184 - Brain Health Breakthrough with Dr Henry Mahncke & Dr Gitendra Uswatte

Dr. Henry Mahncke and Dr. Gitendra Uswatte share groundbreaking research on using brain plasticity principles to treat Long Covid brain fog through a comprehensive approach combining cognitive processing speed training, real-world skill practice, and personalized cognitive rehabilitation strategies.

• Neuroplasticity is the brain's ability to change its structure and function through learning and experience
• Brain HQ training targets cognitive processing speed to improve overall brain function across multiple domains
• Long Covid causes real biological changes to the brain, including vascular damage and inflammation
• CI Cognitive Therapy combines three components: brain training, everyday task practice, and transfer techniques
• 80% of participants in the small initial study returned to work compared to none in the usual care group
• Brain health bridges physical and mental health, challenging the "it's all in your head" dismissal
• The intervention works by repurposing and growing healthy brain tissue rather than healing damaged tissue
• Approaches vary from "bottom-up" (basic processing) to "top-down" (real-world skills) to meaningful goal setting
• Brain HQ is currently available worldwide, with ongoing research to develop telehealth versions of the full intervention

The University of Alabama Birmingham is currently enrolling participants for their Long Covid cognitive rehabilitation study. Interested individuals can call 205-934-9768 or search "Uswatte Long Covid Cognitive Rehabilitation" online.

Links:

Brain HQ:
brainhq.com

Information about enrolling in the current study:
https://sites.uab.edu/longcovidbraintraining/

Research paper:
https://www.medrxiv.org/content/10.1101/202

For more information about Long Covid Breathing courses & workshops, please check out LongCovidBreathing.com

(music credit - Brock Hewitt, Rule of Life)

Chapters

• 1:51 Meet the Brain Health Experts
• 10:24 Understanding Brain Plasticity
• 19:50 Beyond "It's All in Your Head"
• 25:54 How COVID Damages the Brain
• 34:41 The CI Cognitive Therapy Approach
• 42:58 Bridging Brain Training to Real Life
• 51:44 Next Steps and Availability

Transcript

Jackie Baxter: 0:56

Hello and welcome to this episode of the Long Covid Podcast. I'm delighted to have two guests with me today. I've got Dr Henry Manka and Dr Jitendra Iswati and we are going to be talking a bit about research and the brain and well, these guys are going to tell you a lot more about it in just a moment, so I'm really excited to dive into all of this. Welcome, both of you. I'm so excited to have you here.

Dr Henry Mahncke: 1:23

Thanks, it's a delight to be with you.

Dr Henry Mahncke: 1:25

Thank you, jackie.

Jackie Baxter: 1:26

So it's lovely to be kind of discussing research and stuff that we can do. So before we kind of dive into all of that, can you just give us a little bit of an overview of who you are and what you do?

Dr Henry Mahncke: 1:43

Sure, I'll kick us off and then I'll kick it over to my friend G here. My name is Henry Monca and I'm a neuroscientist by training. I did a PhD in neuroscience at the University of California, san Francisco. So I'm out on the West Coast here and I had the amazing opportunity to do my PhD research on the topic of brain plasticity, which is this incredibly important and exciting idea that the brain can actually rewire and change itself. It can change its structure and its function and its chemistry by learning and experience and training, and I'm sure we'll dig into more of that as we talk.

Dr Henry Mahncke: 2:19

But you know, after my PhD I actually worked for the British government for a short period of time. I worked for your Foreign and Commonwealth Office where I served to build scientific partnerships between the US and the UK. And then one day my PhD advisor came to me and he said remember all that brain plasticity stuff you did? We've helped a lot of rats build better brains and we've helped a lot of monkeys build better brains. Don't you think it's time to help people build some better brains? And so that led to the founding of our company, posit Science, where we make Brain HQ, a software based brain training program and we'll probably talk about that in more depth too. But that's what brings me to the podcast. We have a tremendous interest in helping people with all kinds of brain health issues, with the power of brain plasticity.

Dr Gitendra Uswatte: 3:06

My name is Jitendra Oswate, jackie. You're welcome to call me G. I'm a professor of psychology at the University of Alabama at Birmingham. I was trained as a clinical psychologist and my specialty is rehabilitation psychology. My research for many years was in physical rehabilitation, studying actually how to harness brain plasticity to help people with strokes and other kinds of brain injuries to recover movement, to use their stroke-affected hand more effectively, to walk again. And in recent years really the last four or five years I've turned my attention to cognitive rehabilitation, starting with stroke and then that was a pathway into my more recent work in long COVID.

Jackie Baxter: 4:02

So you know, what really excites me is that there are things that help people. So what I would love to know is like, you are developing this Brain HQ and maybe we can talk a little bit about what it is, but also what made you think that that was going to help with long COVID, for example. What kind of led you down that path?

Dr Henry Mahncke: 4:31

Yeah, why don't I say a few words about brain training and kind of what it's all about, and then, gee, I'll throw it over to you and you can kind of tell the story of how you got interested and began and kicked off this study. So you know what Brain HQ is is it's a software-based brain training program that runs on, you know, laptops, computers, phones, ipads, android tablets, what have you and it takes this basic science idea that the brain can reorganize itself through learning, experience and training and turns it into, well, a brain training program that just about anyone on the planet can go ahead and do. And what Brain HQ is is it's a large set of brain training exercises, and these exercises cover all kinds of cognitive domains. They're exercises that focus on speed and attention and memory and even more advanced cognitive skills like people skills or navigation or executive function and decision making. But every one of these exercises is built on the same scientific foundation, and that foundation is the idea that if we can speed up information processing in the brain, if we can make information processing in the brain more accurate, then we can make the brain just overall better at processing the information that comes into us through our eyes and our ears, we can give better quality information to the parts of our brain that are involved in working memory and attention and decision making and if we do that well, the whole brain is just going to work better and people should perform better on cognitive skills and they should perform better in real world skills.

