HIPPOCAMPAL HISTORY TOUR PART 14. May-Britt Moser (Part 2)

LN: Okay, next question. How did you experience the community that you were joining as young researchers in the late 80s? Early 90s, there was this community of hippocampal and related researchers. How did you experience it? I mean, as a social phenomenon as well as a scientific phenomenon.

MBM: Again, I think we were extremely lucky because we felt we came into a family and we brought our children into the family. So they suddenly got uncles and aunts around the world and we were accepted and supported and people were curious about us, maybe because they saw that we are so ambitious not to become something but to understand something. Then people get curious and want to join the team or to help. We have been surrounded by what we call in Norwegian, a lysengel, which translates to English as a light angel. Even people that we didn't see have also been supportive. In this way we survived. The sharks, like Bruce McNaughton would say, exist of course, but we didn't focus on the sharks, rather on the Angels and the family, which make neuroscience a comforting community. So, as all supervisors can be, Per was also sometimes difficult, but at the same time he was like this father. When we had big, big issues, he took on the hat of a doctor (he was trained as a medical doctor) and he was supportive, very, very kind and very, very nice.

LN: Like Hebb, very tough person, you know, on the outside. But very supportive when somebody had problems.

MBM: So when we look back, we have so much to thank him for because even as master students he brought his network to us and we could then get friends that normal students would never dream of even talking to. What happened was when we did our PhD that six of his students wanted to have their dissertation defenses in one week. . And again, I was knocking on his door and saying, Per, please let all six of us have our defense in the same week. This will then be a great event because you can make a symposium by asking all the international top scientists to speak. And since Per’s lab was really, really poor, he could arrange a symposium actually paid by the University since the internationally well recognized opponents (examiners) would be paid by the University (he was allowed to invite one international opponent for each defense). Per finally gave in and said, okay, we will arrange a Grand Slam! They can come here and we can celebrate. And it was in December, we did all the lectures in one week before the examiners arrived and then we arranged the the symposium and dissertations the next week. Finally we went deep into the forest on a sleigh ride. Per bought a lot of wine bought with private money and we had food in a forest cottage. Per was so happy and was singing old sailor’s songs (he was an eager sailor) and he told us fascinating stories. People are still talking about it. You can ask Carol Barnes, she was there.

LN: One of the opponents.

MBM: She was my opponent and Bruce was Edvard’s. And I had David Amaral. John O'Keefe was also part of the group of opponents, like Richard Morris, Kristen Harris, Bertil Hille and Roberto Malinow. What a feast!

LN: Sounds fantastic.

MBM: Yes. And it was so much fun. So, again, being thankful to Per that he did that for us and also for his enthusiasm. And also the way he trained us. Of course, we were very interested in the questions and the stories that you can make from answering a question. And he pushed us even further. If you don't have a story, then wait until you can be really sure that this is a good story and then get it out. And I think that was such good advice. And he said, have one good paper each fifth year and then you should be very, very happy. So good.

LN: Very good advice. All right. Last question. What advice would you give to the next generation? What should they be thinking about? What should they be focusing on? How should they go about their science? What would be the things that you would tell them? These are things you probably tell your students, but share with the rest of the world how you think young, up and coming scientists should approach their careers.

MBM: First of all, science is like art, so you need to have the passion for science or art or whatever you do because you have to put so much energy and work and sacrifices into science. But when you have the passion, then it doesn't feel like sacrifice, of course, because it will be your life, it will be your hobby, it will be your work. So that is one needs to be honest about what is your passion. Then find questions. And the question should be more general than a niche question, because then it will be interesting for a broader community and then to be able to tell a broader community about your data and your stories. It's also rewarding because then you learn. And then to do solid work. So where you publish in the end is not what is important, what is important is to do the solid work that gives this reputation that, okay, people can believe your story, they can replicate your results, they believe in it, and then build your environment stone by stone. Don't start too big. That's a killer. And then don't be married to techniques or methods. And then Per would have said go to those who developed the method or the best ones, the experts, if you want to learn a technique. When Edvard and I were PhD students, we discussed the institute that we were going to build. This was the decision. And then Edvard said, we are not going to be mediocre, then it's not worth it. And I agree(d) with him if you don't feel like going for it fully, don’t do science.

LN: Perfect answer. Great advice. Big, big questions, but small steps. Solid steps, but big questions. Thanks so much May-Britt.

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#HippocampusGurus

HIPPOCAMPAL HISTORY TOUR PART 15: Edvard Moser

LN: So Edvard Moser, what got you interested in the hippocampus in the first place?
EM: That is because May-Britt and I started out at the Institute for Neurophysiology in Oslo, so we were interested in neuroscience. We had decided that we wanted to start research in that area.
LN: I'll interrupt right here. You were trained as psychologists, so what got you to jump from psychology to neuroscience.
EM: Okay. I’ll start a little bit earlier. Starting with psychology was just kind of coincidence, I was interested in behavior and so on. But then having started with psychology, it was pretty clear to me, and I think the same with May-Britt, that much of the current psychology was really not very experimental or not very mechanistically oriented, with few if any links to the biology that makes cognition possible. In the psychology of the time, there was cognitive psychology and then you had all the clinical psychology, and cognitive psychology used mostly conceptual models with boxes and arrows, and they explicitly avoided neural activity in the brain as an explanatory construct, much like the behaviorists had done. But then there were some exceptions, in the textbooks there were 2 or 3 pages about Hubel and Wiesel and there were some people interested in this kind of work at the Institute of Psychology. We found out there was one professor – Terje Sagvolden – who worked at the Institute for Neuropsychology who was a psychologist. We were then admitted to his group.

LN: Would have been around 1990 or something.

EM: That was actually at the end of the 80s because it was in parallel with our studies. Studies in Norway for psychology took seven years and that was far too long to wait. Since we knew so early that we wanted to do experimental psychology, we did that on the side and then worked with Terje Sagvolden on hyperactive rats and animal models for ADHD for about two years and then found out that it wasn't quite what we wanted. But we observed at the same time experiments on visual cortex recording from single cells by Paul Heggelund in the basement. And we also participated in seminars. And there was Per Andersen, and we discovered that we were in one of the world´s best places for research on the mechanisms of memory in the hippocampus. The institute – and at this time Per´s group in particular – had been the Mecca of the hippocampus, people came from all over the world to work mostly with Per. And it still had that atmosphere. It was sort of not so much as it had been a few years before, but still very international. And we felt excitement. There were talks about LTP and we had our psychology background and wanted to know what all this was about because they were mostly interested in the synaptic mechanisms and underlying molecular pathways, while we wanted to explore the role of synaptic plasticity in memory and behavior.

