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

where 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 one. 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. i highly recommend it it's written. masterfully. this is the lex friedman podcast to. support it please check out our sponsors. in the description and now dear friends. here's carl that's roth. 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 for modern psychiatry and. neuroscience so if it's okay let me read.

a few sentences from the opening. you got to 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. deformed 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. creviced 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 one 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 they're 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 to the lay. public to everybody people who. which is i think uh almost all of us who. think and care about the inner workings. of our minds 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. a story to be told where the protagonist. really is the human mind and that was. one thing i wanted to share as well in. projections is that broader story but. still anchored in the moment of. patience 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'm 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 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. it's operational of the moment how are. things working. can we just like linger on the terms for. a second so this uh disease. uh dysfunction. how careful should we be using those. words can we just even in this. conversation. um from a. sort of technical perspective but also a. human perspective. how um. quick. should we be.

in saying that schizophrenia. uh depression. autism. as we kind of go down this uh. across the spectrum of different. maladies like. 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 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.

that's the fairest and. you know most uh 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 and we just have to pick which ones. are are debilitating and for each person. you know if you if you look at the. numbers. there are. uh. you know if you look at how our mental. health disorders are currently defined.

you can uh 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 now what. do we do with that number what does that. mean and in some ways that's the essence. of what i was hoping to approach with. uh 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 one of them exists on a. spectrum of severity from. nearly functional to completely. dysfunctional life-threatening and and. even fatal. and so that that that number 25 more or. less it doesn't capture. uh that that spectrum of. of uh severity to regard that number. where do those numbers come from is it.

self-report 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 or suffering quietly. alone when you look at self-report. numbers that then those numbers get even. higher beyond 25 percent or more. those the most rigorous studies are. done with structured psychiatric. interviews where people. who are trained in eliciting symptoms.

carefully do complete psychiatric. inventories of of individuals and these. are. time-consuming laborious studies that. not often repeated when they're done. they're they're done well. but. very often you'll see a report or. something in the news of a very high. number. for some disorder or 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 another issue that. we have again take nothing away from the.

severity and reality and and biological. nature of these disorders which are very. genetic very you know we we understand. that these are very biological. and yet. we lack right now the lab tests and the. blood draws to make the diagnoses we'll. talk about it just how biological they. are because it's a that too is a mystery. i mean. you know in terms of from a perspective. of how to probe into the disease how to. understand it and how to help it so some. of it could be neurobiological. some of it could be.

uh just the the dance of human emotion. and interaction and the. it's like uh. well it is love when it works and is. love when it breaks down uh biological. or is it something else so we're gonna. talk about it but let me just like to. linger in terms of disorder. what about genius. you know that sort of uh cliche saying. like the. madness and genius that they kind of. danced together uh.

what about if the thing we see is this. order 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 uh you know particularly bipolar. and anorexia these can be fatal. they can cause immense suffering.

but they are heavily genetic all three. of these. and. what's very interesting is each one of. these three 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.

can you say the the three again autism. autism. anorexia and bipolar disorder bipolar. right what's that book forgot the book. name but uh is intelligence a burden. uh. well you know people can get into. trouble when they think they're smarter. than they are i will say that. i don't know. sometimes like. in the deepest. meaning of that statement i think. ignorance is bliss i'm a big fan of. prince michigan from the idiot and um.

i learned from brother karmazov. optimism can be seen as naivete and. dumbness but i think it's a. it's a kind of deep intelligence. maybe inability to reason. uh sort of about the mechanics of the. world but instead kind of feel the world. and it seems like that's a one of the. paths to happiness. there is 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 the abyss of suffering from. patients how much do you let yourself. feel. or how much do you. make it abstract and. and objective and try to make it. clinical. and that range how you're able to move. yourself on that on that spectrum. is very important for survival as a. physician. and the way you. you protect yourself and your feelings. turns out to be very important.

so you quote finnegan's wake uh mad. props for that james joy's book i took a. class on james joyce in college. i think i read parts of finning and way. i might have been on drugs of some kind. or. i um 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 the short stories the dead. and then ulysses i kind of uh i think. read a few cliff notes that kind of got. to the point and then finnegan's wake. was just a hopeless person i it's a you.

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 one that's one. thing i found interesting about. finnegan's week i i never fully. understood it but the words caused.

feelings in me which i found fascinating. and and sometimes i i couldn't predict. it from the 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's that was what i. always was intrigued by with joyce of. course that was his. he he existed on a spectrum too and he. wrote as you say you know more. accessible uh works you know i learned a. lot about irish history from you know. 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 from. you know semantic meaning from their. their dry uh you know dictionary. definition you know there's a funny. story that was told it doesn't matter if. it's true or not but they they said that. uh james joyce when he was young when he. was in his teen years would go around. instead of ireland drinking and so on. and telling everybody that he's going to. be one of if not the greatest writers of.

the 20th century. and uh he turned out to be. that. so the 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. i and. you know you get into certain moods. where you say i'm going to be the. greatest. anything ever you you get like people. tell you this uh young especially young. people. and it kind of.

it makes me feel all kinds of ways but. that story reminds me that. like you just might be. one of the greatest. writers of the 21st century for example. if somebody were to tell me that and. like don't. just don't immediately disregard that. because one 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 it's an. interesting story. i think when someone tells you that then. it creates uh.

one sees an opportunity and then it. would be a tragedy if the opportunity. weren't captured right and so then that. creates a um some some impetus uh some. motivation to do something. something good i think the mind it's. like uh. you know i guess that's what like books. like the books or whatever i don't even. know if it's a book the secret plugs. into uh 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 like. 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 around for some. tiny fraction of the population for. everybody else you descend into uh. you know all the beautiful ways that. failure. materializes in our lifetime. you know you mentioned love earlier i.

mean that's that's a great example of. how belief in something makes it real. right it's 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 and so that's a that's a good. example that doesn't happen i'm also in. a bioengineering department we don't. imagine that a bridge is soundly built. and then it is soundly built that's. something that it doesn't come up in too. many realms of human existence but love. is one of them and and these the ability. to. to have a fixed idea and to say it's.

true and then it is true. a bridge is a kind of manifestation of. love so maybe it does work a little bit. but you know they can break down like. chernobyl did you can't just say it's. safe you have to also prove it safe. uh but on finnegan's wake. i think maybe correct me if i'm wrong. you're using kind of finnegan's wake to. give one perspective on what madness is. of what's going on in the mind how much. of that is. uh that we're simply unable. to communicate with the person on the.

other side. of of their mind like there's almost. like a. 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 a little. person on the other side so if you look. at what shows up in schizophrenia with. many cases the. what we call thought disorders what we. call. uh the. the individual speech symptoms of.

schizophrenia. finnegan's wake is is loaded with them. and it's it's just full of them we we. talk about uh. clang associations in schizophrenia. where the word that is said is. echoes in some way the previous word and. it's we call that a clang association. because there's no other reason than the. similarity of the sound like a like a. clang of a. 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 is full of that and then. uh we 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 um. certainly 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 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 sergey pulling up. stuff young sergei or old sergey i don't. know what to call you but. uh there's drafts of finn can squake. yeah i actually saw pictures of this. from um. i think it was on instagram or something. these are early giraffes of finnigan's. wave 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. um as you're putting it together how. much do you think he was thinking about. schizophrenia this schizophrenic mind i. think a lot i think you know it's it's. known that his daughter suffered from. from schizophrenia and uh. the this is what's depicted here on the. page is something that i'm sure. he either felt himself and some some.

level was able to access this. non-linearity of of processing or had. seen enough in family. that he he knew what it was and was able. to to reflect it down in black and white. on the paper so it was what he was able. to do is 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 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 uh. like i'm imagining hemingway style. what's a very different the 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 uh. you know. elucidating something about the human. mind kind of thing but you could also. probably write. really strong like novels. uh so maybe that's in the future but. anyway what is your how many edits how. many what's your style does it look like. that is it more structured organized. unfortunately i used a laptop so i. didn't have this sort of uh beautiful. recorder typewriter cigarette. and whiskey i did explore i was you know.

which was there a particular altered. state that would help me to be most. creative and and i. i found actually i i actually did the. best while uh you know sober but. slightly disinhibited in the late hours. of the of the night or early morning. yeah particularly late hours of the. night there. you know i i 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 yeah and i actually found that uh. 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 is. each each chapter each story it's about. a different. uh human being with a different class of. of psychiatric disorder that's what each. story each. each chapter is anchored in. by trying to use words that and style. of writing and. and uh you know diction that captures.

the feeling of the disorder and so it's. different in each story in the story. about mania. which is a very. expansive exuberant uh. at least briefly uplifting state uh. where the words come out in a torrent. and they're complex and pressured and. elaborate. i try to capture that feeling with the. the words used in that chapter and then. in the schizophrenia or psychosis. chapter where things slowly fragment. over time and become looser and.

and 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 uh. 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 uh or the people one or two. people based on real patients and the. stories that are that are put forth uh. the symptom descriptions are real.

they're from the patients of course all. details change to protect uh 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 of that. person that i knew. and that's not instantaneous it would. take take some time i needed quiet i. needed to be still that's another reason. late at night is is good. sergey posted that drowsiness gives. creativity boosts according to andrew. huberman. thank you andrew.

uh it's not wrong he's not wrong why. projections is it uh. i mean there's some. instead of putting words into your mouth. because i can imagine a lot i mean i to. me. you know 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 in that way which is like. um. 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 we're um.

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 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 one part of the brain to another. and so it's what binds two. parts of our brain together there are.

projections long-range connections of. axons these are the outgoing. threads that connect. one part of the brain to another part. there's a 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 two parts of the brain. can engage with each other and join. together to form a joint representation. of something so that's one meaning it's. pure neuroscience the word projection is. used all the time and it happens to be. something that optogenetics a technique. that we 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. one 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 you can reduce. something from one level of. dimensionality to another you can. project down into a lower dimensional. space for example. and then finally there's a psychiatric. uh. term projections which comes up all the. time which is uh. we. very often uh will. look at our internal states and to. understand somebody else we'll. project them on to somebody else we'll.

try to understand someone else's. behavior and and make sense of it by. projecting our own inner feelings our. own. uh sort of narrative onto them. and use that as a way to help us. understand them better and we'll do the. reverse too we'll take things we see in. the outside world and we'll bring them. into ourselves and see how well they map. how will they align that's called. introjection so projections is a turns. out to be a really rich word then. finally of course there's the very. common. sense of it as as a projector that that.

illuminates by conveying information. across space with. light. so for english for english language. perfect word to use for this book but. what's funny is. not every. there are a lot of international. translations now and and all those rich. connotations aren't captured in other. languages and so for some. translations uh connections is used uh. 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 you. have to sacrifice some of the rich um. ambiguity of meaning. uh with connections that's interesting i. mean connect. and words are so interesting they have. so many i love language and how much is. lost in translation i'm very fortunate. enough to be able to speak i'm not good. at languages i was just i guess. forced to by life circumstance to learn. two languages. russian and english and it's just so. interesting to watch how much of culture.

how much of people how much of history. is lost in translation. the poetry the the music. the history the pain the way the. scientists actually express themselves. which is funny i mean just. it's so sad um. to see. how much brilliant work. that was written in russian there's a. whole culture of science. in the soviet union that is now lost it. makes me wonder. in the modern day.

how much incredible science is going on. in china. that is lost in translation and i'll. never i mean that makes me very sad. because. i'll never learn chinese in the same way. that i've learned english and in russian. maybe. whenever i say stuff like that people. are like well there's still time but uh. you know uh yeah that's it's that's. actually fair that uh i think the 21st. century. both china and us will have very.

important roles in the scientific. development. and. we should actually bridge the gap. through language and that that doesn't. just mean convincing chinese to speak. english. that means also learning chinese well we. need these bridge people who can do both. you know the. um you know nabakov for example writing. in english beautifully uh uh you know. one of my favorite poets porques who you. know mentioned earlier he wrote both in. english and in spanish i think you know. beautifully in both we need those people.

who can serve as. bridges across cultures who really can. do both. you mentioned borges so. you open your book with a few lines from. a poem by. jorge luez borges a love poem i'm going. to read parts of it because it's a damn. good poem yeah it's called two english. poems i mean there's i'd like to. understand why you used it and the. specific parts you used which is. interesting but then when i read the. full thing.

so i think you used it. as as. a sort of beautiful description of what. it means to delve deep into. understanding. uh offering yourself to the task of. understanding another human being but if. you look at the full context of the poem. it's also a damn good description of. being hit by love and overtaken by it. and uh. uh sort of. and trying to. trying to figure out how to make sense. of the world now that you've been uh. stricken by it. it says a bunch of things.

uh about. chatting and significantly with friends. and all those kinds of things and then. the poem reads. the big wave brought you. i get this is the moment. i guess of the universe where the two. people you fall in love maybe i'm. totally misreading this poem by the way. it doesn't matter you can't misread a. poem. so it goes on words any words you're. laughter and you're so lazily and. incessantly beautiful. we talked and you have forgotten the.

words. the shattering dawn finds me in a. deserted street of my city your profile. turned away the sounds that go to make. your name the lilt of your laughter. these are the illustrious toys you have. left me. so these little memories of these. peculiar little details he remembers. those are the illustrious toys. i apologize to mix my own words of the. poem but you should definitely read it. i turn them over in the dawn i lose them. i find them i tell them to the few.

straight dogs into the few stray stars. of the dawn. your dark rich. life. i must get at you somehow. i put away those illustrious toys you. have left me. i want your hidden look your real smile. that lonely mocking smile your cool. mirror knows. i want your hidden look your real smile. i am so i this is the first part of the. poem and then it goes on which is some.

of the parts that you reference. second part is what can i hold you with. i offer you lean streets desperate. sunsets the moon of the jagged suburbs i. offer you the bitterness of a man who. has looked long and long in a lonely. moon. i. offer you my ancestors my dead men the. ghosts the living men have honored in. bronze my father's father killed in the. frontier of buenos aires two bullets. through his lungs and so on so on i. offer you whatever insights my books may. hold whatever manliness of humor my life.

i offer you the loyalty of a man who has. never been loyal i offer you that kernel. of myself that i have saved somehow the. central heart that deals not in words. traffics. not with dreams and is untouched by time. my joy and. adversities. and i think this is where the part they. include in the book. i offer you the memory of a yellow rose. cena sunset. years before you were born. i. damn that's a good line okay.

