#52. Decoding Concussions: Biomarkers, Diagnosis, and Recovery - Asha Strom

Mild Traumatic Brain Injury, better known as concussions, are poorly understood. This means diagnosis and proper management are difficult often leading to people living with the impacts of milder injuries for years. Asha Strom of the University of Birmingham talks about UoB's current project, Called mTBI predict, looking at multiple aspects of traumatic brain injury to identify biomarkers (biological identifiers) which will help better detect and manage concussions.

Link to project: https://www.birmingham.ac.uk/research/metabolism-systems/translational-brain-science/mtbi-predict

Chapters

• 0:00 Introduction
• 6:20 Mild Traumatic Brain Injury and the MTBI Predict Study
• 16:12 Importance of Objective Biomarkers in Concussion Testing
• 20:01 Types of Biomarkers: Saliva and Blood Flow Dynamics
• 26:20 Long term impacts of concussions
• 35:44 Exploring Cerebral Blood Flow
• 48:41 Changes in Brain Response to Blood Flow (Autoregulation)
• 55:09 Neurovascular Coupling and Cognitive testing
• 1:04:49 Treatment Approaches, Concussion Recovery and Attitudes in Sports
• 1:21:09 Final Thoughts

Transcript

0:03

All right, welcome to the Smooth Brain Society. I am Sahed and we are back. Today we'll be talking to Asha Storm, who is a research associate in sport, exercise and rehabilitation sciences at the University of Birmingham. Her main research focus is looking at biomarkers for mild traumatic brain injury, which is essentially a fancy word for concussions, with a focus on better rehabilitation. Yeah, welcome, Asha. Thank you. Thank you for having me. It's, it's quite, quite the honor actually, just knowing all the big names that have, have fit you on your pod class, um, must be quite desperate if you, if you want me on, but yeah, always, always an honor to hear. I actually know I'm not desperate. I was desperate to have you on actually, because I haven't spoken to anybody in the sports sciences field yet. It's done a lot of other work and I thought that I should hit up the person who I know. who does this work and who does it best considering you don't just come from a research side, but as a former representative footballer and former representative cricketer, you know a lot about sports. So I thought you'd be a great person to get on. Also, as for people who do not know the format of the show, we always have a co-host as well, just to help with the conversation questions and bring perspectives, which I cannot think of as... I guess, one lone host. So welcome, Kristin Crook. I'll let her introduce herself. Kia ora, I'm Kristin. I am a psych intern at Idea Services. We work with people with intellectual disabilities in the forensic space, but I have known Asha since we were at university, kind of before she was doing all of the sport rehabilitation stuff. So I know a little bit more about her background and hopefully I can just like pull out some good questions and be here for moral support. That's the most important part, isn't it? The moral support. All right, Asha, Kristen knows a little bit about your background, but the listeners probably wouldn't. So if you could give us a little bit of a history lesson into yourself and how you ended up doing sports rehabilitation sciences in Birmingham. Yeah, of course. I guess for me, I think throughout high school, I sort of had this interest in biology and that sort of led me to study biology at uni. So I studied at the Victoria University of Wellington and I did an undergrad in biology and psychology. Throughout my studies, I sort of learned that sort of other sort of aspect of psychology, which is sort of neuroscience looking at the brain and I sort of alongside biology, I guess my love and interest for, I guess, the brain, how the brain functions at sort of a molecular level to how sort of it, I guess, contributes to certain behavior and cognitions. It's sort of like just developed as the years went on. And that led me to apply for a master's and do a master's in cognitive and behavioral neuroscience at VicUni. So that was a two year program where the first year sort of allowed me to get a taste for different, I guess, projects. So you could work on a couple of projects throughout the year and then also just doing different coursework which sort of introduced different sort of methods of studying human behavior and cognition. And I sort of fell in love with the idea of just learning about different pathologies and working with people that have sort of brain damage and sort of, you know, what happens when a certain region of the brain is damaged and what sort of leads to, and then how that can sort of contribute to how they are then treated and things like that. So I did a masters with Dr. Carolyn Wilshire, who's also featured on this podcast, sort of looking at stroke patients. and tumor patients, they have specific damage and how that affects their cognition and behavior and things like that. So you absolutely love that, working with people and learning about the brain and how brain pathology can interrupt normal functioning. And then when I was at the end of my masters, I didn't know what I wanted to do in life, essentially. I had been studying forever, pretty much. I wanted to continue in my field because I just loved it, loved learning, but didn't necessarily want to commit to a PhD at the time. Also wanted to travel and live my life. Luckily, I've got a British passport, so I thought, you know what, it seems like there's more opportunities over here career-wise and also to travel. I just searched up Neuroscience Jobs UK. Didn't specifically scout out Birmingham, but blessing in disguise, I think. Um, and sort of found this job, um, which on paper was pretty perfect for me. Cause it sort of makes my, my studies, um, and sort of neuroscience, but also my passion and, and sport and concussion, I guess it was a subject that's close to home, um, as well, so it just sort of worked out for me and then they wanted me. So a couple of months later, I was pretty much on the plane and never looked back. Very nice. Although I don't know how many people will call Birmingham a blessing in disguise. I think it's just great. Like, it's just another city, right? And everywhere has a nice place and not so nice place. And it's quite central. And compared to London, I think I'd love rather live in Birmingham, just because I don't know. And there seems to be a small bubble of New Zealanders as well. Yeah, so it's been even better. Okay. So you also mentioned before we started that your supervisor, there is also a Kiwi. You literally said that small group of New Zealanders. So what are you and your Kiwi boss doing when we talk about concussion and traumatic brain injury? So if you could give us a little overview. Yeah, of course. So at the moment, I guess my main job, the reason why I'm employed is a massive project called MTBI Predict. And it's basically this big study, I guess, trying to identify certain biomarkers of concussions. So I guess a biomarker is sort of this natural characteristic, I guess naturally occurring characteristic that can sort of identify certain pathologies in the brain. So it's... Yeah, I guess the... I don't know. Hang on. I'm gonna pause and think a bit more. Um. So what is MTBI stand for? MTBI stands for mild traumatic brain injury, or otherwise known as a concussion. And what it is, it's a brain injury, right? And I think that's where a lot of people might not actually. I think concussion is sort of just people just think, OK, you hit your head. You have a headache for a bit. But people don't really understand is actually injuring your brain. And what actually happens is that it's sort of caused by other direct or indirect sort of blow or collision to the head. Typically, say in sport, car accidents, things like that. And what happens is that it sort of this rapid has a rapid acceleration deceleration force, which makes the brain move and rotate inside the skull. And what that does it causes neurons to stretch and it has this shearing effect. So the axonal membrane stretches and that generates a metabolic cascade of different effects and impacts normal brain functioning. So I think a lot of people don't understand that your brain is actually damaged. So yes, people might feel a certain way, but that's actually caused by this... structural damage, which generates a cascade of metabolic effects, which is why people sort of have a really diffused range of symptoms as well, because it's a very generalized injury. So it can affect systems rather than sort of a local area of the brain. Yeah, so it's, yeah. I think it's, I'm glad that you kind of broke that down because you're right, there is a, I feel