Understanding the Neuroscientific Power of Video Games with Adam Gazzaley, Founder & Executive Director of Neuroscape at UCSF

(Intro Narrator at 00:00:00) Today, we're talking to the professor behind the first FDA-approved video game, Adam Gazzaley, about the intersection of video games and neuroscience. You're listening to Joel Beasley, Modern CTO.

(Joel Beasley at 00:00:17) I got to speak to one of your writing partners. That's how I got introduced to you.

(Adam Gazzaley at 00:00:22) Oh, that's right.

(Joel Beasley at 00:00:22) Yeah. Larry Rosen. Yeah. How did you meet Larry?

(Adam Gazzaley at 00:00:25) I think he reached out to me with the idea for the book, is my recollection. And first, I was like, no way, because I didn't want to write a book. But he sort of presented it in a way that made me consider, and then I thought it was the right thing. But yeah, we didn't know each other until we wrote the book together.

(Joel Beasley at 00:00:44) And what research of yours did he consume to where he thought, hey, I need to reach out to Adam to be a partner on this book?

(Adam Gazzaley at 00:00:51) Well, our research is so different than each other. So he focuses on, I would call it field psychology. Like, what happens in the real world when texts and brains meet each other, children at school doing Facebook and texting. And I do the opposite. I work in a laboratory. We put people inside an MRI machine or hook them up with electrodes and then challenge them intentionally through an experiment and see what happens in their brain.

(Adam Gazzaley at 00:01:18) So I think it was that work that really stimulated his curiosity, and he felt that it balanced the story. Also, I wouldn't have written the book without him because the science story, as interesting as it is, I think falls flat without the real world aspect, which I didn't do any research on at all. So I think that's what made sense to me and convinced me. So it was my functional imaging work showing that we don't really multitask when it comes to what happens in our brains, even though we try to do it in real life.

(Joel Beasley at 00:01:49) Yeah. That episode got started where I was having a conversation with my wife about multitasking. And I said, I think I read somewhere that that wasn't really a thing. You just hyper-transition between tasks, something like that. So I had my production team go find a—yes. I use my business to win arguments with my wife. So—

(Adam Gazzaley at 00:02:08) That makes tons of sense.

(Joel Beasley at 00:02:09) She's my best friend. She's awesome. But when I saw that you did video games and Larry said that you were an awesome human being, I thought, I want to understand better the intersection of video games and neurology.

(Adam Gazzaley at 00:02:20) Sure. Yeah. We could dive into that. It's a big story. The nugget there is that our brains respond to experience, and they change themselves.

(Adam Gazzaley at 00:02:30) Our brains change at every level: structure of the brain, the chemistry, the physiology, all in response to experiences. This is a core foundational aspect of neuroscience, experience-based neuroplasticity, well-studied in animal models and humans for decades. However, the translation of that fundamental basic science to tools and medicines that we use to actually improve our brains is lacking, tragically. We've done a much better job at translating what we've learned about the molecular neuroscience of the brain, neurotransmitters. That has fed our current paradigm where a pill is used to fix your brain. I was interested in flipping that around and understanding how we can use experiences to improve brain function by harnessing plasticity more effectively.

(Adam Gazzaley at 00:03:24) And that logic-based over-there led to now fifteen years of working on developing and validating video games as experiences, targeted experiences that can improve brain function.

(Joel Beasley at 00:03:38) And how do you make money? Do you sell these video games?

(Adam Gazzaley at 00:03:40) Well, I don't really make a lot of money. Let me clarify that. I wear two hats, and I always have to speak from both of them and make it clear which one I'm speaking from. So I am a university professor, first and foremost. I have a 100% appointment at University of California, San Francisco. I'm the director of a research center called Neuroscape.

(Adam Gazzaley at 00:04:05) And we don't—you know, we're a nonprofit. Yeah, exactly. We're a nonprofit, and we bring in not financial investments. We bring in grants and philanthropy, and we do research and write papers and also publish IP, intellectual property, and patents.

(Adam Gazzaley at 00:04:22) But we're not a company. We don't make products, and so we don't make money in that way. My other hat is that I am the co-founder and a board member of Akili, which does make money and hopefully will make more. And we sell a video game as a medical treatment for children with ADHD. That is their first product.

(Adam Gazzaley at 00:04:42) It is the first ever video game approved by the FDA as a medical treatment, which happened in 2020. We're quite proud of that. It was an over-a-decade journey to get there. And so that's the other side. And that is a for-profit company.

(Adam Gazzaley at 00:04:56) And we are expanding our market by having more people that we could prescribe to and trying to look at different indications.

(Joel Beasley at 00:05:08) So that's the first video game ever for anything approved for a medical treatment?

(Adam Gazzaley at 00:05:13) Correct.

(Joel Beasley at 00:05:13) Dude, that's so cool. You must feel super excited about that.

(Adam Gazzaley at 00:05:16) It is exciting. It's an interesting milestone because it's so sort of jarring in some way. Like, oh, video games, and you could only obtain this by a prescription, and it's for children with ADHD. And, you know, it raises a lot of questions, especially because I wrote a book called The Distracted Mind. But it is really exciting. I think it's exciting in a very practical way for children that are suffering this condition with ADHD right now, and their only real alternative are stimulants, which a lot of children and their parents don't want them to have.

