Understanding & Healing the Mind | Dr. Karl Deisseroth

welcome to the hubermann lab podcast where we discuss science and science-based tools for everyday life i'm andrew huberman and i'm a professor of neurobiology and ophthalmology at stanford school of medicine today i have the pleasure of introducing the first guest of the huberman lab podcast my guest is dr carl deisseroth dr carl deisseroth is a medical doctor he's a psychiatrist and a research scientist at stanford school of medicine in his clinical practice he sees patients dealing with a range of nervous system disorders including obsessive compulsive disorder autism attention deficit disorders schizophrenia mania anxiety disorders and eating disorders his laboratory develops and explores tools with which to understand how the nervous system works in the healthy situation as well as in disorders of the mind dr dyseros laboratory has pioneered the development and use of what are called channelopsins proteins that come from algae which can now be introduced to the nervous systems of animals and humans in order to precisely control the activity of neurons in the brain and body with the use of light this is a absolutely transformative technology because whereas certain drug treatments can often relieve certain symptoms of disorders they often carry various side effects and in some individuals often many individuals these drug treatments simply do not work the channel options and their related technologies stand to transform the way that we treat psychiatric illness and various disorders of movement and perception in fact just recently the channel options were applied in a human patient to allow an adult fully blind human being to see light for the very first time we also discussed dr daiseroth's newly released book which is entitled projections a story of human emotions this is an absolutely remarkable book that uses stories about his interactions with his patients to teach you how the brain works in the healthy and diseased state and also reveals the motivation for and discovery of these channelopsins and other technologies by carl's laboratory that are being used now to treat various disorders of the nervous system and that in the future are certain to transform the fields of psychiatry mental health and health in general i found our conversation to be an absolutely fascinating one about how the brain functions in the healthy state and why and how it breaks down in disorders of the mind we also discuss the current status and future of psychedelic treatments for psychiatric illness as well as for understanding how the brain works more generally we also discuss issues of consciousness and we even delve into how somebody like carl who's managing a full-time clinical practice and a 40-plus person laboratory and a family of five children and is happily married how he organizes his internal landscape his own thinking in order to manage that immense workload and to progress forward for the sake of medicine and his pursuits in science i found this to be an incredible conversation i learned so much i also learned through the course of reading carl's book projections that not only is he an accomplished psychiatrist and obviously an accomplished research scientist and a family man but he's also a phenomenal writer projections is absolutely masterfully written it's just beautiful and it's accessible to anybody even if you don't have a science background so i hope that you'll enjoy my conversation with carl deisseroth as much as i did and thank you for tuning in before we begin i want to point out that this podcast is separate from my teaching and research roles at stanford in my desire and effort to bring zero cost to consumer information about science and science related tools to the general public i'd like to acknowledge the sponsors of today's podcast our first sponsor is roka roka makes eyeglasses and sunglasses that in my opinion are the very highest quality out there the company was founded by two all-american swimmers from stanford 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is such that you could really wear them anywheres indoors or outdoors if you'd like to try roka eyeglasses you can go to roca that's roka.com and enter the code huberman to save 20 on your first order that's roca roka.com and enter the code huberman at checkout today's podcast is also brought to us by inside tracker inside tracker is a personalized nutrition platform that analyzes data from your blood and dna to help you better understand your body and reach your health goals i am a big believer in getting regular blood work done and now with the advent of good genetic dna tests i'm also a believer in analyzing your dna the simple reason for this is that many of the factors that impact our immediate and long-term health can only be measured and evaluated with a quality blood test and now the dna tests further inform our immediate and long-term health one of the problems with a lot of dna tests and blood tests out there however is that you get the information back and you don't know 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year's supply of vitamin d3 and now my conversation with dr carl deisseroth well thanks for being here thanks for having me it's been a long time coming for me uh because uh you may not know this but one of the reasons i started this podcast was actually so i could have this conversation it's it's but one there are other reasons but one of the goals is to be able to hold conversations with colleagues of mine that are doing incredible work in the realm of science and then here we also have this really special opportunity because you're also a clinician you see patients and have for a long time so for people that might not be so familiar with the fields of neuroscience etc what is the difference between neurology and psychiatry well you know i'm married to a neurologist and i am a psychiatrist and we make fun of each other all the time so this is a lot of neuroscientists and a lot of brain clinicians actually think these two should be the same field at at some point in the future they were in the past they started together psychiatry though uh focuses on disorders where we can't see something that's physically wrong where we don't have a measurable there's no blood test that makes the diagnosis there's no brain scan that tells us this is schizophrenia this is depression for an individual patient and so psychiatry is is much more mysterious and the only tools we have are words neurologists are fantastic physicians they see the stroke on brain scans they see the seizure and the pre-seizure activity with an eeg and they can measure and treat based on those measurables in psychiatry we have a harder job i think we use words we have rating scales for symptoms we can measure depression and autism with rating scales but those are words still and ultimately that's what psychiatry is built around it's it's an odd situation because we've got the most complex beautiful mysterious incredibly engineered uh object in the universe and yet all we have are words to to find our way in so do you find that if a patient is very verbal or hyperverbal that you have an easier time diagnosing them as opposed to somebody who's more quiet and reserved or it's i can imagine the opposite might be true as well well it because we only have words you put your finger on a key point if they don't speak that much in principle it's harder the lack of speech can be a symptom we can see that in depression we can see that in the negative symptoms of schizophrenia we can see that in autism sometimes by itself that is a symptom of a reduced speech but ultimately you do need something you need uh some some words to help guide you and that in fact there's challenges that i can tell you about where patients with depression who are so depressed they can't speak that makes it a bit of a challenge to distinguish depression from some of the other reasons they might not be speaking and this is a sort of the art and the science of psychiatry um do you find that there are patients that have well let's call them comorbidities or conditions where they would land in both psychiatry and neurology meaning uh there's damage to a particular area of the brain and therefore they're depressed and how do you tease that out as a psychiatrist yeah this happens all the time parkinson's disease is a great example it's a it's a it can be debilitating in so many ways people have trouble moving they have trouble walking and trouble swallowing and they can have truly severe depression and this is you might say oh well they've got a life-threatening illness but there are plenty of neurological disorders where depression is not a strong strongly comorbid symptom like als lou gehrig's disease for example depression is not a strong strongly co-morbid in that disease but in parkinson's it is extremely common and as you know in parkinson's disease we have loss of the dopamine neurons in the in the midbrain and this is a very uh you know specific population of cells that's dying and probably that leads to both the movement disorder and the depression there are many examples of that where these two fields come together and you really need to work as a team i've had patients in my clinic that i i treat the depression associated with their parkinson's and a neurologist treats the movement associated with the parkinson's and we work together do you think will you will ever have a blood test for depression or schizophrenia or autism and would that be a good or a bad thing i think ultimately there will be quantitative tests uh already efforts are being made to look at certain rhythms in the brain using external eegs to look at brain waves effectively look at the ratios of certain frequencies to other frequencies and there's some progress being made on that front uh it's not as good as it could be it doesn't really give you the confidence for the individual patient that you would you would like but ultimately what's going on in the brain in psychiatric disease is physical and it's due to the circuits and the connections and the projections in the brain that are not working as they would in a typical situation and i i do think we'll have those measurables at some point now is that good or bad uh you know i i think that will be good one of the challenges we have with psychiatry is it is an art as well as a science to elicit these uh symptoms uh in a precise way it does take some time and it would be great if we could just do a quick measurement could it be abused or or misused certainly but that's i think true for all of medicine i want to know and i'm sure there are several but what do you see as the biggest challenge facing psychiatry and the treatment of mental illness today i think we have uh we're making progress on what the biggest challenge is which i think there's still such a strong stigma for psychiatric disease that uh patients often don't come to us and they feel that they should be able to handle this on their own and that that can slow treatment it can lead to you know worsening symptoms we know for example patients who have untreated anxiety issues if you go for a year or more with a serious untreated anxiety issue that can convert to depression you can add another problem on top of the anxiety and so it would be you know why do people not come for treatment they they feel like this is something they should be able to master on their own uh which which can be true but uh usually uh some help is is is a good thing that raises it a question related to something i heard you say many years ago at a lecture which was that um this was a scientific lecture and you said you know we don't know how other people feel most of the time we don't even really know how we feel i mean we could elaborate on that a little bit and the the um dearth of of ways that we we have to talk about feelings i mean there's so many words i don't know how many but i'm guessing they're more than a dozen words to describe the state that i call sadness but as far as i understand we don't have any way of comparing that in a real objective sense so how as a psychiatrist when your job is to use words to diagnose words of the patient to diagnose do you maneuver around that and what is this landscape that we call feelings or emotions this is uh really interesting uh people here we have a there's a tension between the words that we've built up in the clinic that mean something to the to the physicians and then there's the colloquial use of words that may not be the same and so that's the first level we have to sort out when someone says you know i'm i'm depressed uh what exactly do they mean by that uh that may be different from from what we're talking about in terms of depression so part of psychiatry is to get beyond that word and to get into how they're actually feeling get get rid of the the jargon and get to real world examples of of how they're feeling so you know how do you what how much do you look forward into the future how much uh hope do you have how much planning are you doing for the future so these here now you're getting into actual things you can talk about that are unambiguous if someone says yeah i can't even i can't even think about tomorrow i i'm not i don't see how i'm going to get to tomorrow that that's a nice precise thing that you know it's it's sad it's tragic but but it's also that means something and we know what that means that's the hopelessness symptom of depression and and that is what i try to do when i do a psychiatric interview i try to get past the jargon and get to what's actually happening in the patient's life and in their mind but as you say ultimately you know this shows up across i i address this issue every day in my life whether it's in the lab where we're looking at animals whether fish or mice or rats and studying their behavior or when i'm in a conversation with just a friend or a colleague or when i'm talking to a patient i never really know what's