like there is a misconception on kind of what a concussion is and what it actually does to your brain. And I've seen people, like family friends and stuff who have had concussions and they do kind of, they do vary a lot in kind of how long they have to recover. So yeah, kind of like in your job, Do you get to see a lot of people with varying degrees of concussion symptoms or what are you currently doing at university? Should I go into what the study looks like and the structure and things like that? Yes. Yeah. So the project is sort of, the idea of it is to follow patients with MTBI over a two year period. So it's a longitudinal study that we're doing. And what happens is sort of a patient can be recruited either through A&E. We're also funded by the DOD. So we have like a military clinician. So we get recruits through there and they come into the study. They can either come in after sort of around initially, sort of around between zero to seven days, although it's unlikely that we can get, well, hasn't been, we haven't been able to get people straight away. They can either come in at seven days and then 21 days or three months. And what they do, they have like a medical screening with our clinician and then they sort of recruit. are recruited and consented and register for the study. And then from there they have the clinical days, which is, I guess, my main job where they come in and they have a whole battery of tests. So at the moment, everything I guess you think of that's associated with concussion, there's a test for. So we've got nine different work streams that we have, which include like we've got a headache work stream, mental health, imaging. biofluids, cerebral physiology, which is my work stream, sleep, vestibular and cognition. So in these days, they come in and they have biofluids done, so blood samples, saliva, and they have about an hour of vision testing and about an hour of vestibular testing. And they pretty much are with me for the rest of the day doing different sort of cerebral physiology. very different, well, a few different methods that sort of test aspects of people's brain physiology. And then after that, they also, they get a watch, a Garmin watch, they have an app, and they have daily mental health, well, not mental health, daily headache diaries to fill out, daily sleep diaries, a bunch of cognitive tests that they do for the first three months, they have saliva swabs that they have to do. So... It's a very sort of full-on study at the moment because it's this area in terms of biomarkers of concussion is sort of unknown. Yeah, we're sort of throwing the kitchen sink at it essentially. But as well as our patients, we also have variability studies that we're doing. So we have one with healthy controls and one with our patients as well. identify markers that are showing reliable measures across their four visits. Then from there, we can see which markers are going to be reliable biomarkers of concussion, or have more potential rather. We can get rid of the markers that are not really showing a lot and keep the ones that are. That's super cool. It seems like, like you said, throwing the kitchen sink at it. I just, I wanted to sort of take a few steps back and ask a bit about sort of the timelines. Cause you said, cause you said you're looking, I guess, across like at least across three months to what two years is what you said the whole thing. You'd follow a patient across two years. Um, so am I, am I right to assume that of the concussions which you're looking at, you're hoping that they're quite serious in this sense that they last for two years in terms of things or yeah, how do you sort of differentiate between a minor head bang and like the concussion you're after and then what a major traumatic brain injury would be like? Yeah, I guess we don't want people to have symptoms I guess over two years but with mild You don't have to lose consciousness with a, whereas a more severe brain injuries sort of lose consciousness and there was sort of big undergoing other sort of treatment. But we get, it has to be a diagnosed MTBI. So I guess we're not expecting these people to necessarily have, have ongoing symptoms, but we, we do have people like at the moment we've sort of having patients come in for their three months, six months follow ups. and some are actually still experiencing headaches and other symptoms like that. So it's sort of not on the severe side, but it's still, I guess, impacting, I guess, normal functioning. But I can guess it'll be kind of good to, yeah, go into why potentially these people are sort of still experiencing symptoms. I guess that's sort of the rationale behind our study is that, I guess, with a concussion, because it's an actual physiological brain. Let me restart that. Because it is actually brain damage, there's sort of, I guess you need to consider two sort of types of recovery. And that is your sort of subjective recovery. So that's your symptoms. You know, are people still getting headaches? So feeling nauseous, feeling dizzy, sort of more sensitive to light noise, things like that. That's really important, obviously, to know subjectively how people are feeling, but then it's... Physiologically, if they're not 100%, that's sort of the danger area. Some people can be asymptomatic, but still be depleted of this energy because what happens in a concussion is a sort of this energy mismatch where your brain needs more ATP, more energy to sort of, I guess, get the brain back to its sort of homeostatic state, its resting state, but the sort of processes, that are like metabolic processes that sort of provide that energy have been decompromised. So you sort of have this mismatch, this energy crisis, which I think people don't really understand and even if people say that, they're feeling better as soon as sort of a change happens, you know, sort of a change in systemic blood pressure or someone goes outside, goes for a walk when sort of like any sort of change, I guess, in the autonomic nervous system. particularly changes. That's when things maybe start to sort of get worse, worse for people. And that's why it's important, I guess, to sort of have these objective biomarkers to sort of identify if someone is still depleted physiologically, which is, I guess, what we're trying to do. And it's quite an unknown, well, not as well researched, because at the moment, the typical... diagnosis of concussions are sort of more that symptom testing, which is really important, obviously, but yeah, we just seem to have that more objective measures, which is really important. Currently, there are sort of objective measures, or more objective ways to test this, and you have like your physical exertion testing. So for example, like a buffalo test where people sort of gradually increase the intensity of exercise until they sort of start to feel symptomatic. But I guess that needs to be the problem is it needs to be challenging enough to sort of incentive enough to pick up pick up certain deficits. And you do have objective baseline testing. So things like the scat, which is as you said, in sport. But a lot of the time, it's also very subjective. So it's a lot of sort of symptoms and like cognition. And the problem with that is if there's no baseline, if there's no sort of pre-injury sort of measures, it's hard to sort of compare because I guess human variability, right? Like someone just might have poor memory and just because they sort of didn't do well at a sort of memory test on this gap doesn't mean that they are still concussed. It just could mean that's just their baseline level. So there's... I guess that's the problem is the lack of baseline measures with things like the SCAT and other clinical tools used to diagnose concussion. I was thinking of so many questions and you answered them, which is amazing. I think it's nice to hear you talk about the brain and the body connection when you talk about concussion and the symptoms. you know, especially in kind of the neuropsych space, that's something that we really, we know a lot of and it's taught throughout that kind of course. And I think that's kind of missed in kind of people who don't know a lot about neuropsych, kind of how important that brain body connection is. And it's cool to see that you're trying to look at the tests that kind of measure, you know, the difference in both areas. I did have one question, which is also kind of jumping a little bit back, but you said for some of them, they come in and they do a blood test and they do a saliva test. Can you tell me a little bit more about the relevance of the saliva testing? Because I've never really heard of that in terms of kind of like a concussion study. Yeah. So I guess the