Instant Genius - Consciousness and comas, with Dr Adrian Owen

Episode Date: December 6, 2021

Cognitive neuroscientist Dr Adrian Owen explains how he’s been able to communicate with patients in vegetative states and comas, and what consciousness is like for a patient in this condition. Once you’ve mastered the basics with Instant Genius, dive deeper with Instant Genius Extra, where you’ll find longer, richer discussions about the most exciting ideas in the world of science and technology. Only available on Apple Podcasts. Produced by the team behind BBC Science Focus Magazine. Visit our website: sciencefocus.com Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit podcastchoices.com/adchoices

You said this place was steps from the water. We just haven't found the steps yet. How much did we save? Enough. Enough to get lost. Or you could book a stay with Hilton. Welcome to your ocean front room. Just steps from the water.

The Hilton sale is on now. Book on Hilton.com or the Hilton app and save up to 20% to get the stay you expected. When you want savings, not surprises. It matters where you stay. Hilton, for the stay. Just two wheels, two pedals, and you. At Bikes Online, we share your passion for everything cycling.

Whatever bike you're looking for, from mountain to road, either pedal powered or electric, we've got what you want ready for super fast delivery. Quality gear at prices you won't find in your average bike shop. All bikes are pro-built and tuned before shipping to get you riding quickly. If you find a better deal, we'll beat it by 5%. Shop now at Bikesonline.com and ride more for less. You're great at protecting your data. But lots of places could still expose you to identity theft.

I thought it was safe. If that happens, LifeLock gives you a U.S.-based restoration agent who will stick by your side from start to finish. Phone calls, filing documentation, preparing insurance claims, your agent handles it all. In fact, we're so confident restoration is guaranteed. Pour your money back. Isn't it nice to have someone like that on your side?

Save up to 40% your first year at LifeLock.com slash Spotify. Terms apply. This podcast is sponsored by name, audio and focal. Streaming has made music more accessible than ever, but true listening is about more than ease. It's about quality. British audio experts name audio, alongside French acoustic specialist focal,

combine handcrafted tradition with cutting-edge innovation and high-end materials, delivering digital precision with analogue warmth. So you can experience exceptional sound at home. Music just as the artist intended. Visit name audio.com to learn more. BBC Science Focus magazine, this is Instant Genius, a bite-sized masterclass in podcast form. I'm Daniel Bennett, the magazine's editor. And today I'm joined by Dr Adrian Owen, a cognitive neuroscientist who discovered how to communicate

with patients in vegetative and coma states. Now, these are patients who usually after some kind of accident are left unable to move, talk or feed themselves. And in effect, Adrian's work gave these patients a way to tell the world that they were there, conscious and awake. And better still, it gave those caring for them a means to improve their care. Adrian's career is well documented in his book, Into the Grey Zone. And today he joins us to talk about his groundbreaking work, how it evolved over time, and how the advent of brain machine intervators might improve the lives of patients in comas and vegetative states. So commonly we talk about comas, people know about comas and vegetative states,

but there are actually different types of patients that you work with, aren't there? That's right, yes. I mean, coma is what people typically see in Hollywood movies. It's where a patient is neither awake nor aware. So they have eyes closed. They typically don't move. They lie in a hospital bed. And they're typically like that in the first few days or weeks after a very serious.

brain injury. Vegetative state is something actually that's quite different because these patients open their eyes and they'll actually look around the room. They don't look at anything in particular. They have no sort of purposeful visual responses. But they, in some senses, they're animated. That's not to say they get up and walk away or anything, but they do open their eyes and sort of look around the room and they'll go to sleep. They have normal or semi-normal sleeping and waking cycles. You know, they do automatic things like yawn and cough. So that's really the main difference is the, is sort of how animated they are. And is that, is that where your work has mostly focused with patients in vegetative states or is it? Yes, until until a couple of years ago,

everything I'd been doing for the last 20 years or so has been either in patients who are in a vegetative state or in a very similar condition known as the minimally conscious state. And that's a situation where patients can often appear to be vegetative, but they can at least respond to you in some way, albeit a little bit unreliably. So typically they might be able to sort of move their finger if you ask them. Not frequently enough to be able to communicate or anything, but there's some indication that they are aware. Those are called minimally conscious patients. And those in the vegetative state of the patients that I've focused most of my work on. I think, again, just Dipping back into the, I suppose, the pop culture view of this.

