The Promise of Technology for the Aging Brain


Adam Gazzaley

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Dr. Adam Gazzaley, is professor in neurology, physiology and psychiatry at the University of California, San Francisco, the founding director of the Neuroscience Imaging Center and director of the Gazzaley lab. His labs most recent studies explore neuroplasticity and how we can optimize our cognitive abilities via engagement with custom-designed video games. He has filed multiple patents based on his research, authored over 110 articles, and delivered over 450 invited presentations around the world

Dr. Dave:  Well I’m so pleased to have you on the show. I think I first read about your work in the New York Times or it may have been the New Yorker, and then more recently you gave a TEDx presentation in Santa Rosa, California—which is my neck of the woods—and your presentation was titled “The Promise of Technology and the Brain.” Before we get into that, give us a little background on yourself if you will.

Dr. Gazzaley:  Sure. I was trained on the east coast, both in neurology as well as neuroscience. I have an MD and a PhD and I did a full clinical residency in neurology, so I had both exposure to clinical care in terms of treating brain ailments as well as basic neuroscience and understanding how the brain works. I moved to the west coast thirteen years ago and did a post-doc at UC Berkeley where I learned the tools of human neuroscience; functional brain imaging, EEG, as well as brain stimulation, and started my own laboratory at USCF ten years ago, where I act as the director of our imaging center as well as run a large laboratory that is focused on both understanding the brain as well as finding innovative ways of improving brain function.

Dr. Dave:  As you pointed out, you’ve got both an MD and a PhD. Which came first?

Dr. Gazzaley:  Well I was in a program called the Medical Scientists Training Program, which is an MD/PhD combined program. But you actually get your MD before your Ph.D.

Dr. Dave:  And where was that?

Dr. Gazzaley:  That was at Mount Sinai, in New York City: Mount Sinai School of Medicine.

Dr. Dave:  Boy, a very interesting background and fascinating work that you’re doing. How did you first become interested in memory and aging?

Dr. Gazzaley:  Well my graduate school work, which started in the early 90’s, was actually on aging, even though I was in my early 20’s at the time. It wasn’t really motivated by anything other than circumstance, and that we had the opportunity to do some experiments on older brains—actually older animal brains—to understand how they differ from younger animals. I thought it was an interesting project, and so I began my research again at a pretty young age myself. Interestingly enough, animals (aside from humans), when they age, although they show cognitive impairment, they don’t show the real signs of Alzheimer’s disease. That’s a uniquely human disease. So my research interests on the aging brain, as a neuroscience student, focused on changes in cognition that were independent of the pathology associated with dementia, like Alzheimer’s disease; what are the normal changes that occur in our brain as we—and I say “we” meaning all animals—get older, that impairs their ability to function at the same level they did when they were younger?

Dr. Dave:  I’m struck by your mentioning that Alzheimer’s occurs only in humans. I hadn’t heard that before so maybe that’s why research hasn’t been more successful than it has because we have no animal models to study?

Dr. Gazzaley:  Well we have neurodegenerative disease right across the board, Alzheimer’s being one of them, as an immensely complex condition, largely because the brain is immensely complex.

Dr. Dave:  Right.

Dr. Gazzaley:  And we now do have animal models of Alzheimer’s disease. They’re not perfect but through genetic manipulation you can mimic some of the pathology, some of the protein changes that occur in the brain. But they’re still not exactly Alzheimer’s disease in all respects, so I do think that’s been a challenge that it is really a disease of the human brain, which in itself is fascinating. You know, there are other animals even with complex brains that live a long time and it’s yet something that only we suffer from.

Dr. Dave:  In your presentation you highlighted “attention, working memory and goal management,” and you said that they’ve not evolved much since our primitive ancestors. Tell us a bit more about that.

Dr. Gazzaley:  Yes, so those sets of abilities, those three that you mentioned, fall into an umbrella that we call “cognitive control.” And cognitive control is the ability of our brains—of our minds—that enables us to interact in a very complex world based on our goals. So we now have—I would say it might be the pinnacle of human brain evolution—ability to formulate very high level goals; complex, time-delayed goals, sometimes across many years, like getting an MD/PhD.

And we have these goals at such a high level and we carry them out through those abilities you said: through our attention, directing it where we want it, working memory, directing our resources where we want it, working on withholding that information in mind and then managing multiple tasks at the same time. Now if you look at those skills in other animals you see that they’re there. Other animals do carry out goal-directed behavior, although they’re not quite to the same degree. There are limitations of cognitive control, there are limitations of working memory; how much information they can retain in mind, how well they can direct their attention and avoid distraction. How they can switch between multiple tasks is in many ways not very different from what we’re capable of. So although we have higher level goals, we have many of the same limitations of other animals have and that’s why I refer to it as not having evolved all that much.

Dr. Dave:  And what are the key developments in technology that make your work possible?

