The Tim Ferriss Show - #83: The Maverick of Brain Optimization

Episode Date: June 22, 2015

"My lab is interested in pursuing how we can enhance cognition to improve quality of life." - Adam Gazzaley Dr. Adam Gazzaley (@adamgazz) obtained an M.D. and a Ph.D. in Neuroscience at the Mount Sinai School of Medicine in New York, then postdoctoral training in cognitive neuroscience at UC Berkeley. He is now the director of the Gazzaley Lab at UC San Francisco, a cognitive neuroscience laboratory. His recent studies go far beyond mere description — he and his lab are exploring neuroplasticity and how we can optimize cognitive abilities, even in healthy adults. So, what happens when you combine cognitive-focused video games with neurofeedback, magnetic and electrical stimulation, and even performance-enhancing drugs? Well, that’s just one of many things we cover in this conversation. As someone with Alzheimer's disease and Parkinson's disease on both sides of my family, I find Adam's work to be of incredible importance and promise. I hope this discussion blows your mind, in the best way possible. Enjoy! Show notes, links, and resources can be found at fourhourworkweek.com/podcast This podcast is brought to you by a new sponsor, LegalZoom. Matt Mullenweg (CEO of Automattic - now worth more than a billion dollars) first incorporated his company on LegalZoom. LegalZoom, which I've used myself, can help you with almost anything legal, including setting up a will, doing a proper trademark search, forming an LLC, setting up a non-profit, or finding simple cease-and-desist letter templates. LegalZoom is not a law firm, but they do have a network of independent attorneys available in most states. They can give you advice on the best way to get started, provide contract review, and otherwise help you run your business. Use the code "Tim" at checkout to get $10 off your next order. Take a gander at everything you can get for a fraction of what you'd expect -- LegalZoom.com This podcast is also brought to you by 99Designs, the world’s largest marketplace of graphic designers. Did you know I used 99Designs to rapid prototype the cover for The 4-Hour Body? Here are some of the impressive results. Click this link and get a free $99 upgrade. Give it a test run.. Thanks for listening!***For show notes and past guests, please visit tim.blog/podcast.Sign up for Tim’s email newsletter (“5-Bullet Friday”) at tim.blog/friday.For transcripts of episodes, go to tim.blog/transcripts.Interested in sponsoring the podcast? Visit tim.blog/sponsor and fill out the form.Discover Tim’s books: tim.blog/books.Follow Tim:Twitter: twitter.com/tferriss Instagram: instagram.com/timferrissFacebook: facebook.com/timferriss YouTube: youtube.com/timferrissPast guests on The Tim Ferriss Show include Jerry Seinfeld, Hugh Jackman, Dr. Jane Goodall, LeBron James, Kevin Hart, Doris Kearns Goodwin, Jamie Foxx, Matthew McConaughey, Esther Perel, Elizabeth Gilbert, Terry Crews, Sia, Yuval Noah Harari, Malcolm Gladwell, Madeleine Albright, Cheryl Strayed, Jim Collins, Mary Karr, Maria Popova, Sam Harris, Michael Phelps, Bob Iger, Edward Norton, Arnold Schwarzenegger, Neil Strauss, Ken Burns, Maria Sharapova, Marc Andreessen, Neil Gaiman, Neil de Grasse Tyson, Jocko Willink, Daniel Ek, Kelly Slater, Dr. Peter Attia, Seth Godin, Howard Marks, Dr. Brené Brown, Eric Schmidt, Michael Lewis, Joe Gebbia, Michael Pollan, Dr. Jordan Peterson, Vince Vaughn, Brian Koppelman, Ramit Sethi, Dax Shepard, Tony Robbins, Jim Dethmer, Dan Harris, Ray Dalio, Naval Ravikant, Vitalik Buterin, Elizabeth Lesser, Amanda Palmer, Katie Haun, Sir Richard Branson, Chuck Palahniuk, Arianna Huffington, Reid Hoffman, Bill Burr, Whitney Cummings, Rick Rubin, Dr. Vivek Murthy, Darren Aronofsky, and many more.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

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This episode is brought to you by Five Bullet Friday, my very own email newsletter. It's become one of the most popular email newsletters in the world with millions of subscribers. And it's super, super simple. It does not clog up your inbox. Every Friday, I send out five bullet points, super short, of the coolest things I've found that week, which sometimes includes apps, books, documentaries, supplements, gadgets, new self-experiments, hacks, tricks, and all sorts of weird stuff that I dig up from around the world. You guys, podcast listeners and book readers, have asked me for something short and action-packed for a very long time. Because after all, the podcast, the books, they can be quite long. And that's why I created Five Bullet

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dig it a lot and you can, of course, easily subscribe any time. So easy peasy. Again, that's tim.blog forward slash Friday. And thanks for checking it out. If the spirit moves you. Hello, you sexy minxes. This is Tim Ferriss. And welcome to another episode of The Tim Ferriss Show, where my job is to attempt to deconstruct world-class performers. I interview the best of the best, whether they be chess prodigies, hedge fund managers, billionaire startup investors, actors, politicians, special ops operatives, and generals, and everything in between, what I try to do is tease out the routines, the habits, the first 60 minutes of their day, favorite books, all the tools and tricks that you can apply to your own life to emulate and

hopefully replicate a lot of their success. And this episode is by popular demand. Many of you have asked for more scientists, especially more unorthodox scientists. And you've enjoyed past episodes with Dr. Peter Atiyah, Dr. Rhonda Patrick, among others. Those were very, very popular. And today I bring you Adam Ghazali. Adam Ghazali has been requested by name and now you have him. So Ghazali, the gas monster, the gas man, no one calls him any of those things, but he's a buddy of mine. Dr. Adam Ghazali got his MD and PhD in neuroscience at the Mount Sinai School of Medicine in New York, then did his postdoc training in cognitive neuroscience at UC Berkeley. Now he's the director of the Ghazali Lab at UC San Francisco, which is a

cognitive neuroscience lab. And I've spent time in the lab with things stuck to my scalp, getting zapped both as a subject, but also as an experimenter, a very novice data gatherer. And I thank Adam for letting me bumble my way through that. Adam has a very unique research approach in his lab. They use a powerful combination of tools that are very often used in isolation, but in his lab, they're combined. So that includes f they're taking a 9-volt battery equivalent in charge and applying it to their scalps to improve accuracy. It's trippy stuff. And to start with, his research using these tools and others has expanded our understanding of the alterations in the brain that lead to age-related cognitive decline. Klein. But that's not enough, obviously, for me. Most important or most interesting to me, his recent work goes far beyond description. He and his lab are exploring neuroplasticity and how we can optimize our cognitive abilities, even if we're healthy, via engagement with custom-designed video games. And of course, then that leads to the question, what happens when you combine these games with neurofeedback, electrical stimulation, or even performance enhancing drugs? What about using all of them at once? Well, that's just one of the things that we cover

in this conversation, which is very wide ranging and it gets dense in a few areas. Bear with it. Listen, you will pick up a lot, but we also talk about how he came to be as good at what he does as he has. That was a hell of a sentence, and his routines, all of the things that he does to bolster a world-class operation and world-class performance. So without further ado, please enjoy Adam Ghazali. Adam, sir, welcome to the show. Thank you very much. So I am stoked to be in this beautiful office. I've been in the cave all day.

You have more sunlight in your office and lab. We're here at UCSF. And the name of the lab is? Gazali Lab. Of course. Very well named. And I've had my brain shocked here. I have, I suppose, participated in shocking other brains, to use a scientific term.

And you have parallettes under your desk. Yes, I do. Yeah, for working out. And I just found your entire career so fascinating. We've spent a lot of time together. And I wanted to have you on the show to just explore all the nooks and crannies of this multifaceted life you've designed for yourself. And I thought we could start with, of course, you're very good at hosting parties. So when you're at such a party, your own party or otherwise,

if somebody asks you, what do you do? How do you answer that? Oh, it's not an easy question at a party, but I definitely get asked that one. You know, I usually start by saying I'm a neurologist and a neuroscientist because it sort of lays the framework from my perspective. But if I have to get into a very short answer, then I dive right into the fact that my lab is interested in pursuing how we can enhance cognition to improve quality of life. And you have a magazine cover outside of this lab on the wall, and that is Nature. And you have work that is the cover story. What is that work?

What is the tagline on the cover? Yeah, so Nature was kind enough to put the title Game Changer on the cover of the journal, which is quite a favorable pun for our lab, I would say. And the game itself, so that is a reference to, I guess it was NeuroRacer in this case? And why was that such a game changer in their mind? Well, it's a good question. I think that what that paper was able

to show that had not really been documented well before was that a team of scientists could work with video game professionals to build something customized that targets a process in the brain that's deficient in a certain population. In this case, it was older adults and their cognitive control abilities. And then after you build that game, you can go through a careful placebo-controlled study with neural measures to document the mechanisms of the effect and show that you can create sustainable and meaningful changes in the brain using a video game. So the aspect that I found most fascinating is the sustained part.

So if we're looking at using very simple video games, but video games that can be made quite sexy to, say, reverse or mitigate the cognitive decline associated with the progression of age, what did you see in terms of the persistence of effect? Did they have to do it every day or they just fell off a cliff? Well, that was actually one of the most surprising findings of this study. So it took us a year to build the video game.

We worked with friends of mine that were professional video game designers and engineers and artists at LucasArts back in 2008. So after a year of development, it took us five years to do this study, which involved looking at lifespan changes from 20 to 80 years old and using the game as a therapeutic to improve cognition. Our study involved one month of gameplay by older adults, healthy to 60 to 80-year-olds around the Bay Area, and they'd play it for one hour a day, three days a week for four weeks. And then we looked before and after at what changed in terms of their cognitive abilities

and what changed in their brain. Around six months or so, pretty much around six months, I realized, wow, we should at least bring these folks back and see what's going on. As a follow-up. As a follow-up. As a follow-up. It wasn't really planned or funded in the study. But we saw such profound changes in this group a month later that we just wanted to take a peek. So we took these laptops back from them.