It's often likened to like a sleep or going under general anesthesia. Is that true or is that a bit of a misconception? It's actually a complete misconception. I mean, you know, one of the things that happens to almost every student or trainee that comes to work with me is, you know, they'll go into the ICU to start examining a, you know, a coma or a vegetative state paper. And they typically come away really quite shocked because they're nothing like they appear in the movies. I mean, these people have typically had very serious injuries. To get yourself into a coma, you may have had a very severe blow over the head. You may have had a cardiac arrest or a stroke.

And all of these things tend to leave people in a pretty poor condition. They're not the sort of peaceful, sleeping. beauties that we see in the Hollywood movies. That's really, in fact, that's something that I've never really seen in all the years I've been doing this. I wanted to touch on this because it's something I remember distinctly from your book, The Grey Zone, which I really greatly enjoyed a few years back. How did you come into this field in the first place?

What brought you to start sort of investigating consciousness in these patients? Well, my background is in psychology and in a neuroimicum. I'm what we've now referred to as a cognitive neuroscientist, which means that I use tools like, you know, MRI and PET scans to try and understand how the brain works. I'd been doing that for about 20 years when working at Adam Brooks Hospital in Cambridge, one of my colleagues brought a patient to my attention. He said, you know, there's a patient in a vegetative state on the ICU. Perhaps you should scan her. And the reason he said this is because, you know, that was my. my background, I was the sort of local brain scanning guy, was used to, at that point,

it was to putting healthy people into the scanner to see what their brains did when we asked them to do things or to think about things. But this really intrigued me the idea that we could take a vegetarian patient. And really, it was, the question we were asking was very open-ended. We were just wondering, well, is there anything going on? Will we see anything in there? I mean, I think really we expected to see nothing. But the patient that we scanned on that day, we put her into a pet scanner, and we asked, in fact, we showed her pictures of her friends and family. And again, that was based on my background and work that I'd been doing.

At that point, we knew quite a lot about which parts of the brain are involved in perceiving and recognizing familiar faces. So by showing this patient familiar faces, friends and family, we reasoned that, well, if there's anything going on, we'll see activity in those areas of the brain that we know are involved in that sort of processing. And that's exactly what happened. I think it was an enormous surprise for all of us.

I think, as I said, we really expected probably to see nothing. But her brain lit up really like a healthy participant's brain would light up if we'd done the same thing to them in the scan. And that was really the start of the whole journey. You went on then to produce, I guess, what's quite now, quite a famous piece of work, at least in scientific circles, where you were able to actually communicate with a patient in a vegetative state, which had never been done before and had effectively saved their life, you know, it proved that they were conscious to some degree. So for people who might not be familiar with that, could you just explain the kind of how you went from that initial study to the follow-up and the results that you got? Of course. I mean, I should say, you know, it was almost 10 years' work, actually, to do that. And the reason is because there are many things that the brain does completely automatically. I mean, face recognition is an example of that. When you see somebody that you know in the street, you don't decide to recognize their face. Your brain just automatically does it. And, you know, anybody listening to this podcast, assuming that they can speak English, they can't decide not to understand me. You know, speech, as we call it, is not something that is something that you consciously decide to do.

And by the time we, you know, we got to 2006, which, you know, as you've said, was sort of a breakthrough study, we came to realize that many of the things that we were seeing happening in the brains of supposedly vegetative patients could just be sort of automatic responses, you know, brain reflexes, if you like. You know, speech comprehension is one example of that, face recognition is another. We realized that we had to come up with another way of doing things that would actually show us that the person was conscious. It wasn't just that their brain was automatically responding. And the way we reasoned this through was we thought, well, how do you do this, you know, at the bedside? And everybody listening to this will have seen a, you know, a TV

show where a doctor grabs a comatose patient's hand and says, squeeze my hand if you can hear me. Well, if the patient squeezes the doctor's hand, the doctor knows that the patient. is conscious. In fact, they know a lot more than that. They know that the patient can understand language, and they can turn that instruction into a physical action. Now, we know that vegetative patients can't respond in that way. In fact, by definition, they can't make physical responses. So we thought, well, could they make a brain response? If we put a patient into the scanner and said, well, imagine doing this or imagine doing that, as long as we knew what the brain should do, what the healthy brain should do. If the person did it, if they produced that brain response, we would know

