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

0:00Welcome 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 Diceroff. 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.

0:43And so psychiatry 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. We use words. We have rating scales for symptoms. We can measure depression and an autism with rating scales. But those are words still. And ultimately, that's what psychiatry is built around. 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 find our way in.

1:36So 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 I can imagine the opposite might be true as well. Well, 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 some words to help guide you.

2:13And 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 sort of the art and the science of psychiatry. Do you think 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. Already efforts are being made to look at certain rhythms in the brain using external EEGs to look at brain waves effectively.

2:52But 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 do think we'll have those measurements at some point. Could it be abuse 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.

3:39And they feel that they should be able to handle this on their own. And that can slow treatment. It can lead to 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 feel like this is something they should be able to master on their own, which can be true, but usually some help is a good thing. That raises a question related to something I heard you say many years ago at a lecture, which was that this was a scientific lecture.

4:29And 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, you could elaborate on that a little bit. And the, the, on the earth 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 are 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?

5:06And what is this landscape that we call feelings or emotions? This is really interesting. People here, we have a, there's a tension between the words that we've built up in the clinic that means something to the physicians. And then there's the cloak, cloak will use of words that may not be the same. And so that's the first level we have to sort out. And someone says, you know, I'm, I'm depressed. What exactly do they mean by that? 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 rid of the, the jargon and get to real world examples of how they're feeling.

5:48So, you know, how do you, what, how much do you look forward into the future? How much 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.

6:25I try to get past the jargon and get to what's actually happening in the patient's life and, and in that 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.

7:04Are 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 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.

7:45For 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, politely treat panic disorder that way. There are many psychiatric medications that are very effective for the conditions that they're treating anti -psychotic 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 therapy, which is, you know, it's extremely effective for depression.

8:32We 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 sees. 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 heartening as it is to see patients respond to this with who have severe depression. I'm also frustrated by it. Why can't we do something more precise than this for these very severe cases?

9:12In all of these cases, though, in psychiatry, the frustrating thing is that we don't have the level of understanding that a cardiologist has and thinking about the heart. The heart is, we now know, it's a pump, it's a 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 is the circuit really there for in psychiatry. I'd like to take a quick break and acknowledge one of our sponsors, David. David makes a protein bar unlike any other. It has 28 grams of protein, only 150 calories and zero grams of sugar.

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11:13Maybe you could just tell us what you think it. What is the bento box of the perfect cure? I think the first thing we need is understanding what is the element in the brain that's analogous to the pumping part 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 that. We 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, we can study those animals.

12:00And so 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 a typical. We need to know the circuits. We need to know the cells in the various brain regions and portions of the body 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.

12:53So 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 the laboratory and the clinic and an interaction with a patient. So this as I 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 the skull and it's many of the viscera and body. What is the potential for channel red options or related types of algae engineering to be used to manipulate the vagus because I believe in that instance, it wasn't channel options to me like she was electrical stimulation right or to manipulate for instance a very small localized region of the brain.

13:47Let me frame it a little bit differently and lighted what we were talking about a couple minutes ago. So my understanding is that if somebody has severe depression and they take any number of the available pharmaceutical agents that are out there SS rise or a ton of chickage increase 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 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 positive anticipation circuit.

14:32Where 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 bodies of good example because it it highlights the opportunity 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 it invades the gut 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.

15:17And so this is somewhat 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 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 yes really yeah you're not kidding I'm not kidding so stimulating the vagus to treat depression simply because it's accessible it started as actually as an epilepsy treatment and it can help with epilepsy but the vagus nerve lands on a particular spot on the brain called the solitary track nucleus which is just one synapse away from the serotonin and dopamine in the north and effort.

16:02So there's a link to chemical systems of the brain that make it a rational choice it's not it's not irrational but I can tell you that even if that we're not true the same thing would have been tried. You know you got you would have done it because it's accessible. 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 but I would say we don't have evidence for for that and so I just don't know. But what is clear is that it's dose limited 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 patients voice becomes strangulated and horse they can have trouble swallowing they can 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 elective electrode and so you can go up just so far with the intensity and then you have to stop.

