2003 LECTURE SERIES

"Ah yes, I remember it well..."
Remembering, Forgetting and the Movie "Memento"

Dr. Stuart Zola
Director, Yerkes Primate Research Center
Emory University
March 19, 2003

Thank you very much, Jim, it's just lovely to be back and a special honor to be introduced by you. As Jim mentioned, we go back some ways, and Jim I've always seen as a mentor, in fact, he's old enough to be my father and I've always looked up to him. But seriously, thank you, I really do appreciate the opportunity to come back and to talk with you.

I'm going to talk this evening about aspects of memory. It's going to be a little bit different than you might otherwise hear from a scientific talk on memory. It will have, indeed, some science to it, but it will have a number of aspects associated with our everyday memory and with aspects of memory distortion, as well as how memory works in the brain.

And we'll take a little adventure tonight, we'll take a little adventure through the brain initially and look inside the brain. In fact, at some point you will become clinicians yourselves and you will be able to tell who has memory problems and who doesn't. We'll see it's actually pretty easy to become a clinician, it only takes a few minutes, and we'll look at some parts of the brain that are important for memory. We really have made a lot of discoveries about that, both from work in humans and work in animals as well, and we'll touch on each of those areas, and then we'll move to some aspects about our ordinary memory and what happens to us with the passage of time and what happens to our memories as time passes.

So we'll look at a number of things. We have a fairly full agenda and a number of items to cover, and I'll try and do most of those within a little bit less than an hour.

I often am reminded of this story about the Marx Brothers when I talk about an agenda of having more than one thing to do. Some of you may remember the Marx Brothers movies, and Hollywood being what it was in the era of the Marx Brothers movies, and in one of these movies they had to actually play a game of bridge, and Hollywood called in the world's greatest bridge player, a fellow named Charles Goren, some of you may be familiar with that name, and they called in Mr. Goren to teach the Marx Brothers to play a game of bridge so that it would be authentic in the movie, and as Groucho describes it in his memoirs, the Marx Brothers are sitting around a large table in one of the studio rooms, and Mr. Goren is brought in and introduced, and he says now, gentleman, bridge is a game that is played with one deck of cards, sometimes two decks of cards, at which point Groucho jumped up on the table and said Mr. Goren, I think that's about all we can absorb for today, thank you very much. So whenever I have more than one thing to say, I'm always reminded of that.

All right, we're going to, as Jim alluded to, talk a little bit from time to time about the movie Memento, and I am actually gonna start off with one aspect of that movie. I'm gonna pose a question, though for you initially, and this sometimes is useful, sometimes not useful. Some of you have heard and know that I am also an amateur magician and do sometimes tricks to make points about how memory works, and I'm going to do that for you here with this little silk, and if we think of this silk as your memory for this event tonight, for the kinds of things that happen here with us tonight, all I'm doing is simply poking the silk into my hand, and as I'm poking it, it's getting smaller and smaller, and that represents what happens with the passage of time. So this evening when you go home, you will remember a lot of things about this episode, but a few weeks from now you will remember fewer things about this episode, and a few months from now, still fewer things. And eventually, the question is whether you will remember the episode at all.

So the question is, is that the way memory works? This is the case that as time passes, things become less clear, less well-known, and we remember fewer of those episodes, fewer of those components of the episode, and how does that happen? We're going to look at some of those aspects tonight.

As we start off, I'm going to move to a scene from the movie Memento. Now, some of you are familiar with this movie, I know. This is a scene that has the protagonist, Leonard, talking to a hotel clerk, a fellow named Bert, and he's trying to explain to Bert about his condition, and what he is describing is, very accurately, the condition of amnesia, the condition in which individuals who have damage to particular regions of the brain have memory problems, and the nature of those memory problems is well described by the protagonist, Leonard.
The difficulty is that he uses some language that actually is incorrect, and he talks about having a short-term memory problem when, in fact, as we'll see in a few moments, he really has a long-term memory problem, not a short-term memory problem, and he also corrects Bert, who says you have amnesia, and he says no I don't have amnesia, I have a short-term memory problem, because he's thinking that Bert means by amnesia, an individual who forgets who he is, you know, has no memory of his own life and his own personality, and he's trying to indicate no, that's not what his problem is, and he feels that that's what amnesia is, but in truth, separate from those aspects in terms of semantics, the characterization, at least, that Leonard shows for amnesia, is really quite accurate and very useful to hear.

"What can I do for you, Leonard? Um…
Bert.

Bert. I'm not sure, I think I may have asked you to hold my calls.

You don't know?

Well, I think I may have, I'm not too good on the phone.

Right, you said you like to look people in the eye when you talk to 'em.

Yeah.

You don't remember sayin' that.

Well, that's the thing, I have this condition.

Condition?

It's my memory.

Amnesia.

No, no, no, no, it's different from that, I have no short-term memory. I know who I am, I know all about myself, I just, since my injury I can't make new memories. Everything fades. If we talk for too long, I'll forget how we started and next time I see you I'm not gonna remember this conversation. I don't even know if I've met you before. So if I seem a little strange, or rude or something, uh, I've told you this before, haven't I?

Yeah, I mean, I don't mean to mess with you, but you're so weird, you don't remember me at all?

No.

We've talked a bunch of times.

I'm sure we have, yeah.

Well, what's the last thing you remember?

My wife."

All right. Well, that's Leonard, and we'll come back to Leonard a little bit later this evening, but what he describes is exactly what his problem is. I'm just gonna ask the projectionist if we can move the screen, move the projector a little bit, because we're falling off the screen over here, and it will matter later on.