(Adam Gazzaley at 00:05:49) So it's great to have an opportunity to try different treatments that are FDA-approved. But on a bigger level, it is, I hope, the beginnings of a paradigm shift where we're not thinking about medicine as pills, medicine as molecules, but medicine can be experiences as well. And so, hopefully, this is the beginning of experiential medicine being actually moved through the FDA and thought of as real medicine.

(Joel Beasley at 00:06:18) That's pretty interesting. I've read with some of the PTSD patients, they're using light doses of psychedelics to help counsel them through those experiences because of the neuroplasticity effect on it.

(Adam Gazzaley at 00:06:31) We actually do that research right here at Neuroscape. So we have a PTSD trial that was just completed using MDMA, also known as ecstasy, in that study. So it's probably the one that you're referring to. That study is now completed and has been submitted for publication, and the results are outstanding.

(Adam Gazzaley at 00:06:50) Same idea. It sounds very different to talk about a video game and psychedelics in the same breath as a similar treatment, but to me, they are both experiential medicines. Granted, psychedelics use a molecule to initiate that experience while a video game uses a device. But in the end, they are similar because their outcomes are driven by the experience itself. Whether the outcome is positive, negative, or neutral is really a product of that experience that it creates.

(Adam Gazzaley at 00:07:24) And so we study both of them here at Neuroscape because that's really what our focus is. So independent of how those two treatments are initiated, we're mostly focused on how we can shape and guide that experience to lead to better outcomes.

(Joel Beasley at 00:07:41) Earlier, you said that your brain through experiences is shaped even on a physical level. Is there currently any science where you could say something along the lines of, I can tell how much of this specific experience a person has had based off of the brain structure? I could tell they've played hundreds of hours of video games a month, or I can tell that they've gone through really difficult things in their life, and maybe that's why they're hardened a little bit. Or—

(Adam Gazzaley at 00:08:09) Yeah. It's a great question. I would say no. Unfortunately, that reverse inference, like, looking at a person's brain and understanding what experiences led to that are not really in our grasp right now, largely because most of our neuroscience data, especially the human data, is really population data. And so all the individual differences are not really accounted for or explained fully.

(Adam Gazzaley at 00:08:33) I think that's a shift in neuroscience now to understand what we can say about an individual from looking at their brain, but what you described is really out of our reach. The reverse case is true. You can introduce someone to an experience, record their brain before and after, and see what it does. So that's something that's essentially what we do all the time. That's, you know, I would say, a foundational aspect of our experimental design is to understand what the impact on the brain is for each individual that engages in one of our experiential treatments.

(Joel Beasley at 00:09:07) How is this technology—you said specifically, it took like ten years for this FDA thing. You've been doing this for quite a while now. How has the technology changed or gotten better as far as your tools?

(Adam Gazzaley at 00:09:22) Yeah. So, ten years was from the idea in 2008 of a video game. That's actually fifteen years now because we've had approval for a little while. The idea that I had of a video game being built, not just used off the shelf, a video game being developed intentionally for the purposes of enhancing attention. And those early days of research were interesting because we didn't really, in 2008, we weren't really using mobile devices for that, and we were using iPads.

(Adam Gazzaley at 00:09:57) Excuse me, we were using laptops and joysticks. And so, it was a little—even though it wasn't that long ago, fifteen years ago, it was still a little, you know, unsophisticated in how we were delivering it. And that was just our first research trial, and it was actually quite successful in terms of the outcomes. We published it in Nature in 2013 as a cover of the journal. Very exciting scientific moment.

(Adam Gazzaley at 00:10:18) But the technology was pretty primitive compared to where we are now. So now, where that has evolved is that everything is mobile. Right? So phones, tablets being the number one tools that we deliver, which weren't really accessible at that time. We also have immersive technologies that we did not have then that we use now.

(Adam Gazzaley at 00:10:39) So we have a lot of our researchers delivering these closed-loop video games. We could break that down if you'd like, but we call them closed-loop video games in advanced displays for virtual reality type of delivery, which has its unique advantages. And, you know, much better use of the cloud for storage and quicker processing for real-time adaptivity and better tools to create games. You know, tools like Unity that allow us to build them in a research center without engaging a big commercial developer. So all of those are examples of technological advances over the last fifteen years that have made what we do better and easier to do when we're just incubating and really being completely innovative and trying things.

(Adam Gazzaley at 00:11:28) We now have a set of tools that allow us to do that reasonably at a reasonable cost, which is a big deal for us because we're a research center.

(Joel Beasley at 00:11:39) I have three kids, ages five, four, and then eight months. Now my five-year-old and my four-year-old started playing video games about a year ago, specifically this one called Rayman Legends. It's pretty interesting one.

(Adam Gazzaley at 00:11:53) I know.

(Joel Beasley at 00:11:53) And oh, you do know it? Good. Okay. So you know what that style is.

(Adam Gazzaley at 00:11:57) Mm-hmm.

(Joel Beasley at 00:11:57) So they've beaten it now, and they're five and four. And my wife and I, before we even had kids, couldn't beat it. We didn't—how much time are we applying to it. Right? But I'm curious when we were discussing introducing video games to the kids, we were trying to figure out, like, content aside. Right? Like, let's just say it's a benign sort of like racing game or something like that. Are they learning things through that? Is that helping their brain develop? Is it like exercise for the brain? Is it not? Tell me about that.