Dr Henry Mahncke: 6:04

And you know, this is kind of a new approach to thinking about rehabilitation and gee, you'll probably talk a little bit about kind of the history of this as you chat, but that's what we've done is taken this basic science out of the lab and put it into the world science out of the lab and put it into the world. And you know, as we got going, we wanted to not only build a brain training program that was sensible from a scientific perspective, we wanted to build a brain age training program that really had been shown to work in clinical trials, just the way a drug manufacturer or a medical device manufacturer would be expected to do. So as we built the first versions of Brain HQ, we actually ran large-scale studies, first in aging, where we partnered with Mayo Clinic and the University of Southern California, and actually did, you know at that time, one of the largest studies that had ever been done with a broadly available brain training program and showed that in people who were just undergoing normal aging, that we could significantly improve their memory and their attention and their everyday cognitive function. And that was an incredible breakthrough, because I think until then a lot of people had thought about aging like, well, it's kind of a one-way street of cognitive decline. As we get older, our brain gets worse. And, hey, maybe it gets worse faster for me and slower for you, but we're all on that path and there's nothing to be done about it. And what the science of brain plasticity showed, and what that first study showed in particular, was, hey, that's not true. We should think about the brain as something that is constantly rebuilding itself and if we ask it to do the right things, we can build a stronger, healthier brain that serves us better.

Dr Henry Mahncke: 7:34

And that first study just kicked off a wave of research at labs across the country and around the world that was focused not only on aging but, you know, asking this question in all kinds of other brain health conditions, like neurological conditions and psychiatric conditions, just about all of which people have some degree of cognitive impairment, and more and more scientists began to ask well, hey, can we treat these symptoms?

Dr Henry Mahncke: 7:57

Can we improve brain health and cognitive function in people across the spectrum of brain health conditions, whether it's aging or more significant neurological or psychiatric conditions? And more and more of those studies started to come in positive, saying, hey, we just need to change the way we think, we need to not think of these conditions, as, hey, a person who has one of these brain health conditions is always going to have poor cognitive function and poor brain health. But in the same way that we can think about improving their physical health, we can think about improving their brain health as well. So that's what led us to build Brain HQ and that's kind of what's led us down this scientific path. And then I suppose one day we got a call from you, g, at University of Alabama, where we've had many longstanding collaborations. People may not appreciate this, but the University of Alabama at Birmingham is actually kind of a hotbed of brain plasticity research, with all kinds of cool projects going on. But we heard from you.

Dr Gitendra Uswatte: 8:50

G. As I was saying, our pathway into studying long COVID brain fog really started with stroke. Brain fog really started with stroke and stroke was of interest because slowed cognitive processing is common in many, many adults with stroke, with cognitive impairment, and Carlene Ball, who developed the original version of the cognitive processing training software here at UAB, is in my department, so she was a natural person to partner with to identify a way to rehabilitate slowed cognitive processing in adults with stroke. And so I began this work with Carlene and Ed Taub, who was my mentor and then longtime colleague, and so we married the cognitive processing training approach that Carlene had developed with techniques from what we call CI, movement therapy, for promoting transfer of gains from the treatment setting to everyday living, and I'll talk more about that later. So it was really kind of a marriage of work that Carlene had done and work that our lab had done, and we did a case series, small case series in adults with stroke.

Dr Gitendra Uswatte: 10:22

Very, very promising results observed, really very large improvements in performing everyday activities, improvements in cognitive processing speed, and one day Ed and I were, you know, just sitting around and chatting and talking. Of course COVID at that time was on everybody's minds, you know talking about how there was data coming out that slowed cognitive processing was also a hallmark of long COVID brain fog. And then it just seemed sort of a natural to say, hey, if it works in adults with stroke who have slow cognitive processing plus some overlaps in the type of damage that occurs to the brain because there's damage to the vasculature in some people with long COVID and damage to the vasculature in the brain it was just sort of a natural next step to test the intervention we had developed in people with long COVID brain fog.

Dr Henry Mahncke: 11:36

And you know it's. It's so interesting as you raise that because you know my own journey as a, as a cognitive scientist, as a neuroscientist was. You know. It's so interesting, as you raise that because you know my own journey as a cognitive scientist, as a neuroscientist was. You know, when we built Brain HQ originally, we thought about aging and you know, if you read the literature on aging or if you just talk to older people, that you know, you know rapidly, find out that hey just about everyone to some extent feels like, hey, I'm slowing down a little bit, my intention's not as sharp as it.

Dr Henry Mahncke: 12:00

A little bit, my intention's not as sharp as it used to be. My memory is not great, you know. It doesn't mean you have Alzheimer's, that's a much more significant condition. But you know, these sort of mild levels of you know, increasing cognitive difficulty show up.

Jackie Baxter: 12:12

And you know as.

Dr Henry Mahncke: 12:13

I, you know, went forward with Brain HQ over the years and I started to talk to more and more clinicians. And you know, I talked to clinicians who are involved in multiple sclerosis, for example. And when you talk to people who have multiple sclerosis, well, what do they say? Hey, I feel like my brain is slowing down a little bit and my attention's not as sharp and my memory's not quite as good. And then we talked to people who were involved in studying cancer and chemo brain. And hey, when you talk to, for example, women who've gone through breast cancer, what do they say, well, I'm slowing down a little bit and my attention's not as sharp and my memory is not so great.