biofluids, I'm not really like in terms of the research and stuff, that's not really my field. But with the saliva test, all they do is a saliva swab and there are certain, I guess, markers in that sort of have shown up in the past. We actually did, so I'm sort of jumping ship. We actually did and are doing, but I'm sort of less involved this year because I'm too busy with this current project. But Another sort of side project that we have been working on at University of Birmingham is sort of with the sports teams who have got a concussion clinic where we've got rugby players, well not just rugby players but UOB sport teams that sort of have agreed to, well, a concussion clinic available for sports teams rather. And what we've set up is sort of blood and saliva testing. So we're working with, well, we've been working with Michael Health, which we've done a few studies around concussion and they've come up with this, the saliva swab test has picked up, picked up certain, I guess biomarkers. So we're sort of, they're sort of helping us and we're helping them essentially. So they come into this clinic, they see a clinician and I guess that's sort of. They get an idea of their return to play procedure, blah, blah. And then we sort of have jumped in and said, oh, do we, you know, happy to take a saliva and blood test and we sort of look at, I guess, like protein levels in the blood and saliva and then initially, and then when they're sort of declared and are clinically like able to return to play and see like the differences. Um, so that's, that was a really, really neat thing that we've set up. And like I said, I've sort of not as involved this year in that. but I think it's going to be quite a good setup and I think a lot of the research as well and sort of that area and like the saliva swab sort of areas that's only really been done in males because females have hormones and are difficult. And so what we've done this year, I guess we've been a bit more organized and sort of have set up baseline testing. Cause like I said before, it's like important to have your baseline. know what you like pre-concussion as well as during concussion and afterwards. So I can't really say a lot about sort of a, I guess, specific biomarkers of the saliva stuff, but essentially it's, yeah, but it's a neat thing to do. And I think also going a bit of a tangent, it's something that could potentially be used for pitch side testing. So. a lot of the sort of changes or biomarkers that might be sort of significantly different from not having a head injury or not being concussed within that acute period, that 24-48 hour period. And I think one thing that we learned last year with that concussion study with the U of weren't really showing many significant differences. And that's because of like the sort of variation. And we weren't really seeing people in that really acute phase. Because I'd come in like a few days afterwards or a week afterwards into the clinic. So it wasn't really showing much in terms of how it differs. But that's, I guess the nature of that, those sort of biomarkers is that sort of the only sort of different in that really acute period after a concussion. So. I think things like with the saliva swabs, they could be something that's sort of implemented in the pitch side. Say someone gets concussed in a game or potentially like the head gets knocked in the game, they do saliva tests or maybe a blood spot as well just to pick up the initial sort of samples rather in that acute stage that can I guess be more representative of what happens I guess Metabolically, physiologically, and that like straight after a concussion. Um, so I think it's a, it's a really neat thing that could, could happen in the future and be a potential future, um, application of, of that. So exciting stuff and a lot of like cool research that can be done in that field. Uh, I will ask one question about that field, and then I promise we'll focus on your particular biomarkers. Yeah. Um. I find the saliva idea the most interesting because yeah, like you said, you could do it pit side. Do you have, I'll open this up for both blood and saliva. Do you know of any one biomarker which has been associated more or less? I know it's not your study, so I don't expect you, but do you have any idea? In terms of blood, I know that GFAP is probably, there are about three or four that have been looked at consistently in the research, but I know things like GFAP shows the most reliable findings in terms of concussion, that initial differences, so having significantly higher GFAP levels in the blood. around that acute stage. But then I guess the problem is that sort of drops off really quickly afterwards. So I can't really elaborate on any rationale behind that and what that might mean. But I know that sounds like research. I think the fact that yeah, people are able to detect it and potentially you could detect certain things. Bits side for sports is probably very important. Especially because I have friends who play rugby and most of them try to remember things like the date and the time of day and the week and things like that just to be prepared in case they get knocked to answer the question without it being set to sort of beat a concussion test. I don't know how effective they are at actually doing it. Yeah, I guess a lot of those things it's like maybe initially they might not be able to fake it but. I guess it's in terms of athletes that are eager to get back to play. A lot of the subjective testing they can, I guess, essentially make up in a way, potentially, and that's why it's having more objective measures, having that pre-concussion baseline measures are important. So they aren't milking it a bit just to get back to play. Because I think that's the danger area, right? When people were... sort of in a low metabolic state don't have sufficient energy to... do certain things and it's just, A, they're more vulnerable to getting another concussion. So say a lot of like, I guess there are different like phenotypes of concussion in one of the sort of main system it sort of impacts is your cibula system. So if, you know, they might be more susceptible to another concussion because, you know, it's sort of might not orientate their body in space as well as they used to and things like that. And then B, that when they get more concussions or even slightly. head knocks, the effect is just worse, just exponentially worse. And then delays recovery. And you see people that sort of have, still have, you know, migraines, dating migraines after a few years after an MTBI. And I think just having that awareness that it is like an actual brain injury. And, you know, I think there's a, well, probably quite a few, but there's a rugby player recently who He won the World Cup for England back in the day. He's just recently been diagnosed with early onset dementia and he doesn't remember winning the World Cup. There are photos of him celebrating with the trophy, things like that. So I think, I think concussion is a hot topic, definitely at the moment. I'm not saying that's because they happen more regularly. I think it's just the awareness of what they are and that it's sort of... then reflecting back on, I guess, how things were done back in the day and how it was treated. It's sort of, you can see the accumulative effects of multiple, even just minor head knocks, especially in sport. Like you said, I think it's really important, the research that we're doing here and just all around the world as well, and just sort of to change sort of that rehab treatment and actually consider it as an actual injury and it should be taken seriously than it is. Yeah. It's not just a concussion, which is like the common phrase that people say, Oh yeah, it was just a concussion, nothing major, but it's actually like, hold on, that is major. And it could actually have long term effects if it's not treated properly. Yeah. Oh, for sure. Yeah. The interesting thing, which you've repeated by talking about the England player, but I spoke to Josh Faulkner ages ago now. I think he was on this. He spoke about concussion a little bit. I think it was like the sixth or seventh episode, so ages ago. And I remember him talking about how he's seen a lot of people who've had these sort of mild traumatic brain injuries and their symptoms have lasted for years compared to someone who's probably had a more severe brain injury at times and they've seemed to have recovered better. And is there, do you think a little bit of it is basically that sort of, because we think of it as just a concussion that people sort of have that subjective feeling that they're fine without and try to move on with their lives, I think, before completely