that they were conscious for the same reason as when you feel that hand squeeze, you know the patient's conscious. So we chose to ask the first patient in 2006 that we achieved this with. We asked her to imagine she was playing a game of tennis. And that's not because there's a tennis playing area of the brain or anything. It's just because we wanted to find an easy way to get her to vigorously wave her arms or imagine waving her arms around in the air. And we know that. We know that. We know, that that will activate a part of the brain known as the pre-motor cortex. It's just a part of the brain that's involved in sort of setting up complex sequences of movements in your body. And when somebody, when a healthy person lies in the scanner and thinks that they imagine playing tennis, you get this

lovely activity in this one region of the brain. In 2006, we had a patient who'd supposedly been vegetated for several weeks. We said, imagine playing tennis and boom, that part of the brain just lit up. we waited 30 seconds and we said, okay, now stop imagining playing tennis, an activity in that area. The brain stopped lighting up. We thought, we'll try this again. Hang on. Imagine playing tennis. Boom, the brain lit up. You know, the way I tried to describe this is it's really exactly as if we'd asked her to squeeze a hand and then stop squeezing the hand and squeeze the hand several times. But we just said, you know, if you're conscious, if you can hear us, activate this part of your brain now. And that's exactly what happened. And that's how.

how we really made the big leap, I think, from simply showing that some of these patients' brains had some residual function, they could still respond, perhaps reflexively, to actually showing that many of these patients are conscious, they are aware, they know who they are, where they are, and the predicament that they're in. There's an absolute ton of questions that follow up from that, and I feel like it's worth saying, if you do want to find out more about all of this, than it is in your book, which documents this whole process very well. But for the listeners, what were the consequences of that moment, just in terms of patient care?

Because you'd obviously had a person in a vegetative state, and if a patient is in that state, there are lots of questions being asked about how they should be treated and whether their life should be prolonged, et cetera. So what happened after that eureka moment, I guess? For me, the main consequence of that one study was immediately people stopped treating these patients as though they weren't aware. And I mean, as I say in the book, it's human nature, and I don't blame anybody for this, but very often these patients are neglected, not in the sense that they don't receive care, but, you know, people don't talk to them, they don't try and interact with them. I mean, you know, it's human nature.

If somebody gives you nothing back month in, month out, you know, very often you just sort of give up. And, you know, in that sense, they're sort of socially neglected, I think. And that really seemed to change overnight. I mean, it certainly happened for the patients I was seeing at the time. And many of my clinical colleagues since then, when they've been sort of reflecting on the, you know, the discovery and what impacts it had, you know, they'll often say things like, well, no, you know, nobody ever assumes that one of these patients is unconscious anymore. You know, I don't know that the impact has been that wide, but I think, you know, anybody who's familiar with the study and the fact that, you know, we were able to show that

a patient who completely appeared to be vegetative clinically was, in fact, completely aware. I think anybody and, you know, many, many people are now aware of that finding, I think those people change, very much change their behavior, you know, around to the patient. You're obviously careful of the sorts of conversations you're having, actually interact with the patient and try to the extent that it's possible to involve them in the conversation. Yeah, they can't contribute, but you can still address them as human being. So, you know, I think in many ways that's the biggest impact for the patients themselves. You know, that wasn't the sort of be all and end all as well. That ability to communicate

then led to treatment avenues, I suppose. I don't know if that's the right way of phrasing it. but you did have a number of patients who recovered after that sort of first contact. Was the act of sort of acknowledging their presence, as you said, sort of touched on before, did it seem to give them hope or maybe hope's a bit of an emotional word, but give them something to sort of focus on? Yeah, that's an interesting question. It's when I've pondered many times since. I think it's quite interesting that over the course of 20, 25 years,

that I've been working with these patients, you know, very, very few of them actually go on to make a significant recovery. But actually, I can think of three examples, you know, patients who have done very well. And they were all really at the center of, you know, a big sort of media storm after, you know, one of our studies came out in the academic press. And, you know, what happens in these situations, one obviously has to be very careful because you can't get, you know, consent from the patient. But it's often in every other. that people get very excited. You know, there are documentaries made about this.

There have been books written, fictional books. You know, we've had stories on the X-Files and all, Grazer Anatomy, all sorts of programs have been made about these patients now based on that discovery. And, you know, what happens is they get an awful lot more input than they used to. You know, families start to talk to them again. Nursing staff start to, you know, just to chat to them. Once they realize that they're actually there and they're, you know, that they're inside.

