Chapter 1: What is discussed at the start of this section?
Welcome to the Huberman 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. My guest today is doctor and professor Mark Desposito. Dr. Mark Desposito is a neurologist and a professor of neuroscience and psychology at the University of California, Berkeley.
He is a world expert in the brain mechanisms controlling executive function and memory. Executive function is the way in which we are able to designate and carry out specific cognitive strategies, and it is fundamental to every aspect of our daily lives.
And because so much of being effective in daily life involves using specific context-relevant batches of information in order to understand what to do and when, and what not to do and when, and to come up with strategies that are very adaptive for us to move forward in the context of relationships, work, school, and athletics,
and on and on, there's really no separation between executive function and memory. And today, Dr. Desposito explains the neural circuits controlling executive function and memory, how they interact, the key role of dopamine in executive function and something called working memory, and teaches us ways to optimize executive function and memory, that is, how to optimize cognitive function.
In addition to discussing how to optimize cognitive function in the healthy brain, today's discussion also centers around how to restore cognitive function in disease or injury conditions that deplete executive function and memory, such as traumatic brain injury, concussion, Alzheimer's, Parkinson's, and attention deficit disorders.
Dr. Desposito shares with us research findings both about behavioral and pharmacologic strategies to enhance executive function and memory. By the end of today's discussion, you will have learned from Dr. Desposito a tremendous amount about the modern understanding of cognition, that is thinking and memory, and the carrying out of specific cognitive strategies.
You will also learn a tremendous amount about how to optimize brain function and brain health. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public.
In keeping with that theme, I'd like to thank the sponsors of today's podcast. Today's episode is also brought to us by Waking Up. Waking Up is a meditation app that includes hundreds of meditation programs, mindfulness trainings, yoga nidra sessions, and NSDR, non-sleep deep rest protocols.
I started using the Waking Up app a few years ago because even though I've been doing regular meditation since my teens, and I started doing yoga nidra about a decade ago,
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Chapter 2: How does dopamine influence working memory?
But when we're talking about the frontal lobes and talking about its, you know, involvement in higher level cognitive abilities, we're talking about the prefrontal cortex. And this is what's considered sort of the highest level of cortex in the brain. So, yeah, when you think about it, people assign it all sorts of functions.
Almost every function you think of, people have sort of put into the frontal lobes. But I think what we've all kind of... move towards this idea of executive function, this ability to plan, to organize, to really transfer our thoughts into an action and really to be guided by goals and intentions and not be kind of ruled by sort of just automatic decisions.
A word we use in cognitive neuroscience is called cognitive control. So cognitive control, executive function is what we attribute to the frontal lobe. And so you can think of it as the CEO of the brain or the conductor of the orchestra, really the part of the brain that's really controlling the rest of the brain.
So yeah, if you had to choose which part you wanted to not leave home, it's your frontal lobes.
Speaking of which, what are some of the symptoms of mild frontal lobe damage and severe frontal lobe damage, damage brought about either through neurodegenerative disease or physical injury? I know we're going to talk a bit about both today or a lot about both, but how would lack of executive function show up maybe on kind of a subtle level?
Yeah, I mean, at first I should say is that it shows up all the time. And frontal lobe behavior is probably much more prevalent than we realize. Certainly we think about it when you have a brain injury to the frontal lobes. And there's lots of neurological disorders like stroke and traumatic brain injury and Alzheimer's disease that can affect the frontal lobe.
And there's a number of psychiatric disorders, obsessive-compulsive disorder, and schizophrenia and depression that are thought to be frontal lobe dysfunction. But when you're sleep-deprived and when you're stressed and just normal aging, the frontal lobe seems to be the first system that's affected because it really is involved in the highest level.
So when we're having a bad day, when we're having difficulties sort of setting priorities, when we're having difficulties achieving goals the goal that we've set out. When we get distracted, you know, when we're not able to sort of adapt and be flexible, these are all the type of things that reflect that our frontal lobes are not functioning optimally.
Approximately what age does the frontal lobe circuitry come online, so to speak? I mean, when I see a baby, babies can orient their eyes towards things, but they're rather reflexive in where they'll place their eyes. But By the time kids are three or four, they can certainly play with blocks or interact with other children or their parents.
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Chapter 3: How do the frontal lobes and executive function relate?
They're no longer... my spouse are no longer my best friend, they're no longer my father. There's something, they can't put it into words, but they're not them anymore. There's something that's changed. Whereas if you talk to a patient with Broca's aphasia who has this inability to speak, they can't get any words out. You know, this is a devastating problem. They're still the same person.
their personality hasn't changed. They feel the same person. They just can't speak. The way they get around in the world is different. Or if you take a patient with prosopagnosic, which is this inability to recognize faces, of course, the way they navigate around the world is difficult. And it's not the same, but they're still the same person.
So there's something really special about the frontal cortex that allows us to be as you said, sort of who we are. And that's the difficult part, like how does the frontal lobes allow us to sort of take who we are and translate that into knowledge? So we're not, I guess another way of saying it, just having knowledge isn't what makes us who we are, right?
