually plot receptor fields.

23:04 You can plot receptor fields.

23:06 Like the thumb was there.

23:09 Ball of the thumb, index finger, pinky.

23:12 And you can send him home,

23:13 bring him back after a month and it's exactly the same.

23:16 No way he could've memorized that.

23:19 And why is this going on, happening?

23:20 Well we can do a bit of detective work.

23:24 Go back to the Penfield map.

23:28 Notice that the map is completely,

23:32 as a map should be, continuous, except for one fact:

23:35 the face is not near the head,

23:38 where it's supposed to be, near the neck, it's below the hand.

23:41 Is that clear?

23:42 So we said, what's going on?

23:44 And when you amputate the arm,

23:44 these sensory signals don't get to be handed in the brain.

23:48 Signals from the face can normally go into the face area,

23:51 invade, and cross and invade the territory vacated by the missing hand.

23:56 So there's this cross-wiring.

23:58 You ignore the arm and the hand,

24:00 there are no signals coming to this region of the brain, the hand region.

24:04 That region's hungry for new sensory input.

24:06 The sensory input not coming from the face came to the face area,

24:09 invades the territory corresponding to the missing hand, activates the cells,

24:12 and those cells misinterpret the signals

24:14 as coming from the missing phantom hand.

24:16 So when you touch the face he thinks you're touching his hand.

24:20 So you can have fun with this.

24:21 We took a Q-tip and put it in ice-cold water and put it on his face,

24:24 and he said, "Oh my god, my thumb feels ice-cold,

24:27 doctor." So the reorganization is morality-specific, it's not higgledy-piggledy.

24:30 Touch goes to touch, warm goes to warm, cold goes to cold.

24:34 On one occasion, water started trickling down his face,

24:37 accidentally, and he said, "Oh my god,

24:38 I can feel the trickle of the water!" And he took his other hand,

24:41 normal hand, and followed the trickle,

24:43 "It's coming down here, "it's coming down here,

24:45 oh it stops here at the wrist." Where the water stopped.

24:48 So it's exquisitely precise, the reorganization.

24:51 Just for fun I said, "Raise your stump and point to the ceiling."

24:55 The phantom is pointed to the ceiling, upward.

24:56 Then I put the water here, started trickling down, I said,

24:59 "What do you feel?" He said, "Oh my god the water is trickling upwards,

25:02 "defying the laws of gravity." You knew the patients often enough,

25:05 you realize that they don't make up stories like that.

25:11 Alright, I can continue along these.

25:13 I'm running out of time soon, I'm gonna skip a lot of stuff.

25:16 Can do brain imaging to show the reorganization has indeed occurred.

25:21 The other interesting thing about phantom limbs is,

25:23 the patient can often move the phantom.

25:27 Majority of patients can move the phantom.

25:28 But about a third of them, the phantom is fixed or immobilized.

25:31 And often in a painful position.

25:33 The patient will say,

25:34 mimic the phantom positions with his normal hand and will say,

25:37 "It's like this, doctor." Occupying it's like this.

25:39 "My hand is extending, hyper-extending,

25:42 "so my knuckles are touching the back of my wrist.

25:45 "It's anatomically impossible,

25:46 but my hand is doing it." And it's like that movie, what is the movie?

25:50 Where the head spins around?

25:51 (audience member mumbles) Yeah,

25:52 so it's anatomically impossible and it's excruciatingly painful,

25:55 "I wish I could straighten my wrist "and the pain

25:56 will go away." "So why don't you try?" "I'm trying,

25:59 I'm trying, I'm sweating, I can't do it." I'm gonna cut a long story short,

26:04 we hit on the idea of putting a mirror

26:07 there and showing the reflection of the mirror,

26:10 we can go into detail during the question and answer later,

26:14 put a mirror inside a cardboard box, and the phantom,

26:18 the clenched phantom, often they will say, "The fingers are biting into the...

26:23 "The nails are biting into the palm, doctor,

26:24 "and it's excruciatingly painful." There's no nails,

26:26 there's no palm, there's no hand.

26:27 It's a phantom.

26:30 It's a serious clinical problem.

26:31 Become profoundly depressed, lose their jobs,

26:33 on occasion they contemplate suicide.

26:36 So you put a mirror there and you have

26:38 the patient clench the normal hand and look at the reflection

26:41 of the normal hand in the mirror so that the reflection

26:43 of the normal hand is superimposed optically on the phantom hand,

26:46 so you visually resurrected the phantom.

26:49 Then you say, "Okay send symmetrical commands

26:52 "to both hands to open or close." He says,

26:54 "I know you're telling me that I can do that, "my left hand,

26:57 it will not open." I said, "Just take a look in the mirror and see." He said,

27:01 "Oh my god it looks like it's opening.

27:02 "And my god it also feels like it's opening, "it doesn't merely look like it's

27:05 opening." Which is not surprising, it's optics.

27:08 But it feels like it's opening,

27:09 and the clenching spasm is removed, it's gone, the pain is gone.

27:13 Then I said, "Remove the mirror." I removed the mirror.

27:15 Then try with your eyes closed and imagine it, and, "No it doesn't work,

27:17 I keep trying but it doesn't work." Put the mirror and then,

27:20 "Wow, it's opening, it's opening, it feels good." So I said, "Well, maybe...

27:25 "You can't carry around a mirror all the time.

27:28 "Maybe you can get to a point where you

27:30 can practice "with the mirror one hour a day,

27:33 "and after about a week or two or a month, "you can dispense with the mirror,

27:36 "you can just move it on its own." He can just unclench it whenever he wants to.

27:40 So I sent him home with a box, only $2, sent him home with a box.

27:44 And then after two weeks I phoned him up and I said,

27:46 "Have you been practicing?" He said, "Yes I've been practicing.

27:48 "When I keep my eyes open, the pain gets relieved "for about an hour,

27:51 and then it comes back "with a vengeance.

27:53 "And then I put the mirror back and it goes back again.

27:56 "So I keep doing refills.

27:58 "I know you want it to go away permanently,

28:00 but it doesn't." I said, "Fine, c'est la vie,

28:02 you know?" Then after a week he phones me, and he's all agitated on the phone.

28:06 I said, "What's wrong, Derek?" He said,

28:07 "You're not gonna believe this." I said, "What?" "It's gone," he says.

28:11 I said, "What's gone?" I thought maybe the box was gone.

28:14 He said, "No, no, no, not the box.

28:15 "The phantom limb which I've had for the last 13 years.

28:19 "The phantom limb is gone, it's disappeared." I said,

28:22 "What do you mean?" He said, "It's gone." I said, "When?" "Like three days ago.

