Dr. Karl Deisseroth
Appearances
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 like optogenetics help in this setting?
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
In principle, it could because 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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
You're not gonna 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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
I mean, that's effectively what we already do with the vagus nerve stimulation, the doctor in this case. And 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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
Well, because we only have words, you've 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 reduced speech. But ultimately, you do need something.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
Right there in real time. Right there in real time.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
Through a couple steps, but yeah. And I can turn up the frequency, I can turn up the intensity, all with the radio frequency and control, and then it's reprogrammed or redosed, and then the patient can then leave at this altered dose. In most patients, I don't expect an immediate What I do is I increase the dose until a next level up while asking the patient for side effects.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
Can you still breathe okay? Can you still swallow okay? And I can hear their voice as well. And I can get a sense. And you're looking at their face. And I'm 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 then, you know, I stop at a particular point
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 Neuralink work, as you point out, many people have been doing this in humans as well as in non-human primates. And this is pretty powerful. It's important.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
This will let us understand what's going on in the brain in psychiatric disease and neurological disease, and will give us ideas for treatment. I see that as something that will be part of psychiatry in the long run. Already with deep brain stimulation approaches, we can help people with psychiatric disorders.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
And that's putting just a single electrode, not even a complex 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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
You need 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 sort of the art and the science of psychiatry.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
This is a pretty interesting branch of psychiatry. There's no question that people have been helped by the treatments. There's active debate over what fraction of people who have these symptoms can or should be treated. This is typically Adderall or stimulants of some kind. Yeah, for example, the stimulants. That's right. So ADHD, as its name suggests, it has symptoms of...
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 what's going on around them.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
I have to be totally motionless, which is kind of interesting. How do you go about that? I sit much like this, you know, I try to have time in each day where I am literally sitting almost in this position, but without distraction and thinking. And so it's kind of a, it's almost meditative in some ways, except it's not true meditation, but I am thinking while not moving.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
Yeah. Interesting. Yeah. But everybody, as you say, is very different. And so with ADHD, 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 the teacher or the home situation or something. And then you can help patients.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
It's interesting 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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 toward home tests, but we're not there yet.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 typical situation.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 the tick, which can be a motor movement or vocalization or even a thought. And people do, I think these days, do have this.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 check it and relieve 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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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. 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 make it a psychiatric diagnosis, at least in the world of today.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
Well, you're right to highlight both the opportunity and the peril that is there. And of course, we want to help patients. And of course, we want to explore anything that might be helpful, but we want to do it in a safe and rigorous way. But I do think we should explore these avenues.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
These are agents that alter reality and alter the experience of reality, I should say, in relatively precise ways. They do have problems. They can be addictive. They can cause lasting change that is not desirable.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
And I do think we'll have those measurables at some point. Could it be abused or misused? Certainly, but that's, I think, true for all of medicine.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
Now, that said, even as these medications exist now, as you know, there's an impulse to use them in very small doses and to use them as adjunctive treatments for the therapy of various kinds. And I'm also supportive of that if done 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 exist.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
vastly outweigh the risks that we normally tolerate in other branches of medicine. Why would they work?
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
We have some ideas and no deep understanding. One way I think about the psychedelics is they increase the willingness of our brain to accept unlikely outcomes. ways of constructing the world, unlikely hypotheses, as it were, as to what's going on. The brain, in particular our cortex, I think, is a hypothesis generation and testing machine. It's coming up with models about everything.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 book quite a bit, is Many of these are filtered out before they get to our conscious mind, and that's good.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
We think how distracted we'd be if we were constantly having to evaluate all these hypotheses about what kinds of shapes or objects or processes were out there. And so a lot of this is handled before it gets to consciousness. What the psychedelics seem to do is they...