It's to be able to take that knowledge and present it in a way that allows us to live life based on our intentions and our goals and our desires.
So much of things like stoic philosophy and even online wellness culture are about having routines, overcoming reflex by just having recipes, scripts to follow each day. I certainly try to have my mornings be as what I call linear as possible. And I find it's much easier in the earlier part of the day to just –
decide here's what I'm going to do, write out a list, do things in a certain sequence. If I don't do that, I go nonlinear, as I refer to it, and we'll get distracted and things of that sort. But earlier you mentioned sleep deprivation can impair frontal lobe function.
It does seem that as the day progresses, and certainly in the middle of the night, it just becomes much harder to control our thinking, maybe even our behavior, and certainly our emotions. Is there a frontal lobe regulation of emotional states as well? I know you have some recent work on this, so I'd love to hear more.
Yeah, I mean, as I was saying earlier, the frontal lobes is a big place, and half of it is involved in these high-level executive functions, but the other half of it is part of the limbic system. We call it the paralimic system that's involved in social and emotional behavior. there's this intimate back and forth between these two areas of the cortex.
If you have just damage to these frontal, to these areas that are kind of in the frontal lobe, you will have many different impairments that we would call sort of social or emotional impairments, and their executive function will be quite normal. And then you'll have the opposite where patients with the lateral damage will have executive functions, but they seem emotionally intact.
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Chapter 4: What are the symptoms of frontal lobe damage?
Social media is not physical, but we'll rule that portion out. But there's a rule set. There's goal-directed behavior. presumably some of the things that happen in a game of soccer with friends translate to some other domain of life because it's a single context game of soccer. Whereas with social media, I don't know anybody that goes and looks at one account and that's it.
and absorbs the information, maybe comments, has an interaction and goes. It's hundreds or thousands of contexts. So is there any risk or perhaps benefit to being able to get this very detailed portal into so many contexts per unit time? I mean, the forebrains never had done that in the course of human history, as far as I know.
Yeah, I mean, I think there is a risk. But what pops to mind, you know, having kids is watching them navigate in their cars to places totally dependent on Google Maps. I think you're probably old enough to remember real maps where you didn't have one.
I still have one in my car. I love paper maps. I love maps.
Right, where you had to really figure out, you know, you had to go to a certain place and you had to either look at the map or stop at a gas station and ask. These skills were something that you learned and you developed and it was problem solving. And that's all gone now.
I mean, I wonder even if sometimes if people even know the direction they're going, whether it's west, north, or what town they're in because they're just following the directions. So we'll see. I just can't imagine that... that learned skill is not going to be detrimental to us at some point and generalize in a bad way, right? As opposed to a good way. So yeah, it does definitely worry me.
But like you said, there's nothing on the phone that helps you plan a podcast, nothing that helps me in the emergency room, nothing helps a professor when he's giving a lecture. So I agree with you that the sort of having your head buried in a cell phone, I'm not Yeah. I don't see it being healthy for your frontal lobes.
Let's talk about working memory. Some years back, but still now, you use working memory tasks and experiments in your laboratory. If you would be so kind as to explain what working memory is, and then I'd love to talk about some of the work you've done exploring the role of dopamine in working memory, because this is so critical to everyday life.
And I know dopamine is a bit of a buzzword these days, but The listeners of this podcast anyway are pretty sophisticated in terms of knowing that dopamine is not just about reward. It's about motivation and goal-directed behavior. And I think dopamine intrigues for a good reason, that it does govern a lot of our quality of life. So what's working memory?
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Chapter 5: What are the common causes of traumatic brain injury and concussion?
And those are the most worrisome to me because we don't have very good interventions to try and help that. And I don't think we take these patients very seriously when they're complaining of something that seems very vague and not very specific to most, most doctors.
What do you tell a patient who comes in and has clearly had a concussion? Um, mild or severe concussion, maybe a car accident, maybe a sports injury, maybe they were knocked out cold, maybe not, but they're having some headaches, some photophobia, sensitivity to light, just feeling not right. I've had a couple of these, unfortunately, and you just feel off. You don't feel quite right.
And some of that manifests as focus issues. This was some years ago. I like to think I'm through it. I've had scans and I'm good. So thank goodness. But what do you tell them besides don't get another one?
Yeah, well, first of all, I explain what a concussion is. What I found in neurology, a lot of what patients want to know is they just want to understand their problem. They're not walking in expecting a cure. Just understanding what it is, having someone understand what happened to them is very helpful and comforting.
What we mean by concussion, and in the clinical world we use mild traumatic brain injury kind of synonymously with concussion, it basically is a tearing of axons. The brain cells have these long fibers that communicate with each other, and they're called axons.
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Chapter 6: How does emotional regulation relate to frontal lobe injuries?
And when the brain violently moves forward and backwards, if you're in a car accident and you have your seatbelt on and you suddenly hit, you go from 50 to 0, your head violently goes forward and violently goes backwards. And that angular force actually tears and stretches axons in the brain. So if you've had a concussion, you have torn some axons. I mean, luckily we have billions of them.