What we see here is the human brain, a very animated version of the human brain. For those of you not familiar with what you're seeing, if I were standing here like this and I took this side of my head off, that's what you'd be seeing. You're seeing the left side of the brain. This is the front of the brain here, and the back of the brain that we can now see very nicely here, and the brain is organized in a very particular way, and many specialized functions are localized in different regions of the brain, and we don't have time, really, to talk very much about the nature of brain organization in general, but we're gonna focus on the issue of memory and how memory is organized in the brain, and to do that, we are going to move inside the brain, and so the next picture that I'm going to show you is a picture that looks at a different view of the brain.

Now, the human brain in most of you weighs about three to four pounds. It may weigh a little bit less in some of your colleagues, some of your friends, you may suppose that at least, but we're gonna turn this brain now in the following way and that is if I were facing you, and I could take this laser and just slice it down this way, take off the front of my face, the surface that you'll be looking at is what we're going to see next.

So here is this view of the brain, now we are inside the brain. This is the left side of the brain here, the right side of my brain, the top and the bottom, and there are a few things that I want to point out about the brain. One is, first, that this is a real human brain, this is a brain from a deceased individual, a patient that we studied, his initials were R.B. These patients are often referred to in the literature just by their initials to protect their identity, and R.B. was an individual who had an ischemic episode, a loss of blood supply to the brain, following some surgery, and as a result of that, he developed amnesia. He had amnesia.

We'll talk a little more in detail about his amnesia, but I just want to point out a couple of things in R.B.'s brain. One is that you can see a clear distinction here between the outer edge of the brain, that's this dark color, and the inner areas of the brain, this kind of very white mass, and that distinction is one that correlates with the cells of the neurons of the brain, and the fibers of the neurons of the brain. So you have cell bodies here, and their connections or their fibers that are bringing information from one cell here across the brain talking to another place in the brain, so this distinction between the cell bodies and the fibers is an important one for us.

Often, you hear the term grey matter versus white matter. The brain really isn't grey, this is the natural color of the brain, but the reference is to the cells, the literally billions of cells in the brain, and their connections in the white matter.

We're gonna come down to this region of the brain here on this side, and this region on this side. This is an area of the brain called the temporal lobe, and there are two temporal lobes, one on each side of the brain, and buried within the temporal lobe is a very oddly-shaped structure. It's a structure that has a funny-sounding name. It's called the hippocampus, and it translates to a term that refers to a shape of a seahorse. When the Greeks and Romans first began to dissect brains and they found this structure, the shape of it reminded them of a seahorse, and they named it with that terminology. So this little structure, the hippocampus, it's really a tubular structure, it's coming out this way and we're taking a slice through it, so you're seeing a surface of the hippocampus on this side, and you're seeing a surface of the hippocampus on….the brain.

Now, the hippocampus in this individual is actually a little bit abnormal, and that's because in this individual, R.B., the cells of the hippocampus died. A very substantial number of cells in the hippocampus died on each side as a result of this ischemic episode, this loss of blood supply that he had for a rather short period of time, and it underscores both the vulnerability of this structure to a very wide range of conditions, and the importance of this structure for memory.

When we talk about the kinds of conditions that can be affected by this structure, if we think of Alzheimer's disease, for example, the hippocampus and the associated cortical areas lying right adjacent to the hippocampus are the first regions that begin to develop plaques and tangles in Alzheimer's disease, and the presence of those is associated with memory dysfunction, with memory problems. If we talk about certain kinds of viruses, encephalitis, there's an affinity for some viruses for this region of the brain, and it's the first region that is damaged and destroyed. If we talk about aspects of ischemia, loss of blood supply, anoxia, loss of oxygen supply, even for a fairly short period of time, this region of the brain is affected significantly by that, and cell loss occurs here, and accordingly, in all of those conditions that I just described, often it is the case that there are memory problems associated with Alzheimer's disease, and with ischemia and anoxia and encephalitis, and a variety of other kinds of conditions as well, for which the hippocampus becomes, unfortunately, quite vulnerable. Even aspects of stress, as we are now beginning to learn, can have a negative impact on the hippocampus, and if unrelieved stress occurs for long periods of time, chronic stress, then the size of the hippocampus actually can be seen to be diminished in those individuals. So the hippocampus turns out to be quite critical here.

Now, I'm going to modify this slide just slightly by adding these outlines, and these outlines refer to the damage that occurred in two different individuals. One is a patient whose initials are H.M. Some of you may be familiar with this individual or this case study. H.M. is still alive, but in the 1950s he underwent a surgical procedure to reduce seizures that he had as a result of a bicycle accident that he had as a youngster, and following that head trauma that he had, he began to develop seizures, and these seizures grew more serious during his teenage years.

By the time he was in his early twenties he was having several grand mal seizures per day, and this was the early 1950s. There had already been anti-seizure medications developed, but none of these were useful in H.M.'s case, and so he underwent this surgical procedure by which the focus of the seizures in the brain was determined using EEGs, electroencephalograms, which had already been developed by that time, and one could determine where the pathological cells were that were causing the seizures, and they were found to be, in H.M., in both areas, both sides of the brain, in the region of the temporal lobe and right around this region of the hippocampus. I've only drawn it on one side, but he actually had removals, both sides of his brain, of quite extensive tissue in the temporal lobe, including the hippocampus and the structure called the amygdala, area important for emotion and for some aspects of memory and modulation of memory, as well as these cortical areas. I'm gonna name these areas for you, you don't have to remember these names, but I want you to know what they are, at least, and that's the entorhinal cortex and the peri-rhinal cortex and the para-hippocampal cortex. You can't see all of those in one picture here, but those are the cortical regions, together with the hippocampus, that make up what has now become known as the medial temporal lobe memory system, a memory system right in the medial temporal lobe.