recovering. Yeah, I think it's definitely a big part of it is that sort of lack of awareness of what a concussion. is, and even if people are feeling like slightly off, just slightly not themselves, and they just sort of, you know, we get, I've had people that have come into the clinic and they've gone to A&E, they've been told to drink water and have a panadol and go home. And it's just sort of, but with like, I guess a more severe brain injury, you have obvious lack of consciousness, but whereas a MTBI, you don't need that. And I think it's just... So definitely the lack of awareness. And even if you're not concussed, so you have a bad head, not you should still, I guess, treat it as, if you did have a concussion and just be more aware of how you're feeling and just like taking it easy. But yeah, I definitely think it's that lack of awareness of what it actually is. And that if it's not treated right, because at the end of the day, like people are human, you're not gonna stop them. playing sport or walking into a pole or doing silly things and hitting the head. It's sort of not the eye, like, you know, we're not going to prevent, we're not here to prevent concussions. We're just, I guess it's just more about the treatment and that sort of phase. If it's not treated right appropriately, then it's just going to get worse. And you see that with these like people coming out years later and having early onset dementia and other sort of neurological. degenerative diseases that sort of have been associated with concussions in the past. Yeah, Parkinson's has been associated with concussions a lot. Well, in boxers, you see a lot of, well, Muhammad Ali is the famous one, but yeah. I think Beth Facer from Liverpool spoke about Parkinson's and found, and it was just mentioned that you see a lot of early boxers. Yeah, well, but could I assume you could take the same thing to other sports as well? The MMA is relatively recent. I assume you could. Yeah, there's a lot of research logic, research that we sort of Yeah, you see around boxes. So when someone says they did boxing, I just sort of, oh, be careful. Yeah, I'm sorry. Oh, yeah. Sorry. Are you going? No, yeah. I was going to say, like, it's kind of related, not necessarily to boxing, but in terms of, I guess, boxers wear a lot of headgear. I guess rugby players and American football and things like that. I think there's a sort of misconception that sort of headgear is going to help in terms of concussion. But I guess it's sort of understanding the mechanism of a concussion and yeah, it might help like, you know, external hemorrhage and things like that, external damage and things, you know, but it's not going to stop your brain actually moving and rotating inside the skull. And I think, but even like with boxing, it probably creates more of a target to hit the head, right? Like, oh, they've got a, they've got a helmet, like a head gear on, I'm going to hit them a head, they'll be fine. what the mechanisms are of concussion. Yeah, I mean, the goal in boxing and stuff is to actually get a knockout, right, which is a direct blow through the head, which causes you to lose consciousness. So it's just when you think of a sport like that, where's the health and safety? It's actually it's, again, we're on like a completely different tangent here. There's this other thing where boxing started getting more debt started happening in boxing after they added gloves. Apparently when it was bare knuckle, there were fewer debts than when the gloves first came on because people then couldn't feel how hard they were punching. So they were going harder. I don't know. I don't know if this is 100% true, but I've heard this a couple of times and I've heard it enough times from enough people to make it feel like it's real. That like Well, I mean, right. You know, you say the more believable is, especially if it comes out of your out of your mouth. Doctor, doctor. Yeah, it's not my it's not my field. But the theory was basically you don't feel the hits as much on your hands and therefore you can hit more times. Yeah. All right, let's move back on to your work and let's talk about the actual stuff you're doing on the project, because, like I said, it's a big project, multiple areas. But what's your specific area? My specific area is cerebral physiology. Essentially, we've got one work stream, but there's quite a few different modalities and tests that we do. Basically, I guess the rationale behind this is vascular responsiveness is a bit of a biomarker of vascular dysfunction. I guess certain dysfunction is sort of revealed during tests that require movement. So it's sort of different functional testing. So we've got a few different modalities, like we said. So I guess the one, well, four, yeah, four. We have EEG. We have transcranial Doppler, which is sort of my sort of probably the one I'm most interested in, but sort of my main focus. which is essentially, I wish I had a photo, but it's essentially we have a headset and we intonate and have a look at the cerebral blood flow from the middle cerebral artery in particular. And I'll get into cerebral blood flow after I've done this spell, but we have EEG, we have transcranial Doppler, we have NIRS or NIR infrared spectroscopy. and we have transcranial magnetic stimulation or DMS. So within those, we have different, I guess, more specific biomarkers that within the research has sort of revealed sort of dysfunctions in mild traumatic brain injury. So it's, yes, a lot that we do and a lot we put the patients and the healthies through, but it's interesting. It's valuable, right? Oh, very, very. Yeah. I guess the one that I know. Can I? I was gonna say I think I probably have a picture of you doing the trans cranial. What is it? Sorry. Yeah. Yeah, a little bit of a backstory before Asher moved to Birmingham, she was able to go to Massey University in Wellington and conduct some pilot study of the stuff that she is now doing in Birmingham. So it's actually really cool. That's just how New Zealand works. You know someone in a circle and you're able to just kind of do some really cool things within that. And she did a pilot test on me and it was it was really it was actually really interesting you get it's kind of like ultrasound gel, right? I don't want to take away from your kind of and they just like put it on your head, but you will obviously know a lot more of the science behind it. It was for me, it was like jelly in here, strap on and look at the screen, but I didn't know what any of it meant. So I will leave that to you to fully kind of let us know because you know a lot more. But just a little bit. Yeah. I think I've kind of forgot you were making an epic. I guess Transcarina Dock was probably the one. sort of understand the most. And we'd have a few different, I guess, key biomarkers that we look at. But I guess it's sort of important to, I guess, the more the rationale behind the sort of functional testing that we do with Doppler. So I guess cerebral blood flow, not concussion sort of result in a sort of this interruption in or change in cerebral blood flow. What happens is you have this change going back to the external membrane. You have this efflux of these potassium ions and then the influx of calcium. What calcium does, it promotes laser constriction, so it promotes your vessels to constrict, which reduces cerebral blood flow. Essentially you have this, like I said before, this energy crisis. metabolic mismatch where you have this increased need for energy to pump the potassium ions back inside the cell against its normal gradient, whereas you don't have the things that promote that generate that energy are sort of decompromised. When you have issues with cerebral blood flow, that's where you have symptoms of sort of like headache, migraine. People feel nauseous and that's because of not this change in cerebral blood flow. So essentially we're looking at three main things that relate to cerebral blood flow. The first thing is cerebral vascular reactivity. And I guess that's the ability of your cerebral vessels to dilate and to constrict in response to physiological changes and demands. So what we do, we put this in this, then put patients in a sort of hyper, into hypercapnia, which is this increase of carbon dioxide. And what is seen there is sort of your blood vessel should change in a way that increases oxygen, so increases blood flow. decreased or diminished change. So they don't see, I guess, they don't have sufficient blood flow into certain areas. And that's why they have things like headaches and other symptoms because of the sort of insufficient amount of cerebral blood flow, this insufficient amount of oxygen going to areas that they sort of need