(Adam Gazzaley at 00:12:29) It's a great question. It's one that I think about a lot both as a researcher and as a developer in the space, but also as a dad of a two-year-old now. And there are video games for toddlers, you know, for the littlest ones, and they're really educational video games where they're learning letters. And but I think that's pretty—pretty cool of if you have to expose to some screen time, it seems like a pretty good one. Yeah.

(Adam Gazzaley at 00:12:54) Unfortunately, the answer is not easy. I wish it was easy, but it is always the answer of for a scientist. It depends. Right? So it really depends on the content.

(Adam Gazzaley at 00:13:04) And I would say in general, you know, if you go back to the foundational principles, our brains respond to experiences. It's experiences. It's the entire basis of learning, and it is really rich and robust in little ones. Right? Their neuroplasticity is the highest it's ever going to be, which is why they could just pick up languages, you know. Our daughter is two, and she's already on her third language acquisition now.

(Adam Gazzaley at 00:13:28) So that's the opportunity is to really present content that is valuable and approaches and processes that help their brains develop. And are video games an option there? And I think, for sure, they're just like any other type of experience in the sense that they could be presented, and you can decide which ones and how much. But all of that are the details that we don't understand yet, and that's why it depends. Right?

(Adam Gazzaley at 00:13:58) So any experience, whether it's a game or playing outside, you know, or going to school, can change their brain in some way or in a non-meaningful sustainable way also. And so it's just picking what are those exposures that are going to have the most value and then, you know, applying them also in moderation, keeping a broad diversity. So I would say, you know, it really depends on the child. It depends on the game, and it depends on how much time they're being exposed to it. But there's not a ton of research yet on younger children and these types of targeted video games and what their outcomes might be.

(Adam Gazzaley at 00:14:40) But it's an area that we're already working on at Neuroscape and want to understand better.

(Joel Beasley at 00:14:44) Yeah. How can I—is there—do you have a mailing list or some way I can sign up to—what is that? For—

(Adam Gazzaley at 00:14:49) For sure. So if you go on our Neuroscape website, neuroscape.ucsf.edu, we have a mailing list there. And we definitely don't over, you know, sort of email our guests. But we do let people know when there are research studies that they can participate in. A lot of people sign up for that reason.

(Adam Gazzaley at 00:15:10) And I would say it's about to get a lot better to be on that mailing list because our research has largely focused locally in San Francisco because we would have our research participants come down to the laboratories, usually get brain scans. And so we were only calling from a small area of people that can reach, you know, UCSF within a reasonable amount of time. But we have been developing for the last five years a research platform that we call Nexus that allows us to do large-scale remote distributed trials. And so the studies that we will be announcing later this year, pretty much anyone can join. Well, you know, right now, most feasibly within the US because there's a lot of complexities with data being transmitted around the world.

(Adam Gazzaley at 00:16:00) We would like to fix that problem. We want these to be global studies. But that's a direction that we're going in is having people anywhere, even if they're not near a large university, have the opportunity to participate in research, especially this type of research that has low side effects and people play video games anyway. So that's something we're excited about.

(Joel Beasley at 00:16:22) Why go the prescription route if the goal is to sort of maximize effectiveness and the data you could get? It would—to me and I'm ignorant. I don't understand your business model at all. Yeah. So I would just think by a layman from the outside, oh, making this available in an app store would yield you a significant amount of traffic.

(Joel Beasley at 00:16:41) Parents would buy it left and right because it's like, get your kid off Adderall, get them onto, you know, a video game. Like, yep, I'll do that. But I'm assuming there's some strategy as to why you went FDA and prescription and all of that. Can you share?

(Adam Gazzaley at 00:16:53) Yeah, I can share it. So first, you know, wearing my Neuroscape hat, we have many games that we've built. Some are meditation-based. Others are, as I said, in VR.

(Adam Gazzaley at 00:17:03) We have a rhythm game, a virtual reality navigation tool. Those are not necessarily targeting FDA routes. Those are still in the lab. Right? So their future is unknown.

(Adam Gazzaley at 00:17:15) They may go a complete wellness model or an educational tool or maybe the medical path. So that's important to note that most of the things that we've developed are still in the research setting. We just had a number of publications, and so now the goal is to move them out of the lab in some way. So that's one hat. On the Akili side, yes.

(Adam Gazzaley at 00:17:35) Our treatment right now is FDA-approved and is prescription only. The reason why we started that, well, there's two things, so I'll dissect that a bit. We wanted to take this game through the FDA and have it approved as a medical device. And that was a really tough pathway. No one had ever done it, as we've talked about.

(Adam Gazzaley at 00:17:54) And because of that, the FDA has a pathway called the de novo pathway as opposed to that predicate pathway. Predicate means what, like, almost every drug that's come out recently, you know, including SSRIs, they're resting on a predicate that came before them, and the pathway is a lot faster. If you have a treatment that has never gone through the FDA, it's completely new, de novo, then it's a lot longer path. And we had a de novo treatment because no one had ever tried to have something like this approved. So it was a lot to move the game through this.

(Adam Gazzaley at 00:18:29) We did a big, large-scale research trial. We pre-submitted. The process was like five years from submission all the way to approval, and our results were quite strong, which is why it was approved. So why the FDA? Well, right now, as most people are aware, if your child has ADHD, the FDA-approved pathway is a stimulant like Adderall.