Many of them were upset to have lost access to the game, which is pretty funny because they were pretty much all technically non-savvy, to say the least, before they started playing. And they get really good at the game, and they feel a connection with it. So they haven't played the game in six months. We bring them back, and we just had them play the game again. What we found, shockingly enough, was that their ability to multitask on this game, which is a notoriously challenging activity for older adults, as we've documented in dozens of papers over the years. Not to interrupt, when we say older, when does that start to, is it like a 30 plus,

you just start to lose incrementally this ability? Well, you know, traditionally we tend to, we tended to think of older as 65 and then it was 60 and then it was 50. And now from my perspective, older is being more, you know, older than 23 years old. Because when we look at cognitive abilities, especially like these very fluid control abilities, processing speed, working memory you only have limited funding and you can't do the entire lifespan. So we were pretty surprised to see that their ability to multitask in this game, in this 3D environment, had not declined six months later. even though it was very deficient prior to training, reached levels of 20-year-olds after a month of training and then preserved at the 20-year-old level for six months. Had we known that, we would have done a lot more detailed study

to see what other skills persisted. And in our current studies, we're doing that. We're very focused on the follow-up and to see this sustainability. What does it mean? What causes it? It's definitely very that's just it's so amazing to me because i it it brings up all sorts of interesting questions uh and i mean you're the master at formulating these questions and you're also the i think a master at not fooling yourself right i mean as a scientist you have to really question your

assumptions and look for all alternate alternate explanations for what you think is happening. But I remember just before we started recording, we were talking about Arnold Schwarzenegger and how anxious I was before interviewing him. But when I asked him about Transcendental Meditation, what I thought was so fascinating is he said that he embraced TM, did it on a daily basis for something like a year, and then felt even years later that the effects had persisted. And if that is the case, there are many different ways you could explain it, but if you're, let's say, trying to tie it together with NeuroRacer and other tools, what are the possible, the theories or the plausible

explanations? Is it some type of plasticity change? Is there a biochemical element? What are the possible explanations for that or mechanisms? Yeah, I would say that there's two main mechanisms for sustainability effects, such as we found in our study and other people have observed in their lives. And one is what you just described, plasticity. So our brains are plastic, meaning that they modify at every single level from structure to chemistry to physiology, all in response to interactions with the environment, right? It's the very basis of all learning. And plastic changes, when they occur in a deep way and involve all those multiple

levels of change, can last for quite a long time. So it's possible that the changes were deep enough that the system just reached a new sort of homeostasis, right? In addition to our brain being plastic, it also has a great deal of stability as well, right? It just doesn't change very easily. That would be very dangerous and detrimental. So it's possible that it's been moved into a new, more optimal state, and then that state preserved just because the plastic changes were so profound. Another possibility, which is interesting, and no, I don't think any less interesting, but a different one, is that you engage in training that's very different, that then moves your brain into a different state and a different set of abilities that you didn't have before.

It's possible that because of that, you have now modified your behavior and how you interact with the environment. And that new manner of interaction is what leads to the sustainability. So what would be an example of that? Here's a sort of lowball example, right? Not so complicated, but let's say you go to the gym for a couple months and you get some benefit, right? Now, no one really thinks that if you stop working out for a year, that benefit will

maintain, right? We got a pretty good idea that you do need to keep sustained physical activity to see a benefit. So you stop going to the gym physical activity to see a benefit. So you stop going to the gym because you moved and the gym is no longer accessible for whatever reason. You let your membership run out. But then because you're feeling more empowered by being in shape, you start taking the stairs and not the elevator. And so there is an example, sort of obvious one, of a change that you made in your life, a behavioral change in response to the training, right? It was caused by the training, but that change in your life then leads to the sustainability of those effects, not because of the direct effects, but because you continue to

exercise them in a different way than you were trained on. Which is very common, right? I mean, for instance, if you're looking at behavioral change and you want to get someone to change their diet, but if you're disallowed from saying change your diet, get them to start exercising. And they'll start being more conscious of health-related decisions across the entire spectrum of their activities. It's what we always hope happens, right? Because that really has profound effects and reverberates. You get this cascade of beneficial effects that feed on each other. So it was caused by the training program,

but the sustainability of it is caused by the behavioral influences that that training program have that then allows you to maintain. And the Nature magazine, I just want to I suppose it would be better called a journal.

Yeah, that's a journal. Yeah, with a very nice glossy cover on it. Well, yeah, there's like two top science journals, general science journals in the world, Nature and Science, and Nature being one of them, and please correct me if I'm wrong, is having the cover of nature is kind of like in the business world, walking into the airport on the way to your gate and your face is on the cover of every business magazine. Because there are dozens and dozens of business magazines, but like you said, there are kind of two big players in this space. How did that feel when it was 100% and you were no longer worried about bad juju and jinxing yourself when that day came when you knew it was a hundred percent you were going to have

the cover of that magazine i mean it was definitely ecstasy you know i mean i where were you when did it when did it really when you're like okay now it's a hundred percent yeah i was you know not in a very glamorous location sitting in front of my computer checking email, of course, is the way I found out. It's not like someone drops in on a parachute and gives you a golden ticket. It's not quite dramatic. But it was incredible because you spend your whole life. I did an MD and a PhD. And I was in school for 18 years after high school and just

a long pathway and then build a research program, create a lab, do a very risky study that most people thought was crazy, building a video game to rewire brains of older adults and go through all those stages. And then just the act of getting published is just incredibly grueling. And then obviously go all the way to being accepted into nature. And then the cover, it's just a very drawn-out, painful process. So when it ends, like you said, in one moment where it's there, it's absolutely thrilling. And the risk that you mentioned, I think, is an interesting topic to explore with you because you've crafted a very,

from my perspective as an outsider, but also from the perspective of PhDs who have worked with you, Daria, for instance, a very unorthodox setup here for yourself. What gave you the confidence to build the game and tackle that despite the perception by many people that it was a very risky thing to do? What was the internal self-talk? What allowed you to do it? I mean, mostly it made sense to me. To me, it was a logical approach. We've been building up

confidence in the video game genre in general as being able to transform or to have an influence on behavior. Our research had pointed to it in many directions that this was possible. And to me, it just seemed that it was time that we challenge the system, not step in the footsteps of everyone that went before us. Much of the field looks at molecular approaches, pharmaceuticals. And I was incredibly excited, as everyone is, about all the innovation in the tech world. And to be able to bridge that with neuroscience for health outcomes just seemed incredibly exciting. And I've never really been too afraid of doing things like that, of stepping out when it seems risky?

Why is that? Do you define risk differently from other scientists? Or is it from experiences you've had that other scientists haven't? Because it is a very, when looked at sort of amorphously, it's a risk-averse community, it would seem, in a lot of senses. I think that we were sort of trained to travel through our scientific careers in a very iterative process. You know, you build on the discoveries that came immediately before you and you advance them. And that's not really how I want to do science. I want to do fundamental breakthroughs if possible.

And so if you have that mindset, if that's how you challenge yourself, that that's what you want to do with your life, with your like, you know, small amount of time that you have here to make a difference, then the only way to do it is to do the type of research that other people would think of as risky or even foolhardy. You know, I mean, that's just part of the game. Which person, historical figure in science or elsewhere, do you most admire? Well, I could tell you who I was most inspired by. When I was a kid, I didn't grow up with science or medicine in my life. I grew up in Queens. My parents didn't go up with science or medicine in my life. I grew up in Queens. My parents didn't go to college. No one in my family did.

And they were very academic, supportive of me as a kid. But I just didn't have that influence. And I was watching Carl Sagan's Cosmos series. And I know it's a pretty common one because I've heard other people, but it was a really powerful, just friendly way of being introduced to complexities and wonders that was gripping to me as a kid. And I watched it with my dad. It was a great bonding for us. And, you know, the way he delivered it was just captivating. And it was really what sort of sealed the deal for me that I wanted to be a scientist.

When you decided you wanted to be a scientist, was it just a scientist? Or was there an area that you thought you wanted to explore? Well, I decided somehow that I wanted to be a scientist at age seven before I actually knew what that meant. But I think I was largely very stubborn. And so if someone asked me, what do you want to be when you grow up? I'd say a scientist. And I kept saying that my entire life. And maybe that's why I'm a scientist now. At some point, it's probably around when I was exposed to cosmos, I thought I wanted to be an astronomer, something in that space, whether it's more on the physics

side or astronaut side. I didn't really know, but i was really captivated with uh the cosmos and it was missing something for me that i didn't know until i discovered the brain and neuroscience research which was when i was an undergraduate so not really all that young where did you do your undergraduate i was in upstate new york at bing University. And I was a biochemistry major taking one of the very few non-science classes that I was required to take. I feel like if I could go back, I'd take all humanities classes. But at that time, I had a pretty heavy science schedule. This class was called History of the Future. And they were talking about –

That's an amazing title. It's an amazing title. It's an amazing title. And it was an amazing class because it really tried to capture lessons from our past that guide how we view the future. And one of the other elements of the class was to see movies like Soylent Green and Planet of the Apes. And, you know, it's just amazing. And these were obviously a very popular class. And one of the lessons was on the future of the brain and nanotechnology in the brain. And I had not really thought about the brain.

And when I went, I literally immediately went to the library the next day and took out like 40 bucks, just 20 at a time, just carrying them back to my room. And I felt like that same just immense excitement when I first discovered cosmos and astronomy, but in a much more profound way because it was more connected with people and humanity. And that's what I always felt missing. The space was looking out and this was looking in. And so at that moment, I knew that I was going to spend the rest of my life on it. And now it's 30 years later. What did that, what does that excitement feel like? Because it's very different from the excitement that you would feel if you just drink too much coffee, for instance, right? I would imagine for you, what does that feel like when you're like, Oh, Oh, I think I'm

about like, this is the precipice or the plat, you know, the, the springboard. I mean, I think it's what people feel when they describe having an epiphany. You know, I mean, it's a transformational feeling. It's the type of sensation that you know you will never be the same. Like something has fundamentally shifted in you that will last probably the rest of your life, which turned out to be true. Turned out to be true. Yeah. What makes this lab unique or unusual? Well, we are unusual in several respects.

The first is that we do some very basic science in this lab. So we try to understand how neural networks in the brain underlie higher order cognitive abilities, attention, memory, perception. We try to understand how those abilities of our brain are vulnerable, for example, to distraction and multitasking. We look at how the brain changes as we get older in that regard. So I classify all that as sort of basic science. We're trying to understand how the brain works.

