A research talk with Lynn Nadel on the ecological act of cognition & navigability, particularly related to the #hippocampus. Andrea & Lynn discuss the 'superhero lair' of #McGill in the early years of #neuroscience & follow Lynn to #UCL where he & O'Keefe write their famous book. #hippocampushistory #lynnnadel #johnokeefe #mcgill #ucl
#HippocampusHistory
Some of you may be interested in this second part of an interview I did recently, with Ben Kuper-Smith.
HIPPOCAMPAL HISTORY TOUR PART 16: Brenda Milner (Part 8)
Nadel: I have to go I'm afraid. Wow.
Milner: Well, it's been lovely.
Nadel: This has been really lovely. Thank you so much for taking the time.
Milner: Oh no, it's so nice.
Nadel: This is so nice for me. We haven't had a chance to talk for a while, in a while.
Milner: No, not for ages and ages. On one of those trips when we were in Europe at the INS...
Nadel: Yeah, well you know we used to be at that meeting a lot.
Milner: That's right.
Nadel: But then, you know, you stopped going and we've stopped going.
Milner: Oh you've stopped going?
Nadel: We haven't been for years. We'd like to go again maybe one more time because we have a lot of friends but you know, most of our friends are not going anymore or they're not there you know.
Milner: Yes, that's right.
Nadel: Time moves on.
Milner: Time moves on, yes. So you're going back now.
Nadel: Well I have a student...
END OF INTERVIEW
At this point I had to run to meet a former student (at Schwartz's deli for Montreal afficionados), but not before Brenda showed me her kitchen and where she had tea every morning.
HIPPOCAMPAL HISTORY TOUR PART 16: Brenda Milner (part 7)
Milner: Ah yes.
Nadel: Ok, so how did you end up there?
Milner: Well I went to Cambridge in mathematics.
Nadel: Right, I think I knew that.
Milner: And I, well first of all, the thing that I'm really good at is languages. (Milner laughing)
Nadel: Right, you started with that, yeah. (Nadel laughing)
Milner: But I didn't want to do languages because I thought I could do languages without going to university or anything and I loved maths, this was in high school so I wanted to go on a nice school. They all wanted me to go to Oxford. I had to get scholarships, right? We've no money. My father died when I was 8 you know. So I was going, the idea was that my school didn't like me to do languages, get a scholarship to Oxford and so on. I said I don't want to go to Oxford, I want to go to Cambridge. (Milner and Nadel laughing) And I don't want to do, I didn't do languages. I was sure that somehow or other not to the same level, but that I would be able to do languages on my own, you know, whereas...
Nadel: Sure. But this was during the war.
Milner: What?
Nadel: This was during the war.
Milner: This is before the war.
Nadel: This was before the war. '30?
Milner: This was when I was in high school. So I insisted, but of course I probably was better at languages than at science. (Milner and Nadel laughing) I had to get the scholarships I had to, you know, to get to Cambridge. And I soon discovered, you see, when I was at high school, I thought that mathematics, well it was arithmetic, geometry, algebra, right, I thought it was a matter of logical reasoning. Well, or course it is, to some extent. And I thought I was logical and could reason well, which is probably true, it was true. But this is not enough. What I did not realize when I was at high school, I did not realize how perceptual mathematics was. I just didn't realize you had to look at something and make sense of it before you could have the privilege of reasoning about it. I could do the reasoning but I couldn't organize what I was looking at. And that was quite a shock you know.
Nadel: How are you with visuospatial things?
Milner: I'm terrible.
Nadel: Yeah, me too.
Milner: Are you?
Nadel: With the Shepard Metzler rotating figure thing? I'm terrible at that. I have very bad spatial awareness like that.
Milner: It's good to get out of mathematics if you can. (Milner and Nadel laughing)
Nadel: Exactly! (Nadel laughing)
Milner: I just thought it was pure reasoning, you know. I put reasoning on a kind of pedestal. Oh it was so beautiful and logical!
Nadel: And it's perfect. It always works out.
Milner: You can't see what you're supposed to be reasoning about, you know. Oh, I didn't know you were like me in that.