Dr Henry Mahncke: 13:32

And then, when the COVID crisis hit, you know it wasn't that long, probably six months into it, where the first patient report started coming, where people said, hey, I've kind of gotten better from the infection of COVID, right, I don't have the immediate respiratory symptoms, but boy, I've not bounced back, right, my brain just feels foggy, I feel like I've slowed down, my attention isn't as sharp, my memory is not so great, and I remember reading those first patient accounts and thinking, holy smokes, maybe this is, you know, going to be representative of something that is, you know, sadly not that uncommon after COVID, but maybe there's going to be some underlying similarities to these other brain health conditions that we've been aware of in doing trials, and that's what was both scary from a clinical perspective but pretty interesting from a hey, do we have something new from science we might put together to help people?

Jackie Baxter: 14:21

And to just go back to something, henry I think it was that you mentioned earlier the sort of physical health and brain health. I think you said Now, what's the difference? Here we often talk about physical health and mental health. So brain health, is that the same as mental health, or is that another category? How would you sort of class that in the sort of spectrum?

Dr Henry Mahncke: 14:49

It's a great question, I think, of the term brain health. It's almost bridging between the physical health and mental health, and the reason I say that is this you know, the brain is, of course, is part of the body, right? The brain is, you know, three and a half pounds of kind of wet, squishy goo that sits inside your skull. And you know, just like your heart can be healthier or less healthy, or your liver can be healthier or less healthy, your brain as a piece of biological tissue can be healthy or less healthy. Biological tissue can be healthy or less healthy. And that's the sense in which I think we have, you know, thought so much and learned so much about how to keep our hearts healthy and how to keep our livers healthy and how to keep our bodies healthy. But often we think about that kind of from the neck down, and we should remember that, hey, that we can keep our brain healthy, probably with some of the similar techniques, but also some different techniques, and keep that healthy. But you know it serves as that bridging concept because, of course, you know, when we think about mental health difficulties, if we think about depression or anxiety or stress or more significant mental health conditions like mental illness like schizophrenia or bipolar disorder. You know those aren't imaginary psychological issues. Those are very real health conditions that emerge well fundamentally from the health of the brain. And so I tend to think of physical health and brain health and mental health as all actually kind of very deeply related in that sense that these are true issues that emerge from the health of different biological systems.

Dr Henry Mahncke: 16:24

But I often do use the term brain health because, as we are thinking about building tools and brain HQ in particular, you know we are thinking about improving the health of, again, those three and a half pounds of goo inside your skull, and that's a very different approach than other approaches that are perfectly valid and helpful in mental health. You know, talk therapy, for example, is clearly helpful for depression. All kinds of behavioral therapies are helpful for schizophrenia and bipolar. They probably work by changing how the brain works. That's how they help improve mental health. But we often talk about brain health at Brain HQ because we really do want to come at this from a very neurobiological perspective. Let's help improve the health of the brain, let's fix information processing, and then people should see these broader benefits. But I don't know, gee, how do you think about that spectrum as you go from physical health to mental health.

Dr Gitendra Uswatte: 17:15

So you know, there are multiple pathways to impact brain health and it can be done by changing how people think. That's one way, but it also can be done by a diet, so really sort of physical interventions, diet. It can be done through electrically stimulating the brain in different ways, like the trans magnetic magnetic stimulation, for example, but it also can be done through training exercises. And that's the approach used by brain HQ and and that's the approach we take in in our study, that by exercising capacities of the brain in the right way you can improve how it functions. And we believe that that improvement in function is reflected in changes in the very structure of the brain.

Jackie Baxter: 18:19

I love this idea of brain health being the sort of what umbrella that joins together your physical and your mental health. I think that's that's brilliant, because you know our brain, you know it sits at the top of our well, literally sits at the top of our body, doesn't it? And it impacts every part of our body, doesn't it? I'd love to hear more from you guys about you know why is our brain so important? And if we improve our brain health, is that going to impact, therefore, all parts of our body and therefore potentially not just I say just brain fog? Brain fog is quite significant, but is it going to also help other symptoms in other parts of the body, as well as just again using that word the sort of brain fog and cognitive issues that a lot of people describe?

Dr Gitendra Uswatte: 19:12

So of course you know the brain connects to all our organs, so it controls how all of our organs functions. But interesting, how? How? Henry's talking about how the brain and the body are connected, right? So you know, as our understanding of human beings grows, you know there's sort of a mini brain in our stomach mini brain in our stomach, right so and also there are parts of the nervous system that are connected with the heart, that also are connected to how our brain functions. So there's kind of a kind of a two-way street between our brain, the centers of the nervous system that control the heart and also that control digestion of the functions in the gut, and so there's kind of a yeah, sort of a two-way street here. And when we get to talking about the latest things we're doing in the lab, the vagus nerve, which connects the brain to many organ systems, is one way we are now trying to affect brain health too. But I will come back to that later and flip it over to Henry.

Dr Henry Mahncke: 20:43

For now, yeah, no, g is exactly right, of course. And you know, hey, cards on the table. I'm a brain scientist, so you're going to hear from me that the brain is pretty important, but maybe that's why I became a brain scientist is because I thought the brain was really important, you know, for all the reasons you just said. And then you know, the brain, of course, is the center of your experience, right, I mean, you know your memories, your experiences, your even, you know, I would argue, your sense of connection with the greater humankind and the greater world. These are all mediated through your brain and you know how well your brain is working. As a result just has an enormous impact on everything you do, you know, and, of course, very direct scientific ways. Right, hey, if your attention is not so good, if your working memory is not so good, you're going to have challenges in everyday life. Right, it's going to be more of a hassle when you get to the ATM, or you're trying to check out at a grocery and you're trying to remember your PIN number, or you got 16 people behind you who are upset because you're not bagging your groceries fast enough, right, you know these kinds of cognitive abilities, have these kinds of real world skills.