You're using a lot of imaging. And we use functional MRI, EEG, transcranial stimulation, tools of human neuroscience, right? Human cognitive neuroscience. In that sense, we're similar to many cognitive neuroscience labs, but we do something different. And now it occupies more than half of our labs efforts. And that's, we also have a research program to say, how can we use our expertise, our methodology, our perspectives to not just understand the brain, but to try to develop novel approaches to enhancing it and then even filing patents and moving concepts out of the lab into industry to really connect at that sort of scope. I don't really know any other labs that do that. So I think that's a really unique aspect.

I think it's very ballsy too in so much as, and again, this is just from someone who spent a lot of time around scientists, but who has never practiced as a real serious academic in any way in the hard sciences, is that you're not only describing these basic scientific phenomena and answering these science questions, but you're also bleeding into the prescriptive, right? Where you're looking at recipes and technologies that can be used to improve function, potentially even in so-called like normal, healthy adults, right? And that's, I think, one of the many reasons we get along so well. But what are some of the concepts or the insights that have made the jump out of this lab into the private sector? Yeah, so it was, you know, just to reflect on that a moment, you know, sort of when that happened. It was around 2008. So I've been doing this for a long time already. I already had my own lab, already made some really important discoveries on the brain and the aging brain and distraction and multitasking.

That's what I was largely known for in my research. And then I basically became a little dissatisfied at just reporting the bad news, that our brains were fragile in ways that we didn't fully understand, that it all got worse as we got older. I mean, that's like a great intellectually fascinating story for a bunch of scientists. For the general public, it's sort of a crappy story. You know? It's not the happy ending we're hoping for. No.

I joke around. You know, the first time I gave a big talk to an audience of older adults about our discoveries on the aging brain. And I closed the talk. I was staring at all these faces and they had the look on their face like, wow, I'm watching a movie, everyone died and the credits rolled. And I was like, you know, this is not how I want to end the movie. We could have gone on for another 40 years as most labs do and try to understand all of the details and complexity of why these things happen, why our ability to focus and our attention declines with age. And we're going to continue to do a lot of that. But to be able to actually create things that can help these people, that's what is something I always wanted to do. And I wouldn't

say I lost track of it. It just took a long time for us to get to that point that we could do it in a responsible way. So over the years, since we've had that transition, and it really started with NeuroRacer, now it's become much more extensive and expansive in our approach. The things that have left the lab are really largely built around our design principles on how we construct games from scratch, working with professionals, because I give a lot of respect to video game professionals and artists and designers. But we work very closely with them and create the algorithms and how multiple algorithms interact with each other to challenge the brain in an adaptive

and high-feedback way that actually leads to change. And so that's what most of my patents surround, that concept that you can build that methodology to advance how our brain functions. And the algorithms, this is where I massacre concepts that are sacred to a lot of people, but is it safe to think of the algorithm as, in this case, I guess, probably sort of an adaptive algorithm, which is a series of kind of if-then statements that are formulated in a proprietary way and ordered in a proprietary sequence? Yeah, that's appropriate. I mean, we tend to think of them rather than if-then as a full closed loop. So that's how we sort of visualize what we're

doing. We're creating a closed loop between an intervention. So you intervene in some way, you record the impact with as low latency as possible, right? So as short a time as possible, you see what happens. As little delay as possible. Little delay. With that information, we then cycle back, reformulate the intervention, apply again. And if you do that with as little delay as possible, you create this very powerful closed looploop feedback system. Got it.

And that is the most powerful way to change anything, whether it's a physical system with a diamond drill and you're trying to pummel into the earth or you're trying to change a biological system like the brain. Our current approach to therapeutics and improving the brain, largely in the pharmaceutical world, using molecules, is a very open-loop system. Very long time delays between the intervention, knowing what's happening, even the ability to know what happened is usually not quantitative at all, and then a very poor feedback system that leads to updating it, right? I mean, just imagine you go to the doctor, you have an attention problem or depression, you take a medicine, you go home, you subjectively record the effects and side effects. You go back a month later, you recount them, and then, oh, we're going to go up on the dose a little bit. And that is just not a way to change something, especially something as complex as the human brain.

Playing darts with a blindfold on. Yeah, and that's like the basis of our entire mental health care system. You don't even get the dartboard for a month. And some people respond well, and maybe they they got lucky and other people are just struggling and um this is you know a broad big big global problem we don't have effective means of improving how the brain functions across people that are suffering that have disorders and people that are healthy and just trying to improve their brains when you think of the word successful, who's the first person or who are the first people who come to mind?

That's a really good question. I mean, I think I've spent too much time thinking about people that are not successful to answer that question immediately. Why have you spent too much time thinking about people that are not successful, to answer that question immediately. Why have you spent so much time thinking about people who are not successful? Well, maybe not people that are not successful, but approaches that are not successful. Because I'm trying to find the holes in the system, the way of changing it in a meaningful way. And to do that, I'm looking for where we're missing the

boat. And by system, you mean just this kind of scientific establishment? Yeah, changing the scientific establishment, but changing more of what we think about as medicine, especially when it comes to the brain. And I'd say education when it comes to the brain. So it's probably, I don't know, maybe it's a fault, maybe not, but I really don't spend a lot of time looking at success cases. I really spend most of my time looking at where we're not reaching the high bar that we should be, both in education and in medicine. How do you vet people who want to be in your lab? Most people that want to meet in my lab are pretty aggressive at trying to get into the

lab um usually that's a good sign it's not people just so for those oh yeah with i mean we have a you know a core group of full-time you know fts on the payroll of a little over 20 but our extended team of interns and volunteers is close to 100 people. So it's quite large. A lot of people come in the lab and spend time volunteering or interning just to get to know what we do and for us to get to know them. I'm looking for people that are very rigorous, very careful. I like people that are, how I describe it, sort of optimistically cautious.

They're conservative in that they're not overinflated in what they say, but they're excited and they're enthusiastic and they think that there's something really here that drives them to be here. How do you establish that? So the rigorous side. I mean, is it just all on their resume, their CV? Or are there behaviors you look for, questions you ask in interviews? No, I don't really have a really tight methodology on how I do that. A lot of it is that connection you get with someone when they're talking about what they do, what excites them. I mean, that's usually where I start. You know, what do you think about that really gets you excited?

Because I'm more interested in what drives someone and motivates them and makes them want to get out of bed in the morning than a list of, you know, classic resume check boxes. And once I hear that and look at them and hear them, and, you know, obviously in the context that they have been successful in many ways and have the type of requirements that we'd want in this lab. But once we have that back and forth, then I know that that's, you know, the person that's perfect for this place. What are common misconceptions about the brain or cognitive function that just refuse to die? Like, I'd love for you to comment on the, you know, we, as we all know, we only use 10% of our brains. Yeah, I was going to say that one. So could you just dive into that for a second? Yeah, you know, I have been unable to find where that originated from. The best I could find is that it seems that when the early researchers were exploring brain function in different areas,

they would, in animal models, they'd make little ablations. They would destroy little areas of the brain and look what was happening. And there were large areas of the brain that you can do that to that you wouldn't see an impact. You wouldn't see a negative impact. You do that over the motor cortex, over the sensory cortex, over the visual cortex, bam, you can't see, you can't move, you can't feel. We know that this does that. But there's lots of areas of the brain whose function is a little bit more mysterious. And you have to see it a higher order way that you can under anesthesia or even in animals.

And so it started leading to the impression that there were some areas that just didn't seem to be doing anything. We now appreciate that that's not true at all. The most complex structure in the entire universe doesn't have just like a vacant parking lot, you know, waiting for someone to drive in and start building. It's all used all the time and in complex ways that we didn't always understand. I mean, for a long time, we tended to think about brain areas as sort of like islands of blobs of function. We now know that real higher order brain processing and function comes more from network interaction,

how brain areas are communicating with each other. And so one brain area might do something very different depending on the context of what other brain areas that it's communicating with are doing at the same time. So it's a very complex, we call multivariate system that's dynamic and constantly changing over time. And I think this complexity that we've only really recently begun to understand to any degree led to sort of very sort of naive views of the brain that we didn't use at all what are some uh and and the idea that there are very specific discrete areas of the brain that are kind of like separate people on an assembly line who only do one thing is still very persistent and i mean it's yeah i'd say it's another sort of myth of the brain what uh what are some red flags that people can keep in mind to avoid the charlatans of who claim to be scientists of the brain because there are a lot of people running around

kind of jumping up and waving their arms and so on. Yeah, it's a frustrating thing for scientists and neuroscientists. And to speak specifically what I mean by that, the brain and science in general could be a very powerful marketing tool. It's had millennia of successes in technology, which is right in our face all the time, really grew out of scientific exploration. And so we're constantly reminded of what a powerful tool science is. But the challenge and the way you can think of challenging someone that you think might

not be using science in a legitimate way is that science is not really about what we have done. Science is a methodology. Science is an approach. And so basing something on science doesn't really make that much sense to me. I mean, almost everything is based in some way on science. If it's not based on science at all, we shouldn't almost even be talking about it, you know, or it really falls into another realm. The more... Because you're talking about rational inquiry and the sort of structured way of thinking about evidence or lack thereof. Yeah. And, you know, we have this really, really massive framework that we've built to understand the world that gives us so much leeway into how we consider things that basing something on science

is super low bar. It doesn't mean that much. Like in the next hour, we could sit here with a glass of wine and put a thousand things based on science on the board. What's more important and what's sort of being used in an imprecise way is the concept of being validated by science and what that means and how hard that is to do and the details and the complexity of getting there in a rigorous way that's peer-reviewed and defensible and reproducible, that's a different story. And so the basing on science is not so exciting to me. The being validated by scientific methodology, that's what we're all trying for. And I think that

people should keep that in mind when they're reading something about science. Is it really just being used as a marketing weapon or tool? Or is there really a careful description of the research approach that went into it? And of course, those limitations that exist that are inevitable, everything has those. And I think that's a huge one for me is if someone is painting their data or their approach to be the best, the perfect, and they're not very upfront about the limitations or the potential flaws in the data, that to me just reeks of pseudoscientists. Yeah, it's impossible to do something that doesn't have a long list of limitations. I could easily go through them of my work and I do all the time. Some of the complexities are driven by the media. I mean I spend a lot of time with the media trying to hone my message and make a balanced message. And if you look and you'll see I have articles in New York Times, New York Magazine, I'm quoted.