Nadel: Yeah. I had a funny interaction with a mathematician when I was at Dalhousie which is where my last contact with Hebb was when he had retired to Dalhousie, to Chester and he was coming into the department at Dalhousie on a weekly basis.
Milner: I see.
Nadel: And I was at Dalhousie for two years.
Milner: So you've known Hebb more recently than I have.
Nadel: I was at Dalhousie for two years from '77 to '79 when Hebb was coming in every week at Dal so I saw him on a pretty regular basis through those years.
Milner: Oh that's nice.
Nadel: And during those years I was friends with a mathematician and I said to the mathematician it must be great to be a mathematician. You know everything is so logical. It's all so reasonable. I mean two and two equals four. And then he looked at me and he said are you crazy? (Nadel and Milner laughing) See you don't understand mathematics at all. It is not like that at all. It's just as messy, it's just as confusing, it's just as everything as your field is. Don't be misled. It's exactly the same, and ever since then, I've understood.
Milner: Well it was quite a shocker to me, I must say.
Nadel: Yeah, it was a shocker to me. I always held mathematics up as this special thing.
Milner: So I got out of it.
Nadel: You got out of that. Right. And then you went into behavior.
Milner: What?
Nadel: So how did you get from mathematics into Bartlett's lab?
Milner: Well I went from mathematics to psychology, well what field am I going to change to. Psychology was a moral science and language and moral science's director of studies unit was in my college, you know and I think it was a sort of why not try psychology kind of thing. It was a terrible disappointment to my mother you know. My mother was, I'm good at languages but that's just a pleasure on the side, but my mother I get this... My father was a musician and he wrote for his living but with a guardian but my mother had a real talent for languages and I think I inherited that from her. But the science just somehow I felt that languages were things that you could do on your own.
Nadel: Right. But psychology was you know just by default, I mean it just seemed like it might...
Milner: More or less, by default. Yes, moral sciences. It was moral science, right?
Nadel: Yeah, the moral sciences. And there still is a department of moral sciences there by the way.
Milner: Is there?
Nadel: Yeah, yeah.
Milner: It was a lucky break.
Nadel: It was a lucky break, exactly. So what was Bartlett...
Milner: Well I started in mathematics you see and I knew I should not go on in mathematics. I got through part one mathematics but I didn't color myself a mathematician. I knew that it was time to get out.
Nadel: Well that was a wise decision.
Milner: Yes.
Nadel: What was Bartlett like?
Milner: What was Bartlett like? He was very tall. (Milner and Nadel laughing)
Nadel: He was like J Z Young, a tall imposing kind of person.
Milner: He had a big big smile when he was smiling. He had a wide mouth. I didn't have any close any relationship with him, it was always Zangwill influenced me most and his lectures on perception, I really liked his lectures on perception. I got really interested in vision perception that I was interested in first and I wanted Zangwill as my supervisor and I managed to get him as my supervisor rather than those, there was a woman in college and she would have been the logical person to be my supervisor because she was in my college but I wanted Zangwill because I'd been impressed by his lectures.
Nadel: And you got him.
Milner: And I got him and that was...
Nadel: And it worked out.
Milner: It worked out very well. Very well.
Nadel: Alright.
Milner: So I had to write an essay for him once a week, right.
Nadel: Oh really?
Milner: Yes.
Nadel: And did he correct it?
Milner: Oh yes! Well, they read it I think. So in Oxford, you read the essay, you write a page essay.
Nadel: You write it and read it.
Milner: Yes, you don't do that in Cambridge. You give it to him the night before and he reads it. Then he comes back and criticizes it and puts comments on it, yes.
Nadel: And this is a one-on-one kind of tutor?
Milner: One-on-one, although there were some that were two-on-one and some that were as in my case, I was one-on-one.
Nadel: Yeah, we don't do that now. Yeah that isn't the way it works now very much.
Milner: So one-on-one is good.
Nadel: I'm afraid we have run out of time.
Milner: Aww.