Dr. Gazzaley:  Well I feel like we’re really on the verge of a face shift right now, as I referred to it, in that we have consumer level technology, much of it pointed in the entertainment, communications, media space, that I feel now has the potential to act as tools to improve the function of our brain and enhance our minds. So the types of things that we’re interested in are video games. That’s one of the core pieces of technology that’s been around for a while but it has advanced dramatically, given the improvements in processing power of our computers—motion capture technology that we can sense our movements in space and feed that information into our software, wireless physiological devices, you know, the tools that many people wearing around to track things like steps and even heart rates, like you have right there…

Dr. Dave:  [Laughs] Yeah, Apple watch.

Dr. Gazzaley:  Exactly…are now allowing us to sample really detailed aspects of our physiology and also send that into our software. So we have all these amazing ways of detecting how we’re interacting in the world in a very sensitive real time manner, and now we’re also developing new technology to present environments that are rich and engaging using new technologies like virtual reality and augmented reality. So on both the signal of detection side—understanding how you’re performing—and on the presentation side, creating rich environments that might challenge you. There are a lot of technological advancements that I think could be used to actually harness the plasticity of our brains and improve function.

Dr. Dave:  Yeah, yeah, and that work is so exciting. There was something you said in your presentation that confused me a little bit, and maybe I didn’t get it right. You said, “We’ve recently discovered that we don’t have the ability to multi-task.” Did you mean to say that? Because later on you talk about improvements in multitasking.

Dr. Gazzaley:  Yeah so it’s a sort of a semantic issue. It really comes down to the definition. So we don’t have the ability to multi-task in the purest sense of what that word might mean in terms of actual parallel processing of tasks that demand attention. You could multi-task at a low level; chewing gum and walking being a common example. But if you have two things that really demand attention, like listening to a podcast and trying to type an email let’s say—and I’m sure many people are guilty of that type of behavior—you’ll find that you really can’t do them both at the highest level at the same time. You’re really switching between them. And so multitasking is a behaviour that we engage in, meaning that we attempt to do multiple tasks at the same time. So yes multitasking exists in that it’s something we try to do, but if you look at the mechanics of what occurs in the brain during a multitasking event, what you’re really seeing is task-switching.

Dr. Dave:  OK, so it’s more serial than parallel.

Dr. Gazzaley:  Yes.

Dr. Dave:  Another interesting thing you said was, “We are ancient brains living in a modern world.” Maybe say a little bit about that.

Dr. Gazzaley:  Yeah so I would say it harks back to the conversation we just had about these limitations in our brain in terms of how we engage our cognitive control abilities, these very fundamental limitations in attention, working memory, and goal management—being essentially task switching—that these limitations are very ancient ones. They are parts of our abilities that have not really changed very much and don’t differ from many other animals. So in that sense our brains are ancient, but we are now exposed to such rich stimuli and such dense information content that’s so accessible that it has created challenges for us in terms of managing all these streams of information that really put pressure on those fundamental ancient limitations. So that’s why I like to think of it in that way; that brains are ancient in many ways, and our modern world especially, in terms of information technology, has really created some very salient challenges to us.

Dr. Dave:  Yeah I should mention that I’m an ideal subject for your research. I’m seventy-five years old, and so for example, the multitasking that you’re talking about, I find it challenging to be listening to music and trying to do another task at the same time that involves writing an email or something like that, or paying my bills. It’s a little bit distracting, particularly if there’s singing involved as well as just music.

Dr. Gazzaley:  So the research that I think we’re most known for recently is our experiments and our development using video games as a way of training the brain and improving these cognitive abilities that have these limitations. But where we started from was understanding these limitations in the first place and especially how they get worse as we get older. So the first discussion about aging and memory, we’ve really extended beyond that and I’ve done a lot of work on healthy, normal aging—so independent of things like Alzheimer’s and other types of dementia—and tried to understand what happens in terms of those very cognitive control abilities we’ve been discussing, like attention, working memory, and we find that they decline as we get older—not just older, 50’s, 60’s, 70’s—even across the whole lifespan from 20’s on.
These declining cognitive control abilities increase the amount of interference that we feel in our lives by all of the information technology around us, and that’s what you’re noticing. Even a 20-year-old does not multi-task perfectly. They are still challenged by limitations in cognitive control. It does get worse as we get older. And that information, those results of our early work, is what inspired me and our laboratory to start trying to build technology as a tool to then improve those very cognitive control abilities that decline with age.

Dr. Dave:  Yeah well tell us more about your work. You probably don’t need a lot of prompting from me, so…

Dr. Gazzaley:  Sure. What I just described to you was what my lab did in its first 5 years: understand how neural networks in the brain—which are the connections between all the different brain areas—how these very complex, what we call “multi-varied networks,” meaning that it’s brain areas interacting dynamically across time. That is how the brain works at its highest level. It’s not that separate areas of the brains are little islands of function, it really works as a network and how that network underlies cognitive control abilities and how they decline with age, really form the basis of our laboratory. Around, I guess it’s almost 7 years ago, I became motivated to not just study the brain—how it works and how it changes with age—but how we might build innovative tools to improve brain function. And for that we went to the world of technology.