We didn't know that, or surgeons didn't know that at the time, in the 1950s, and when they removed this region of the brain, on both sides of H.M., they actually were essentially removing a substantial portion of his memory systems. Why did they do that? They did that because it was known, at least, that you could remove the temporal lobe region on one side, or the temporal lobe region on the other side, the left side or the right side, with relative impunity, and often patients would actually improve. Patients who were having seizures would actually improve, even sometimes their cognitive function, because they were no longer having to take a lot of medications and they were no longer having these seizures. So, although it was known that you could remove the left side or the right side, H.M.'s seizures were coming from both sides, and so it was presumed that you could remove both.

The result was a reduction in his seizures, but the result also was the most profound amnesia that we have had the opportunity of studying. Upon his recovery, H.M. was found to have severe inability to make new memories, so that if we, as in the case of Leonard that we saw, had a conversation with him, a few minutes later came back and asked him about the conversation, he would have no memory for the details of the conversation, or even having had the conversation just as Leonard has described. It wasn't that he just didn't remember telling Bert about the stuff, or the details that he told him, he didn't remember ever having had the conversation with him. And so although we don't really know Bert's, we don't really know Leonard's damage, the supposition would have to be that Leonard had quite significant damage to his temporal lobes, as in the case of H.M.

So we know that damage to this large region can produce severe memory problems. On the right-hand side is the damage that occurred in R.B., the individual that we talked about before and whose brain this actually is, and you can see how much smaller this damage is. It involved just a portion of his hippocampus, just one group of cells in his hippocampus, but it turns out that we discovered that damage to just that region alone was sufficient to produce significant memory problems. Now, his memory is not as severely impaired, or his memory wasn't as severely impaired as H.M.'s memory was, but in every aspect, in every qualitative aspect, it was the same. He had difficulty making new memories, recounting, consciously recollecting the facts and events that had happened to him after [inaudible] occurred. So everything that we see in H.M., we also see in R.B., although it's not as severe in R.B. But it makes the point that this region of the brain is a critical region for memory.

Now, these patients are rare. R.B. was published in the late 1980s, 1986, and it was the first case in a hundred years of this work, where there was such a limited lesion, and where we knew enough about the neuropsychology of this case and enough about memory impairment to be able to describe it with accuracy. So that was the first time in about a hundred years of work with patients that we ever saw such a case, and accordingly, trying to develop ideas and theories around work with humans is problematic because we simply ordinarily don't have enough pieces of information, we don't have enough cases that have very similar or identical lesions to be able to ask questions [inaudible] about the brain.

That's one of the reasons we turn to work with non-human primates, and with rodents, and with other species of animals, because there, we can ask these kinds of questions in a systematic way.

All right, so we have the opportunity, then, using experimental animals, really to begin to look systematically at the effects of damage to particular regions of the brain, and it's hard to overstate the fact that research with animals, whether it's monkeys or rodents or other species, it's hard to overstate how much that information has contributed to our understanding of how memory is organized in the brain. It really has helped us in extraordinary ways. The work with humans and human patients has been very useful and important for us in laying out aspects of how memory might work and how memory might go awry, but the ability to look at this in a systematic way in experimental animals provides for us the ability to ask questions about the roles of specific structures, and to ask and address questions about how these structures are connected to other structures, and indeed to begin to map out what the memory system is, and that is really how we have come to understand what the system is in the temporal lobe that is critical for memory.

This illustration simply shows one way that we can address questions about memory in animals, in this case, in monkeys, and it's a very simple task, and it's a task, as you'll see in a moment, that's very similar to the kinds of things we do with our patients as well. Here in this top panel, the animal here is simply displacing an object, and there are some food wells here. He displaces the object and gets a small food reward, and then an opaque door is lowered, and an interval of time later, and this interval of time can range from just a few seconds for what we talk about as short-term memory, to many, many minutes or hours or even days, that is long-term memory. The door is lowered and then eventually raised again, and now the animal sees two objects, the original object that it saw before and a new object, and we simply ask the question of the animal, do you remember which object you saw before. There are many ways to do this. We can ask the animal to go to the same object they saw before and then get rewarded, or we can ask the animal to go to the novel object and also, in that case, get rewarded. There are various reasons we would do one or the other kind of task, but the important thing is that we have a way, without having to use language, to ask animals what it is that they remember, and once animals learn what the rule is, always go to the same object or always go to the novel object, we can then increase the delay interval from the time we show them the sample to the time we ask them to make this choice, and we can ask the question what happens when you have damage to the hippocampus, for example, or to some of these other regions of the brain that were beginning to be explored in terms of their role in memory.

And it is just these kinds of tasks, not only this task but many other tasks as well, but this really is an analog for asking questions about memory, both in humans and in animals, and it is really very much the same kind of task we use in our human patients when we assess their memory as well. We have another little device here, a table model of that device you just saw, and we use here, monetary reward instead of M&Ms and peanuts, but in all other ways, the task run in the humans and the animals is exactly the same, and this is an important point because it gives credibility to the tasks that we use in animals. When we know we're assessing memory in the very same way in animals, then it gives that kind of task validity. If animals are impaired following hippocampal damage, then that tells us something about the role of the hippocampus in memory.

Well, I wanna come back to just one final point here, and this is the place where you will become clinicians. The brain that you saw of R.B., that you saw of R.B. earlier, is a brain of a deceased individual, and often it was the case that one had to wait until the individual died before we could look at the individual's brain in order to know where the damage was and to begin to make relationships between damage in the brain and memory problems or other kinds of cognitive problems, but over the last 20 years, as many of you are aware, we really have had a revolution in technology that has allowed us to look inside the brains of living individuals. Technologies like magnetic resonance imaging, as shown here, and other kinds of brain imaging techniques like PET scanning, positron emission tomography, P-E-T, PET scanning, and other ways of looking into the brain, have really revolutionized our ability to do diagnostics and our ability to do treatment and research on the brain, because now we don't have to wait until the individual dies. We can look at the kinds of difficulties that the individual may be having right on line.