Nadel: This could go on for quite a while. (Milner and Nadel laughing)
Nadel: Well this gives me a very, a better impression of how you came to be the person you are, you know. The curiosity and the good observer put together.
Milner: You know, I think that's right. I think you're absolutely right that because I'm not at all a theoretician you know.
Nadel: But that’s fine. I mean a good observer who's also curious.
Milner: Yes.
Nadel: So curiosity's an interesting word. Curiosity implies a certain knowledge, like what are you curious about.
Milner: Oh yes! Yes, yes, of course, of course, of course. Otherwise you won't even, no...
Nadel: Curious isn't random.
Milner: It's in a context, yes.
Nadel: It's in a context, right and that context channels that curiosity and if you also happen to be a good observer...
Milner: Yes, which I am. I know I am.
Nadel:...which you are, that's a very very good combination. Some people are one, some people are the other. But you put the two together.
Milner: I hadn't thought of that.
Nadel: Yeah, that's a powerful combination, as we have seen.
Milner: In many ways. So it means that I'm sort of good at empirical things.
Nadel: Yes, right. Exactly right. Well, and that's what science is about in the end.
Milner: Well it's the basis of it, right?
Nadel: But you need the context, but again you have that context. It sounds like, I mean your background, you had the right context, the right way to think about things, right? Without having a theory, you can't - everyone has a theory. You have a metatheory...
Milner: I don't have theories.
Nadel: Well you don't have a theory, explicit theory but you have a general sense about the way things work.
Milner: Oh, yes. Possibly.
Nadel: Right, and that's a kind of a metatheory about the way the brain is organized, networks matter, I mean that's a kind, you know those are...
Milner: Well I don't know that I had that back in 1936.
Nadel: Probably not.
Milner: I don't think anybody did.
Nadel: I don't think anybody did.
Milner: No, no, no.
HIPPOCAMPAL HISTORY TOUR PART 16: Brenda Milner (part 6)
Milner: That's right.
Nadel:...given the setting you were in, you had to be even more practical than your average...
Milner: Well that's true. That's true.
Nadel: You were forced to actually pay attention to the...
Milner: Certainly a certain kind of patient, that’s right.
Nadel: That's an important fact actually.
Milner: Of course, I was very lucky to have the patients.
Nadel: Well, you were in the place where very good patients came through. You were lucky to be in the spot you were in.
Milner: Yes, yes, yes.
Nadel: Right, that's true. So the advice you would give to a young, any of the young people. You know, I'm here at a meeting, there's a meeting going on.
Milner: Huh?
Nadel: The Psychonomics Society is meeting here in Montreal. That's why I'm here.
Milner: Right now they're meeting?
Nadel: They're meeting here. This week.
Milner: I see.
Nadel: And that Mary is here at that meeting and she's involved in some stuff at the meeting and I'm not. Anyway, so there are lots of young people there.
Milner: Yes, yes, that's great, yes.
Nadel: And they, as happens at these meetings, they sometimes get together with older, more established scientists for advice. So your advice to a young up-and-coming would be methods, pay attention to the methods? Learn everything you can about the methods?
Milner: Yes, yes, I think so.
Nadel: Hmm, hmm. What about the theories? What about understanding the...
Milner: You see, I'm not a theoretician. I've never been a theoretician.
Nadel: Right, you don't want to talk about yourself that way.
Milner: I meant, no I don't mean I don't want to talk about it. I'm telling you what my intellectual gaps are. I have working hypotheses, I have these little bits of theory that you need to guide your research, of course. I'm not doing my research just because oh well everybody is working on T-mazes now. I'll do a T-maze. I'm guided by some curiosity, some I've got a lot of curiosity, but about everything. (Milner laughing)
Nadel: Yeah, that's obvious (Nadel and Milner laughing). You always have.
Milner: Yes, I always have. I'm nosey!
Nadel: Yes, you've always been like that! (Nadel laughing)
Milner: But I've never been one for some overarching...
Nadel: For grand, grand pontificating. You're not a pontificator.
Milner: I'm not. Not at all. I'm very British.