EM: So it was a convergence between Per´s interests and our own, and that defined what we wanted to work on. And then finally one day we decided to leave the hyperactivity studies and work on the hippocampus instead. We went to Per Anderson and asked whether we could start in his group, which was a big group. He didn't have space, but we did convince him in the end that he should try to have us around. And he gave us a task of designing or building a Morris water maze. Because he had for a while had the idea that he wanted to include behavior in his group. And then we came with a psychology background. So it was an opportunity that he wanted to test out. That was our way into the hippocampus. And at the same time we still had people like Theodor Blackstad and Terje Lømo around, as active researchers. So we were acquainted with all the history of early hippocampal research by being there.

LN: Right, Right. Did you have interaction with Kaada? Was Kaada still active at that point?

EM: No. Kaada had left several years before. We only heard about him. But the only one who was left from the Kaada tradition was Sagvolden, who was a former student of Kaada. Right.

LN: And that would explain his interest in hypertension and more emotional, motivational things. Yes.

EM: This came from when he worked with Kaada. He worked on the lateral septum and aggressive behaviors. So that's where he came from. He developed the interest for emotions and behavior. His analysis was very behaviorism oriented. This was good for us because we learned rigorous experimental and statistical methods.

LN: Was about to say, was that training, even though you moved away from it, was it nonetheless sort of helpful to you down the road.

EM: Absolutely. It was not for the reasons we maybe thought at that time, but it gave us excellent training in behavioral studies, which was extremely useful because even if we didn't agree with the sort of black box approach, it taught us how to do experiments, taught us how to analyze data statistics, and also even using simple mathematics. And that has come back in more recent years and always been a good thing. But I am still glad that we switched to hippocampus because it was so much richer in terms of research questions and the hippocampus had reached the stage where it was possible to build bridges between physiology and psychology.

LN: Right, right, right. Okay. So that's how you got started. Obviously people know a lot about what you've done ever since. So the next question that I am interested in was aside from your work, when you looked out at the field and as you were developing in the field, what were some other inspirations that took you down the path you followed?

EM: There are many inspirations, but there was one I wanted to emphasize, having thought back on it and again, this is somewhat retrospective because I didn't realize it at the time, but I think what really has shaped my views on the hippocampus or my approach to hippocampus were the computational studies that had taken place on hippocampal activity, many of which explored dynamics in large cell populations, although mostly at a theoretical level only, in the absence of the kind of data we have today. Much of that I learned through Bruce McNaughton, and his inspirations go all the way back to Marr in 1971 and Hebb in 1949. But I think with Marr and later Hopfield and Amit, Gutfreund and Sompolinsky, and Rolls and Treves, they showed how you could actually explain much of the dynamics in memory in terms of attractor networks, more like discrete attractors. You could explain many of the properties of memory in terms of pattern separation and pattern completion, which was quite popular in the 80s and 90s. So that got me interested. But some of our early training was experimental, with John O'Keefe. It was short but very, very, very decisive to our careers. Of course, following this training, we wanted to understand place cells or spatial coding in a more mechanistic manner, following up our dreams from the days of psychology studies. And that's where Bruce McNaughton especially had an enormous influence on our thinking. And he also introduced us to continuous versions of attractor network theories, which he had contributed to conceptualizing, along with others. The theories have a long history, and my understanding is that while they emerged well outside the hippocampus, it was very quickly understood how they could account for head direction cells, and with Bruce, place cells (grid cells had not been discovered yet).

EM: It was several people, Amari had touched upon it, and then there was a long break, until Sompolinsky developed a ring attractor model for orientation-tuned cells in the visual cortex, and then that was applied to head direction cells. Bruce was very prominent in this, along with a few others, and it all was happening at the same time around 1995. And then Bruce took that further to explain place cells at the time in two dimensions. And then of course there was a natural extension of that to grid cells when we came on board, as grid cells were periodic and could be explained by dynamics on periodic surfaces, unlike place cells. But I think all this early development of computational neuroscience in the hippocampus is somewhat exceptional. Computational neuroscience has many roots in visual cortex and early sensory systems rather than high-end cortices like the hippocampus. But I still think the hippocampus comes as a good second to the visual cortex in the development of functionally oriented computational neuroscience because it is quite structured with organized circuits, and there were many, many observations and single cell recordings that could be put into a common framework. With single-unit recordings, we had the necessary resolution for asking mechanistic questions. So I think that is a major part of the reason for the success of hippocampal research, that it was possible to take that computational and neural network mechanistic turn at a much earlier time than for most other brain regions.

LN: True. I mean, all the reinforcement learning stuff came afterwards, basically. I think you're absolutely right about that.

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HIPPOCAMPAL HISTORY TOUR PART 15: Edvard Moser (Part 2)

LN: So you've referred on a number of times to sort of this being driven by wanting mechanistic explanations. I mean, what in your own life do you attribute that to? Does this go back to when you were a kid in school? Not everybody says, I want to figure this thing out mechanistically.

EM: No, you know what? That was when we had our interview with Andersen, we came in there and then we said it was interesting, the psychology, but it was too descriptive. And then we told him we want to do mechanistic neuroscience, and that's what we're going to do, a PhD with you to start introducing mechanisms. So I think the idea was very early, but, it's just an idea that I think I've had since the early days that I wanted to understand how neurons actually produce behavior, right? So that's what everyone, every psychology psychologist wants to do now but at the time when we started most psychologists lacked the concepts and were not trained in physiology, whereas physiologists often lacked insights about behavior, often treating behavior as just one extra parameter to include in a battery of experimental tests. It has been the case that many psychologists have just been afraid of it because it's a new world. So many of them have stayed out of the neuroscience field. But I think that's the goal, should be the goal of every psychologist in the end.

LN: Right. And when you went back and read Hebb, you realized that that was what he was saying from the very beginning.

