James McGaugh: I think it all changed with the invention of the printing press. So, once you're at the printing press, there was no pressure to preserve these important dialogues of the past. I mean, after all, why would you spend much time memorizing things if it's all written down? Then, more recently, the computer was invented, and now we have cellphones, and you wonder why you need to remember anything? You can just ask Siri, or you can get on Wikipedia, and you don't have to carry any information. So, just contrast that with the world of the ancient philosophers and poets in which, if you had to write it down, you have to find a piece of stone and a chisel in someplace.

Jesse Lawler: That's a great point. Do you think that there's effects that we're not even really seeing it, that we might just sort of be on the cusp of seeing, because somebody's changes are so new as to how we remember things? Are we basically creating cognitive deficits in ourselves by relying so heavily on our technologies?

James: Well, it may be deficits of a kind, but it's also a new knowledge of some kind. That is, should we be criticized because we learned how to use a cellphone? Should we be criticized because we're forced to learn how to type in order to use a computer or a cellphone? Every time we lose something like that, we're forced to gain some other technology. I don't know that the balance is out, but it's not as if we're losing skills. It's not as if we're dropping important, and thereby diminishing the brand. Things change.

Jesse: Tell me about some of your work with the significance of certain memories, why some things stick in our heads and others are gone 20 minutes or even 20 seconds later?

James: Yeah, this is an ancient concern. First of all, let me assert a premise, which I don't think anybody will doubt, and that is that memory is our most important ability. Memories are us, and memories are not about the past, memories are about the future. The reason we have memory is order to be able to predict what's going to happen to us in the future and do something about it. So, it is a puzzle, then, that as we go through life, most of the experiences that we have are not retained. They're just not.

For example, if you're wearing shoes, right now, I can direct your attention to the pressure on your left foot that's given by a shoe, and you would never remember that if didn't draw your attention to it.

All kinds of things are just rapidly forgotten, but some things are remembered, and they're remembered well. Alright, I'll give you two major reasons why we remember. One is repetition. Since it's been studied in the latter part of the 19th century and up until now, there's no doubt it's one of strongest findings ever in the history of psychology, and that is that repetition makes memory strong, and that's how we memorize things. We repeat things again and again until we get it right.

The other is that important events are remembered better than unimportant events, so that if you stubbed your toe, you would remember that toe more than you do at the present time. For most of my life, I've worked on the body and brain conditions that are involved in creating strong memories of unique experiences and investigated the role of stress hormones and the role of activation of very specific brain regions in generating that kind of strong memory.

Jesse: It seems like we're very likely to remember both strongly positive and strongly negative events, do we have a particular bias there?

James: No, we don't have a bias. It's just that sometimes the negative memories are more powerful in influencing us. It's easy to remember when we are insulted, when we failed, when we've had an automobile accident than it is when somebody gave an ice cream cone and says "There, there, that's nice," and "Isn't that a nice shirt you're wearing?" and so on. They just doesn’t have the same effect, but if you can equate for effect, then the memory will be equally strong.

Now, that's done in pictures are shown to people and people rate them as being slightly positive, moderately positive, or very positive, and then other pictures are negative, and people will rate them as being slightly negative, somewhat negative, and very negative.

When you control for that, then you find the ones that are very positive and very negative are equally well remembered, but you have to do controls to make sure that the presentations are equal in order to find out if they're equally well remembered, and they are.

Jesse: It seems like there's been a lot of recent research into proper forgetting, how the brain intentionally clears up no longer needed memories to make space for new learning. Tell us about the balance between acquisition of new learning and correct forgetting.

James: I think what we can do is to learn, and I can’t give you a magic formula and say, "Oh, I want you to think about this and then forget about it." What you can do is deliberately try to avoid thinking about, and then you decrease the repetition. I think it's a pretty good idea if you don't think about the names of any president for the next couple of weeks. If you can avoid doing that, of thinking about them, then you're going to avoid rehearsing, and rehearsing makes things strong. But, there isn't any magic way that you can just say, "Boy, I had a bad argument with somebody. I think I'll decide to forget that," you can’t do that.

So, the suggestions that there is, it may be slightly misleading, because the only way that I know of that you can without physiological intervention, the only way that I know of is simply to avoid doing something and focus other things, and let it rest. That's an expression that we use, isn't it? We just say "Okay, let it rest." Now, there are treatments, however, to the things that we can do that will impair memory, but that involves physiological treatments, and that's a different story.

Jesse: Can you tell us about some of those? Especially treatments that are based on isolating certain memories, not generally worsening a person's memory, but trying to be fairly memory-specific.