Dr Henry Mahncke: 21:48

Think about driving safety. Right, particularly in older adults, but I imagine it's true in just about every kind of health condition. If you have a slower visual processing system, hey, you're much more likely to be involved in a car crash. Right, you're not going to notice something coming out of the corner of your eye until it's too late. You know, as my dad got older and he had difficulties driving, he would say well, that car came out of nowhere. I'm like well, dad, I'm not really sure it came out of nowhere. I think that your brain has slowed down a little bit and you just didn't notice it in time to be as safe as we would have all would have liked you to. So you know, your brain affects your cognitive function and all those kinds of important role-world ways, but it affects your mood as well. Right, if you have a less healthy brain, you're more likely to suffer from some of the mental health issues we talked about, like depression, anxiety or stress. And, of course, if you're feeling foggy all the time, you know that's an enormous challenge, as you and your listeners know, jackie around, hey, your ability to be with your family, your ability to hold down or succeed at a job, your ability to be part of your community. So the brain is just at the center of all this.

Dr Henry Mahncke: 22:53

And you know, I think it's only recently that we've started to take that seriously because, you know, we've had a physical health revolution, right. Everyone has the idea that we can change our physical health with some of the things actually G mentioned, right, with exercise and with diet and various things like that. And so you know, we have different genetics and we have different lived experiences, but you know, to a large extent we can change our physical health outcomes with those kinds of things. But we haven't really realized until more recently. We can do the same for the brain. Like I still talk to people who are older, for example, and we'll talk about the risk of Alzheimer's and they'll say well, you know, my dad got Alzheimer's when I was 82, so at some point, you know, the alarm clock's going to go off for me and I'll have Alzheimer's, nothing I can do until then. I'm like, well, that's a terrible way to think about brain health. There's a lot of things you could do to change your risk factors.

Dr Henry Mahncke: 23:42

Or, even more broadly, I'll talk to people who say I've never been good at math, right, I'm terrible at languages. I can never learn French Like well. I actually really do not believe that nobody is capable of learning French or being good at math. I believe you might have had life experiences that have told you you were bad at those. I think you might have had educational experiences where you had bad teachers.

Dr Henry Mahncke: 24:07

But hey, everyone can learn math and everyone can learn French, and that's because the brain is incredibly powerful that way. But we're just now starting to move out of this very fixed notion that my brain's kind of like a computer chip. It's wired the way it's wired. There's nothing I can do about it. And we're only starting to now enter this kind of period of a brain health revolution where we recognize, hey, there's lots of things we could do to improve our brain health and change our cognitive function and hey, we should start thinking about that both at the personal level but frankly also at the societal level and the policy level as well. So anyway, brains are important. That's our perspective as brain scientists here.

Dr Gitendra Uswatte: 24:38

Yeah, and I want to talk a little bit more about cognitive processing speed and why it's central to cognitive function and to long COVID brain fog. So and I think Henry touched on this right so it's cognitive processing speed, sort of a basic capacity of the brain, and it speaks to how efficiently we process information that we take through our senses. So the example of driving you come to an intersection, right, you see a red light. That's a signal to stop and then when you're sitting at the light deciding to go again, you may look for pedestrians crossing, somebody may honk their horn, and all of that is information coming through our senses and then that's processed at higher levels in the brain and then ultimately that feed making a decision about whether to go or stay. Um, or, if you're reading right, uh, that is also a matter of processing information that we're taking in through through our eyes.

Dr Gitendra Uswatte: 25:56

So it is a basic cognitive capacity that underlies many other cognitive functions and it ties to the experience of long COVID brain fog. I mean many people with brain fog talking about experiencing slowed thinking and also they uh talk about, um like having uh trouble bringing up a memory or holding a memory and uh processing speed, uh how efficiently process that affects our working memory, which which, which is which is key to sort of connecting one thought to another. And people with brain fog also talk about difficulties making decision and again that's connected to working memory, because you've got to hold the pieces of information necessary to make the decision in your brain and if they're not arriving in synchrony or one piece is taking a long time to get there, that sort of assembly of information that's needed to make the decision are not present in synchrony and then that sort of can fall apart.

Jackie Baxter: 27:15

Yeah, it's like you know the real world example, that kind of oh, that word it was on the tip of my tongue and it's gone. You know that kind of you know not quite being able to lay your hands on things. But what I hear from people who experience the kind of you know more severe end of things like brain fog it's, you know almost sort of things like dissociation and not being able to really understand where they are or finding it cognitively, you know, finding it hard to speak. You know not just I can't find that word, but like I can't find any words, and you know these kind of real difficulties with you know being able to sort of, yeah, put those pieces together. It's like you know the pieces are just everywhere, you know there's. You know putting them together is like they're not even on the same table, um, so yeah it. It sort of makes sense when I hear you sort of describe some of these sort of different um ways of you know processing and how important that is. You know in you know functioning as a, a person in life, which I think is what people with you know long COVID, really feel like they're not part of life a lot of the time. You know, certainly that was my experience. You know I was living this kind of like, you know, parallel life of a person in this little weird bubble and the world was going on outside and I just felt completely disconnected from it, which was really well. It was quite unpleasant on many levels.

Jackie Baxter: 28:45

Now I'd love to kind of touch on, before we get stuck into the study, the issue of it's all in your head Now. Physically, your brain is all in your head. You know that. That's where it is. It's that, what do you say? Three and a half pounds of squish. Um, that is, uh, based, you know, housed in your skull.

