Karl Deisseroth is a professor of bioengineering, psychiatry, and behavioral sciences at Stanford University. Please support this podcast by checking out our sponsors:
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EPISODE LINKS:
Karl's Twitter: https://twitter.com/karldeisseroth
Karl's Website: https://web.stanford.edu/group/dlab
Projections (book): https://amzn.to/3NKmdiJ

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OUTLINE:
0:00 - Introduction
0:48 - Mental disorders
9:21 - Intelligence
11:59 - James Joyce
20:36 - Writing
24:00 - Projections
27:35 - Translation
30:06 - Poetry
38:49 - Love
44:23 - Psychiatry
47:35 - Sigmund Freud and Carl Jung
56:19 - Data in cells
1:00:23 - Optogenetics
1:15:50 - Neuralink
1:28:39 - Psychedelics
1:35:02 - Depression
1:50:28 - Talk therapy and psychoanalysis
1:54:09 - Good Will Hunting
2:04:44 - Darkest moments
2:06:15 - Suicide
2:23:21 - Autism
2:42:58 - Schizophrenia
2:54:07 - Why we cry
3:01:19 - Consciousness
3:15:50 - Mortality
3:17:30 - Meaning of life

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Where are the darkest places you've ever gone in your life?

The following is a conversation with Carl Deisseroth, professor of bioengineering, psychiatry, and behavioral sciences at Stanford University.

He's 1 of the greatest living psychiatrists and neuroscientists in the world.

He's also just a fascinating human being.

We discuss both the darkest and the most beautiful places that the human mind can take us.

He explores this in his book called Projections, A Story of Human Emotions.

To support it, please check out our sponsors in the description.

And now, dear friends, here's Karl Deisseroth.

You open your book called Projections, a story of human emotions with a few beautiful words that summarize all of humanity.

The book draws insights about the human mind from modern psychiatry and neuroscience.

So if it's okay, let me read a few sentences from the opening.

You gotta give props to beautiful writing when I see it.

Quote, in the art of weaving, warp threads are structural and strong and anchored at the origin, creating a frame for crossing fibers as the fabric is woven.

Projecting across the advancing edge into free space, warp threads bridge the formed past to the ragged present, to the yet featureless future.

Yet featureless future, Well done, well done, sir.

The tapestry of the human story has its own warp threads rooted deep in the gorges of East Africa, connecting the shifting textures of human life over millions of years, spanning pictographs backdrop by crevice ice, by angulated forestry, by stone and steel, and by glowing rare earths.

The inner workings of the mind give form to these threads, creating a framework within us, upon which the story of each individual can come into being.

Personal grain and color arise from the cross threads of our moments and experiences, the fine weft of life, embedding and obscuring the underlying scaffold with intricate and sometimes lovely detail.

Here are stories of this fabric fraying in those who are ill, in the minds of people for whom the warp is exposed and raw and revealing.

What have you learned about human beings, human nature and

the human mind from those who suffer from psychiatric maladies for those for whom this fabric is warped?

And 1 thing we learn as biologists is that when something breaks, you see what the original unbroken part was for.

And we see this in genetics, we see this in biochemistry.

It's known that when you have a mutated gene, sometimes the gene is turned up in strength or turned down in strength.

And that lets you see what it was originally for.

You can infer true function from dysfunction.

And this is a theme that I thought needed to be shared and needed to be made communicable to the lay public, to everybody, people who, which is, I think, almost all of us who think and care about the inner workings of our mind, but who also care for those who have been suffering, who have mental health disorders, who face challenges.

But then more broadly, it's a very much larger story than the present.

There's a story to be told where the protagonist really is the human mind, and that was 1 thing I wanted to share as well in projections, is that broader story, but still anchored in the moment of patients, of people, of experiences of the moment.

Is there a clear line between dysfunction and function, disorder and order?

This is always debated in psychiatry, probably more so than any other, you know, medical specialty.