And of course, we get very involved. I mean, one of the patients that we saw early on in this process, we scanned, I think, 17 times. And so, you know, he was seeing me and my staff several times a week for many months. And, of course, that was a lot more interaction than they never had before. And it's hard to escape, and this is completely anecdotal. I really don't have any scientific evidence to back this up. But it's hard to escape the idea. I think, that perhaps all this positive input that it's going into them,

all this encouragement and socialisation is perhaps contributing in some way to them, to them improving. As I say, we don't have enough data to show that that is the case. But I find it remarkable that the three big stories we've had over the years, all three of those patients actually went on to do quite well. And to add a little context here, what was the sort of, because you sort of travelled quite a lot. around the country finding patients in vegetative states.

What was, I suppose, the success rate, the rate at which you were able to communicate with patients. So I should probably just describe a little bit about what we mean, or what you mean when you say communication. I mean, after basically getting somebody to imagine playing tennis to show that they're conscious, we used a variation on that technique to actually get people to, some of these patients, to answer yes or no questions.

And I'll, you know, I won't overcomplicate it. But, you know, for example, if you were in the scanner, we would say things like, you know, okay, I'm going to ask you a question. If the answer is yes, imagine playing tennis. And we would look for that signal in the pre-motor cortex. And in that way, we managed to communicate with quite a few patients getting actually yes and no responses to a lot of questions, both questions that we could use to verify that they really were communicating with us. That was generally facts about their lives. You know, is your. father's name this or is your father's name that, but also some sort of clinically relevant questions like, are you in any pain? Is there anything we can do to make you more comfortable, you know, these sorts of things? So that's sort of how we went on to communicate. And what we found is in our sample of patients, and I think in 2010 we published a baby with, I think, 54 patients. And 20% of them were not as they appeared to be at all. 20% of these patients could respond. And although we didn't actually communicate with all of them, it's reasonable, I think, to assume that they could communicate. I mean, 10, what is it, 10, 11 years on, more than a thousand

patients have been tested using these techniques now, not just in my center here in Canada, but in many places in the world that have adopted this technique to try and look for signs of consciousness and communicate with these patients. So more than a thousand patients, and again, the overall number is about 20% of them are able to respond. and communicate despite being completely physically non-responsive. So there's an important message there. Really it's that not all vegetative patients are conscious. You know, we're talking about a minority, 20% of them. But also bear in mind there are hundreds of thousands of these patients around the world and they'll survive often for for decades. So we're talking about many, many people,

20% of a very, very large number. This is a lot of people that have been treated one way, or assumed to be one thing, sometimes for one or two decades, when in fact it turns out there's something else entirely. And that volume of people affected, I suppose, brings me quite nicely to the next question, which is, so since then, we've also been doing lots of different research, but one thing we spoke about in the past was trying to find ways to make this work, make this body of work, something that can actually improve patients' lives.

So, yeah, I'm just curious to know what you've been doing since then to kind of get this into hospitals and get an intervention at the point where it most matters. Yeah, so that's a great question. About three or four years ago, I realized that although, you know, we could do these fantastic things like discover that people are conscious and, you know, communicate with them. And I've written that whole story in the book, as you've kind of mentioned. it wasn't clear what we can do for these patients beyond asking them questions like, you know, are you warm, are you cold, are you in pain? Which is, I think, contributes meaningfully to their quality of life, but of course it doesn't change their lives in the sense of it doesn't bring them out of their vegetative state. And this is where the work with coma comes in.

The problem with the vegetative state is these patients aren't typically on sort of so-called life support systems. In some senses, they can often be quite healthy, despite the fact that they're vegetative. They're not sort of their heart pumps normally. They breathe unassisted. Obviously, you have to feed them and provide them with hydration, because they can't do that themselves. But they can survive for many decades, you know, like this. And because of that, it's very complicated if a decision is made to allow them to die or, you know, to, you know, if it's decided that they don't have sufficient quality of life or there is reason to let them die. In most civilized countries, it involves a court case and a prolonged amount of sort of decision making. And the decision sometimes

is that they should be allowed to die and in which case nutrition and hydration are withdrawn. But it's sort of very complicated. The other side of this coin is coma in the first few days after a serious brain injury when those patients are in the ICU, to say you've had a patient that's gone through the windscreen of a car, totally unconscious, terrible brain injury, they're in the ICU, then in the first few days, a decision will be made