[Laughter]. i offer you explanations of yourself. theories about yourself authentic and. surprising news of yourself. i can give you my loneliness my darkness. the hunger of my heart i am trying to. bribe you with uncertainty with danger. with defeat. that is a man who's in love and longing. if i've taken but i just want to go back. to maybe you could say why you want to. include that poem but also. your dark rich life i must get at you. somehow i put away those illustrious.

toys you have left me out when you're i. want your hidden look your real smile. that lonely mocking smile your cool. mirror knows what sometimes i meet a. stranger. and i just. it's like it's like a double take. it's like who are you. have we met before somewhere who's that. person behind there. and i want to get at that whatever that. is and of course maybe that's what love. is because maybe. uh maybe that's the whole pursuit like a.

lifelong pursuit of getting at that. person maybe that's what that is and. like that uh insatiable sort of. curiosity to keep getting like who's. that person then you're on private life. yeah so that absolutely i think that it. was a beautiful description of what you. just said when there's that first moment. and then you want to dive deeper you. want to know what the what the hidden. mysteries are. in a way it's it's a it's a love poem. as a as a scientist though it also. it's a bit of how a scientist can love.

science and and. that. wanting to dive deeper is. it's almost like again where the it. could be a love affair with. investigating the human mind for example. and and that was one reason it spoke to. me also. again thinking about. the broader sweep of where the human. mind came from uh. the steps it took. to get where it is today what was given. up along the way what compromises were. made and here's where the darkness of. the poem starts to come in a little bit.

too it doesn't shy away. from the negativity. from. the confusion from the danger. and then at the very end. the board faces offering up. scenes from his life parts of himself. and this is how we connect with people. we offer up parts of ourselves just here. it is and then we see how well does that. map on to what you have and it's it's. that offering up. that i liked and not not the good stuff. or not only the good stuff the yellow.

rose is nice but but he's offering up. the bad stuff too. and that that to me was important for. the for the book because. i'm offering up hard stuff too and in. fact a lot of it and also hard stuff. from within me from my my own personal. side too and that was there's a lot of. vulnerability that comes with that but. that's. that comes with love that comes with. writing you have to be open you have to. be vulnerable and so. i thought that reflected what i was. trying to do and i thought it was a as. an epigraph it kind of.

made it clear. how vulnerable. i was in taking this step but also. what what could come out of it and also. in a meta way because i was not familiar. with this poem. it uh. it made me curious. of the poem itself to pull at that. thread of finding out more. so you picked a very particular part. that kind of made you want to um. pull at that thread and and then and see. where did this.

where did these few lines come from. because i i read it as a curiosity of a. scientist those lines were. alone and also. as a desperate. uh human being. searching like offering himself for an. understanding or connection with with. another human being and then because i. wasn't sure if it's a love poem or not. or if it's desperation or if it's. curious whatever it is and then you see. the love poem i mean i don't know that. that's gonna stick with me for a while. the.

your dark rich life. and then a few lines in here are just. i mean those are i'm going to just use. them as as pick up lines at a bar i. offer you the memory of a yellow rose. seen at sunset years before you were. born. now that's a pickup line i've never if. if i've ever heard one anyway sorry but. this is universal you know you see it in. so many forms of of art you know like. you know we're in texas now you see this. in country uh country and western songs. it's it's often a list of things like.

here's how i describe myself there's. this and there's that and there's the. other thing and here you are these. things matter to me and i hope they. matter to you too it's a it's a pretty. universal form but it's but he did it in. this very. artful uh. and very. vulnerable way it was it was both both. beautiful and you could you could feel. the hurt coming from him too and that. was important. the dark stuff too i offer you my. ancestors my dead men the ghosts the. living men have honored in bronze and. talking about two bullets through his.

lungs bearded and dead. wrapped by his. [Applause]. soldiers in the height of a cow my. mother's grandfather just 24 heading a. charge of 300 men in peru now ghosts. on vanished horses. so all of it the whole history of it. um since it is a love poem. what do you think about love. carl what's what's the role of love in. the human condition we'll talk about the. dark stuff yeah but uh maybe love is the.

dark stuff too i mean it's it's the most. powerful. connection we can form and that's that's. it's. that's what makes it so important to us. it's the it's the strongest. and most stable connection that we can. form with another person and that. matters immensely. it matters for. for the human family to. have evolved to be. something that could survive against the. odds that that that we've faced over the. years that.

un. reasonable bond that becomes reasonable. by virtue of its own existence. and of course. that joy the the wild raw joy of love is. not a bad thing either. so you put these together. the four the strongest bridge we can. form. and the reward and the joy that that it. brings that's that's what love is to me. and. from you know my perspective this is.

something that you know. it can be hard to capture fairly because. you want to talk about. the positive and the negative sides at. once they need to be wrapped up together. for full honest description of what it. is. and that that's hard to do in a in a. compact form and so. you have to take time to talk about love. you have to take time to. to do it justice um it takes a book or. at least a poem. or several thousands of them i don't. know so is there could you pull up.

there's a video i saw. yeah like right here so can you pause. for a second. uh so so there's march of the penguins. so you always see like penguins huddling. together. against i i mean sorry if i see just. metaphors and everything but uh them. huddling together against the harshness. of the conditions around them that's. very kind of. that's like a metaphor for life like. finding this connection that's kind of. what love is it's like it allows you to.

forget whatever the absurdity whatever. the suffering of life is together you. get to like. huddle for warmth and that's why i love. the uh sort of just the uh the honesty. and the intensity of the way penguins. just in the middle of like the cold do. this and then this video i saw. a lonely this is this is misinformation. so the name of the video is lonely. deranged penguin i don't know if he's. deranged so if you play it. so he left his pack.

and uh. and there's a nice like voiceover and. you don't need to play it but he for. some reason left the pack and journeyed. out into the mountains. and so the the narrator says that he's. deranged he's lost his mind. now i'd like to project the idea that. he's actually. there's so many stories you could think. of he's returning to his homeland he's. an outsider thinking journeying out into. the unknown thinking he may be able to. discover something greater than the.

tribe he might be looking for a lost. love. why is he deranged immediately why has. he lost his mind anyway but this you. people should look up this video because. to me i might be the only one who uh. romanticizes this but it's such a nice. kind of it's both a picture of perhaps a. mental disorder which is what the video. kind of describes and it may be some. deeper explanation that's not. that that has to do with the motivation.

of a. of a mind. yeah i don't know if i don't know if you. have a deeper analysis on this penguin. well i i. like you as a psychiatrist. i i would i would want to sit down with. a penguin and go. i want to see the notes from his prior. therapist and. but. this this actually is. relevant not knowing what was. that penguin's motivation we have. very clear. situations where there are both within. an individual we go through periods of.

time when we. stay in one place. and we. reap the benefits from what we've built. and then we go through periods of. foraging of of of wandering even if. there may be resources where we are we. we. have periods of time in our lives where. we want or where we where we. go in an exploratory mode and different. people express that trait in different. ways this is not a human specific trait. if you go down to to the tiny little.

nematode worm. c elegans with 302 nervous system cells. they go through these phases of foraging. and rest and different individuals have. different propensity to forage or to. rest and stay in one place. at the level of the species that's. really good. that there's that. diversity in their willingness to forage. some. stay where they are the species is. somewhat on a firm footing then. but some carry a burden. a risk for themselves but.

it's good for the species that they're. explorers and they will venture out. the migration patterns that. different species blunder into and that. turn out to be really good they weren't. logically derived. they. most certainly started from. something like this an exploration. humans do this too you think and we do. it too in fact it's that's something we. do extremely well. let's talk about psychiatry a little bit. so my book you're a a rock star first of.

all for people who don't know you're one. aside from sort of um. the neurological view of the brain and. neuroscience view of the brain you're. also one of the great psychiatrists of. our time i've always. not always but when i was younger i. dreamed about being a psychiatrist. um. so it's like it's like getting to meet. your heroes. and also um. you know getting to meet the people who. uh. the best.

at the top of the world at the thing. you've failed to pursue so there so. there's i'm getting a free therapy. session on top of that okay so what uh. big picture what is the practice the. goal the hope of modern psychiatry if. you could try to describe the discipline. as you see it maybe historically. throughout the 20th century. in contrasting to what it is today or. maybe if you want to describe to what. you hope psychiatry becomes or longs to.

become in the 21st century yeah. it's been an interesting journey uh it. psychiatry started out. pretty firmly grounded in neurology and. pathology some of the initial. founders effectively of the field were. very well grounded in microscopy looking. at cells. working with patients uh particularly on. the neurological side and this certainly. included you know freud and some of his. contemporaries. and. but they rapidly discovered that.

what they could work with at the level. of. cells and microscopy was so far. from the realm of what they could get. from a human being. and what they were getting from the. human being was so much more interesting. and had was so mysterious and so unknown. that many of them. just said we're going to inhabit this. domain and we're going to work with the. people with their words. and understand what we can. based on verbal communication because. that was the only tool that people. really had.

and. that was. a very. important step for the field i would say. one of the interesting things that came. from the early decades of psychiatry. really was this distinction between the. conscious and the unconscious mind. and paying particular attention. to the unconscious mind is something. that was worthy of consideration uh that. that might be important in explaining. people's actions. and that perhaps even insight into that.

was valuable in its own right. and out of that psychoanalysis uh. became a practice that. it was not always focused on. cures or treatment but was more focused. on insight what does it what does it. mean how can we help people understand. why they're. feeling something or thinking something. or dreaming something. and that insight separate even from. treatment was was an interesting thing. as long as. one was honest about that and said you. know we're we're going for understanding.

we're going for insight maybe it's. useful to just pause on that let's if. you look at the father psychoanalysis. sigmund freud. what do you make of the ideas that he. had so you mentioned. taking the unconscious the subconscious. seriously. that's like step one like that there. could be worlds we do not have direct. access for we. probe at them. through conversation or. um is it too simplistic to call.

psychoanalysis conversation that's not. too simplistic but that's right and i. think that was valuable where where. freud ended up breaking from some of his. contemporaries he was very focused on. this unconscious as being so tightly. linked to libido and and really he. from his perspective you couldn't really. separate the operation of the. unconscious mind from these aspects of. the libidinous aspects and that was one. reason. you know sex sexual sexually related uh. you know drives. carl jung who was his you know.

uh you know contemporary that's one. factor that led to them separating was. you know carl jung felt there was a lot. more. to the unconscious than than this. libidinous aspect of it and he saw it as. a much more. complete uh. uh alternate representation of the the. conscious self one that maybe reflected. a whole range of different. motivations and and desires. um.

and. to to properly treat it one had to. consider all of them rather than the. ones that destroyed us called young chef. thank you. thank you for the high level of uh of. images that sergey is pulling up for. people who are just listening he pulled. up a. as a quote from uh segment four it's a. meme your mom quote uh freud uh so the. the shadow the carl young shadow. encompasses. everything not just the desire to have. sex with your mother.

or sex period that's right that's right. if you look at those two folks. on mass i mean there's a kind of. it's almost like a technique for. philosophical exploration of human mind. human motivations. so it's not even like necessarily. it's also doubles as a methodology for. helping people but it's almost like a. it's a kind of philosophical method. right.

this is the fascinating thing about. about psychoanalysis and and. it even though it's it's i would say. mostly not considered a treatment today. it persists for a couple reasons one is. it it's it's thought that it gives. people some insight. but. second there's been a huge influence on. on literature on philosophy on art. and the the opening up of discussion. about what was. below our conscious mind was uh so so. fertile in the implications that it it.

sort of reverberated and still does. throughout all these different realms of. human endeavor from. our. different artistic. uh you know. experiences that people have can be. colored by this this uh. concept of the unconscious. now the other thing that was interesting. is is is this distinction. you know what what are the parts of the. unconscious and and so there were these. id and ego and superego uh.

subdivisions that. you know that that freud for example. would would talk about them and and the. the id was the primary the primal drives. that an infant would have uh or that a. very young child just warmth and feeding. and then then later the you know the. sexual or libidinous aspects and for. freud the later happened very quickly. that's the controversial thing about him. i think i guess he thought like even.

children had sexual desires that they're. like dealing with contending with so. it's the full thing hungry wanting to. eat wanting to poop wanting to have sex. yeah and he was extremely focused on. that on on that aspect. but then there was then there was this. the superego which brought on these. later sort of moralistic uh. sort of codes of conduct and and that of. course was very often in intention but. all this could play out subconsciously. and then the ego. this third aspect was mediating and for.

its conception mediated this tension. between the different uh parts. now i think that's interesting uh i will. say that. in some ways. it's maybe unnecessary. from the perspective of modern. neuroscience to divide things up that. way from the you know the moralistic. drives and the primal. gratification drives. in some ways they're all drives and.

maybe they're even all primal drives you. know the the moralistic drives they're. they're taught and they're taught in. ways that ultimately relate back to. survival and. you could even say selfish aspects of. of health and life for the self and. family and. so this is uh i don't i think it's maybe. an artificial distinction the concept of. the unconscious is very valuable and. very interesting um but. these categorizations.

uh of id and and uh superego may not. map onto neurobiology in any particular. way if there's a town hall of competing. drives and desires and there. they. interrelate to each other they involve. different aspects of the of the brain. and the history of the person. and actions and choices come out of the. result of that overall you know shouting. in the town hall so in some sense carl. jung was a step into the direction of. liberating yourself from such harsh.

categorizations. do you think. i mean you have daniel kahneman with. system one of system two. there's just these very compelling. categorizations of the human mind that. seemed to be. sticky. in our uh. in the super ego no uh in the you know. the how we talk about these ideas and so. on yeah do you think those are helpful. or do they get in the way is it some. kind of balance in terms of deeper. understanding of how the mind actually. works you know it's from the from modern.

neuroscience uh. whenever we. seem to get closer to. addressing a question like this at the. level of cells. it seems to get farther away and i'll. give you an example of what i mean by. that so one thing i'm doing in my. laboratory and many people are doing is. we are listening in on the activity of. cells neurons in the brain of mice or. rats or fish or monkeys individual cells. individual cells exactly of which there.

are you know in our brain many billions. and. when we do and we. try to predict what action will be taken. by an animal. to address this question where does. the choice arise where does the. impetus to make a particular selection. of one action versus another action. where does that start in the brain if. you're recording listening in on the. activity of cells all across the brain. where's the earliest spot you can pick. up. a choice being made.

well that's so awesome. yeah at one level you might think how. excited would young have been to see. this or freud or the early you know. psychoanalysts to see where this starts. but it's not so simple because. an emerging theme in very recent. neuroscience literally over the last few. years. is that. things sort of all start together all. across the brain and so you can be. recording from the cortex this rim of. cells at the surface of the brain or you.

can be recording deeper in a structure. called the striatum which is a little. older. it's more tightly linked to to action. and then structures called the thalamus. other parts of the brain and if you. record from these these. all sort of. represent the action and the choice. more or less all at about the same time. very close and so it's you can't point. to a particular spot. and say here's where. the choice or the action originates it's. a.

finding the free will neuron. that's relevant to that question nobody. is is close to being able to point to. such a thing well close. is a relative term. and nobody. uh what i what i tweet today uh all. generalizations are wrong. [Laughter]. so including this one let's actually. talk about that sort of the study of. individual cells. if you could linger on your. sense that as you get closer to that. understanding it feels like you're.

getting farther away. why is that because that that often is. the feeling until you're actually there. so. so like uh you know see that's when i'm. running. and i know there's only a mile left it. just feels like that mile is just. getting longer and longer but eventually. you finish so maybe we're getting close. to cracking open these like beginnings. of ascent like we'll talk about. consciousness or these very difficult. big. questions about the human mind where do.

they start. you're right to say we shouldn't uh. generalize or make absolutist statements. but i would say. right now the reason things are looking. even. harder to crack than we had initially. thought. we now have the data streams that we've. wanted for so long. in terms of activity patterns all across. the brain at the level of cells we can. literally see. what cells are doing. immense data sets you know we get. these are you know time series of one.

individual cell with you know sub second. resolution and you can collect this from. you know enormous numbers of cells. across the brain. so very rich data sets that we've wanted. for a long time and yet having these. uh has not led. to. an understanding of truly where actions. uh initiate um in terms of regions or. locations let's get a few questions on. that is the answer. high-level. question by your intuition. is the answer within the data or do we.

need. different kind of data so we should also. say that when you collect data about the. the brain there's like the richness of. information you're collecting. but there is also human doing stuff. um like. and the information so static. information about the human and dynamic. information about the human and you can. get them to do different stuff and you. can select different humans. and that's part of the collection of. data aspects so like when you're.

collecting data about the brain. there's some truths. that you can you know in machine. learnings like annotations like. supervised learning there's some true. things you can hold on to before you. look at the full. rich mess complexity of the human. mind so given the data you've looked at. do you think the answer. for the for the origin of free will in. the human mind is can be found. well. one one.