going on inside the mind of the other person i get i get some feedback i get words i get behaviors i get actions but i never really know and as you said at the very beginning of the question you know often we don't even have the words and the insight to even understand what's going on in our own mind i think a lot of psychiatrists are pretty introspective that's part of the reason they end up in that specialty and so maybe we spend a little more time than the average person thinking about what's going on within but it doesn't mean we have answers so in this uh area of trying to figure out what's going on under the hood through words it sounds like certain words uh would relate to this uh this idea of anticipation and hope um is it fair to say that that somehow relates to the dopamine system in the sense that dopamine is involved in motivated behaviors i mean is that an if i say for instance and i i won't ask you to run a session with me here for free um we'll do that off camera okay right um if i were to say you know i i just can't imagine the tomorrow i just i i just can't do it so that's that's not action based that's purely based on my my internal narrative um but i could imagine things like you know i i have a terrible time sleeping i'm not hungry i'm not eating so statements about physical actions i'm guessing also have um validity absolutely and there are now ways to measure the accuracy of those statements like for instance if i gave you permission you could know if i slept last night or whether or not i was just saying i had a poor night's sleep yes that's right so in moving forward through 2021 and into the next 10 and 100 years of psychiatry do you think that the body reporting some of the actions of a human are going to become useful and and m mesh with the words in a way that's going to make your job easier i do think that's true and these the two things you've mentioned eating and sleeping those are additional criteria that we use to diagnose depression these are the vegetative signs we call them of depression poor sleep and poor eating and if you have a baseline for somebody that's the real challenge though what's different in that person some people with depressed they sleep more some people who are depressed they sleep less some people who are depressed they're more physically agitated and they move around more some people who are depressed they move less even while they're awake and so you need here's the challenge is you can't just look at how they are now you have to get a baseline and then see how it's changed and that can be a challenge that raises you know ethical issues how do you how do you collect that baseline information from someone healthy i don't i don't think that's something we have solved of course you know with phones and accelerometers and phones you could in principle collect a lot of baseline information from people but that would have to be uh treated very uh carefully for privacy reasons and in terms of measuring one's own behavior you know i i've heard of work that's going on sam golden up at the university of washington um who works on aggression and animal models was telling me that there's some effort that he's making and perhaps you're involved in this work as well i don't know of um devices that would allow people to detect for instance when they're veering towards a depressive episode for themselves that they may choose or not choose to report that to their clinician maybe they don't even have a clinician maybe this person that you referred to at the beginning uh this person who doesn't feel comfortable coming to talk to you they um maybe something is measuring changes in the inflection of their voice or the the speed at which they get up from a chair do you think that those kind of metrics will eventually inform somebody hey you know you're in trouble this is getting to this question of the back to the statement that i heard you make and wrong in my mind now i think for more than a decade which is oftentimes we don't even know how we feel yeah you know that that i do like because that gives the patient the agency to to detect what's going on and even separate from modern technology this has been part of the the art of psychiatry is to help patients realize that sometimes other people observing them can give them the earliest warning signs of depression we see this very often in in family they'll notice when the patient is changing before the patient does and then there are things the patient may notice but not correctly ascribed to the onset of depression and a classic example of that is what we call early morning awakening and this is something that can happen very early as people start to slide into depression they start to wake up earlier and earlier you know just inexplicably they're awake this is like 2 a.m 3 a.m it could start yeah it could start at 5 00 a.m could go to four and unable to fall back asleep and they will fall back asleep exactly uh so that's and that they may not know what to do with that it could just be from their perspective it's just something that's happening but if you put enough of that information together that that could be a useful warning sign for the patient and it could help them seek treatment and i think that is a something that could be really valuable interesting so in this framework of you know needing words to self-report or machines to detect how we feel or and maybe inform a psychiatrist uh how a patient feels i want to touch on some of the technologies that you've been involved in building but as a way to march into that are there any very good treatments for psychiatric disease meaning are there currently any pills potions forms of communication that reliably work every time or work in most patients and could you give a couple examples of great successes of psychiatry if they exist yes yeah we are fortunate in this coming back to my uh you know the the joking between my wife and myself in terms of neurology and psychiatry we actually in psychiatry despite the depths of our the mystery we struggle with many of our treatments are actually you know we're we may be doing better than some other specialties in terms of actually causing you know therapeutic benefit for patients we do help patients you know the patients who suffer from by the way both medications and talk therapy have been shown to be extremely effective in many cases uh for example people with panic disorder cognitive behavioral therapy just working with words helping people identify the early signs of when they're starting to move toward a panic attack what are the cognitions that are happening you can train people to derail that and you can very potently treat panic disorder that way how long does something like that take for on average for a motivated insightful patient you can have a very uh you know cookbooki series of sessions you know six to twelve sessions or even less for someone who's very uh insightful and motivated and it can have a very powerful effect that quickly and that's just with words there are many psychiatric medications that are very effective for the conditions that they're treating antipsychotic medications they have side effects but boy do they work they really can clear up particularly the positive symptoms of of schizophrenia for example the auditory hallucinations the paranoia people's lives can be turned around by these um we should clarify positive symptoms you mean not positive in the in the qualitative sense you mean positive meaning that the appearance of something abnormal exactly yeah thank you for that clarification when we say positive symptoms we do mean the addition of something that wasn't there before like a hallucination or a paranoia and that stands in contrast to the negative symptoms where something is taken away and these are patients who are who are withdrawn they have what we call thought blocking they can't even progress forward in a sequence of thoughts uh both of those can be part of schizophrenia the the hallucinations and the paranoia are more effectively treated right now but they are effectively treated and then you know this is a frustrating and yet heartening aspect of psychiatry there are treatments like electro controls electroconvulsive therapy which is where you know it's extremely effective for depression we have patients who nothing else works for them or they can't tolerate medications and you can administer under very safe controlled condition where the patient's body is not moving they're put into a very safe situation where the body doesn't move or seize it's just an internal process that's triggered in the brain this is an extraordinarily effective treatment for treatment resistant depression at the same time i find it as as heartening as it is to see patients respond to this with with uh who have severe depression i'm also frustrated by it why why can't we do something more precise than this for these very severe cases and people have sought for decades to understand how is it that a seizure is leading to the relief of depression and we don't know the answer yet we would love to do that people are working hard on that but that is a treatment that does work too uh all in all these cases though in psychiatry the the frustrating thing is that we don't have the level of understanding that a cardiologist has and thinking about the heart you know the heart is we now know it's a pump it's pumping blood and so you can look at everything about how it's working or not working in terms of that frame it's clearly a pump we don't really have that level of what what is the circuit really there for in psychiatry um and that's that's what is missing that's what we need to find so we can design truly effective and specific treatments so what do you what are the pieces that are going to be required to cure autism cure parkinson's cure schizophrenia i would imagine there are several elements in bins here understanding that the natural biology understanding what the activity patterns are how to modify those maybe um you could just tell us what you think what is the the bento box of the perfect cure yeah i think the first thing we need is understanding we need we need is almost every psychiatric treatment has been serendipitously identified just noting by chance that something that was done for some person also had a side effect like lithium like lithium is a good example is it true that it was the the urine of guinea pigs given lithium that was given to manic patients that made them not manic is that true i don't have first-hand knowledge of that but uh i would i would defer that but it's it's true for essentially every treatment you know that the antidepressants originally you know arose as anti-tuberculosis drugs for example do not know that yeah and so this is a it's a classic example for uh uh and this is across all of psychiatry um and of course there's the seizures as well that was noticed that patients who had epilepsy they or had a seizure there and also had depression that they became much uh at least for a while they were improved after the seizure that's amazing i don't want to take you off course of the question that uh answering the question i asked but um i've heard before that if autistic children get a fever that their symptoms improve is that true i've i've done a fair bit of work with autism in my clinical practice i work with adult autism and i have heard uh statements like that and descriptions like that from from patients and their families um it's uh it's that is very hard to study quantitatively because often with the children you have this not as quantitative as you'd like collection of symptom information uh from from uh from home but i have heard that enough that i think there there may well be something to that and you know what is anytime you have a fever what's going on well we know all the cells in the brain and i know this as an electrophysiologist if you just change the temperature by a few degrees everything changes about how neurons work and that's even just a single neuron it's even more likely to be complex and different with a circuit of neurons that are all affecting each other just elevate the temperature a little bit everything's different and so it's it's plausible for sure that things like that could happen and do happen now but and yet when you think about autism to take your example yes we see changes but what is the element in the brain that's analogous to the pumping heart when we think about the symptoms of depression that's maybe you know we think about motivation and dopamine neurons when we think about autism it's a little more challenging you have there's a deficit in social interaction and in communication and so where is that where is this where is that situated what is the key principle uh governing the social interaction um this is where we need the basic science to bring us a step forward so we can say okay this is the process that's going on this is what's needed for the incredibly complex task of social interaction where you've got incredibly rich data streams of sound and meaning eye contact body movement and that's just for one person what if there's a group of people this is overwhelming for people with with autism what's the what's the unifying theme there it's a lot of information and and that maybe is unmatched in any realm of biology the amount of information coming in through a social interaction particularly with words and language and so then that turns our attention as neuroscientists we think okay let's think about the parts of the brain that are involved in dealing with merging complex data streams that are very high in bit rate that need to be fused together into a unitary concept and that starts to guide us and maybe we can and we know other animals are social in their own way and we can study those animals and so that there's that's how i think about it there's hope for the future thinking about the symptoms as an engineer might and trying to identify the circuits that are