about the likelihood of them recovering. Are they going to recover? Are they going to have a meaningful recovery? Or are they going to be like this for the rest of their lives or turn into a vegetative patient? And there there is what one might refer to as a window of opportunity,

the clinical staff, the family, together make a decision about whether to use the colloquialism pull the plug. I mean, these patients typically are in life support and you literally pull the plug and they'll die within a few minutes. That happens to many, many patients around the world. If you go, if you end up in the ICU with a very serious brain injury, there's a very high chance that you're going to die. But you won't die of natural causes. You'll die because a decision is made that you're going to have no meaningful life. I realized about three years ago, we

could take all of this work that we'd sort of done in the long-term vegetative patients and actually take it into the ICU? What about if we could actually find patients that had a better chance of recovery than others? What about if we could overturn the way decisions are made about whether people in the ICU should be given a chance or not? Now, I don't have a strong opinion about this. I'm not coming from a position where I think everybody should be kept alive because obviously there are emotional and economic reasons why these decisions are made when they're made. But if we can get better at predicting, who would have had a good recovery, then I think we're in a much better, a much stronger position. So all the work that I've been doing for the last two or three

years has been in these sort of comatose patients. We take patients in typically about five to ten days after an injury. We do the same thing. We put them in the scanner or put electrodes on their head to look for signs of residual activity. We try to communicate with them and try to better understand both exactly what their condition is as far as the extent of their brain damage, but also whether or not all other things being equal,

they are likely to survive and what that survival might look like. And we're making huge, huge progress in that respect. I mean, it's worked actually much better than I could have ever believed it would work. We really are, getting to the point where we can improve our ability to predict the good outcomes from the bad outcomes. And so when we started talking about this and sort of when you started this research,

we were talking about FMRI scanners, which are these absolute hulking great machines that you put patients in and you can't wheel them around, although I think they used to be a psychologist who had one of the trailer once in America. But that's by the by. But you've managed to shrink the technology and the technique. I suppose, down to things like EEG scanners, which are kind of available in most sort of good hospitals, aren't they? What are the other, so there's the tech side that you shrunk, and that would be interesting hear about,

but also what are the other barriers to this sort of, because when you hear about it, you think, yeah, that should be, clearly that should be in most hospitals. And so it leaves me wondering what is blocking it in a sense? Well, I think the thing that's really blocking it is, is inertia, to be honest. You know, some of these discoveries we made, you know, getting on for 15 or 16 years ago now. And, you know, I for one, think that any patient who is able, and there are some patients who can't go into an MRI scanner because if you have parts of metal parts in your body, for example, you can't do it. But for any patient who's able, who's had a serious brain injury, for whom the prognosis or what's going to happen to them is uncertain.

And I think they all deserve to get into an MRI scanner. But for that to go from being a research tool to being widely used in clinical practice, does require that the various regulatory bodies that decide what's an appropriate treatment and what isn't make that decision. And if they made the decision, yes, every patient deserves an fMRI scan. We would be in a very sort of different place today. But you know, there are economic reasons. there are some practical considerations. I mean, most of the discoveries that we made were made on not the sort of MRI scanner that is in every hospital.

It's typically, I mean, it's a sort of a rolls voice of an MRI, if you like, which just basically means it's a bit more powerful than the most hospital scanners. But actually, you know, we tried to mitigate this whole issue by showing you can do much the same thing, on an old hospital scanner. We're fortunate or unfortunate, however you want to think about it, here in London, Ontario, where I'm sitting right now. We have the oldest MRI scanner in North America in our hospital. It is going to be replaced soon.

But right now, it's about 20 or so years old. I mean, it's not the, it's the oldest working scanner. It's still going, it's still scanning patients day in, day out. And we used that scanner to show a few years ago that actually you can do the same thing. You obviously have to make a few compromises, and it's not quite as clear and reliable as it is with the sort of state-of-the-art research scanner. But you can do it on a sort of cheap and cheerful hospital scanner. And I tell you, if you can do it on the scanner we have here in London, Ontario, then you can do it on pretty much any hospital scanner, you know, around the world. But it requires people to dedicate themselves to it.