amazing thing is that. nobody's nobody's found it but we have. these rich data sets and and then. there's a conundrum which is. uh is it in the data and we just don't. know how to look at it maybe we don't. know the right scale the right. projection to make of the data the right. way to interpret it. and here's where. causal testing becomes very valuable. because then instead of just passively. observing. well here are. here are the activity patterns and then. here's the choice made by the animal.

as we've gotten more. powerful at reaching in and causing. things to happen in the brain turning up. or down. the activity of certain types of cells. or defined populations of cells and. seeing how that affects actions these. causal perturbations have turned out to. be very valuable. we're just now getting to the point. where we can apply these in very. wide. swaths of the brain at cellular. resolution and so we're going to be able.

uh hopefully to make some headway on. this question with with causality and. those that's. the one thing that optogenetics provides. us this way of using light that we. develop to control cells. this. is an untapped relatively untapped at. this broad brain wide scale and. hopefully we can get there in the near. future but i would say that the answer. may be maybe in the data uh but we don't. know how to find it. well there's this interactive element. like where you can cause stuff that's. really powerful because you get to. i mean.

uh as opposed to collecting data. passively you you're collecting data. actively so can you maybe describe. one of the many things you're known for. one of one of the big things is called. optogenetics what is it. optogenetics is a way of causing things. to happen it's a way of. determining what what actually matters. in terms of the activity of the brain. for. the amazing things it does. sensation cognition action. and what it does is it provides activity.

it's a way of playing in if you will. activity patterns into precisely defined. cells and the way we do it is pretty. cool i think it's you know. right away there's a problem if you. think about how do we do this how could. we play in well-defined activity. patterns and provide a stream of of. activity. into this cell and that cell and that. cell but not these other cells so just. for for context we're talking about the. brains of mice. uh. monkeys.

humans. and then the goal is to try to control. accurately the behavior of a single. neuron and then to be able to monitor. a single. collection of single neurons to then say. well to draw some deeper insight about. the. origins first of all the function of. different parts of the brain different. neurons different kinds of neurons but. also the origins of the big things the. uh the the flap of the butterfly wing. that leads to an actual behavioral.

thing yeah so if you could exactly so if. you could turn on or off. the brain or parts of the brain or cell. types or individual cells. at the. natural rate and rhythm and timing of. normal brain activity. that would be immensely valid because. you could determine what actually. mattered what what could cause complex. things to happen and what could prevent. complex things from happening in a. specific way. but right away you've got a problem if. you want to do this and and scientists.

neuroscientists have wanted to do this. for a long time francis crick of double. helix of dna fame he wrote a. famous paper in 1999 he got interested. in neuroscience later in life. and he said. what we need. in neuroscience is a way that we could. turn on or off. the activity of individual types of. neurons. in a behaving animal. and he even said. the ideal signal would be light because.

it would be fast it could uh. penetrate through the. brain to some extent. and. he had no idea how to do it he said this. would probably be very far-fetched but. it would be a good thing and so that's. what you're actually saying like if you. want to do this kind of thing. and then. it's you imagine like how do i get. inside the brain it's pretty difficult. it's very difficult and then even once. you get in it's hard because all brain. cells are electrical all neurons are.

electrically activated and so if you. wanted to use electricity. as what you were putting in. you won't have any specificity at all if. you have an electrode a wire and you put. it in the brain and you send current. through it all. the cells near the electrode will be. stimulated it's like trying to control. fish by spraying them with water. yeah right because there's already a lot. of. electricity going around anyway and. you're adding more but there's no. uh specificity even among the different.

kinds of cells either because all around. the wire that you've put in they're. going to be so many different cells. doing totally different things many of. them in opposition to each other we know. that's one way the brain is set up there. are parts of the brain that. where neurons side by side are doing. completely different things and maybe. even antagonistic to each other. so what do you do how do you play in. activity with any kind of specificity. well. what you do is use what we found is what. what you can do is. make.

some cells responsive to light now. normally. no cells deep in the in the brain really. respond to light they're not built for. that there's no reason for them to. respond to light in there. which is a great situation to start with. because any light sensitivity you can. provide to some cells will be a huge. signal above the noise. and so that's that's what we do with. optogenetics we take. genes bits of dna from. microbes single-celled organisms.

and these single-celled organisms like. algae they. make uh little proteins that sit in the. surface of their cells. that receive light capture a photon of. light. and open up a little hole in the. membrane of the cell and let charged. particles ions like sodium and potassium. flow across the membrane of the cell. and that they these algae and bacteria. they do this for their own reasons. because that helps them move it helps.

them. make and use energy. but that's a beautiful thing for. neuroscience because movement of ions. charged particles across the membrane of. the cell is exactly the kind of. electricity that neurons work with so if. we can take this. bit of dna. that encodes this beautiful protein that. turns light into electricity from algae. and if we can put it into. some neurons but not other neurons which. we can do using genetic tricks. then you've got a situation then you can. shine on the light.

and only. the cells that have the gene and that. are expressing the gene. will be the initial direct cells that. are activated by the light and so that's. the essence of optogenetics is the. ability to do that we get that initial. specificity that you could never get. with an electrode okay so let me say. that this is uh we recently got uh the. alaska prize for this. is a brilliant idea. um. so. i talked to um andrew huberman who's a. friend of yours friend of mine.

um. not to jinx things but he believes that. he deserves the nobel prize for this so. um. i do too but what uh my votes. anyway the thing is does it doesn't. matter prizes will be all forgotten all. of us will be forgotten one of the cool. ideas cool idea is a cool idea that's a. really powerful idea it's actually the. the origins of it you might be. interested in are even are very deep uh. there was a botanist in saint petersburg. named andrei fomensen.

in 1866. he published a paper. on the single-celled green algae and he. was the botanist who first noticed that. they moved in response to light these. are tiny single-celled algae that have. flagella so they swim through the water. and. he noticed this he was a botanist and he. published this it was as a paper you. know he wrote in. in german but he published it in a. french journal and he was doing it from. st petersburg so it was a very.

international effort. but you have to go back to 1866 and that. i just i like to highlight how far back. the that. discovery goes is back to to andre. feminism and this is a. it highlights the value of just pure. basic science discovery that always. originates uh somewhere in the eastern. european bloc uh but i don't think he uh. expected the splicing of genetic. material from into the human brain and. one of the cool things we've been able. to do now with modern methods is to.

really study these these proteins and so. we we've discovered some of these. proteins other other groups have as well. we've dived deep into their structure. just like the double helix structure of. dna was uncovered with x-ray. crystallography we used the same method. x-ray crystallography to see how these. beautiful little. proteins work we re-engineered them for. all kinds of function we can make them. instead of responding to blue light we. can make them respond to red light. we can speed them up slow them down we. can make them. with genetic engineering we can make. them have different ions flow through.

them. and so it's it's this convergence as you. said like the botanist in 1866 couldn't. have predicted what we could do with. this uh and and the fact that we've been. able to discover how these beautiful. proteins work and then. uh apply them to neuroscience is really. a thrilling story is it possible to. achieve scale do you think with this. meaning. like greater like what is the progress. of the next 50 years 100 years looks. like in terms of the precision and the. scale of control of using light it's. going so fast it's hard to to predict.

i'll i'll give you a sense of it though. in. you know first paper you know. we published. in 2005 that was just in cultured. neurons by 2007 so that was in a dish by. 2007 we had it working in behaving mice. by 2009 we had a pretty general so we. had methods to really make it a. versatile method could be applied to. essentially any cell. by 2012 we could get to single cell. resolution we used light guidance.

strategies to target individual cells in. the brain of a of a living mouse. by. 2019. we were able to control up to. 20 to 50 individually specified single. cells in the brain of a mouse and in. ways that specifically changed its. behavior that could bias its decisions. one way or the other in fact. we could take a a mouse and. without any visual stimulus at all we. could make it act as if it had seen a.

particular visual stimulus by playing in. using the single cell resolution. optogenetics a specific pattern of. activity into you know 20 or 25. individually specified cells that's 2019. it's your question of scale now in 2022. we're controlling hundreds of. individually specified single cells. over. all of visual cortex of a mouse all the. part of the of the. of the brain that that is the initial. direct target of the incoming. information from the from the retina are.

you constrained to specific types of. cells currently like you mentioned long. range is a little easier is there. constraints on which cells uh now there. really isn't now that we have this. individual cell guidance we can target. any individual kind of cell very. reliably. and. so now to your question of scale. uh. how far can we go well. things are moving quickly it's hard to. say uh we we can access individual cells.

across the entire brain now. if you look 10 20 years in the future um. you know i think we'll. we'll surprise ourselves but the fact. that we're already able to yeah to cause. specific perceptions to happen and. specific actions means we're essentially. where we want to be and now it's a. matter of. just uh. you know. more experiments more discoveries but. the the basic. principles are clear now the basic.

capabilities is there is there a pathway. to doing. the same for humans. optogenetics is primarily it's a. discovery tool it really is well suited. for use in mice and rats and and monkeys. because it's uh. it involves putting in a gene. uh and also delivering light and those. are two things that you can do in human. beings but you'd want to do in a very. careful way now that that said there is. actually just less than a year ago um my. friend bhoton raska in switzerland.

he did the first human optogenetics. uh. therapy and he published this in the. journal nature medicine so about. uh. 10 12 years ago he and i published a. paper together where. we gave him one of our. optogenetic tools one of these. light-activated. regulators of ion flow. these are called microbial opsins by the. way opsins. and he put one of those into an.

extracted retina from a human being. who had died so it was a catavaric. retina and he was able to show that. optical control in this in this paper. uh was able to turn on or off individual. cells in the human retina so that was a. while back. he spent about 10 years of going through. all the regulatory. you know hoops and hurdles and going. through primate studies and finally he. was able to take a human being.

with a retinal degeneration syndrome so. someone who's blind in both eyes. and he gave a one of these options. into. one eye of this human being. who was blind. and. with the goal of conferring light. sensitivity onto this retina that. was not able to see light. and he was able to to make this person. see through that eye so he took a blind. person and the blind person could could. see now could reach for objects.

selectively on a table uh. and. he published this in nature medicine and. it was. you know that's an amazing thing um do. you know the title of the pit what's his. name again uh roska r-o-s-k-a. can you look up the nature paper yeah. nature medicine. nature medicine so that that's sort of. proof of principle now the retina is. very accessible it's near the surface. you can use natural light or you can use. brighter natural light. i'm myself. i see optogenetics as as a discovery.

tool it's a way to figure out the. principles by which the brain works and. how it operates partial recovery of. visual function in a blind patient after. optogenetic therapy so he went through. the full process of. doing primate societies and then and. then going well that's dedication and. that that's really exciting to see yeah. as beautiful as that is and i'm glad he. did all that work. there there are so many other ways that. optogenetics could help with therapies. once you know the principles.

then any kind of therapy can become more. powerful once you know the causal cells. in a symptom. like. in lack of motivation or inability to. enjoy things or altered sleep or altered. energy. once you know the cells that are causal. then you can make medications that. address those cells you could address. brain stimulation treatments that might. address those cells also diagnosis. very effective systematic way of. diagnosing or at least providing you. rich.

data to some of these deep questions. about schizophrenia about bipolar. all those kinds of things that are. the tools are low resolution currently. for determining what like the degree to. which you have a thing and whether you. have a thing at all. yeah and exactly and so the the hope is. you know that's a this is a great. example of how you can cure or you can. you know provide some relief for a. symptom of a person who has a serious.

degenerative disease. but. but the principles are what what we're. after and. that's why i spend even though i'm a. psychiatrist even though i i still see. patients i'm not myself trying to drive. any clinical trials in the lab i'm. trying to discover. and then. any kind of therapy could result from. that. what do you think about. uh. my friend elon musk and his efforts with. neuralink so this is another.

i mean there's a lot of things to say. here because there's a lot of ideas. under the umbrella of neuralink. but one of them is to use electrical. signals to stimulate and then. you also record you collect electrical. signals from the brain at a higher and. higher resolution. and you go. implant. surgically. the methods by which you do the. stimulation and the the data collection. so it's possible for the ideas of. optogenetics to play well with this.

and we can even zoom out outside of just. neural link and just the whole idea of. brain computer interfaces. what are your thoughts. well i think the engineering that. they've done is actually pretty cool so. i i like the uh robots yeah from the. from the design perspective and it. wasn't a it was a design approach that. wasn't being taken in academia. and it's great that they did it and i. think it's it's pretty cool um so i'll. say that. also there are many ways that you can.

record from many thousands of neurons. and that's not the only way it's a it's. a very interesting way. we and others are using uh. brain penetrating electrodes that. actually get quite deep this whole. structure the brain is very interesting. we there's the surface cortex where it's. the most recently. emergent part of the brain in evolution. uh. mammals have it reptiles have something. a little bit like it but it's not really. the full thing. it's a this is a very recent thing.

that's what we can access with some of. these you know like the neural link. approach and with some of these short. electrodes. this part of the brain the cortex is. only a few millimeters thick there's so. much that's deep though that's so. important there's the striatum there's. the thalamus there are the parts of the. brain that. drive. motivation that drive hunger and thirst. and and social interaction and parenting. and. and flight and fear and anxiety all. these things are there's so much that's.

deep that these surface approaches are. not getting to and so we and others are. using these very long. electrodes that help us get deep and we. can still record for many cells many. thousands of cells. we can have multiple of these at once in. the same animal. and so there's a diversity of methods to. get to this goal um i think it's great. that that people coming from you know. the you know outside academia will bring. ideas that weren't being worked on uh at. least approaches they may turn out to be. synergistic.

these things work very do work very well. with optogenetics because all these. electrical recording. methods. that's one channel of information flow. light delivery is a separate you know. more or less independent there can be. some some artifacts that happen but if. you're careful that it's another. independent. pathway of information flow. and we've done. really fun experiments in mice where we. play in patterns of activity with light. and we record activity from all across. the brain of a mouse electrically and so.

using optical and electrical together is. extremely uh powerful so like opto. electric brain computer interfaces. which by the way there's uh efforts on. the computing side to build optoelectric. uh servers so like where you have both. electricity so because optics is really. interesting light is a very interesting. method of communication that's like you. said orthogonal many ways. it doesn't have some of the constraints. of bandwidth that electricity does going.

through wires. but. you're able to but it's less ability to. control precisely at scale. so like there's challenges and there's. benefits and having those two interplay. is really really really fascinating. especially when obviously on the other. side. of your signal is a biological. um. [Music]. well the the mushy mesh is kind of. interesting because we we have there are. problems with light light scatters in. the brain so the the photons don't just.

go you know linearly through they. whenever they hit an interface between. fat and water lipid and water. they they bounce off in different. directions and so you can come in with. all the resolution you want you could. play in an incredibly detailed high. resolution pattern of light but the. photons start scattering uh quite. quickly and by the time you've gone a. couple millimeters deep you've lost. almost all that fine spatial information. so. but we've developed workarounds the. longer wavelength light you use if you.

get into the infrared there's less. scattering you can use two photon. methods or three photon methods where. the photons have to arrive all together. at the same time. you can put in fiber optics we developed. these fiber optic methods in 2007 where. you can access these deep structures. with fiber optic methods and you can put. many of these fiber optics at the same. time in an animal we've used holographic. methods. 3d holograms to play in. hundreds of individual cell sized spots. of light and we can and we can change. those quickly and so there are a lot of. tricks a lot of interesting optics.

engineering that has come together with. neuroscience in a pretty exciting way. but it's engineering too it was just. super super super exciting i should. mention because i remember mentioning. elon. um i recently got. for the first time ever. got covered. um. how did i go so long. without finally so i'm all vaccinated. and everything like that and so i got uh. because i think he he mentioned it. publicly so i can mention it but i won't. mention anybody else involved but.