likely working to make this typical behavior happen and that will help us understand how it becomes atypical so that seems like the first to me the first bin of this what i call the bento box uh for lack of a of a better analogy that we need to know the circuits we need to know the cells in the various brain regions and portions of the body and and how they connect to one another and what the patterns of activity are under a normal quote-unquote healthy interaction if we understand that then it seems that the next step which of course could be carried out in parallel right that work can be done alongside work where various elements within those circuits are tweaked just right like the tuning of a piano in the subtle way or maybe even like the replacement of a whole set of keys if the piano is lacking keys so to speak you've been very involved in trying to generate those tools so um tell us about channel options why you created them and where they're at now in the laboratory and perhaps also in the clinic well this is a first of all i give nature uh the credit for for creating channel rhodopsins these are beautiful uh little proteins that are made by algae single-celled green algae and it's a great story in basic science that our understanding of animal behavior sensation cognition and action in our brains all the way back to a botanist in the 1850s and 1860s in russia is where the story begins so this was a a botanist named andre feminism who uh worked at st petersburg and he had noticed in the river uh near his laboratory that there were algae that he could look at in a dish and a saucer he could put them there and we had light shining from the side the green tinge in the saucer of water would move to a particular distance from the light that he was shining from the side which was an amazing thing if he made the light brighter uh the green tinge would back off a little bit to a more optimal location so just the right light level so this was plant behavior it was light-driven plant behavior and he delved into this a little bit he identified that with microscopy he could see that there were little single-celled algae with flagella that were swimming uh to the right light level so behaving plants and this has been the secret that's that's helped us unlock uh so many principles of animal behavior so uh turns out uh you know these algae achieve this amazing results with a single gene that encodes a single protein what's a protein it's just a little biomolecule that does a job in a cell and these are proteins that sit in the surface of cells in their surface membrane and when a photon a light particle hits them they open a little pore a little hole in the membrane and charged particles ions like sodium rush across the pore now why do they do that they do that to guide their flagella that signal coming in those ions coming in through the pore in response to light guide their flagellar motor that guides them to a particular spot in the saucer okay now that's plant behavior but it turns out as you know uh this movement of ions across the membrane this happens to also be neural code in our brains for on or off sodium ions rushing into cells turns them on makes them fire away fire action potentials communicate to the next cell down the the chain and this is an amazing opportunity because we can borrow these proteins in fact we can take the gene that directs the creation of the protein and we can use genetic tricks modern genetic tricks to put that gene into neurons in the brains of mammals and then use light to turn those cells the specific cells that we put this gene into turn them on there are other opsins we call them that you can use to turn cells off it's all fast real time you can play in patterns of activity in real time into cells or kinds of cells just as a conductor elicits the music from the orchestra the strings and the woodwinds and and and you can see what matters what matters for sensation what matters for cognition what matters for action and we call this optogenetics beautiful and i must say it was quite a an honor and a privilege to watch optogenetics move from idea to discovery to the laboratory i think we were postdocs at the same time which is living proof that uh people move at different rates because that's a it's a joke at my expense by the way um but it's we end up in the same spot more or less physically if not um professionally but nonetheless um it's been a marvelous story thus far and i'd like to um maybe you could give us i'd like to just touch on a couple examples of where the technology resides in laboratories now so maybe the range of animals that it's being used in and some of the phenomenon that uh channel up chalmeradopsins and um and their related genes and proteins are starting to elicit what you've seen um and then i'd like to talk about their applicability to the clinic which is i think the the bigger mission if you will yeah so this is uh you know this this uh whole thing uh you know it's been about now going on uh 17 years that we've been putting channel rhodopsins into neurons it started just like andre feminism's work in a dish uh by 2000 that was in 2004 in 2007 we were putting these into behaving mice and we were able to to with a flick of a switch cause them to move one direction or another by 2009 so basically you're controlling the mouse's behavior yeah exactly in real time so we could make a mouse that was just sitting there doing nothing to then turn left very consistently in fact go around in a circle and as soon as we turn off the light it would stop that was an eye-opening moment uh it took really a few years to make optogenetics work uh there was a lot of putting all the there are a lot of problems that had to be solved these these channel rhodopsins actually don't move many ions they have a small current small conductance as we say and so we had to figure out ways to pack a lot of them into cells without damaging cells and still make them targetable so we don't want to just be in all the cells because then it becomes just like an electrode you're just stimulating all the cells that are nearby we had to keep that specificity make them targetable to just one kind of cell or another while still packing in large numbers of them into those cells and we had to get in the light and safe in specific ways and so it took probably about four or five years to really create optogenetics between 2004 and 2009 by the end of that time though we had uh all the basic light delivery gene delivery principles worked out and people started to apply the technology to uh to fish to rats to mice uh to non-human primates uh like monkeys and just a couple months ago uh my colleague botan roska in switzerland uh succeeded in putting uh channelrhodopsins into the eyes of human beings and making a blind person see and so that's pretty uh cool uh this was a patient a patient with retinal degeneration and he was provided a channel rhodopsin into the eye of this patient and was able to confer some light sensitivity onto this patient that wasn't there before an amazing paper and discovery i realized it was one patient but it's such an important milestone and well it's a as you say it's a very important milestone and and the the history of that is is very deep uh almost 10 years earlier botan raska and i had published a paper in science in human retina but explanted taken from cadavers from someone who had died the living retina taking out opsins put into this retinal tissue and showing that that it worked recording from the cells showing that in these human neurons retinal neurons that you could get light responses but then from that moment you know almost 10 years of you know how clinical development goes and this is a gene therapy so you've got a all the regulations and concerns and all that it took almost 10 years to get to to this point now where a living human being has a new functionality that wasn't there before now that's incredibly inspiring you know uh and uh it's it's a it's a beautiful thing i would say though that the the broader significance of optogenetics is really still understanding because once you understand how the circuitry works and which cells actually matter then any kind of treatment becomes more grounded and logical and specific and principled and whether it's medication or talk therapy or brain stimulation treatment with electrical or magnetic means if you actually know what matters that is incredibly powerful and i think no no uh you know not intended to disparage this the beautiful you know retinal work and and conferring you know vision on on someone who couldn't see of course that's wonderful but and that's direct what you might call direct optogenetics in patients indirect is everything that comes from understanding you know okay we know these cells matter now for this symptom well how can we target those those cells and help them work better in patients by any means and i think that's the broader significance of optogenetics clinically you and i know botoned well and um you and bhutan share this incredible uh big vision that i think only a clinician can really understand you know being in close contact with and uh the suffering of patients as a ultimate motivator of developing technologies which makes me have to ask did you decide to become a scientist to cure fine cures for mental disease uh uh no i didn't uh it's a it's a really important question to actually look back and and see the steps that brought you to a particular place and that was not uh what brought me uh initially to science and and it's okay to i think to embrace the twists and turns that life uh brings to you but i was always interested in the brain and so that was something that for me started from a very early age i was you know we talked about being introspective i i noticed very early on i had a deep love of poetry and and stories and i i was a voracious reader and i was amazed by how words could could make me feel in particular ways just even even separate from their you know of course dictionary meanings the the rhythm and how they work together even separate from meaning and i was stunned by poets that could use words in new ways that were even divorced from their meaning at all and yet could still trigger specific emotions and i was that's this was always fascinating to me so uh you know i i wanted to understand that and so i was interested in and i became interested in the brain and i thought well i'm gonna have to study the human brain because only human beings can describe what's going on inside enough so in in college i began to steer myself toward medicine and with the idea of becoming a neurosurgeon and so i i i came here uh to medical school and did an md phd program uh planning neurosurgery all the way through the first rotation i did at the end of medical school as you know you do rotations you go through different specialties and some of these are required rotations that everybody has to do some are elected where you can you can pick what you want to do i elected to do neurosurgery first even before regular surgery i was that sure i wanted to do it and i loved it i had a fantastic time there was an amazing patient who had a thalamic damage and there was a neglect syndrome where the patient you know was not able to be aware of something that was you know right in front of him even though their vision was perfect even though their vision was perfectly fine exactly um and so i was and and i loved the operating room i loved uh the the rhythm of suturing and the precision of it and and i love being able to help patients immediately but then a required uh rotation was in psychiatry which i was not looking forward to at all and that uh completely reset my whole life that that experience in psychiatry and and it was it was that at that moment that i saw this is first of all the greatest need the the depth of suffering and the the depth of the mystery together and also it was i almost feel a little guilty about this it's so interesting too you know yes yes there's yes we can help yes there's need but as a scientist this is uh amazing that someone's reality can be different from my own you know with with everything physically as far as we can tell the same uh with the measures we have and yet we've got a different reality that is an amazing thing and if we couldn't understand that and help these people that would be uh just uh you know more than anybody could ask for and so that's that's how i ended up uh taking this path just a a a required rotation in psychiatry it all started with poetry and it started with poetry yeah out of um respect for poetry are are there any favorites that you spend time with uh on a regular basis i mean the the ones who who got me down this path uh early on i remember in in childhood in high school uh uh borges had an immense influence on me um i i studied spanish all the way through and and and uh reading his work he was a a great writer he wrote both in english and in spanish and and being able to appreciate his poetry both in english and in spanish was was a pretty amazing thing not many uh poets can can do that you're bilingual i i'm not i wouldn't say now i i became at one point i was effectively fluent in spanish and i have i'm pretty good with medical spanish still because uh you know we use uh spanish all the time in the in the clinic here uh i wouldn't claim full fluency but it's something i can i definitely use all the time um and it's been very helpful in the clinic yeah borja is this wonderful as the son of an argentine i grew up hearing about it and i learned that borja's favorite city was geneva so i spent time in geneva only for that reason it also turns out to be an interesting city yes um so you developed methods to control neurons with these algae proteins using light in 2015 there was this what i thought was a very nice article published in the new yorker describing your work and the current state of um your work in in the laboratory in the clinic and an interaction with a patient