28:26 "I've been trying to reach you." And I was

28:28 a bit worried about this because human subjects and ethics,

28:30 because I've permanently modified this guy's body image,

28:32 if what he's saying is true.

28:34 Then I said, "Well does it bother you?" He said,

28:36 "No, the pain that I had "in my phantom elbow,

28:38 my phantom wrist, "and my phantom fingers, I've never had those pains.

28:41 "In the last three days I don't have a phantom."

28:44 We can go into the question of why this happens later,

28:47 but clinically, this has been tried in several clinical trials,

28:50 one in the New England Journal of Medicine, so you can see the...

28:55 Published in the New England Journal of Medicine from Walter Reed.

28:58 You can see with the mirror they say the pain drops to almost no pain.

29:03 With the covered mirror and visual imagery the pain actually goes up

29:08 until they crossed over and then the pain drops again in the mirror.

29:11 And now it's widely used in clinics around the world.

29:17 Now, surprising, curing pain in a phantom

29:20 limb with a mirror is surprising enough.

29:22 Now as you see there's a lot of variability.

29:24 Only about half the patients are helped.

29:26 In about half of them the mirror does nothing,

29:28 typically patients who've seen them for a long time.

29:30 These variables need to be studied.

29:32 There's another disorder which I want to tell you about.

29:34 Speaking of mind and body and Lekov here has done more

29:37 than anybody else to talk about links between mind and body.

29:40 But here is a powerful example you see in the clinic.

29:43 Ordinarily we think of pain as one thing.

29:44 But there's in fact two kinds of pain.

29:46 There's chronic pain and acute pain.

29:48 Acute pain, you touch the kettle

29:49 and you withdraw to prevent further tissue injury.

29:52 Obvious adaptive value.

29:53 Chronic pain is the opposite.

29:55 Immobilize the arm.

29:56 You've a tiny metacarpal bone fracture, and your finger becomes painful,

30:01 immobilized, there's a reflex immobilization

30:04 to prevent further injury to the finger,

30:06 and it gets swollen and it gets inflamed and it gets warm and it gets red.

30:11 All signs, it remains swollen, warm, red, painful, and inflamed.

30:16 And then the bone heals after two weeks, all the change is reversed,

30:20 the inflammation subsides, pain goes away, the finger starts moving again.

30:23 That's normal, 99% of people.

30:26 In about one or two percent of people that does not happen.

30:28 The injury heals, the bone heals, in x-ray,

30:32 but the pain persists with a vengeance.

30:34 It continues to be immobilized, paralyzed.

30:37 It gets swollen, it gets warm.

30:41 Normally then it spreads to the entire hand.

30:43 Entire hand gets warm, swollen, painful, immobilized, paralyzed.

30:46 Entire arm gets paralyzed, swollen, immobilized,

30:49 from the starting from the little metacarpal bone fracture.

30:52 So what's going on here?

30:53 I don't know.

30:54 We still don't know.

30:55 But one thing, the paralysis I think is

30:57 partly due to what we call learned paralysis.

30:58 Every time you attempted to move this finger,

31:00 move the arm, brain was sending a single, "Ouch, it's painful,

31:04 stop moving it." So there's a habean link between

31:07 the very attempt to move the hand and the excruciating pain.

31:10 So the brain gives up and says "Stop moving

31:11 your hand." So you get this pseudo-paralysis arising from punishment.

31:16 So we said, "How do you cure this?" Well let's put a mirror here, of course.

31:21 And put the other hand there, and send a symmetrical command,

31:24 you're gonna get a visual illusion that the paralyzed,

31:26 swollen, painful hand is actually moving with impunity.

31:29 But he's not actually moving it.

31:30 There's an optical twin that's moving.

31:32 He's seeing the reflection of his normal hand moving.

31:35 But with that unlearned the learned pain phenomenon.

31:38 But this is a wild hunch, even by my standards, and we're setting out to do it,

31:44 fortunately another group did it, Halligan, Marshall and Wall, in England.

31:49 And they...

31:51 That shows you an example of RSD.

31:59 They did a similar experiment with a mirror and found dramatic recovery.

32:04 In fact, what's astonishing is, when you put the mirror there...

32:08 Here's a guy for months he's been

32:10 swollen and paralyzed and inflamed and painful.

32:13 He moves the normal hand, in a few minutes the inflammation stops,

32:17 not only the pain, but the mobility returns and the swelling starts subsiding.

32:23 And the temperature starts falling.

32:24 You can't fake a fallen temperature.

32:26 So that convinced me that it was real.

32:28 And then when I saw one of the authors was Patrick Wall,

32:31 who's the world's leading expert on pain,

32:33 he's experimented on placebos as well, so his name was in the papers,

32:36 I figured this must be a real phenomenon.

32:37 Since then, there's been about four or five controlled studies,

32:42 there's been blind controlled studies, placebo controlled studies,

32:44 also now it's the accepted first line

32:46 of approach treating RSD in clinics around the world.

32:49 It's an extraordinary example to me of mind-body interaction.

32:53 That a mirror is producing changes...

32:56 Vascular changes in sympathetic pain, changes in swelling,

32:59 all of it, temperature, all of that.

33:03 All online.

33:06 It's also being used for stroke by the way now, mirror rehab,

33:09 and also for neglect, which I won't go into now, for a lack of time.

33:13 Now just when I thought I was done with phantom limbs,

33:17 I came across another phenomenon.

33:19 I started reading Rizzolatti's work on mirror neurons.

33:23 I speculated on this, and jumped off my seat when I first heard the talk.

33:27 Everybody here knows about mirror neurons, especially here in Berkeley.

33:31 They're neurons in the front of the brain,

33:32 prefrontal cortex, roughly homologous to Brocal's area, B5.

33:37 These neurons normally are the garden-variety motor command neurons which when

33:40 a monkey or a person reaches out and grabs a peanut,

33:44 a neuron fires, orchestrating the series

33:47 of motor twitches required for grabbing the peanut.

33:51 About 10% of these neurons Rizzolatti found.

33:54 They'll also fire when I watch George here reaching out and grabbing a peanut.

33:58 They've been quickly dubbed monkey see, monkey do neuron, or mirror neurons.

34:03 So they're sort of simulating doing a virtual

34:05 reality simulation of your impending action, is the claim.

34:10 Now, there's also sensory mirror neurons, they're equally interesting.

34:14 Discovered by Christian Kaiser in S2, the sensory cortex.

34:18 Remember I showed you the map of the sensory areas of the brain.

34:21 When you touch my left hand, right somatosensory cortex,

34:25 S1, S2 cells are activated, there's a map.

34:28 This has been known for a long time since Lord Adrian,

34:30 goes back 70 to 100 years.

