Video Games on the Brain

Mice that get migraines have helped scientists in the US to uncover what might be going on in the more than 10 per cent of us who suffer from the condition. What K.C. Brennan at the University of Utah has done is to make a genetic change in his mice, so they mimic the make-up of one group of humans who suffer regular migraines. By watching the brains of these animals, they’ve found that, periodically, surges appear of an excitatory nerve signal called glutamate. This, they speculate, causes overstimulation of the nearby nerve cells, starting the neurological equivalent of a Mexican wave that ripples across the brain. As it does so, it activates pain pathways that cause the ensuing headache. As K.C. Brennan explained to Chris Smith, these new insights should enable the Utah team to unpick how this happens and better ways to control it…

K.C. - We, on the most fundamental level, are trying to understand how migraine works. The approach we took was to use mice, carrying a gene that comes from a family of people who have hereditary migraine. This is a rare form of migraine, but it allows us to place the gene in the mouse, and actually ask very detailed questions that we wouldn't be able to ask with humans directly.

Chris S - But critically you can't ask a mouse if it's got a headache. So how do you know when the mouse is experiencing migraine phenomena?

K.C. - It's a very good question. For migraine with aura, this is migraine that many people will be familiar with, where you have a change in your vision, flashing lights, or sometimes people get numbness or tingling that moves, or some people lose the ability to speak, for migraine, with aura, we know that there's an event in the brain called a spreading depolarisation that underlies the migraine aura. We can look at this spreading depolarisation in the mice, and if they have the spreading depolarisation, there's other work that shows that we can assume that they have the beginnings of a migraine. So it gives us a real purchase on the subject.

Chris S - So when a person is having a migraine, there is some kind of abnormal electrical activity in at least one part of the brain to start with. And you're saying, you then get this spreading wave of changed behaviour that goes across the brain, might take in some other areas, including visual areas, which is why people see these flashing lights and so on, or experience abnormal sensations for awhile. How does that then link to the headache that comes later?

K.C. - People have found that the spreading depolarisation, this spreading wave of excitation that moves across the brain will cause pain sensing nerves to fire. And those pain sensing nerves are what generate the sensation of the headache.

Chris S - So that argues then, if we can get underneath what causes the initial wave of depolarisation, because that's upstream of the headache, we ought be able to knock the migraine on the head.

K.C. - Exactly.

Chris S - What did you actually do with these mice, that then gives us insights into that mechanism, and what might be causing it, and what might be causing it to spread in this way in the first place?

K.C. - So the mice have a little tiny window carved into their skull that allows us to look at their brain cells as they are going about their business. And this was where the surprise came. We saw these, what we call plumes, basically puffs or clouds of something called glutamate. So glutamate is the major excitatory neurotransmitter in the brain. It is used for brain cells, neurons, to communicate. It's absolutely essential, but it's kept within very, very tight bounds under normal circumstances. It's a substance that's absolutely essential for me to be talking to you right now and for you to be hearing me. And it looks like it was not kept in tight bounds in these animals.

Chris S - Putting this together, then. Would you say that a way of thinking about this is that for some reason, in individuals who are prone to migraines, that the normal rigid tight control of their glutamate occasionally gets a bit out of control in one bit of the brain, and they get this geyser goes off. And the big plume of glutamate showers a patch of brain, and the nerves there become more active than they should. And that then triggers the ones next door. And you get this sort of domino effect radiating out from where this started, spreading out that burst of activity across the brain surface. And that's the migraine kicking off. You'll see the aura, then, it's followed later by the pain. And because the brain is a bit more susceptible to not keeping control of its glutamate level, that's why it's easier for that wave of glutamate to spread across the brain in that way in those people.

K.C. - That's a lovely summation. And in being a responsible scientist, I'd have to say that's a lovely hypothesis at this point, but we can actually be as precise as you were in formulating that hypothesis about how migraines start. And that's, I think one of the exciting advances of this work,

Chris S - The problem is that glutamate is an incredibly universal transmitter, nerve transmitters, isn't it, it's an excitatory transmitter throughout the brain. So it's going to be quite tricky to turn it off without causing enormous numbers of side effects. So what do you propose to do, now you understand this a bit better for people who are prone to migraines.

K.C. - It's a very important question. So on the one hand, this does validate certain treatments that we use. We have migraine preventive drugs, for example, that suppress glutamate related excitation. So this validates, those presently used treatments, but like you said, drugs that willy nilly take glutamate levels down, have profound side effects, the best example of that is ketamine or "Special K," what we would really like to do in future is dive deeper into the very basic mechanisms of these plume events, so that we can develop more precision, fine tuned drugs that could prevent the onset of plumes, but preserve normal activity in the brain.