(Adam Gazzaley at 00:18:54) And we felt strongly that we want to have the approval of the FDA showing that the rigor and the validation was there so that parents, which all care about their children very much, would be able to have confidence that someone, somewhere smart was vetting this at a level that sort of took the pressure off of them to read our primary papers and understand that this is something that has been shown to be effective and low side effect, at least enough to have approval. So that was really important to us. And also, like what I've mentioned, the paradigm of medicine is a pill. We want to change that paradigm. And an important pathway to do that is to essentially sort of play by the rules and like, okay, this is how medicine is approved. We believe we're medicine. We're going to run the trial just like it's a drug trial and get approval just like it's a drug, and we did that. Now, most devices and drugs that are approved then enter the market as prescription. There is another pathway called over-the-counter.

(Adam Gazzaley at 00:19:56) And, you know, we're exploring these right now. So this is part of where we are as a business and understanding how we can most effectively deliver to as many people as possible and be able to, you know, be successful as a company. So we're exploring those models right now.

(Joel Beasley at 00:20:14) And now that I hear you talking about it, the marketing side of me says prescription out first would probably be pretty good because it has the additional validity to it. Like, it makes me feel like it's more effective knowing that it's prescription only. I don't know why, but that's how I feel.

(Adam Gazzaley at 00:20:28) I think that that's part of the psychology that we were aware of, and also, its competitors are prescription-based. Right? Adderall is. So we want this not to seem like alternative. We want this to seem like mainstream medicine and not seem to be mainstream medicine. And therefore, we approached it that way.

(Adam Gazzaley at 00:20:49) Because, unfortunately, experiential treatments, whether they're therapy or meditation and mindfulness, and there are many real-world experiential medicines. I would say we're a technologically delivered experiential medicine, which is what makes us quite unique. They have often been marginalized as alternative. Right? Medicine is this pill or this operation.

(Adam Gazzaley at 00:21:10) Everything else is like, you know, stuff we do in Northern California or, you know, it's just sort of not medicine. It's the alternative if you're not comfortable with this. But that is not how we believe medicine should be viewed. This should be considered every bit as real medicine as taking a pill. And so that was part of the strategy to do the hard work, both the research and the regulatory approvals to enter that domain.

(Adam Gazzaley at 00:21:36) And now that we are there, we have much broader discussions about how we effectively meet and serve the most people.

(Joel Beasley at 00:21:45) Yeah, I like that. I don't know if you know this about me, but I've got a lot of doctors in the family. And so my parents have a clinic down in Florida, and they have either primary line of business, but it's called Peaks of Health. So it's health and wellness.

(Joel Beasley at 00:21:59) But the things that they get most excited about is they'll take rare cases or cases where people are getting rejected from other doctors. You can think of it like a very basic House, you know, that guy. And so they'll take these strange, odd cases, and they'll help work through them and find treatments, and they'll explore things that aren't necessarily the exact known treatment and all of this stuff. So I'm around that quite a bit, and I was actually thinking I was like, if I want to call them up after this and be like, hey, can they prescribe it? That's one question. Can any doctor in the United States prescribe this?

(Adam Gazzaley at 00:22:33) Yeah. You know, it's like every other prescribable treatment. People prescribe it on-label, off-label. That's, you know, at the discretion of the physician just like it is for Adderall, for any drug. And so, you know, they're going to make a decision based on the data and based on the patient. Yes.

(Adam Gazzaley at 00:22:48) And I would like to also point out our indication right now by the FDA is for children eight to twelve years old to treat their attention, improve their attention. But we just have top-line results of two research studies, one that was announced earlier this year showing that the attention improvement that we found with children and adolescents is twice as strong. So that has now been submitted to the FDA to expand our indication from eight to twelve that will go from twelve now to eighteen. And just a couple weeks ago, we announced our adult ADHD data, which showed seven times the benefit that we saw with children. So we're really, obviously, really excited about that because adult ADHD is increasing probably because of combination of awareness, and the pandemic, to some degree, could be contributing to that as well, all the fallout of what we just all experienced globally.

(Adam Gazzaley at 00:23:46) So, and, you know, there's an Adderall shortage. It's not a bad time to have an alternative treatment for adults. So that's another focus area that we're now going to move into because we have the data. So we're a very data-driven company. I think it's maybe frustrating to a lot of people that we don't have more things out there, but we choose to take a very slow, rigorous path and get them out there when we think it's appropriate and reach the level of evidence that we're confident to say that, you know, this is reasonable for you to take.

(Adam Gazzaley at 00:24:21) So that's sort of the next step for us.

(Joel Beasley at 00:24:24) Because you're new kids on the block type deal with being the pioneers putting this video game out, it's prescription-based. How did the insurance companies respond to you?

(Adam Gazzaley at 00:24:34) It's a process. You know, insurance companies don't really like taking risks and doing things that are unknown in general, nor does the FDA. So it's a process. And not just for us. It's true for any new drug or device. There is always a gap between FDA approval and insurance reimbursement because the type of data that they consider when making decisions are very different.

(Adam Gazzaley at 00:24:58) So FDA is like, and requires randomized controlled trials, pre-submitted. There's a method. And then insurance companies care less about that. They want to understand the real-world impact, and that just takes time. So we're in the market now.

(Adam Gazzaley at 00:25:11) We have almost 10,000 prescriptions written for children in all fifty states. So, and we just really launched our sales force. So it's growing consistently. But, you know, it's still early days, and that data that will be generated from the real-world use by children, hopefully, will convince insurance companies that this is an important thing to reimburse for. So we are getting some organic, natural insurance reimbursement for this, but we need a lot more.