EM: He was really a giant saying all of that at that time. It's impressive. And even the concepts and ideas at the time when there essentially were no neural data at all. So he should have received a Nobel Prize.

LN: There were many who thought that at the time.

EM: It was theoretical.

LN: Yeah. You don't typically get it for theory. And he was not much in the lab. I mean in the years that I knew him, he had great ideas and he had good post-docs and students who were carrying out the research that he encouraged. But he himself, I don't think I ever saw him in a lab coat or in, you know, in a lab situation. That wasn't what he did, more or less. He must have done that back in his early days at the Yerkes. He did do experiments back in the 30s and 40s, so obviously he was experimentally oriented, but he was also very descriptively oriented watching his animals a lot, basically. All right. That's great.

LN: So the third question then was, was more about the kind of community, sort of the hippocampal community and how you experienced it. Was it a welcoming community? Was it a competitive, you know, kind of the sense of the community and some personal anecdotes that might have influenced you and how you yourself developed in the community?

EM: So I think what strikes me is how it has changed. There is a before and an after. The before is when I came into the field. I really perceived it as a split field and it was very much about the space people and the non-space people. And I found that disturbing really, because I knew people on both sides. So just by coincidence, on one of the sides, I met Larry Squire very early. He visited the institute. We even invited him to come there and he came and we had lots of interesting scientific discussions with him, but his was a largely human derived view of the world and then I thought that all made sense. But at the same time, we also knew about studies of spatial learning that Richard Morris had conducted and, all the literature that had been so elegantly summarized in your book, a long history that finally made sense when reconceptualized into a cognitive map framework. And that converged on showing that there was something special about space. And of course then the discovery of place cells. And we got to know John at the same time. And it didn't quite make sense because I then learned that, well, it is 3 or 4 labs on the one side doing place cell research and then there were some other labs trying to find all the non-place properties. And of course the answer is both so, so often, right? And that's also something I actually learned when I was in the early days in Oslo thinking about LTP, because then there was this discussion about presynaptic or postsynaptic mechanisms, pre vs. post. Or course, it is both, but that wasn't obvious at the time.

LN: So mechanistically it wasn't obvious, but conceptually it had to be right.

EM: But it was so emotional. That is the thing. And I felt it was so emotional with the spatial versus non spatial debate at that time too. At the same time, I was neutral. I came from the outside. I didn't really have anything invested in it, but I thought that it was much more interesting just to understand how the hippocampus works both as a memory machine and a space representation machine. Whatever it was, it would be interesting. Now so many years later, there is a generational shift and there are many new people who have come into the field. We haven't really invested in one or other sides and find that, yes, it is very much dominated by space, but there are these other things encoded together with it, just like you actually said in the book.

LN: That part wasn't paid attention to.

EM: No, it's just like Freud. Right. And Freud also was much more nuanced than his descendants.

LN: Yeah.

EM: So I think then it makes much more sense. And then with the discovery that we made with grid cells and so on in the entorhinal cortex, that to me appeared like a purer low dimensional spatial representation, whereas I think the hippocampus has that, but has all the other things on top, which it requires for producing memory. It's come much more to a point now where it all makes sense, both the spatial and the non-spatial starting points, one coming more from the human-research side, the other coming more from the animal side. And neither are wrong unless they go to the extreme and say that the other one is not true. So that is about the community. I felt it was split and that was a little bit discouraging in the beginning. But I think coming from that physiological tradition in Oslo, I was more interested in the physiology and that was a good thing, I think. And now I think the hippocampal field is like a friendly community when I go to conferences and I think people talk to each other, share data, trust each other to a quite large extent. So if you compare with some fields, for example, like some areas of molecular biology, where you don't dare to share your data, we share our data in this community many years ahead. Posters at SfN and people are generoous, because you don't scoop your colleagues result really. I mean, you respect their work and at least wait for a long time until you pick it up if you know someone else is doing the same. So I think it's a friendly and constructive community. To some extent this was the case also in the early days, at least in subcommunities; it's just that if you went into one or the other sides, you heard all these stories about the other side. That was not a healthy thing, but I think the community worked itself out of it and that's great.

#Hippocampus #HippocampusHistory #HippocampusGurus

HIPPOCAMPAL HISTORY TOUR PART 15: Edvard Moser (Part 3)

LN: Do you have any specific anecdotes you remember from the early days that sort of gave you this, the sense not just of the scientific community, but the personal interactions? I mean, is there any moment when somebody did something particularly nice that helped you along your way? You know, no names necessary, but you know, from a kind of a more interpersonal perspective. What was it like?

EM: Yeah, I know. I am not sure I have a specific episode, but I have obviously received help from many people in the field. I am very thankful to both Larry Squire and Eric Kandel. Independently of each other they came to Per and convinced him to publish our early work, which was on dorsal-ventral functional differences in the hippocampus, which to him as a physiologist, viewing the hippocampus in terms of lamellae that were similar from one end of the hippocampus to the other, it was very uncertain whether it was publishable at all, whether he should actually shame his name by putting that out there. They both came and told Per you should publish it. And we did, and it was received well. So I think that was the difficulty of starting out in the physiology institutes where we had to rely on outsiders to come and tell. And then many, many came in after a while. With Per´s help we established connections to the outside world. And then we had our PhD defenses, and many in his network were there, like Bruce McNaughton and Carol Barnes and that created connections to the Tucson community. And John O´Keefe and Richard Morris. We went to Richard and John allowed us to go to UCL very shortly afterwards. So it was our time in Oslo that really gave us connections out in the world. And it was a community of people who tried to help each other and certainly I think, May-Britt and me, which was extremely important for us because we came from families that had no academic background really at all except that my grandfather and so on were ministers, and we needed that extra advice, at a time when formal mentoring did not exist in Europe.

LN: Ministers!

EM: That's the only academic.

LN: Right? It's a special kind of academic.

EM: But they appreciated the value of books. A few books at least.

LN: Yes, that's impressive in that sense. I mean, it's not that typical, I think.

EM: Not typical. But therefore it was so important to get advice and the diverse viewpoints. It was actually good. And in the end, we can make our own decisions, but at least hear what other people think and not being dominated by anyone in particular.