after sort of a change in stimulus. That's sort of like the main thing, yeah. I just wanted to ask, how do you do it? How do you sort of get your patients or participants into a condition where you increase the carbon dioxide so that they have to sort of, yeah, so that they have to sort of like get more oxygen? Like what the red hell is it? Yeah, so we set the doper up. So like Kristen said, you've got this really cool fancy looking headset with these two ultrasound probes and we find the signal from the middle through the artery. That's just the main artery that supplies oxygenated blood to the brain. And we get them to do this, we call it the gas challenge essentially. And they have this mouthpiece. It's kind of like what you use. I don't know if you've been snorkeling, but put this mouthpiece in. The mouthpiece is attached to two tubes. So and one of the tubes, what is it? In tube and out tube. The inhale tube. I don't know why it's, I think there's a specific word for it, but one of the tubes is attached to this bag of gas. And in the gas, it's important to remind them as well. It's the same oxygen content. We're not depriving them of oxygen. It's just slightly higher carbon dioxide that we put into this bag. And with the bag, it has like a little nozzle that we can turn on and off, which controls the airflow. And then we have the tube that they exhale out of. essentially set them up sitting like yes and comfy enough for the situation. All wired up. They've got a blood pressure machine, I guess, attached to them as well. So they're all wired up. They have this mouthpiece and gas bag on, headset on, and they breathe normal room air for a bit. Because obviously it's important to have that baseline measure to see what their blood flow is like at rest. are able then to turn the bag on, that just changes where air is flowing in from. And they sit and breathe this gas mixture for four minutes as well. And then turn it off and then we also get them to do another sort of procedure which has the opposite effect of the gas. So they get them sort of, I guess, hyperventilate which has the opposite effect. So then we see... the cerebral blood flow decreased when they do that. So it's quite, I know it sounds intimidating, but it's a lot of the time people are fine and it's just mainly people don't even necessarily notice a difference in what they're breathing. So yeah. Yeah. So just for like my clarification, I'm guessing that someone with a concussion, they won't be able to control that change as much as I'd say. baseline, like a normal participant or non-concussion, but non-concussed participant would be able to in terms of like their arteries, sorry, yeah, the cerebral blood vessels sort of like expanding and contracting based on the oxygen, right? Yeah, I mean, I guess it's just a natural physiological occurring, well, occurrence, right? So I guess what research suggests we're not like, don't really know with what we'll find, I guess. Oh, okay. research is suggesting is that they have this sort of diminished decreased effect from baseline and that's that sort of can explain some of the symptoms that they're experiencing. I guess with a lot of the research that we're doing, it's very exploratory in terms of we don't, there's not a lot of research out there. So it's also why it's quite cool and quite exciting what we're doing because a lot of the things sort of unknown. there's only like, I guess, limited research compared to other fields as to what we might see. And we're doing on that, one of the reasons why we're doing other variability studies is just to sort of narrow down which biomarkers do show potential in finding which biomarkers have potential and are reliable, showing the variance in healthy controls because some of the measures really know what normal looks like. So we sort of have healthy controls come in. We've actually just finished that study, which is a small milestone, which is great. I know healthy controls, they do four visits over two weeks, the exact same tests, trying to keep it as consistent as we can to try and identify which biomarkers are, I guess, showing variability consistently. So it's identifying what... Normalist then identify what abnormal is and our MTV population. I, I still find it so funny that we don't know a baseline yet in terms of, I feel people have been having concussions for so long that you would have thought, you know, that you have some sort of idea of what changes or how a non concussed physiology looks like that you could be looking at. Yeah. Something that's hard because you're working with people in physiology and everyone is different. Like depending on your demographic, like anything can sort of impact someone's physiology, like medication, like just any sort of external substances, I guess. And it's just like exercise, fitness, blood pressure, it's sort of, you know, because concussion is a thing where it's a, it's a very diffuse generalized injury where systems are impacted. And, you know, just because you're one system might be impacted more, it sort of then accumulates to other systems and that's why you see a range of symptoms and it varies from person to person. So it's sort of hard to identify without these baselines and that's, I guess, why we're trying to be as consistent as possible in doing these variability studies to sort of, I guess, that will help identify and individualize. certain, certain pathological sort of impacts of, of concussion and just sort of identify what normal is. Um, yeah. You had said three things and I cut you off for one. So let's talk about the other two now. So we just touched on cerebrovascular activity. Yeah. I guess the other thing, well, the second thing that we do with transcranial Doppler is, well, other, I guess, biomarker that we're looking at is cerebral order regulation. And that's just how, I guess, the brain vasculature sort of responds to changes in systemic blood flow. Well, not systemic blood flow. I'm going to restart that. You can edit that. So cerebral order regulation is how the brain vasculature responds to changes in systemic blood pressure throughout the body. So I guess, like I said before, someone might feel fine and then as soon as they stand up or do some exercise with that change in blood pressure throughout the body, that's when they sort of experience these symptoms. Um, so with that, after they do the, the gas challenge, um, we get them to do a few things that just change their blood pressure. So firstly, we get them just to stand up, um, and just hold that stand for two minutes. And then we, we get them to essentially squat and stand for five minutes. Um, so I do a long time with them because I'm not going to make, make them do anything, um, that I like, I'm not going to make them squat for five minutes without, without doing it. About time I had the exercise too. So yeah, again with the cerebral autoregulation, I guess that's more of an exploratory or secondary outcome that we're looking at. But I guess research, I guess, suggests that it's sort of, you have a delayed response in terms of when there's a change of blood pressure, there's a delayed response in terms of getting, yeah, the changes in cerebral blood flow. So they're not getting sufficient blood flow and these changes aren't happening as they should to sort of combat that change in blood pressure. And I guess that's why you get these other symptoms as well because it's just not, yeah, I guess there's still that mismatch. So that's sort of more of a solitary thing, but it's, I think the challenge with that at the moment for us is, I think there's no research out there of how to actually measure and process that data. So that's a whole other can of worms that we sort of need to figure out is actually how to process the water regulation stuff. Yes, that's through water regulation, squatting and standing. Sorry, I'm just thinking as I go by. When there's kind of that delay in people who have concussions or kind of that's kind of what the data is showing, is that kind of similar for when you get head rush if you stand up too quickly or is that the opposite? Is that when it's actually, is that when there's a delay and then you have that sensation of maybe, I mean, I don't know if anyone else, but you know, like your vision might go a little bit blurry and you feel a little bit witty, is that kind of the... Yeah, it's similar to that, right? It's just sort of like, there's a moment of, there's this like sudden change of blood pressure and sort of then it sort of impacts, yeah, your brain has, I guess, got some catching up to do. So I guess you can consider it to be something like that, for sure. Do you have a helmet on while you're doing the squats along with