Jackie Baxter: 29:07

Um, but you know we've talked about how important the brain is in processing and um, our nervous system, which controls so much in our body. You know all the signals that go everywhere. What people find distressing is, you know, if they feel like they're being told oh well, you know it's all in your head. Um, these symptoms are caused by your brain or they're not real. Um, you know, and I think everyone with long covid is very aware that the symptoms feel very real. Um, but I'd love to kind of hear your kind of take on. Where does the brain health fit in this debate, so I'm going to throw that one out there and see where it lands well, there is persuasive evidence that there is damage to the brain as a result of COVID-19 infection in many people.

Dr Gitendra Uswatte: 30:37

So there's evidence that there's damage to the vasculature all around the body, including in the brain. All around the body, including in the brain. There's evidence of chronic inflammation in the brain and there's also evidence we were talking about the vagus nerve and its importance and its connections to the brain and so there's evidence that the virus actually attacks the vagus nerve in some people. So there are many pieces of evidence that COVID-19 damages brain tissue.

Dr Henry Mahncke: 31:24

Yeah, that's absolutely right and you know, in a way way, we've like seen this movie before, right. So one, one great example is, of course, the history of chemo brain and, um, you know, cancer of course, uh, historically a deadly disease and and most people passed away. Um, and you know, as medical treatments got better, we started to have more and more people surviving cancer. We had many more people entering long-term remission and as that happened, of course patients started to say, hey, I may have been in remission from cancer and that's wonderful, doctor, but hey, I feel foggy, right, I have these brain health conditions. And if you look at the history of chemo brain, it looks exactly like the emerging history of long COVID, which is, at first, doctors, you know, did not take it very seriously and, you know, I suppose the kindest way to say it would be, I think oncologists were perhaps feeling like, hey, we have put your cancer in remission. You should be very happy with this outcome and, it's fair to say, that's a great outcome no debate there.

Dr Henry Mahncke: 32:22

But you know, as we have survivors, different issues emerge. And you know, as we have survivors, different issues emerge. And you know, oncologists are wonderful clinicians but they're not cognitive scientists, they're not psychologists, they're not occupational therapists and you know these kinds of complaints were just new and different and foreign to them. And so you know there was this, I think, idea at first that hey, this is all in your head if you say you have chemo brain and it's going to get better on its own, or you know, just pep up a little bit, get off the couch, right. But now of course we know that there are, as G said, for long COVID. We know that there's, you know, kind of distinctive issues that show up on brain imaging scans for patients with chemobrain. We know they have very distinctive patterns of neurocognitive results and I don't think anyone would say anymore that chemobrain is a, you know, simply a made up phenomenon or that it's a psychological phenomenon. You know it's clearly a very real consequence of cancer or cancer treatment. And you know, with long COVID I think we're speed running that, which is good right. You know some of the initial comments may have been hey, this is all in your head or it's not a real phenomenon.

Dr Henry Mahncke: 33:22

But I think a lot of people you know, like me and imagine like G, sort of said okay, but we've been through this and other indications, let's just jump ahead to the end where we realize that this is a real biological condition. Nobody wants to feel this way. People who have these complaints, I think, really do want to get better. So let's figure out what we can deliver to them. Now, you know that has all kinds of interesting implications. I mean, even though chemo brain and long COVID, for example, both are true brain health conditions, as G said, you know, they probably can be helped by a spectrum of interventions. Again, you know, talk therapy helps with depression by rewiring the brain right. You can see changes in brain imaging after talk therapy. So I wouldn't want anyone to think that talk therapy for depression is a, you know, means that that person really wasn't depressed, they just got talked out of it. That's not really how talk therapy works.

Dr Henry Mahncke: 34:14

I think a lot of interventions are going to be helpful for people with long COVID. You know, cognitive behavioral therapy, I think, will probably be shown to be helpful over time, if it hasn't already. You know all kinds of occupational therapy kind of approaches and these kinds of things, and I think that the stuff that we at Brain HQ and GE at University of Alabama have pioneered with brain health treatments are going to be helpful as well. But none of it means these are made up symptoms or they shouldn't be taken seriously. It means they are real biological symptoms. But the good news is we have a lot of tools in the toolbox that I think we can bring there that are going to be shown to be helpful over time, and that's. I'm an optimist by nature. That's my sense of where this field is going.

Jackie Baxter: 34:53

Yeah, and this idea as well, that just because it might be in your brain doesn't also mean that it's not in your body as well. Because you know, we started this conversation out, didn't we you, saying, well, brain health is body health, brain health is mental health. You know it straddles the two. So you know, I think you know, you can't really separate the two. They are all so connected.

Dr Henry Mahncke: 35:16

Well, it's almost hard for me to even answer the question. I mean, I get that it's out there in the world, but I'm often just so stumped by this when else would it be coming from exactly so?

Jackie Baxter: 35:26

now, gee, you mentioned damage in the brain, um, and that this has come up on studies and mris. I think now we started this conversation off again by talking about neuroplasticity and how the brain does change and can change and so damage that is showing in the brain. Is this something that through neuroplasticity, through improving our brain health, that can be reversed or improved upon? Or is damage in the brain? Is that like forever?

Dr Gitendra Uswatte: 36:00

my lab's approach and the way I think about it is our interventions harness healthy aspects of the brain. I don't hypothesize that our interventions are healing the damaged brain tissue, but rather that it is taking advantage of healthy tissue and sort of redirecting healthy tissue to take on other functions, and actually healthy tissue can grow. So it's not like a close sum right. So we may be actually increasing the amount of brain tissue that is committed to a particular function, but it's not healing or repairing the damaged tissue, it's repurposing and regrowing healthy brain tissue. Is what I understand, what our approaches are doing.