And so if you tear a couple of thousand, you will recover, but you have torn axons. It's a real neurological, it's a real brain problem. injury, even if you haven't lost consciousness and you've only had symptoms for a couple of days. And there's a correlation, the longer you've lost consciousness and the longer your symptoms last, the more axons you've torn.
There's kind of a direct relationship between the two. So the mechanism is these torn axons, so now nerve cells don't communicate with each other and different brain regions are not communicating with each other. And it turns out the most common place for axons to tear is in the frontal lobes.
And so now we talked about all these things that the frontal lobes do to orchestrate the rest of the brain. Well, it has some injured pathways. And that's why a lot of the symptoms that patients have are these kind of mild executive symptoms. This mental fogginess that they're describing is just this inability to... to get things get things done.
They don't lose knowledge of who they they don't forget their name or, you know, forget where they live or lose memories from the past or anything like that. But they just they don't officially get things done as well as they used to. It only takes a little bit of a drop, right?
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Chapter 7: What role does sleep play in cognitive function after a concussion?
You people think you have to have a big drop in performance to have it have a real life impact, just a 1% drop. And you're you're having a hard time doing your podcast or teaching a lecture or whatever you might do.
A 1% drop sounds like a frighteningly small change required to negatively impact life. So how about a poor night's sleep? I mean, what kind of drop in prefrontal cortical function are we looking at? Let's say I normally get seven or eight hours or six to eight hours, and I suddenly only get three or four. Are we talking a significant detriment?
I do think so. I do think that, yeah, that it is significant, a poor night's sleep. And we all notice that. I mean, it's very obvious. I mean, and, you know, it's hard to sort of quantify. I'm a baseball fan, so I can quantify it like if you think about it in a pitcher and how fast they throw, you know.
A small drop for them, someone who's throwing 100 miles an hour, just a small drop turns them from really elite to someone mediocre. Maybe it's more of a 10% drop, but a still relatively small drop can have a huge impact. I think people think that just because you're a little bit off, that's not a big deal. You kind of work through it. And that's what most doctors say. Just plow through it.
Just work your way through it. You're going to get better. As opposed to saying...
yeah you really had a brain injury um this is what happened we need to rehabilitate you just like we would do if you tore your anterior cruciate ligament i don't know why tearing your crucial ligament or your achilles tendon gets more interest than than tearing axons in in your brain it's it's it's amazing to me that that there's more emphasis on orthopedic injuries than brain injuries
Yeah, I don't know why that is either. I think the brain is mysterious enough that most people and many clinicians just kind of back away with hands raised. But if you are in the field of neurology or psychiatry, I suppose, then one has officially signed on to try and resolve these matters.
So for somebody that has a traumatic brain injury or low level concussion, excuse me, would part of the primary advice be to try and get one's sleep as good as possible? Given that sleep deprivation can compound traumatic brain injury-induced deficits in working memory.
And who knows, maybe a good portion of the deficits in working memory due to traumatic brain injury and concussion is because of the sleep deprivation that it can cause. So it can get circular.
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Chapter 8: How can mindfulness meditation enhance executive function?
Not only that, but one of the most common symptoms that my patients with concussion have is their sleep is disruptive. And that's true in neurology. It's fascinating. Almost every neurological disorder, my patients complain of their sleep.
And I started asking, you know, not a lot of neurologists ask you how you sleep, you know, but I remember back from my residency, one of the first things my attending would do when we got to the ward is, I said, how'd you sleep last night? And it's just across the board. Patients are not falling asleep, they're not staying asleep, and we still don't understand why just brain injury does that.
So almost every concussion patient says, I'm not sleeping well, which then compounds the problem. So optimizing sleep, obviously optimizing nutrition. There's a question about activity. It used to be that we used to recommend, you know, you had a concussion, you should don't go to work, you know, sleep, you know, just take it easy for a while. Don't exercise. Keep the blinds drawn.
But now it's the idea that you should really get up and moving. You got to do what you can tolerate. You don't want to give yourself more of a headache or more light sensitivity. But as much as you can tolerate is...
the thought these days about sort of promoting recovery and then really getting your brain back working i think you know a lot of my patients they're off from work for a couple weeks and they feel fine and they think they're pretty much normal and then the first day of work is a complete disaster because until you actually test it in real life you don't know how what kind of troubles you have so i don't recommend going back full steam but i do recommend going back trying to build up these
these skills again. And then I think we, you know, I think we need to develop therapies that people will use. You know, things like goal management training, which involves a therapist and, you know, health insurance doesn't pay for this. So 99% of my patients don't get any help, you know, by any kind of intervention.
uh unfortunately but now we talked about technology things like um brain hq do you know about brain hq so mike merzenich um which i know you've talked about with eddie um developed a a a company called posit science where developed these brain training games that that can help improve specific cognitive functions and they're very easy to do because they're online and they you know they're
There's science behind them and you can do them. So in that way, you don't have a therapist in your room, but you can online sort of do these sort of things that are targeting specific mechanisms to try to improve the kind of things that we think are impaired by concussion. And I'd like to see more patients get started on some of those things.
Unfortunately, if you go on the web and just say, I won't do brain training, you'll be overwhelmed with things and you don't know what works and what doesn't work.
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