34:33 Now, a subset of these neurons,

34:35 about 10% of them will react to my watching George's thumb being touched.

34:40 So this is very interesting because we can call them empathy neurons.

34:44 Because the neuron is effectively saying,

34:46 what's happening to George is similar to what

34:49 would happen to you if your thumb were touched.

34:51 So empathize with George, you know what it's like to feel his touch.

34:54 Same thing with pain, you go to anterior singular,

34:55 there are neurons sensitive to pain.

34:57 If you poke my thumb with a needle, it goes to my anterior singular and I say,

35:01 "Ouch." But if you poke George's thumb with a needle,

35:04 a subset of the same neurons fire and I can empathize with George.

35:09 But here's an interesting question: Wouldn't I shout,

35:12 "Ouch" when he's poked with a needle?

35:13 The same neurons are firing.

35:15 Wouldn't I withdraw my hand and I will simply watch George's hand being poked?

35:21 A couple of possibilities.

35:22 One possibility, obvious possibility,

35:23 is I wear my normal skin sending a veto signal saying,

35:26 "Don't worry, you're not actually being poked.

35:28 "Empathize with George, by all means, "but don't dissolve into him.

35:33 "Don't withdraw your hand suddenly "because that's maladaptive,

35:35 it'd be a waste of time.

35:38 "So empathize with him, know what it's like to be George,

35:41 "in George's shoes right now, "but don't withdraw your hand,

35:44 that would be foolish." So I looked at this and I said,

35:46 "Well the obvious prediction is if I amputate

35:48 my arm "and look at George being poked,

35:50 "I should feel the pain in my phantom." Because the afferent signals are gone.

35:55 There's no veto signal.

35:55 Is that clear or obscure?

35:58 So in the hundred years that we've known about phantom limbs,

36:01 nobody answers this question.

36:02 If you poke somebody with a needle when a phantom limb patient is watching,

36:06 does he feel the poke in his phantom?

36:07 The answer is yes.

36:08 We've seen in three patients now, they watch another patient being poked,

36:12 they feel the pain in their phantom.

36:15 So we call these empathy neurons or Gandhi neurons.

36:18 (audience laughing) Now there's some debate

36:21 about whether mirror neurons are significant,

36:25 whether they're important or the same mysteria of the minds,

36:28 action understanding action, production,

36:31 all of this, just is it old-fashioned psychology,

36:33 new words to describe empathy and things like that.

36:36 We won't go into that.

36:37 This patient went home and he had a smart

36:40 idea and we talked about it before he went home.

36:43 He feels excruciating phantom pain in his phantom arm,

36:46 cramped, phantom cramping pain.

36:48 He can't do anything about it.

36:49 We were already getting ready to start him on the mirror protocol,

36:52 before that he simply watched his wife's hand being massaged.

36:58 And of course he felt a phantom massage in his phantom hand, he claimed.

37:03 'Cause he needed to relieve the phantom pain.

37:06 This is not, unlike the mirror procedure, this has not been tested in clinics,

37:10 in a clinical setting using placebo controls.

37:12 But if it works, it'll be a clear example

37:14 of a practical application of the idea of mirror neurons.

37:17 Leaving aside all the arcane,

37:19 theoretical debates about how significant they are,

37:21 practically, in the clinic, to alleviate phantom pain.

37:23 That guy doesn't care (mumbles) the theory or the mind or what it is.

37:27 His pain goes away.

37:30 Now another prediction we made, this is kind of cute, actually.

37:33 Going back to the motor neurons,

37:36 there's a condition called OCD, obsessive-compulsive disorder.

37:39 In one particular variation which is particularly

37:41 troubling to the patient is ritual hand washing.

37:44 A person accidentally touches a doorknob,

37:47 this mere minor contamination elicits acute anxiety, almost panic,

37:50 and the guys incessantly wash their hands,

37:54 to the point of erosion of the hand, fingers and skin.

37:58 And then we said, "Well what if he

37:59 simply "watches another guy washing his hand?" Sounds stupid.

38:03 Some of my best experiments begin as jokes, by the way.

38:06 (audience laughing) So I said,

38:09 "What if he watches somebody..." There's an experiment done with Jalal,

38:11 Baland Jalal, a student in my lab.

38:14 So sure enough, in about two thirds of the patients we've seen with OCD traits,

38:20 hand washing compulsions,

38:21 they watch another person washing his hands, they get relief.

38:26 And the interesting thing about this is it

38:28 can't be response bias because they're surprised by it.

38:30 "How the hell...?

38:31 "Why should him washing his hand produce relief in me?

38:34 "It doesn't make any sense." They express surprise.

38:37 So I think we're on to something, a potential treatment for OCD.

38:41 Because you could have an app that shows you, as soon as you get the urge,

38:45 you look at your self washing your own hand,

38:47 you don't have to go to the toilet and spend half an hour, right?

38:50 So another example of a clinical application for something like OCD.

38:54 It's a topic that I know very little about, by the way.

38:58 I'd like to switch gears now

38:59 and talk about phenomenon which we call synesthesia.

39:03 Which was documented first by Francis Galton,

39:07 in 19th century, first cousin of Charles Darwin.

39:09 He noticed some otherwise normal people in the general population.

39:12 He said it was rare, one in 1,000, one in 500,

39:15 now we know one in 50 people have synesthesia.

39:18 So this condition is one where a person is otherwise completely normal.

39:22 If he sees a printed number on a white sheet of paper, like five is red,

39:26 six is blue, seven is green, eight is chartreuse,

39:28 nine is indigo, and so on and so forth.

39:29 The color remains constant for any

39:32 particular individuals over years, stable over years.

39:35 It's different for different people, not the same colors for different people.

39:37 Although there are trends, we can get to that if you want.

39:40 Now since the discovery of synesthesia by Galton,

39:47 there have been hundreds of case reports,

39:48 but no attempt to understand what's going on in the brain or what causes it.

39:52 And in fact, people brushed it aside, classic example of an anomaly in science,

39:56 a Kuhnian anomaly, which people brush under the carpet and say,

39:59 "It doesn't make any sense.

40:00 "What do you mean five is red, six is blue?

40:01 "It doesn't make any sense." Well often anomalies can pave

40:05 the way to new discovery and new areas of research.

40:09 So we thought, well why not study these people?

40:12 And the standard explanation of synesthesia, by the way,

40:15 one explanation is these are just crazy.

40:18 That's not an explanation.

40:19 Even if it's true, let's put that aside for the time being,

40:22 come back to it as a last resort.

40:24 Second explanation is, they're high on drugs.

40:28 And sure enough, it's about seven times more common in Berkeley than at UCSD.

40:32 (audience laughing) But leaving that aside,

40:36 the fact that drugs influence synesthesia is

40:38 not evidence against synesthesia being a legitimate phenomenon.