17:04So you know to your initial question could a more precise stimulation method like optogenetics help in the 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 acts 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 larinks and the fairings and the projections passing through so that's the hope that's the opportunity to problem is that we don't yet have that level of specific knowledge we don't know.

17:41So okay it's the cell starting point A going to point B that release this particular sense we want to fix this key on the piano yeah I'm imagining a little tiny blue light emitting 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 each edge half a millimeter in size I could imagine that being put under my skin and then I would what I hit an apple my finger. So I'm going to say that's a doctor Dicer off 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 Vegas nurse stimulation the doctor in this case and I have this in some of my patients in the clinic I do Vegas nurse stimulation I talked 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 in real time you're holding the remote control to essentially to their brain although it's remote remote control through a couple steps but yeah yeah yeah and I can I can turn up I can turn up the frequency I can turn up the intensity all with the radio frequency and control and then it's it's reprogrammed.

18:58Or a redost and then the patient can can then leave at this altered dose in most patients I don't expect an immediate mood change what I do is I increase 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 get a sense looking at their face and looking at their face and so I can get a sense is there a am I still on a safe side effect regime and I can and and and then you know I'm not going to do that. 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.

19:39What are your thoughts about brain machine interface is something that's been happening for a long time now devices little probes are going to stimulate different patterns of activity and ensembles of neurons. First of all it's an amazing scientific discovery approach as you mentioned we and others here at Stanford are using electrodes collecting information from tens of thousands of neurons even separate from the neural link work as you point out many people have been doing this in humans as well as a non human primates. And this is pretty powerful it's important this will let us understand what's going on in the brain in in psychiatric disease in neurological disease and we'll give us ideas for treatment.

20:22I see that as something that will be part of psychiatry 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 complex you know close 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. I'd like to take a quick break and acknowledge our sponsor eight sleep eight sleep makes smart mattress covers with cooling heating and sleep tracking capacity. One of the best ways to ensure a great night sleep is to make sure that the temperature of your sleeping environment is correct.

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23:43Yeah. This is a pretty interesting branch of of psychiatry. There's no question that people have been helped by 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 treated. This is typically aterol or stimulants. For example, stimulants that's right. So ADHD it's 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 what's going on around them.

24:29So that body can be still but their their mind is darting around. That's right. That's where they can be very hyperactive with their body. They have some spokes. Probably rarely a somebody hyperactive with their body but their mind is still. 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 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 emotional.

24:58Which is kind of interesting. How do you go about that? I sit much like this. You know I try to have time eat in each day where I am literally sitting almost in this position but without distraction and thinking. It's almost meditative in some ways except it's not true meditation but I am thinking while not moving in. You're trying to structure your thoughts in that time. But everybody as you say is very different. With ADHD you have the key thing is we want to make sure that this is present across different domains of wife, school and home to show that it really is a pervasive pattern and not something specific to the teacher or the home situation or something.

25:49And then you can help patients. It's interesting that ADHD is one of those disorders where people are trying to work on quantitative EEG based to diagnoses. And so there's some progress toward making a diagnosis with looking at particular externally detectable brain wave 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. It has to be done in the clinic. Yeah, in the clinic right. You have to have the right recording apparatus and so on. But that's in principle as increasing confidence comes in exactly which measurements one could even imagine moving towards home tests but we're not there yet.

26:33Amazing. I think 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 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 me more like OCD and I'll come clean here by saying when I was younger when I was a kid I had a grunting tick. I used to hide it and actually used to hide in the closet because my dad would make me stop. And I used to I couldn't feel any relief of my mind until I would do this.

27:11And actually now if I get very tired, if I've been pushing long hours it'll come back. I was not treated for it. 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 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 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 he had just disappeared.

27:47So I have great 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 all these email etc. 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, this is a great question. I think about it a lot. And you mentioned this 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 that the tick which can be a motor movement or a vocalization.

28:37Or 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, build up, build up until they can check it and really leave it. And there's some similarities. You know, there is a little reward that comes with the checking. But the key question in all of psychiatry, what we do is 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 psychiatric diagnosis requires that it has to be disrupting someone's social or occupational functioning.