Nadel: Yeah, exactly right. Ok. But you said before and I think it's important. You said it's very important to understand the behavior.
Milner: Oh yes.
Nadel: So it's not just the methods.
Milner: Oh no, no.
Nadel: Included in the methods is a good understanding of the behavior.
Milner: Well I'm a good observer. I think that's been true.
Nadel: Ah ok.
Milner: What, are you writing that down?
Nadel: Yes, I'm writing that down because it's a very, yeah...
Milner: But I think I am a good observer. I think this is true of me in my ornery social dealings you know.
Nadel: In life, yeah.
Milner: I think I'm a good observer.
Nadel: And that's really important in science.
Milner: Well, probably in any science.
Nadel: In any science, but all the more so in a science where you're looking at behavior and you're trying to figure out what's going on here. Yeah.
Milner: But it's certainly, you see, I'm interactive and extrovert yet some do like Peter who is an introvert but he was a very good observer too you know.
Nadel: But a different kind of person.
Milner: But he didn't feel he had to do anything about it you know.
Nadel: Yeah. (Nadel laughing) Yeah Peter. See he is of course the one I had most to do with.
Milner: What?
Nadel: Peter is the person I had the most to do with when I was a graduate student.
Milner: Oh well that was lucky for you. (Milner laughing)
Nadel: Very lucky for me. Very lucky for me. I mean he was my hero as a graduate student because I, you know. DB was a nice guy but he...
Milner: Very nice guy.
Nadel:...but he didn't understand what I was working on. He had no idea so Peter was my source.
Milner: Peter was quite a deep thinker right?
Nadel: Yeah, he was. And that book, of course he was writing his book, this is the 1970 book...
Milner: That's true, that's true.
Nadel: ...during those years. And we were reading the chapters as graduate students in the seminar. That was very lucky to be at McGill at that particular time. It was a very lucky thing and Peter was really the hero for all, I think for all the graduate students.
Milner: Well that's so nice.
Nadel: He was the most accessible.
Milner: Oh yes, he would be.
Nadel: He may have been shy but he was the most accessible. You could go and ask him anything and he also knew the literature. It was mind boggling. It was... did he just like spend all of his time reading? He seemed to know everything that had been done.
Milner: Oh it's so nice to hear that.
Nadel: It was, he was such a, he was so impressive in that way. I mean if I had to model, if there was anybody I said I'd try to model myself after of the people I had connected with, Peter would be the closest.
Milner: That's lovely to hear.
Nadel: He was really, and I think a lot of the students felt that way. He was the one you could always go to.
Milner: Well he was totally approachable, that's right.
Nadel: Totally approachable about science. I mean in other things, you know, whatever. About science.
Milner: Well he was an introvert but that's something else.
Nadel: Yeah, but of science and he seemed to know everything (Nadel laughing) so what a wonderful sort of environment to take advantage of. Yeah, Peter was quite something. And now again, when teaching the history course so I teach and I talk about you know, everyone knows about you.
Milner: (Milner laughing) Well they know about HM.
Nadel: Everyone knows about you because of HM.
Milner: That's right!
Nadel: Because of your connection with HM, fine. Fair enough. It's not a bad thing. And then we get around to something else and we talk about self-stimulation and brain reward and I said oh by the way, do any of you know of Peter Milner? Who?
Milner: They know Olds and Milner.
Nadel: They know Olds and Milner but they don't connect.
Milner: I see.
Nadel: There's no necessary connection and it is you know, who's this? It's Olds and Milner. If they know it at all, they know it's these two people, Olds and Milner. Now I'm talking about 20-year-olds now, 30-year-olds.
Milner: Yes, yes, no I understand.
Nadel: They had no idea. And I say well, this is Peter Milner who happened to be married to Brenda Milner. Imagine those two together, right? You know, what was life like you know, and kind of thinking about the brain at that time must have been quite something. But he was the leader I think.
Milner: He's what?
Nadel: Peter was the leader of the physiological psychology group. Hebb was around but nowhere near as engaged with the students.
Milner: No, I think this is true. Well Hebb was interested in teaching. He was interested in undergraduate teaching.