LN: There was a unique feature about your situation, which is that is that it was really two of you, and that that's a little bit unusual. I certainly didn't have that in my early days. John O’Keefe didn't have that and also not Richard Morris.

EM: We could bounce back and forth, both ideas, but also the more practical things, how to survive in in this world. And certainly that was useful. While it was good, at some times it was also tough at other times. Many coincidences that we survived and finding the right supervisor was also not an obvious thing. So hyperactivity was not our thing. And then we went to another lab, which was not successful, not the place we wanted to be, not the type of work we wanted to do. But in the end we understood that Per Andersen really was an excellent scientist, and was highly regarded in the international neuroscience community. And I think it was very helpful to work with him. Of course, that also had its challenges. He had a strong personality with very strong opinions on many things which we didn't always agree on. But nonetheless, it was very good training.

LN: Well, Hebb was like that, so to be in the environment where you had to deal with him was a little bit like having to deal with Per.

EM: One had to navigate both the science and the person.

LN: Yes. Exactly. Last question. Advice to the young. And mostly it's young, up and coming scientists who are reading these interviews. What's your advice to someone getting started in the field now? What should they be focusing on? What should they be paying attention to? What should they make sure that they acquire knowledge about and so on? I mean, what would be your advice to a budding young neuroscientist?

EM: I mean, many, many things. One of the biases is that I would encourage them to learn all the new methods that come from physics, statistics and machine learning computation to handle data at a large scale. So that is all important.

LN: Brenda Milner said exactly the same thing to me about learning new methods.

EM: But that´s only the first part of the suggestion. At the same time, it's so important not to just collect data but you also need to know why you do it. And you need to, you need theory, concepts and ideas to guide your questions. So one of the things where I maybe I'm a little bit extreme compared to many others is that I really believe in hypothesis driven research. You need to know why you're studying something. You need to have an overall question and then you go and look for it. And very often it's wrong. You find something else, but that's okay. But the so-called data driven research, although of course all research is data driven, in which you just collect data and then happen to find things, I find very inefficient and also not fun really. You want to have fun, and you have to try to make sense of things.

LN: But when you say hypothesis, how specific a hypothesis are you meaning.

EM: That can be at many levels. I think it can be at many levels of specificity. There are almost no theories in neuroscience, but models, at least specific models that say how you can obtain functions on neural patterns out of certain kinds of connectivity or activity. That's very useful and then you go back and forth and test it out on the computer alternating with experiments -- that I find very useful. But I also think you don't need to have a model, but you at least need to have a question. That question can be very specific and sometimes it's too specific. And of course you don't find what you want, but you can also have the question like when we started out in the entorhinal cortex, we wanted to find spatially tuned cells because we believed they would be there, but we didn't know what they would be like. No clue. But that was a starting question.

LN: That was enough.

EM: So it doesn't have to be more than that. But I think sometimes, you know, in this technological revolution, you see some papers where people collect lots and lots of data, but then it's not really useful to generate anything. It's very hard to get the more mechanistic understanding of what's going on. So I think that's a balance one always has to work on. So I would advise young people two things. Do learn to use these new techniques, but at the same time make sure that you have a theoretical foundation and place it in relation to the literature. Literature means the latest research. So there is so much done before, which often isn't on the internet. Knowing what has been done over the years is useful. And then one would also see that actually the basic questions that have been around in the hippocampal field are still very much the same. They are not solved but we know a lot more than before. You don't understand really how the hippocampus makes memories and there are many ideas around. But this most accessible region is still poorly understood, I think. So there's a lot to do.

LN: There is a lot to do. Well, this has been very helpful.. Thank you.

#Hippocampus #HippocampusHistory #HippocampusGurus

@nadel another really great interview!! Thank you so much. I love that you ask them about the advice for new neuroscientists - that’s really kind and useful.

Who is next on the list?!

In November 2019 I attended the meeting of the Psychonomics Society in Montreal, and took the opportunity to arrange an interview with Brenda Milner, for my history project. When I arrived at the Montreal Neurological Institute where I thought the interview was going to happen I was informed that instead I would be taken to Brenda's apartment some blocks away, and that I had to limit my time with her to about 30 minutes, given her age. What actually happened was a free-ranging discussion that covered much of her early history and was more of a two-way conversation than an interview. The taped conversation was transcribed by a graduate student at Arizona (Alana Muller) who I thank for doing this hard work. Then I sat on it for the COVID years and beyond, but now I have priced it up a bit and will post it next, in a linked set of postings. The quality of the transcription is far from perfect, but I hope readers will find it informative. I could have taken out a lot of the conversational chatter, but decided to leave it as close to the original as possible.

Some notes: Peter Milner was married to Brenda Milner for decades and as my comments in the interview make clear, Peter was a wonderful mentor and an incredibly well-informed scholar. He was also the co-discoverer (with Jim Olds - whose name came up in Phil Best's reminiscences) of brain self-stimulation -- the original finding of so-called reward centers in the brain. Yet virtually no one of the current generation knows about Peter at all.

Another name that came up was Mort Mishkin -- another giant in the field who died a few years ago. His contributions were enormous.

I hope readers enjoy this rather lengthy interview and get from it some idea of just what an amazing person Brenda Milner is. Still going strong at 105 I believe.

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#Hippocampus
#HippocampusHistory