them? Or do? Or? So they're doing it with weights and you're not? Essentially, they've got a mouthpiece and they've got this headset on annoying. They've got all these wires attached them with the blood pressure. Because obviously, it's important that we measure blood pressure continuously while they do that. So they definitely have it worse than me. Although I tend to do it twice a day. But I'd rather do it twice a day than do it with a mouthpiece. Everything they've experienced, I've also experienced as well. And I think it's, yeah. We do warn them that they will do some light exercise. And obviously, if they do want to stop, that is allowed. Yeah, because I was wondering, like you mentioned variability a lot. And I feel fitness would be a big factor in how particularly the exercise side of things would show up in brain activity. Okay. But I'm guessing you haven't actually done much data analysis for it just yet to see, but I feel you'd be taking note of those things as well, right? Yeah, so we, a lot of, like I said before, like there's a lot of things that affects physiology. So we make note of everything, I guess that sort of might impact them. We try and we tell them not to have caffeine, things like that as well. before coming in and all of our tests done in a specific order. We know which tests are done before lunch and after lunch and things like that. We take note of other, I guess, because they have thorough medical history done before and we are aware of certain things that might impact them, whether they have asthma, things, just other things that can confound or, I guess, explain, have some contribution in explaining certain. physiological effects. So fitness is a big thing. He Yeah, because I was thinking back to how you said you first do the gas test and then this one and I was thinking, yeah, it would probably be a lot. You'd see a lot weirder results if you had got people to exercise first and then try to get them to do like, you know, They didn't even like at least an hour break and have lunch after that. So it's a very well deserved, well deserved, so to say the least. So at number three? Number three is something called neurovascular coupling. And that's, I guess, describes the relationship between local neuroactivity and subsequent changes and again, cerebral blood flow. And I guess it sort of. It ensures that there is. The oxygen supply, I guess, supplies the demand in areas with increased neuronal activity. So I guess the areas of your brain that are more active, blood vessels will dilate in that area to get more blood, get more ATP, oxygen to it, compared to areas that are not so active. And for this test, well for this biomarker, we use NEARs or near infrared spectroscopy. We have a combined NEAS EEG. So NEAS, it uses NeoInfrared lights to measure the changes in cerebral hemodynamics in the brain. And we look at that during what they do this cognitive task. They have this mental cognitive demand, and then as well as a physical task. And alongside NEAS, we also do EEG as well. looks like it's like the electrical changes in frequencies of like certain alpha waves in the brain. I don't really know a lot. I think we're working well. I think a good thing is that the study is so big is that we have a lot of resources, a lot of people that are helping us out. The NEARs, EEG, neurovascular coupling, that's again not a primary outcome, but it's an area where I'm less... to date with that research, but it's sort of this really interesting, I guess, biomarker that could potentially show certain things after concussion because I guess certain areas are more active, but it's not getting sufficient blood flow again. It's sort of cool to look at, I guess, the two different modalities and compare more sort of a spatial. measured with a temporal measure. I guess we have ideas of potentially combining that with Doppler as well. So you have that again, more spatial measure of where things are happening. And then I guess the others were in terms of like the time over doing different tasks. So it's quite complicated. I don't know enough about it, unfortunately, but I think it's just something that we're all trying to, the team is just trying to work out. and how we can, I guess, use that and do different, I guess, functional tests that, um, with these different noidelities. So I guess we have a lot of resources over here. So it's, it's quite cool and yeah, very exciting. Watch the space. Yeah, that is awesome. Um, I think, yeah, and you've, I mean, so the, the trans cranial. Doppler, I keep forgetting the name. Is that kind of the primary outcome, which is what you're working on in terms of kind of like the biomarkers out of the three, would you say that one is kind of the main one for gathering evidence or gathering the kind of... Yeah, so I guess our primary outcomes are, we have our cerebral vascular reactivity, so that's with Doppler. Autoregulation, which is... Unless so, I'm a primary outcome, but still. Yeah. So let me restart that. So we have cerebral vascular activity, which is Doppler. We have NERS. So not necessarily looking at neurovascular coupling, but just using NERS as a primary outcome to look at the cerebral hemodynamics. It changes in deoxygenated oxygenated blood. And we have TMS as well, which I haven't, I guess, tapped into. So transcranial magnetic stimulation. And with that one, we're looking at the cortical silent period, which is, I guess, the brief moment where there's sort of... Let me restate that. Should I, I might explain, yeah, okay. Cut all of that out. Wait, do you want to start from like the start of Kristin's question then? Because then. Yeah, maybe, maybe. Yeah, so I guess we have cerebral vascular reactivity that may be with our Doppler. We're also looking, not necessarily the neurovascular coupling, but we're using NIRS to look at the cerebral hemodynamic. So the change in oxygenated, deoxygenated blood. And then we also have transcranial magnetic stimulation, which, or TMS, which I mentioned earlier. But in that one, we sort of, I might explain what TMS is. So it's, I guess, it's this magnetic coil. And we're able to stimulate using this magnetic coil parts of the brain and sort of excite or change, briefly changes the electrical signaling in the brain. So what we do, we find a particular hotspot, I guess we call it. over their motor cortex, which because of the signaling pathways, through the signaling pathways, we can activate a little muscle in their hand. And with that one, we're looking at the cortical silent period. So what we do, we get obviously arresting measures and then we get them to contract slightly. When they're contracting, when we snap them. It's totally safe, by the way. It just feels like a hook on the head. But you're totally safe. We're not exactly zapping them. But when we zap them, when they're contracting, they have their initial response. And then there's a sort of like period, very, very brief period with not as aeroelectric activity, but almost aeroelectric activity. And that's called the cortical silent period. And there's some research that suggests that there's sort of some sort of delay in that signaling pathway. And so people opt in. a traumatic brain injury might have maybe a slightly longer cortical silent period. That one, the research is quite variable with that. So it'll be interesting to see whether afterwards process our data if we actually keep that in the protocol or not. That's an interesting one. I think the patients and the participants we get enjoy that one the most because... The hand's moving and they're not telling it to, so it's quite cool. That's all I find that fascinating. But, you know, I've studied it, but just hearing you say it as part of your research, it's just like that is so cool that there is, you know, tools out there that can do that. And I think it just, yeah, that's crazy. Not TMS brought up an interesting thing, which I'm not sure you know the answer to this, but I still want to ask it because I because I know TMS only really works on the outer parts of the brain. In terms of like the outer cortical areas of the brain, you sort of zap it and certain functions are kind of stopped in the sense for a little period of time. But do concussions happen further inside the brain? Like I know again, concussions are generally external knocks, but can you see damage further inside the brain as well due to the twisting? That's another thing, like a lot of, it's not like necessarily used as a, like a, that's own diagnostic tool, but, um, people often get CT scans and if MRI scans and a lot of the time that doesn't show much structurally because the damage is actually at the very molecular level, like I said, the influx and efflux of