40:41 It makes it more interesting.

40:42 Why would some drugs enhance this propensity to see numbers as color?

40:47 The third explanation is they're just childhood memories.

40:50 They've been playing with the refrigerator magnets and five was red and six was

40:53 green and seven was blue and eight was yellow and so on and so forth.

40:56 This doesn't make any sense to me because why does it run in families?

41:00 Galton himself showed that synesthesia runs in families

41:02 and possibly in a Mendelian fashion, so it's inherited.

41:06 So you have to see the same madness

41:08 as being passed on from generation to generation, which didn't make much sense.

41:11 But you had to keep in mind the possibility.

41:15 And then if it's true, if it's just magnets, why don't we all have synesthesia?

41:18 Why only a subset?

41:20 Obvious questions.

41:21 The fourth possibility is more ingenious but a bit vague.

41:25 Along the lines that George and I have been thinking.

41:27 I'm not saying you're vague, but I'm vague.

41:30 That is that maybe they're being metaphorical when they say five is green.

41:34 Maybe it's like oh, say, F sharp is blue.

41:37 It's like saying cheddar cheese is sharp.

41:39 The cheese isn't sharp.

41:40 You rub it on your skin it's soft.

41:42 You say, "No, no, no, the taste is sharp." But there's a circularity there.

41:45 Why do you use a gustatory metaphor,

41:47 a tactile metaphor to describe a gustatory sensation?

41:50 There's a whole area of research that this leads

41:53 to which we don't have time to go into.

41:57 But this may be on the right track,

41:59 as you can see, this is what I'm gonna argue.

42:01 First of all, are they crazy?

42:03 We did a number of experiments to show that they are not.

42:05 It's a legitimate phenomenon.

42:07 And in a subset (mumbles) there are two kinds of synaesthetes,

42:10 the projectors and the associators.

42:12 Projectors are the minority, maybe about 10 to 15%, synaesthetes,

42:15 and we stumbled on two of them,

42:18 luckily when we started doing the research on synesthesia.

42:21 Associators are more difficult to study.

42:23 They constitute 80 to 90% of them.

42:24 So let's talk about projectors.

42:27 So we said, "How do you know they're

42:28 not making it up?" Well we designed this display.

42:32 You've got a synaesthete who sees numbers as color.

42:36 So we show normal people this panel of fives with some two scattered among them.

42:42 Can you find the twos?

42:43 One there, one there, one there.

42:45 They form a shape, either a square or a triangle or a circle.

42:48 And it takes ages.

42:49 Takes 20, 30 seconds before you spot the upside down triangle.

42:55 A synaesthete looking at it sees it much faster.

42:57 He says, "Oh I see an upside

42:59 down red triangle." If you're a projector synaesthete.

43:03 Now if he's crazy, how come he's better than us?

43:07 This has been confirmed by Jamie Warr,

43:08 by the way, in London, in a larger group of...

43:11 This experiment done with Ed Halbert,

43:13 he used to be a student here at Berkeley before he turned into a grad student.

43:18 Also there's phenomenology.

43:19 You talk to these patients,

43:21 for them it's not a patient, subject, sorry about that.

43:25 Synaesthete I saw recently said, "Eight is blue." And I said,

43:29 "Do you see the blue in your mind's eye?

43:32 "Like when you think of Cinderella "you think

43:33 of a pumpkin or you think of a chariot?

43:35 "Or do you literally see it blue?" And she said,

43:39 "No, no, I actually see it blue.

43:41 "It's not like Cinderella and the pumpkin.

43:42 "Because there I can think of Cinderella and her gown, "Cinderella and mice.

43:46 "Whereas here I can only think of blue.

43:48 "The irresistible urge to see blue.

43:50 "And not only that, in my case, it spills out of the color,

43:53 "Spills out of the letter and forms a halo,

43:55 "a dusty halo around it." Now why would that be?

43:58 The first thing I did was simply put an amoeba around it,

44:02 and the halo gets blocked, part of the halo gets blocked by the amoeba.

44:05 These kinds of phenomena you can't

44:07 explain in terms of vague psychological associations.

44:10 Suggests strongly that they're sensory in character.

44:12 You can even put an illusory contour around

44:14 the A, it gets blocked by the illusory contour.

44:17 We can get back to where that's happening in a minute.

44:19 So what's happening in synesthesia, what's going on?

44:22 Rumor that it runs in families, that's one clue.

44:25 It's also (mumbles) that synesthesia is seven

44:26 or eight times more common among artists,

44:28 poets, and novelists and other creative people than in the normal population.

44:31 That's another piece of the puzzle.

44:32 We've got all these pieces of the puzzle.

44:34 Why is it eight times more common among novelists, poets, and artists?

44:38 Why?

44:38 We'll see in a minute.

44:41 And in the subset of synesthesia we've got the projectors,

44:45 we stumbled on, the anatomy is straightforward.

44:48 Greg Hubbard and I were looking at brain atlases.

44:51 We saw that the area for numbers shown in the red,

44:55 discovered by Stanislas Dehaine and Tim Ritger in our lab,

45:03 in our department, shows where graphemes are represented, including numerals.

45:08 And the green path is (mumbles) Z4.

45:13 This is involved in processing color.

45:15 We said, "What's the likelihood of the most common "type of synesthesia,

45:17 number-color synesthesia "and these two are right next to each

45:20 other "in the fusiform gyrus of the brain?" Well we said,

45:25 "It's very unlikely to be a coincidence.

45:26 "Maybe there is some accidental cross-wiring "between number and color."

45:30 So every time they see a black and white

45:31 number it activates a number node and cross-activates

45:34 a color node spontaneously so they see a particular color.

45:37 Now why would there be cross-activation of this kind in these people?

45:40 Remember the clue comes from the fact that it runs in families.

45:43 Remember that in the fetus, in early embryology,

45:45 in early, early childhood, perhaps, everything is connected to everything.

45:49 That's an overstatement, but a tremendous redundancy of connections.

45:53 But then these excess connections are pruned away by pruning

45:56 genes to create a modular architecture that characterizes the adult brain,

45:59 including number area and color area.

46:01 So if these pruning genes are mutated, there's defective pruning,

46:05 then some redundant connections are gonna be left behind,

46:10 for example the mutant pruning gene is selectively

46:15 expressed by transcription factors in the fusiform gyrus alone,

46:18 you get this quirky number-color synesthesia.

46:22 And what about the higher synaesthetes?

46:23 Where it's not just the number that produces,

46:25 visual appearance of the number that produces...

46:27 So-called associators, what about them?

46:29 Well we did a simple experiment on these people, these projectors.