(Adam Gazzaley at 00:25:43) We need the big insurance companies to step up and recognize that we have, you know, a crisis going on of attention fragmentation and challenges and that this is a treatment that has gone through the rigorous research and is important to reimburse for because people, you know, need that financial support for treatment. So that is something we feel really strongly about, and I hope someone's listening to this that is associated with insurance companies and realizes that this is something that is worth, you know, covering.

(Joel Beasley at 00:26:14) Do you have any stories of a parent whose eight to twelve-year-old was on an ADHD medication, and then they flipped them to this game, and they successfully weaned them off that medication, and they're having the same effect or something like that?

(Adam Gazzaley at 00:26:33) We have many, many stories. It's interesting for me as a scientist because, you know, I publish papers. I look at statistical effects. That's the world I live in. And now, for the first time in my life, I have a treatment out there, and that data is equally important.

(Adam Gazzaley at 00:26:49) But now it's just as important to hear from a single, an N of one, parent and family tell a story to me. It's amazing. And we've published many of those. I did a nice little podcast with Sanjay Gupta from CNN.

(Joel Beasley at 00:27:06) Oh, yeah.

(Adam Gazzaley at 00:27:06) Yeah. Yeah. That one's out there. And he talks to a family, which is just like the family you described, and the mom is tearing because she was so profoundly affected. I mean, it's dizzying for the inventor of this technology to listen to this because I only had my exchange with Sanjay.

(Adam Gazzaley at 00:27:22) I didn't actually hear her part until it was finally released. But, yeah, I have met those families and the children, and it's incredibly powerful for me to hear those reports and know that it's not just statistically significant in a paper, but it's meaningfully impacting people's lives. It's just incredible. It's every scientist's dream.

(Joel Beasley at 00:27:47) If I ever got to talk to Sanjay, I'd be like, so if you could do Joe Rogan over again, would you do anything different?

(Adam Gazzaley at 00:27:56) Yeah. Sanjay, Sanjay is great. We've known each other for many, many years. And we did a whole segment at CNN a long time ago before this was approved. Yeah.

(Adam Gazzaley at 00:28:05) We have a three-part segment on this, and he actually plays the game. And, you know, I'm like, this is going to be FDA-approved one day. And it was like so many years later that it finally happened. So at some point, I was like, oh, this better happen because I really did call that out pretty boldly. But we got there.

(Joel Beasley at 00:28:22) You do a pretty good job of personal branding. Like when Larry told me about you, we started, we knew a little bit about you because you were co-author of the book. But when we were talking, we said, wow, this guy actually sounds pretty interesting. Let's see if we can get him on the show. And we started researching you, and one of the things that stood out was that you do a really good job with being articulate, clear, data-driven. You can express your ideas well. You've got a good presence online. Do you think about that a lot? Do you have a team that helps you with that? What are you doing there?

(Adam Gazzaley at 00:28:53) Oh, well, thank you, first of all. Yeah, I care about it a ton because I think a mandate of being a scientist is to communicate science. And so I don't have a team. It's just something I think about a lot.

(Adam Gazzaley at 00:29:06) I practice a lot, and I do it a lot. So, you know, I've learned from, you know, I've given over 700 talks and many podcasts, and I also talk to friends about science a lot that are not scientists. So you just learn through exposure. But it is really important to me to do the rigorous work and then to present it in a way that is accessible and as real and as close to what the research shows as possible. And it's been really challenging, because when we present research to each other, to other scientists, there's a statement, and then there's 15 caveats.

(Adam Gazzaley at 00:29:43) We always talk in caveats because it's appropriate, because nothing is 100%. There's always this or that or that. And then when you talk to the public, no one wants to hear a statement followed by, you know, a citation and then fifteen caveats. So it's tricky business of how do you present science in a way that's as close to what's appropriate as possible and still make it accessible. So a lot of scientists completely, you know, shy away from any contact with anyone other than scientists because of that.

(Joel Beasley at 00:30:16) Yeah. Yeah. The general public, like, if you just go out and do man-on-the-street interviews, well, you've seen the videos. I won't comment further. Diagnosing ADHD.

(Joel Beasley at 00:30:26) I'm curious. So I believe that this is such a common phrase, ADHD. Like, in society, we go about, and then there's this, what I would call, collective consciousness understanding where it's like, okay. The kid's bouncing around. ADHD. Give them a pill. Maybe they focus. That's clearly probably pretty wrong. Can you explain to me exactly what ADHD is and how it manifests itself inside of children?

(Adam Gazzaley at 00:30:52) Yeah. This is a challenging question. It shouldn't be, but it is. Because unlike many fields of medicine, let's say cardiology, and we'll talk about, you know, blood pressure, hypertension, and high cholesterol, hypercholesterolemia, right? We have very well-defined biomarkers that we set levels at.

(Adam Gazzaley at 00:31:15) If your blood pressure's over this on two visits, if your cholesterol's this level and it maintains that way, it triggers something and we have a treatment. And those levels change as data presents itself, and what you do with that data changes. That's true of everything in medicine. But there are those real quantitative markers that inform decisions. In psychiatry, unfortunately, most of the conditions like ADHD and autism and even depression, anxiety, are really a list of subjective symptoms that sometimes they're presented not even by the patient themselves.