this was as i recall a woman who was severely depressed and you reported in that article some of the discussion with this patient and then in real time increase the activation of the so-called vagus nerve this 10th cranial nerve that extends out of the skull and innervates many of the viscera and body what is the potential for channel rhodopsins or related types of algae engineering to be used to manipulate the vagus because i believe in that instance it wasn't channel ops and stimulation was electrical stimulation right or to manipulate for instance a very small localized region of the brain let me frame it a little bit differently in light of what we were talking about a couple minutes ago my understanding is that if somebody has severe depression and they take any number of the available pharmaceutical agents that are out there ssri serotonin agents increased dopamine increase whatever that sometimes they experience relief but they're often serious side effects sometimes they don't experience relief but as i understand it channel options and their related technologies in principle would allow you to turn on or off the specific regions of the brain that lead to the depressive symptoms or maybe you turn up a happiness circuit or an or a a positive anticipation circuit where are we at now in terms of bringing this technology to the nervous system and let's start with the body and then move into the skull yeah so starting with the body is a good example because it it uh highlights the opportunity and and how far we have to go so let's take this example of vagus nerve stimulation so the vagus nerve it's the 10th cranial nerve it comes from the brain it goes down it innervates the heart innervates the gut and by innervate i mean it sends little connections down to help guide what happens in these these organs in the in the abdomen and chest it also collects information back and and there's information coming back from all those organs that go also go through this vagus nerve the 10th cranial nerve back to the brain and so this is somewhat of a of a of a super highway to the brain then it was the idea and maybe the idea is maybe we could put a little cuff a little electrical uh device around the vagus nerve itself and maybe have just like a pacemaker battery have a little power source here under the clavicle everything under the skin and have a little cuff and and drive signals and maybe they'll get back to the brain so a way of getting into the brain without putting something physical into the brain and why the vagus i mean it's there but and it's accessible that's the reason that's the reason that's the reason yes really yeah you're not kidding i'm not kidding so stimulating the vegas to treat depression simply because it's accessible it started as actually as an epilepsy uh treatment and it can help with epilepsy but yes it's simple because i love medicine as a scientist i get this is where i get to chuckle and just say i'm in the field of medicine from that perspective from from the perspective of a scientist and outsider the field of medicine as a field that goes in and tickles pathways because they're there it's um i don't know what to say it's um a little shocking yeah um and we all at least in my laboratory i always say you never do an experiment because you can you you do an experiment to test a specific hypothesis yeah yeah i mean we there are there are stories people tell so that the salt the the vagus nerve lands on a particular spot on the brain called the solitary tract nucleus which is just one synapse away from the serotonin and the dopamine and the norepinephrine so there's a link to chemical systems in the brain that make it a rational choice yes it's not it's not irrational but i can tell you that even if that were not true the same thing would have been tried yeah you know you guys would have done it because it's accessible yeah okay and and but and and why well it's not again not to disparage uh what what's been happening in this branch of medicine there's immense suffering treatments many treatments don't work and and we try things and and this is how so many advances in medicine happen you think about a kidney dialysis which has kept many people alive that that was just started by someone saying hey let's let's try this maybe there's something building up in the blood maybe we can dialyze something and help them yeah it worked and and it was just sort of a test pilot mentality we can we can access the blood let's run it across a dialysis membrane put it back in the body oh my god that actually works and sometimes you do need that that test pilot mentality of course to do it in a in a rigorous safe control way which is what we do and so um anyway that's how we we ended up uh with but but still with the vagus nerve stimulation okay so what is it does it work it has its fda approved for depression this vagus nerve stimulation but on the population level if you average across all people the effect sizes are pretty small some patients it has an amazing effect in uh but some patients it doesn't work at all and average across everybody the effect size is pretty small how do you think it's working when it does work is it triggering the activation of neurons that release more serotonin or dopamine it could be uh but i would say we don't have evidence for for that um and so i i just don't know but uh what is clear is that it's dose limited uh in how high and strongly we can stimulate and why it's because it's an electrode and it's stimulating everything nearby and when you turn on the vagus nerve stimulator the voice patient's voice becomes strangulated and hoarse they can have trouble swallowing they can have trouble speaking for sure even some trouble breathing because everything in the neck every electrically responsive cell and projection in the neck is being affected by this electrode and so you can go up just so far with the intensity and then you have to stop so you know to your initial question could a more precise stimulation method uh like optogenetics help in this setting in principle it could because that would if you would target the light sensitivity to just the right kind of cell let's say cell x that goes from point a to point b that you know causes symptom relief of a particular kind then you're in business you can have that be the only cell that's light sensitive you're not going to affect any of the other cells the larynx and the pharynx and the projections passing through so that's the hope that's the opportunity the problem is that we don't yet have that level of specific knowledge we don't know okay it's the cell starting at point a going to point b that really is this particular system we want to fix this key on the piano yeah and then i see two other uh steps that are required one is to get the channelopsin gene into the cell in the case of boton rosco and colleagues rescuing vision in this patient um they did that by an injection of a virus that doesn't damage the neurons the virus itself is fairly innocuous um but carries a cargo and it's a one-time injection the cells express and then they used light to stimulate so um let's say uh i'm depressed um which i don't think i am although now sitting in front of a psychiatrist you probably can see signs that maybe i am or maybe i'm not but let's say we put channel opsin into my a specific branch of the vegas that we understand is responsible for mood um how are we going to get it in there and then how are we going to deliver the light because we're not talking about sunlight or standing in front of a light bulb necessarily but what are what are the mechanisms for the body yeah so we had to solve exactly these questions you're saying how do you get the light in how do you get the gene in in a in a potent and robust and safe way and it's that's now solved and that's not a challenge so there are very safe well-tolerated gene delivery mechanisms that are called adeno-associated viruses aavs and these are things that are associated with the common cold they themselves don't cause uh any symptoms they've been engineered and there's been a broad community of viral engineering that's been going on for decades making these uh safer well tolerated and so on we can put the channelrhodopsin gene into these viral vectors uh that deliver the the gene and we can have little bits of additional dna that govern expression only in one kind of cell but not another these are called promoters and enhancers all genetic tricks built up by a very broad community of great scientists over the decades we can put these different bits of dna package them into this aav this little virus and that can be then injected into a particular part of the body and sticking with this vagus nerve example we know that there are particular clumps of neurons there's one called the nodos ganglion that has a clump of cells related to the vagus nerve and you could for example target a little injection into that ganglion would that be an outpatient procedure yeah yeah so you come in in the morning get your injection maybe walk out a few hours later yeah that's right and so that's the gene um then the light delivery this is also something that that we've worked out we've worked on making very very light sensitive opsins one challenge and and botan uh uh would be the the first to state this in fact in solving this problem for the patient he had to build uh goggles that uh created much much brighter light than normal ambient light uh delivery because as i mentioned earlier you have to pack a lot of these channel rhodopsins in they don't have much current you have to really make sure that you've got it tense enough light to activate enough of them to cause a stimulation and it has to be the right wavelength going back to your example of the algae moving toward or away yeah uh the light it has to be tuned just right so could you i could i'm imagining in my mind as a non-engineer i know you're also a bioengineer the i'm imagining a little tiny um blue light emitting um thing object that's a little bigger than a clump of cells or maybe about the size of a clump of cells and for those that don't know you know your credit card is about 200 um microns thick on the side and micron is a thousandth of a millimeter and so we're talking about a little tiny stamp um that's basically uh half a millimeter in size um all around each edge half a millimeter in size i could imagine that being put under my skin and then i would what i'd hit an app on my phone and i'd say i'd say dr dice roth i'm not feeling great today can i increase the stimulation and you say go for it and then i ramp it up is that how it would go i mean that's effectively what we already do with the vagus nerve stimulation the the doctor in this case and i i have this in some of my patients in the clinic i do vagus nerve stimulation i talk to them i say how i go through the symptoms i use the psychiatric interview to elicit their internal states and then i have a radio frequency controller that i can dial in right there in real time right there you're holding the remote control essentially to their brain although it's remote remote control through a couple steps yeah yeah yeah and i can i can turn up i can turn up the frequency i can turn up the intensity uh all with the radio frequency and uh uh control and then it's it's reprogrammed or redosed and then the patient can can then leave at this altered dose so this is happening now this is happening right now electrically you do this routinely i do it routinely in my clinic electrically and you're getting the verbal content which as you described earlier is the indication of how well something is working in real time yes so this what maybe you could just describe a little bit of the interaction with that particular patient or or another patient what's a typical arc of um narrative as you go from no stimulation to increased stimulation in most in most patients uh the actual therapeutic effects the benefits actually take uh many days two weeks um and so what i'm mostly focusing on in the office in real time is making sure i'm in a safe low side effect regime and so first i talked to the patient you know how who has been on a particular dose of the stimulation for weeks or or longer and i i talked about symptoms how were things over the past uh month how is your hope how is your energy level uh sleep uh you know how what is your mood um and and then we talk with the patient we decide oh this is this is not yet where we'd like to be and so then i can turn up the intensity of the stimulation real time in the office i don't in most patients i don't expect an immediate mood change what i do is i increase the the dose until a next level up while asking the patient for side effects can you still breathe okay can you still swallow okay and i can hear their voice as well and i can guess and they're looking at their faces and i'm looking at their face and so i can get a sense is there a uh am i in a still on a safe side effect uh regime and i and and and then you know i i i stop at a particular point that looks safe and then patient goes home comes back a month later and i get the report on how things were over that month uh i asked uh if you're looking at their face because in your book you describe the incredible complexity of social interactions and at one point you described the incredible amount of information that the eyes inform about the brain and and the context of somebody's inner experience whether depressed or happy or otherwise i want to make sure that we get back to how to maneuver them and manipulate the nervous system for sake of mental health but what are you looking for so as a vision scientist i think you know pupils dilating as a sign of arousal but that could be a positive arousal positive valence like excitement or it could be terror you're gonna get the same dilation of the pupils um and and i'm always reminding people these two little goodies are two pieces of brain basically they're just outside the