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
change the threshold for us to become aware of these incomplete hypotheses or wrong hypotheses 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's pretty interesting and it goes wrong in psychiatric disorders.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
I think in schizophrenia, sometimes the paranoid 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 stuck.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
They can't look into the future world of possibilities as effectively. Everything seems... hopeless. And what does that really mean? 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
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
I think 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 they feel that they should be able to handle this on their own. And that can slow treatment. It can lead to worsening symptoms.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
And what these agents may do that increase 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 tendrils of process, of forward progression through the world. That's a concept. It's how I think about it. There are ways we can make that rigorous. We can indeed identify in the brain by recording.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 working with these agents in the laboratory to say, is this really the case? Are these opening up new paths or representations of paths into the future?
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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?
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
I think the brain learns from those experiences. That's the way I see it. And so, for example, people who've taken MDMA, they will, as you say, they'll be the acute phase of being on the drug and experiencing this extreme connectedness with other people, for example. And then the drug wears off, but the brain learned from that experience.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
And so what people will report is, yeah, I'm not in that state, but I saw what was possible. I saw, yeah, you can, There don't need to be barriers, or at least not as many barriers as I thought. I can connect with more people in a way that is helpful. And so I think it's the learning that happens in that state that actually matters.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
It's a part of intimacy, really. It should be when we have time. I think all good psychiatrists try to achieve that level of connection and learning, try to help patients create a new connection. a new model that is stable, that is learned, and that can help instruct future behavior.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
I am. And 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 read it. And yet at the same time, I wanted to... stay absolutely rigorously close to the science, what was actually known.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
When I was speaking about science, when I was speaking about the neurobiology of the brain or psychiatry, I wanted to not have any of my scientific colleagues think, oh, he's going too far, he's saying too much. And so I had 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
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
on this path of staying excruciatingly rigorous in the science and yet letting people see the hope, where things were, have everybody see that we've come a long way, we have a long way to go, but the trajectory and the path is beautiful. And so that was the goal. I think, you know, of course, that sounds almost impossible to jointly satisfy those two goals,
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 much more mysterious. And the only tools we have are words. Neurologists are fantastic physicians.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
This is really interesting. People, here we have, there's a tension between the words that we've built up in the clinic that mean something 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 depressed. What exactly do they mean by that?
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
That may be different 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 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 hope do you have?
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 don't see how I'm gonna get to tomorrow. That's a nice, precise thing that, you know, it's sad, it's tragic, but it's also, that means something. And we know what that means.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
That's the hopelessness symptom of depression. 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 address this issue every day in my life, whether it's in the lab where we're looking at animals.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 some feedback, I get words, I get behaviors, I get actions, but I never really know.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
And psychiatry, despite the depths of our, the mystery we struggle with, many of our treatments are actually, you know, we may be doing better than some other specialties in terms of actually causing, you know, therapeutic benefit for patients.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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?
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
You can train people to derail that 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 patients. anti-psychotic medications. They have side effects, but boy, do they work. They really can clear up auditory hallucinations, the paranoia.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
And then, you know, this is a frustrating and yet heartening aspect of psychiatry. There are treatments like 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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 heartening as it is to see patients respond to this who have severe depression. I'm also frustrated by it.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 autism with rating scales, but those are words still. And ultimately, that's what psychiatry is built around.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
Why can't we do something more precise than this for these very severe cases? In all of these cases, though, in psychiatry, the frustrating thing is that we don't have the level of understanding that a cardiologist has in thinking about the heart. The heart is, we now know, it's a pump. It's pumping blood. And so you can look at everything about...
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
I think the first thing we need is understanding. What is the element in the brain that's analogous to the pumping heart? When we think about the symptoms of depression, 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 depression.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
Yeah. So starting with the body is a good example because 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, innervates the gut.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
By innervate, I mean it sends little connections down to help guide what happens in these organs in the abdomen and chest. it also collects information back. And there's information coming back from all those organs that also go through this vagus nerve, the 10th cranial nerve, back to the brain. And so this is somewhat of a superhighway to the brain then, was the idea.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
That's the reason, yes. Really?
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
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 tract nucleus, which is just one synapse away from the serotonin and dopamine and the norepinephrine.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
Yes, 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 you would have done it anyway. Because it's accessible.
Huberman Lab
Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
It could be, but I would say we don't have evidence 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 patient's voice becomes strangulated and hoarse. They can have trouble swallowing.