And this illustration is one such example, as I mentioned. This is a magnetic resonance image picture, an MRI picture of the brain, and you can see how similar it looks to the brain that we showed of R.B. You can see the difference here between the grey matter and the white matter, and here it really is grey because of this black-and-white picture, and you can see a lot of the details of the structures. We have a special advantage in being able to use these pictures because we can outline the structure of interest, and then ask the question, is the volume and the area of the structure normal or not? And we can compare this structure in this individual to that structure in a number of control individuals that we have imaged who are matched in age and education and gender and other kinds of aspects, other kinds of variables that may influence brain size and brain shape, so that we have a particular advantage here of being able to do this.

This turns out to be a picture from a graduate student in my laboratory, and this is actually a screening device we use in my laboratory, you have to have a good looking hippocampus if you want to work in the laboratory. So this is a young fellow in his twenties or so, so you can see a very nice looking hippocampus here and here and on both sides.

All right, well, you have actually learned enough now, as I mentioned, to become clinicians, and the next picture that we're going to look at is going to have two pieces to it. There's gonna be a picture of an individual who has amnesia, and a picture of a control subject who is matched in age and education, other important variables, and your job is to pick out which of these individuals has memory problems. All right, here we are, we're showing only one side of the brain in these pictures, but here's the temporal lobe of this individual, and here is this individual's hippocampus. Here's the temporal lobe of the second individual, here's this individual's hippocampus. One of these fellows has memory problems, the other does not, and let me just ask by calling out how many people think it is the top picture who has amnesia? How many people think it is the bottom picture who has amnesia? Everybody, okay? Yes. So very good, you have graduated, you've passed, you are now able to practice in your community.

So clearly, this individual's hippocampus looks abnormal, and indeed it is abnormal. It's reduced by about two thirds, and it's actually that way on both sides, this was a bilateral lesion. This occurred as a result of an ischemic episode, much like R.B., the patient that we saw earlier, but much more severe ischemic episode, and as a result, this individual had some significant impairment. Not as severe as H.M, because remember, H.M. had all of this tissue removed, as well as his hippocampus, but nevertheless, this is a significant enough deficit for the individual not to be able to live by themselves. If they put water on to boil, for example, and the phone rings, they're gonna forget that the water is there, and so they can't--I hear some rumbling in the audience that this may not be the best example that we use, but you get the picture. So it's an individual who simply could not live by himself. Again, not as severely impaired as H.M.

This individual here is a normal individual. I should say, these two individuals are somewhat older than the picture we saw earlier. These individuals are in their seventies, but nevertheless, this is a very nice looking hippocampus. If you had this and you were 70, you would be really proud to be showing this picture around, you'd be carrying pictures of your grandchildren, let me show you that, here's my hippocampus, I wanna show you this too. Very good looking hippocampus.

So the point here is now that with these two developments, with animal research and with new technological developments that allow us to look inside the brains of living individuals, we have really made some tremendous advances in understanding about how memory is organized in the brain, and what happens when things go wrong to these regions of the brain.

The next question, of course, has to do with how we might be able to intervene once those kinds of things happen, and I'm pleased to see so many high school students and youngsters here because that is gonna be your job. Your job is gonna be to find out the next generation of questions and answers about brain and brain function, and how, given what we now understand to be some of the issues associated with brain dysfunction, how can we intervene and slow down those processes or hopefully reverse those processes or prevent them from happening in the first place, and that's the kind of horizon, that's the frontier that is out waiting for all of you to be able to accomplish, and I hope that you do it soon, because Jim and I are, we're waiting for that.

We're going to look now at a few rules about memory, and then we'll talk about aspects of memory distortion, and these rules are rules that have come about from some of the work that I have described. This is some of the knowledge that we have discovered in this research, both in humans and in animals.

The first rule is that there's actually more than one kind of memory. It turns out it's much more complicated than we supposed, and when people have amnesia, they have memory problems, but they have memory problems of very particular types, and there are some kinds of memory that are spared, and some kinds of memory that are affected in amnesia, and we don't have time really to go into a lot of the details of those differences in that aspect, but this illustration here simply makes a couple of points about the aspects associated with these different kinds of memory.

If we think of you right at this moment as you are watching, as you're listening to me, this very minute what you are processing now as you're listening and watching is initially in short-term memory. Short-term memory is a memory processing and storage system that has a very small capacity and things last in here for a pretty short period of time, and the time is not so much the critical thing as the capacity of the memory. You just can't squeeze very many things in here, and as soon as the memory storage area is filled, things have to move out to another kind of memory, and that other kind of memory, it turns out, is long-term memory, so long-term memory typically is for things that have happened earlier than this very minute, but even just a few minutes ago, and that's where some of this difficulty comes in the terminology. You may remember Leonard said he had a short-term memory problem, that after he talks with Bert for a while, he's not gonna remember what Bert has said. But that's not a short-term memory problem, that's really a long-term memory problem. Short-term memory typically, in fact, is intact in patients with temporal lobe amnesia, with damage to the hippocampus and to these other regions of the brain.

There's a very simple test used for assessing short-term memory, it's called the digit span task, and it runs as follows. If I say to you, I'm gonna tell you some digits and I want you tell me back these digits in the same order that I tell them to you. Seven, three, one, two, five, you would say back to me seven, three, one, two, five, and then we'd go on to another trial with another series of digits, and each trial I would add one more digit, and eventually you would get to your limit of digits, and the limit, as it turns out, is about seven, plus or minus two items, seven plus or minus two digits. That's about what can be stored in short-term memory, but it turns out that H.M. can store as many digits in short-term memory as you can, and R.B. could store as many digits in short-term memory as you can. Short-term memory is not where the problem lies --other regions of the brain are involved with short-term memory, but long-term memory is where the difficulty lies.