hanging out we've all got you and got. covered and the interesting thing about. maybe you can comment about this so i. was only sick for like a half a day i. got a fever of like 104 i just went up. and then crashed and then i was. now maybe i'm just seeing the silver. lining of everything but. afterwards. uh. i have like a greater clarity about the. world. you just think it's greater clarity. maybe maybe i just it was so.

uh maybe so intensely. the. mind fog kind of thing for such a short. amount of time but the people were. involved were also reporting this it's. kind of interesting it's like uh because. i i do know. like the immune system. uh is involved with the brain in very. interesting ways so like the human mind. also incorporates all these other it's. not just the. it's it's not just the nervous system. and i i just want it because everyone. always says no not like everyone always.

says lykova does all these bad things or. whatever the disease is or whatever the. virus but i wonder like i hate to be a. stephen pinker on this but like i wonder. what the benefits of certain diseases. are if you're able to recover. like what is there some like uh again. don't want to romanticize it but if your. system goes to some kind of hardship and. you come out on the other end i wonder. sometimes if there's a greater um maybe. killed off a bunch of neurons that i. didn't need anyway and they were. actually getting in the way there were. the hater neurons well that was your.

inner critic that i was talking exactly. killed off your critic well you know. there are mechanisms for what the. potential mechanisms for what you're. talking about. there are uh there's actually been a. fair bit of research on. post-covered. neurological. function and actually my wife michelle. mange who's at stanford she's done a lot. of this work uh akiko iwasaki yale has. done a lot of this. but what what they found is that. there's a loss of myelin this is the.

coating of those long range projections. that go from one part of the brain to. another myelin is this sort of insulator. that coats these long-range projections. and makes the impulses go faster and. more reliably. and there's altered. function of the myelin producing cells. uh an altered myelin in. the case of of covert they've looked in. both mouse and and human brains. and. but of course it could be very. idiosyncratic.

many people have cognitive problems. postcoded you're definitely aware of. that so many people report this. persistent brain fog inability to. function. but it depends on where the inflammation. was you know maybe the people who have. dysfunction. postcode they had a global effect. maybe you. lost some of these projections that were. restraining you in some way and and. these plausibly exist and it's known. that there are. cell populations in the prefrontal.

cortex that actively restrain. deeper structures from expressing what. they do. and it's it's theoretically possible. that you had a lucky. uh somebody has to get lucky right. somebody has to get like. all right if we can actually uh go back. to. this idea of trying. through optogenetics. to find origins of. when the wave first starts. origins of a decision.

origin of. uh idea. origin of maybe. consciousness or. the subjective experience the origin of. things in the mind. uh so one thing it's carl jung. um is there a god neuron. is there a belief neuron. is there so through this methodology of. optogenetics can you start. getting.

to like where. a belief. begins or an idea begins. and especially looking at the strongest. of our beliefs maybe beliefs of love and. hate but. religious belief into some something. like really. grand. on the grandest of scale. neuroscience. and. uh neurology point us a little bit uh we.

don't have an answer to that but yeah a. lot of these questions i'm going to ask. you there's no good answer but they're. you're providing the tools that give us. hope to find the answer one day yeah and. we have early clues so for example. when patients with epilepsy have. uh experiences of religiosity as part of. their seizure or the aura before their. seizure. very often those are uh in the in the. temporal lobe uh in these parts of the. brain that are.

at the side. and so that's initial. clue. there are also. parts of the brain that. are involved in the. definition of the self. uh and defining the borders or. boundaries of the self. and. we know this there's just some. experiments that we did in my lab. there's a part of the brain where if. there's a rhythm. of a particular type you can cause a. separation of the sense of. self.

from the sense of the body. what's normally bound up and unitary we. normally think of ourself in our body as. is pretty tightly bound up together. those can be separated it turns out we. can't take that for granted and there. are certain conditions certain patterns. of activity in. one part of the brain called the. retrosplenial cortex where you can. actually separate those two out and so. if you think about. these very big questions. you know what is. where are the origins of religiosity. where how do we define the boundaries of.

who we are relative to others and to the. world. how do we link. our self to our body and how can that. become separated these are actually. believe it or not now. accessible and rigorously and. quantitatively so we did an experiment. with optogenetics where we provided. this abnormal rhythm. to this particular part of the mouse. brain and we saw this separation of.

detection of a stimulus. and. caring about it so that's that's like. stimulating something about the model's. brain that affects these. neurons that give the conception of self. so you're able to dissociate the. experience from the impact of the. experience unto you that's right exactly. right. so like these are the goals of. meditation. uh these are the goals whenever i get. drunk pretty much effective i mean. that's not a scientific statement just. an experiential anecdotal one um also.

psychedelics seek to this. uh to attain this kind of state that's. so interesting well you mentioned. psychedelics you know dmt and five meow. dmt these these create this religious. experience this connection people. describe them as a strong connection to. god. in theory these are accessible with with. modern methods we we now that we have. these rich uh recording methods. we can explore what are the. precise.

millisecond resolution cellular. resolution. brain wide. manifestations of these altered states. so. like you could uh look at an altered. state like an on dmt. record it across many people. and then from there see where do these. experiences originate in the brain in. terms of single neurons. and then. how do they how do they propagate and. interact with everything else and if. there's some kind of. uh common.

signal like how do you. narrow down the set of neurons that are. responsible for particular experience or. for a particular behavioral effect yeah. here's where optogenetics is so useful. because any time you give an agent like. a you know an agent like. ketamine or pcp which we used for our. dissociation experiments that i was. mentioning or you have a psychedelic. lsd or dmt. for this uh altered perceptual state. if you. if you give either of those these.

change everything across the brain okay. so just just the fact that you maybe. give them to a mouse let's say or. eventually to a human. you won't know. yet. which cells to hone in on as the causal. players in all this just by recording. the activity. but then what we found is that. optogenetics providing a causal pattern. of activity guided by what you see. can let you test hypotheses and we saw. this rhythm. with ketamine and pcp for dissociation.

and then we said okay let's test what's. causal. we came in and provided that rhythm we. tried a few different things but only. one of the causal tests we tried. actually caused the behavioral. dissociation. and so that's how we hone in on what. actually and is it repeatable once you. see the cause so like that's one. definition of causality is like you try. and repeats across different mice and. all that kind of stuff exactly. and so you could do that for dmt you. could do that for like the really.

fascinating mind expanding uh uh. thank you. thank you for so the meme for people. just listening this is again another. disagreement between freud and and uh. uh carl jung religion and spirituality. this is the i guess the ring scene from. uh. lord of the rings religion spirituality. freud says cast it into the fire destroy. it. carl jung says. no so so for people who don't know. sergey is. the slavic lord of the meme thank you i.

appreciate that. so what we're talking about so do there. is i mean i think a connection between. gmt and religious experiences or some of. these psychedelics do you think it's. possible to. sort of stimulate religious experiences. so religious experiences are one of the. most. deep kind of experiences and so here you. could. first understand. where they originate. how they propagate to the brain.

and then to stimulate them yeah. yeah. and so this is and these that can happen. in. people who had no predisposition um. you know people who who are. you know as agnostic or atheistic as. you'd like uh they can have these they. can feel connected to god in these in. these states. now to be clear i'm not advocating these. we don't know what's safe uh in human. beings but we definitely. have not yet but we definitely can do. these experiments in in mice and that.

was already. very productive in understanding. dissociation so we can already imagine. making headway on these methods. and then you know i had a and this this. does map on to the non. psychedelic human experience i had a. patient. who's actually described in in the book. projections this was the patient that's. in the mania chapter the bipolar chapter. here was a guy who had never had a. psychiatric illness or symptom in his. life he was a retirement age gentleman.

and. nobody in his family either so no family. history no personal history of any. psychiatric illness and he had never. been religious particularly before. either certainly no no passionate you. know uh type of religion. but he. not through any psychedelic or drug he. he had a stressful experience actually a. post 9 11. change in how he was thinking and he was. pushed into a mania a manic state. revealing that he had bipolar never. before known in this case in this person.

and his mania his elevated state and. bipolar included this profound. religiosity he. which he had never had before and he was. he was you know. preaching in a. elevated you know vigorous way to his. family and so this this state. can be created and people even late in. life who had no predisposition for it. and know. even without a neurochemical so. there's the the the causality of that is. very interesting to explore how did the.

the manic state. unleash this religiosity but you see. that in other realms of of psychiatry. too ocd. can manifest as religiosity also you can. take people who never really had a. a. religion ever played a powerful role in. their life. but then when their. obsessive compulsive symptoms become. severe they can manifest in this i think. i'm in that group so i'm a bit ocd. we have uh. there's i think this is subreddits uh. one is oddly satisfying things.

so there's certain things that are. really satisfying to my ocd in my mild. ocd i think it's pretty much a religious. experience. so i understand that there's it if it's. not direct it's at least uh rhymes. so maybe can you speak to the. sergey is probably uh desperately. scrambling to pull up oddly satisfying. thank you uh people can check it out. themselves it is as as the subreddit.

promises oddly satisfying. um can we talk about. bipolar. it may be depression. well let's talk about i mean i don't. know if there's a. a nice way to discuss the differences in. the full landscape of suffering. that's here but maybe what is depression. and. what are the types of depression what. kind of depression. have you. seen and experienced and researched and. how can people overcome it how can.

humans overcome it and deal with it live. within overcome it. so this is my clinical. specialty i see patients in my. outpatient clinical work with. treatment resistant depression so very. hard to treat severe illness where. medications haven't been been working i. also see patients with. autism spectrum disorders these are my. two. clinical. focal areas. but then i do emergency room work.

as well. but. the depression. why do i focus on that it's so uh. one feels tantalizingly close to helping. these. uh people who are suffering. so deeply that's and that's why i. focused on it is. these are people who. there may not even be anything. situational that's that's difficult or. challenging in their life you can have. people who. seem to have have everything that you. would want every objective measure of. the life is fine and yet they can be.

just. hit with this. unstoppable. hopelessness and inability to see into. the future. a. discounting of the value of their own. action anything they. can imagine themselves doing seems. worthless or they. are unable to enjoy things we call this. anhedonia there's no reward no pleasure. not in food. social interaction movies books.

anything that they would enjoy. positivity gone. they can have a profound. negative internal state psychic pain. and these things can seem and. in the severe cases are inescapable. so what is going on why why is this. state part of the human existence it's. got a strong. biological genetic link we know that. it's been linked to certain genes.

certain regions of the chromosome and. twin studies there's a clear genetic. link. it doesn't explain everything but it's a. big part of it genetics are a strong. contributor. and although you can have depression. without anything terrible going on in. your life the symptoms can be made worse. by stressors by trauma. and. but at a very deep level. there's nothing we can measure in a. person objectively so we don't have.

there's not a known. chemical not a known structure. that's different not a known brain. activity pattern that we can pick up. with eeg. a lot of people are exploring this but. right now we have no objective measures. all we do is talk to people and we. elicit these symptoms. we explore them. distinguish them from other possible. causes. and then what do we do. well we have a range of treatments we. have medications that. can help people do help people but not.

everybody um. and if they don't work then we can go to. brain stimulation methods we can do. things even like electroconvulsive. therapy which is uh a very effective but. it's that's a sort of the final thing we. go to in the end. and. so we have treatments they they work uh. for some people they don't do everything. we'd like but here's the problem is at a. very deep level. we don't understand really what's going. on in the brain we don't have a physical.

interpretation of the problem. we have all these symptoms. but we can't yet point to a set of cells. or a set of circuits or an activity. pattern that is causing major depression. this disease state per se in human. beings. why do you think you can't yet from an. optogenetics perspective is it because. there's so many possible causes is it so. much so many things involved. so i think the answer is there are many. things involved and all these different. symptoms that i've mentioned.

those we can study and those we can fix. the individual symptoms and we can do. this in animals to be clear so in a. mouse for example we can instantaneously. and precisely. turn up or down. the motivation of an animal to overcome. a challenge we can turn up or down its. ability. to to to be motivated by or we think. experience reward. from from uh. situations or actions. we can increase its apparent energy.

level it's it's uh it's it's its drive. uh to meet challenges. we can turn up or down social. interaction uh. all these individual features of. depression individual symptoms we now. can point to exact. projections and cells. that are causal in mediating these but. we don't know is why. all these different symptoms show up. together. in major depression in the human disease. syndrome and that's that's the mystery.

it's sort of. in other fields of medicine you know. someone with congestive heart failure. who comes into the clinic they have very. different symptoms they have shortness. of breath and they have swollen feet. okay couldn't be too. more different. across the body. sets of symptoms. neither one obviously related to the. heart but they're both happening because. the heart is not working as a pump okay. and and now. thankfully in cardiology. we understand these disparate symptoms. that seem totally unrelated.

can be completely understood because. there's an altered pump action of the. heart that's that's what we are hoping. for in in psychiatry and in the study of. depression or any disease. these different symptoms the inability. to enjoy things. the hopelessness. uh what's the what's the unifying. unifying i mean is there is there some. truth to that the tolstoy quote. that all happy families are alike and. each unhappy family is unhappy in its.

own way so basically. i mean this is the human condition. and and it basically that might you know. the physicists long define the theory of. everything. it doesn't understanding depression. essentially. require you to really have the big. theory of everything for the human mind. i think we. it would certainly be nice to have a. theory of everything don't get me wrong.

i don't think we need a first date. of the century it would be nice. it's also a good question if it's. possible yeah yeah well that that i i. have uh some thoughts on too but but to. your to this specific question um i. don't think we need a theory of. everything i think there will be. unifying principles principles we can. get to but even shy of that if we can we. can treat symptoms and that's a big step. and as you say different different. unhappy families are different different. unhappy people are different. if we have somebody who comes to the.

clinic and i see someone with a profound. anhedonia as one of their main symptoms. inability to enjoy things and if i know. based on optogenetics work and animal. work that a particular medication. can treat anhedonia even if it doesn't. fix major depression in everybody if i. treat that one symptom in that one. person. that's a good thing. and and so i we don't need. the theory of everything and we don't. even need the unifying principle to help. people with insights that come from.

optogenetics. so how much does talking help. for diagnosis and for treatment. would you say for depression. it's a big part of what we do every good. psychiatrist is. should be pretty adept in. these verbal communications and talk. therapy as part of what they do. i give medications i deliver brain. stimulation treatments but. a big big part of everything i do with. every patient is. talk therapy because it works so well.

together with. these other modalities even alone it can. help people with moderate or. or mild depression by itself. people with severe depression people. with other. psychiatric illnesses that are are. severe. you don't want to do talk therapy alone. that's not going to do it but it still. is crucial to do together with the. others and it's it's it's critical. because. it's uh part of how you re shape. cognitions you know. complex activity patterns and and you.

won't get to that with a medication or. brain stimulation treatment. do you have advice for people who suffer. from mild forms of depression. or feel. as they might. both for those people and do you have. advice for people. who. love the people who suffer from. depression and want to help yeah. one of the incredibly. frustrating things about depression is. the very nature of it. makes it hard for the people who suffer.

to. get treatment because they they're. hopeless so they don't think treatment. will help they have low energy. so they're not motivated to participate. in treatment in many cases. they're sometimes they're actively. suicidal that certainly doesn't help. they have all these things that. seem to prevent. treatment from being effective so the. loved ones that's where the loved ones. are so important is is helping them. overcome these barriers to treatment the.

motivation the safety. and the insight. that's critical uh. and particularly for the severe cases. for the mild cases where people still. have you know. have some insight and motivation and. energy to get something done. there are many things you can do. uh. exercise is extremely important in in. mood maintenance. regulation of sleep and getting. sufficient and regular enough sleep is. very important.