Dr Henry Mahncke: 37:01

You know it's probably here worth jumping in and saying sort of the differences between you know the kind of damage that G and I are talking about. You know when we think about damage in the context of, let's say, long COVID or chemo brain, you know it's not like stroke damage and obviously you've worked a lot in stroke but probably listeners know, hey, a stroke is, you fundamentally have had a brain bleed or something of that nature and you know there's a definable like anatomical part of your brain that you know literally is quite damaged by this or, you know, dead to some extent. And you know, as we think about rehabilitation for that, like G is saying, we're not bringing that part of the brain back to life. That's unfortunately not quite how the brain works but, as G says, we're encouraging other healthy parts of the brain to kind of take over and kind of, through the power of brain plasticity you know, take on those functions that were previously performed by the damaged piece of the brain. You know, with long COVID the damage is much, much subtler. You know it's not like there was a specific part of the brain that was, you know, damaged by a bleed or a traumatic brain injury where you have a, you know, a chunk of your brain that just gets damaged by an impact With long COVID and probably with chemo brain and all these other kinds of conditions like this. It's more like across lots of the brain there's a little tiny bit of damage, but as a result of it being so pervasive across all parts of your brain, you know, as a result your brain is, you know, is less good as an information processing system.

Dr Henry Mahncke: 38:29

You know, sometimes at my company we talk about it kind of like being a radio that's kind of gone off the signal and there's kind of a little more static in the brain information processing. Because you know where we used to have 100 brain connections called synapses that were all doing their job. You know, maybe now, as a result, we have 98. That we're all doing their job. Maybe now, as a result, we have 98. And it doesn't seem like a big change. But if you lose two at every point of your brain information processing, then hey, things aren't working so good anymore.

Dr Henry Mahncke: 38:54

And so in healthy aging there are actually been quite a lot of brain imaging studies now that show, hey, how does this work? How does brain training work? And we see all kinds of changes. Right, we actually see, for example, that the insulation that surrounds the wires, so to speak, that connect different parts of the brain to each other can get more thick. We actually see that, hey, if you sit around doing nothing in a brain imaging system, we can actually see that different parts of your brain are more in sync together than they were before training.

Dr Henry Mahncke: 39:25

So we're restoring that kind of broad neural connectivity. You know, we can even see that the brain becomes more activated during certain cognitive tasks after brain training, and so in that sense it seems like we are, you know, I'll broadly say fixing the brain or improving brain health to do these tasks, but it probably is through this very diffuse process of rebuilding the brain, so that, hey, maybe we lost two synapses and every sort of point in information processing and hey, we grew two back, and probably not the ones we started with, but we grew two back that are doing the same task in some kind of helpful way. Now, to be clear, that hasn't been shown in long COVID yet, or many of these other conditions like chemo brain, but if they work out like aging, you know, I predict that's what we're going to see over time as those scientific studies roll in.

Jackie Baxter: 40:15

So it's like replenishing, isn't it so replenishing the brain rather than fixing the bit that is broken.

Dr Henry Mahncke: 40:21

Well, that's a good way to think about it.

Dr Gitendra Uswatte: 40:24

So in our latest work we're pairing vagus nerve stimulation with cognitive rehabilitation, and there our hypothesis is that the vagus nerve, by stimulating the vagus nerve, we will turn down chronic inflation, including in the brain. And so there our hypothesis is that our intervention would repair the brain. And so there our hypothesis is that our intervention would repair the brain.

Dr Henry Mahncke: 40:51

Yeah, that's a really kind of novel technique and really kind of pushing forward the boundaries of how we think about rehabilitation. That's very cool, g, because you're kind of mixing software, brain training and, of course, the intensive in from your CI coaching approach and then this very novel approach of brain stimulation and bringing together all these modalities to, you know, hopefully supercharge what we can do from a rehabilitation perspective.

Dr Gitendra Uswatte: 41:14

Yeah, I'm very excited to see what the results are when we unblind the trial.

Jackie Baxter: 41:20

Yes, yeah, so yeah, I love this idea of like pairing stuff. Yeah, so yeah, I love this idea of like pairing stuff. You know, it's like you know there's so many things out there that people are seeing improvement with, so, ok, let's shove some of them together, why not? That's such a cool thing. So we've kind of talked around it a lot, um, but this trial let's get into that a little bit and what is involved and what is starting to be shown so in the study that was just just published, um, we, we call, we pair, uh, three components, um so um.

Dr Gitendra Uswatte: 42:05

One, brain training using the double decision part of Brain HQ, which targets cognitive processing speed. Then we do training in the clinic on performing everyday tasks. So these that can range from setting up appointment calendar, shopping for an item on the internet, writing an email, setting up a grocery list, right, so, training on everyday tasks. But we do that in the treatment setting. We organize it using an approach, a psychological approach to training, called shaping. And then the last component is a set of behavior change techniques that we call the transfer package package, and those are aimed at promoting transfer of the gains that are made in the therapeutic setting to everyday life, and these are things like goal setting, self-monitoring and problem solving. And it's, those are the three components of the intervention. We call it CI, cognitive therapy, and it is done on an outpatient basis. And now to 30 hours over two to four weeks is the dose we're testing now.

Dr Gitendra Uswatte: 43:52

And in the study that was published we compared it to what people get sort of through usual care, which at the time where we are in Birmingham, was largely nothing. Folks were really not getting offered treatment in the community. At the time we did the study. The findings were really, really striking. The one that really got my attention was we found that 80% of those for whom getting back to work was relevant did so in the CI cognitive therapy group and none did in our usual care group. Small study seven and seven in each CI cognitive therapy group. Large improvements in fatigue, very large improvements in brain fog symptoms and very large improvements in depressive symptoms. So large changes across the board. I will. It's a small study. We need to verify those in subsequent studies, but we're doing that work now. We have a second study underway, as I was mentioning, to see if we can confirm the results from this initial study.