If I came back after a while and said to H.M. or said to R.B., after a few other events had occurred, or if I strung numbers out for longer than the capacity for short-term memory so that long-term memory would have to begin to take over, they would have difficulties, because the hippocampus is associated with long-term memory, and damage here produces long-term memory impairments. So if we have a conversation with H.M. and we wait a little while and come back and ask him about it, he simply doesn't remember--not only the details, but any aspects of having had the conversation.

Other kinds of memory, referred to as remote memory, memory from a really long time ago in your life, towards your early years of your life, and those, again, are less hippocampus involved and again, unfortunately, it's a very exciting area of research in how these discoveries are made about what parts of the brain are important for these different kinds of memory, and it's so exciting and I have to resist beginning to talk about it, because it really is a way of discovering how memory is organized, but I can only say to you that it is not important for the hippocampus in terms of remote memory. When we ask you about childhood memories, they are elsewhere in the brain by that point in time, and the hippocampus isn't critical, and we know that because people who have damage to their hippocampus can still recall, quite accurately, events that have happened earlier in their lives.

We move to the most extreme part of our lives, our infancy, and there there's another very interesting and exciting story, and I'll just tantalize you with this so that some day Jim will invite me back to tell the rest of the story, and that has to do with infantile amnesia, and the fact that some of you may not have been aware of, but that you all have amnesia. All of you, all of us, are amnesic. We have no conscious recollection for the first couple of years of our lives. If you think for a moment and try to think back to your earliest childhood recollection, it is unlikely that you will be retrieving a memory from the first couple of years of your life.

Lots of things happened during that period of time. We learned how to walk, talk, toilet training, all kinds of events and episodes, and yet we have no conscious recollection of any of those kinds of episodes. Lots of reasons and suppositions about why that is the case, and perhaps we will get to talk about those possibilities during the question period, but only to say that it's a complicated issue. When we talk about there being more than one kind of memory, it's important to understand that there is more than one kind of memory, and there are different regions of the brain that may be responsible for different aspects of these memories. The hippocampus is critical for long-term memory, and that's the thing that we see and talk about the most, and that's the most typical kind of problem that we see in amnesia.

The second rule is that amnesia can be quite pure, and what do we mean by that? We mean simply that people can be amnesic, have memory problems, but have no other kinds of problems. Their IQ can be quite normal, personality, no changes, perception, no difficulties, reasoning, no problems. Lots of things can be quite normal and intact despite the fact that they have memory problems and memory difficulties. And it's an important point to keep in mind. It's especially true as we talk about aspects of aging, where memory problems begin to sometimes show themselves, but that doesn't mean, necessarily, that the person isn't capable of having good judgment, or isn't capable of reasoning out aspects, or isn't capable even of running a company, or in one case, for some period of time, of running a country.

Rule number three. Certain memory abilities can be spared, and we already have really mentioned this, and I don't want to dwell on that, but there are some classes of abilities that are very clearly spared. For example, motor skills and motor abilities. H.M. has a sparing of certain kinds of motor abilities, and by that I mean that he can learn things and retain them over very long periods of time, completely normally, despite his profound amnesia. An example of one of these episodes with H.M., it was described several decades ago but it wasn't understood, it wasn't clearly understood how he could have had this good performance on this task, and a lot of hypotheses were developed before it was understood that there is more than one kind of memory and one kind of memory system.

This is a simple task illustrated here, this is not H.M., but this is a simple task illustrated here showing an individual drawing within the pathway of a five-pointed star. It's a five-pointed star with an outline, and your job is simply to draw within the pathway of the five-pointed star. Ordinarily a very simple task, it's made a little more difficult by putting this barrier here so that the individual cannot see his hand directly but can only see his hand in this mirror. Now, that change in the way the task has to be done really creates a problem for the brain, because the brain now is receiving two conflicting pieces of information. When you move your hand away from you, you see in the mirror your hand moving towards you, so you're getting motor information sent to the brain that is different from the visual information that is being sent to the brain, and that causes a conflict and indeed, people have a lot of difficulty. They become almost spastic, they begin to knock over the mirror and do other things, and they are outside the lines for some period of time. Often, in fact, they become almost paralyzed. They will just hold the pencil, and the only force they can exert is a downward force because they can't figure out how to exert a force closer and further away from them, so they'll just simply poke the pencil through the paper. You can try this with your kids at home, you know, set up this with a piece of cardboard and get them to this point, you see, I told you you should have done your homework. Now look what's happened.

Turns out the brain is very flexible, and after several trials of this, you begin to settle down and you use the information in the mirror to help control your hand accurately, and pretty soon you're able to stay within the lines. H.M. has exactly the same experience on this that you would have, and indeed, these are data from a study with H.M. showing just his performance across three days. Here he is on day one; the high number here is errors going outside. As you can see, he's making a lot of errors initially, but he gets better within the day across ten trials, and then we wait 24 hours. Twenty-four hours in the life of an individual who can't remember things from moment to moment. And what happens here? Is he back up here, does he forget everything? No. Look at this, he starts off the next day just about where he left off the previous day, so he's retained this ability and continues to get better, and by day three he's performing errorlessly, so that he has learned and retained a motor skill quite normally, despite his impairment, and this indicates the understanding, now, that some of these kinds of abilities are not the purview of the hippocampus and lie outside this medial temporal lobe memory system and can be accomplished quite normally.

The difference between you and H.M. at this point is if I ask you how come you're doing so well here, you'd say to me, kind of surprisingly, what do you mean, how come I'm doing so well? You made me come here, you know, for three days and we did this task, and don't you remember the first day I got so spastic I knocked over the mirror, we broke the mirror? And, you know, I said oh no, seven years bad luck, he said no, no, you know a lawyer in Irvine who could get it reduced to three years, and so--I write some of this myself.