and talk therapy can be helpful in those. mild or moderate cases just looking at. cognitions looking at patterns of. thought. that. people may have fallen into. where they catastrophize where they. spiral from small things into big things. a little bit of talk therapy 10 12. sessions can help people identify. those patterns they may have in. themselves. that are. taking. occasional negative thoughts which.

everybody has. and magnifying those into. more persistent negative states. once you if you work at this it's kind. of like homework this is what we call. cognitive behavioral therapy. it's very structured very organized you. work hard it requires insight and. motivation and you have to be motivated. but if you are then you can identify. these triggers that send you down. particular pathways and work to. intercept them and that is. amazingly very effective in mild to.

moderate cases so you're basically. have to train yourself to see the world. as a. collection of triggers and you have to. first understand like collect the data. like basically see every experience. as a thing that creates a follow-on. emotion of feeling. and like i've learned this. you know like on social media.

where like early on. you know like all of us. um you know i'll i'll say something i. kind of respond to negativity. with negativity. and then you observe. the results of that. over time. you think wait a minute. th this thing that i've been doing where. when somebody says you suck and you say. no you suck. that never produces the result you.

thought it might. and so might not want to just. don't say you suck back. and i do this through a lot of things in. life. i'm very fortunate to. not suffer from. depression but. i. first of all i have had and have people. in my life who do. and and also you know all of us. have depression who don't suffer from. depression have depression out.

like uh it's always knocking on the door. right yeah and so you you have mild uh. i mean uh. if you're very careless with the. triggers. all around you. then you you're just i think all of us. have the capacity to really suffer. uh from that kind of. uh chemical or psychological or. philosophical existential crisis. but then it raises a question why are we. built this way it seems like it doesn't.

make sense right um and here's where. some of this thinking about where we. came from. uh. as the human family is is kind of. interesting. does it make sense that somewhere on. that spectrum. that it's good to detect that there's an. array of. adverse forces out there in the world. right now at this moment. and to withdraw. to. to hunker down. to not fight not strive not try to meet.

the challenge. and. outweigh. these. negative forces that are present out. there and that makes a lot of sense. uh. and all. animals that have been studied in one. form or another show this even the worm. that i mentioned earlier. c elegans with 302 neurons. it can effectively give up in. challenging situations we've done this. with zebrafish tiny little transparent. fish. you can give them a challenging. situation and they.

will give up but then if you. stimulate a couple very specific brain. regions in particular ways you can. motivate them to overcome the challenge. and if you inhibit those regions they. give up much more easily than they would. otherwise you can do this in mice you. can do this in rats. so this is an ancestral conserved. pattern to detect. that things are. pretty bad out there. and to conserve energy. to hunker down to wait out the storm it.

says use unfortunately. many of our maladies have. useful roots in in our uh. that contribute to our survival so both. depression and motivation. have uses. and in the pain sometimes it's nice to. just. shut the hell up and huddle with the. penguins. right uh versus. for some unknown reason venture out on. your own into the mountains like a david. goggins type character. so what's the difference to you.

between you see patients between sort of. rigorous. um psychoanalysis i don't know if you. consider where you like talk therapy and. psychoanalysis are they neighbors are. they overlapping their their neighbors. uh psychoanalysis is. it's um. they're relatively it's not nearly done. as much as the talk therapy like the. cognitive behavioral therapy i mentioned. uh. the the psychoanalysis is is a little. more niche now and partly because it's.

it's not. data isn't um. in terms of actual treatment of actual. therapeutic effects. data not as supportive as for cognitive. behavioral therapy. but it's still interesting as for. insight people a lot of people still do. it to gain insight into themselves. and in general it's a good uh sort of. conversation starter those methods you. know they're good for. getting things out you know. we don't focus on dreams uh typically. these days in psychiatry but they're.

great conversation starters they're. great ways to get things out if people. have. uh and so we like to use those methods. just to get the ball rolling sometimes. get people to open up a little bit but. the actual treatment. that tends not to involve these. psychoanalytic approaches where you. are really probing uh the unconscious. mind and its manifestation through. through dreams. for example as as the as the goal that's. not the goal modern talk therapy we're.

really focusing on treatment how to get. people to feel better see i use that as. a conversation opener to the freudian. thing where i try to delve at a bar. of the deep sexual desires in a person's. subconscious and i find that opens up. possibilities very quickly no um all. right. what's i mean this is a silly sounding. question but what's the difference. between cognitive behavioral therapy. and conversation. so. um because i personally as a fan of. conversations is a fan of just i like.

listening to podcasts. um versus like audio book i like both. but they're very different and i like. conversation i like um it makes me. personally very anxious so i like to be. the listener. uh like like a third wheel like. overhearing a conversation kind of thing. but. it's a really powerful method for humans. to explore each other's mind just raw. conversation so. do you think. it can be more productive to be very. systematic about it or is conversation.

itself the art form of. of helping each other understanding each. other and helping each other. there are forms of talk therapy that are. essentially conversational or they much. more approach pure conversation there's. uh there are there's a befriending. therapy there's interpersonal therapy. these are these are approaches that are. purely talk therapy. but they're. not as structured as cognitive. behavioral therapy cognitive behavioral. therapy has is there are manuals there.

are guidelines you can almost go through. it in a very cookbooky way there's. there's homework that you get done so. it's. in its fullest form. it's very different from these more. conversational strategies but what's. interesting is sometimes people compare. them and so you'll see. almost like randomized controlled. studies um. comparing cognitive behavioral therapy. with interpersonal therapy for example. and they both can work and actually in. some studies they look uh comparable. um so there's.

to your point. conversation and insights that come from. conversation if done well if done. artfully. can be as powerful this reminds me of. robin williams so i have to ask you. several questions here on that but one. of my favorite movies is goodwill. hunting. i don't know if you've seen it with. robin williams. so. as a psychiatrist yourself can you do a. deep analysis of this other famous. psychiatrist which is the movie. character. played by robin williams at goodwill. hunting.

this is just a caricature between a. psychiatrist and patient relationship. or is there some. something to you was that was moving. about his ability to connect to this. obviously struggling young kid. i think you've hit on the key thing. there which is the the depth of the. connection if. if there's a. too powerful connection. that can impair uh therapy because it. could impair. open communication if if someone.

if a patient has a. sees the role sees the relationship in a. particular way. like in a friendly way maybe or like a. parental. child. type way. that can cause problems because then. what they choose to share what they. choose to bring up. is selected to be appropriate for that. view of the relationship. and so i and many other talk therapists. actually prefer.

not to let things get. um. not let the connection get that deep. you want to have trust you want to have. a therapeutic alliance we sometimes call. it. but it's got to be enough of a blank. slate. that the patient. is not. consciously or unconsciously constrained. in what they. choose to share. and so. great movie. great actors.

it's all good no complaints except uh. realistically. the relationship should be a little more. uh arm's length than that. let's pretend this is real life. sometimes can't you leave a little bit. of yourself. in the interaction with the patient i. mean it's another human being yes so. it's a balance and actually you do need. some of it um because let's say this. person is having. challenges interpersonal challenges in. their life.

the best way. to notice what those are. and to identify them and to work with. them. is if you can elicit some of those. problems. in. in the office in the therapeutic. interaction. and. this is really powerful as long as. you're. alert to it aware of it. and you don't let it go out of hand. this transference we call it is when.

you. transfer. in between. the current therapeutic relationship and. external relationships that the patient. may have had with others. and so if the therapist starts to feel. an inner feeling. like anger. let's say so let's say you have a. patient who is stirring. frustration in you or even an extreme. case is anger. the the best thing for the therapist to. do in that case is to recognize it.

and to realize. that's probably being stirred by other. people in the patient's life and that. could be the source of a lot of problems. and so instead of trying to wall it off. and say oh i shouldn't be feeling that i. better. be a better therapist instead and. recognize it and use it. and help the patient that way and so. you've got to be a human being you've. got to be a person who feels. and you've got to be open. but be in control of it and be aware of. it. if if i may i just want to read the. because my favorite scenes probably one.

of the greatest scenes. one of the greatest scenes in movie. history because robin williams does a. single take. is that right so this is a very. interesting interaction between them so. um will and i'm sure this is a common. interaction. um. maybe with the therapist and a patient. maybe with the father and son. where. will the young character the young. brilliant mathematician and sean is the. therapist the older. uh therapist where will looks at a. painting that sean.

painted and then does a like a deep. critical analysis of the painting that. basically. you know describes. uh. pretending as if he can understand. another human being completely but just. looking at their painting. and then sean gives this whole speech. that contrasts sort of raw intelligence. and the wisdom of experience. and sean says single take. he says you've never been out of boston. right. and will says nope.

all this in a sexy boston accent by the. way. uh and then sean gives the speech. if i asked you about art you probably. give me this skinny and about every art. book ever written michelangelo you know. a lot about him life's work political. aspirations him and the pope sexual. orientation the whole works right. but i bet you can't tell me what it. smells like in the sistine chapel. you never actually stood there and. looked up at that beautiful ceiling seen.

that. if i asked you about women you'll. probably give me a syllabus. of your personal favorites. you may have. even been laid a few times. the language here is just beautiful. but but you can't tell me what it feels. like to wake up next to a woman and feel. truly happy. you're a tough kid. if i asked you about war you probably. throw shakespeare at me right probably. not but. let's say. once more into the breach dear friends. but you've never been near one you've.

never held your best friend's head on. your lap and watch him gasp his last. breath looking to you for help. if i ask you about love. you'd probably quote me a sonnet. but you've never looked at a woman and. be truly vulnerable. known someone who can level you with. their eyes. feeling like god put an angel on earth. just for you. who could rescue you from the depths of. hell and you wouldn't know what it's. like to be.

her angel. to have that love for her. be there forever through anything. through cancer. and you wouldn't know about sleeping. sitting up in a hospital room for two. months holding her hand because the. doctors could see in your eyes the terms. visiting hours don't apply to you. you don't know about real loss because. that only occurs. when you love something. more than you love yourself. i doubt you've ever dared to love. anybody that much.

i look at you. i don't see an intelligent confident man. i see a cocky scared shitless kid. but you're a genius well no one denies. that. no one can possibly understand the. depths of you but you presumed to know. everything about me because you saw a. painting of mine you ripped my fucking. life apart. you're an orphan right. do you think i know the first thing. about how hard your life has been how. you feel. who you are because i read oliver twist.

does that encapsulate you. personally i don't give a shit about all. that because you know what. i can't learn anything from you that i. can't read in some fucking book. unless you want to talk about you who. you are and i'm fascinated i'm in but. you don't want to do that do you sport. you're terrified of what you might say. your move chief. well done sir i know it's a movie it's. interesting right so some of that. conversation is at some intellectual.

level too. it's not just emotional it's something. uh it's like i the reason i kind of. connect with that is. that's a lot of work. for a therapist. like to really understand another. because he's i mean from okay i know. this is fictional but just. there's calculation happening he deeply. cares. to say the words that the other person. needs to hear but also a little bit. loses himself in.

the pride. but then catches himself again. switches from anger to uh to connection. yeah. a lot is brought up there that you're. right there there has to be some emotion. in the therapist to care enough to keep. going to to keep probing to open up. as he's doing so right. he revealed a lot about himself his own. vulnerabilities but that gave him. authenticity. he had to open himself up so that the. the kid would see the authenticity and.

open himself up in return. so so how do you do that as a as a as a. psychiatrist as a therapist. you have to be careful you know you. don't want to do. too much uh but opening up a little bit. does. help it does create. uh a chance you know you're offering up. something and that helps the patient. come back in return. and it gives it gives you that that. believability and authenticity do you. pay the price for that for opening it up.

you can um. you have a family you have an incredibly. like difficult research like you're. doing a lot of things in your world i. mean it's the price you pay for like. well this is one of the terrifying. things about about writing the book was. was. i i do open up uh in a little bit about. my own personal life my own personal. challenges and that was a considered. decision because. uh i could i could have done. the the patient work and the science.

work and the. and the history of the human family work. and and tied it all together. but but it wasn't and i i in an early. draft it was it was like that. but it wasn't it wasn't real yet it. wasn't. it wasn't uh something that that. everybody could connect with and i said. then i realized look if i'm going to do. this. i i've gotta i've gotta open up myself. and then and then people can connect. with me and see. what i'm really saying and so i did and.

that was. it was not something that um i'd gone in. planning to do. in retrospect i learned a lot about. myself it was actually really i think a. good thing that i i did but. it was scary. where are the darkest places you've ever. gone in your life. you know i had uh. things haven't haven't always been been. easy personally or you know or. professionally i had i had moments you. know i was effectively a single dad for.

for a while a number of years and these. came at probably the hardest also. professional. life times for me too. the absolute hardest uh days of late. medical school internship you know. taking call. you know getting up at 3am you know. surgery uh. medicine rounds unforgiving environments. and then all the while you know personal. life uh you know stripped down to the. bear um.

and these were low moments and then i. was hit particularly hard by. just experiences on. on the clinical ward connecting too. deeply with patients like you know a. child with a brain tumor and feeling it. too strongly and and those. things uh. when you get down to those lowest of the. low moments when everything is is. stripped away and and there's there's. only this this raw. core well yeah. that's pretty hard those that was.

probably the the lowest moment and you. learn a lot about yourself in those. moments you know what's what's left and. and then what are the. the the roots out from there and and. that's. that's that can be powerful to to see. uh in yourself. have you thought about killing yourself. i have not. i have not have you seen that thought in. the distance. i am fortunate that that has not. come to my mind and i have not seen it.

in the even in the distance and i in in. in some ways i've i've wondered if. that's made me. am i a less. you know effective psychiatrist because. of that i've been. i've felt everything stripped away i've. been at the lowest of the low. and yet the the that there's still hope. there's a light of hope still at the end. of the day. right. so you never lost even for brief moments. that um. i never did. i don't know. you don't know why there was no reason.

you don't know why no reason to feel. hope at that moment honestly. uh. so it was just the light without reason. yeah that's right. what wisdom do you draw from that time. about. so first of all. you said something funny which is i. wonder if it. that it's somehow not having. thoughts of suicide. limits your capacity to truly understand.

somebody who is. having those thoughts. so how many demons must the psychiatrist. have. in order to be a good psychiatrist yeah. you know this is a really interesting. question i think everybody knows and i. can say this that psychiatrists. can be a little unusual there we. we think about ourselves right we think. about our brains that may be one reason. why we become psychiatrists is we think. oh that's interesting going on in there. what's that about so a little little.

introspective a little introverted maybe. and that's what can make us good. when we're good. and. but also that. that may select for people who have some. unusual aspects but you don't have to. have all of them. there's a lot that can can go wrong in. the in the psychiatric realm uh i think. having. some of those some of it but not all of. it is enough you get to see. how low things can can get. you can get a.

you get empathy from that even if the. symptoms are not the same um just. empathy for struggle for suffering. that's right that's right. do you yourself have to practice. observing triggers. just as a human operating in this world. i've definitely those those skills that. have come from. from therapy i've i've found i found. them useful yeah if i noticed that uh. we've all been through experiences where.

we wondered oh i got really mad in that. interaction. why did i get that mad you know yeah. sure maybe i could have been irritated. but man why did i yeah and and and then. thinking about it and realizing okay you. know. back up here think about the broader. context. um uh. think about. what how that relates to you know prior. events in my life okay yeah so this is a. thing for me uh when something of this. class happens. then it triggers me.