I'm a psychiatrist, I treat patients still, I see acutely ill people who come to the emergency room where there's no doubt that this is not something that's working well, where the manifestation of disease is so powerful, where the person is suffering so greatly, where they cannot continue as they are.

But of course it's a spectrum, and there are people who are closer to the realm of being able to work okay in their jobs, but suffer from some small dysfunction and everywhere in between.

In psychiatry, we're careful to say we don't call it a disease or a disorder unless there's a disruption in social or occupational functioning.

But of course, psychiatry has a long way to go in terms of developing quantitative tests.

We don't have blood draws, we don't have imaging studies that we can use to diagnose.

And so that line ultimately that you're asking about between order and disorder, function and dysfunction.

Can we just like linger on the terms for a second?

So this disease, dysfunction, how careful should we be using those words?

Can we just, even in this conversation, from a sort of technical perspective, but also a human perspective, how quick should we be in saying that schizophrenia, depression, autism, as we kind of go down across the spectrum of different maladies, just to use the word dysfunction and disease.

I would say to give ourselves license to capture the whole spectrum, let's say disorder, because that captures, truly, I think, the essence of it, which is we need to talk about it when it's not working, when there's disorder, and that's the fairest and most inclusive term to use.

So is it fair to assume that basically every member of the human species suffers from a large number of disorders then?

Well, we just have to pick which ones are debilitating for each person.

You know, if you look at the numbers, if you look at how our mental health disorders are currently defined, you can look at population prevalence values for all these disorders.

And you can come up with estimates that somebody will have a lifetime prevalence of having a psychiatric disorder that approaches 25% or so.

And so that's, and in some studies it could be more, some studies it could be less.

And in some ways that's the essence of what I was hoping to approach with the book is to reflect on this spectrum that exists for all the disorders.

There is, and taking nothing away from the severity and the suffering that comes at the extreme end of these illnesses, but nearly every 1 of them exists on a spectrum of severity, from nearly functional to completely dysfunctional, life-threatening, and even fatal.

And so that number, 25%, more or less, it doesn't capture that spectrum of severity.

To linger on that number, where do those numbers come from?

Is it people who show up and say I need help, is it somebody else that points out that person needs help, or is it like estimates that even go beyond that for people who don't ask for help but are suffering quietly alone?

When you look at self-report numbers, then those numbers get even higher, beyond 25% or more.

The most rigorous studies are done with structured psychiatric interviews where people who are trained in eliciting symptoms carefully do complete psychiatric inventories of individuals.

And these are time-consuming, laborious studies that not often repeated.

But very often you'll see a report or something in the news of a very high number for some disorder or symptom.

And very often, if it's shockingly high, that's coming from a self-report of a person.

And so that's another issue that we have.

Again, take nothing away from the severity and reality and biological nature of these disorders, which are very genetic, very, you know, we understand that these are very biological, and yet we lack right now the lab tests and the blood draws to make the diagnoses.

But we'll talk about it, just how biological they are, because that too is a mystery.

In terms of from a perspective of how to probe into the disease, how to understand it, how to help it.

So some of it could be neurobiological, Some of it could be just the dance of human emotion and interaction and it's like, is love when it works and is love when it breaks down biological or is it something else?

But let me just like to linger in terms of disorder.

You know that sort of cliche saying, like the madness and genius, that they kind of dance together.

What about if the thing we see as disorder is actually genius, unheard, or misunderstood?

Well, here again, the numbers help us, and here's where being rigorous and quantitative actually really helps.

If you look at disorders like autism, and bipolar disorder, and eating disorders, anorexia nervosa, for example.

These, you know, particularly bipolar and anorexia, these can be fatal, they can cause immense suffering, but they are heavily genetic, all 3 of these, and what's very interesting is each 1 of these 3 is actually correlated positively, positively, with measures of intelligence, of educational attainment, and even of income.

And so you look at this, severe disorders in many cases causing quite immense morbidity and mortality, and yet they are positively correlated at the population level with positive things.

What's that book, forgot the book name, but is intelligence a burden?

Well, you know, people can get into trouble when they think they're smarter than they are, I will say that.