In Roald Dahl’s famous book “George’s Marvellous Medicine”, a young boy called George decides to make his grandma less cranky and horrible by replacing her usual medicine with his own invention. His improvised concoction uses items from all over his house, from shampoo and toothpaste, to floor polish, engine oil and antifreeze. When his gran drinks it, she grows as tall as the house, a result that real-world paediatric doctors Graham Johnson and Patrick Davies decided needed checking. And so, helped by their own kids, they’ve analysed George’s recipe, as Graham explained to Phil Sansom…

Graham - He wasn't quite as scientific as we would have liked him to have been. He didn't write it down. And that means he comes a bit unstuck when grandma becomes really invigorated and grows enormous. And his father is really excited by that because he thinks, "Oh, wow, we can make a lot of money out of this." And because he hasn't been systematic and noted everything down, medicines two, three, and four have very, very different effects.

Phil - Right. Obviously we frown on that kind of process, not scientific. So what's the right way to do it? What did you do?

Graham - We employed five very junior researchers.

Phil - How junior?

Graham - Well, the youngest was seven and didn't have his school pen license at the time. They worked in three different groups, and they went through the book, writing down every single ingredient. Then we compared those groups. So there's three independent groups that they were in. We made sure that all their results were the same, which they were, and went to the national poisons information service website called TOXBASE, and looked up all the different ingredients, and what possible toxic effects that they would give.

Phil - All sounds very rigorous, all sounds very above board.

Graham - I'd like to think so.

Phil - What did you find?

Graham - Uh.

Phil - You're making noises that make it sound not good!

Graham - There was quite a lot to find. So, basically grandma would not have been very well at all. Actually some of Roald Dahl's descriptions were really accurate. So she talks about how her stomach's on fire. There are lots of ingredients that might cause indigestion, or nausea, and vomiting, and gastric ulcers, and things, sheep dip in there, and shoe polish. She starts to swell and there were a few ingredients in there that might cause some foaming in particular in there, in that things like the shampoo. Then there's, she has this sudden sharp twist and jerk and flips herself out of the chair. There were several ingredients that would cause convulsions. But from there, she starts to grow, and she becomes invigorated, and she bursts through the roof of the house. That's not really what would have happened, unfortunately. There are several ingredients in there that would make her very sleepy. In addition to the convulsions, she might have stopped breathing, developed kidney failure. There were several ingredients that would cause vomiting. And then these erosions in her oesophagus, and maybe through to her aorta and all sorts, you'd have been in a right mess.

Phil - This is not looking good for grandma.

Graham - Not at all.

Phil - What do you predict would have happened to her?

Graham - It is highly unlikely that she would have survived such a toxicological insult.

Phil - It's interesting. Because it's very different from the results reported in the book.

Graham - It is.

Phil - I'm just wondering maybe, are there some interactions maybe that you don't have in your database, something like that, that make a person become giant?

Graham - Yeah, that's possible. I mean, we weren't able to reproduce the singing and the chanting, and obviously we are just extrapolating from known results, and we haven't recreated making this medicine.

Phil - It's not really a way around that is there?

Graham - Not so much. No.

Phil - If I want to tinker with the recipe myself, what do I have to do? Do I have to go through the rigmarole of what you did, and go through the database or do I have to make one or what?

Graham - Well, we've tried to make this easier for you, or the BMJ have. So if you go to the bmj.com and look for George's Marvellous Medicine and our paper is there, they have made a simulator so that you can mix all the different ingredients from around the house, and see how poorly that they would make you. And there are some little Easter eggs in there as well, that are not on the achievements board. So please go and have a look at that and have a play.

Phil - If I unlock any of those Easter eggs, do I become an honorary marvellous medical doctor?

Graham - Absolutely. I would be delighted if you tweeted both me and Patrick Davies, if you managed to unlock one of the three Easter eggs, you'll know that you've found one because I'll give you a little clue, a chicken appears, a certain chicken. So please tweet me if you managed to find out one of those.

Adam Murphy's been taking a look at how important what you hear can be when enjoying a video game, and how hard that can be to make as the game gets bigger and bigger, as he found out when he spoke to Paul Weir from EarCom, and audio Chief for the game No Man's Sky...

Adam - Games aren't just pushing buttons. The music in a game can be vital for setting a mood. You know you’re walking into a boss fight when the music gets uncomfortably intense. The problem though, is at any given time the player could be doing anything, walking in the right direction, enjoying the scenery, leaving their character motionless while they get a cup of tea, so how do you get the music right? I spoke to Paul Weir, video game music composer from EarCom, and Audio Chief for the game No Man’s Sky about how you make music for a video game.

Paul - I guess, as a composer, you know, you're trying to find those key moments, and the overall tone, you have the difference with film is all those moments in film are engineered for you and laid out for you. You can't really often do that in games. So you're looking for just those key moments where you can inject a certain feel, certain type of emotion, and often they may be very specific. It may be like in No Man's Sky. First time you leave a planet after building your spaceship. So it's just allowing the game to breathe and injecting those moments with a certain key emotion.

Adam - No Man’s Sky is a procedurally generated game, that means as you rocket around space in your ship, the game builds the galaxy as you go using random number generators, and some very sophisticated algorithms. That means no two players will see the same planets, or have exactly the same experience. So how do you match music for a game that everyone experiences differently, and you don’t play easy listening jazz during a big fight? Well, you use something called generative music.