so going forward i'm going to be aware. of that. um. and i've definitely used that because. it's. you don't you don't want to be out of. control those emotions you want to. identify them you want to know where. they come from and. you want to head them off as a as a. civilized human being living on this. earth trying to get along with other. people you want to understand those. moments let me um. return to robin williams for a second. and looking at robin williams the. the actor the uh sorry the human.

and because you mentioned um. for depression you can have everything. going well. and i think there's just. uh. famous cases of just public figures. because a lot of people know them. where. they they suffer quietly. and it seems like from the outside. perspective that they. have everything going for them that. they're top of their career. you know two people that come to mind. are. robin williams and anthony bourdain.

what insight do you have and why. either of those taken why robin williams. a comedian one of sort of the most jolly. humans obviously there was always the. darkness that he was channeling. channeling in order to. present the happiness but it feels like. that realness is only possible when. you're deeply self-honest and analytical. and. and then then if you're deeply. self-honest you're going to realize that.

there's a lot of beautiful things about. life that you can discover and if you do. that how can you possibly then take your. own life and you go through all these. thoughts and. i think a lot of a lot a lot of people. really loved robin williams which is why. it was really difficult to see how can. even. him how can even robin williams take his. own life so. i don't know if there's something to be. said about the nature of depression from. just looking at his case. i think.

the action of suicide is not well. understood uh it it doesn't always. although often is correlated with. depression there are cases of suicide. where there is not clear depression that. that's in the minority by the way if i. just look because you said it's so. interesting action of suicide because. there's also thoughts of suicide that's. right and probably those that probably. somewhat understood but it's an. interesting. because you can think of suicide. if you have suicidal ideation you can.

think of that for so many reasons. that's right. and. and the. i mean i. thoughts. sometimes like painful thoughts. angry thoughts or thoughts in general. can be very different like fantasies for. example you can fantasize. like sexual fantasies you can um. fantasize i was just for humor's sake. wanted to mention stuff but then people. think i'm serious i'm not going to.

mention anything but. sexual fantasies and then there's i know. there's people that have sexual. fantasies and they don't want to. actually do that in real life that that. that sexual fantasy serves some kind of. purpose in imagination only and in that. same way suicide might serve a purpose. and imagination only is very unlikely to. lead to action and yet there's other. thoughts that maybe are more amorphous. that do lead to action and that leap. uh yeah that oh boy that's a facet and. that's such a philosophically powerful.

thought to not exist right like that. question uh that's this uh is it sarcher. or kamu. kamu well the mythicist. who says like basic question of why live. question yeah right. so. that's a great question actually and. there are other related questions some. people. may have the thought of suicide. because.

there seems no point there's no joy in. life that's one reason that some people. can put forward. sometimes there's an it's not just the. absence of of joy there's an active pain. an active psychic pain in some people. and that the inescapability of that. is enough to drive the thoughts of. suicide. and then there are interpersonal and. cultural reasons as well that can show. up. the but the act this act of ending of. the self is. in all these cases there's no real way.

to study this in animals no other animal. as far as we know that we can study. has this concept of this is myself. the situation is not. tolerable therefore i will end the self. to our knowledge this is not something. that that can be studied in other. animals so it remains this this uh. uh very poorly understood action and. in predicting it so what do we do with. psychiatrists we have this challenge.

people come to the emergency room. they say they're suicidal or their. friends say they're suicidal or they've. taken some action. that that didn't lead to death what do. we do well there's a whole range of. options you know was it a suicidal. gesture in the sense of not intending. death. or was it. was the intent. death. and if it was the intent was was death. what were the reasons are the reasons. transient are they gone now. what's the probability that it'll be. repeated.

so we do all these things just to decide. what sort of treatment should be carried. out but nowhere. is there a deep understanding of the. biology of the cells and circuits. and activity patterns that underlie the. end. the action to end the self. it's a very. it's so it's this. frustrating thing it's it's so. timely it's so common it shows up in. veterans it shows up in kids it shows up. in people at every stage of life.

and yet we're very bad at. understanding it and we're relatively. poor at predicting it and our tools are. are not very. powerful we can put people in a locked. unit we can give them care therapy for a. while at some point. we release them and there's only so much. we can do it's one of the most. frustrating things and the suffering. that is linked to suicidality but it is. a decision and it is an action. and if you look at optogenetics you. should be able to.

one day sort of understand the dynamics. of such. weighty decisions. the individual causes then if someone is. anhedonic if there is no joy in life. that. very likely is addressable by. optogenetics we know how to. turn that dial very robustly in animals. the. motivation to overcome challenges that. we have some some hope of understanding. psychic pain internal negative states we. have actually a handle on that as well.

there's a structure in the brain called. the habenula. and some linked structures around it. that seems to generate this negative. internal state that's it's active when. a state of acute disappointment acute. outcomes that go wrong uh not as. expected. you know. moments of unexpected pain uh the. habenula is there it seems it's active. to report on internal uh negativity with. its with its action.

and so you could imagine strategies to. target this brain structure that. might have the effect of reducing. psychic pain reducing the negativity of. internal states that is a very concrete. hope it's precise it's anatomical. optogenetics has given us all the firm. foundation we need. to go. after that question so i think there is. hope uh if you look at the individual. causes the individual symptoms relating. to suicide. and then it's like a puzzle you put. together the puzzle pieces well by the. way i do think my.

uh habenula. is uh. very functioning very actively. and i wonder if it's like because. because you you can also learn to. channel these things right some some of. the things we suffer from. i mean there's degrees of suffering can. be. um a source of. progress and personal growth and. development and all those kinds of. things and i mean i. um.

what is it nietzsche suffered from. stomach issues. you know. i wonder if you've written some of those. things if. if his stomach was all great. right i mean that there's i kind of. think that. uh a difficult life in some form you can. get you get to choose in some regard and. some of you don't the difficulties you. have and the ones you do have it's nice. to use if possible it's sometimes it's. nice to treat sometimes it's nice to.

it's nice to use well the way you phrase. it i think you're using it i could be. wrong. but if you you phrased in this. semi-humorous way about your habenula it. seems to me that you're you're using. that. to good effect now. but one never really knows what someone. else's internal state is as i look at. you i don't know the depths of what's. going on and it's possible uh that that. it's it's it's a much harder situation. in there um yes. so that's i actually worry about this a.

lot so i'm extremely self-critical like. in the privacy of my own mind which is. an interesting thing when you get to. meet the internet and the internet will. tell you you suck. uh. but. for for now now this is what i worry. about and i'm very paying attention for. now it's really i just have this like. very negative voice. but that voice seems to be very useful. for productivity yes and so i channel it. i just put on the table and let that. voice like talk to me but i'm very i'm.

like. monitoring that voice because looking at. robin williams you know you get older. your brain changes or like your and and. then that voice can now all of a sudden. grow. right and then where you can't control. as much just be very careful with these. kinds of things you're very right about. that i so my my negativity i have this. uh i never think i've done enough is. sort of where my my negativity comes. from inside i i i never think. that i've.

i've. met the potential of the moment i. haven't done. uh i haven't you know. made the most of the opportunities that. are available. still early i haven't you know. you know progressed as far as i should. and exactly as you're saying. that works for a while. but then what happens as as you get. later in life and there's less. runway. to. you know fix that and then maybe maybe. then maybe then that negative voice is.

is a problem but also at that point the. negative voice starts having more and. more of a point that's when when you're. being when you're being very successful. it's easy to be like no okay well. like later in life you're really. literally just sitting there on a. on a rocking chair doing nothing and. then. it's. or maybe any kind of tragedy happens. loss of a loved one. loss of a job. loss or you get screwed over in some. kind of. um some kind of way i don't know those.

and then also in the negative voice is. just you and the negative voice for. days and days and days and so i don't. know. to go back to your example of robin. williams i don't know what was going on. inside him i don't know the nature of. his internal state was it a was it. active psychic pain that. may have mentioned may interrupt to just. say that sergey posted an examination of. robin williams's brain tissue suggested. that he suffered from quote diffuse. l-e-w-y lewy body dementia.

lbd depression is a symptom of lbd and. it's not about psychology it's rooted in. urology this is words from. his brain was falling apart yeah louis. body dementia this is a very interesting. neurological disorder where. among other things there are there's. neuron death indeed so you've got frank. neuron loss it's not just a matter of. some long-standing. psychic pain but you've got a. progressive.

loss and so clearly you've got a. situation where he could have finally. reached a point where. the balance that he'd worked out between. negativity and positivity uh. was disrupted due to loss the wrong. cells died the wrong projections were. cut by the lewy body dementia certainly. dopamine neurons die in lewy body. dementia those are neurons that give. rise to. much of the feelings of reward and. pleasure that we experience among other. roles. so. uh clearly in his case there could have.

been a very. concrete cellular neurological issue. that was progressive and pushed him to. that point. but what were you uh. were you about to make a point about. broader that if there isn't another. neurological degeneration yeah so in his. case not knowing that uh. it could have been simply that let's say. he had. an internal psychic pain state and it. was in. he was in sort of a compensated mode for. much of his life able to generate enough. joy from his his comedy and his social.

interactions and. and then but eventually later in life. you know the. the those things drop away the balance. shifts you get tired of fighting the. pain for that long and then so you've. got this time dependent. non-stationarity that happens and then. the same. symptom becomes no longer tolerable in. the end. what is autism what do we know about. autism. human beings exist on a spectrum of uh. how social we can be.

and this is pretty interesting actually. scientifically but also. very important uh clinically. there are hypersocial states where. people are. almost too social there are chromosomal. deletion states where people have. instant. affinity and bonding and and rich deep. seeming. connections with people very verbal. on the other end. people with autism spectrum disorder are.

not. able to. keep up with social interactions and. it's a it's a spectrum some have. mild to moderate difficulties they. may have inability to understand what. the next thing to do in a social. situation is but may have. perfectly good language abilities. and as you progress further along the. spectrum that gets more and more severe. so they. can't make eye contact because it's too. overwhelming to think about what has to. be done next if a person looks in a.

particular way yeah. and then as you go farther then. language. and social communication themselves. break down so there's no. reciprocity there's no shared enjoyment. and that this gets very hard then as you. get to this far end of the spectrum. where there's. really an absence of social cognition at. all uh and and social bonding. so why why does this exist what is it uh. it's very genetic as i mentioned it's. it's one of the you know top three or. four most biological in the sense of.

most genetically determined of the. psychiatric illnesses it does have these. interesting positive correlations slight. positive correlations with. intelligence and education. and. the reason for that is kind of. interesting to think about. is there something good about it just. like. or. at least with at least part of the. spectrum is there's something good about. it just as we were talking about for. depression. as you could say for mania as you could. say for schizophrenia.

and. here it's kind of interesting to think. about the. the underlying science of what it means. to be good at a social interaction the. someone who's very good at a social. interaction is incredibly good at. dealing with unpredictable. information. is able to handle this torrent of. information coming through. rapidly changing. a model of the other person and of the. interaction and their model of you.

your model of them. with each word that changes with each. new bit of information that comes in. through the conversation each bit of. body language all this is rapidly. changing and some people. are. able to keep up with that fire hose. information perfectly well. but that's a special brain state to be. in that's working with. unpredictability that's. you know uh. the only way that can be done is most. likely by constantly. running models of what the other person. might be about to say.

so you can't stop and think oh what did. that word mean what did that. shift in eye contact mean. you know what do they mean together. there has to be some advanced work going. on where you're predicting what's going. on if you're to keep up with a rich and. fast social interaction. now. on the flip side. there are. brain states that maybe don't have to. work so fast that are extremely. important still dealing with something. that's not moving. or that's predictable still complex.

like. uh you know mathematical proof or a very. complex arrangement of geometrical. shapes uh a large number of individual. non-moving things. there's a. possibly a way of being that's. particularly good at dealing with these. static unmoving or predictable. situations. and less so with these rapidly changing. social situations. and so the way i conceptualize autism. is these are people who whose brains are.

not so good with the high bit rate. unpredictable information but may be. quite good at giving enough time. given. the. grace to work with. the system. to look at it from different angles. to take different perspectives with the. confidence that it's not changing. in between perspectives. that's a brain state that's valuable. it's something that has probably. has contributed to a lot of the success.

of the human family being able to design. something being able to consider. the. the. all the different contributions to a. static predictable. system. so autism in a sense is a. is a spectrum that has. identifiable characteristics about the. way people deal with dynamic information. often expressed itself as like social. that's right dynamic information but you. critically your use of the word often.

there is really i think smart because. it's not just social interaction that is. a challenge in autism and so many people. conceptualize it purely as a social. dysfunction. disorder. but it's really any unpredictable. information that's a problem that's a. challenge for for people on the spectrum. they react very. negatively to unexpected sounds even if. not social sounds unexpected lights. unexpected touches.

and so it's really unpredictable. information that is uh in my view the. core problem with with the processing. and autism not just social social just. shows up because it's so unpredictable. yeah it's so interesting i mean um. i tried to not to think about that stuff. um. i'm afraid of thinking disor about. disorders and things like that because. just like i don't like sort of economics. or game theory. uh i won't be careful with it because.

it uh whenever you have a category or a. model it's too easy to just uh for every. i mean it's the ocd thing i like models. too much i like categories too much the. moment you acknowledged yourself well i. have an eating disorder for example or. something like that as opposed to just. being a well i'll just i'll just leave. it at that for my own critical. understanding of myself uh let's just. say i don't know how to moderate eating. fruit people make fun of me they think. all fruit just fruit is healthy.

i know. [Laughter]. i don't well i don't know how to. moderate anything but even even fruit uh. this apples and cherries is a nightmare. anyway. that's such a psychiatrist thing to say. very interesting um. but uh but there's characteristics and. and i it's. it's interesting to think about like for. example i have trouble making eye. contact. but i actually as you said it now. it's not that i'm.

shy at all in that sense. it's. literally i'm getting way too much. information it's distracting me like i. need to just close my eyes so i can. like all the things that people seem to. be able to do in parallel it's just. you just ask me a question. for me to think about the answer to that. question i can't have all this cool rich. visual information coming my way that's. literally because i often close my eyes.

to think it's not because. i'm afraid of something whatever it's. just like too much information happening. here yeah well that's a beautiful. description it's it's amazing that that. is how you experience. the the eye contact uh aspect. i think that's. i mean you've articulated what uh. you know. captures it for for so many people which. is that it's overwhelming there's just. just too much information just coming in. through the eyes. and. to keep up with it to know.

you're going to be expected to keep up. with it first of all so there's that. that aspect you know you learned. socially that there's going to be an. expectation if you're making eye contact. people are going to think you're keeping. up with it and. you don't want to because you want to. focus on other things and make progress. in other. you know dimensions. yeah and so that then there's a strong. desire to look away or to close the eyes. because. it's it's it's it's overwhelming it's a. distraction and it's going to cause. errors of of understanding and of course.

our eyes that's part the way we use our. eyes as part of the human communications. you have to kind of be aware of that. of that um. that element of it so yeah i mean but. it's fascinating you should be aware of. your own self in those those little. characteristics. whether it's uh. whether it's classified on some aspect. of the uh autism spectrum or just in. general whether it's eating whether it's. depression. whether it's um even like schizophrenia. that would i hope we get a chance to.

talk to a a little bit yeah but those. things are all made up of different care. symptoms and characteristics. and use use them as a superpower i i. suppose this is the best we can hope for. in mild cases i guess i do think both. brain states can't coexist at the same. time the way of dealing with something. unpredictable and dealing with something. predictable. there those are different ways of being. here's a huge opportunity for. very creative.

model building in theoretical. neuroscience. and linking that to these data streams. we're getting across the brain. that we talked about earlier these. immense data sets of activity across the. brain. here's where i think there could be a. real convergence of theoreticians and. experimentalists to say okay. given what we know about wiring of the. brain. here is what. the brain state is likely to be that. deals well with unpredictable.