Sometimes, like, in the deepest meaning of that statement, I think ignorance is bliss.

I'm a big fan of Prince Mishkin from The Idiot and Alyosha from Brother Karamazov.

Optimism can be seen as naivety and dumbness, but I think it's a kind of deep intelligence.

Maybe inability to reason sort of about the mechanics of the world, but instead kind of feel the world.

And it seems like that's 1 of the paths to happiness.

How much you think versus how much you feel, this comes up all the time.

In medicine, we encounter this all the time.

When you, day after day, you encounter this, you know, the abyss of suffering from patients.

How much do you let yourself feel or how much do you make it abstract and objective and try to make it clinical?

And that range, how you're able to move yourself on that spectrum is very important for survival as a physician.

And the way you protect yourself and your feelings turns out to be very important.

So you quote Finnegan's Wake, mad props for that, James Joyce book.

I took a class in James Joyce in college.

I somehow got an A in that class, which probably refers to some kind of curve where nobody understood anything.

The only thing I understood and really enjoyed is his short stories, The Dead.

And then Ulysses, I kind of, I think, read a few Cliff Notes that kind of got to the point, and then Finnegan's Wake was just a hopeless pursuit.

For people who haven't looked at it, maybe you can elucidate to me better, but I felt like I was reading things, words, and the words made sense, like standing next to each other, but when you kind of read for a while, you realize you didn't actually understand anything that was said.

Right, but did you have a feeling though?

That's 1 thing I found interesting about Finnegan's Wake.

I never fully understood it, but the words caused feelings in me, which I found fascinating.

And sometimes I couldn't predict it from the semantic, you know, black and white context of what I was seeing in front of me on the page, but the rhythm or the melody would make me feel certain ways.

And That was what I always was intrigued by with Joyce.

Of course, that was his, he existed on a spectrum too.

And he wrote, as you say, more accessible works.

I learned a lot about Irish history from a portrait of the artist as a young man.

And there was just, He could be as objective as he wanted to be, but then when he let himself loose, he was in this realm where the words had their own purpose separate from semantic meaning, from their dry dictionary definition.

You know, there's a funny story that was told, doesn't matter if it's true or not, but they said that James Joyce, when he was young, when he was in his teen years, would go around sort of violent drinking and so on and telling everybody that he's going to be 1 of, if not the greatest writers of the 20th century, and he turned out to be that.

I always think about that little story that somebody told me, because I have a lot of people come up to me, including myself, I'm a bit of a dreamer.

You get into certain moods where you say, I'm going to be the greatest anything ever.

You get like people tell you this, especially young people.

And it kind of, It makes me feel all kinds of ways, but that story reminds me that you just might be 1 of the greatest writers of the 21st century, for example, if somebody were to tell me that.

And don't immediately disregard that, because 1 of the people that say that, that's almost like a pre-condition, that's like a requirement just to believe in yourself.

Maybe it's not a full requirement, but it's an interesting story.

I think when someone tells you that, then it creates, 1 sees an opportunity, and then it would be a tragedy if the opportunity weren't captured, right?

And so then that creates some impetus, some motivation to do something good.

I think the mind, it's like, I guess that's what books or whatever, I don't even know if it's a book, The Secret plugs into, they kind of make a whole industry out of it.

But there is something about the mind believing something, making it a reality.

It is just time and time again with Steve Jobs, your belief in yourself, your belief in an idea, sort of embracing the me versus the world, embracing the madness of this idea and making it a life pursuit, somehow morse reality for some tiny fraction of the population, for everybody else, you descend into all the beautiful ways that failure materializes in our lifetime.

You mentioned love earlier, I mean, that's a great example of how belief in something makes it real, right?

It's not reasonable on the face of it, but because you believe it's reasonable, then it actually does become reasonable, and then it is real.

We don't imagine that a bridge is soundly built and that it is soundly built.

That's something that, it doesn't come up in too many realms of human existence, but love is 1 of them.

