Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth

Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. And now, my conversation with Dr. Karl Deisseroth. Well, thanks for being here. Thanks for having me. So, for people that might not be so familiar with the fields of neuroscience, etc. What is the difference between neurology and psychiatry? Psychiatry focuses on disorders where we can't see something that's physically wrong, where we don't have a measurable, where 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. Uh and they can measure and treat based on those measurables. In psychiatry, we have a harder job. 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 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 hyper verbal, 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 reduced speech. But ultimately, you do need something. You need some some words to help guide you. And that in fact there's there's there's challenges that I 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. Do you think we 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. Already efforts are being made to look at certain rhythms in the brain using external EEGs to look at brain waves effectively. 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 a typical situation. And I I do think we'll have those measurable at some point. Could it be abused 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 we're making progress on what the biggest challenge is, which I think there's still such a strong stigma for psychiatric disease that patients often don't come to us and uh 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 uh untreated anxiety issues, if you go for a year or more with a a serious untreated anxiety issue, that can convert to depression. You can add another uh problem on top of the anxiety. And so, it would be you know, why do people not come for treatment? They 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 uh some help is is is a good thing. That raises a 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." If I may, you 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 there 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 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 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 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 and in their mind. But as you say, ultimately, you know, this shows up across I I I address this issue every day in my life, whether it's in the lab, where we're we're looking at animals, whether fish or mice or rats, and studying their behavior, or when I'm in 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. 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. And psychiatry, despite the depths of our the mystery we struggle with, many of our treatments are actually, you know, we're 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, patients who suffer from By the way, both medications and talk therapy have been shown to be extremely effective in many cases. 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 and you can very potently treat panic disorder that way. 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 auditory hallucinations, the paranoia. And then, you know, this is a frustrating and yet heartening aspect of psychiatry. There are treatments like electroconvulsive 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 a 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 a 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 as heartening as it is to see patients respond to this with with who have severe depression, I'm also frustrated by it. Why why can't we do something more precise than than that for these very severe cases? In all of these cases though, in psychiatry, the the frustrating thing is that we don't have the level of understanding that a cardiologist has in 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 this circuit really there for in psychiatry? What are the pieces that are going to be required to cure autism, cure Parkinson's, cure schizophrenia? I I would imagine there are several elements in bins here. Um 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 it What is the the bento box of the perfect cure? Yeah. I think the first thing we need is understanding. What is the elements in the brain that's analogous to the pumping of heart? When we think about the symptoms of depression, that's maybe, you know, we think about motivation and dopamine neurons. 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, but 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 at to make this typical behavior happen and that will help us understand how it becomes atypical. We need to know the circuits. We need to know the cells Yeah. in the various brain regions and and portions of the body and um and how they connect to one another and what the patterns of activity are under a normal, quote unquote, healthy interaction. Yeah. 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. 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 your work in in the laboratory and the clinic and an interaction with a patient. So this is a recall 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 skull and innervates many of the the viscera in and body. What is the potential for channelrhodopsins or related types of algae engineering to be used to manipulate the vagus because I believe in that instance it wasn't channelrhodopsin stimulation, it 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, SSRIs, serotonergic agents, increase dopamine, increase whatever, that sometimes they experience relief but there often serious side effects. Sometimes they don't experience relief but as I understand it, channelrhodopsins and their related technology 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 body and then move into the skull. Yeah. So starting with the body a good example because it it 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 uh guide what happens in these these organs in the in the in the abdomen and and chest. Uh 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 superhighway to the brain then, was the idea. And maybe the idea is maybe we could put a little cuff, a little electrical uh uh device around the vagus nerve itself, 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. reason, yes. Really? Yeah. You're not kidding. I'm not kidding. It's So, stimulating the vagus to treat depression simply because it's accessible. It started as actually as an as an epilepsy treatment and it it can help with epilepsy, but 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 dopamine and the norepinephrine. a link to chemical systems in the brain that make it a rational choice. It 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. You got to would have done it anyway. Because it's accessible, yeah. I see. How do you think it's working when it does work? Is it triggering the activation of 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 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 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 to your initial question, could a more precise stimulation method 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 in point A going to point B that relieves this particular symptom. to fix this key on the piano. Yeah. 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. So, we're talking about a little tiny stamp uh each edge half a millimeter in size. I can 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. Deisseroth, 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 and I say, "How are you I I would go through the symptoms. I 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. in real time. the remote control to essentially to their brain, although it's remote remote control. Through a couple steps, but 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 uh redosed uh and then the patient can can then this altered dose. In most patients I don't expect an immediate mood change. What I do is I increase the the dose until uh uh 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 and I can get a sense looking at their face. looking at their face. And so I can get a sense is there a am I in a still in a safe side effect regime? And I and and and then, you know, I 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. That's very exciting. What are your thoughts about um brain machine interface? It's something that's been happening for a long time now. Devices, little probes that are going to stimulate different patterns of activity in ensembles of neurons. First of all, it's an it's an amazing uh scientific discovery approach. Uh as you mentioned, we and others here at Stanford are using uh electrodes collecting information from tens of thousands of neurons. Even separate from the Neuralink work, as you point out, many people have been doing this uh uh in humans as well as in non-human primates. Um and this is pretty uh powerful. It's important. This will let us uh understand what's going on in the brain in uh in psychiatric disease and neurological disease and will give us ideas for for treatment. I see that as something that will be part of psychiatry