So the point is, you have conscious recollection. You know what's gone on over this period of time, and you have your recollection of your episodes from this period of time 'cause you have your hippocampus…

How come you're doing so well here? He doesn't know, he says I guess I'm just lucky. Well, have you ever done this before? No, he has no memory of the episodes, he has none of the hippocampal part of the information, but he does have the motor part, it's the motor part of the brain that's doing this, and so he can do it, but he doesn't remember the episodes. Have you ever seen this apparatus before? No. Have you ever been in this room before? No. Have you ever seen me before? No. He doesn't have any of the other kinds of information that you have, pointing to this distinction between different kinds of memory and the fact that you can have sparing, as this rule suggests, of certain kinds of information, even though you may be quite impaired otherwise. I'll leave that to you, you can vote.

Rules four and five bring us to the kind of last portion of the talk, and that is that memories are vulnerable to distortion, and confidence does not always correlate with accuracy, all right? This may come as a surprise to some of you, and we're gonna see why. We're gonna come back to the movie and Leonard talking to his colleague here, in crime, and he has the right insight about memory and memory distortion.

"Memory's unreliable.

Oh, please.

No, no, no, really. Memory's not perfect, it's not even that good. Ask the police. Eyewitness testimony is unreliable. Cops don't catch a killer by sitting around remembering stuff, they collect facts.

That's not what I'm…

They make notes, and they draw conclusions. Facts, not memories. That's how you investigate.

I know, it's what I used to do.

Look, memory can change the shape of a room, it can change the color of a car, and memories can be distorted. They're just an interpretation, they're not a record, and they're irrelevant if you have the facts."

Very profound statement, they're just an interpretation, they're not a record, and we're gonna look at what some of the evidence for that is, and we're gonna look at that in the context of an experiment that has to do with a rather tragic episode, and unfortunately, this episode has just recently been repeated. The episode we're going to look at is one from over a dozen years ago, and it was referred to as the Challenger disaster, and it was the NASA spacecraft Challenger that, upon launch, had a faulty component in the launching rocket, and the rocket blew up during the launch, and the spacecraft itself, the Challenger, crashed into the ocean and all of the astronauts on board were killed. As some of you may remember, there was actually a teacher, a guest astronaut, on board as well, and her school kids were there watching the launch.

Now, a fellow named Ulrich Nicer, who was a psychologist at Emory University in Atlanta at the time, asked the following question. What happens to memories for very emotionally-laden events? Questions were being asked bout what happens to our memories normally in terms of how they change over time, but one possibility was that memories for very emotional events are somehow insulated against change, and they are liable to have less distortion or less change over time. Now, in fact, Jim McGaugh and his group have been doing some considerable work in the issue of emotion and memory as well, and there's a very independent and exciting story to tell about that. I'm going to focus on just this study, however, for this evening.

What Nicer did was to go to his introductory psychology class and ask them the very next day after the Challenger disaster, tell me where you were, what you were doing when this event occurred, when you witnesses this event. And I'm gonna read two accounts for you here. This is the first account.

"When I first heard about the explosion, I was sitting in my freshman dorm room with my roommate, and we were watching TV. It came on a newsflash and we were both totally shocked. I was really upset and I went upstairs to talk to a friend of mine, and then I called my parents."

And here's the second account.

"I was in my religion class and some people came in and started talking about it. I didn't know any details, except that it had exploded, and the schoolteacher's students were watching, which I thought was so sad. Then after my class, I went to my room and watched the TV talking about it and I got all the details."

Now, Nicer did two important things for us in this study. The first is that he followed up with this same group of students about two years later and he asked them the same question. Tell me where were you, what were you doing, when the Challenger episode occurred. And what you see here are two accounts by the same individual, separated by two years. So you can see how some of this has really changed. Now, what Nicer did was to score the two accounts on a scale of zero to seven, where zero is very poor agreement between the two accounts, and seven is very good agreement between the two accounts, and shown here are the percentage of students in the study who obtained different aspects, different scores in terms of accuracy. So there are some students, for example, that scored sixes and sevens, others that scored somewhere in the middle. This is the important group for us and the interesting group for us, and that is 34 percent, about a third of the students in the study, scored zeroes and ones. That is, their account the second time had significantly changed from what they described the first time.

Now, Nicer is a psychologist, and he knows something about how memory works and how to cue memory, and he said to himself, well, probably the best cue that I can provide is to simply give the students back their original accounts and have them re-read those, and they will then be reminded of how it really was as opposed to what they're now describing. And so that's what he did, but that is not what happened. The students said no, the way I'm telling you now is how I remember it. In fact, some students said, I'm not sure that's my handwriting on that first one. They were so convinced and so sure that what they were describing was the way it was, as it had changed over these two and a half years, and there are some remarkable examples of lack of logic, that is, students would say that they were with a person that they would then say I didn't know at that period of time, but they remember their memory as being with that person.

So this issue of how memories change over time is a very important and dynamic one, a interesting one to ask about, and what Nicer did next was to ask the question the second time around, how sure are you that what you are describing is correct? He asked the students when he asked them the second time around to rate their confidence on a scale of one to five, where one is just guessing and five is absolutely certain, I am sure what I'm telling you is correct. And then he asked the question, what's the relationship between confidence and accuracy?

And these are just samples of the kinds of data that he found. There were some individuals who were quite confident and quite accurate, others who were not very confident, not very accurate, but here's the important group for us in terms of memory and memory distortion. These are individuals who were absolutely certain what they were saying was correct, and they are absolutely wrong about it. This has been replicated many times, and the correlation or the relationship between confidence and accuracy is not a very good one, as it turns out, and this is important especially for things like eyewitness testimony, where people are virtually certain that they're identifying the suspect accurately and swear to that, when in fact, as it turns out, they have been in error, as subsequently shown with DNA tests or some other kinds of pieces of evidence.