HIPPOCAMPAL HISTORY TOUR PART 16: Brenda Milner

Nadel: Let’s just put this here and see what happens.
(Milner laughing)
Milner: Anyway, I don’t know what I was trying to tell you.
Nadel: About lobotomies. You got caught up in frontal…
Milner: And when I came, well I was teaching at the French University, University of Montreal,
Nadel: …Right…
Milner: In those days, this was the heyday of lobotomies, they were doing some frontal lobotomies in the Department of Psychiatry at the Allan Memorial along with the Montreal Neurological Institute (MNI) and so that was my first...but what was I going to tell you about. You mentioned lobotomies.
Nadel: Well, I mentioned that you know this is focused on hippocampus but of course your first love was the frontal lobes.
Milner: That's right, yes.
Nadel: But what I'm trying to write about is, or trying to gather is really the hippocampal story, trying to track it.
Milner: That's fortunate because that's what people ask me about more than about the frontal lobes.
Nadel: I know. Probably you'd like to talk about the frontal lobes.
Milner: No, no, no, not especially. The hippocampus is a sort of more straightforward in a way. I don't mean that it's straightforward.
Nadel: Sure.
Milner: But it you know, there's been so much research done and there's animal work and human work.
Nadel: The animal work has really changed it.
Milner: And the anatomy, too you know. It's a very, it's a beautiful structure.
Nadel: That's it, isn't it?
Milner: Yes.
Nadel: That's the same thing that John and I wrote somewhere. It attracted attention from pharmacologists, anatomists, physiologists who didn't care about the hippocampus. But this beautiful structure that's easy to study, that has this great lamination. You could be attracted to it.
Milner: It had to do something important, right?
Nadel: Yeah, exactly. (Nadel laughing) And then the frontal lobes, In the 1940s they were still trying to figure out if the frontal lobes did anything, right?
Milner: That's right. Well that was the backswing, right, from having studied it. I was one of the people in that group, probably, because there had been so much written that the frontal lobes were the seat of, I was very sarcastic about that.
Nadel: No, not you. (Milner and Nadel laughing) So what I did was, I picked a group of maybe 20 people, 25 people who are my generation or even a little older. Ok, a little older (Nadel laughing). And people that I knew, that I interacted with.
Milner: Not Hebb. Not going that far.
Nadel: Not going back, no. People who were still alive. People that I have been connected to for a long time. And just sent them a series of questions and I sent them to you too but I'll repeat them. And I wanted just to get people to sort of give a sense of what got them excited about the hippocampus, how did they get involved in studying the hippocampus and so on. So I had a... you may forget them. I'm going to ask you them just for...
Milner: I think I've got them there.
Nadel: So how did it happen that you first got started, what got you involved in the hippocampus? Tell the story again. I'm sure you've told it many times. It's in there.
Milner: It's there. It's in that book you know.
Nadel: Well, repeat it again, roughly speaking.
Milner: That's more accurate right?
Nadel: Ahh who knows?
Milner: You know about memory.
Nadel: Ah I know. (Milner and Nadel laughing). But as you recall it now.
Milner: Well, it really began with Hebb giving me a chance to go up to the MNI to study patients. And Hebb told me...
Nadel: And that was pre-HM, right? All of that was before HM?
Milner: Oh yeah. Oh yes, yes, yes.
Nadel: That was way before HM?
Milner: Way, way before then.
Nadel: You were looking at interesting patients with memory problems.
Milner: Well, I hadn't even got to that. I was teaching at the University of Montreal.
Nadel: Right, right. You were saying.
Milner: I realized to get anywhere in North America you have to have a Ph.D. which wasn't true in England you know.
Nadel: Right.
Milner: And so he sent me up to study patients at the Neuro but he said to me no psychologist can survive for long at the Montreal Neurological Institute. And he meant, you know, because Penfield was a very autocratic character.
Nadel: As they all were. Neurosurgeons in particular.
Milner: Well, I like neurosurgeons. I like Penfield.
Nadel: Okay, fair enough.
Milner: In a way. But well I guess Penfield was rather an intellectual neurosurgeon or something so it gave weight to it. He knew perhaps how to do it to be effective. I don't know.
Nadel: Right.
Milner: I mean he had built up the institute after all.
Nadel: Right. And I would say you survived the MNI pretty well. (Milner and Nadel laughing) Hebb was wrong about that!
Milner: Hebb was wrong about that, yes, yes. Did you know Hebb?
Nadel: Oh yes.
Milner: Yes, well, curiously about Hebb is that he had this reputation of being very aggressive because he could be very blunt.
Nadel: Yes.
Milner: But the bluntness was a defense against shyness. He was an extremely shy man. I'm not shy particularly, I don't think, but he was a very shy man and he was very, I think when he knew that he, because you see in those days - it was difficult in those days was that Penfield was totally inconsiderate. I don't mean that he was hostile. It's just that he did what he wanted to do and thought it was important. He did it when he wants to do it and he would call in on a Sunday night and tell his resident, “Oh I've decided to do Joan Smith on Tuesday rather than Mary…” or whatever you know. So it was terrible because in order to do my thesis, I had to have the preoperative data on these patients.
Nadel: Ah so those kinds of things, yeah.
Milner: This was my problem, that I couldn't just see the patient for the first time postoperatively and talk about the effects of the surgery. I had to know the patient beforehand and so on...
Nadel: Which means you needed some...
Milner: And I meantime had a full-time job at the University of Montreal, don't forget that.
Nadel: Right.
Milner: So I was teaching and I had to be at work at the University of Montreal. I had to have a lecturing schedule there. So during the weekends and Penfield was going to operate on the Tuesday, I had to know in advance who he was going to operate on. And he could just change like that. So this is where Roberts was such a help because he was the chief resident and he believed in psychology. Really believed in psychology. And so he would call me, you know, to bring me the latest Penfield decision. You know the change from Penfield to Rasmussen was just hell to heaven you know because Rasmussen was so considerate and he would call and he'd say I'm thinking of operating on Mrs. Smith on such and such a day, but he said so I'd like you to tell me when you're through with the psychology test so that I can schedule the operation, because in those days that put the patient totally out of action.
Nadel: Right.
Milner: They had this, they were alright lying like that but as soon as they had to sit up they got this terrible pressure headache. And they got nauseated, you couldn't work with them.
Nadel: Right, right, right.
Milner: So you really had to feel your way around when they were going to be doing the operation.
Nadel: And it was hard or impossible with Penfield but changed completely - when did Rasmussen take over?
Milner: I'm not sure. That's where you'd really have to look it up.
Nadel: Yeah, okay, I'll go back and I'll check that. Okay.
Milner: Because I honestly don't know, don't remember.
Nadel: Yeah.
Milner: I got my Ph.D. in '52 didn't I. But that was Penfield's - I'm not sure. '54? I really don't know.
Nadel: Okay. Don't worry about those details. Okay, so you were full-time teaching at University of Montreal.
Milner: Well that was my job, yes.
Nadel: That was your actual job.
Milner: I was actually paid (Milner laughing).
Nadel: You were paid to do that. Were you a graduate student at that point?
Milner: Uh well no, I had come from England, right. We didn't go in for Ph.D.s in that day.
Nadel: Right, exactly. So you were full-time.
Milner: People at the U of M - well I suppose, the great thing about me as far as the U of M was concerned was that I spoke French, you know. I'd never been to France. I'd never had enough money to go from England to France, but I just happened to be good at languages and I spoke French. My mother had taught me French and my school. And so the first job I got was at the U of M and teaching neuropsych, teaching psychology in French. And the students were wonderful. They would certainly say, “Madame Milner, do you want to know a new word?” and they would write something up on the board and it was really nice, you know. Yes, yes.
Nadel: So then how did you get involved in research with Hebb?
Milner: Mort Mishkin was a student here then at the same time, right.
Nadel: Right, right.
Milner: Well the psychology department at McGill was in complete shambles when I came over in '44, because all the people had been involved in the war effort and they were in Europe, the department was nothing. And the U of M in a sense was better because there were more scholars and the McGill department was really zero. And then they got George Ferguson.
Nadel: Of course.
Milner: As he'd been teaching statistics and they got him at the department. I think it was Ferguson who recruited Hebb but I could be wrong about that.
Nadel: Aha, and George was still the head of the department when I was a grad, when I started as a graduate student. He retired during that period of time, I believe.
Milner: That's right. Yes, yes.
Nadel: Okay. And I remember the parties at George's house and the terrible poems that he would write.
Milner: Oh that's right! I've got some here.
Nadel: Yeah, I have the book as well.
Milner: You've got the book! (Milner laughing.)