And you'll see these little disclaimers and these balance points that I work very diligently with those journalists to say, hey, could you put this in for me as a sort of thank you for me taking the time to do this interview with you? Because without this, it's just not fully balanced. Right. Yeah. But if you don't do that, very frequently you wind up with something that's really only capturing the highlights and it's not that the highlights are wrong, they're just not the complete story.

They're incomplete. They're incomplete. For example, in our research and even our Nature paper, we're massively excited by the elements we found, but it is a step one. In my mind, it is a proof of concept. It's the reason we get excited that we have a signal there that something's going on that leads to larger studies to reproduce it and to show even more aspects of its sustainability. And also, we never even looked at how those changes in the brain and cognition translate into people's lives. We would have needed much larger numbers. And it's very hard to even tell that in any study because we don't have great quantitative markers of how

someone's life is being impacted by something that we're doing. So those are just obvious limitations to me that I like to also express in addition to the things that we're excited about. Is it possible that, or what is the likelihood, do you think, that some video games that are already out there, pre-existing video games, have some of the cognitive enhancement effects or maintenance effects that those devised in the lab do. I think it's beyond likely. I think there's no doubt that that is true. As a matter of fact, we were inspired into the video game research in a pretty profound

way by the work of colleagues of ours, Daphne Bevelet and Sean Green, who showed in also in a Nature paper. There's only several Nature papers on video games, but another one in 2002 showing that consumer video games, first-person shooter games, the games that some people have the most trouble with because of the violent nature of them, that young people that played them would show much superior cognitive abilities compared to the peers that don't play these games.

And if you take someone naive that doesn't play video games and you haven't played, you also see these effects, especially compared to other games like Tetris. And so I would say undoubtedly in my mind, there are ingredients of the active ingredients in consumer video games that could lead to brain changes in a meaningful and sustainable way that they're there but because these games are built for entertainment purposes i don't think they're going to go there as far as they can if they were designed with an understanding of the brain and cognition in mind and the population you're trying to impact but on the flip side of that you also don't want to build something that's not fun and

entertaining. And that's what makes this field so challenging, to build from scratch and reach something that has the engagement, immersion, and enjoyment that a video game does. Because people have a pretty high bar for what they expect out of a video game now, especially young people. They're like, that's not fun. I'm not going to engage in that. So to get there and then to also have all of the mechanics and the video game engine itself target these brain processes, to do both of those, that's why we don't have a ton of examples of this being done at a really high level because

it is so challenging and requires it's expensive and it requires people working together that have that traditionally have not and so it requires an openness and a communication between professionals both of whom feel that and and are experts you know video game professionals and artists and engineers and designers talking with scientists, both very strong-willed people, high-level performers, both feel that they know how to do their job. And you're like, no, you're actually not doing your job. You're doing a new job that never existed. You're creating something together that's a hybrid. That's the challenge. One of my – the mention of first-person shooters reminds me of one of my uh the mention of first person shooters reminds me of one of my more embarrassing uh outings in any activity ever was i think it was my first game ever and i could get this wrong

pretty sure it was halo it was my first game ever and i sat down to play this guy who i literally felt like i couldn't be on screen for more than a second without dying ended up being this guy named fatality with eyes as the ones who i think is a world champion i think if your name is fatality you don't want to play video games but his but his the the hand-eye coordination and just his ability almost like presciently to know exactly where i would be in this sort of three-dimensional artificial space, this virtual space, was mind-blowing. I mean, I could not believe how fast this guy was.

I'm going to switch gears for a second, because I want to talk about some of the other aspects of your life as well. But what books, they don't have to be science-related, what book have you gifted most often to other people? I'm a big fan of science fiction books. Most of my reading is on the future. I'm really mostly satisfied when reading books that's describing future possibilities and realities. I read a tremendous amount for my work.

And so I read articles all the time. And when I'm not reading that, I find it most gratifying to just push my creativity and not read about things that other scientists are doing, but read about potential futures. So, you know, starting with Asimov when I was a kid, Foundation series, you know, life-changing for me as a kid and still have read it multiple times throughout my life. So that's probably the biggest share that I've done is introducing people to Asimov and the Foundation series. But I continue, you know know i'm reading right now uh books uh by author peter

hamilton and and others that uh the reality dysfunction is a book that i i tell people to read all all the time it's called reality dysfunction it's a series called the night's dawn trilogy um takes place in the distant future great, great human interactions. And it just stimulates my creativity to read really talented authors that are describing future possibilities. Now, I want to drill into that because I love science fiction. I love fantasy too. I'm kind of a fantasy nerd from way too much Dungeons and Dragons. I think also from too much Dungeons and Dragons, I tend to get obsessed with world builders. So like Frank Herbert and Dune blew me away.

Stranger in a Strange Land. Heinlein also. What aspect of reading science fiction, what type of, what aspect of the science fiction helps you to push your creativity? I'm also a fan of world or even beyond that, like sort of the space opera genre where you just have so many characters and ideas interacting over thousands of pages. Those are my favorite things to read. And there's a lot of that out there. It's a definite category within science fiction and fantasy. I mean, no doubt I'm inspired by futuristic technology. You know, people that have some background,

that are smart enough to come up with things that are far beyond our capabilities, but reasonable, really excite me. So I would say that that's the part that drives, you know, my creativity is thinking about the technology and saying, wow, we don't have that. What would it take to have that? Sometimes you just can't get there, but it sits in my mind.

And even now in the lab when I'm seeing all these things coming together and sometimes I'm talking about it with someone, I'm like, it sort of sounds like I'm describing a science fiction book. But it's what I do every day. So I guess those worlds are starting to meet. Well, so we watched a movie recently. I guess it's Ex Machina is how you say it. Yeah.

Perhaps say it. Exactly. Of the machine or from the machine, I guess, technically, which seemed imminently feasible in a lot of ways, which made it fun. You have a project that's going to be getting underway soon that I'd love to hear you talk more about. I'm not sure if this is the official name, but the nickname, at least, Neuroman. It doesn't really have an official name. That's the name that we call it around the lab.

I like it. That's the Neuroman Project. So tell me about the Neuroman Project, because you work out every day, or is it? Five days. Five days a week. Yeah. Very fit guy. You've got the Silver Fox thing going, which I'm really envious of, because I do not have that. I have sort of the true detective detective uh woody harrelson thing going uh and uh moving

into hopefully jason statham territory but i digress uh where the hell was i going with that oh you're very fit you're very sharp cognitively uh and yet or uh i should say most interesting to me is this this uh this experiment or series of experiments you're going to be jumping into. So tell us and tell me more about this. Okay, so this is a recent development in my life is this Neuroman project that we're calling it sort of a fun title and a fun idea. You know, as a scientist, we have a very prescribed regimented methodology that we go about doing an experiment, very carefully placebo-controlled, blinded experiments, very rigorous analysis, very careful comparisons against other groups.

And that's what we do and what we'll always do. That's how science works. That's how we're going to figure out if many of the approaches that we're taking in this lab actually work, the approach of validation. And while we're doing that, what I'm seeing happen is we're developing all these new games that are really exciting. Three of them we've been working on for two years now. And it's going to take us a long time to figure out if these work and to really understand the mechanisms and the individual differences why some people respond why some don't but what's going to take us even longer is to figure out how these games interact with

each other right because i don't think the wind there's not a holy grail out there there's not one thing that's going to fix us or elevate us to our satisfaction. What's most exciting to me is what we call a multimodal approach. How do all of these games interact to elevate you? How do they, what are the other synergistic effects? How do they add on each other? Maybe pharmaceuticals can be dropped to a way lower dose and be act to enhance it. Brain stimulation, neurofeedback. We do all of these things in the lab and it's going to take us decades to look at how these all interact. But given that, we don't think certainly the

video gameplay is likely to be very dangerous. I've decided to do a very unorthodox study on myself, more of a project to sort of what I say to labs, put my time where my mouth is and say, I'm going to treat myself like a research participant, even though it's not a formal study. There's no control group. More of a case study, which exists in our field in many ways. And play three of our games, MetaTrain, Body Brain Trainer, and Rhythmicity. I can tell you what those games are. Play them all concurrently, which we don't

do. We usually study one at a time. We will only study one at a time. And these are in study right now. Play them all at the same time over the same period of time for two months and see what I can do to my own brain, my own cognition, other aspects of my physiology. And so that's one goal is to see, you know, if I look across a med, you know, so we'll be doing everything in pre and post testing on me that we normally do in a study. So MRI, structural and functional, EEG during cognitive testing, stress measurements, blood work, inflammatory markers, epigenetics, sleep recording, all of that over a two-month period before and after many things during to see how engaging in these change these levels. And we have dozens and dozens of 20-year-olds in the lab

that come into the lab as participants as data to act as a sort of baseline. So my question is, well, how do I compare on these metrics to a 20-year-old? I'm 46 right now. And with this type of training approach, what can I do to move these metrics closer? How close can I get? Or can I exceed them? So that's one challenge. Turn on the womb. Maybe it's like H3.

Yeah, well, that would be a down swing. No, I'm kidding. I'm totally kidding. Seriously, it's actually a really good point because there is that turning point, you know, this sort of peak where you develop, you develop, you develop, and then you don't really plateau for very long, we think. And a lot of data suggests that. And, you know, that peak is probably for these type of abilities, maybe around 23 years old.

So that would sort of be some of the highest levels we see. So the project gives me the ability to just have fun and see what I can do with my own abilities using approaches that I designed that are lab developed. Um, but you know, there's other benefits. It gives me like a very humbling experience of being a participant in my own lab and learn it from that perspective, like where, where it's a burden, where it's not. I get to see my games that I've designed from the inside out, like how they really function. I think that I can improve all these games by the experience and even improve my skills as a game designer through this. And so I think there's a lot of real benefits.

It's definitely nothing that I've ever heard a colleague doing. I mean, you know, the reality is some people work on things that would just be plain inappropriate or dangerous experimental drugs. But, you know, where we just don't know the side effects and it certainly would be unwise. But, you know, I think in this case, because of the type of interventions we're working on, I really have a sort of a little opening to do something pretty fun. No, I'm very excited about this. I wanted people to hear about it on the podcast because obviously we'll want to follow up. But the N of 1 guinea pig sort of Adam 2.0 project is not surprisingly very fascinating to me.