cranial vault so they're not unlike the vegas in that sense but they're more of a report than a control knob although i like to think they could be used as control knobs too um so without putting you on the spot again to diagnose me not something i would never ask you to do with the cameras rolling but what are you looking for that the patient might not be aware of in other words can you see depression in somebody's eyes and if you know a patient or if you don't can you see it in their body posture when they walk in realizing of course that a trained psychiatrist like yourself develops an intuitive sense that's aggregating lots of different features of a patient but what about the eyes what's what's going on there yeah the eyes are incredibly rich in information and uh as you as you allude to though it's not as if any one measurable conveys all the information you need it's what we you know what an engineer would say joint statistics it's it's it's many things all at once whether they're in synchrony or out of synchrony that that actually uh turns out to matter and uh you know the eye contact question we all know eye contact is incredibly important you don't feel you've connected with with somebody unless you unless there's eye contact but eye contact can go awry too it can be it can be too intense or it can be mistimed or if there's someone with autism it can be barely there at all and and this is one of the most striking symptoms of autism is the avoidance of of eye contact as if it's um if it almost as if it's a harmful uh a quantity and so there's an immense amount of information you can't you get from the eyes but it's it's the pairing of what's going on in the eyes with everything else going on the body language the what's the verbal content of what's what's coming out all that together is is is is the art of of psychiatry and and social interaction but you know sometimes you don't have the eye contact this is an amazing thing and i do talk about this in the book as well in in many cases you know in psychiatry sometimes it's over the phone that you have to make key decisions and as a and i recall you know vividly being as a resident uh very often you have to take these phone calls from uh people who are not in the hospital people you can't see you can't see their eye you can't see their body anything about them just the sound of their voice and you can ask them questions and you have to make in some cases life or death decisions you know is this person truly suicidal something like that as it comes up all the time and so i developed over the course of training and i think all all psychiatrists do this is you develop a way to whatever data stream you have whether it's the eyes or whether it's just the sound of a voice coming over the phone you learn to hone in on that data stream you have and focus on it and identify changes and it's quite amazing uh i i found that you can actually if you know a patient you can detect very precise changes in mood just from the sound of the voice and and you can have a a a realization that oh this patient's depression has improved you know by by about half just by the tone of their of their voice and same with eyes you can with enough practice you can get in enough information from a single data stream to give you some information but when you do have the whole picture that of course is best so um so many theories out there about um excessive blinking and lying lack of blinking and sociopathy um i like to remind people that uh people have varying degrees of lubrication of the eyes which also influence the frequency of blinking and presumably have nothing to do with uh whether or not what they're saying is true or not uh but in incredible nonetheless that it's that the eyes are a portal to overall arousal state i'm fascinated by the effects of light on circadian biology and just overall desire to be awake or asleep etc um so the eyes are on the outside of the cranial vault the vegas is outside uh the cranial vault obviously um what about the goodies in here um parkinson's we know the at least one of the major sites of degeneration and failure that lead to those symptoms um i can aim off any number of other things in your book you talk about the beautiful work done with optogenetics of active versus passive coping that there are areas of the brain like the vanilla that make when active make animals and presumably people passive and un willing or uninterested in fighting back against pressures of life whereas another region with the raphe you stimulate that and and they actively cope they they get their grit going and they and they are able to lean into life so how do how does one get to those structures in a focused way and um what what is the next two to five to ten years look like yeah well this is the this is the promise on that and it is on that time scale uh that i think things may start to play out you know that the specificity of optogenetics uh is really only useful if you have some idea of how to use that specificity um and it's actually it's a frustrating aspect of psychiatry that in many cases the most effective treatments we have have the least specificity electroconvulsive therapy being a great example where you're causing a brain wide which looks barbaric but as you mentioned is effective i mean it is it it these days it's it's much more clinically you know it doesn't look like one fluid the last scene and one floor over the cookies now it's a very clinically uh safe and stable procedure but i i where i i i would say yeah it is it is it's got this almost medieval lack of of specificity even if the procedure is well controlled and clinically safe and stable and it has a it's not very specific you're causing a brain wide seizure how could you be less specific than that and we don't know that the the source of the relief we don't presumably it's a dump of neuromodulators like dopamine and serotonin but we don't there certainly is a dump of neuromodulators we don't know that that's the the cause for the relief uh and likewise with medications this is also an interesting thing so for some of the most effective antidepressants some of the most effective antipsychotics are the ones that are have the most side effects and many examples of this for example the most effective antipsychotic is something called clozapine which has it's unquestionably has the most side effects it has terrible terrible size it's a d4 antagonist it has basically every receptor does it really yeah it acts it's interesting yeah it has prominent serotonin prominent muscarinic uh certainly acts on dopamine receptors but uh it causes uh you know blood uh blood cell uh counts how do people feel so if if um if i were schizophrenic and uh i was getting auditory hallucinations etc and i took clozapine um what could i expect to feel well uh so you would notice uh side effects and you would notice resolution of symptoms both and so the voices would go away if in in a good situation the voices would go away that's right but i would feel not good in my body you would have uh you might have dizziness you might have a drooling you might have uh any number of uh physical sensations that that would be due to these off-target effects the the medication acting on these other receptors and i'm certainly not suggesting this but what if somebody without schizophrenia to close the pain uh you have the same side effects presumably yeah and so it would not be something that that i would recommend um do psychiatrists take the drugs that they prescribe i just finished up for the third time uh oliver sachs's um autobiography which is marvelous and and i highly recommend to people um he certainly took a lot of drugs um not as part of his professional role um but just out of curiosity what is the interest or kind of role of of drugs in the field of psychiatry because for i would imagine for a group of very curious introspective people who are making recommendations about what to take there could actually be some benefit for understanding what the experience of those drugs was like for their patients i think that's that's true and i i will say that probably many or most psychiatrists have uh you know sampled a number of these for exactly the reason that you're saying is is to understand better and to help treat their patients better and i've i've spoken to people who have you know really been uh i found this very helpful to know okay this this sleep disruption caused by this medication or the libido disruption caused by this other medication wow that is that is a big effect and and it really helps with empathy for the for the patients to understand i'm not i'm not suggesting that physicians or anybody um uh experiment with drugs but i but i am relieved to hear that because i think that when you're talking about accessing somebody's mind and their basic physiology as you mentioned relate to appetite libido and sleep you really you're really um one is acting as a mechanic of of their the person's whole experience they walk out of the office and they have a life experience um that extends beyond the script yeah and so and yeah and so that so with at the same time though you can't let that completely guide your clinical decisions because as i mentioned some of these medications that have the most side effects they are also the most effective and clozapine is a great example that will work in patients where nothing else works and believe me we don't take the step of clozapine uh prescription lightly because of all these these side effects you have to come in for a weekly blood cell or every few weeks of blood cell check to make sure that the blood counts are not off uh for example but there are patients where no other medication works for schizophrenia and clozapine works amazingly well and and and so we do it even though there are the side effects and so then this comes back to your your question what if we had better and better specificity well only if we know exactly what we're doing is the point and so because as we become more refined uh we better be right about where we're refining to and you imagine a day where it will be a single maybe even outpatient neurosurgery would go in through the skull or the back of the year deliver a small viral injection of one of these adenoviruses a little sticker of light emitting diode is that um it deep in the brain is that how you envision this that certainly could happen what i what i actually prefer as a vision is is still medications uh because those are you know minimally invasive if we knew what we were doing we could make them more specific uh have fewer side effects but optogenetics that'll arm us with true causal understanding and so we'll know uh and we're already moving rapidly toward this point we'll know okay this symptom the loss of pleasure in life that we call anhedonia or the loss of of motivation or or energy to overcome challenges active coping these are largely subserved largely controlled by this circuit or that circuit or the cell that inhabits this other circuit and we will know that because of the work done with channel ops exactly yeah i agree in ways that we never could have the confidence otherwise and so we'll know that this is the circuit that that underlies the symptom or its resolution and then we'll get to understand these cells very deeply okay these cells that are causal that do matter who are they what do they what's their wiring what are the proteins that they make what are the little things that are on the surface of the cell that could be receptors for specific medications or combinations of receptors that would give us the specificity we need and then armed with that causal and precise and rigorous knowledge then you can imagine medication development becoming totally different no longer serendipitous but truly grounded in causality i see so using channel options as a way to probe the circuitry and figure out the sites that are disrupted what patterns of activity are required and then by understanding the constituents of those cells like what they express and what they make then developing drugs that could target those cells not necessarily putting light inducing diodes into the brain or walking around with wire packs attached to our skull or something that's fantastic and and you i realize no one has a crystal ball but um what do you think the arc of um of that is meaning are we going to see that in a year in two years three years let me reframe that if how soon will a pill-based treatment for a psychiatric disease be available that targets a specific set of cells that we know are important because of the work done with channel options i think uh that is in some ways it's already uh happening at the level of individual patients uh and here at stanford yeah yep uh and and and more broadly in terms of uh new new drugs new multi-center you know clinical trials that will play out over the next few years um and these could be drugs that are already safe and approved for other purposes but we might say okay now we know that this medication based on what we know from causal optogenetics this could be useful for this other purpose this psychiatric symptom and so the path uh to to helping patients is could be relatively swift that's very exciting what are your thoughts about brain machine interface and neural link always comes up although i do want to point out it um a tremendous respect for the folks at neural link including someone who came up through my lab is now there is a neurosurgeon but um the brain machine interface is something that's been happening for a long time now some of the some of the best work uh among the best work being done here at stanford and elsewhere too of course how is the what you just described compatible with or different than brain machine interface meaning devices little probes are going to stimulate different patterns of activity in ensembles of neurons and what are your general thoughts about brain machine interface as going forward yeah i mean this is uh first