Jackie Baxter: 45:43

Yeah, this is super cool. I mean, I'm coming in here from a background who I'd never understood research at all until I started interviewing researchers on the podcast, which kind of blew my mind, because suddenly it was like wow, and what I hadn't really understood was that in research, you know, you, you got to start somewhere. You do a little study and then you do another study, and then you do another study, and each one kind of takes you further, gives you more and more answers, it opens out more and more and you're able to maybe direct things more and more as you get more answers. Um, so that sounds like. So what? You guys, you've sort of started with the little one and you're now moving into the next one, which is going to start giving you more and more, and the more answers you get, the more you're able to help people because you're able to direct them to, I suppose, certain things when you're starting to see results. And so is that? Is that correct?

Dr Gitendra Uswatte: 46:39

yes, yes, I mean science is a sequential process and one study builds on the other.

Jackie Baxter: 46:47

Yes, and as a creative, I'm like oh, you've got to be logical, what?

Dr Henry Mahncke: 46:56

There's always more overlap than I think. Science is itself a very creative process, and I think a lot of creative people move step by step as well. So I always like to look for those similarities, and I want to emphasize that what is so cool about the study that Gee did is by combining those three components that he talked about. Right, when we think of the brain HQ component, we think about something that we almost call bottom up right, we think about it as fixing information processing or improving information processing at the basic level. But of course, you know, you know he combined that with hey, let's take down a more what I might call top down skills training. Right, we know what people are struggling with in the real world. You know your shopping lists and your your organizational plans, and let's give them real skill training, almost the kinds of things that occupational therapists or cognitive rehabilitation people would offer in the clinic.

Dr Henry Mahncke: 47:46

And then, of course, that's marry that with some coaching that really helps people, you know, set goals for themselves. Because, hey, everyone's goal in improving their brain health is different, right, some people want to go back to school and some people want to take care of their family and some people, you know, want to be able to, you know, get outside and enjoy the world and by, you know, connecting the dots to hey, what's really important to someone with these other skill things, it really brought together what you've correctly called gee, a package right that really says, hey, we need to come at this from all these different angles to have the hope of really delivering something helpful. And, of course, you got these spectacular results showing improvements in cognitive function and symptoms like fatigue and getting people back to work and cognitive function and symptoms like fatigue and getting people back to work, and so it was a very thoughtful and creative approach pulling this together.

Jackie Baxter: 48:33

And you know this is a very small study but even so, like you said, 80% were able to return to work in some form. That's huge, you know, even despite it being a small study. So you know, as you're able to move this into sort of bigger numbers and expand it a bit, you know I'm super excited to see what that shows and hopefully continues that trend. Now you mentioned the different tasks, the three different tasks. Now you mentioned the different tasks, the three different tasks, and are these all targeting different parts of the brain or different types of processing? Is that why you picked the three different sort of things?

Dr Gitendra Uswatte: 49:15

I would kind of build on what Henry was saying. So I think about it as the brain HQ component, the training on cognitive processing speed, that's training a basic brain capacity, and then by doing the training in the lab on everyday tasks, we're giving our participants the opportunity to practice the improvements in, to apply the improvements in cognitive processing speed. We're giving them opportunities to practice applying those improvements to actual tasks. And so it's a sort of scaffolding or a bridge from the cognitive processing to everyday tasks. And then we have a second bridge, which is from what they're doing in the lab setting to their everyday lives. And that's how I think about it, yeah.

Dr Henry Mahncke: 50:15

Yeah, I agree. I think of it less like targeting different parts of the brain and more like targeting almost different levels of organization in the brain, ranging from the most basic, like how does the brain processing information to this sort of very intermediate, how's a person tackling real world tasks to this very high level in the hierarchy of hey, how's a person thinking about their goals and how's the person organizing their work ahead of them? And it's by coming at this, from all these levels of the hierarchy, that I think the approach turned out to be so powerful.

Jackie Baxter: 50:47

And it's making it like useful in people's lives as well, isn't it? I mean, you know you can do brain training on the brain HQ and that's great and you can say I'm improving my brain health, that's great health, that's great. But then when you can sort of use it in your daily life and go, oh, I can do that thing, or that's helping me to do this, or that's actually showing up in parts of my life, that's what people really care about, isn't it? It's that it's making a difference rather than it's improving a metric, I suppose. So it's sort of building that up, isn't it?

Dr Gitendra Uswatte: 51:25

I like to talk about it as making it meaningful. So, for example, for one of our participants, one of their goals was to build a beauty website right, and so we directed the things that she practiced every day in the clinic towards, like working on those skills that she needed to do that. Or for another participant, it was, like you know, her long COVID had affected her functioning so much she felt like she had lack of confidence about caring for her children, right. What could be, you know, more meaningful than that? So you know we work with her on that, yeah.

Dr Henry Mahncke: 52:08

You know, I almost want to throw this analogy to like physical performance training from what Gia is saying. You know, imagine I'm in the States, I might think of basketball, but in the UK you might think of football, I suppose. But you know, let's say you're in charge of physical performance training for your team. Right, you probably want to do some training that's at the very basic level. Right, they're going to spend some time in the weight room exercising particular muscles. They're going to do some just basic running and endurance and speed training to build that foundation.