46:33 We said, we asked a very simple question which had not

46:36 been asked about synaesthetes since the 100 years we've known about it,

46:38 since Galton's time.

46:40 Instead of showing them a five, why don't you show them a V, a Roman five?

46:45 Instead of showing them an Arabic six or an Arabic seven,

46:47 I should call them Indian by the way, but instead of showing an Arabic number,

46:51 why when you show them a Roman five, what do they see?

46:53 Do they see a color?

46:54 The answer is, I've never met a synaesthete who's seen color in a Roman number.

46:57 So it's not the concept of the number creates the color,

47:00 it's the visual appearance,

47:01 which fits the idea that fusiform gyrus encodes the visual appearance,

47:05 not the higher level concept of numerosity,

47:08 ordinality, cardinality, and all that good stuff.

47:12 Which, by the way, I think happens in the angular gyrus.

47:14 We've long known that the angular gyrus,

47:17 if the left angular gyrus is damaged, you get discalculius.

47:19 If you ask him to subtract 17 from 21, he'll say,

47:24 "Oh it's 14." He will glibly say it's 14,

47:27 and is sure that he knows it for certain.

47:31 Discalculia's another whole lecture.

47:37 So I think in the projector synaesthetes, the cross-wiring gene is expressed,

47:41 you have the cross-wiring gene, we get number-color synesthesia.

47:45 In the associator synaesthete, it's expressed higher up so the idea of sequence

47:50 is mapped onto higher color areas in the brain.

47:54 In the color processing hierarchy.

47:56 So it's expressed higher up.

47:58 I can show you a diagram later.

48:01 In the vicinity of the angular gyrus

48:02 you get higher synaesthetes or lower synaesthetes.

48:04 Which would explain why some of these higher synaesthetes also experience

48:08 not only numbers as color but days of the week as color.

48:14 Monday is red, Tuesday is blue, Wednesday is chartreuse.

48:17 And months of the year as color.

48:19 Again, it seems completely and utterly incomprehensible.

48:21 What do they all have in common?

48:23 Months of the year, days of the week, and numbers?

48:24 Sequence.

48:26 So I think the angular gyrus is where the action is.

48:28 And now there's some research using DT imaging by Rumka Holt in our lab,

48:33 she's visiting our lab, she has shown that in fact, if you do DT imaging,

48:37 there's more white matter in the vicinity of the angular gyrus

48:40 in the associators and in the fusiform gyrus in the projectors.

48:43 But this is still very preliminary, I should add a note of warning.

48:47 Okay here's another fun example, and we can play games with these people.

48:51 How many of you can read that?

48:53 Raise your hand.

48:55 Very tough.

48:56 Now squint your eyes.

48:58 (audience laughing) George you can't read it yet?

49:03 Remove your glasses.

49:09 Okay.

49:11 Alright, now guess what happens when you show this to a projector synaesthete?

49:16 Projector synaesthete says, "Well I see a jumble of colors but I don't know why,

49:19 "because you know I can't see any letters." Then they say,

49:23 "Oh wait a minute, I know why that's red.

49:25 "It's an N.

49:27 "It's an O, that's why it's blue.

49:29 "S, E, oh I see, ha ha ha." Okay so

49:33 they're seeing the colors being activated but it's hidden numbers.

49:37 Before they reach consciousness and register as graphemes.

49:40 So the blind side for numerals in synaesthetes.

49:43 So what I'm claiming is, in these individuals,

49:48 those hidden numbers are activating the color area of the brain,

49:52 and then they're evoking a proper (mumbles)

49:55 they're evoking a number area of the brain.

49:58 Activating the number area.

49:59 Evoking the appropriate color even before the message is

50:01 sent higher up to be recognized as a grapheme.

50:05 So you're seeing the colors and using the colors to infer what the grapheme...

50:08 The most striking example of this I've seen is two colorblind synaesthetes.

50:13 Sounds like an oxymoron.

50:15 This person could see a limited range of color

50:17 because of vision cone pigments in the eye.

50:19 Limited range of color in the external world, but when they saw numbers,

50:22 they would see colors that you would never see in the external world.

50:24 They call them, charmingly refer to them as martian colors.

50:28 And the reason again...

50:30 We've seen two patients like this.

50:31 The reason again is because the cone pigments are

50:34 deficient so they can't see colors in the real world,

50:37 they see only limited range.

50:39 But they saw a number,

50:40 the number activates a number node and cross-activates color neurons which can't

50:45 experience those colors in the real world because the receptors don't exist.

50:49 It's hardwired for seeing quote-unquote martian colors.

50:52 Is that clear?

50:53 This again eliminates any possibility

50:54 of learning being the basis of synesthesia.

50:56 How can you learn a color you've never seen?

50:59 Another phenomenon Galton,

51:00 the astute Galton noticed was what he called number lines.

51:04 When I ask any of you to imagine numbers in front of you, one to 10,

51:07 you may be crudely going left to right, one, two,

51:12 three, four, and it's very vague, there's nothing really clear.

51:15 But in some individuals, Galton noticed, and again we find this about one in 50,

51:19 to one in hundred, will see a vivid,

51:21 three-dimensional layout of numbers in the visual field.

51:24 One is here, two is here, and it's convoluted, not straight line left to right.

51:29 It's convoluted, 1, 2, 3, 4, 5, 6, 7, 8, 9,

51:31 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20.

51:34 And often doubles back on itself like this.

51:36 So fifteen may be close to two,

51:39 instead of being close to 16 or 14 in Cartesian space.

51:43 And this has been ignored for 100 years and Ed Hubbard and I

51:47 and David Brian did some experiments to establish

51:49 that the people are not faking it.

51:50 We used the number-distance effect, I don't have time to go into it.

51:53 So they're not faking it.

51:55 The number line affects their reaction time to numbers.

51:58 So then there'd be mixed results on this phenomenon.

52:01 But everybody agrees with me about the phenomenon,

52:04 the question is why does it arise?

52:05 Why would some people see numbers and imagine numbers like...

52:12 Again, it's a classic example of an anomaly in science.

52:15 And people ignore it for that reason.

52:17 I don't know the answer to why they see it this way,

52:19 unlike the grapheme color synesthesia where I had a clear answer.

52:23 But only one reason, the one thing I can think of is arithmetic

52:25 and numbers and mathematics is a recent event in human evolution,

52:29 maybe 5,000, 10,000 years old.

52:31 And the brain can't invent a completely

52:33 new algorithm from scratch to handle numbers,

52:36 ordinality, sequences and all of that.

52:38 So what it does is, it adopts a trick using preexisting maps in the brain.

52:43 Maps go back into Ionian times in our fish-like ancestors.

52:46 Brain is full of maps.