of all it's a it's an amazing scientific discovery approach as you mentioned we and others here at stanford are using uh electrodes collecting information from tens of thousands of neurons in humans i should add and even yes there is there's it is quite even separate from the neural link work as you point out many people have been doing this in humans as well as in non-human primates and this is pretty uh powerful it's important this will let us understand what's going on in the brain in and psychiatric disease and neurological disease it will give us ideas for for treatment um it is of course it's still uh invasive you still are talking about putting a device uh into the brain and that has to be uh treated as a as a situation that has some risks and and a step that has to be taken carefully i see that as something that will be part of psychiatry uh in in the long run already with deep brain stimulation approaches we can help us people with psychiatric disorders and that's putting just a single electrode not even a complex you know closed-loop system where you're both playing in and getting information back even just a single stimulation electrode in the brain can help people with ocd for example quite powerfully and that would become much more powerful when we get to a true brain machine interface collecting information back stimulating only when you need to if we could identify a pathological activity pattern a particular almost like the the drone or the early stage of a seizure maybe there are events that happen leading up to on some time scale uh a psychiatric uh symptom we could intervene in a closed-loop way detect what's happening what's starting to go wrong feed that back to the brain stimulation electrode have it be you know in that way more efficient and more principled this is is i think it's great it's it's a something that of course will be grounded again and causal understanding we'll need to know what is that pathological pattern that we're detecting and we need to know that it matters and so again that's where optogenetics is helping us helping us know okay this this pattern of activity in these cells in these circuits this does mean that there's a particular kind of of symptom that's happening but armed with that knowledge absolutely even the even the simple closed loop device detect and stimulate is going to be part of psychiatry in the future and then and then of course as you get to more cells more connections the ability that we have to help people will become more powerful one of the questions i get asked a lot is about um adhd and attention deficit of various kinds i have the uh hunch that uh one reason i get asked so often is that people are feeling really distracted and challenged in um funneling their attention and their behavior but uh and there are a number of reasons for that of course but what is true adhd and what does it look like what can be done for it and what if any role for channel options or these downstream technologies that you're developing what do they what do they offer for people that suffer from adhd or have a family member that suffers from adhd yeah this is a it's a pretty interesting branch of psychiatry there's no question that people have been helped by the the treatments uh there's you know active you know debate over you know what fraction of people who have these symptoms uh can or should be be uh treated this is typically adderall or stimulants of some kind for example the stimulants that's right um so adhd it's as its name suggests it has symptoms of it can have either a hyperactive state or an inattentive state and uh those can be completely separate from each other you could have a patient who who uh effectively uh is not hyperactive at all but can't uh remain focused on the the what's going on around them so their body can be still but their their mind is darting around that's right or they can be very hyperactive with their body yeah probably rarely is somebody hyperactive with their body but their mind is still although i have to say and this is a benevolent shout out to bhoton roska botan has an incredibly sharp and focused mind yeah and his hand movements are extremely exact also so i do sometimes wonder whether or not our body movements and our head movements are whether or not they're coordinated or not is a is a readout of of how directed our attention is i notice i have to think complex abstract thoughts i notice i have to be very still so my body has to be almost completely unmoving for me to think very abstractly and and deeply other people are different some people when they're running they get their best thoughts i can't even imagine that my brain does not work that way at all i have to be totally emotionless which is kind of interesting how do you go about that i i i sit uh much like this you know i i try to have time in each day where i am i'm literally uh sitting uh almost in this in this position um but but without distraction and thinking and and so it's kind of a it's almost meditative in some ways except it's it's not a true meditation but i i am thinking while not moving and you're struggling you're trying to structure your thoughts yeah in that time yeah interesting yeah so but everybody as you say is is is very different and so with with adhd you have the key thing is we want to make sure that this is present across different domains of life school and home to show that it really is a pervasive pattern and not something specific to you know the teacher or the the home situation or something and then you can help patients it's interesting that that adhd is one of those disorders where people are trying to work on quantitative eeg based diagnoses and so there's some progress toward making a diagnosis with looking at particular externally detectable brainwave rhythms so skull cap with some electrodes that don't penetrate the skull that's right and this can be done in an hour or two hour session that's right has to be done in a clinic right yeah in the clinic right you have to have the right recording apparatus and so on but but but uh that's in principle uh as you increasing confidence comes in exactly which measurement uh one could even imagine moving toward you know home tests but we're not there yet amazing i think um one of the reasons i get asked about it so much is a lot of people wonder if they have adhd do you think that some of the lifestyle factors that inhabit us all these days could induce a subclinical or a clinical like um adhd meaning if i look at people's phone use including my own and i don't think of it like addiction it looks to me and feels to be more like ocd and i'll come clean here by saying when i was younger when i was a kid i had a grunting tic i used to hide it i actually used to hide in the closet because my dad would make me stop and i used to yeah i couldn't feel any relief of my mind until like we do this and actually now if i get very tired if i've been pushing long hours it'll come back i was not treated for it um but i will confess that i've had the experience of i always liked sports where i involve a lot of impact fortunately not football because i went to a high school where the football team was terrible maybe that would have avoided more impact but things like skateboarding boxing they bring relief i feel clarity after a head hit which i avoid but but i used to say that's the only time i feel truly clear for a lot and then eventually it dissipated by about age 16 17 just disappeared um so i have great uh empathy for those that feel like there's something contained in them that won't allow them to focus on what they want to focus on and these days with the phone and and all these uh email etc i i wonder and i empathize a bit when i hear people saying like i think i might have adhd or add do you think it's possible that our behaviors and our interaction with the sensory world which is really what phones and email really are could induce add or reactivate it you know i this is a great question i i think about a lot there's you know and you mentioned this this uh tick like behavior in yourself it's very common that people who have ticks have this building up of something that can only be relieved by executing the tick which can be a motor movement or or vocalization or even a thought and people do i think these days do have this if they haven't checked their phone in a while they do have a build up and build up a build up until they can they can check it and relieve it um and and and there's some similarities you know there is a little reward that comes with the with the the checking um but the key question in all of psychiatry what we do is we we don't diagnose something unless it's disrupting what we call social or occupational functioning like you could have any number of symptoms but literally every every psychiatric diagnosis requires that it has to be disrupting someone's social or occupational functioning and these days you know checking your phone is pretty adaptive that pretty much helps your social and occupational functioning and so we can't we can't make and we can't make it a psychiatric diagnosis it's interesting at least in the world of today yeah opting out of communication now makes it uh makes you in some ways less adapted though i would point to you as an example of somebody who is quite good at managing his uh interactions at least from from the outsider perspective i do want to ask you a little bit about you and um first of all um and i realize this is only a partial list but your clinician you see patients you run a big laboratory how many people are in your laboratory now that's a huge laboratory um from experience i can say that's that's an enormous laboratory um you have a family of five children and you're happily married to a wonderful colleague of ours as well who just does incredible work um how how do you organize at a kind of conceptual level the day and the week um and i should say what stress mitigation practices if any do you incorporate i've received emails from you at three in the morning uh i sometimes send emails at three in the morning but that's when i wake up maybe i'm depressed but i go back to sleep so maybe you just describe um the arc of of the blocks of the day not hour by hour necessarily the details of what are in those blocks but how do you conceptualize the day how do you conceptualize the week and how do you feel about how that's um lined up with your your larger goals of of you know making sure these five uh young people you know flourish which i hear they are um but how do you go about this what for most people would just be an overwhelming set of of items well it's uh of course uh it's sometimes it's just to take it day by day and and uh and so i i don't claim do you bring the horizon into the unit of the day i i i do i do it's the unit is the day that's right and um what i i try to have in each day as i mentioned earlier some at least an hour of time where i can think uh and and that can be it can be when kids are napping it can be um you know actually because like while driving i can do that too uh because i'm sitting still but uh that that's the one thing i try to preserve when i was writing the book i adapted that time to be my my writing time but it wasn't enough uh it's you know so i had to add in a new block of time which was sort of midnight to 2 a.m writing time um and and so that carving out these even small protected times are very important uh there's of course you know obligations will will expand to fill the time available and you have to be disciplined in my at least i found i had to be disciplined in in truly protecting those uh times where one can think so that means no phone that means no phone no checking of the phone um uh i would you know when i was writing the book i would i would have uh uh there's a focus mode on the the the macbook but which kind of removes the border and you just have your your your document and it's it's very pure and you don't have uh a temptation of distraction i'm a big believer in because the vision and the eyes play such a prominent role in directing our cognition something you talk about in the book um really beautifully and with a lot of depth and rigor uh using visual tools to harness one's complete mental attention when you do this practice of sitting and just thinking sitting still and thinking you said your eyes are open um are you hearing your own verbal voice although in your head so you're actually in conversation with yourself yes and and hearing literally i mean not quite literally i don't actually hear a phonation but i i i'm hearing words uh and so it's i'm i discovered this about myself other people uh i think you know may operate uh differently but i'm extremely verbal in how i think that's how all my reasoning is done it's with sentences and construction of of uh you know almost equations with words complete sentences complete sentences or completish anyway uh mostly complete and then and when writing the book everything about the writing i would always every sentence was always played out in my mind listening for for rhythm and timing and and and i would obsess over exact placement of words to get the right rhythm of the spoken sentence in my in my mind could i i don't mean to interrupt your flow but when you do that and having experienced this process a bit although differently do you experience any kind of welling up of anxiety when you're hitting the the friction points um and if so do you have tools or uh ways that you quell that anxiety in real time because what we're really talking about here is um your mind but what we're really talking about is this process of of converting the activity of neurons into something physically concrete in the world and these intermediate steps are so mysterious to everybody we hear you know just write the book just do it whatever that means in fact the statements like that to me are kind of empty and meaningless um but when you hear your voice and you're trying to find the correct