What – could you go through the three games and explain each of them? Sure. So the three games, Metatrain, Rhythmicity, and Body Brain Trainer. So Metatrain is an iPad-based game. We've been working on all of these for years. This started as an NIH-funded study. And what the original design was, I took- National Institute of Health. National Institute of Health, correct, where a lot of the more traditional scientific funding comes in. And it's been challenging to get video game therapeutic research funded, but it's slowly happening. And so what Meditrain is, I was inspired by mindfulness practice and some of the data showing that these contemplative practices that have been around thousands of years have impact on our minds and attention beyond stress relief, but even cognitive impacts.

And so what I've done in Meditrain is take design principles from concentrative meditation and integrated them with our video game mechanics of adaptivity and feedback and put it in an iPad. And then we've built this out several times with a big team here. Zynga philanthropically donated time and engineering support and money to help us actually build this out, which is really fun to work with professionals that are trying to do some good in addition to their standard bottom line. So that's what MetaTrain is. So MetaTrain teaches you how to better self-regulate internal distraction.

At least that's what its goal is. And the hypothesis of MetaTrain is that if you learn how to do that through the game algorithms, that we'll see a benefit that you can hold your attention to your breath for longer periods of time without being distracted. But the biggest win is that we'll see benefits on other aspects of cognitive control, like working memory and other externally focused attention, and that we'll see changes in the brain and be able to understand the mechanisms of that. That's Metatran.

So a couple of real quick interruptive follow-ups on that. The first is, are you measuring things like cortisol, C-reactive protein, and so on primarily as related to Metatran? We're doing that for all of our studies. Okay, got it. Yeah. But in your particular case, do you hypothesize the highest correlation on primarily is related to meditrain we're doing that for all of our studies okay got it yeah so but in your particular case do you think the highest do you hypothesize the highest correlation in those biomarkers will come from meditrain um not necessarily one answer i i think that all of

them have the potential for uh stress management in addition to cognitive improvement um interestingly enough and so i don't know and that's an example of why this is not a great controlled study because for stress management in addition to cognitive improvement, interestingly enough. And so I don't know. And that's an example of why this is not a great controlled study because I won't be able to see the differential contributions of the different games. But that's okay because we have many studies that are doing that. We have studies where all of these are done independently, and we'll see which has the most impact on that type of blood-based sort of stress-related outcomes. So we'll see that.

So that's MetaTrain. BBT, we call it BBT in the lab, body-brain trainer. We built that one entirely in-house with our own game design team and game development team. It is a motion capture game that's played using the Kinect 2, part of the Microsoft Xbox One gaming platform, which is a pretty unique use of that platform. And what BBT does is that it challenges you both cognitively and physically at the same time in one integrated game experience. So it's the first thing that we know that's really designed from scratch to do this with adaptive algorithms, both in the cognitive domain and physical domain. So let me explain what I mean by that. All of our games are adaptive cognitively, meaning that as you improve, the game detects

that on a second by second basis and then scales the challenge appropriately to your ability. That makes it harder. The better you get, the harder it gets. It's like a personal trainer there every single second, picking up your abilities in a very quantitative way and inching you forward. And if you're overwhelmed, it'll back off. But it'll hold you at a high level of challenge where it's not so hard that you're frustrated, not too easy where you're bored. That's like a big part of our game engine. So cognitive

adaptive engines are part of BBT as it is Metatrain. But BBT also has physical adaptive engines. So by that, what I mean is that before you play BBT, you get a VO2 max, which determines, it's a way of determining at what heart rate you should be challenged to be right at that sort of anaerobic zone where we're looking for this type of benefits. What we then do is have our participants, including me, when I start playing this soon, wear a heart rate monitor. And we feed your heart rate into the game algorithm. So what happens is if you're under our goal, the game will push you to have larger amplitude movements, faster movements. Once you to have larger amplitude movements,

faster movements. Once you hit your heart rate goal and exceed it, it could titrate it back. So just like we do on the cognitive side, from a physical cardiac side, aerobic training side, we can also hold you right at that perfect level. How are those instructions delivered? Is there like a big mime on a screen that you have to mimic? Well, you're seeing your hands move, but that's really it. You're basically just being challenged with cognitive demands across a 3D beautiful game environment, pushing your working memory, your selective attention, your ability to

switch between tasks. But you're not thinking about this from the cognitive or the physical perspective. You're just seeing these challenges in this sort of Mayan-inspired world that you're trying to return treasures to, and you're just grabbing for objects and making decisions and playing a game. Got it. Got it. And that's the goal, is to make it just a fun game that you work through over a two-month period of time.

So Metatrain, in its current formulation, is played three days a week for an hour each session for two months. So that's what I'll be doing. So that's body brain training. Sorry. MetaTrain is played for 30 minutes a day, five days a week. Got it. At home. So MetaTrain is a home game.

BBT we play in the Neuroscape Lab, this new lab we have that we created just to be able to do experiments like this we hope that this also goes home but the technology is so new um we actually just today interestingly enough set a bbt in my loft so uh i give attention play actually i think my girlfriend joe is going to be training on bbt at home cool very cool that's a that's a still discussion, but she's into it. My lab's into it. So we might have Neuro Woman Project going alongside. And now she's like, I want to do Metatrain as well. So we'll see what we do there. End of two. Yeah, end of two. I know, exactly. The couple, the neuro couple. So the last game that I'll be training on is called Rhythmicity. Rhythmicity is a game that we're working on with an indie game designer, Studio B. And the hypothesis here is that if we have a game that, through adaptivity, teaches you to become more rhythmic, which is also a question, can you become more rhythmic? We think you can.

We're going to document that you can through gameplay. And then the question is, if you are now more rhythmic, is your brain more rhythmic, right? Rhythm is a fundamental aspect of how our brain works. It's not just an artifact that we've discovered, you know, that you have alpha, theta, gamma at different frequencies, but it's a core property of how our brain functions at a highest level from attention, perception, memory, all are driven by these rhythms. And not just the rhythms in isolation, coherence and synchrony, phase locking between rhythms. So because our brain, as all of our biology and even all of our physics, is rhythmic in nature,

does becoming more rhythmic improve the rhythms of the brain, improve your function and other aspects of cognition? And so that's the hypothesis. So the game is a fun game, similar in some ways maybe to a little bit of the interface and things like Rock Band and Guitar Hero. But instead of just playing different songs and having some level of complexity, adaptivity there, we have a very high level of adaptivity. We're feeding you more complex rhythms at a faster tempo with less time across the audio and the visual domain. So that's the last game, Rhythmicity. What is the protocol, the frequency and duration of sessions? Rhythmicity is probably going to have a similar protocol to Metatrain,

although we're still formulating that. That's the least developed. So both Metatrain and BBT are already in study. Rhythmicity is just finishing game development, but will be ready for me in July for my training. It'll probably be five days a week, 30 minutes a day. Now, you've spent a good amount of time just coming back to the rhythm with world-class drummers, have you not? Yeah, that's actually how Rhythmicity was inspired through my relationship and friendship with Mickey Hart, who's the percussionist from The Grateful Dead. We were doing a talk together in New Orleans for the AARP because he had a really profound experience in his life because his grandmother, who had Alzheimer's disease, and he was a caregiver for her.

She didn't speak to him for a long time. And then he's playing the drums with her one day and all of a sudden she just like got into the groove and said his name and he was just blown away. And all of a sudden music and rhythm from being a tool of entertainment became something more. And he's been different ever since. I mean, he's always been on this kick.

He's spoken in front of Congress many times. We've spoken together at White House, at the White House and Congress together, South by Southwest, all over the place about rhythm in the brain. And so I was really inspired by his own impressions and his own passion for rhythm as a therapeutic tool and his own frustrations that no one's really done the study that I described to you. We know that people that have high levels of music training experience in their lives, when you look at their brains

when they're older, they're not like other older adults. There are definitely some improvements and some advantages, but there's not really a carefully controlled study of what elements of music. I mean, there's many things that go into being a musician. And so it's provocative.

Not to mention just the kinesthetic element. Oh, exactly. And so many, so many things. And so it's interesting. It's a signal. Something might be there. Same thing with meditation training. Very hard in a very carefully controlled study to pull out what are the active ingredients.

And is this element of either meditation or physical fitness or rhythm, so that's a commonality, is that these practices often sit in what we think of as alternative. And I don't think that that is doing them justice, right? Because people are not, they're not being prescribed, they're not really part of what we think of as medicine. And hopefully through these type of studies that we're doing now where we take active ingredients of them, drop them in our game engine, and then do placebo-controlled studies, we'll start validating this at the level that professionals like I would prescribe that. Yeah, potentially.

For sure. And that's what we hope to see in the future. One is there's a great short movie called The Lady in Number Six, which is about 30 minutes long. It's about the world's great interest to me and why I was for a very short stint sort of a dilettante neuroscience guy at Princeton for a year or so and why I've enjoyed spending so much time in this lab, among other reasons. But it's a video, and I think if people just search Alzheimer's patient listening to music from his era, they took this gentleman, must have been, I guess, in his 80s, maybe even 90s, African-American gent, pretty much mute, vegetative, practically. I've seen this video. Oh, my God. And then they take music that he would have heard when he was young and play to him, and he starts having a normal,

I mean, holding an entire conversation. Yeah, it's profound. It's really profound. Yeah, that's so when, you know, Mickey and I first started interacting, I was looking for other examples of that and sharing them with him. You know, there's so much we do not understand about the brain and its wonders and how to control it and how to allow our ability to impact it, improve our lives. And it's just those type of things are inspiring.

And if we could distill them down and make them systematic and reproducible. So it's not just some like, you know, very amazing, but rare event, but something that's reproducible and prescribable and deliverable. That would be just game changing. Yeah. So it's not something you hope for, but something you can engineer. Right. What, uh, what is the fascination with photography? And obviously those of you listening can't see this. You've got two gorgeous, large dual screens cycling through photographs. I know you are an avid photographer. until I was in my late 20s. And I was at my family's house and my uncle who had sort of recently married into my family was a radiologist and also a very avid photographer, amateur photographer, but even more than that, he was very into collecting cameras and photography equipment.