James: Let's suppose for a moment I wanted to erase your memory, this discussion that we're having. That seems unlikely, doesn't it? You might forget it slowly, so that two weeks from now, we won't remember too much about what was said, but if you were to have an electroconvulsive shock treatment immediately after we said goodbye, then your odds of remembering it very well go down considerably, so that if one can create amnesia by the use of electroconvulsive shock treatment, that's one thing that can be done. We do that routinely in animals and with other treatments as well.

For example, of we have this discussion and if I should give you a beta blocker - that is a drug that's used for heart treatment - if I should give that to you, immediately after we finish, that would weaken your memory of it. Why? Because adrenaline, which is what beta blockers block - adrenaline and noradrenaline - play a role in strengthening the memory, and they do it for some time even after the experience is over. So, if you have an experience, and the experience is sufficiently exciting, that will cause the release of adrenaline in the body and noradrenaline in the brain. Those increases will cause an increase in the memory that is stored. It's called consolidation. So, influence the consolidation.

As long as the increases in adrenaline and noradrenaline, occur within about a half an hour, there will be a stronger memory. The reverse, then, is if you have the experience and you get a treatment, a strong treatment with beta blocker, then that will block the formation of the memory, so you can make memories strong, or you can make memories weak, and that's been the focus of much of my research.

Jesse: What have been some of the methodologies in those studies?

James: Well, a lot. Let me first start with the animal, then I'll tell you some of the human experiments. With the animal experiments, what we do is train animals on a little task in which they simply walk into an alley, and as they reach a certain point in the alley, they get a little mild shock to their feet. We put them back the next day, at the start of the alley and ask them, "Would you like to walk down the alley?” Well, they might like to walk down after waiting for a minute, because they got a shock the previous day. But, if on the first day, we give them an injection of adrenaline immediately after that training trial, they won't go back the next day into that area for several minutes, maybe four, five, 10 minutes, showing that they have stronger memory of having received the shock because we give the booster of adrenaline, which they would have been given to themselves if it were a stronger shock.

Then, we do the opposite. We train them and give them a stronger shock, and then if we give a drug that blocks the action of adrenaline, which is a beta blocker, then that will prevent the added effect of the increased shocks. So, we can make strong memory, or a weak memory, or no memory just by varying the level of adrenaline in the blocker of adrenaline.

Now, the next step is to figure out this works in the brain. On the basis of a lot preliminary work, we got the idea that adrenaline acts by turning on a very specific region of the brain called the amygdala, which is in the temporal lobes of the brain, right in from the ear. It's on either side towards the middle of the brain. What we did then was to train animals and inject them with a little needle down into their brains and inject a small amount of norepinephrine, which is the first cousin of adrenaline, and we that immediately after they're trained, and we could produce very significant enhancement of the animals memory as long as that was administered within, let's say, 10 to 15 minutes after the learning occurred.

We did the reverse of that. We trained animals and put them in the beta blocker, and we could prevent the learning from occurring. So, we did the last of experiments of that kind in which we manipulated the level of noradrenaline in this very specific region of the brain to investigate its effect on the consolidation of memories that were created just shortly before the injection. What the injection showed was that we could regulate the degree of a fixation, or consolidation, or making firm the memories which were just established.

Jesse: I'm wondering how far that ability to disrupt the formation of memories -- you can think of spy movies scenarios where somebody could get a piece of information out of you and then keep you from being able to remember that you divulged something. But, in human testing, how extreme is that? Does the memory erasure really work that predictably?

James: This is all time-dependent. So, if the treatment is supplied immediately after the learning, there'll be a maximum effect. If it's given several hours later, it'll be ineffective. So, there's a gradient that is induced by these treatments. It's not possible just to take an established memory. For example, tomorrow, you decide that you don't want to remember this discussion today, and so you take a pill and get rid of it, that's not going to happen. If you want to eliminate the memory, you'd have to take a beta blocker instantly after we finish with this discussion right here. Even if you waited half an hour, that's too late, because the memory of this will have been consolidated by that time. So, you're dealing with a time-dependent fixation of memory after an experience.

Jesse: What's actually going on during that consolidation process within the brain?

James: We know a little bit about it, so here's the sequence that we believe occurs, that as you have the experience, the experience releases adrenaline and cortisol. It takes a while for the cortisol to become active, but adrenaline becomes active right away in order to influence the experience. So, in human subjects, we've done the same kinds of experiments we did with animals. We trained subjects and gave them beta blockers, and we found that that dampened the memories of things that they have just learned. Also, we did that with Cortisol, as well. So, that's the beginning of an understanding.