word and you keep hitting th it doesn't sound quite right what is the experience in your body yeah i when it's not right it's definitely uh it's it's aversive uh it doesn't feel good um but it's not um but i but there's also a hope because i know i can solve it too and and so there's there's this uh it's almost like you're you're almost there you know you've there's a path that you know is there you you don't quite see it but it's there and and i keep that in mind and so there's there's a there's a there's this uh propulsive force forward uh because i know that the solution is there and and that said i you know there were there were single words that would occup you know i would spend days on you know because i was just not happy until i got it right and there were some things that i never quite got perfect and so i left out of the book entirely because it was so close but not not quite there and so i at the end i was like no i can't put that in everything you just said is entirely consistent with my experience of you and the way you go about uh everything i have to ask are your kids writers do they like books and words and poetry i i know one of your children is going on to a career in medicine and science yeah they're each different which is amazing yet they all i think do have some appreciation or a lot of appreciation for for reading um but some are very musical two of the five are extremely musical very very talented with guitar and singing and and vocal you know impressions uh it's just astonishing uh and and some of them are are great with drawing and and artistry and and some are very physical and vigorous and and are never uh happy except when you know leaping about and so it's it's just amazing how different they are honestly but i think there is a shared appreciation for for language do you think the uh that one can train their mind in using these practices i i i really like your description of the um sitting staying physically still and and learning to grapple with those those challenges it's something that especially in laboratory science we aren't really trained to do um like many professions we're taught to come in and just get into motion and and i found that very relaxing as someone who probably has an underlying uh tick or something like that it felt great to be in motion one of the hardest things about becoming a university professor and running a lab was that i no longer working with my hands and it felt like i was i it felt like some big important part of my life had been amputated but what sorts of practices do you incorporate there and do you think um people can learn to get better at focusing through a dedicated practice of the sort that you describe i think you know i also you know i i remember the rhythms of of physical work in the laboratory very well i i uh my work uh you know these days as as as the laboratory leader my job has returned mostly to words now again and and so it's it's kind of coming full circle it was uh um so it's a different mode i think you just have to embrace that that different stages of life come with different modes but you can definitely train yourself for each mode i was not um you know i i i i loved you know the as i mentioned the the the rhythm of sewing and and and suturing and surgery um and i worked really hard on that and became you know good at it and now i never do it um but it's what's the next challenge you know there's all the various experimental techniques the dissections of the brain you know i can't tell you how many thousands of brain dissections i've done in my life and now i don't do them at all and then you developed a method so that we don't have to dissect brains as you mentioned maybe tell us for a moment about clarity and for the for um people who will probably never set foot into a laboratory um what an incredible yet another incredible discover discovery and development clarity is uh and why it helps us understand how the brain is structured yeah so this is this is a different technology also developed in in my lab here and it's a part of a broader approach that we call hydrogel tissue chemistry and what this is is it's building a gel like a clear jello like substance with from within all the cells of a tissue uh or even an animal all at once so you're building a effectively building a gel inside all the cells at once now that's a odd thing to do why do we do it well we do it to transform the tissue into a more tractable accessible object and the reason that works is we having built this gel this new infrastructure inside the tissue we can then use chemical tricks and we can link the molecules we care about like proteins or rnas which are the things as you know right before they become proteins we can link them physically anchor them to this gel which is a scaffold basically it's an interlocking network of polymers we can link all these interesting molecules in place lock them in where they were initially in the tissue in the cell in all the cells and then we can remove very vigorously everything we don't care about that's blocking our light that's blocking our molecules coming in to exchange information with the tissue we can get rid of everything else like the lipids the fats we can effectively use detergents to to get them all out and then we can see in all the things that were absorbing our scattering light are gone you can have a brain that's completely transparent and yet all the interesting molecules are still locked into place there at the cellular and subcellular level and so this is hydrogel tissue chemistry the first form we described was called clarity uh we use that quite a bit still but there are many variants now that we and others have developed on this basic concept of building this gel within the tissue and anchoring molecules into places literally glass clear brains i've done this i've taken a brain cleared with this method and looked at somebody through it and although you don't want to get it too close to your eye i don't want to touch it to your own eye but um and you can see direct all the way through it um that's incredible for the it raises an important question which is again about the human brain and as somebody who essentially started out in neuroanatomy and then got into other things i i always am um bothered by the fact that we actually know very little about the microstructure of the human brain compared to the brains of other organisms and in thinking about understanding the circuitry and the the piano so to speak that and how to manipulate it in order to relieve suffering one wonders are the structures in these animal brains and how they behave in active coping passive coping add etc those models how well they translate to the human condition do you think it's fair to say that there are entire regions of the human brain that aren't just bigger but that exist only in the brains of humans especially given that we have this speech although i do wonder sometimes if you know animals are reporting to each other there maybe they have little psychiatric sessions with one another you know i i'm always careful to not uh assume we do things better we certainly understand what we're doing better than we understand what animals are doing and they certainly do things better than we do that said we do have amazing wonderful brains and many structures that are very highly developed in our brains that are are not nearly so developed in mice and uh and fish for example now um that said when i look at the big picture you know what what is the mammalian brain really doing there are things that you would never have thought we could study in in animals in laboratory mammals like mice uh that it turns out you can actually uh and and so i would never draw the line and say here's something you can't study in mice or here's something that has no parallel in mice i would be very careful before making any any statement like that a good example of that is we've been able to study just in the past year come to an understanding of dissociation and both we had a paper that came out in late 2020 both mouse and human work in which we got to the sort of the circuit basis for dissociation what now what is dissociation a lot of people might not have experienced it but it's actually very common more than 70 percent of people who've been through trauma experience dissociation it shows up in borderline personality it shows up in ptsd what it is is a separation of the sense of self from the body and so you can have someone who's it's not as if you're numb you're not anesthetized you can still you know that something's happening to the body but you just don't care because you don't ascribe it to yourself which is very interesting right that is how interesting is that report narrative yeah almost in your book you touch on this um and i i will say is the most um precise and meaningful and eloquent description of what might be consciousness this this narrative toward the self or of the self and where it might reside so in dissociative conditions um people are are feeling as kind of an absence of emerge between mind and body is that one way to describe it and as i recall this paper involved um an exploration of ketamine ketamine was a big part of it yeah that's right and so ketamine is is another one of those cases where people can experience dissociation ketamine or pcp we call these the dissociative drugs they cause it just like these these other psychiatric uh conditions can cause it and so we but we were able to manifest this in in mice administering these dissociative agents in mice we could make them still able to detect stimulus but not care that it was happening all the while we were recording in the activity of individual cells in the brain to see what was going on what what was happening along with this dissociation and then use optogenetics to see that it mattered to actually provide that pattern of activity and see oh that actually causes the dissociation so we could do all that in mice yeah which which was you know just uh who would have thought that that you could study something like this in mice and we were able to go back and forth with uh human uh work because here at in our stanford comprehensive epilepsy center there are a lot of what we call stereo eeg recording patients who come in and in the course of normal clinical care they have electrodes recording in their brain to identify where the seizure is so they can be candidates for removing a little patch of the brain that's causing the seizure this is done for patients who medications are not helping their seizure disorder and there was a a patient who had a dissociative state before every seizure so this was a human being who was really dissociating who could tell us literally as it was happening and we could see this pattern the same pattern that was happening in the mice in the same patch of the brain we could see that happening in the human being at exactly the right time in the same patch of the brain that's homologous across these immense evolutionary distances and we knew that it mattered too both in mouse and human because in the human we could cause it to happen and i just want to underscore the power of not just that i want to underscore the power of of optogenetics and the ability to not just remove a particular experience or behavior by lesioning or destroying but then to go back and and actually activate the same structure or group of structures and see the emergence so it's essentially these days you hear a lot about gain of function research in the context of viral manipulation but gain a function is something that we do in the laboratory and and you do in patients to both take away something and put it back and which gives you causality that's right yeah and so and exactly and so with optogenics we were able to provide uh in animals without being on any any ketamine or any any drug and we could cause the dissociative state by playing in a precise pattern of activity and that who would have thought you could do that but there was a combined mouse and human paper like likewise we've been able to play in uh you know visual sensations into the brains of mice uh and by observing which cells in the visual part of the brain visual cortex are naturally responsive to for example vertical bars instead of horizontal bars in the visual world we could see which cells were normally reporting on vertical bars and then we could use optogenetics to come and play in activity just to those cells so these animals are not viewing anything not doing anything at all and we could activate just the vertical bar cells and not only did the animal act as if it was seeing a vertical bar behaviorally it was trained to do a particular thing if it saw a vertical bar and it did that just as if it was seeing something visually but everything in the brain that we were recording to the internal representation of this external world was naturalistic too it looked like the the the brain was seeing something visual so that was another that's gain of function too you know playing in providing a complex sensation or percept that wasn't there before and we can do that and uh you know across species so i i we haven't you know and of course mice are social and and they do they do amazing acts of information processing and so i'm i don't uh i try not to disparage our cousins too much they certainly have helped the field of neuroscience and medicine i should mention and i know that people have various sensitivities about animal research but the work that's been carried out in mice has been absolutely um vital and instructional for the for treatment of human disease that's right since we talked about uh dissociation and dissociative uh states rather and ketamine i'd love your thoughts on uh psychedelic medicine you know i uh sort of half joke having grown up in this area in northern california when it was much more counterculture than it is now uh that many of the things that we're hearing about now uh at least from my read of the of the