52:47 So you map on the ideal concept of numerical sequence,

52:50 ordinality and cardinality and quantity.

52:52 Onto spacial map to create a graph.

52:55 If something goes awry with this remapping

52:57 of this concept of sequence onto a spacial map,

53:01 you get these peculiar number lines.

53:03 Now how do you test this idea?

53:04 I have no idea.

53:07 But it's an interesting idea nonetheless.

53:10 Now some of these people also have, I'm almost done...

53:14 Some of these individuals,

53:15 and we've studied a number of these, David Brian has studied them in our lab.

53:19 Have what we call calendar lines.

53:21 Here is a woman we studied recently.

53:25 And when I ask any one of you to imagine a calendar in front of you,

53:29 typically most people imagine a rectangular calendar.

53:33 Like a real calendar, January, February, March,

53:35 and then you know, so on and so forth.

53:38 Very vague, nothing very clear.

53:40 It's in your mind's eye.

53:41 These people see a very clearly laid-out,

53:44 three-dimensionally laid-out calendar, always circular, never rectangular,

53:48 and never in the cardinal plane but in the transverse plane,

53:51 like a hula hoop going through their chest.

53:53 January, February, March, April, May...

53:55 Current month always occupies the ego of the calendar.

54:01 You see this repeatedly in different subjects.

54:04 And here's an interesting one that George would like.

54:08 You'll do interesting experiments on them like

54:10 what if you tilt their head like this?

54:12 Does the calendar tilt?

54:14 The answer is no, it stays like a water level, where it is.

54:17 Here is the best part.

54:19 If you ask them to rotate their head like this, what happens to the calendar?

54:24 The calendar's here like a hula hoop.

54:25 Rotate their head like that to the right, what happens to the calendar?

54:28 Calendar, in this particular case, remains attached to the head.

54:31 Sorry, attached to the body.

54:33 It's in sort of...

54:34 Put it crudely, body-centered, not head-centered.

54:37 But the exciting thing is, she noticed that the left side of the calendar

54:41 became fuzzy as she rotated her head, like a real, physical calendar.

54:46 Why in the hell would a mental calendar be like a physical calendar?

54:49 And she said also, she organizes her life, her time and space and calendar,

54:53 using this calendar helps her organize

54:54 her otherwise chaotic and meaningless life.

54:58 And then she looks back and she looks on the other side the opposite happens.

55:02 So she can use this mental calendar

55:04 to organize her daily activities and her future,

55:08 project herself into the future.

55:09 Surely a vital part of what you call the self.

55:12 And not only that, here's what we're testing currently.

55:16 If she does this, memories, episodic memories,

55:19 events that happened in January, February, become fuzzy.

55:21 She has to look there to retrieve memories.

55:24 She's an undergraduate student, I don't think she's read Lekov's book,

55:28 so I don't think she's making it up, but we don't know yet for sure.

55:31 We're testing her.

55:32 Lovely example of embodied cognition,

55:34 her neck muscles are gaining access to memories, episodic memories.

55:39 Now, where is it happening?

55:42 This is what we always do, when we look at peculiar phenomenon,

55:44 to nail it down, show what's going on, so it's a real phenomenon,

55:47 the patient's not making it up,

55:48 and try to figure out what's going on in the brain

55:50 and a possible cure if it requires curing.

55:53 What's going on in the brain?

55:54 Well, I said the angular gyrus must play a critical role in sequence.

55:58 I think it plays a critical role in calendars.

56:00 This can be tested.

56:02 But then, what about hippocampus?

56:04 It's got play cells,

56:06 it's got two kinds of cells involved in spatial and temporal labeling of events.

56:11 And now it turns out, looking at atlases,

56:15 there are direct connections between the angular gyrus and the hippocampus,

56:17 the inferior longitudinal fasciculus.

56:21 And that's shown in the next slide.

56:24 So I'm claiming that the human mental calendar,

56:26 which we take for granted but we use for organizing our lives,

56:29 life would be completely meaningless...

56:30 People usually attribute it to fondle structures.

56:33 I think fondle structures only involve paying

56:34 attention to specific regions of the calendar.

56:36 Calendar itself is constructed by interactions between

56:38 the left angular gyrus and the hippocampus.

56:44 Okay I'll just conclude there by saying that all

56:46 of these problems which are tangentially related to the problem of self,

56:50 how you construct the body image, how you feel a hand cut inside your body,

56:54 embodied cognition, projecting yourself into the future

56:56 and creating a calendar around which your life revolves,

56:59 your problems are considered intractable but we can

57:01 sort of begin to just scratch the surface.

57:03 Thank you.

57:05 (audience applauding)- Hi, my name is Eric.

57:13 So I have a question about synesthesia.

57:15 Sure.

57:16 You mentioned that synesthesia runs in families.

57:18 So there's a genetic factor.

57:20 In your studies, did you notice that the same synesthesia,

57:25 the color-number synesthesia is hereditary, or is it different?

57:30 It's a problem statistically because the most

57:32 common form is number-color or letter, grapheme-color.

57:36 I think there is a tendency for the same form to be inherited,

57:38 but it's not been...

57:39 The only thing we know for sure is if you have one type of synesthesia,

57:42 you're much more likely to have another unrelated type of synesthesia as well.

57:45 Which supports my defective pruning theory.

57:48 The same transcription factors are expressed

57:50 in two different regions in the same brain.

57:53 And you're gonna get two unrelated types of synesthesia co-occurring,

57:55 more often than by chance.

57:57 Are these like functional areas that are sort of...

58:02 The function's kind of fused together?

58:03 To give you an example,

58:05 the number-color synaesthetes are often the ones with the calendar synesthesia.

58:09 And often the ones with tone-color as well.

58:12 They don't always have to occur together but often do,

58:15 or much more often than by chance.

58:17 Thank you.

58:18 Sure.

58:19 I didn't mention about creativity, but I'll get to that later.

58:23 Hi, thanks for a great talk.

58:24 I wanted to say something here a little more about the metaphorical

58:28 views or the anthropomorphism involved with talking

58:31 about the neurons in the brain.

58:33 When you say that an area that normally

58:37 corresponds to an amputated limb or something,

58:39 when you say it's starved for stimulation or it's

58:44 hungry or something like that, so what is that describing?

58:48 Why would a non-stimulated area in the brain

58:52 care whether or not it was stimulated or not?

58:55 So in what sense is there a causal explanation for saying...

58:58 Or the cross-wiring sounds a little more plausible than saying oh

59:04 it's hungry or it's starved or stimulation wants to move around?

59:09 I was just being loose with the terminology.

59:12 Sorry.

59:14 It's a legitimate question.

59:16 I forget the name of that syndrome where somebody wants to have an amputation.