And the ability to have a fixed idea and to say it's true and that it is true.

a kind of manifestation of love, so maybe it does work a little bit, but it can break down like Chernobyl did.

You can't just say it's safe, you have to also prove it's safe.

But on Finnegan's Wake, I think, maybe correct me if I'm wrong, you're using kind of Finnegan's Wake to give 1 perspective on what madness is, of what's going on in the mind.

How much of that is that we're simply unable to communicate with the person on the other side of their mind.

Like there's almost like a little person inside the brain and they have some circuitry that's used to communicate emotion, communicate ideas to the outside world, and there's something about that circuitry that makes it difficult to communicate with the little person on the other side.

So if you look at what shows up in schizophrenia, with many cases, what we call thought disorders, what we call the individual speech symptoms of schizophrenia, Finnegan's Wake is loaded with them.

We talk about clang associations in schizophrenia where the word that is said echoes in some way the previous word.

And We call that a clang association because there's no other reason than the similarity of the sound, like a clang of a garage door being hit.

And it has a, and sometimes it's not even a word, and we call that a neologism, a new word being created.

And of course, Finnegan's Wake is full of that.

And then we also, in schizophrenia, where there's what we call loose associations or tangential thought processes, of course full of that where things just go off in directions that are not linear or logical.

And you can't read Finnegan's Wake, I think, without, certainly as a psychiatrist, you can't read it without thinking about schizophrenia.

And then when we look at the families of people with schizophrenia, and Joyce was no exception, There very often are people within the family who are on the spectrum.

Some have it, some are able to see it from a distance, from a safe distance.

There's an association between schizophrenia and what we call schizotypal personality disorder, where people are not quite in this severe state of schizophrenia, but have some magical thinking, have some unusual thought patterns.

Very often those are family members of people with schizophrenia.

So this points to this, again, to this idea that there is a range, even along this very severe, very genetic biological illness that human beings dwell on different spots along that spectrum.

I should mention that we have my friend Sergei pulling up stuff, Young Sergei or Old Sergei, I don't know what to call you, but there's drafts of Finnegan's Wake.

Yeah, I actually saw pictures of this from, I think it was on Instagram or something.

These are early drafts of Finnegan's Wake.

And it's so beautiful to see, for people who are just listening, there's just random paragraphs and writing all over the page with stuff crossed out.

And it's great to see that Joyce himself was thinking in this kind of way as you're putting it together.

How much do you think he was thinking about the schizophrenic mind?

I think it's known that his daughter suffered from schizophrenia.

And this is, what's depicted here on the page is something that I'm sure he either felt himself and some level was able to access this non-linearity of processing, or had seen enough in family that he knew what it was and was able to reflect it down in black and white on the paper.

So it was, what he was able to do was quite authentic in that sense.

Of course, I don't want to pigeonhole him, he was doing much more than that.

It was much more than talking about altered human thought processes and thought disorders.

But that was an aspect that he was so good at representing that it had to be intentional to some extent.

And a tiny tangent, what does your own writing look like for this book, because it's extremely well written.

How many edits, did you just drink some whiskey and like imagine Hemingway style.

What's a very different, the writing is very different.

I mean, it's really, really well written, which was like, I was reading it.

It makes you realize, because I was expecting sort of a science kind of, which it is like, you know, elucidating something about the human mind kind of thing, but you could also probably write really strong novels.

But anyway, what is your, how many edits, how many, what's your style?

Unfortunately, I use a laptop, so I didn't have this sort of beautiful record.

I did explore, you know, which was there a particular altered state that would help me to be most creative?

And I found actually, I actually did the best while, you know, sober, but slightly disinhibited in the late hours of the night or early morning.

Yeah, particularly late hours of the night there.

I have a friend who would tell me that she thought that very early in the morning her inner critic was still asleep and she could write more effectively before her inner critic woke up.

And I actually found that outstanding advice for me, that I often found that there was, I was looser and could write more in the morning.

But the other interesting thing is each chapter, each story, it's about a different human being with a different class of psychiatric disorder.

That's what each story, each chapter is anchored in.