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HIPPOCAMPAL HISTORY TOUR PART 16: Brenda Milner (part 2)

Nadel: I've got the book of his poems, I know it. Yeah, right. Okay. So you were connected through Peter - Was Peter working?
Milner: Peter was at Chalk river. Peter was a physicist, right. I mean he was at Chalk river. I was writing to him and telling him all about what was going on and he got interested and he decided to change fields and he gave up the job at Chalk river and he came here and he got a job in the physics department right here, and to pay his way through doing psychology. So then he, because he was...
Nadel: Got it, got it. So he was one of the first who went the physics to psychology route.
Milner: Yes, yes, yes, yes.
Nadel: I knew that but when you said it in historical context, he was one of the earliest to do that.
Milner: His original degree of course was in electrical engineering in Leeds.
Nadel: Interesting. Interesting. So you know that O'Keefe started as an engineer also.
Milner: What?
Nadel: John O'Keefe was an engineer, an aeronautical engineer.
Milner: Oh I had forgotten, I must have known that.
Nadel: prior to going to graduate school.
Milner: I didn't know that.
Nadel: Prior to going to graduate school, he worked for Grumman Aircraft on Long Island.
Milner: I see.
Nadel: And somehow he got, I actually don't know the progression.
Milner: Yes, because I didn't know really, I think I knew you (Lynn) before I knew John.
Nadel: Yeah, definitely. John was working with Melzack and they were in a separate building over in a little house where the cats were kept in the basement.
Milner: That's right. So I had nothing to do with that.
Nadel: They had very little interaction.
Milner: I had nothing to do with Ron Melzack.
Nadel: They had very little interaction with the rest of the department until we moved into the Stewart building. Then everybody moved into that building together.
Milner: Yes, yes.
Nadel: Right. Then we got together with Melzack and his students. That was in '65 or '66. But for the first, when I was here in the beginning, we were over in the Donner building, which is where Peter was.
Milner: That's right.
Nadel: Right? And then all the people who did rat work really make up the group in Donner.
Milner: Well I had a little office in the Donner building.
Nadel: Oh did you?
Milner: Yes, yes, yes.
Nadel: Oh okay, alright. Alright, so you went, so then you started working with the patients...
Milner: Yes.
Nadel:...on Hebb's recommendation.
Milner: Yes.
Nadel:...along with his warning that you wouldn't last very long there.
Milner: That's right.
Nadel: (Nadel laughing). Okay.
Milner: No psychologist could survive for long.
Nadel: Right, but when you started, you started working with frontal lobe patients?
Milner: Uh, it's all in my…
Nadel: Yeah alright, don't repeat if it's not necessary. When did you first hear about hippocampus? When did that first sort of appear on your radar screen?
Milner: Well of course it was because of the operations. Penfield was doing these operations for temporal lobe seizures.
Nadel: Right. Already?
Milner: There were seizures coming from the temporal lobe, yes.
Nadel: But he was doing unilaterals, wasn't he?
Milner: But yes, of course.
Nadel: Right. Staying away from the language. Staying away.
Milner: Oh yes, well that works very well. Stimulation. The patients were awake and the stimulation works very well for those. They have some dysplasia after the surgery which they don't anymore, because that's just sort of technical advances. But he began just, he was very cautious, Penfield, at first, but because these lesions were unilateral, and also because in fact temporal lobe epilepsy usually comes from, not always it's temporal lobe gyrus too, but often has its origin in the medial structures.
Nadel: Right.
Milner: If you're going to treat temporal lobe epilepsy surgically, you've got to be prepared to do this.
Nadel: Right.
Milner: And so we were not expecting this global memory impairment.
Nadel: So when did you first notice a memory impairment?
Milner: You have a little bit of verbal memory difficulty after a left temporal removal and you have a bit of aphasia that you get better on. That's part of the course. It was going to cure your seizures, it's okay and it’s probably transient. But it was, this PB, it's all written up in detail but it was suddenly this, PB came first. PB was very instructive because PB was an electrical engineer from the states who had already had a lateral near temporal removal, I think, before I met him and it hadn't controlled his epilepsy and Penfield was beginning to realize that he, it's not true of all cases of course, but in most cases if you were hoping to treat the epilepsy surgically, you had to be prepared to go after the medial structures.
Nadel: Yeah.