(Adam Gazzaley at 00:31:53) Like in the case of ADHD, it's often the parent's impression or teacher's impression. And so you wind up with a moving target, which creates a lot of confusion, a rapidly moving target of what ADHD is. So there's a checklist of symptoms that basically you move through, a doctor will move through. And depending on how many you get in different columns, you could be diagnosed with inattentive ADHD, you could be diagnosed with hyperactive ADHD, or mixed, where you have features of both. And that's really it.

(Adam Gazzaley at 00:32:22) And what's in that list changes a lot. So there are cognitive tests that offer quantitative data, but they are just supportive. They don't really help define the diagnosis. And so this is the challenge is that we move the mark a lot, and they are subjective. So that creates a lot of confusion for people about what these conditions are.

(Adam Gazzaley at 00:32:48) So with ADHD, in particular for children, most fall in the mixed type where you have a bit of inattentiveness and a bit of hyperactivity. They're both forms of inattention, but one presents itself motorically with a lot of movement, jumping out of the seat, more behavioral. And the inattentive doesn't present itself that way as much, but presents itself as maybe poor school performance, thinking that someone's not focusing and losing the train of conversations. Girls, young girls, have more of the inattentive type, and so they're often missed, including women as well, because their behavioral manifestations are less. And so a teacher may not notice it and misdiagnose it as something else that's contributing to maybe a mood disorder.

(Adam Gazzaley at 00:33:37) So this is a little bit of the complexity with ADHD. And I would say that complexity that I described, like the poor subjective diagnostic features that are changing all the time, collides with the fact that everyone has trouble with attention to some degree. And, you know, that was the basis of the whole book, The Distracted Mind.

(Adam Gazzaley at 00:33:59) You know, our brains have a set of abilities that are really impressive, but they have limitations, and they collide with our technical world and create all of these challenges that everyone experiences all the time. So when you're thinking about ADHD, like, well, I have some attention problems. I find myself distracted. I can't get something done without moving over to social media. And I would say that the fact that people know what the burden of attention is complicates the diagnosis more.

(Adam Gazzaley at 00:34:30) So, for example, diabetes, either you have it or not. You know? Like, you don't say, oh, I feel a little diabetic now. You don't have the subjective experience, which keeps it a little cleaner diagnostically. So that's a little bit of why I think it's so challenging, especially with the pandemic, I would say.

(Adam Gazzaley at 00:34:51) The presence of inattention and its clear impact on people's lives became really prominent when you're locked in your house with your kids and kept away from work, so that's, you know, another factor that is impossible to ignore.

(Joel Beasley at 00:35:09) Yeah. So it's an attention disorder, right?

(Adam Gazzaley at 00:35:12) It's defined as an attention disorder that has a set of features that establish the criteria upon which the diagnosis is made. I'd say that's the simplest way of presenting it. That being said, there could be lots of causes for it, and it also has a lot of comorbidity with other conditions like autism and mood disorders. So it doesn't have, you know, here's let's look at someone's brain. Oh, they have ADHD.

(Adam Gazzaley at 00:35:38) That's what I mean that it doesn't have that real quantitative marker. But it is an attentional disorder where the challenges with attention are reaching a level of functional impairment that something is advised to be done for it when you reach that criteria.

(Joel Beasley at 00:35:54) So you can measure this attention, right? You can measure it before, and that's what you would do? You find some way to measure the length of attention?

(Adam Gazzaley at 00:36:02) Yeah, so that's what I was trying to allude to. So those tools exist, but they're not required for the diagnosis and often not used for the diagnosis. The diagnosis can exist totally on the subjective aspects of it. But the tools to measure attention exist. We use them all the time.

(Adam Gazzaley at 00:36:19) We use those tools, those diagnostic tests of attention, as outcome measures in our clinical trials so that we can actually quantify it.

(Joel Beasley at 00:36:27) Sorry to interrupt you, Guy.

(Adam Gazzaley at 00:36:28) Please.

(Joel Beasley at 00:36:28) I'm excited, and I just wanted. Yeah. I'm an engineer. I'm not a scientist. But I'm trying to—it's an attention disorder. We have tools that measure attention.

(Joel Beasley at 00:36:37) In order to diagnose it, we don't use the tools that measure attention to create the diagnosis. How is that a thing?

(Adam Gazzaley at 00:36:43) It's historical. I've argued about this quite a bit, that we need to bring objective measures to this field as they are in every other field. But it's slow. These big institutional systems are really, really lagging. It's not only true for the diagnosis as I described, but it's also true on even what the FDA considers as meaningful outcomes in studies. They would reflexively go to those subjective measures before objective measures, interestingly enough.

(Adam Gazzaley at 00:37:13) So it's part of a shift that I think is occurring now as we validate these tests more and more. And they need to be validated and show that they have real world meaning. But I agree, we need to have them. And we have many of these tests. We use them in the laboratory all the time. They could tell you how stable your attention is.

(Adam Gazzaley at 00:37:28) So we could look at how response times change across periods of exposure. We call that response time variability, RTV. And there's lots of other measures that can be assessed from tests that really give us a fine-grained understanding of how your attention is operating. And attention is really a broad concept. There's selective attention, sustained attention, bottom-up attention, top-down attention. It's really quite complicated, but we have tools to assess all those things.