And he gave me a book by a photographer by the name of Galen Rowell. I'm actually a Bay Area photographer. How do you spell Rowell? R-O-W-E-L-L, Rowell. And Galen, G-A-L-E-N. And he is one of the world's most amazing photographers. He unfortunately passed away right at the time that I moved here. And I had met him once at a lecture of his, and he was looking forward to discovering the brain because he had a great interest in cognition. And he wrote this book called Mountain Light

that my uncle shared with me. And Mountain Light is an amazing book because one page is a beautiful nature photograph, and the other page is a complete text. And in there, it describes the nature experience, which was amazing to me being in New York or not exposed to nature all that much. The technical elements of photography, which appealed to my geek personality, you know, all the little details and numbers to get it perfect. And then really a little bit of a view of cognition, which is my field, talking about perception and attention. And this was something that Galen really appreciated.

And page after page of beautiful photo and then all those descriptions just captivated me. Probably what I'd call another epiphany, life epiphany. And my uncle saw that. I read the book for eight hours, went up to his room and brought down a camera from the year I was born, a Nikon from 1968, and said, here you go. This is a gift. This is your camera.

It was totally manual, almost impossible to use. He gave me like 32 rolls of film, like a case of unopened film, and then basically took me up to their balcony and overlooking – this is Long Island – overlooking sort of a wooded scene and taught me how to use the light meter. I went back. I was living in Manhattan at the time, going to medical school on the Upper East Side at Mount Sinai. My balcony overlooking Manhattan, i got really lucky i had about you know i had i had a support i didn't even own a tripod then and took a couple photos of this amazing sunset in august that i after i had developed i was like they were just amazing and i showed them people and they're like you're really good photographer like i am which wasn't true of course at all i just got really lucky but that like early like positive feedback made me think that maybe I could do it.

And so I spent months being not a good photographer in Central Park, learning how to do nature photography. And it captivated me. And I went and spent many years traveling around the world doing photography. I started a company called Wanderings. I built my website, Come Wander, in 1999 using HTML, not even any program, and sold a lot of photos. I did my own printing. Most of my sales were to hospitals, interestingly enough. I had a nice connection there since at this point I was a neurology resident.

And I had a lot of, you know, I had a captive audience late at night of all the nurses and other support team that were just sitting around with me at 3 in the morning in an ICU and say, here's some of my nature photography. And so I do my own printing, and we realized that hospital rooms, waiting rooms, ORs, ICUs could use a little bit of nature. And they're just pretty sterile places. And so we started realizing that it was having a sort of profound impact on on patients and so i uh i had a nature photography career for a while um you know people have often asked over the year what is sort of is there a relationship between me being a scientist and and a photographer especially when i was active in both of those things and one part is was quite obvious to me is that, to me, they're both an exploration of nature, right?

That's what science is. You know, you're looking for organization and meaning. And that's what you do in, you know, what I would do in nature photography is look for organization. And granted, in the photography, it's more looking for aesthetic and meaning from an emotional response. And in the lab, you're looking for more of an organization at a different level, but they really weren't all that different.

No, not at all. I think often of this video. There's also an essay, and it's probably at this point a book, which is an interview, comprises an interview with Richard Feynman, who won a Nobel Prize. Yeah. When you're asking me people that are successful, he was actually one of the first people that jumped into mine.

He's a great one. I mean, bongo player, safe cracker. Yeah. Yeah. I would put him at the top of the list. So the video, which people should be able to find, if you search my name in the video, I've kind of tracked down a higher quality version, is the joy of finding things out. And he would have these debates with some of his artist friends.

They say, well, you think on the molecular level and the beauty of the flower is lost on you. And he'd say, no, actually, I totally disagree. He said, if I understand the inner workings of the flower, I think it gives an extra layer of depth so that I have more appreciation of the flower. And, you know, started learning to paint when he was well past his prime in terms of his career and his work with, you know, after the Challenger disaster and so on and so forth. But fascinating character. That's one of my favorite books. The Surely You Must Be Joking, Mr. Feynman. Yes, I read that many years ago.

What a hilarious, incredible guy. You operate at a very high level in the lab, managing a lot of people, juggling a lot of different projects. What are your morning rituals or routines? What does the first 60 to 120 minutes of your day look like? A little coffee involved, a little breakfast. When do you wake up?

I wake up like 6 a.m. I'm going to bug you with the details. I wake up at like 6 to 6.30 a.m., no matter what time I go to sleep. I try to get up. I usually don't set an alarm. I'm very responsive to light. I have a big loft with open windows and skylights, and I don't close them in any way. And so I like to wake up with the light, so easier in the summer. And get up, shower, coffee, small breakfast, usually like an egg or some protein. How do you take your coffee?

Just a shot of espresso. So pretty straight up. How do you make your espresso? I usually use an espresso. So just get it nice and fast. On a weekend, I'll go out and get a nice higher quality cup of coffee. But for the most part, I'm just really about just getting things done in the morning so I can get out of the house and usually go to the gym. So lately I go to the gym, train in the morning

before I start my work day. What time do you get to the gym? Do you wake up at 6, 6.30? Yeah, I'm at the gym by 8, 7.38. 8 o'clock, I'm actually just reworking my schedule now, which is why I hesitated for a moment because I'm going to be moving to 7.30 where I'll be doing BBT training as my physical workout in the morning, three days a week starting in July, July 6th. But yeah, so traditionally I've moved between afternoon and morning workouts, but I've really been enjoying the morning workouts for a bit now.

I feel really energized by it. And so I'm in the lab, even the fact that I woke up, had breakfast, worked out in the gym, 30 minutes cardio 30 minutes weight training this is usually my routine i've been doing it since i've been 17 years old in one form or another and then you know i'm in the gym by like you know i'm in the lab at 9 30 so some people 10 at the latest and most people just like rolling in to start their day at that time do you i hate that feeling i'm that guy who comes in it's just like i hate you adam you've already done more than I'll get done in the next six hours. The working out, do you record your workouts in any way? No.

More of a kind of instinctive? Yeah. Yeah, I've been doing it. No, I mean, I have a regimen. You know, I work out two body parts a day, three days a week. And then on the other two days, I sort of just have fun, do whatever I'm in the mood for. So that's my weight training workout. And then the cardio workout is bike, treadmill, or elliptical for 30 minutes.

And you and I were chatting before we got started with the record button pressed about exercise. And I enjoyed getting into it. And I want to explore it a little bit because it seemed like we exercise perhaps for very different psychological needs. So I was mentioning that I almost always train by myself and have historically because it's been my meditative time, my time to say count, which is how a lot of people meditate. It just happens that I do it while moving in this particular case. And so I would almost always have earphones in, oftentimes even without music, just so people wouldn't talk to me. And I train by myself. But you seem to get something else out of it. So I was hoping you could just elaborate because it – Yeah, I've always, for the most part, always had a single workout partner over the last 20 years of gym time.

And it's someone that's also very compatible from a physical fitness point of view of what they're trying to achieve. And it was my friend Brian back when I was in New York City, my friend Daria over the last eight years here in San Francisco. And there's an intensity there. You're definitely pushing each other to work out, both to get to the gym, to not miss, and also to get through like a high-level workout, not cheat. But then there's also like just a little human connection, a little talking without an agenda, just what's going on in your day, what are you thinking about? Do you have any crazy visions you want to talk about? Some small talk. And I don't really have a lot of that in my life. Everything's pretty intense and pretty goal-directed. And so it's, I think, a type of relaxation that, and maybe like a little

bit of humanity that served a valuable role to me. A therapeutic release, it seems. And what struck me when we were talking about this is that I don't have a lot of that in my day either, because I'm typically working by myself. Every once in a while, I'll work in one of the offices, one of the startups that I advise or invested in. But I also need that type of therapeutic non-agenda, no agenda time. But the way that surfaces then, the way that I satisfy that is by going out and having drinks. And I think that is probably one of the reasons. It's not because I do enjoy wine, but I don't feel compelled. I don't have a wine deficiency. I don't need to drink it five nights a week, but I'll go out and I'll be like, okay, I don't want it to be 15

minutes long. So I'm going to have more than one drink. And so we end up kind of waxing philosophic for an hour. And so it just struck me that maybe I should start working out with someone because it would satisfy that need, scratch that itch. and I would be less inclined to have three glasses of wine four nights a week. Yeah, I think it's a great place to do that. You also get the added benefit of having someone push you from a physical fitness point of view. But I agree. I think it's incredibly valuable. Everyone needs that just little open time to let their minds wander and to laugh and to say things that you're not so worried about because you're not in front of an audience like I am frequently. And so I do think it's valuable. And if you're looking for a workout partner, I actually have a slot opening up.

That's true. We should, actually. You know what? Lightning strikes. And you mentioned Daria. So Daria, many of you know, I do – one of my close friends is Kevin Rose. He is you mentioned Daria. So Daria, many of you know, I do, you know, one of my close friends is Kevin Rose.

He is married to Daria. And I saw something funny recently, which was somebody on Twitter said, you know, at Kevin Rose just announced that he's moving to New York City and related news at T-Fair has just changed his relationship status too. It's complicated.

That's awesome. Yeah, I'm going to miss those guys. But yeah, me too. I'd imagine you spent a fair amount of time in New York. It's complicated. That's awesome. Yeah. I'm going to miss those guys, but yeah, me too. I'd imagine you spent a fair amount of time in New York. Yeah. Yeah. New York is my, my home. Uh, my original home. I mean, San Francisco is most definitely my home now and I love it here and I have no intentions of leaving. Um, uh, although we have so many good friends in New York now and I'm very good friends with Kevin and Daria as well. Um, but my family lives in Chelsea, my parents, my sister and my other sister lives in upstate New York now and I'm very good friends with Kevin and Daria as well. But my family lives in Chelsea, my parents, my sister, and my other sister lives in upstate New York.

And so I go back to New York all the time and that's where I spent my whole childhood and early adult life. And going to New York to me, I always say it's like jamming like a bat, like energy right into your brain. It's like charging, charge you up and nothing, no place I've ever been has that amount of just pure human energy. Yeah. It feels great.

And so, you know, even a long weekend in New York, I'm like, okay, ready to go back to San Francisco. Well, that's,

that's, I feel like it's kind of like holding on to the third rail in a way. It's, it's so stimulating that I find it excessive for my system past a certain point. I mean, in reality, though, having been someone that's lived there for a long time, it's different when you live there. Yeah. You learn like the guy that sells you coffee on the corner and your way to go to work and

all of a sudden your block feels really familiar and then your neighborhood. So it's not always like that when you're actually a resident. But it's not as much as you might expect. Once you live there, you do get into that routine and it does feel smaller. But it's a unique place in how energetic it is and how energetic the people are. And so, I mean, I do agree. It's a lot. It has a lot of horsepower per square foot. It's a very dense, energetic environment.