these, of these ions that sort of, sort of creates this metabolic cascade. So structurally, you don't really see the damage. So in terms of concussion, yes, it's sort of internal, very internal. And I think that's sort of, again, the problem and why we sort of are doing the study is to find that sort of those more specific like physiological biomarkers essentially that can sort of help us identify the... most common disabling sequelae of MTBI. So yeah, to answer your question, you can't really see much structural damage even though there is damage inside the cell. And a lot of the time, it doesn't really cause brain cell death, but it does disrupt that normal functioning. And it does recover. I think it's important to know people do recover from this as well. It's not. Um, you know, going to, I don't know. Yeah. One concussion doesn't end it kind of doesn't anything, I guess it's just that accumulation if it's not treated. Um, yeah. Yeah. Awesome. So you, you segue that very well into the question, which I wanted to ask, which is about treatment now. So you're looking for all these biomarkers. Some have not been studied or some, you have some indication of like the saliva and blood, as you said, um, But what does this mean for treatments? Because I still feel that it's very hard to treat something internal inside the brain. So yeah, what does it mean for rehab and treatment? That's a very good question. And I guess it's. think of it as different phenotypes of concussion. Like I said before, it's based on the different systems that are impacted. A lot of the time, multiple systems are impacted. Things like issues with cerebral blood flow, that's usually, you have more of a headache phenotype where the main symptom is headache. The idea is that if we find these deficits in cerebral blood flow, for example, then we can sort of, that A can explain or help explain certain symptoms, but then B, we can sort of, treatment can be based off what people are feeling. So if we do find deficits in physiological biomarkers, it's like, okay, we know this person is sort of not right 100%. We shouldn't rush them into returning to sport, returning to normal daily functioning. And then again, it's important that treatment is sort of, I think people get the idea is like, when you get concussed, you should just rest completely. And I fully agree, like for the first, you know, that period you should be, you know, resting completely and have, I guess, a little stimulation, but it's important to, I guess, expose people to certain things that can trigger symptoms, not to a point where they're debilitated and we're not gonna. not debilitated, but to a certain extent, right? Because that exposure to doing certain things will actually improve. For example, exercise, it's important that people actually exercise gradually and to the right level. But one of the main, I guess, phenotypes or types of concussion is anxiety. And that's essentially this increase or overactivation of the sympathetic nervous system. And that causes people to be in this fight-flight state where I guess that's why they have trouble concentrating, things like that. They're sort of, I guess, not their normal self. They have this high level of cortisol and they're always in this stress state. And things like exercise, which actually activates the parasympathetic nervous system, helps with that. So I think, again, this could be a misconception that doing exercise is bad. but it's actually good in introducing it earlier. And in the right ways, obviously, you don't want to sort of overexert that. By doing it in the right ways gradually, the right sort of exercise actually helps with that sort of that balance between the two branches of the autonomic nervous system. So I think like identifying certain, whereas there are certain deficits in someone's physiology, A, just sort of says identifies that, okay, this person is not right physiologically, we shouldn't rush them into certain things, but could identify more specific stuff like, I guess, doing things or introducing exercise that might be more specific. Say if they've got a lot of vestibular problems, doing exercise that challenges that system and then from then it can actually learn and get better and improve. And I guess that's a sort of more specific targeted treatment that ideally would help people recover and recover better. It's not about actually not using certain systems that are sort of impaired or decompromised, it's actually challenging them to a certain level that actually helps them and helps the individual. And like I said, the things like exercise, when it's introduced earlier, people have better outcomes. Bye for now. super interesting. I'm just going to go back over some of the points that stood out. The relation between anxiety and concussion, I think that's super interesting. And I really like that there's that really fine balance between the parasympathetic and the sympathetic not doing exercise is kind of within concussion or that, you know, when you think about concussion coming from someone who doesn't do concussion studies, it's like, okay, you have to rest. You shouldn't be doing any type of exercise, right, as you said, but finding that balance and actually doing a little bit of exercise in the right way, counteract that anxiety, which will make you feel better. Like that's, I mean, it's simple when you, you said it perfectly, but actually in hindsight, yeah, I just think that's really cool stuff that you're doing and the research that you're doing, it's great. Yeah, I think I'm quite passionate about it, obviously, but I think it's really important, especially as like, well, not really doing any team sports at the moment, but like having experienced new concussions myself and teammates and I think mental health is a massive thing. as well, especially for athletes. And, you know, knowing that they can't do what they love to do all the time, while that mental health impacts them. It impacts a lot when you're a concussion, they can't do anything. So I guess it's sort of understanding that having a concussion actually impairs that. And it's sort of why saying, I guess, gradually to exercise and stuff, it's quite positive to positive for them, but also to know that to not rush into it. And it's really like refreshing to hear like I've had you obviously, I love to I love to chat, love to chat to the patients and say if they're, I've had a few say like, I'm just going to make sure that I'm actually feeling okay and stuff. I'm not going to rush into sports. It's really refreshing to hear that. And I think that awareness is finally getting to people. I guess we'll get it getting across right that's important because otherwise if you don't have this the right recovery, these athletes are their careers are just going to end sooner than expected. So it's really important to consider that mental health and that's the anxiety that they might be feeling or stress or things like that. Actually there's a physiological I guess mechanism as well, not just sort of yeah, I guess their state so it's sort of good to objectify things. It's also important to have your subjective people yeah a bit bias can you tell but um yeah no it's not yeah and it's not just the case of I'm not playing the sport which I'm really passionate about so that's causing you know that's causing me to feel anxious thinking about when I'm going to get back into the sport if this kind of um you know changes the projection of my career it's actually more of a if you've been There's, it's not just that it's actually the physiological things going on in your brain related to that condition is contributing to that feeling. So it's a, I mean, I feel like that just puts an emphasis on the importance of your research and how, you know, concussion shouldn't just be concussion. It's there's so many trickle down effects that it has on your, your mental state, your physiological state, like that just pushes the importance of the research that you're doing. For sure. Oh, for sure. Yeah. Like I said, it's just really, really important just to have that, like, I guess, basic understanding of what the actual, what the injury actually is. And that it's okay to feel certain ways, even if you feel slightly off. It's fine. It's okay. It's just sort of, and that people will get better as well, I think. Yeah, for sure. I quite enjoyed your specificity part of it for your treatments because I'm thinking back to when I had a couple pretty big concussions and I remember sort of because at the same time I was studying at the same time and I had some exams coming up or something and I remembered them during my rehab process, them trying to get me to get back into focus of being able to