(Joel Beasley at 00:38:02) Okay, so trying to make sure I get this out right. So I'm cool with that. I don't imagine everything's logical, because I'm 35, so I have a little bit of experience in life. And that's one of the things I tell my team all the time. Step one, throw logic out the door.

(Joel Beasley at 00:38:15) Step two, figure out how the system's working and play the game.

(Adam Gazzaley at 00:38:18) Yep.

(Joel Beasley at 00:38:19) So I just want to better understand and use the right phrases. So you said subjective, but if I create some sort of test and I say, okay, I think they might have this symptom—by definition, disorders, anything that's like, you would take the average and you'd say, okay, over here is what the standard is. This is what a normal kid is.

(Joel Beasley at 00:38:42) And if you deviate from that by some degree, eventually, if the deviation's large enough, you have this disorder.

(Adam Gazzaley at 00:38:49) Correct.

(Joel Beasley at 00:38:50) Who is that group that they're using as, like, here is what a perfect kid is at this age, and then here is how far you deviate from that as far as your manifestation of attention disorder?

(Adam Gazzaley at 00:39:01) So there's this big manual called the DSM, Diagnostic and Statistical Manual, and there are groups of experts that convene to form the criteria for every condition that exists. And they put out a recommendation, and then they update it, and it usually changes. Sometimes conditions disappear. Sometimes new conditions enter. I've not been on one of those, so I don't know the process in detail, but they're looking and, you know, a lot of times probably using intuition and logic and their clinical experience to determine what those criteria should be, how many you need to check, and things of that nature.

(Joel Beasley at 00:39:39) Okay. All right. And then so they are determining the framework for what constitutes somebody meeting that criteria.

(Adam Gazzaley at 00:39:47) Correct.

(Joel Beasley at 00:39:47) And then if you meet that criteria within those rule sets, you have this condition.

(Adam Gazzaley at 00:39:52) Correct.

(Joel Beasley at 00:39:52) And then they let the people subjectively answer questions that could potentially meet that criteria and have that condition. Correct. Okay. As a parent, I've got boys and girls, very different, right?

(Joel Beasley at 00:40:05) The girl, she's technically about to start kindergarten in three or four months. She's about to finish grade one because we homeschool her and we have a tablet system and a whole thing we pay for, and they can just go through at their own pace, and she happens to just want to wake up every morning and do it. Also, the checkmarks to get through school—school is highly inefficient. It's a giant babysitter club because you could teach your kids everything they need to know to pass the standardized exams in 35 minutes a day.

(Joel Beasley at 00:40:33) That's a whole other conversation. But for her, the way she does attention and the way she does things is vastly different than her brother. But when I put certain activities in front of her brother, you get that laser focus. When I put certain activities in front of her, you get that laser focus.

(Joel Beasley at 00:40:48) And they tend to be good at different types of focusing and activities. So with it being so ambiguous, how—I know I already asked you how they do it, but—what am I reaching for?

(Adam Gazzaley at 00:41:01) There's another piece, which is the medical professional. So it's not something that you just check all these boxes, done, I have this. It occurs in the context of a clinical visit. It could be with a psychologist. It could be with a pediatrician.

(Adam Gazzaley at 00:41:14) It could be with a psychiatrist, a primary medical family doctor. And the decision is a collection of that data, maybe even some cognitive tests. I think that's great if that occurs because it gives little quantitative metrics that can be followed. And then it's a clinical impression that, you know, based upon my experience, based upon your child and these other details that might not fit directly into the list, I think your child has ADHD. And, you know, it's not entirely dissimilar on the other end of the life spectrum.

(Adam Gazzaley at 00:41:47) So dementia diagnosis is also a checklist of things that, you know, your cognition is not great, but it's now reached the level that it's impairing your life, is causing functional impairment, and thus your dad has dementia. So, you know, that's the other piece, is that there is a medical system of experts that have lots of experience that help guide you through this diagnosis and whether or not the diagnosis is even appropriate. And that's a good thing. Humans are in the loop here, and they should be, at least where we are right now. And so I think that's another factor, is that hopefully that clinician has a lot of experience and spends the appropriate time with a parent and their child and cannot just reflexively check a list, but say, yeah, I think that there's something here that is deviating enough from my experience of normal—not just checking the boxes—that I would say that diagnosis is appropriate.

(Joel Beasley at 00:42:51) Yeah. I guess—so I'm definitely biased because I have looked at the—not anytime recently, but about two years ago, I looked at the rate of increase in children being prescribed stimulants for this, and I'm just like, there's no way 80 percent of our population—or it wasn't 80 percent, but it was growing and it was higher than I wanted it to be. This is before I had kids, right, couple years ago. And I was like, wow, that's bonkers.

(Joel Beasley at 00:43:16) And so one of the general stories that I would just hear people talking about in life would be, oh, yeah, you know, Bobby, he wasn't sitting still in class, and his teacher brought it up to us, and we put him on ADHD medication. And then I had my son, right? And he's about four.

(Joel Beasley at 00:43:29) And I was like, wow, if he was in school, he wasn't homeschooled, right? He wouldn't sit still in class. This kid wants to run around. He wants to play. He wants to do things. But then he'll like certain things, and then he'll sit down and want to do those with laser focus. And so it's more of finding, okay, what type of kid is Lachlan? How do I engage him? We have found these great—so this is just feedback from us

(Adam Gazzaley at 00:43:52) Mhmm.