Let me ask a couple of rapid fire questions. I always say that, and then I'm very long-winded, so I'll try to keep them short. But the answers don't need to be short. They can be, though. When you are feeling down or self-doubt, fill in the blank, negative emotion, what do you look to for inspiration or to get you back on track? What do you do? Well, I mean, in all reality, I'm pretty even keeled in terms of my mood and in terms of my outlook. Have you always been that way? As far as I can remember. I mean, I don't really fluctuate all that much.

I mean, I get stressed and, of course, something crappy happens and I'm bummed out. But I don't really get too derailed or get caught in a rut. I don't really have that many memories of that. Usually, if I am derailed in any way, my favorite thing is just interacting with my friends, going out and having a nice dinner, getting a drink, and watching some music. Live music is a frequent source of release for me.

Live music? Live music. Any type? I mean, lots of different music. I like what most people would call alternative, which has changed dramatically from new waves to whatever it is now. But yeah, I mean, watching musicians perform that are talented and passionate and feeling the vibe of the music and dancing and just being in a festival,

I love that. So I'm a very, very social person for someone that spends as much time in academics in a lab as I have. I throw a party every month and I feed off of that human energy. And so I'd say if I am feeling not at my normal level mentally or emotionally, my social interactions is usually the way that I find to get back. Well, you're very, I would say, extroverted also. So it's kind of medicine for the extrovert. I would say that's true. Do you listen to music when you work?

Often. What type of music? What is your most played band or track or station at the moment? Well, I have a very unusual way, I think, of listening to music. I almost always listen to music I've never heard before. I have my favorites in the gym i have of course have a playlist you know when i really you know want a quick fix i have my favorite of whatever that time is um well it changes all the time i mean most of the bands that i listen to i might have just

discovered a couple months ago so like for example recently i've been using the discover feature on spotify and you know you have these recommendeds and i'll just let it let it go for a Spotify and you know you have these recommended and I'll just let it let it go for a bit and you know if it like sort of in a bottom-up way something like triggers and I hear it I'll be like oh you know let me listen that oh Tame Impala well they're interesting I sort of like their vibe and so I'll listen to them for a while um you know I mean class you know bands that have kept me to be for a long time like Radiohead. I like bands that are explorative, musical styles, Dave Matthews' band. But for the most part, I really try to listen to as much new music as possible. Cool.

And you use Spotify on the desktop as well? Spotify on the desktop, yeah, for the most part. So when I'm sitting here, it's probably open right now on some screen here. So I was just flipping through. I look at what other people whose music taste I like, what they're listening to. And I keep a pretty active playlist for my party. And I like it to be fresh. So I'm constantly looking for music that can attract my attention away from what i'm

doing i'm like oh i like that and then once i hear that i'll go and pull that band out and see what other stuff they've created and then listen to them along uh you walk into a bar what drink do I mean, it really depends. I would say my go-to is a really nice whiskey, maybe with just a cube in it. If I'm feeling a little fancy, maybe an old-fashioned. There are some times I just want a glass of wine or a beer. So it really depends. Any – you're just a scientist. It really depends for everything.

It really does. The whiskey, any particular whiskey? I'm a rye whiskey fan. Rye first, then bourbon, and scotch, then Japanese whiskey, and then a scotch, I would say, in that order. And rye whiskeys, I mean, I like so many of them, and I'm always changing what's my favorite. Give me – give a recommend. I'll recommend one, and I'll try it tonight. Whistlepig? Whistlepig.

Yeah, that's a good one, sure. I'll try it just for the name. Yeah, it's a great name. I think I have some in my lab. I think that's my nickname. It's in my office here. I could pull some of that out. Yeah, I know.

I mean, ryes are an interesting whiskey because they really were the dominant form of American whiskey pre-prohibition because the industry was more north, Pennsylvania, Vermont, New York, where rye did really well. And then with prohibition and the move south with corn and bourbon really exploded, which is still by far dominant. But rye is coming back, it i love it it's really like earthy and just delicious i agree 100 what let's see uh what biography is your favorite if any do you read biographies i don't read all that many um i've read some on uh well i mean i most recently read the steve jobs biography the is Isaacson one, which was pretty fascinating. Anyone that lives around this neighborhood, it's like you sort of have to read it. They could ask you to leave San Francisco.

So that's a requirement. Yeah, but when I was a kid, Ben Franklin, Teddy Roosevelt, I was really influenced by a bio. I don't even remember who wrote it, of Teddy Roosevelt, which was really pretty cool. Why were you so – how did it influence you? I mean, I like hero stories. I've always been attracted to people who have sort of challenged their status quo and were successful at it and sort of marched to their own beat. I have a recommendation for you since you gave me Whistlepig. Yeah.

There's a book called Tuxedo Park about Alfred Lee Loomis. Okay. Who was a masterful stock market investor, got out before I think the 1929 crash. He's one of the few who not only survived, but really exited at the top. And he was an amateur scientist, but one of those kind of old-timey, really impressive amateur scientists, like in the sense that Ben Franklin was kind of like an amateur scientist, but you're like, wait a second. And he financed this place similar to Bletchley Park in a way, which for anyone who's seen the Imitation Game will sound familiar, because that's where, of course, they were cracking Enigma.

But he brought in scientists who would otherwise have no contact with one another to develop technologies, some for commercial use, but many of them for wartime use. Fascinating story. Wow, sounds great. Yeah, and I mean, like almost all of these heroes too,

a very flawed character. I'll put it on list yeah it's a great book uh if you had to choose between losing your hearing uh your smell and taste or one eye which would you choose and why oh man that's bumming me out. Even thinking about any of those things. I couldn't make it both eyes cause that, that I think is too much. No, everyone would keep their eyesight. I mean,

we just, you'd be too incapacitated by it. Um, I would say one eye. I mean, I love food without even just smell alone. You'd lose so much of, of those things that give me pleasure, you know,

multiple times a day. And, you know, like you just heard, I listen to music all day long. I mean, it would suck losing an eye, but at least I could see and hear and smell. So I'll go with that. And you'd get a cool eye patch out of it as well, probably. Oh, yeah, yeah. Probably. What are your hopes for... Let me rephrase that, actually.

That's too speculative. What do you hope to do with virtual reality in the near future? We don't fully understand the potential of virtual reality in any domain because it doesn't really exist. So even from an entertainment point of view, it's fascinating. But the ability to create such a real and immersive experience, both visual and sound, that's the real goal. And obviously haptic too if we could have tactile feedback. But even just visual and sound, I mean, I don't think of it as a visual modality at all. To create that real experience in a setting that would otherwise not be accessible to that type of experience gives us the potential to heighten the human experience in many ways. You can heighten it from a pure enjoyment perspective, which is where most of the technology is driving right now,

but to use it as a way to elevate our minds is really, really exciting to me. And so we in this lab have been putting a lot of thought into what type of interactivity in a virtual reality environment would lend itself to enhance how our brains work and improve our existence. And we don't know all those answers, but we're experimenting with them. And there's some really interesting things that it would seem you could do potentially in this lab also. I mean, if you had an Oculus and then, for instance, what are the – I'm sure you've seen this.

It's effectively an unpowered treadmill with a waste harness. Omni. It allows you to run in any direction. Virtuix's product Omni. Exactly. We're like slated on the top of the list. I just had a conversation with their president and CEO about that will be delivered to my lab as soon as it's finally out there.

We're actually a Kickstarter investor in that. We're serious about our technology. We've invested in many Kickstarter projects, many of which we haven't seen yet, but we're hopeful. But you've had 700 update emails, I'm sure. Yes, a lot of emails. But yeah, so the Omni gives us the potential that we can actually move and walk in virtual reality.

So that's incredibly exciting because the more I play BBT and think about embodied cognition, not being a floating jar with some fingers and eyeballs, but actually being a moving human being, I see the value in that. And so I love the idea of most of our games having an embodied format. And so virtual reality where you could walk in and move is pretty exciting. create movies that have animals that are so photorealistic that they're indistinguishable to most people from actual nature footage. And if we're at a point in the very nascent game of virtual reality where we have something like the Omni and so on, it seems epistemologically arrogant to think that we are the only people at any time in any dimension who have achieved that ability. I mean, it brings up a lot of interesting sort of philosophical questions that would have only previously existed in like a freshman, undergrad philosophy class. Oh, for sure. I mean, I'm even more excited about not using virtual reality as a way of expanding outward but expanding inward. So we have a project here where we created something called the Glass Brain.

If you look that up online, you'll see plenty about it and see some videos on it. view of our brain, both structurally using an MRI scanner in our center here, as well as EEG to capture online electrical activity in your brain. Oh, this is the animation that you showed me of Mickey Art. Yeah, exactly. That's amazing. You guys have to Google this. Yeah, that's how we first did it for a gig that Mickey and I were doing in many places. We wound up doing this, as I mentioned before, in front of Congress

and South by Southwest and other places. But now we keep advancing the technology, and we have a virtual reality version of it. So you could put on, let's say, an Oculus Rift, grab an Xbox joystick, and if we've already scanned your brain and we've done all of our processing and you're wearing an EEG cap, fly inside your own functioning brain, which is an amazing experience. And where do we go with that? Well, one really sort of amazing potential is that you can essentially play a video game using the signals in your own brain as the stimuli in the game. Wow.

That gets super recursive very fast. We're exploring that. So basically a very sort of futuristic view of neurofeedback where you learn how to control your brain rhythms by interacting with them sort of in situ in the place in your brain where they're coming from. And this is what I was saying earlier when what I do on a day-to-day basis starts sounding a little like my science fiction books. But we're there. We're doing this already. There's an image here. This is these two guys.

So the image we're looking at is two people sitting down. It looks like they have VR headsets. Both of them have VR headsets. The person on the left is Mickey Hart. So grateful dead percussionist. He's wearing a VR headset and a 64-channel wireless EEG cap. So he's in VR, and he's playing a rhythm game, an early version of Rhythmicity. And just for people listening, so 64-channel basically means 64…

Electrodes. Electrodes. Yeah, electrodes. So it's a high-density cap, but it's mobile. It's custom-built for this lab and pretty exciting technology on its own. So he's in VR playing this game. He's looking at this beautiful space scenario with all Grateful Dead little shout outs everywhere. And he's having fun. And that's showing up on one screen. This is a 120-foot wide screen, 24 feet high, a keynote that I gave at the NVIDIA GTC conference in San

Jose. So 3,000 people in the audience, giant screen. This is the demo after my talk. So Mickey's in there doing that. The guy next to him, his name is Tim Mullen. He's one of our head engineers, really brilliant guy from UCSD. He's wearing a virtual reality goggles, an Oculus Rift, but he's actually flying inside Mickey's functioning brain while Mickey's in his own virtual reality.