Now, what it does, it goes up into the brain, and activates this region that I mentioned that's an almond-shaped structure called the amygdala. There, that almond structure integrates the influence of both cortisol and epinephrine, which turn on the amygdala. If the amygdala gets turned on, then it has projections to many regions of the brain that are involved in processing and storing that information. So, it's an amplifying system.

It gets turned on and then it sends those projections, and in effect, it says, "Hey, something really important happened, make a memory. We got to keep that memory." That can be regulated by activation of the amygdala. In our experiments, what we've done is to influence the amygdala and show that memory has changed. Also, in human subjects who lack an amygdala, and there is a disease called Urbach-Wiethe disease that some humans have, in which the amygdala is lacking, and those people do not show stronger memory following emotional experiences.

Jesse: Yet, they do form the same amount of memory as regular folks?

James: Yeah, for regular memories, they're just like everybody else. But, if something very powerful happens to them, they don't remember that any stronger than an ordinary experience.

Jesse: Calls into question what your autobiographical memories, sort of your identity memories would be like if a trip to the grocery store was just as likely to get recorded for the long-term as like a big fight you had with your dad or something?

James: That would be a different kind of life, wouldn't it?

Jesse: Yeah, it really would.

James: Yeah.

Jesse: Can you talk a little bit about autobiographical memory in particular, and how that ties in with our sense of identity and who we feel like we are at any given moment?

James: There are two things: one is our autobiographical experiences create who we are. We live in a world which has been created by the experiences that we personally have, our personal record over our lives, our personal aspirations, our accumulations, that's all us, and we draw on that to remember the past. That's why you call it autobiographical. But, they create us, they create our personalities, they create what it is that we want to do, what it is that we expect to do, because all of these memories converge to create who we are.

Now, 17 years ago, a woman contacted me to say that she had a memory problem, and I emailed, and I wrote back and I said, "Well, this is a research institute, not a clinic. I can direct you to a clinic," and she said "Oh no, I think we should meet, because I don't forget." Well, we met, and we studied her for many years. By don't forget, what she meant was, "I don't forget my autobiographical experiences." She does not forget the events that shaped her life. She doesn't remember things that are not autobiographical any better than the rest of us do. But, as far as personal experience that has shaped her life, she can remember the day on which they occurred, the date on which they occurred, what happened on the days for almost any day of her life since she was 13 years old.

After we studied her for a while, we came to know other people like that. Now, we have an accumulated approximately 60 individuals who have what we call Highly Superior Autobiographical Memory, which means that they have a very strong, actually uncanny ability to remember what happened on most of the days of their lives since they were maybe 10, or 12, or 13 years old. They know what happened on a particular date, and they can do this with great ease. If I ask one of our subjects what they did on September 12, 1998, they would answer within about 2 or 3 seconds, and to the extent that we have the ability that we have to check on the reliability, or the validity of their assertion, we find that they are absolutely correct in what they assert.

This is a new category, people that have only been studied less than 20 years now, and we are using the subjects as a window into understanding unusual memory, which will give us more insights on how the brain works to create and preserve autobiographical experiences.

Jesse: Okay, so I'm going to ask what I'm -- here is a stupid question here. I feel like we all know the answer to this one, but it's interesting that the answer is what it is. Can memory fill up? Is there an upper limit on the amount of episodic memories that a person could conceivably store?

James: Well, I don't think it'll ever fill up. You know, we have literally billions and billions of nerve cells, and each of those has at least 10,000 connections. So, there's no capacity limitation. I wonder how that plays into autobiographical memory. I think I should point out that the autobiographical memory doesn't always consist of as many details as you might think. Think of it as what you and I remember about yesterday. You don't remember every single second of yesterday; you remember events that occurred, sequences of events, and if I interviewed you about yesterday, you'd be able to tell me quite a bit, but you wouldn't tell me second by second, and you wouldn't tell me about all of the experiences, you wouldn't be able to tell me about all of the auditory signals that you've heard throughout the day. You might say, "Oh, I heard a tune."

Jesse: It would be like the CliffsNotes version of the day.

James: Yeah, and so these people's memory, let's say, 10 years ago, usually about as strong as our memory of yesterday, but no stronger. It's just that, over time, we forget our autobiographical experiences for the most part, and they don't. So, one way to look at it is that they're not very good at forgetting, and for some of them, that is a problem because they have or may have had some very unpleasant experiences, and they wish that they could forget them, and that's the reason some people contacted me, because they have these very strong, unpleasant autobiographical experiences and say, "Please help me. Do something to get rid of them," and of course that they are old, there is nothing that I can suggest, nor would I, because we are a research institute, not a clinic.