Paul - Generative music. I mean it to be that you use rules, so probabilistic rules that are imposed on small, granular elements of music. So it may be a simple phase, maybe a bar loop, or like a base phase. Deconstructing the music into its components and then reconstructing it live based on certain rules that you've created. It may be "play a melody, every X number of seconds from a pool of say, 200 melodies." So it really requires you as a composer, to work in a different way, to work in a much more kind of modular, nonlinear way. It's like a recipe. You're creating all the components putting in all the ingredients. But instead of baking it before the game, you're letting the game create it for you. And then often drawing information from the game, in order to control what plays, how it plays, what the combinations are, when the changes happen. And that can be very powerful because you're reacting to what the player's doing, or what the game environment is doing. So it feels much more reactive to a player.

Adam - What gives it an impact though? How do you create emotion ahead of time with just the pieces of music?

Paul - It's hard to create those engineered emotional moments. So what you need to do is create the opportunity for those moments to happen without necessarily hard-wiring them. In No Man's Sky you may happen to be on a planet that generates beautiful sunsets, and you may happen to be there at the right time on a mountain to see that sunset, and to you, that feels very personal. It somehow connects with you because you're the only person to have ever seen that sunset on that planet. And the music is the same, maybe 80% of the time, it just exists and it's supporting the game. It's fine. It's not doing anything particularly spectacular, but there are those few moments where everything comes together, and it's random, but we've allowed those random opportunities to happen. And when they do happen, they're very powerful.

Adam - And if everyone plays for long enough, they'll run into one of those moments.

Paul - So that's the beauty of a procedural game. Everyone does have those moments and it has those stories to tell, and their stories are very individual. And that's, I think that's one of the really powerful things about procedural games. You know, everyone's experience is slightly different. Everyone tends to be very proud of those moments that they find. They'll game capture them, whereas a game which is much more linear, you know, everyone's experience is essentially the same. It doesn't mean it's any less fun, but it's a different kind of personal experience.

There’s a lot more a game can do to get into your head than just playing with your senses, the right game can change your whole worldview as Adam Murphy found out from Matthew Whitby at the University of York...

Adam - Games are often challenging, but not in the way you might think. Sure, they can be hard, as anyone who's almost broken a controller in frustration can attest to, but certain games can get into your head and challenge the way that you think. Matthew Whitby from the University of York, has been studying which moments in which games can do that.

Matthew - The type of work that I do is very much focused onto studying how games can challenge the way people think or feel. And the way I've kind of, gone about it is by asking people. I've done my first study, which I managed to get published out there, was asking people to report moments in games. And we ended up with something like, I think it was 132 different moments from 100 different participants all across, you know, the genre of games saying that, yeah, I've had a moment in a video game that has challenged me either emotionally, like philosophical considerations, or even, you know, how they hold themselves on a day to day balance. And so my research has kind of been developing from that moment of saying, you know, that there's a lot going on with games, games are a powerful medium, but what can we do to try and as best as we can, capture the lived experience. So as someone encounters one of these moments where you know, their perspective is being challenged, what's actually going on there. And that's what my recent up-to-date research has been trying to capture.

Adam - That is a lot of different moments from a lot of different people. So what causes that kind of thing?

Matthew - That tends to need to be some level of, at least emotional connection in some way. One participant kind of expressed how one mini game, it kind of made them reflect on their relationship. Unfortunately, you can't design a game with the assumption that everyone is in a relationship or vice versa, but being aware of the possible life experiences, people maybe having, as they enter. Alternatively raising topics that players just would never have considered. Papers Please is a really interesting example.

Adam - Papers Please has you take on the role of a border guard in a dystopian regime. You check people’s papers against an increasingly long and arbitrary list of rules. But then desperate people come begging you to do the right thing and let them. But if you do, you’ll be putting your family, who rely on your salary, in danger. It’s monotonous, tense, and incredibly compelling.

Matthew - It is rare that anyone on a day-to-day basis had to balance; Should I break the rules of my work in order to essentially make someone's life better? Or am I willing to do something morally questionable to save my family? It's these weird things that, you know, on a day-to-day basis, most people would probably never experience that. You'd hope not anyway. And by leaning into them and including mechanics, because that's an important part giving the player agency to willingly put themselves in the shoes of whatever thought game situation you're presenting. Yes, it seems to be one of the most important things.

Adam - It's not just massive moral thoughts that can be brought about. The changes can be simpler, more introspective, but just as important.

Matthew - This person was going through the motions, playing through this sort of repetitive mini game, which had themselves cleaning around the house. And they realised that this loop within the game of cleaning the house, speaking with someone, cleaning the house, is in its own way, weirdly representative of life, that the cleaning is never done. And those sort of, rare moments in between all the chores where you'd call and connect with your partner or family or loved ones, you can sort of relish those moments. And again, it was weird that this was something that this person had been doing passively. And it's not until this game asked the question that they hadn't really considered, that it recontextualised a good chunk of their day-to-day life.

Adam - At the end of the day, why does all this matter?

Matthew - There are so many questions about video games and the potential harm that they can do. But I think as gamers and people who play are living, I'm sure they can attest that a thousand times over, all the good that gaming can do and games offer an experience that other mediums can't necessarily compare with.