So it's an important issue for us, and an important one for us to understand. Elizabeth Loftus is here now at UC Irvine, and a large part of her career has been involved with aspects of suggestibility and aspects of eyewitness testimony and understanding what the dynamics are that are involved with this component of memory. Confidence is not a good way, typically, to judge whether somebody is accurate or not. We know that from discussions with our spouses, we know that, all right.

All right, we want to move to one other piece of information here. This is Elvis Mitchell, he's an interviewer, and he's going to be talking to Christopher Nolan in a moment, who is the director of the movie Memento, and Christopher Nolan is going to be describing, much like you are probably feeling now, that your memories are a little more vulnerable than you had previously supposed, and Christopher Nolan describes that in the process of making this movie and beginning to research aspects of memory, he has come to realize that his memory is more vulnerable. He calls it, again, short-term memory, but he begins to realize his memory is more vulnerable, and he begins to develop various strategies for dealing with that.

"I'm very interested in the process of memory and the way it can be distorted and all the rest, and I know that Guy, the same as me, in going through making the film, we went through an intense process of questioning our own memories and the way it works, and I sort of came out the other side, very much less confident of the way my memory worked than before, and then the script and Leonard's systems and the way the plot points come together relating to memory, they are just extrapolations of the way I try and help my short-term memory myself, you know, I write phone numbers with my hand and I take notes, and…"

So he's developed some strategies for helping his memory, and I have listed here some strategies that indeed have been found to be useful in some cases. One is simply decide what you need to remember. It sounds a little silly in a sense, but it's important for you to have a sense of your own resources and the kinds of things that you can take on. If you are working for a new company or needing to learn a lot about how that company works, you have a manual that you have to read, you can try and read and remember the manual, or you can try and find somebody who knows all the rules and regulations and just hang around with that person. But the important point is that you need to be able to focus on the kinds of things that are important for you in terms of what you want to remember. Paying attention turns out to be a critical one.

As you are watching and listening to me now, as you are focused, as you are paying attention, the more focused and the more attention you pay, the more encoding, presumably, is going on in the brain, and the more information you're gonna have available to you at the time of retrieval. Not being able to focus, being distracted, having attention difficulties as in the case of attention deficit disorder, or having difficulties focusing and concentrating, sometimes in cases of depression, for example, individuals who have those difficulties have a lot of difficulty with their memory, and the difficulty with their memory comes not from so much the difficulty retrieving information, but from the fact that they never got the information in initially, appropriately.

Use memory aids, make lists, cards. As he said, he writes things on his hands sometimes. There's no problem with this. People often are quite embarrassed or ashamed to think that they have to depend on some other kind of aid than their own memory, but it's not a difficulty. If you work with medical students, you'll find that medical students are doing that all the time. Their pockets are filled with notes and reminders and cues, they're dealing with patients, with a wide range of kinds of difficulties, and they need to be able to make decisions appropriately, it's life-saving for them, and so they use memory aids every way that they can, and there's no problem associated with this.

You'll notice, for example, I don't use any notes or anything with me as I talk with you now for 40 minutes or so. I haven't ever consulted any notes. You may wonder how that is, and that's simply because I make this stuff up as I go along. No, it's because the slides act as the cue, those are my reminders. Be consistent, another simple aid and assistance to memory, develop routines, as we talked about a little bit, aspects of motor behaviors and habits are spared, we didn't have time to go into the details of that, but being consistent and doing things in a similar way is a terrific memory aid, and this is probably the most important, keeping your mind busy and staying active.

If there is one piece of information that we have learned from studies on maintaining intellectual function later in life, it is that a key factor is continuing to remain active throughout your later period of life. Do not become a couch potato. You want to stay engaged, take up a new hobby, take up something that is challenging. You don't have to become expert at it, but it's important to continue to stay actively engaged in things, and we have a lot of data, and we'll come back to that point in just a minute as we come to the end of the talk. So you wanna keep your mind busy.

A woman, not long ago when I was giving a similar lecture, asked, well, what about things like computer chess games? Is that a good thing to be doing? And I said, well, computer chess games are kind of intellectually stimulating, you have to be challenged by the computer, chess is an intellectual game in its own rite, so that sounds like a pretty good idea, and she said well, what about if you're doing this several hours a day, doing this? I said, well, it's better than watching TV, probably passively, for several hours a day, and you're always being challenged.

As a magician, we use a lot of misdirection, and that, a little previous discussion actually was misdirection, it was meant to be a little bit informative, but it actually was misdirection to take you off task, and the task is the following: in the previous video that we just saw of the interview with the director, you may remember that there was a brief period of time when they cut to the audience and showed a person in the audience as the director was still talking, and the question is, what kinds of details do you remember?

How good an eyewitness would you make if someone came back to you now and said, can you identify that person in the audience? So let me just ask, female or male? Male, very good, all right, universally so. Hairstyle? Bald, short, how many people feel bald, just raise your hands. How many feel he had short, curly hair? Okay, good, good. So his hair color? Blond. How many people feel he was blond? Blond, a lot of you see blond, okay. What about his facial hair? Mustache, beard? How many people saw a mustache? Unshaven, how many people thought he was unshaven, clear, no facial hair? No beard, no mustache? A lot of you, all right. Was he wearing glasses? How many people think he was wearing glasses? Okay. Clothing? Did he have clothing, to begin with? Was it good quality clothing? All right, so think about what his clothing might have been. What about his build? Big husky guy? Short little guy? Okay. Are you ready? Now, I can't stop the video, so this fellow's going to appear on here for a short period of time, but you will have all your questions answered at that point. You were right, he was a male, by the way.