(Joel Beasley at 00:43:52) for you. So we have found these great videos that work really, really well for Lachlan on YouTube. And they're super cheesy, but he'll be running and then jumping, and there's stuff going across, like, storyboard style on the screen. And so it basically gets him, like, oh, we're running from the dinosaur, and there's this cartoon dinosaur.

(Joel Beasley at 00:44:11) And it's an actual human child on the screen, right? So it's like—have you seen these before or no?

(Adam Gazzaley at 00:44:16) No. But I want to get a link from you at some point.

(Joel Beasley at 00:44:20) So that is when—well, we live in Tennessee. So when it's too cold or too hot to go outside, we will use that as their sort of PE.

(Adam Gazzaley at 00:44:28) That's fine.

(Joel Beasley at 00:44:28) Right? Because they'll sit there and they'll run and they'll jump, and then they have different versions of it. And these videos, man, have 58 million views. It's ridiculous.

(Joel Beasley at 00:44:37) So we have found those to be incredibly useful. So when you start talking about this idea of experience or video games or videos or something like that actually having an impact on the way they think or their body, I'm 100 percent on that train. And I'm definitely on the train of we should just take a step back from the ridiculous amount of stimulant prescription for children and consider things like video games.

(Adam Gazzaley at 00:45:00) Yeah. You know, it's a good connection point that you made, and I just want to pause on it because we've been largely talking about diagnosis. But diagnosis and treatments are woven together. And depending on what the treatment is, diagnosis is a really different concept, right? So making an ADHD diagnosis in the setting in the status quo that the really only FDA-approved treatment is a stimulant is much more complicated in my mind than a future where, hopefully, we're just the first, that there are experiential treatments that have very low side effects that can be offered, that have the level of validation that you could at least trust them to try.

(Adam Gazzaley at 00:45:44) That changes a lot, because now the ADHD diagnosis is offered to a parent as, this is the reality with a whole set of options that are going to have different comfort levels for different people. That really changes the whole thing, right? Because offering a diagnosis with, and here is your choice and it is Adderall, you know, it is a stimulant, is not really ideal, right? We need to have more options that have gone through the rigorous process of validation that can be presented by a physician as, here's the list, and we could try this, we could try that. And that's a much better future. And it changes how you think about diagnosis, because now I'd say diagnosis really needs a high bar because that diagnosis really leads almost like a direct path for a lot of people to these treatments, which I think are less than ideal. So that's another way of thinking about the complexity of diagnosis.

(Adam Gazzaley at 00:46:45) When you have one treatment, what happens with diagnosis is a lot more serious.

(Joel Beasley at 00:46:50) Yeah. What else do we want to get out there to the world? I want to make sure I'm cognizant of your time, and I want to make

(Adam Gazzaley at 00:46:57) sure we get

(Joel Beasley at 00:46:57) the right message out to the audience. How can people—if they want this prescription for their kids, we got a lot of parents that listen, right? If they're interested in this prescription, what do they tell their doctor?

(Adam Gazzaley at 00:47:06) Yeah. That there is a game that is FDA-approved. It's called EndeavorRx. And that they want to hear more about it or they want to try it. I think that that is certainly something that I would recommend if friends reached out to me. I'm not saying that this is a panacea and it's a cure for everyone.

(Adam Gazzaley at 00:47:26) I mean, there's lots of variability. But it is, you know, we did the work. And it is certainly something that should be presented as an option, especially because the other options are just so limited and, you know, big decisions for a parent. I feel it not just intellectually as a scientist, but as a dad of a two-year-old right now. So I would hope that it's at least something that they could talk about with their physician, and they could look at the data and make a decision together if this is an option for them.

(Joel Beasley at 00:48:01) If people want to watch stories or read stories of other parents who've made the transition from stimulant to video game, where can they do that?

(Adam Gazzaley at 00:48:11) That is a great question. I believe that we have some of those testimonials up on our website, and I could share those links with you. But we should do more of it because we really have a large collection of them, and I think that it is really valuable.

(Joel Beasley at 00:48:25) Cool. We'll add those to the show notes. If we can't find them, we'll just put in more useful, cool information. I've actually gotten to see a couple of videos of you on YouTube showing the video game off. And so there's definitely visuals that we have, and you can see it for sure.

(Joel Beasley at 00:48:39) Yeah.

(Adam Gazzaley at 00:48:39) Yeah. For sure. And but those testimonials, you know, we think of them as valuable, especially for physicians to say, oh, look at this. This is not just a paper or a series of publications, FDA approval, but these are parents that are like, wow. Okay. This was meaningful to me. But it is also very valuable to other parents to know that. So I think that it's a good message that we could communicate. We should find ways to really make that accessible for people.

(Joel Beasley at 00:49:07) And what's the website?

(Adam Gazzaley at 00:49:09) EndeavorRx. And yeah, I'll put that. Akili is the name of the company, so you could find it either way.

(Joel Beasley at 00:49:15) Cool. We did it. Adam, we made a podcast, man. How do you feel?

(Adam Gazzaley at 00:49:19) Great. It was so much fun.

(Joel Beasley at 00:49:21) Thank you so much for listening. And if you found this episode useful, please share it with a friend or colleague who you think would get value from it. And if you have topics that you'd like to hear discussed on the podcast, either add me on LinkedIn, or send me an email [email protected]. Every time I get an email or LinkedIn message, it absolutely makes my day and inspires me to keep going.