You know, it's not something, actually, I guess it is like a, I was going to say it's not like a blood. test, but in many ways it is like a blood test. I mean, probably most of us could be trained to take blood. But, you know, it requires some expertise and some machinery behind the scenes to analyze a blood sample to decide, you know, what's, you know, what the answer to whatever the question the person that wrote the prescription had. It's the same thing with the MRI that we use. It's not, the answer just doesn't pop out of the machine. It requires somebody to interpret it and think about it a little and that requires some expertise. But I think it just requires that the will is there and those regulatory bodies that make

these decisions sort of deem that this is a worthy enterprise. I certainly think it is and I've been campaigning for it now for many years. For someone like me outside of, I suppose, medicine and those systems and how they work, so is it a case of you have prepared, you know, these different techniques for investigating the consciousness of patients in these states that can work at, you know, an ICU level that can, when a patient comes in, you can do an assessment. So whether that, you know, and it can adapt to whatever equipment, I suppose, is at hand for these doctors. So is it then a case of you have to then talk to these medical bodies and

make your case until they hear you and then, I suppose, a bit like a select committee at government way. It is quite a lot like that. But I mean, the problem is, I mean, again, this is one of the things that prevents it happening probably is it's not really my job to do that. You know, I'm a neuroscientist. I'm around to sort of discover things. And once I've discovered something, I typically move on to the next thing. I don't generally spend a lot of time persuading the various people that need to be persuaded that they should adopt this thing. I just get on with it, you know, and do the next thing. And this is the way that science, you know, becomes clinical practice. I mean, there's a, we have a beautiful example that everybody can relate to. Think about, you know, the way the COVID-19 vaccines

were rolled out. And everybody has read about, you know, how amazingly quickly this went from being, you know, that science in the laboratory to being, you know, vaccines in people's arms. And, you know, the story that everybody's getting is that this was extraordinary, and it was extraordinary. It wasn't too fast. It was just that the motivation was there to make it happen quickly. And all the barriers that typically sort of stand in the way were pushed aside because everybody was invested in this. That's not typically how things work. You know, typically we make scientific discoveries and then, you know, maybe 20 years before they actually make it into clinical practice because they often have to go through.

of prolonged trials and with things like MRI or techniques like MRI, what typically happens is people just naturally start to use them more. I mean, this is certainly the case in where our methods are, you know, are concerned. As I said, there'd be more than a thousand patients scanned using these techniques around the world now. And, you know, probably only a, I don't know, a couple of dozen of them were scanned in my lab. These are other people around the world have sort of adopted it. And some of them are scientists. Some of them are interested doctors that, you know, have a patient that's quite interesting. I certainly get calls like that all the time from somebody,

somewhere in the world that says, yeah, there's a very interesting patient and I'm pretty sure there's something going on. Can you tell me how to do this tennis imagery thing? And I'll just instruct them to do it and, you know, they'll carry it out. So, yeah, I think it just sort of by some kind of process of people gradually adopting it, eventually the regulatory bodies will say,

okay, this is a thing we should be mandating this for every patient. but it's a slow process. It's not like the COVID-19 vaccines. That was Adrian Owen there explaining how his work, communicating with patients in comas and vegetative states, could find its way into more hospitals. If you'd like to hear Adrian I dig a little deeper into the science of consciousness

and the future of brain-reading machines, check out Instant Genius Extra, a bonus podcast available via spruity. on Apple's podcast app. And of course, if you want to learn more about agents' work, check out his book, Into the Greyzone, which is published by Faber and Faber in the UK. Thank you for listening. The Instant Genius podcast is brought to you by the team behind BBC Science Focus magazine,

which you can find your sale in supermarkets and newsagents, as well as your preferred app store. Alternatively, do come find us online at ScienceFocus.com. See you next time. This podcast is sponsored by Name, Audio and Focal. The texture and emotional depth of music can be lost through digital sources or poor signal. Name Audio believes you can have digital precision with analogue warmth. Alongside French acoustic specialist focal, Name creates high-end audio systems combining innovation with craftsmanship,

so you can listen to music, just as the artist intended. Discover more at name audio.com. Ambition comes in all shapes and sizes. At First Citizens Bank, we roll with your goals because we're built for what you're building. Fit for your ambition for Citizens Bank. Relax and let Ralph's delivery handle your grocery shopping this week. We start with only the freshest items, then review your list and carefully choose each one. Then we pack it all up and deliver it in as little

as 30 minutes, so you can feel confident it's what you ordered. Fresh groceries, your way, with Ralph's delivery and pickup. And right now, you can save $20 on your first delivery or pickup order. Ralph's, fresh for everyone.