Jesse: I imagine that you're probably getting a lot of questions in the last decade or so about posttraumatic stress disorder which definitely touches on what you were just talking about. I mean, that seems like it's an active area of research right now.

James: Let me say something about that. Let's go back to what I said about the strong experiences leading to the release of epinephrine, which makes them strong memories. So, that's well worked out both with animal and human research.

Well, a number of years ago, I got a call from Dr. Roger Pitman at Harvard University, and he said he had been reading this research and that he wanted to talk with me about its implication for posttraumatic stress disorder. So, we got together and talked about it, and then he went back to Harvard.

Then, the following study, he had nurses stationed at the major hospitals in Boston, and when people came in with an injury, or they may have had an automobile accident, they may have been mugged, they may have been raped, they may have a bad fall, something of the kind, and they were asked if they would like to participate in this study. If they agreed, half of them were put on a placebo, and half were put on a beta blocker and then two months later, he studied them for signs of PTSD, and the subjects that were put on a beta blocker as quickly as possible after the accident or injury had fewer signs of posttraumatic stress disorder than the ones that were put on a placebo, suggesting that we what had found with animal and human research applied then to the development of posttraumatic stress and suggested a possible way of preventing the development of posttraumatic stress disorder if subjects could be treated sufficiently early on after the experience. That kind research is ongoing at the present time with people continuing to investigate the role of beta blockers and other treatments to try to prevent the development of posttraumatic stress disorder.

Jesse: Are there downsides to taking a beta blocker that would make that not something that somebody would want to necessarily take cavalierly or prophylactically?

James: Not that we can see in our research. There have been a lot of published experiments by other investigators of memory and people who ordinarily take beta blockers, but they're just studying road memory. For example, in the laboratory, how good are you at learning nonsense syllables and things of that kind, and the beta blocker does not appear to do anything. Because, what the beta blocker does is prevent the enhancing effect of an important experience.

So, I would guess - although I have no data on this at all - that people who are on beta blockers are not going to have as good memories as they would like when their daughter gets married, the birth of a grandchild. That may not be remember as well by people who are on beta blockers as people are not, but that has not been investigated.

Jesse: What is the scientific consensus now on why autobiographical memory starts when it starts for people? Most of us have our first memory around four or five years of age, whatever it might be. But, why does it start then?

James: I think the other question is the same question, but it's turned around, "Why is it that we don't have memories of the first four years of our life?" and there are various hypotheses about that. Some are purely just biological that the nerve cells are not mature enough to hold that information for a period of time. There is evidence that new nerve cells in regions of the brain that are important for memory are grown during that period of time, and the ones that were involved in initial learning are no longer used.

There are lots of hypotheses of that kind, but the truth is that we do not have a very powerful, well-understood and well-supported understanding of why it is that we have what's called infantile amnesia, that is we do not have a memory of the first, let's say, four years of our lives. But, after that, autobiographical memory, at last, kicks in.

We're currently studying young children for their autobiographical memory, and we've identified several who are, say, eight or nine years old who have remarkable memories of what they did and what they experienced when they were five, six, and seven years old. Strong autobiographical memory is not something that's restricted to adults. It can also be found in children, and when it is found, it is truly remarkable. We have eight-year-olds who can remember, day-by-day, of what was going on when they were five, six, and seven years old. We even had a set of twins - they're now 13 years old - but we studied them when they were younger, and these are identical twins. One of whom has the ability and the other one does not, and you can imagine the disagreements that probably occur in the lives of these children.

Jesse: Do people in the real world with this ability tend to use it for anything? Is it something that they are able to use to their advantage, or is it just kind of one of those things like being able to wiggle your ears? That's interesting, but it doesn't really matter.

James: I think we have yet to determine it. I haven't thought of it about wiggling your ears, but it may well be more like that because, in our research, we haven't identified a strong advantage that occurs to people who have this ability, other than being able to recall a lot, and to entertain their friends and neighbors. One of them was on Jeopardy for 28 weeks, which is pretty good. But, some of them have even asked me repeatedly, "Please tell me what I can do with this."

Now, let's go back though. Let's suppose that we lived in a more primitive world. You see, now we're all organized. We have cellphones, we have computers, we have transportation, we have everything, which is well organized for us, and so there's no pressure for us to remember what happened in the past to the extent that we probably used to in the past.