Last rule. This is an illustration that is very abstract in nature, and it could be any kind of behavior, many different kinds of behavior that we're looking at, and it simply makes the following point, and this has to do with aspects of aging, and it is typically, if we think of better performance as being up in this direction, younger individuals typically can perform better, often, than older individuals, and that is the rule. Generally, the younger you are, for various kinds of things, as long as some aspects are balanced in this in terms of experience with tasks, the younger you are, often the better you can perform. But there's an important caveat to this, and this is an important caveat that has been found in all of the longitudinal studies on aging and cognition and performance, whether it's the Framingham heart study that's been going on for over 50 years, the Johns Hopkins study, the Harvard study, all of these studies have found exactly the same outcome for one aspect of this, and that is that individuals in their seventies, eighties, and nineties can often perform just as well as individuals in their forties, fifties, and sixties, and it's an important one to underscore, individuals in their seventies, eighties, and nineties can often perform just as well as individuals of younger age.

And it's actually illustrated here, you may not have noticed it, but some individuals in this aged group are performing well within the range of the individuals in the younger group, and it's an important aspect to keep in mind. We know something about some of the variables that are important and that may separate out these individuals from these individuals. One of those is what we already talked about, and that is individuals who stay intellectually engaged are more successful in terms of cognitive aging. Individuals who stay socially engaged, more successful. Individuals who actually develop some routine exercise generally fare better. So there are a number--and, as you might suppose, diet has a role as well. All of the kinds of things that you might suppose are important turn out to be important and have some correlate with more successful aging.

Other things like drugs are available to us as well, to help our aging, and this is just to indicate that there are some new drugs being developed, a drug called Directra, and a dose of this given to males before leaving on a car trip actually caused 72 percent to stop and ask for directions, it's a all right, we won't go on with the others, but you get the point.

All right, we're gonna do one last aspect here associated with memory. This is a final test for you. I want you to just watch the screen. I noticed a lot of you are taking notes. I don't want you to take any notes on what you are going to see here, so just put down your pens and papers, and just watch the screen.

Now your task, for those of you who do have some way to write down these things, write down as many words as you remember seeing, don't worry about the order of the words, just write down as many words as you remember seeing. Those of you who don't have writing instruments, just try and think of as many words as you remember seeing. I'll give you a moment. Okay. We're just gonna do this with a show of hands, and those of you in the front, you have to just kind of jog around and look behind you and see all the hands going up. How many of you had the word bed on your list or remember seeing the word bed, if you'd just raise your hands, bed? Lots of you, great. Almost all of you, it looks like. Terrific.

All right, what about automobile, automobile? How many of you wrote down automobile or remember seeing automobile on the list? None of you? Anybody, automobile? None of you, all right. It was a trick question, good. All right, sleep, how many of you remember seeing sleep, hold up your hands, sleep? Good, just look around you, hold up your hands again for sleep. Look around, okay. Here's the list. Anybody see sleep on the list here? All right, how many of you remember seeing the word sleep, just hold up your hands again, if you would?

All right, so you've had another kind of memory distortion, this is called a false memory. You actually believed that you experienced something that you didn't experience, and it's not that difficult for these kinds of things to happen. Now, this list is designed in such a way that there are many words that are strongly associated with the word sleep, yet, nevertheless, you never saw the word sleep, even though many of you believed that, and if we translate this into the courtroom, you can see how vulnerable individuals can be, because I know that many of you are sitting there thinking darn it, he switched that list, 'cause I know I saw the word sleep on the thing, and you would be willing to swear, judge, your honor, I saw the word sleep.

So we have to be very cautious about our memories, all right? And that is the real message. We've come to two areas tonight, one has to do with clear and solid science about how the brain works and how memory is organized in the brain and the kinds of pieces of information that we know about with regard to how memory is organized in the brain, and to a second area of research that involves something that is, in many ways, less clear and less systematically studied, although, again, people like Elizabeth Loftus and others have really done a terrific job at beginning to bring to us a systematic set of studies that helps us to begin to understand these kinds of distortions, and it's important for us to understand that we do have these kinds of difficulties with our memory. I don't want you to leave here thinking that all is lost and that we have no future in terms of memory, but it's important to know that we do have these vulnerabilities.

I want to come back to the issue of aging and make one final point here in that regard, and this is a story that comes from a colleague of mine, Barbara Malamut, who is a neuropsychologist in Philadelphia and who studies aged individuals and individuals with Alzheimer's disease, and other debilitating conditions in aging, and she does cognitive testing with them and looks at them through their life. She was visiting a nursing home on this particular occasion and she came upon a very elderly woman and a very, very elderly gentleman sitting on the back porch of the nursing home, and they were having a conversation. Barbara didn't wanna intrude, and so she just stood by the screen door and listened in on the following episode.

The elderly woman was saying to the elderly gentleman, I'll bet you that I can guess how old you are, and the old fellow said, well, go ahead, you can try if you want. And she said, well, I need you to do one thing for me, I need you to just stand up, if you would. So the old fellow got himself up, and she said I need you to do one other thing for me, if you would, just unbuckle your belt and let your pants drop down. He said what? And she said, well, there's nobody else here, if you do that, I'll be able to tell you how old you are. So he did, he unbuckled his belt, let his pants drop down. She said, now, if you would, would you just turn this way a little bit? So he turned that way, now could you turn back a little bit, he turned back a little bit, and she said you are 87 years old. And he said, that's remarkable, that's exactly how old I am. How did you figure that out? And she said, well, you told me that yesterday.

And so it's an important lesson for us all that elderly people can still have fun with regard to memory and memory function. I hope we have had some fun, as well as learned some things about memory, and I want to thank you all very much for your attention and for your time. Thank you.

2003 LECTURE SERIES

"Ah yes, I remember it well..."Remembering, Forgetting and the Movie "Memento"

"Ah yes, I remember it well..."
Remembering, Forgetting and the Movie "Memento"