Dr Henry Mahncke: 52:34

And then you're going to have this middle layer which is, hey, let's work specifically on basketball skills. Right, we're going to practice our three-point shots. We're going to do our no-look passes. Right, we've got certain formations we're going to run. And then at the top you have motivation. Right, you've got a coach who's like this year we're going all the way to the finals. I want to see every one of you with a trophy and a ring in your hands. And you know, it's only by bringing those kinds of three levels of the organization together that you have that winning team. If you were missing any one of them, you know they wouldn't be performing. But by bringing them all together you're developing like optimal physical performance and I think I think, gee, what you sort of put together. There is kind of that same logic for developing, you know, better brain performance and better cognitive health.

Jackie Baxter: 53:14

Amazing. So maybe just very quickly. Finally, you know people listening are going okay, this is great. Very happy for those people in the study. How is that going to help me right now? So Brain HQ, I think, is available for people to use and you can maybe say that a bit about that in a moment and are any of these other things that you used in the study available for people to access.

Dr Henry Mahncke: 53:51

So that's exactly right. The Brain HQ component of this study is available right now to anyone in the world and, in fact, anyone who wants to try this out. You know the great news anyone can come to wwwbrainhqcom. You can register for free. It will actually give you one free exercise per day to sort of try out and see if you like it. And, hey, if you do decide, it's for you. You know a person can subscribe and it's. You know, it's really relatively inexpensive on the scale of things. And hey, we've got users all over the US and the UK and all over the world.

Dr Henry Mahncke: 54:20

Brain HQ is available in 14 languages and all over the world. Brain HQ is available in 14 languages and lots of people who want to maintain their brain health, to improve their brain health, recover their brain health, are out there using Brain HQ today. But, that being said, and in general, I would encourage someone who wants to improve or maintain their brain health to come register for free and give it a try. But of course, as we've talked about, brain HQ is one component of this more broad piece, and so G when you think about the broader piece. Do you think about training occupational therapists? Do you think about publishing a book that tells people how to do this? Do you think about running a center where people come to the University of Alabama and learn these techniques? I mean, how do you imagine that the other elements of this sort of start to get out into the world so you can help people?

Dr Gitendra Uswatte: 55:06

I would like to do all of those things, indeed, but I think the first next step is completing this second study and confirming the results from our first study. But you know, as Henry was saying, brain kit q is available around the world. Uh, it's on the internet and and and and right can be logged in access to the brain platform anywhere. Um, and then you know the other parts of the ci cognitive therapy. They're not high tech and so they, with proper understanding and training psychologists, occupational therapists, anywhere in the world, could implement the intervention. So it has the potential to be broadly available as a result, and we are working on developing a telehealth version of the entire intervention.

Dr Gitendra Uswatte: 56:16

Of course, brain HQ is already a telehealth intervention, so to speak. It's available on the internet, so to speak. It's available on the internet, but we're working on developing the other parts in a telehealth format, so then we won't be restricted by geography. And then other pieces. We do have an ongoing study here in Birmingham, alabama. You have to come to Birmingham to take part in the study, but we are enrolling folks in the trial. The telephone number for the lab is 205-934-9768. That's 205-934-9768. Or you could Google Oswate that's my last name, uswate Long COVID Cognitive Rehabilitation and you'll be able to get to our lab.

Dr Henry Mahncke: 57:14

And you know, to step back, I think the world that G and I would both like to see over time is, hey, that world where people's cognitive symptoms, their cognitive complaints after long COVID, you know taken very seriously as a true issue of bodily, by which I mean brain, by which I mean mental health. And then, hey, when a person has those symptoms because they just didn't get better after COVID, that there are resources that they can reach out to, whether it's their doctor or rehabilitation clinics or telehealth clinics, the way that G is laid out there and those resources are available to them. They're part of their ordinary healthcare treatment. Right, you know, you might need an inhaler because you have, you know, asthma symptoms and you might need this kind of cognitive rehabilitation because you have cognitive symptoms, and that's an ordinary thing. When you say, hey, I've got fog after long COVID, your doctor says, well, great news, this resource is evidence-based resource, this proven resource is available to you, part of your health plan in the US, part of the NHS in the UK. And hey, here's who you call. Maybe you're gonna go in and visit a clinician in person. Maybe you're gonna do this in hella health. Here's your Brain HQ subscription. Hey, you're gonna get a very focused period of treatment.

Dr Henry Mahncke: 58:22

You know G has talked about 30 hours of treatment over the course of just really a few months. And then, hey, we're going to check in, we're going to see how your cognitive symptoms are. Maybe we'll do a brain scan see how your brain is doing. And hey, we're going to ask you, most importantly, and if you're feeling better, fantastic, get back to life. And hey, if this hasn't helped you, some more would help you. Let's take you down for a second round of treatment. If this exact approach didn't work, let's give you something else. But it should be like any other kind of healthcare you get for your physical health, right, if you go in with an infection and one antibiotic doesn't work, they measure it and try a different antibiotic. Let's get to the one that works. And that's exactly what we want to see, I think, for this kind of rehabilitation in all of these brain health issues. But long COVID, for sure. And you know we're not there yet, but that's the future. I think that we're all fighting for that we're all working towards over time.

Jackie Baxter: 59:13

Amazing. You guys have made me so excited for the brain Guys, thank you so much. It's been amazing hearing all about the brain, about the study where you're going next. I'd love for you to come back after you've done the next study and we can talk more brain. So I will make sure that all those links you've mentioned the study and, of course, Brain HQ go into the show notes. So if anyone is wanting to check any of that out, you know where to go. Henry G, thank you so much. It's been my pleasure.

Dr Gitendra Uswatte: 59:47

Thank you for hosting us.

Dr Henry Mahncke: 59:49

Thank you, jackie. It's been a delight to talk with you and I hope this is fun and interesting for everyone who listens to your podcast. Thanks,