uh in in in the long run. Already with deep brain stimulation approaches, we can help people with psychiatric disorders. And that's putting just a single electrode, not even a 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. One of the questions I get asked a lot is about ADHD and attention deficit of various kinds. I have the hunch that one reason I get asked so often is that people are feeling really distracted and and challenged in 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 channelrhodopsins 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 pretty interesting branch of psychiatry. There's no question that people have been helped by the the treatments. There's, you know, active, you know, debate over, you know, what fraction of people who have these symptoms can or should be be treated. This is typically Adderall or stimulants of some kind. Yeah, for example, stimulants, that's right. So, ADHD, it's as as its name suggests, it has symptoms of it can have either a hyperactive state or an inattentive state. And those can be completely separate from each other. You could have a patient who effectively is not hyperactive at all, but can't remain focused on the the what's going on around them. body can be still, their their mind is darting around. That's right. That's Or they can be very hyperactive with their body. Yeah. It happens both Probably rarely is somebody hyperactive with their body, but their mind is still. I 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 motionless. Which is just kind of interesting. you go about that? I I I sit much like this. You know, I I try to have time in each day where I am I'm literally sitting almost in this in this position, but but without distraction and and thinking. And and it's kind of a it's almost meditative in some ways, except it's it's not a true meditation, but I am I am thinking while not moving and I'm thinking about this. to structure your thoughts in that time. 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 a diagnosis with looking at particular externally detectable brainwave rhythms. 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. It has to be done in the clinic. Right. Yeah, in the clinic, right. You have to have the right recording apparatus and so on, but but but that's in principle as you increasing confidence comes in exactly which measurements uh one could even imagine moving toward, you know, home tests. Um 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. Uh do you think that some of the lifestyle factors that um 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 cuz my dad would make me stop. And I I used to Yeah, I couldn't feel any relief of my mind until I would do this. And actually now, if I get very tired, if I've been pushing long hours, it'll come back. So interesting. 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 uh but I used to say that's the only time I feel truly clear for a long And then eventually it dissipated. By about age 16, 17, it 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 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? Yeah, know, This is a great question. I I think about it a lot. There's you know, and and you mentioned this this tic-like behavior in in yourself. It's very common that people who have tics have this building up of something that can only be relieved by executing the tic, which can be a motor movement or or a vocalization or even a thought. And 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 a 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 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 we can't make it a a psychiatric diagnosis. It's at least in the world of today. I'd love your thoughts on psychedelic medicine. Putting them into patients and seeing tremendous positive effects, but also tremendous examples of 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. Uh 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 would 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? Well, you're you're right to highlight both the opportunity and and the peril that is there. Um And of course, we want to help patients, and of course, we want to to explore anything that might be be helpful. And but we want to do it in a safe and 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. Now, that said, uh even as these medications exist now, as you know, there's an impulse to to use them in very small doses and to use them as adjunctive treatments for for the therapy of of various kinds. And I I'm also supportive of that if done, you know, carefully and and rigorously. Of course, there's risk, but there's risk with many other kinds of 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 that indeed their main effect is to create more uh more connectivity at least in the in the moment uh between brain areas. So, psychedelics seem 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, of 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 dream-like experience somehow relieve depression long-term? Do we have any idea why that might be? Okay. I, uh, we have some ideas and no no deep understanding. Uh, one way I I think about the psychedelics is they, um, increase our willingness to our they 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, uh, quite a bit, is many of these are filtered out before they get to our our conscious mind. And that's good. We 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 is handled, uh, uh, before it gets to consciousness. What the psychedelics seem to do is they change the uh, threshold for us to become aware of these incomplete hypotheses or wrong hypotheses or or concepts that might be noise, uh, but are just wrong and so are never allowed to get into our our conscious mind. Now, uh, you know, that that's pretty interesting and it goes wrong in psychiatric disorders, I think, uh, in in schizophrenia, that sometimes the paranoid, uh, delusions that people have are examples of these, uh, poor models that escape into the conscious mind and become, uh, 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 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 escape of some some tendrils of process of forward progression through through the world. Um that's a concept. That'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 see are is this really the case? Are are these opening up new paths or or representations of paths into the future? Mhm. MDMA, ecstasy, is a unique compound in that it leads to big increases in brain levels of dopamine and serotonin simultaneously. And I realized that the neuromodulators like dopamine and 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 these serotonergic compounds like LSD and psilocybin. And there are now data um still emerging that it might be an an in some cases can be useful for the treatment of trauma, PTSD and 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 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 the let's stay with MDMA the experience of huge levels of dopamine, huge levels of serotonin, atypical levels of dopamine and 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 the 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 don't need to be barriers or at least not as many barriers as as I thought. I can connect with more people in a in a way that that is helpful. And so I think it it it's the learning that happens in that state that actually 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 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 it is intimacy really. It it should be when we have time I think all all good psychiatrists try to achieve that that level of of of connection and learning. Try to help patients create a new a new model that is stable, that is 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 many very tragic cases and and sadness and a lot of the the the weight that that puts on the clinician on you also that there's a that there's a central chord of of optimism that where we're headed is not just possible but very likely and and better. Yeah. And um you know, it 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 dual goal. I wanted it to be for everybody, literally everybody in the world who wants to 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 I speaking about science, when I was speaking about 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 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 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 I and I hope that came through in the book. Well, 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 somebody who is a uh fellow brain explorer uh hits all the marks of of rigor and is incredibly interesting, and there's a ton of storytelling. Definitely uh check out the book. Um there are other people in our community that of course are going to uh uh be reaching out on your behalf, but it's it's incredible you juggled 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 opsins clarity and all the related technologies, and 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 it's it's so valuable and thank you for taking the time and and for all your gracious words about the book. Thank you.