It’s quite fitting we’re in San Francisco, I have many friends and colleagues around me that work in the tech industry. I started looking at the approaches that they used as potential tools to help brain function. And so the first project that we did was a collaboration between my laboratory and friends of mine that worked at George Lucas’ video game company, Lucas Arts, and we built a video game that I designed for older adults to improve their cognitive control abilities. That game was called NeuroRacer. It was a 3D video game that challenged them in multitasking on two tasks that they had to perform at a high level on at the same time, by using adaptive algorithms. And what that means is that the game senses the performance of a player and then adjusts the difficulty and scales it to their ability. So as their brains get better, which happens through a process known as plasticity, the game constantly ratchets up the difficulty, ratchets it up so that it keeps pushing them to the next level. And we showed in a paper that we published in Nature in 2013—it was the cover of the journal—that we were able to improve not just performance on the video game itself in a group of healthy older adults, 60 to 80 year olds that were playing, but it also improved cognitive control abilities, like working memory and attention.

So that’s really the study that launched the vast majority of the work that’s occurring in the lab now, where we take that core—where we could create adaptive, what we call ‘closed-loops,’ between a person interacting with the game that’s challenging them right at the edge of their ability, and to use that as a tool to improve brain function. And now we’re taking that to the next level by bringing in all the new technology that we talked about earlier, such as motion capture, physiological devices and virtual reality.

Dr. Dave:  Yes, so that game NeuroRacer that you’ve been talking about, did that ever become available to the general public? Can I go buy that somewhere?

Dr. Gazzaley:  What we decided to do at NeuroRacer was a little different than what a lot of other groups have done what might globally be called “brain games.” We decided to take it to the next level of scientific validation as opposed to just releasing it as a consumer product. Although we were very excited with the results from that study, the NeuroRacer study, I always viewed that as a signal that something important is going on here but not enough in itself to start distributing and prescribing it. We needed to build A) a better game, and B) do more studies on larger numbers of people and different populations, and really understand if we had something impactful here. And so I use that game and the patent behind that game as the seed for a new company called Akili, that I act as an advisor for, and what that company has done now is build a much better game. It uses the same type of algorithm that we had in NeuroRacer, but bringing on way more engaging game dynamics and more art and music and story, more usability using an iPad, iCloud data capture, and so we’ve been able to build that game at a much higher level. Now it’s going through multiple clinical pilot trials to understand its ability to improve cognition in different populations. And we’ve really focused on clinical populations here, so from ADHD, autism, post-traumatic stress disorder, traumatic brain injury, Alzheimer’s disease, and more underway.

Other groups are looking to see whether or not the mechanics of this game can improve the same type of cognitive control abilities that we showed we improved with NeuroRacer in these different populations. And the big exciting part of that company’s future hopefully, is what is going on now, which is the launch of a full FDA trial to see if we can reach the end points that would allow it to be approved as a therapeutic tool for children suffering from ADHD.

Dr. Dave:  Yeah that’s all very exciting. I’m thinking back to a time when large numbers of parents were alarmed at the time their kids were spending playing video games, including me and wife I guess, when one of our youngsters just seemed to be almost addicted to video games. I’m happy to report that he’s gone on to obtain gainful work at a fairly high level and still enjoys video games, but is far from addicted. And certainly I reflected, “well there must be possible positive uses, they’re so compelling, and surely these will come to a place where they’ll be useful in education and so on.” But let me ask you about one control that I think would be important to have, would be other standard video games; in other words, there are video games out there not developed by people like you, but focusing entirely on entertainment. How do we know that those aren’t equally engaging in terms of developing brain plasticity, etc?

Dr. Gazzaley:  Well I can answer that in several ways. First I’d say that in the studies that we’re doing, we are using other video games as placebo controls. We have a whole process by assuring that they’re placebos, meaning that they are matched for expectation what people think that they might do, so that is actually part of scientific validation method that we use.
Dr. Dave:  Good.

Dr. Gazzaley:  But putting that aside, it is very reasonable that there are consumer games that do have positive impacts on cognition. I mean, our games are not entirely different from the same type of mechanics that exist in consumer games. As a matter of fact, a lot of the motivation for our first work was by studies done by colleagues of mine, Shawn Green and Daphne Bavelier who showed that the games that some people are most aggravated by, to put it mildly—we tried the first person shooter games, the very violent video games—that they do show benefits in cognitive control abilities in the young adults that play them. And so you do see positive effects of video games, and of course positive effects open the potential for negative effects, which is entirely responsible to consider as well. Our premise is that if there is the potential for games through this inter-activity to help improve brain function in consumer games, which are targeted really at entertainment, then if we take those active ingredients and really just direct it in a much more targeted way towards the brain systems that are deficient in a condition let’s say, then we’ll have even a bigger impact than a consumer game that sort of did by accident.

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