So I always think of it and say it's like Russian, like, neuro-nested dolls, you know? Like, Mickey's in his virtual world playing his rhythm game, wearing his EG cap, and Tim is just looking around his functioning brain while he's doing that. So trippy. Yeah. I mean, how much of our current reality at some point are we going to realize is just like that set of nested Russian dolls? Yeah. I mean, we did this live in front of an audience last year. This is all possible. I want to kind of sniff test a theory that has floated around for a few decades. And you may have come across this before, but I'd be curious to get your thoughts because I just saw an article today.

This was actually not an article. It was linked to a study abstract, which was, I want to say, on PubMed. And it was looking at the historical use of hallucinogens by indigenous people, primarily in South America, to improve the hunting ability of their dogs. Really fascinating stuff.

And we could go down that rabbit hole, but just to try to keep myself talking about multitasking, try to keep myself focused for a second, there's a theory of hallucinogenic experience. There are many theories, obviously, many of them completely speculation. But one of them is that the hallucinations are not all internally generated, and instead that the hallucinogens are basically deactivating filters that would otherwise block out this noise that we see or hear as hallucinations. Is that conceivable based on our current understanding? I mean, we get a lot of signals into our brains through all the receptors we have. Obviously, there's many signals out there that we don't have receptors for. So I wouldn't think that a hallucinogen would allow you to receive signals that you don't

have receptors for. I mean, you know, that would be, you know, a little bit of a stretch from my perspective. But, you know, I mean, I never say never. I just don't have any hypothesis of how that would happen. But it is possible that you could be interpreting things that may have not been in your awareness or even been inhibited by your top-'s sort of coming internally but your internal world has been painted and sculpted by your external experience so i bet you know it's some combination uh if you were to we talked earlier about the the multi-modal approach and uh let's just say you have Meditrain, you have BBT, and then you have Rhythmicity. And you mentioned you could potentially at some point add in a pharmacological intervention.

And potentially the multimodal approach would allow you to get a kind of higher yield from a lower dose. What compounds, if you, when you get to that point, or if you ever got to that point here, what are the compounds that would be kind of on the short list for exploring? Well, you know, there's a whole class of drugs that, you know, fell into the cognitive enhancement domain that really became Alzheimer's drugs called cholinesterase inhibitors, boosting the acetylcholinergic system, acetylcholine system. And these cholinergic agents act pretty bluntly to, in many ways, improve attention. But there's a limit and side effects associated with higher doses. So I think it would be pretty interesting to see what they might look like

at a lower dose, but when you're activating the attention networks appropriately. I think that that is a really important question of how do they interact? We don't know that yet. Modafinil is a drug that has had some cognitive enhancement data that seems interesting enough to look at an interaction as well. So I'd say those two. On the cholinesterase inhibitor side, are you looking at something that is potentially a prescription medication or would it be like a Hooper's ENA type over-the-counter thing? I mean, there are plenty of prescription medicines out there that we, you know.

Is it Aricept? Yeah. That's a colon estrus inhibitor. Exactly. That's the most prescribed one. It's a drug I'm most familiar with because that's what I prescribe the most when I'm seeing patients. So as a neurologist, I saw patients for many years. And most of them had early Alzheimer's disease, cognitive impairment associated with aging.

And Aricept was usually, was really our first line agent and still largely is. And, you know, I mean, to me, it's still crazy. Like we really give people these drugs, uh, when they have cognitive impairment and most of the time we don't tell them to do anything. Right. So it's like, to me, it's always like, you know, like a bodybuilder taking steroids and not working out anymore or getting like high-performance oil for your sports car and then leaving it in the garage. Like you got to run it through the engine to get the benefits. really, like as I mentioned, blunt instrument like these neurotransmitter receptor modulators are, how they interact with something that activates a network in a selective way, like what you get from a video game.

And the modafinil, of course, well, I shouldn't say of course, but I believe it was originally provisional, designed as an anti-narcolepsy drug. Funny how many sprinters had prescriptions written for narcolepsy when that came out. Now it's more broad than that. Now jet lag is on the list. Now jet lag. Yeah, and shift workers. Do people at this point understand the mechanism of action, modafinil?

I'm not an expert in that, but I don't think that we fully understand the mechanism of action. I mean, I think – I remember when I first started putting it on my list of things to prescribe as a neurologist, we didn't even know what receptor systems it acted on. It was just like, we don't know. We found this by accident, but it doesn't seem very dangerous. Matter of fact, that is pretty low in adverse effects and addictive potential. So it's a pretty good one. But now from doing some reading, although we have never used it in the lab, so I haven't dove so deep, it does seem like there's a lot of receptors that it acts on. And so I would say that we probably do not have a firm idea on the intricacies of the mechanisms that lead to its effect.

Yeah. What is the most exciting data that you've come across or studies or otherwise related to TDCS or technologies like that? And if you could explain for folks what that is. Yeah. So TDCS is a technique that falls into a larger category that I call TES, transcranial electrical stimulation. TDCS is direct current, picture a nine-volt battery, right? And that's literally what we're talking about in terms of voltage and amperage is at that level, very low. There's another related technique that we use in the lab a lot, which is TACS. So that's alternating current, just AC current.

And then there's another technique that's also related to this because of our brain under the scalp, through the scalp, right? So not invasively. So not like neurosurgery or implantable electrodes, which we use also as clinical care for, like, example, Parkinson's disease. So, you know, our brain is really an electrical machine and using rhythm as a fundamental principle. And so if we manipulate it, we can hopefully get beneficial aspects of it. You could get negative aspects as well, which is why I always feel that we're a little premature in putting this tool out there without more appropriate guidance and testing. But I do think there's exciting potential in this field.

We actually just published our first TDCS paper that you contributed to, and I appreciate that in several different ways, even as a data collector. And we showed that you could get some benefits. And this was just an opening study to start getting our feet wet with this technology in multitasking abilities over a very short period of time that you don't seem to get without it. Now, it's very subtle, but the fact that there's any change at all in a controlled study like that is interesting, to say the least. like this from other labs showing that you can boost certain cognitive abilities by applying low electrical fields, low-embridge electrical fields through the scalp, either DC or AC. But seeing it from your own lab as a scientist is always like, hmm, interesting.

It really does seem to work. And now we have several studies going on using alternating currents where we can actually target rhythms in the brain, right? Because alternating current is essentially a rhythm. So we can make an alternating current at, let's say, four hertz, theta rhythm. We know that theta rhythms from the prefrontal cortex are involved in attention. As a matter of fact, that was the metric that was low in older adults in the neuroracist study beforehand that we normalize with video game play. So what does it mean if you're playing a video game and we know that, you know, we have the impression from our data that boosting this level over a month is what

helped performance on this and even other tasks that we didn't train on the game. Well, how about if you play the game and we boost this rhythm by applying the rhythm across your scalp? Can we lead to a more rapid learning curve? So let's say you just got back from war and you're a wounded warrior and you have traumatic brain injury and you have cognitive impairment and we have these games that target networks that are deficient in you, but you need a little extra boost of those underlying rhythms or the plasticity, can we use an electrical current during gameplay to lead to a more effective outcome?

That's what we're interested in. That is a cool study. Yeah, we're doing that. Super cool. Well, Adam, I know that we're going to go paint the town red after this, so I want to be cognizant of budgeting enough time for us to really get into trouble. But a few last questions.

One is if you could give your 30-year-old self some advice, what would that advice be? Let's see. Advice to the 30-year-old. I would say to have no fear. I mean, you got one chance here to do amazing things, and being afraid of being wrong or making a mistake or fumbling is just not really how you do something of impact. You just have to be fearless.

I like that. And last, where can people learn? No, this isn't the very last. Okay. That was a head fake. Second to last. Second to last is where can people learn more about the lab, photography, everything?

Yeah, so we have a lab website. The short cut in has a long edu, but gazlab.com, G-A-Z-Z-L-A-B.com will get you there pretty quickly. My last name, Ghazali, made up in Ellis Island, is an entirely unique name as far as I can tell by Google. SEO optimized. Yeah, yeah, it's perfect.

So if you search my last name, G-A-Z-Z-A-L-E-Y, you'll find tons of links to talks I've given, to my photography, to our lab website, to lots of media surrounding the type of work that we do. And the final question is, if you had an additional $10 million just came in a secret Senta envelope or whatever, what might you do with that? Because, I mean, when we sit here and play on the whiteboard, I'm always just blown away by kind of the number of not just options, but attractive, interesting, impactful options that you have. What might you do with that? I would just do exactly what we're doing. I

would just funnel that right into the momentum that my lab already has. You know, the things we're doing are pretty edgy for traditional scientific funding sources like the NIH, which also happens to be pretty broke right now. NIH, the National Institute of Health, is at an all-time historic low in terms of their funding of science. Not great times. So we're forced to go to non-traditional sources like philanthropy to try to get money from people that believe in what we're doing to do this work. This work is expensive. You know, we have to hire experts, you know, programmers,

and we're trying to get cutting-edge technology into the lab, and it takes a lot of money and time and expertise. And so there are things that I want to do, technologies I want to try, people I want to hire that we just don't have the resources to do. We have the vision of what we want to do. We have more games we want to build. We want to look at how the games interact. These studies are large.

They're expensive. I would just funnel it into our ongoing research program and try to get it to the next level as rapidly as possible. I like it. I like this plan, Adam. And the other plan I like is going to maybe go out and have some wine as our cognitive handicap before we get back to the focus on cognitive enhancement. Thank you so much for the time, man. Always fun. And everybody listening, check out the lab, check out Adam's work, and we will be definitely following Neuroman and the adventures of Adam and co. Very closely. For show notes, guys, links, resources, et cetera, books, things we talked about, just go to 4hourworkweek.com forward slash podcast. And until next time, thank you for listening.

Thanks, everyone.