information and here's the brain state. that deals with predictable information. here's why they're incompatible at least. at the same time here's why you've got. to be able to detect. which state you should be in here's how. you could switch between them here's the. kind of cells that you would predict. almost like predicting the higgs boson. here's the kind of circuitry that i. would predict should govern the. switching. or. might make one. state too sticky too hard to get out of. right yeah that is a huge opportunity. for an interaction from the theoretical.

and experimental side together. make one state too sticky. the. sort of uh measure the stickiness of the. state and how to lessen the stickiness. that's right get some oil in the machine. yes yeah what would predict the kind of. oil that would work well. uh what in your practice is um. treatment or advice. for the people on the autism spectrum so.

right now there's no real medical. treatment there are behavioral. treatments. that are most effective early in life. they make sure people don't fall too far. behind. if you're not interacting socially you. create this. you know vicious cycle where you fall. farther and farther behind because. you're not interacting and these these. therapies which are applied early in. life. therapists work with the kids. train them to deal with these things. that otherwise would be aversive to them. teach them how to predict things and.

interact and that. has a big effect but it's behavioral. therapy there's no medicine that works. there are ways of reducing individual. symptoms though that sometimes come. along with autism and those do respond. to medications so you can you know one. thing very often my patients with autism. are very anxious. because. they live in a world that they have a. really hard time predicting what's going. to happen and so they find. and some of these are high functioning. you know silicon valley types who you.

know they might make you know. great livings but they're very unhappy. because they're on the spectrum. they. don't. understand how social interactions. really work they're very. uh anxiety provoking because they don't. know what to say they don't have any. clue how anybody else knows what to say. they're constantly worried they're going. to say something that's completely. inappropriate and so they're very. anxious and i can i can treat their. anxiety it doesn't touch the autism per. se but i can help them with their.

anxiety. what i just talked about eye contact. i. am richly even with eyes closed and all. those kinds of things i'm richly. experiencing the world and it's not like. you're afraid of the world or you're not. able i don't know what to do no i know. everything in fact i know way too much. there's so many cool options like at any. one moment. there's all the stuff happening and it's. all beautiful and at any one moment you. can do anything you want you can take. off your clothes you can punch that guy.

over there you can uh. run away you can go in for a hug you can. say something profound and deep or you. can say something generic or you could. use so many things you can say. and then and then it'll go it'll unravel. in all these kinds of ways and this. moment could be completely life-changing. or it can be mundane and meaningless and. all of those options are before you at. any one moment. and so that's amazing. it's amazing and overwhelming if you.

allow yourself to think about it yes. which uh what whatever exactly like well. unfortunately with chess you have a few. set options two-dimensional dimensions. constraints. there is unlimited possibilities and. unlimited beautiful things happening all. around you so i don't think there's a. kind of sense that somehow you're. limited. in your. in in the places. of uh. in the way you can see the world and how.

you can interact with that world i am. overwhelmed by. the lack of limit. that all of us should be have you looked. around you could do whatever the hell. you want nobody will remember you anyway. mo all of us will be dead one day you. could do anything. you can uh. i don't know you can get naked and run. around the city as long as you're not. hurting anybody and it doesn't matter. so it's austin anyway. exactly seems like uh a to-do item for.

anybody living in austin for sure. but you know the the spectrum is an. interesting concept because. that is you know when i say when i refer. to the spectrum. uh i'm actually referring to it's a. precise clinical term but you're right. it's been co-opted more broadly and it. is widely used and it can be. an unfair categorization of someone. who's. socially and occupationally very healthy. and that. is critical. because we we don't define a disorder.

unless there's social or occupational. dysfunction it doesn't matter what the. symptoms are i've had. patients who are pleasantly. hallucinating so frankly psychotic but. doesn't affect their lives so i don't. give that person. as diagnosis because there's not social. or occupational dysfunction. same with. any anything on this. you know any of the diverse symptoms of. autism spectrum disorder. if someone has them. but they're.

successful socially and occupationally. we don't say that there's a disorder. but then you're right the concept of the. spectrum does become a useful uh you. know pigeonholing um device which is. maybe not not the best thing. yeah and eye contact is interesting one. is interesting one i'm torn on it. talking about the usefulness of eye. contact because people kind of make fun. of it but. let me just say one thing about eye.

contact and about life in general it's. okay to be weird. but like some people when you have your. eyes closed and there's that weird what. is happening to this creature like you. see a weird creature on the side of the. road it's interesting yeah and you want. to i mean the the weird stuff i'm going. to go back to robin williams with the. that's the good stuff. right he has that whole speech about him. and his wife and what he loves all the. little peculiarities all the weird stuff.

and that like um. let those flourish yes uh let the like. celebrate those in yourself and not in. some kind of woke way but in some like. very human way this is what makes us. this is the weirdness yeah. i i'm 100. on board with that i and i don't think. you know. people who are. happy and who have. people in their lives. who are happy with them these are. i think let let the weirdness flourish.

let the let the. all the different ways members of the. human family can be different let's see. them all that's one of our. that's one of the joys of being alive is. seeing all the ways we can be human. and i i think about it all the time. why. do we have all these ways of being human. uh. and. even within one individual you go. through phases of life where you express. different. sides of your way of being which is also. a pretty fun opportunity right you can. go through.

phases where you're in one mode and. phases in another mode. and let that you know just. let that let that flourish too let the. ways that you can be you uh vary as well. i think that's important for people to. explore and i should. like because if you can address the uh. the. uh the internet but i i would like to. sort of ask the internet. to celebrate. the uh the the weirdness of people like.

that's. uh that's the robin williams uh. uh people call these imperfections but. they're not that's the good stuff for. any one individual person. find the weird stuff and celebrate it. as opposed to. what the internet often does which is. find the weird stuff. and criticize it. because when you criticize the weird. stuff you're creating conformity which. is another human thing.

but that that conformity creates a a. boring. world you want the weird. you want the crazy that's what fun is. made of that that that's the uh the. foundation of humor and. the all the ways in which we deal with. the with the with the suffering in the. world with the injustices in the world. is. like this like huge variety of weird. okay. uh.

yeah i don't know. and that's what at the depth of. psychiatry is like you want to. uh acknowledge the weird celebrate the. weird like step around it to find. the particular aspects of weird that are. debilitating like you said they're. somehow negatively affecting your. ability to function in the world as. opposed to trying to. shut it all down that's right. well on that topic i mean i'd love to. talk to you about schizophrenia.

what what is schizophrenia. from your research and from your general. understanding and what is the full. landscape of suffering. and uh. wisdom that schizophrenia explores. schizophrenia is a state where. there is a break from reality and so. this can show up as we call. them the positive symptoms of. schizophrenia. these include hallucinations. hearing something or seeing something.

that's not there usually auditory. hallucinations. paranoia people can have complex. fears delusions which we call fixed. false beliefs people get an extremely. unshakeable but completely implausible. idea about something sometimes it. relates to themselves sometimes to the. world. these we call the positive symptoms. break from reality as we know it. then there are the negative symptoms. that come with it and these are. progressive these are.

flattening of of emotion as we call it. so starting to express less and less. positive emotion ending more in a. neutral or flat state. thought disorder inability to. work with complex patterns of planning. or thinking so you can't make plans. you'd have poor working memory you can't. keep track of where you were. in a conversation. in a sequence of actions. so. poor.

and impaired working with the thoughts. of oneself and then these. these positive symptoms of break from. reality okay now why does why does this. why do these come together. what's the neurobiology of it again we. don't know schizophrenia extremely. genetically determined if you look at. the numbers could be upwards of 80. percent genetically determined. um. one percent of the human population. around the world it's it's universal. okay it's not confined to any one.

culture not even really biased in one. you know. culture another about one percent around. the world. and. has this progressive quality to it. untreated so it's very interesting. there's a break that happens we call it. first break. when. someone experiences their first. disruption of reality they can have a. completely typical life up into that. point so you might have a and i've seen. you know just heartbreaking cases of. like this like this in the.

stanford emergency room where a kid. who's come there has been. extremely. you know high functioning in that sense. of academic achievement and athletic and. interpersonal and then comes to college. usually in men it's it's around 18 19. when the first break happens. some terrifying. paranoia hits or some. auditory hallucinations start they're. getting screamed at by a voice in their. head so devastating. with women.

comes on also often a little later. sometimes in the 20s. and it can be progressive if it's not. treated. it just progresses and progresses the. the voices become. overwhelming the delusions and paranoia. extend and expand the thought the. negative symptoms particularly become. more and more severe. so one can't even. maintain thoughts in any sort of ordered. fashion. and then eventually uh you know it can. be fatal can lead to suicide it can lead.

to erratic behavior that leads to. accidents. now. it can be treated there are medications. that help uh. fortunately they have side effects so. they're not perfect you can have. movement problems and. uh. actually a whole host of different side. effects that come from the medications. but we can help people now with with. schizophrenia very very significantly. but the amazing thing and this is. emblematic of where psychiatry stands.

we don't have the deep understanding. just like with depression we don't have. that heart as a pump. level of understanding. that we'd like to have with. schizophrenia despite it being so. biological so genetic in its nature. so is there a way. once. a wait to return to the other side of. the first break. so when you have a break with reality. it's a way to kind of. stitch it together yeah so some people. that that works.

but we don't really know how so. medications antipsychotic medications we. call them they block a particular. neurotransmitter receptor called the. serotonin. 2a receptor. and they modulate dopamine as well and. other neurotransmitters. these can take someone who's actively. hallucinating actively paranoid put them. back in a completely normal state and. some people. stay that way.

indefinitely and so you can bring people. back from from that back to the other. side have it stitched together. more typically um. you'll end up in some intermediate state. where. there's a symptoms are reduced. powerfully but there might be still. something there and you've got a drop. down in. functioning that may be persistent for a. while. but. concepts what physically is going on one. idea is that. it's communication.

within the brain one part of the brain. is not able to tell other parts of the. brain what it's doing and so the. auditory hallucinations are very. interesting in this regard. they often have this conversational. inner monologue like quality as we're. walking along the street we may have an. inner monologue thoughts about what's. going on. if we see somebody we don't like we. might have a thought out where somebody. would punch that guy something like that. or maybe i should punch that guy but we. these are so far below. where we would ever you know act or even.

think of acting but they're just things. that come up and and people with. schizophrenia. those inner thoughts that inner. monologue is not recognized as the inner. monologue of the self and so it's it's. perceived as something coming from. the outside. uh or from inside but from a another. entity another. another room yeah inside the same. building another room on the inside.

there yeah yeah. and so that that's so it's a it's a it. could be conceptualized as a. communication within the brain problem. notifying what's another part of the. brain what's going on and there's some. evidence uh consistent with that. i don't know if you can help with this. but i sometimes. have been talking to quite a few. homeless folks recently just. that's what i do is i. hang out at night. um. and. uh talk to interesting people. and some of them and i've known people.

in the past who suffer from. schizophrenia and some of them like self. will describe. uh as as a as that as something they. suffer from. and they seem to understand something. deeply about this world. i don't know if it's correlated. or. or maybe it's it's another aspect of. like depression all those things that. i've encountered. in my own life. is maybe just the struggle and the.

suffering. has taken you through a life where you. think deeply about life like there's. like self-reflection. that society forces on you. because it's a disorder somehow or some. kind. is it interesting i i guess my only sort. of anecdotal observation is people who. suffer from schizophrenia. seem to be very interesting and. very thoughtful in a non-linear way. about the world. i've noticed that it's not always.

positive uh they're the unusual ways. they view the world it was. but it's always interesting it's uh it. could be conspiratorial thinking too. yeah like but like the the theories they. have about the way the world functions. it often very well read which is also. interesting. because they're almost like looking for. helpful answers from somewhere. absolutely and so they're you know they. might be citing some very interesting. literature and then using that.

um. there's a stickiness in their mind to. different models of the world and trying. to make sense of that world and those. models could include conspiracy theories. yeah. they're very attuned to complexity and. they come up with unlikely. explanations uh which is one of the. things that makes them it makes it hard. for them to function in the in the world. is how unlikely their explanations are. but but you're right there's a depth of. consideration of the complexity of the. world. and a concern about it and a work uh a.

an impulse to work to understand it that. is actually quite refreshing um. but. you know the first case in the medical. literature. uh there was a. classical schizophrenia. there was a patient named james tilly. matthews who. had this uh he sketched out for his. doctor the. uh experiences he was he was. sensing and he drew himself as a. a cowering figure on the ground.

controlled. by a loom a weaving device that was. sending threads. long threads projections across space. from the loom to him to his arms and to. his body and controlling him. from afar. and he called this the heirloom. a loom in the air. and. it was such an evocative thing because. you know this was the start of the. industrial revolution or mid and it was. where you know. really industrial strength.

you know looms and weaving devices were. really uh kind of the. emblematic of the most. complex. powerful technological achievements of. the time and so that was the explanation. available to him to explain how. his body was seemingly moved without his. volition uh. and these days of course people with. schizophrenia will have more. technology appropriate interpretations. they'll. have a. you know delusions of satellite or alien.

control or. beamed information very very common to. have this delusion of. a government agency. you know sending electromagnetic or or. radio frequency information to control. their limbs. but it's this it's the same thing it's. that whether it's a thread from an. industrial revolution loom. or. you know rf you know radiation it's the. same thing just adapted to the to the. moment explaining trying to explain the. world they live in in their relationship. to the world but unconstrained by sort. of.

the thing that's socially acceptable. which is that's right both refreshing. and dangerous yes. i wrote down a question. why do we cry. our tears a window into some depths that. we ourselves don't know. i almost want to make fun of myself for. that question but you do talk seriously. about crying in the book in fact the. whole first chapter really really. tussles with crying as a as why do we do. it what does it mean why is it. involuntary it seems like a weakness.

right it's because it's so involuntary. and it's reflecting something true and. inside. at the level of the individual that. seems like a problem right wouldn't it. be better if we could control it if if. we could. not show that emotion. when it's not useful show it when it's. useful but it's not it's it's largely. involuntary. and so. there's a value to it i think as an. honest reporter of a need of hope.

and frailty at the same time i i'm a. human being. there's a. frail. a frailty to myself or my situation. where i need social help i need help. from my community. i have hope that that is possible. uh but. i'm not enough for myself i need the. community that that i think is what the. the social signal of crying is now. people have studied crying. uh it's an extreme you can you can. quantify.

the extent to which the presence of. tears on a face. triggers. reactions in onlookers and. and you can show the same face in the. presence or absence of tears and show. that to to people under quantifiable and. rigorous uh you know. psychological conditions. and. tears are much more powerful at stirring. the desire to help. in. viewers than any other. facial uh feature.

which is pretty interesting that it's. the it's the honest one that's also the. most powerful right it kind of indicates. there's a certain logic to our design. at as social beings that we have an. honest. report. that's hard to uh hard to control and. but is it is it well understood. what how that connects to. the internal state. of emotion yeah. there are. long-range projections that come so.

where where is crying generate this is. the confusing thing about it so that we. have a little tear duct the lacrimal. gland that leads to the release of fluid. it ejects fluid and it comes out and. those of course. that whole system was designed to keep. the eye clean to wash out particulate. irritants so it's it's a long standing. as long as we've had eyes and have been. out of the water. uh in our evolution we've needed this. sort of thing so long-standing. biological structure recently co-opted. it seems by our evolution as social uh.

primates. now how could that happen well the. lacrimal gland is controlled by. structures in the ponds which is a. structure deep in our. just above our neck between our neck and. our head. and reflecting its ancient origin right. as you go farther down toward the spinal. cord these are the more basic early. evolved structures and and in the ponds. that's where breathing is controlled. tear. duct uh contraction.