Milner: And this was probably a good exchange if the thing was really unilateral, it was probably a good exchange for control of epilepsy.
Nadel: Right.
Milner: But where he ran into trouble was with this patient that in fact had damage...
Nadel: On the other side that you didn't know.
Milner:...on the other side yes. And had this global memory impairment.
Nadel: And PB was that...?
Milner: That was PB.
Nadel: PB. So PB preceded HM?
Milner: Oh, PB and FC preceded HM. But HM was not a Montreal patient.
Nadel: I understand that.
Milner: I have to defend Penfield! (Milner laughing).
Nadel: Exactly. But why did HM make it clear that it was the hippocampus that led to memory deficits and not PB...
Milner: Well because HM had bilateral removal...
Nadel: Because it was the bilateral removal.
Milner: It was a removal. It wasn't a removal on one side with a bit of abnormality on the other. It was a bilateral removal of it.
Nadel: So in other words, you already were kind of down the path of thinking medial temporal damage resection is going to cause memory problems. You had reasons to think that already prior to HM.
Milner: Yes, now well there you just really are going to have to read because I'm now sure if I've had the- 1952 I went down to see Scoville's patients. I saw lots of Scoville's patients.
Nadel: Pre HM?
Milner: Well, he had done, this is a kind of psychosurgery I suppose, he had done bilateral amygdala and he knocked out - Scoville, funny man. I actually liked Scoville but he was a bit of a rascal. But he was very, very, good, I'm sure he had very good parietal lobes and very good motor skills. He was an excellent driver. Everybody said, “Oh you let Scoville drive you around when he drives so fast”. I said, “I'm very confident” but in the end, of course, he died in a traffic accident...
Nadel: Oh I didn't know that.
Milner:...when he was 85. His son called me to tell me that his father had died after a traffic accident. He was driving. He shouldn't have been driving at 85, no. But he wasn't 85 when I knew him. He was in his late 50s and he was a very good driver. But...
Nadel: See why did you...
Milner: And so Scoville was, he was quite a character well, but Scoville was very flattered, very pleased with the idea of contact with Penfield. Penfield was quite a figure.
Nadel: He was, yeah he was a big figure.
Milner: Yes, yes. Scoville was an extremely successful run-of-the-mill, well very good spatially, but you're a surgeon, you know, doing lobotomies, doing all sorts of things you shouldn't do.
Nadel: But with no particular academic profile.
Milner: No, no, no, no. He was from Yale. He was a bright man, but not really a scholarly man I wouldn't say. But he loved the idea of this contact with the MNI you see. And so that was how I got invited to go and test any of his patients I was interested in. I went all over the place. I went to Chicago to follow up some of his patients.
Nadel: Oh I didn't realize that there was so much interaction between you and Scoville and that, and his patients in that way. And all of that was before HM or contemporaneous with HM?
Milner: It was probably contemporaneous I would think, yes, yes, yes.
Nadel: Oh, that's interesting. Okay. So when did you first meet HM?
Milner: Well I'm trying to say, usually I...
Nadel: Again, I'll look but... If you...it's okay.
Milner: '52 was my thesis but he wasn't in my thesis. You know, you have to look it up. But '54.
Nadel: When did Sue come into the picture? That's years later.
Milner: Well, Sue was my graduate student.
Nadel: Sue was your graduate student. But that was...
Milner: And she was working on touch.
Nadel: Right.
Milner: I remember that because I was so delighted you know. Doreen Kimura had worked on vision and audition. But anyway, we thought, it was always vision or hearing in the temporal lobes and I remember Sue Corkin coming to me... you knew Sue right?
Nadel: Oh, I knew Sue very well.
Milner: And she came and she put her hands together like this and she said I want to work on touch. And I said bless you! (Milner and Nadel laughing).
Nadel: So Sue's former husband, where she got her name, Corkin.
Milner: Yes, Bud. Bud.
Nadel: Bud. He was my college roommate.
Milner: Oh really?
Nadel: I roomed with him as a second year undergraduate.
Milner: Oh really?!
Nadel: Yes! That's when I first heard about HM. I knew...
Milner: (Milner laughing). That's so funny!
Nadel: I tell this story all the time. I tell the HM story and it kind of runs through Scoville to Hebb to you to Corkin and then at the end I say and oh by the way, I roomed with Corkin's husband...
Milner: That's really funny.
Nadel:...in 1962 and that's when I first heard about HM.
Milner: That is really funny.
Nadel: I was not even a psych major then. I was at that point doing biology. This was before I had gotten involved in psychology. So I roomed with Bud Corkin. That's how I knew Sue.
Milner: That's so funny.