Nadel: Yeah, yeah, he loved it.
Milner: He was interested in that very first contact you have with the field, you know.
Nadel: He understood something. If you get them right away...
Milner: Yes.
Nadel:...if the first thing they hear...
Milner: They're hooked. (Milner laughing)
Nadel: If the first thing they hear is something like Hebb, they're on. It was talking his course that, I mean I wouldn't be sitting here otherwise.
Milner: Is that right?
Nadel: Oh absolutely. No no, Hebb turns on people. He turned on a lot of people in that intro class. He got them excited about it and then some of them stayed with it.
Milner: I went to his seminar because I was teaching at the U of M and I went to the seminar with Mort. That's where Mort and I became friends was in that Hebb seminar.
Nadel: So Mort must have been younger then, right? He's younger than you by about 20 years.
Milner: Mort's a lot younger than me, 9 years or something. Mort's a lot younger than me.
Nadel: 9? Oh.
Milner: I think something like that. He's a lot younger than me.
Nadel: A lot younger, yeah. Right. Wow. Ok. I think the good observer part is important because that is part of why you were successful as a neuropsychologist, your ability to observe people and their behavior and to sort of see what's going on.
Milner: I've been interested in that all my life I think. Well it was you know, not knowing I was like that, that's as far as I can remember. I've always been interested in that.
Nadel: And is that what drew you to psychology in the first place? How did you get into psychology, so you, were you actually in Bartlett's department?
HIPPOCAMPAL HISTORY TOUR PART 16: Brenda Milner (part 5)
Nadel: The heavy levels of analysis, the distance one is from the actual raw data. The conclusions one draws from an fMRI study was drawing them from data that you're quite a distance from what you're actually measuring.
Milner: Right.
Nadel: And it's not like a single cell study in an animal...
Milner: Right.
Nadel:...where you're looking at cells.
Milner: Right, right, right.
Nadel: The data are heavily analyzed and so you have to trust the analysis in essence.
Milner: I suppose I hadn't thought about this before but I think that it must be a product of the environment I work in maybe, you know. I'm not working in a psychology department. I'm working in a medical school and where all this is part of the milieu, right?
Nadel: Absolutely. So it's a given there.
Milner: It's a given there.
Nadel: It's a given there whereas it's not a given...yeah, that's an interesting point. Where you were located...
Milner: I think it's relevant.
Nadel:...that is very relevant here. Yeah ok. That's meaningful, right. So when did you switch over to the MRI? I'm just now bouncing around. So when you stopped being Hebb's graduate student, you got your Ph.D.
Milner: I was teaching at the U of M.
Nadel: You were still teaching at the U of M.
Milner: Yes, I was earning my living.
Nadel: (Nadel laughing) You were earning your living! You were supporting Peter, I presume.
Milner: A little bit at one time. Yes, that's right. No that's not quite true because he worked in the physics department to support his psychology.
Nadel: Ok, that's fair. You mentioned that. So then after you got your Ph.D., what happened then?
Milner: Well I wanted to stay on at the neuro and Hebb told me I was a fool, I told you that.
Nadel: Yeah, right.
Milner: No psychologist is going to survive and so on. And I said I'd like to try. So Hebb said he would support me for a year or two years out of his funds. Hebb supported me. And then after I'd been at the neuro, well we ran into these memory loss cases, Penfield said we need you. The great Dr. Penfield said to me we need you. It was right on the street here, I remember meeting him on the street and he said we need you. You have to transfer to the neuro and we'll find you a small office. Which is the office, that, yes...
Nadel: Is it the one that I just...
Milner: I was on the first floor, that one.
Nadel: So you basically proved that they needed you.
Milner: That Hebb was wrong.
Nadel: Well first of all, that Hebb was wrong, you could survive there, but that they needed you. That they needed a psychologist.
Milner: Yes. Well that's what he said. Penfield said we need you.
Nadel: Wow, and then you've been there ever since, that was it.
Milner: Yes.
Nadel: (Nadel laughing) What a great story!
(Milner laughing)
Nadel: Wow.