and. what we found and with optogenetics we. helped sort this out there are long. range projections from fear and anxiety. regions in the forebrain. that project all the way to the ponds in. and around those areas the reason those. are there. we think is to regulate the respiratory. rate changes the breathing changes of. fear and anxiety so we know when we're. in a state of fear and anxiety we need. we cope better if we have elevated heart. rate elevated respiratory rate more.

blood pumping around more oxygenated. blood we're ready to meet the threat if. it happens. all those cells are down there in the. ponds too right next to. the lacrimal gl duct the tear gland. neurons and so almost certainly this. fear anxiety anxiety-induced. crying arose from a very slightly. misdirected long-range projection that. was there. to regulate. breathing and a little twist just a. little misdirection a little missing.

of one sign post to stop here and going. on a little farther. getting to the lacrimal gland neurons. gave us crying. and that's and we just have it that. peculiar sort of structure neuronal. structure that resulted in that that's. that's that's what we're stuck with and. then and ends up being in terms of. social interaction one of the more. important. uh authentic. involuntary displays of interstate. that's right and social communication.

oh. yeah is there other stuff like that i. mean do you. yeah i mean the human face is. fascinating as a display of emotion as a. display of. truth and lying and all those kinds of. things i personally. i mean we're all. i suppose. have different. uh sensors that are sensitive to certain. aspects of the human face but to me it. seems like uh the eyes are really. important communication or something.

you know i've talked to a few sort of. girls about like botox and stuff like. that it always bothers me when i guess. guys could do this too but like. when women. speak negatively of i guess you can call. them wrinkles. at the uh at the tips of of an eye but. like to me when you smile. when you. wait not wink but like narrow the eyes. to community something is communicating. and those that stuff is really useful.

the human face and when it's gone that. something is missing and a lot of little. stuff it feels like can really it's. almost involuntary i guess but it's. harder to describe as the presence or. absence of tears it's like something. about this person you can tell they're. not bullshitting you yeah yeah. and so that was that was what made. presumably that that. tier recruitment so powerful is it just. landed in this very. high value real estate for social. communication if it had gone to you know.

there's a lot of. neurons in the in the ponds that control. you know movement of. large you know muscles uh you know. elsewhere that would have been much less. effective as a social signal than. something around the eye so it was. however that that little misdirection. happened it it landed in a great area. for social communication. and because it was coming from the fear. and anxiety. circuits that regulate that necessary. involuntary change in. heart rate and respiratory rate it also. was involuntary and that became valuable.

as a as a truth signal as social beings. so. very interesting when you think about. the origins of the human family the. origins of social. structures and our ability and need to. call for help when there's hope. but but need at the same time. what is consciousness. bro so you're actually using techniques. i mean even putting psychiatry aside. just looking. at optogenetics.

you're trying to understand some of. these deep aspects of the human mind. and maybe this is a good time to return. to a question you mentioned. you might have an opinion on if there's. such a thing as a theory of everything. for the human mind. because surely answering of what is. consciousness is as. well that's not sure. but it seems like it's a fundamental. part of the human. experience in the human mind and solving. that question. will result in solving.

the bigger thing about the human mind. the flip side could be consciousness. it's just the few neurons that are. generating some useful thing that make. us it's like uh. the the sense of self that you talked. about in the uh in the mice maybe it's a. subset of those cells that are just. creating a richer sense of self and. that's it. so. this is a great question. all neuroscientists think about this and. a lot of non-neuroscientists too it's.

it's such a. it's the reason a lot of people came to. the study of the brain is to think about. consciousness and not just. being awake or alert but really. what's sometimes called the hard problem. of consciousness which is. what is that nature of that inner. subjective sense we have not just. information processing. but feeling something about the. information that what is that inner. state of subjectivity physically what is. it.

and that's called the hard problem of. consciousness and. it's not an extremely well-defined. question everybody has sort of a sense. of what it means. but. it's such a hard problem because you run. into paradoxes quite quickly the more. you think about it and that. is exciting also because it makes us. think actually there's some. there's a big thing that we're missing. the brain is not just a collection of.

little tricks there is a big. big concept so that's your sense of. because like a flip side could be with. optogenetics you can. there's an engineering question can you. turn consciousness on and off like a. light switch okay so here here's where. exactly consciousness frames the problem. extremely well and it frames it the. following way so i told you earlier that. we can stimulate 20 or 25 cells in. the visual cortex of a mouse and we can. make it.

behave and we can make its brain act as. if it's seeing something that isn't. there we have that level of control now. we can pick out 25 neurons play an. activity. in both behavior and in the brain it's. as if it's seeing something specific. okay. now let's do a thought experiment you. know a good duncan experiment and let's. play this out. let's say we could do the same thing for. every single neuron in the brain of a. human being let's say we had total. control. and i could do something like i could.

show you. a rich deep color red and you could look. at it and you would be aware that it's. red but also you might have some. feelings about it some something would. be stirred in you some subjective sense. as you looked at that rich color red. and then. i would take away. the visual stimulus and i would in this. thought experiment i would. using some hyperoptogenetics i would. play in. exactly the same pattern of activity in. every cell in your brain. for as long as it was needed whatever 15.

seconds something like that. that exactly matched. what was going on when you were feeling. that inner subjective sense. okay so in that thought experiment a. question for you is would you. be feeling that same inner subjective. sense stimulus is gone every neuron's. doing the same thing because i'm. controlling it. there's a philosophical question there. i'm if if you ask me specifically i. would say yes. okay good most people would say that.

because it's hard to say no right it's. very hard to say if every cell in your. brain is doing what it was doing. what what else could be different how. could most normal people would say yes. of course philosophers would then. start saying no they're they're the ones. that say. um i'm i'm going to sort of to parallel. and sorry if it's a bit of an. interruption but if there's you know if. there's a robot that's conscious in. front of you. if it appears conscious.

then. it's conscious like to me. uh of course philosophers again speak up. and say well no how do you know it's. conscious well. how do you know anything is conscious. and sort of as normal humans. we tend to uh. lean on the experience versus some kind. of. philosophical concept. so the great thing about the the what. you just said the the turing test is. it's very practical if it acts conscious. it is conscious.

but i think that's limiting i like the. the thought experiment i think it's. actually more informative and so i'm. halfway halfway to the to the conclusion. there but let's let's let's take it as. your answer was yes that's that you. would be feeling the same thing okay. now here's where it gets fun. now that every cell in your brain. is knows what it has to do in the sense. that we know it and we're providing it.

your brain cells don't need to be in. your head anymore at all right. the only reason they're next to each. other the only reason they're wired. together is to affect each other to. stimulate or inhibit each other. but we don't need that anymore because. optogenetically we're providing that. activity pattern for as long as needed. we're providing the effect of the. communication they don't need to be. connected anymore. they don't even need to be in your head. i could spread your neurons. all over the continent all over the. galaxy.

and i could still provide. the same stimulus pattern over 10 or 15. seconds to all those neurons and. somewhere lex friedman would be. would have to be even though no longer. existing as a. physical object anymore would be feeling. that subjective feeling. and it's inescapable because it's. exactly the same as the previous. situation all the neurons have to be uh. spatially. like the locality constraint they have. to be spatially close to each other. uh.

and you talk about light opto which is. funny because you know light. is the fastest traveling thing that we. know of. well maybe let's not put them all over. the universe because we might get. relativistic problems then let's let's. just keep them on let's keep all your. neurons let's spread them over north. america okay and let's let's play them. out. same pattern of activity. and right it seems absurd right there's. no way that could be true there's no way. that that that lex would be feeling that. internal sense if his neurons were.

spread all over north america. and yet it's exactly the same as the. previous situation where you said sure. wow so we've got a paradox and it and. this is what makes people say paradox. though sorry. yeah yeah maybe products is the wrong. word we got a problem. we got a problem because it reveals. that. there's something big. about. those that internal subjective state. that we we're not explaining and we. don't really have a hope of explaining. in the near future but don't you think. we would still have that. it's just the word internal loses.

meaning but don't you think we still. have that internal subjective state. where's. uh. if not then where the heck is the magic. coming from. okay well i just think. i think they're one one of the problems. that i think we need to let go of. is we tend to. outside of the experience of. consciousness the heart problem of. consciousness. we tend to think that we individual. humans are really special.

not the subjective experience but the. entirety of it like the body. that contains the things so the local. the the constraint of all the stuff has. to be together and it's all mine. that's a very. i don't know if that has anything to do. with the mechanisms that are creating. this. so i and in fact one really nice way. to break through that is to. either achieve either observe or create.

consciousness that spans. multiple organisms. sort of so like that say it's not. it's not an organism-dependent. uh phenomena that the phenomena can. that's just a peculiar way it has. evolved. on earth. but it's it's a it's a phenomena that. doesn't have anything to do with a. specific. biological system.

all right so and we have different parts. of. our brain exist and sometimes. create. complex awarenesses. of things that involve. different. neurons that are distributed widely and. that need to communicate with each other. to form this joint representation the. state of consciousness. but indeed why do they have to be in the. same. head we don't. know why that would be the case that.

they do. and so that's a. huge. unanswered question in the field is is. what is it. that binds. the activity of neurons together so they. can form a joint representation and. actually this comes back to the. dissociation experiment we talked about. before where you can your sense of self. becomes separated from your your. your body. those things that were refused in a. joint representation the same concept. unitary. are now separate.

and. in late 2020 we published a paper in. nature showing how this could be. we used optogenetics to. drive this rhythm that ketamine and pcp. cause in retrospinal cortex and we got. different parts. of the brain to be out of sync and when. they were active. never able to be active at the same time. never able to form. a joint representation at the same time. and so we've got a toehold into these. questions we don't have the answers but. and that mimics the dynamics of ketamine.

effects exactly exactly and you're able. to find that kind of oscillation that. wow wow wow let's see if you get even. greater and greater control. with more control over individual. neurons and understanding. like if you think of certain neurons. that having some. role to play in in the sense of self you. can play like an orchestra. um that to create this certain degrees.

of consciousness decreases subjectivity. and thereby. understand what is consciousness. but. by having a very complicated light. switch essentially. that and here's the here's the challenge. is. the nice thing about the the thought. experiment is it it kind of highlights. that we're going to hit a point where. we're. addressing some very very fundamental. questions what what. what allows the activity of.

two sets of neurons. to become mutually relevant to each. other. this is this is in some ways. maybe the. one of the deepest remaining questions. in neuroscience is is what allows. activity patterns to become. relevant to each other. do they have to be in sync temporarily. do they need to be. is there some other. quality that we don't know about that. also needs to be present to allow cells. to to fuse together into a joint.

representation. just just so i understand because it uh. it feels. close to some very very deep idea. so there's a bunch of semi-distributed. signals going on in the brain. and. you're saying there could be. something like a theory of everything if. one to exist is to understand why how. and why signals close to each other.

start becoming. relevant to each other that's right. that's right as part of some very much. bigger signal that they're producing. that's right how they coordinate. essentially. um. because it's very distributed i mean. that's a kind of. within a distributed system how is order. achieved. and this is a very specific kind of. distributive system that is one of the.

most intelligent that we're aware of. in the known universe. and that would maybe be something also. an understanding of the the full. conscious experience too. that this kind of coordination how does. the coordination between different. neurons that are responsible for sense. of self. how do they begin to form a big picture. that we see as a human experience. that's really really interesting so. uniting the small and i mean. that's actually literally theory of. everything.

uniting the small the sort of the theory. of the neuron. um the functioning of the neuron with. the big. just the um. the functioning of the entire mind. that's right and i think keeping a toe. hold in both at the cellular level of. resolution. and the brain wide resolution will be. critical if you lose touch with either i. think you'll miss the big. insight so that's what we're trying to. do. keeping our. keeping grounded in the cellular. resolution trying to keep the the.

broadest brain wide perspective. and meet in the middle. do you think you'll see it in your. lifetime a major breakthrough in that. dimension i have hope i have hope i'm. i'm uh it's very hard to predict what. will happen with with big things like. this. if we don't get there there'll be plenty. of other exciting stuff so it's okay. but the other aspect of this whole thing. is that your life is pretty short. that's true so first of all you can die. any day. i tend to try to think about that that.

it ends and get in at any moment because. it really really can and if not it'll be. soon anyway do you think about that do. you think about your mortality. i do yeah it's it comes back to what we. talked about earlier i. you know i never think i've done enough. and it's it's relevant to that for sure. there's a deadline yeah. do you think there's ever going to be a. feeling where you sit back and you're. really proud of yourself.

i hope so. like i've done enough i've done. everything there is like like you know. because the thing is. a warrior has some number of battles in. them. and at a certain point if you're deeply. honest it's like well this that was a. pretty good run. as far as runs goes that was pretty good. you can hang up your helmet. and then. go sort of drink some ale.

listen to some music. with the old lady yeah i'd say i did. pretty good you think you'll get there. i i you know with something. with nature always has surprises for us. we're always the curious mind is always. after more. but yeah true but biology gives us other. rewards you know. children and. family community um and and one can feel. good about those things.

biology is full of rewards but do you. think. uh about those rewards what do you think. is the why of those rewards what's the. meaning of life and this existence. what's uh. what's the why of biology. what does it want from us why are all. these cells very busy. putting together an organism that seems. to want to. just be in a hurry to do stuff and. survive but it also just doesn't it's. not happening being survived like you. said it's curious. it keeps wanting to get into more.

trouble. why. yeah that you know. that we're clearly designed for that. right this is we're clearly designed to. to ask why and to answer and and that i. think is. i don't i don't know the meaning of all. life. i think a meaning of our lives is that. and you know this is the the. aristotelian you know happiness this is. an organism is happy an animal's happy. if it's performing to its design right. if it's it's. he's doing what it was made for. yeah well you have to understand what.

what's what's the design. and. uh. you know. who's the designer and. what were they up to. and. how hard is it do you have to build the. whole universe and does the design even. know what the hell they're doing because. uh. you know maybe the designer built. humorous to find out. about themselves. that's what i would do like if i had the. power to build clones.

i'll build a lot of clones and i'll get. them into different trouble. to understand. like what am i design what's this body. designed to do how far can i go that way. exactly. and then and i dissociate myself. completely from having anybody to know. like that i know that person that's good. i mean i suppose you could do that in a. single person's body but dissociation. you can you could yeah. well but i do wonder what.

if you if you look at earth. as a collection of humans as the. collection of biological organisms it. seems that we're busy doing something. and. it just seems too beautiful and too. special to be a random. a random experiment. it seems like it's an experiment that's. cleverly designed. that's right. by by some forces of nature that are.

beyond our current understanding and. maybe that's part of our design is to. keep asking why he said answer i'm not. sure that's part of the design. the answer. no i think we're given just the. sufficiently limited cognitive. capability that. we know how to long to to find the. answer and we lack the ability to find. the answer. that's basically a summary of your. career no i'm just kidding um and then. we give each other nobel prizes for for.

having even an inkling of a. good step towards the right direction. carl you're an incredible human being um. i'm a huge fan of who you are as a. person who you are as a scientist who. you are as a writer i. just thank you so much i'm so honored. that you would sit down and talk to me. today it was amazing it's been. incredibly fun uh let's do it again. sometime it's been really great your. your insights and wit and and. modesty are really uh. quite rewarding thank you so much.

thanks for listening to this. conversation with carl diceroth to. support this podcast please check out. our sponsors in the description and now. let me leave you with some words from. carl young. knowing your own darkness is the best. method for dealing with the darkness of. other people. thank you for listening and hope to see. you. next time. you.