So, I would ask the rhetorical question. I go back to the 12th century. Would this have been an advantage to anyone in the 12th century before the invention of the printing press, before there were newspapers, before there were computers, before there were cellphones. "Oh yes, I remember we did that on June 13th, and that's when the battle was occurring, and that's when they wrote the treaty," and so on. I can see some important value in a different kind of world. But, in our world today, the technology for retaining and using information is so far different from that, and maybe that the use has gone down simply because of the technical world in which we live.

Jesse: Well, if you've identified 60 people, even if you're only getting 1 out of 1,000, that's only 60,000 people worldwide out of 7 or 8 billion. To me, that says that this never must have been that useful of a trait, or otherwise, it would have propagated in the population, and we'd see more people like this.

James: The way I look at it is that if we could understand what's going on in the brain of these people, if we could really get detailed information, then we would have a new chapter of the neurobiology of memory, because it would say, "This is something that a brain is capable of doing," and here are the mechanisms that allow that to happen, and that's why I work on the problem, because I truly believe that, one of these days, we're going to find what is going on in the brain that enables this to happen and that we'll have a very different view of the brain process this underlying memory.

Jesse: Are there any things that you'd like to touch on with sort of the differences between an episodic memory and more procedural memories?

James: Sure. We're going to start back in 1890 when William James wrote his very famous textbook of psychology, and it is of interest to note that he had a chapter on memory, and very far along in the book was another chapter on habits - separated memory and habits into two different chapters. Now, isn't it that interesting? Wouldn't you think it was a habit as being a memory?

Jesse: Yeah.

James: It turns out that the nervous system honors that distinction, that what we know about the neurobiological processes underlying cognitive memory that is of learning of facts, information, autobiographical memory, and so on, the substrate of that kind of memory differs from the substrate of the memory of learning how to do something. So, you can distinguish at least two different kinds of memory simply based on whether it involves a motor system memory, or whether it involves cognitive memory, and that is a scientific discovery that was made many years after William James. I don't know whether it was on accident or on purpose that he separated these two chapters so far, and implicitly said, "There are different forms of memory." The implication is that these different forms of memory are based on different neurobiological substrates, and we now know that they are.

Jesse: And the third type of memory, I believe that's called semantic memory, the idea that, "I know that James Buchanan is the 15th President of the United States, but I can't remember exactly when I learned that. It doesn't have anything to do with me personally." Is that also neurobiologically distinct in the way that it's stored from the other two types of memory?

James: Probably. Although, the investigation of neurobiological substrates of those two is not well-examined at the present time. In human memory, the new techniques that were developed 20 years or so ago with imaging are attempting to ask that very question where if I put you in a scanner and said, "Who was the first President of the United States?" would that be any different from what you're saying am I asking you "Can you remember what you did the first thing in the morning yesterday?" Are those different things?

Then, you can ask, "How does the brain respond to those questions?" and then you can make inferences about the brain process underlying a well-learned piece of semantic knowledge, and it's retrieval differs from the retrieval of something which has been a personal experience. So, those kinds of experiments are underway.

Jesse: That would be really interesting to learn. What does the inner section between episodic memory and narratization or internal storytelling, what do those two have to do with one another? Because it seems, thinking about it, that the way that you're mentioning how our memory of yesterday is almost kind of like a CliffsNotes version of yesterday rather than the full data stream, that at some level, we must be crunching this down into a story about yesterday, rather the actual raw data?

James: Yeah, that's what retrieval systems do. I ask you what you did yesterday, and you don't say, "Pain on toe, flash of light, loud sound, pressure on rear end." You don't do it. It's a narrative. I got up in the morning, I did this, I went there, I saw this, I did that, and so on, and we are story tellers, because our lives are stories, and we retrieve in that form.

The kind of work that we typically can do in a laboratory is artificial. We give you a list of things to remember and then test them on you. Well, the only time that it happens in life is somebody gives you a list to go to the grocery store and buy something. Most of our remembering involves remembering important events that occur are sequences of events, and when we're asked to retrieve that information, then usually we're storytellers. That's just the way we're organized, and that's what we do.

Memory is not just a curiosity that's kind of interesting. How is it not nice to know about memory? It's kind of nice to know about how to paint and how to play a musical instrument - that's fun to do. No, memory is more than that. Memory is central to our existence, and you can see that in its clearest form when you see people undergoing dementia. They lose their substance, they become somebody they weren't before as a consequence of moving on into dementia. Why? Because for the most part, they're losing their memory of who they are, who they were, and without that, they can't plan for their future.

So, that's the importance of memory. Memories are us, and the terribly exciting issue for me, as an investigator - also, a very important issue for those of us who are undergoing memory decline because we lose the substance of who we are.