Milner: Well Penfield was worried by the memory loss cases. If you're the surgeon, you're going to worry about that.
Nadel: Absolutely. Yeah, right. Did he continue to do those kind of surgeries once HM, once it was clear that bilateral surgeries...
Milner: Well, they got to be much more careful about, well it was Rasmussen, I remember getting, getting to be, you know, very careful about these preoperative assessments.
Nadel: Right, right, right, right, so things got much better on that front.
Milner: We didn't run into any more trouble of that kind.
Nadel: Right. Alright. Well, those are the questions I had. Now it's really sort of, I mean are there any other, again...
Milner: Well I want to know what you're, tell me about you. What are you doing and what you'll do with this.
Nadel: Well, with this project, so I retired so to speak. Technically retired about a year and a half ago, two years ago but I'm still teaching.
Milner: Yes, yes.
Nadel: And I'm still on student committees.
Milner: Well I haven't retired, you know I do less and less.
Nadel: That kind of retirement. I mean I get my money from somewhere else, not from the university. So I get it from my retirement program.
Milner: Yes, yes, I get my money from the university.
Nadel: Yes, well I get a little because they hired me back to teach. And I'm writing papers with various former students and such.
Milner: No, you're very productive.
Nadel: So I'm still being, I'm still trying to be productive, but this is a kind of a pet, this is a hobby, a pet project to pull some history together, because the history fascinates me. I mean it's interesting how these ideas flowed and, you know, how people then dissected, you know, the kind of, the chance, the details fascinate me...
Milner: Did you know Zangwill, no?
Nadel: I met, I may have met him once but I did not know him, no. So you were a student with Zangwill?
Milner: That's right.
Nadel: Right, right, ok. I knew him, I knew of him, but by the time actually got to experience him, he was on the other side of the, he kind of had lost...
Milner: His interest was very in visual perception. That's what I was interested in initially, but when you find that your patients have memory impairment, you can't say I'm interested in visual perception so don't talk to me about memory. You have to survey what's wrong with the patient.
Nadel: Yeah, what's in front of you.
Milner: The patients determine why, I have a good background in memory because of Bartlett because I wasn't particularly interested in memory. I was interested in perception, but when the patients have memory impairment, complain of it, those are the patients you've got. You've got to study memory, no choice.
Nadel: Sure, so in that sort of chapter you wrote with Luke Teuber, the 68' chapter.
Milner: Oh, my goodness, yes.
Nadel: In that chapter, and in other writings then you were very much within this kind of perception is over here and memory is over there kind of story. I mean the standard psychological story.
Milner: Well it's just main chapter headings.
Nadel: Exactly right. They were chapter headings, but people tend to think about them as separate processes, right.
Milner: Yes, yes.
Nadel: You could, for example, have a deficit in memory without any problem in perception and vice versa. People would have said such a thing.
Milner: You could have said that. You could have said that.
Nadel: You could have said that. You can't say that anymore, right.
Milner: No, I supposed you can't. I hadn't thought about that.
Nadel: Yeah, so in that era, when you said...
Milner: No, it's true. They were separate.
Nadel: They were really quite separate.
Milner: Yes, you said that HM didn't have, they didn't have perceptual memory.
Nadel: Exactly right, in fact you had to say that because if you want to say...
Milner: Otherwise, it'd make us dirty, yes.
Nadel: Exactly right. But you can't say that anymore because it's clear that these things are, because of the network. Now you come back to neuroimaging.
Milner: That's right.
Nadel: It's clear that the hippocampus is engaged in all kinds of things, you know, before it gets to memory, so to speak. So does that change...
Milner: You know, I haven't thought of it. To tell you the truth, I haven't thought about this.
Nadel: Yeah, this is kind of what's happening now, I would say. The lines between kind of the old, this is where, I would say this is where Larry Squire hit the wall. The medial temporal lobe memory system was the kind of the apex of that particular approach.
Milner: I see.
Nadel: This is a purely memory system, it does nothing else.
Milner: I see.
Nadel: That was Larry's position.
Milner: I don't think I've ever said that.