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HIPPOCAMPAL HISTORY TOUR PART 16: Brenda Milner (part 3)

Nadel: And that may have been some connection to how I got caught up in psychology. I mean maybe that got me excited about it. It's possible. Okay, so Sue was your student?
Milner: Yes.
Nadel: She was interested in touch?
Milner: Yes.
Nadel: How did she get to HM?
Milner: I don't know. Her thesis was all about touch...
Nadel: Right.
Milner:...and Sue was remarkable. You know that because we had absolutely no money, you know, there's no money from the institute for research and no we had no money really. And Sue went to business around Montreal. She did this and she said she wanted to raise some money for McGill for research. And she collected money for her own research that way.
Nadel: Wow.
Milner: That was pretty good.
Nadel: That was pretty good.
Milner: Yes, yes.
Nadel: That was like a kickstarter. You probably don't know this. I mean people do this now all the time on the internet.
Milner: Oh, yeah there was no such thing then.
Nadel: They raise money for causes. Well, Sue was a very determined person.
Milner: Oh yes.
Nadel: I mean she, when she set her mind on something, she did it. Okay. So she got put on to HM as a kind of like post Ph.D. ...
Milner: Treat.
Nadel: Treat.
Milner: I think so, as I remember. You shouldn't trust my memory. I mean, you know my age. My memory is not good obviously.
Nadel: Oh well, it's pretty darn good so far.
Milner: No, maybe good for my age but look at my age.
Nadel: (Nadel laughing) Right.
Milner: I mean there are other things...
Nadel: Come on, you're only 101. I mean, really (Nadel laughing).
Milner: I always think of myself as 100. It's so funny you should say that because I was just clicking over that book and I suddenly say this about 101 and I thought I'm not 101. (Milner and Nadel laughing).
Nadel: How can that be?
Milner: I thought I was 100.
Nadel: Oh, that's amazing actually. Alright, so tell me a little bit about the history behind the monkey experiment. So you did that experiment in 1960 where you tried to replicate HM's surgical damage in the monkey's. This was Rasmussen, Orbach, Milner. Was that the three? Just three of you, right?
Milner: Yeah, I forget now.
Nadel: Yeah, very famous paper obviously. Very important paper and the one that I always reference because you didn't see any memory deficits. So how did that experiment happen? This is a piece of history. How did that experiment happen?
Milner: I don't suppose I remember. I mean I think you're better off reading.
Nadel: You talk about it in there?
Milner: I don't know. I haven't reread that.
Nadel: I do not remember seeing any discussion of how it is that that experiment got done. Whose idea was it do that, for example? You know, let's make a monkey model of HM's...
Milner: No, but I mean that's the way everybody was thinking about animal work. Animal work was everything. Nothing was worth anything without a monkey model in those days.
Nadel: Right.
Milner: I mean that wasn't original. It was obvious you had to have monkey model.
Nadel: Okay.
Milner: You know, I think what you're losing because you're younger is the fact that this was all before we had neuroimaging.
Nadel: Ah no I know, yeah. Right.
Milner: Makes a huge difference. With neuroimaging you could now see what you're dealing with in the human brain but in those days you couldn't until the patient died and then it was already changed because the brain had deteriorated.
Nadel: Exactly right. No, no, I think I sort of understand that although it was the same for me. When we were writing the book in the 70s, we had no data about any - I mean we were talking about Korsakoff patients. And then without any knowledge of where the damage was. There was very, there was very little precise information about where the damage was.
Milner: Yes, yes, that's true.
Nadel: Right, exactly. And you were shooting in the dark. You had no idea what you were trying to do essentially.
Milner: Yes, yes, yes.
Nadel: Alright. So what happened when the experiment was done...
Milner: Which experiment?
Nadel: - the monkey experiment, 1960 -
Milner: Oh, yeah.
Nadel: -and you didn't get a general memory deficit. What did you think? When you were looking at the data and you sat there and you look at the data and here's HM and here's the monkeys with supposedly the same lesions and you don't see any memory deficits. Well, what did you say? What did you think?
Milner: I don't remember. We obviously we were not using the right tests, I suppose was what we thought.
Nadel: That's clearly what turned out to be the case.
Milner: Yes, and that was the case.
Nadel: Yeah. Right. So you didn't give up on the idea that the hippocampus might have something to do with memory.
Milner: Well, I mean, no. Of course not.
Nadel: Clearly not, right.
Milner: Well, I mean.
Nadel: Alright. Okay.
Milner: And there were, I mean you're asking, your straining my memory too much now because it was such a long time ago but there were several individual cases in the clinical literature in England and so on of people who had memory impairment and then they had an autopsy...
Nadel: And there was some indication...
Milner: That's right, that's right.
Nadel:...of temporal lobe involvement, right? Yeah. Right. Alright, so that's how you got involved in the hippocampus and when Sue started working with HM, did...
Milner: Well Sue was my student.
Nadel: Sue was your student. But when, but when Sue left and continued working with HM...
Milner: Well then she moved back to Boston.
Nadel: She moved back to Boston. Right, exactly. I visited her quite often in those years so I know a fair amount of what happened then. So did you and your students here continue to work on temporal lobe much after that or was it, were your interests more again on frontal lobe at that point?
Milner: It's hard to say. I mean, obviously worked on the patients that were coming through. I really liked Dr. Rasmussen very much and we were working very much with his patients.
Nadel: So it was kind of luck of the draw, whatever you got to see.
Milner: Luck of the draw. It's a luck of the draw, yes, yes.
Nadel: So the motor learning stuff. Do you have any sense of how you got involved in...
Milner: Well that was just that we had to test all... well that was obvious to me as a psychologist.
Nadel: Right.
Milner: You have somebody, you can't go around and say somebody has no learning ability, no memory ability. And then you say did you test them, you know? And you haven't tested them, you can't just sit like you and I sitting now.
Nadel: Sure.
Milner: I find, oh you don't remember who brought you here today? Oh you've got a double memory impairment. I can't do that, you know. You've got to...
Nadel: You've got to dig in.
Milner:...look at different kinds of memory and motor learning is a nice thing because it's something that you can quantify very nicely you know, more than a casual conversation. Do you remember what we talked about yesterday? This is something you can very systematically draw graphs and things like that.
Nadel: Sure. But historically in that era, in the 1950s, 1960s, motor learning wasn't really referred to as memory. I mean it was this kind of...
Milner: Well, it's learning.
Nadel: It's learning.
Milner: But learning is what I was working on. Learning and memory. You can't be, you can't be tested for memory of something you don't know.
Nadel: Absolutely right. So you benefitted from entirely growing up within a Hebbian framework, psychologically.
Milner: Probably, and before that in England, don't forget I started in psychology.
Nadel: Exactly, but you were not infected by the American behaviorism that was popular at that time?
Milner: Oh no, no! It was not popular here at all.
Nadel: It wasn't popular here at all.
Milner: It wasn't popular in England...
Nadel: And it wasn't in England? Alright.
Milner:...and it wasn't popular here.
Nadel: When I, I teach the history of psychology now...
Milner: Yes, yes.
Nadel:...so I'm very caught up in these. So at that point in time, people in America, you didn't talk about memory, actually. The word was rarely used.
Milner: Oh I see. Well I've always talked about memory because of...
Nadel: Bartlett.
Milner: Well, yes.
Nadel: Ok, so go back to in England and in Canada, people could talk about memory and they understood that memory is the result of learning and if you have learning you must have memory.
Milner: Yes, that's right.
Nadel: All of that's pretty obvious.
Milner: That's obviously true.
Nadel: That's pretty obvious. But that was not what American psychology was about in those years.
Milner: Well, they said they were studying learning though.
Nadel: They said they were studying learning, but the word memory was, if you look, if you do a search on the word memory, it disappeared for 50 years. People didn't talk about memory in America very much for 50 years. So...
Milner: They talked about the laws of learning, that's right.
Nadel: Exactly right. It was all about the laws of learning. And this notion, so motor learning was not...
Milner: Yes.
Nadel: Memory in those years was simply what we now call episodic memory.
Milner: Right, right.
Nadel: That was the only thing you could use the word memory for then. And it didn't get...
Milner: (Milner quietly sneezing). Excuse me. I don't have a cold. I don't know what made me sneeze.

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