study and read a research paper. So it was first like okay read this paragraph explain it a few days later, trying to push me a bit more than trying to push me a bit more by giving me a research paper to read. And it's that same kind of exercise for the thing, but based on what I needed. So we're not just talking about physical exercise, I guess, treatment-wise, we're talking about like, working your brain in whichever ways needed, but also like, increasing it slowly. And doing it enough to actually, for it to be sensitive enough to I guess for you for you to learn as well right like yeah, you want to be pushed and challenged whether it's physically whether it's mentally it's You still don't need the right sort of intensity of stimulus to not over exact you but also just to challenge your brain to actually Learn these things and okay, like that's how I should Function and just sort of incrementally um get better Yeah, and then the subjective aspect of like whoever I was working with my the people at rehab were basically being like, okay, you are a master's student. So you were able to read so many research papers in a day. So we need to get you to that point until then. We don't think that you're ready. So, yeah. So then, like, I remember them following up like a month or so later being like, OK, how many papers can you read now in a day? Don't get this. Don't ask me this. But I get I get the idea. Yeah, but it's but it's a good idea, right? Being because you want to get anybody who's had a concussion, get them back to whatever standard they were performing at before. And now having sort of like biomarkers, which you can also look at and be like, okay, they're feeling okay, but actually, there's still this little bit left to go. Yeah, I think it's a very big thing. Because yeah, a lot of the time, like I've experienced this with when I've had concussions in the past, I might be feeling fine. I might really not have a headache or feel nauseous or dizziness or anything of like, I guess the typical symptoms, but I just might be feeling a bit off, might not be able to concentrate for as long, things like that. And yeah, that can be quite subjective. That actually is telling, that's your body telling you something that you're not quite, that you don't quite have the sufficient energy to sort of do things. And yeah, I've talked a lot about sport and obviously a lot of things happen in sport, but just like work, just going to the supermarket, doing daily tasks can be quite challenging for people. with concussions like sort of over stimulation and can trigger these different systems that aren't getting like sufficient energy supply. So like you said, it's just it could be applied to apply to anything. Yeah. Awesome. In the interest of time as well, Asha, any final things which you wanted to say which we haven't covered about your work? Um, I don't think so. I think I've covered a lot. I've talked a lot. I've probably jumped here and there a lot. Apologies. But no, I think I've got everything I want to say. I guess it's the importance of what we're doing over here and the importance of finding more objective biomarkers and understanding what the mechanisms are behind the injury and that it should be taken as a serious injury. that happens and without the right treatment, then that can just have other detrimental impacts. And I think the more research that is done around concussion, you might start to see other technologies come in. There are some instrumental mouth guards that are used and it's like another way to measure velocity. So say during a game, there's a collision and it reaches a threshold of a certain velocity these people might be checked for. concussion. And again, it's really novel technology. And there's no one thing that's just going to say, okay, you have a concussion. It's sort of, I guess, all of everything that we're doing just wants to, well, we're trying to find markets that are going to support, I guess, a clinical decision not we're not trying to make over it, because obviously, you need a clinical decision at the end of the day, but it's sort of to support, I guess, more evidence into someone's state after after hitting their head. So I think there's going to be a few changes, potentially changes to protocols in sport. I know there's some stuff around hitters in football, especially at a young age. And I guess, yeah, there's going to be a lot of change, I think, within sport and how it's treated and new technologies coming in left, right and center. And I think New Zealand as well is quite a... or up their intents of concussion research. So I think, yeah, it'll be interesting for sure, but it'll all add. Whoa, New Zealand has a lot of, a lot massive sample size, considering you're born with a rugby ball in your hand. Oh, for sure, for sure. That's probably the main motivation, hey. We wanna play more rugby, but we wanna do it safely, so. How can we do it? No, but I used to hear... You always hear this from like the older generation, quote unquote, where it's just like, oh, if you can talk, then you're fine to play. And like, I'm like, bro, but you can't fill a glass of beer up all the way anymore. Do you really want to say this? I love that that's the objective measure. Yeah. Like I said, like with mild concussion, that's, that's a danger. It's like a lot of the time there's no, you know, obvious loss of consciousness. Yeah. That's why I like to go undetected and untreated because there's no sort of obvious thing that happens. And that's why you might see better outcomes when people have a severe brain injury compared to mild. It's because, okay, they've lost consciousness. We need to, you know, we know what they have, I guess. We know how to do better. Whereas, I guess the accumulation of little concussions goes unnoticed a lot of the time. But I don't know if we can change the attitude of the oldies, eh? Yeah, it's like the classic New Zealand kind of, you know, mentality of, oh, she'll be right. I was going to say, she'll be right can only go so far. All the way to burning apparently. Halfway around the world. All right. In that case, final thoughts, Kristen? I have learned a lot more. I know that I've kind of spoken to you a lot about the work that you do. But I think it's really cool to kind of hear you speak about it and be so passionate and knowledgeable on it. And as you said, watch this space, like you're doing some awesome stuff. And I think it really highlights just how you should take care of yourself in sport and throughout injury and that, you know, in the background there is work being done to. make sure that it is done safely and the treatment is right for the injury that you have. So thank you for enlightening me. It's awesome. I'm proud of you. Thank you for listening team. It's passionate about an important topic. So thank you. Thank you for listening. Thank you for having me. It's been a pleasure as always. Thank you for coming on. One last question, which we ask every Um, if you, if you had one piece of advice to give, to leave us with, to leave the audience with, what would it be? In life or in within. In life, whatever, whatever you're a well-traveled person with two passports, tell us what you've learned. In life. Um, my one piece of advice is listen to more ABBA. I could have... You're related. You were going to say that. I've got to throw it at everyone somehow, right? There's rumours that you're related to them. Yeah, I've heard them too and I fully believe that I am. I know. I'll find some objective biomarkers somewhere. Go back far enough. No, I'm just guessing life. Take your opportunities. I mean, I applied for a job on the women I didn't think I would necessarily get and It's led me to, you know, take a leap of faith across the world. Um, and I feel like I'm contributing somewhat to society and just living my life and yeah, I just take opportunities, you know, you regret the things you don't do. So, and another piece of advice, listen to the Brain Society podcast. There we go. Listen to us follow, like subscribe, all those things. Exactly. sign up to our Patreon. You know what to do. You know it by now. Thank you guys. Thanks so much again. And yeah, thank you everyone for listening. Oh, one last thing. While you were talking, I did look up and apparently, yeah, there were no recorded deaths in bare knuckle boxing. Although a lot of it, because a lot of the rules were that you could not hit the head, which I guess is different from, which makes it different. But yeah. There you go. Just wanted to say that factually we figured that out. You didn't notice you do that? Yeah, none of that. I can multitask, I guess. Awesome. But yeah, thanks guys. And thanks everyone. Bye. Thank you.