59:21 Xenomelia.

59:22 Xenomelia?

59:23 Yeah.

59:24 Great.

59:25 Just a question of ethics in that regard.

59:30 Before it's not done yet.

59:31 Well but do we mutilate somebody because their heart wants to look differently?

59:37 That's the kind of issue that has come up and have

59:40 you seen some advances in figuring that ethical question out?

59:44 I'm interested in those issues,

59:45 but it doesn't come up in our case because the patient,

59:48 no surgeon will ever do the amputation.

59:50 They have to go across the border to get it done.

59:53 At least in the US.

59:54 At least in the US.

59:55 Thank you.

59:58 Hi.

59:59 Do you have any thoughts of what is going on in schizophrenia, for example?

1:00:04 The self is broken or I don't know how...

1:00:08 Maybe do you have some thoughts about it?

1:00:11 I've thought about it, but not enough to say anything intelligent.

1:00:16 Thank you.

1:00:20 These unexplained thought forms like synesthesia,

1:00:24 any evidence or maybe a feeling of immortality of the soul?

1:00:32 (audience laughing)- It's a question for George.

1:00:40 Quick question.

1:00:41 You didn't wanna touch on, in this talk,

1:00:44 but just a brief background from you on the ancient civilizations of India,

1:00:52 the whole Vedic tantra Agama literature.

1:00:58 How do you connect it yourself with some

1:01:02 of the phenomena that you've talked about today?

1:01:05 There's the metaphysical issues that are being

1:01:06 dealt with in Vedic literature or (mumbles).

1:01:10 In Hebrew literature, in neo-Christian literature which I haven't touched

1:01:14 on because I don't have any expertise in that.

1:01:15 I'm very interested in it, obviously.

1:01:18 The self is something that I can come to grips with, at least partially,

1:01:21 so I focus my attention on that.

1:01:23 But I like sharing this quotation from the Upanishads,

1:01:28 where he says that the individual self, human beings are like windows.

1:01:32 Let the light pass through.

1:01:33 And there's a central light illuminating the building from inside,

1:01:36 which is called (foreign language),

1:01:38 or universal spirit or consciousness or whatever.

1:01:40 When an individual dies, the window shuts,

1:01:43 but the universal spirit continues shining through other windows.

1:01:46 It's a comforting thought but I don't have any deep thoughts about it.

1:01:52 Thank you.

1:01:53 It's a good question, though.

1:01:55 I wondered if you'd done any research on photophobia?

1:01:57 People's feeling pain with regards to color.

1:02:01 I know a couple students who have that.

1:02:02 We haven't studied it.

1:02:04 Fascinating question.

1:02:06 But I can't tell you anything about it.

1:02:08 Like whether pain's...?

1:02:09 Okay.

1:02:10 Thanks.

1:02:12 Hi.

1:02:13 You just briefly mentioned that you hadn't explored creativity in synesthesia,

1:02:17 and I'm just wondering about work done on...

1:02:20 I know with music, different composers

1:02:23 who are very skilled who have synesthesia,

1:02:26 different composers see different colors, like Scriabin and Messiaen.

1:02:31 These composers...

1:02:32 Has there been any research on where

1:02:35 that happens or what's the effect that's going on in the brain and why they each

1:02:39 see different colors with sound and all of that?

1:02:42 Well we can't get that specific, but I do have a theory about why

1:02:44 synesthesia is so much more common among artists,

1:02:46 poets, and novelists, why it promotes artistic talent.

1:02:50 The reason is, I think that the same gene that's expressed selectively

1:02:54 in fusiform gyrus or angular gyrus

1:02:56 producing this quirky association of synesthesia,

1:02:58 if it's expressed throughout the brain,

1:03:01 there's gonna be creative cross-connectivity throughout the brain,

1:03:03 and ideas and concepts are also in far-flung regions of the brain,

1:03:06 like when you say Juliet is the east and Juliet is the sun.

1:03:09 So Juliet is the sun, does that mean she's a glowing ball of fire?

1:03:12 You don't say that.

1:03:13 You say she's warm, she's nurturing, she's radiant like the sun,

1:03:16 she rises in bed like the sun rises in the east.

1:03:19 She's the center of my solar system like

1:03:21 the sun is the center of the solar system.

1:03:22 You can make as many associations as you want.

1:03:25 And these people have excess connections connecting far-flung brain regions,

1:03:29 have a greater propensity to link seemingly unrelated ideas.

1:03:32 And this is what we call artistic creativity or facility in metaphor.

1:03:37 In fact, you can even think to put it in phrenological terms,

1:03:40 each node has a penumbra of meaning,

1:03:44 like Juliet of the sun has a penumbra of meanings associated with it.

1:03:48 And because of the excess connections, the penumbra is bigger in synaesthetes.

1:03:52 There's greater zones of overlap between two seemingly unrelated ideas,

1:03:55 so it makes them more creative.

1:03:57 Hence the higher incidents of...

1:03:59 And hence, by the way, the higher prevalence of synesthesia gene.

1:04:03 Why would one in 50 people have this quirky ability of linking five and red?

1:04:07 Because there's a hidden agenda because the gene makes

1:04:09 the outliers in the population more creative and imaginative in general.

1:04:13 And the penalty you pay for that is the minority

1:04:15 who sees five as red but doesn't do them any harm.

1:04:18 Otherwise there would be no selection process

1:04:20 to maintain this gene in the population,

1:04:21 it would've drifted away a long time ago.

1:04:24 Thank you.

1:04:25 Thank you.

1:04:26 But regarding specific details of colors and all that, we haven't studied that.

1:04:31 It's a good question.

1:04:33 On the same subject of creativity, I'm coming from linguistics like literature,

1:04:39 and I'm trying to bring new findings of neurolinguistics

1:04:46 into how the brain acts and reacts in writing.

1:04:50 And I know a little bit about words

1:04:53 that has to do with visual and kinesthetic and auditorial,

1:04:58 but I wonder if there's something that is written on the subject

1:05:03 of the self seeing itself in words or not seeing, you know?

1:05:09 Did you write anything about it?

1:05:11 'Cause you said you—- There are literatures dealing

1:05:12 with that but I'm not the right person to ask, but it's a good question.

1:05:16 There is literature pertaining to that which

1:05:18 I can't think of it off hand, but...

1:05:22 Okay because the last doctor that you

1:05:25 said that you're not gonna discuss is self-awareness.

1:05:28 And I wonder if there's some passages

1:05:32 there in terms of self-awareness in creativity.

1:05:36 No?

1:05:38 Not that I know of.

1:05:41 I had a question regarding the phantom limb.