history books happened before there was a movement aimed at taking the very same compounds essentially putting them into patients or people were obviously using them recreationally but putting them into patients and seeing tremendous positive effects but also um tremendous examples of um induced psychiatric illness in other words many people lost their minds as a consequence of overuse of psychedelics i'll probably lose a few people out there but i do want to talk about what is the state of these compounds and i realize it's a huge category of compounds but lsd and psilocybin as i understand trigger activation of particular serotonin receptor mechanisms may or may not lead to more widespread activation of the brain more that one wouldn't see otherwise but when you look at the clinical and experimental literature what is your sort of top contour sense of how effective these tools are going to be for treating depression and then if we have the time we could talk about trauma and mdma and some of that work well your your right to highlight both opportunity and and the peril that is there and of course we want to help patients and of course we want to to explore anything that might be helpful and but we want to do it in a safe and rigorous way but i i do think we should explore these these avenues these are um agents that alter reality and alter the experience of reality i should say in in relatively precise ways they they do have problems they can be addictive they can cause lasting change that is not desirable um but we have to see these as opportunities we have to uh first of all study in the laboratory and i'm doing this uh here uh you know we have big uh we have safes with many interesting psychedelics that are all very carefully regulated we get inspections from the dea and so on anyone's hoping to find these labs they exist in outer space so you need uh you need to be on board one of the one of the spacex um missions in order to access them so don't try and come find them no that's exactly true yes um and and uh and and we're doing exactly this we're saying this is an incredible opportunity if we could understand how you know the perception of reality is altered we could be create new kinds of intervention that don't have the uh risks and and and the problems of causing lasting change or addiction now that said uh even as these medications exist now as you know there's uh an impulse to to use them in very small doses and to use them as adjunctive uh treatments for for the therapy of various kinds and i i'm also supportive of that if done you know carefully and rigorously of course there's risk but there's risk with many other kinds of treatment and i'm not sure that the risks for these medications uh vastly outweigh the risks that we normally tolerate in other branches of medicine why would they work i mean the um you know let's say uh that indeed their main effect is to create more uh more connectivity at least in the in the moment uh between brain areas so the way i think about a very um i think about the two extremes of of my experience anyways a high degree of stress and focus for whatever reason is going to make create changes in my visual field and cr changes in the way that i perceive time so that i'm going to micro slice time i might in a very contracted view of whatever my experience is whereas on the opposite extreme in a in a dream or in sleep space and time are very fluid and i'm essentially relaxed although it might be a very interesting dream it might not be uh psychedelic seemed to be a a trajectory i'm not off too far off from the dream state where space and time are essentially not as rigid and there is this element of synesthesia blending of the senses um you know feeling colors and um hearing uh light and things of that sort it you hear these reports anyway um why would having that dreamlike experience somehow relieve depression long term do we have any idea why that might be i uh we have some ideas no no deep understanding uh one way i i think about the psychedelics is they um increase our willingness to increase the willingness of our brain to accept uh unlikely uh ways of constructing the world unlikely hypotheses as it were as to what's going on the brain in particular cortex i think is a hypothesis generation and testing machine it's coming up with models about everything it's got a lot of bits of data coming in and it's making models and updating the models and changing them theories hypotheses for what's going on and some of those never reach our conscious mind and this is something i talk about in projections in the in the book uh quite a bit is many of these are filtered out before they get to our conscious mind and that's good we we think how distracted we'd be if we were constantly having to evaluate all these you know hypotheses about you know what kinds of shapes or objects or processes were out there and so a lot of this is handled uh uh before it gets to consciousness what the psychedelics seem to do is they change the threshold for us to become aware of these incomplete hypotheses or wrong hypotheses or or concepts that might be noise but are just wrong and so are never allowed to get into our conscious mind now you know that that's pretty interesting and it goes wrong in psychiatric disorders i think uh in in schizophrenia sometimes the paranoid uh delusions that people have are examples of these poor models that escape into the conscious mind and become accepted as reality and they never should have gotten out there now how could something like this in the right way help with something like depression patients with depression often are are stuck they can't look into the future world of possibilities as effectively there's everything seems uh hopeless and what does that really mean they they discount the value of their own action they discount the value of the world at giving rise to a future that matters everything seems to run out like a river just running out into a desert and drying up and what these agents may do that increase the the flow through circuitry if you will the percolation of activity through circuitry may end up doing for depression is increasing the the escape of some some tendrils of of process of forward progression through through the world um that's a concept it's how i think about it there are ways we can make that rigorous we we can indeed identify in the brain by recording we can see cells that represent steps along a path and look into the future and we can rigorously define these cells and we can see if these are altered on psychedelics and so that's one of the reasons that we're uh working with these agents in the laboratory to say are is this really the case are these opening up new paths or representations of paths into the future um mdma ecstasy is a unique compound in that it leads to big increases in brain levels of dopamine and serotonin simultaneously and i realize that the neuromodulators like dopamine serotonin often work in concert not alone the way they're commonly described in the you know the more general popular discussions however uh it is a unique compound and it's different than the serotonergic compounds like lsd and psilocybin and there are now data um still emerging that it might be and and in some cases can be useful for the treatment of trauma ptsd and similar things why why would that work and do you and a larger question perhaps the more important question is psychedelics mdma lsd all those compounds there to in my mind there are two components there's the experience you have while you're on them and then there's the effect they have after people are generating variations of these compounds that are non-hallucinatory variations but how crucial do you think it is to have let's stay with mdma the experience of huge levels of dopamine huge levels of serotonin atypical levels of dopamine serotonin released having this highly abnormal experience in order to be normal again yeah i think the brain learns from those experiences that's that's the way i see it and and so for example people on who have taken mdma they will as you say they'll have they'll be the acute phase of being you know on the the drug and experiencing this extreme connectedness with other people for example and then the drug uh wears off and but the brain learned from that experience and so what what people will report is yeah i'm not i'm not in that state but i saw what was possible you know i saw yeah you can there need to be barriers or at least not as many barriers as as i thought i can connect with more people in a a in a way that that is helpful and so i think it's the learning that happens in that state that actually uh matters and this as you described that that sounds a lot like what i understand to be the hallmark feature of really good psychoanalysis that the relationship between patient and therapist hopefully evolves to the point where um uh these kinds of tests can be run within the context of that relationship and then exported to other relations is that exactly right yeah and and that probably i'm assuming is still the goal of really good psychiatry also it's a part of uh intimacy really it should be when we have time i think all good psychiatrists try to achieve that that level of connection and learning uh try to help patients create a new a new model that is stable that has learned and that can help instruct future behavior one of the things that i took from reading your book in addition to learning so much science and the future of psychiatry and brain science was um you know amidst these very many main kids very tragic cases and and sadness and a lot of the the uh the weight that that puts on the clinician on you also that there's a that there's a central cord of optimism that where we're headed is uh not just um possible but very likely and and better yeah and um you know are you an optimist i am and this this is by the way this was a really interesting experience in writing projections because i had a a dual goal i wanted it to be for everybody literally everybody in the world who wants to to to to read it and yet at the same time i wanted to uh stay absolutely rigorously close to the the science what was actually known um when i was speaking about science when i was speaking about the the neurobiology of the of the brain or or psychiatry i wanted to to not have any of my scientific colleagues think oh he's he's going too far he's saying too much and so i had these these two goals which i kept in my mind the entire time and a lot of this trying to find exactly the right word we talked about was on this path of staying excruciatingly rigorous in the science and yet letting people see the hope the the where things were have everybody see that we've come a long way we have a long way to go but but the trajectory and the the path is is beautiful and so that that that was the the goal i i think uh you know of course that sounds almost impossible to to jointly satisfy those two those two goals but i kept that in my mind the whole way through and yes i am optimistic and i hope that came through in the book but it certainly did and at least from this colleague um uh you you did achieve both and um it's a wonderful it's it's a masterful book really and one that as a scientist and um who is a bri fellow brain explorer uh hits all the marks of of rigor and is incredibly interesting and there's a ton of storytelling i don't want to give away too much about it but people should definitely check out the book um are you active on social media if people want to follow you and connect with what you're doing now and going forward yeah i have a twitter uh that's where i i mainly do uh exchange you know tell people about things that are happening we'll provide a link to it but that's carl deisseroth as i recall with a k that's right yeah that's right and um so you're on twitter and um people uh will hear this definitely uh check out the book um there are other people in our community that of course are going to uh be reaching out on your behalf but it's it's incredible that you juggle this enormous number of things um perhaps even more important however is that it's all in service to this larger thing of relieving suffering so thank you so much for your time today for the book and the work that went into the book i can't even imagine for the laboratory work and the development channel options clarity and all the related technologies and for the clinical work you're doing and and for sharing with us well thank you for for all you're doing and reaching out i i i i'm very impressed by it it's important and and uh it's it's so valuable and thank you for taking the time and for all your gracious words about the book thank you i hope you enjoyed today's discussion with dr deisseroth as much as i did be sure to check out his new book projections a story of human emotions it's available on amazon audible and all the other standard places where books are found if you'd like to support this podcast please subscribe to us on youtube as well you can subscribe to us on apple or spotify at apple you also have the opportunity to leave us a five star review and to give us feedback please put any questions you have in the comments section below the youtube video if you'd like us to address certain things in future episodes or if you have questions about this particular episode in addition please check out our sponsors that's a terrific way to support us we also have a patreon it's patreon.com andrew huberman there you can support us at any level that you like last but not least if you're interested in understanding more about how the brain works and how it functions and how it breaks down in various conditions check out the first episode of the huberman lab podcast the title of that episode is how your nervous system works and changes if you're watching this right now on youtube you can simply click on the title card for that episode and last but not least thank you for your interest in science [Music] you