But I'm trying to use words and style of writing and diction that captures the feeling of the disorder.

In the story about mania, which is a very expansive, exuberant, at least briefly uplifting state where the words come out in a torrent and they're complex and pressured and elaborate.

I try to capture that feeling with the words used in that chapter.

And then in the schizophrenia or psychosis chapter, where things slowly fragment over time and become looser and separated, I tried to capture that in the writing too.

So for each, it wasn't as if there was a single mode I could be in for the whole book.

For each chapter, I had to put myself into a different mode to capture that inner feeling of the disorder.

When you put yourself in that mode, does that change you?

Yeah, I couldn't turn it on and off right away.

I had to, first I would start by thinking about the person or the people, 1 or 2 people based on real patients and the stories that are put forth.

The symptom descriptions are real, they're from the patients.

Of course, all details change to protect privacy, but the actual symptom descriptions are real.

And I would sit with them and really try to inhabit the space of the mind of that person that I knew.

And that's not instantaneous, it would take some time.

That's another reason late at night is good.

Sergey posted that drowsiness gives creativity boosts according to Andrew Huberman.

Is it, I mean, there's, instead of putting words into your mouth, because I can imagine a lot, I mean, to me, no, I will start putting words in your mouth despite what I just said.

So, I mean, to me, projections, working on neural networks, for example, from artificial neural networks, from a machine learning perspective, it's often, that's exactly what you're doing.

You have an incredibly complex thing and you're trying to find simple representations in order for you to make sense of it.

So I was kind of thinking about it in that way, which is like this incredibly complex neuronal network that is kind of projecting itself onto the world through this low bandwidth expression of emotion and speech and all that kind of stuff.

And the way it's, we only have that window into your soul, the eyes and the speech and so on.

So that, in that way, when there's any kind of disorder, we get to only see that disorder through that narrow window as opposed to the full complexity of its origins.

The word projections definitely serves that purpose here, but it's got a few other really appropriate other connotations as well.

So the first thing is a projection in terms of neuroscience is this long range connection that goes from 1 part of the brain to another.

And so it's what binds 2 parts of our brain together.

There are projections, long range connections of axons.

These are the outgoing threads that connect 1 part of the brain to another part.

There's a projection that links, for example, auditory cortex where we hear things to reward centers where we can feel, where feelings of pleasure and reward are initiated.

And it's been shown that if you have reduced connectivity along that dimension, you are less able to enjoy music.

And so these connections, these projections matter.

They define how effectively 2 parts of the brain can engage with each other and join together to form a joint representation of something.

So that's 1 meaning, it's pure neuroscience.

The word projection is used all the time and it happens to be something that optogenetics, a technique that maybe we'll talk about a little later, it works particularly well with, we can use light to turn on or off the activity along these projections from 1 spot of the brain to another.

And this is particularly referring to the long range connections.

It's particularly straightforward along these long range projections that connect different parts of the brain, but it works over shorter range too.

But then there's this other meaning of projections which you were bringing up, which is very relevant, which is at some point you can reduce something from 1 level of dimensionality to another, and you can project down into a lower dimensional space, for example.

And then finally there's a psychiatric term projections which comes up all the time, which is we very often will look at our internal states and to understand somebody else we'll project them onto somebody else.

We'll try to understand someone else's behavior and make sense of it by projecting our own inner feelings, our own sort of narrative onto them and use that as a way to help us understand them better.

We'll take things we see in the outside world and we'll bring them into ourselves and see how well they map, how well they align.

So projections turns out to be a really rich word.

And then finally, of course, there's the very common sense of it as a projector that illuminates by conveying information across space with light.

So for English language, perfect word to use for this book.

But what was funny is not every, there are a lot of international translations now And all those rich connotations aren't captured in other languages.

And so for some translations, connections is used instead of projections.

In fact, even in England, the British version is connections instead of projections because apparently projections doesn't have the full connotation I was told.

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Karl Deisseroth: Depression, Schizophrenia, and Psychiatry | Lex Fridman Podcast #274