1:05:43 Did you try using different mirrors like concave and convex mirrors

1:05:46 and seeing what kind of effect it would have in removing the pain?

1:05:49 Or was it just?

1:05:51 So the types of mirror that you used in the phantom experiment...

1:05:54 Yes.

1:05:55 The only thing we've seen is if you use a magnifying mirror,

1:05:57 the phantom looks bigger, the pain also is amplified, momentarily, fortunately.

1:06:03 So there is a direct correlation in terms of...

1:06:06 Yeah.

1:06:07 Hasn't been studied carefully but appears to be, yeah.

1:06:11 Good question.

1:06:12 Thank you.

1:06:14 So I had a question about the case

1:06:16 of martian colors and the correlation of synesthesia.

1:06:18 So is there a difference between people who develop colorblindness later in life

1:06:22 due to macular degeneration or those who

1:06:24 are colorblind from birth so congenital?

1:06:27 We only studied the ones who are from birth.

1:06:29 Okay, alright thanks.

1:06:30 Two of them, but it's a good question.

1:06:34 I have a question about synesthesia.

1:06:37 You seem to argue in your talk that synesthesia is more inborn, not learned...

1:06:43 Or no?

1:06:44 It doesn't make any sense if synesthesia is inborn.

1:06:46 You're not born with letters of the alphabet and numbers.

1:06:50 Right that's what I'm wondering about.

1:06:51 What I meant to say was the propensity to link

1:06:54 arbitrary shapes like numbers and colors is inborn in some people.

1:06:59 Not that the phenomenon of synesthesia is inborn.

1:07:02 But why would it be always letters and numbers?

1:07:04 And why is always letters or numbers...?

1:07:08 There's a tendency for that region

1:07:10 of the fusiform to represent arbitrary shapes,

1:07:12 and there are rare cases of synesthesia with faces showing colors,

1:07:15 and faces are also in the fusiform gyrus,

1:07:17 as Charlie here has shown many years ago, very elegantly.

1:07:21 Alright, thank you.

1:07:25 Hi, thanks for being here.

1:07:26 Sure.

1:07:27 Two short questions.

1:07:28 One is, you mentioned something about neck muscles

1:07:33 and memory at the very end of your talk and I missed—- What I meant to say was

1:07:38 that in the person with episodic memory who claims,

1:07:40 we're not testing this rigorously by measuring her repeatedly

1:07:43 after a few weeks and a few months,

1:07:45 giving her some striking episodes and not telling her about it,

1:07:48 but if you go by what she's saying, if she looks to the right,

1:07:53 a portion of the calendar is on the left becomes fuzzy,

1:07:57 as it would if it were a real calendar.

1:07:59 She said the memories of those events become

1:08:02 fuzzy too and hard to drudge up in consciousness,

1:08:06 until she turns around and looks directly at the calendar.

1:08:09 So it's helping her to...

1:08:10 That's what I meant with the neck

1:08:11 muscles gaining the access to episodic memories.

1:08:16 That's the extreme version of the hypothesis.

1:08:18 Okay.

1:08:20 Also, what do you think is happening when

1:08:23 someone sees someone getting massaged across the room,

1:08:27 and let's not use the anomalous case,

1:08:30 let's just say anybody, they see somebody getting massaged...

1:08:34 Can they start feeling a little bit better or...

1:08:37 I know you haven't studied that but...

1:08:40 Like what do you think is happening?

1:08:41 Seems to me that because of your afferents,

1:08:43 you know that you're not being massaged, and that kind of silences it.

1:08:45 So I doubt very much you'd experience any benefit from that.

1:08:48 But there are a group of people

1:08:52 who congenitally have some (mumble) of hyper-empathy.

1:08:56 It's claimed by Sarah Blakemore.

1:08:58 I haven't seen subject myself, but I trust her judgment.

1:09:02 So what you're saying may be true of a minority of the population,

1:09:06 20% of the population.

1:09:07 But in the case of phantom limbs, the majority of the phantom limb patients

1:09:10 experience this hyper-empathy syndrome because of the deafferentation.

1:09:15 Okay thank you.

1:09:17 Thank you.

1:09:17 I have a question about the soul.

1:09:20 Okay.

1:09:22 Largely because of you, I got invited to the Gifford Lectures after you came.

1:09:27 And these are the Gifford Lectures on natural theology.

1:09:30 And I couldn't resist putting in stuff on the soul so I said,

1:09:35 look if the soul has to not, to exist after you die,

1:09:40 and goes to heaven, et cetera, or the other place,

1:09:44 then it has to, the question is,

1:09:47 it has to not have anything that is required by a body.

1:09:51 So the question is, what is required by a body?

1:09:54 And if it's required by a body, the soul can't have it.

1:09:56 So you can study the properties of the soul that way.

1:10:01 So can the soul see?

1:10:02 No.

1:10:03 Hence, can't see, doesn't have a visual cortex, et cetera.

1:10:07 Can the soul hear?

1:10:08 Sorry, doesn't have the hearing apparatus for that.

1:10:13 Can the soul feel touch?

1:10:15 No.

1:10:16 Doesn't have the appropriate part of the cortex, et cetera.

1:10:20 And you go through this list.

1:10:22 Can the soul remember?

1:10:24 Doesn't have what is required for memory for that.

1:10:29 And so you go through that, and the next question is,

1:10:32 does the soul have a personality or your personality?

1:10:37 So the question is does personality depend upon the brain in any way?

1:10:43 And this is a question I asked Nina, who knows much better than I do,

1:10:47 and she pointed out that the Phineas

1:10:50 Gage phenomenon would say that it's lost control,

1:10:54 it doesn't have inhibition, et cetera,

1:10:57 sort of like Donald Trump or you know, (laughs).

1:11:03 That's certainly one kind of personality change,

1:11:07 but also there could be larger brain injuries

1:11:09 that could produce sort of positive changes of all sort

1:11:13 and if that's the case then the soul would

1:11:16 not have a fixed personality and therefore not your personality,

1:11:21 so in what case is it your soul?

1:11:25 So the question about personality is something I really wanted to ask you about,

1:11:29 if you've thought about that at all?

1:11:32 Short answer is no, I haven't.

1:11:35 We should chat at length and develop the idea further.

1:11:39 Okay good.

1:11:41 What's it like for a man like you

1:11:43 to be living in what I call deep south California?

1:11:47 It's a strange culture down there that we have no understanding of up here.

1:11:52 No I mean you've lived down there for how many years?

1:11:55 25, 30 years.

1:11:56 25 years, yeah.

1:11:57 It's very surreal.

1:11:59 Ah.

1:12:01 You have a favorite example?

1:12:03 (audience laughing)- I still have to think about it.

1:12:07 (audience applauding) (cheerful music)