Nadel: No, you never said that.
Milner: I never said that.
Nadel: But he built on the work...
Milner: I never thought about that.
Nadel: ...and he came to that, you know, this is a purely medial temporal lobe memory system and most of the debates in the last 20 years have been well no it actually plays a role in this, and it actually plays a role in that, and so on.
Milner: Yes, so I've not been involved in it.
Nadel: No, no, you haven't been involved in that debate, but you worked within that framework initially it seems to me. Yeah, ok. Because now you can't talk about them as separate. Now everybody, the lines are completely blurred and basically that the hippocampus contributes to decision making and to this and to that and to this and everything under the sun, basically. Yes, it's a memory structure but the memories in service of these points.
Milner: That's right, that's right.
Nadel: Right, which makes perfect...
Milner: Makes perfect sense.
Nadel: Makes perfect sense to a psychologist. Obviously that's what it's doing, but the theories took a while to catch up.
Milner: No, but you have to look at it from the point of view of what experiments you are going to do too, because you have to, you can't just study everything.
Nadel: No, no, right of course. You have to be practical. You have to be practical and focused. And it sounds like also you had further constraints. You had to deal with the patients that showed up...
HIPPOCAMPAL HISTORY TOUR PART 16: Brenda Milner (part 4)
Nadel: No, that's alright. Anyway, it's not surprising that you, from a very different framework, understood that there are these different kinds of learning...
Milner: Yes, yes.
Nadel:...and you need to look at them differently.
Milner: Well. Yes.
Nadel: Exactly, but that was not the current view at that point.
Milner: I see.
Nadel: Yeah, that's the interesting thing, because of a different kind of training and background...
Milner: Totally different.
Nadel:...totally different. And I have trouble getting people to understand that. Even in North America, there was a big difference between America and Canada.
Milner: Well, I didn't realize that.
Nadel: No, there was because of Hebb. Hebb's influence was, by the 50s, Hebb's influence was enormous. Most Canadian departments used Hebb's textbook. Nobody in the states used Hebb's textbook...
Milner: I see.
Nadel:...as an intro textbook. But Canadians were brought up, you know...
Milner: Yes, Peter was brought, you know, Peter was a physicist but when he started psychology, he took Hebb's textbook, yeah.
Nadel: Exactly right. When I was an undergraduate, I took Hebb's course as an undergrad.
Milner: Yes, yes, yes. Well Mort Mishkin and I took his graduate seminar.
Nadel: Yes, of course. Everyone, that's the famous seminar. (Nadel laughing). Hebb's famous seminar.
Milner: Yes, yes,
Nadel: With him blowing smoke rings across that table. (Nadel and Milner laughing). All right. So, so now I'll switch gears a little bit from your... I should be mindful of the time. (Nadel moving recording device). Okay, do you have a clock?
Milner: I have a watch.
Nadel: You have a watch. I don't wear watches so I don't...
Milner: It's 18 minutes, 17 minutes past 11.
Nadel: Oh okay. We have another 20 minutes or so.
Milner: Well, I mean, we have what you want.
Nadel: Yeah, yeah, yeah. So I...
Milner: Well, I... who says that? I mean, I'm not concerned about the time very much.
Nadel: Yeah, no, no. I have to be somewhere.
Milner: Oh you have to be? Oh that's...
Nadel: I do. And I also don't want to take too much of your time. I appreciate that. By the way, I really appreciate your...
Milner: Oh don't be silly!
Nadel:...your willingness to sort of spend some time with me this way. So when you look now, let's go back 20, 30, 40 years, alright? Your work on HM, all of this is already part of the history of the field and then other things started to happen. So when you look at the hippocampus world, you know, leaving your work aside, which few things would you pick out, and you say oh that one really caused me to change my thinking. Or who's other work, I mean when you look at the field as a whole, I'm trying to get people to talk about other people's work that really excited them.
Milner: Yes, I understand but that's difficult for me because I think, I think first of all my interests have really shifted to the frontal lobes.
Nadel: Right.
Milner: There's no question about that.
Nadel: Yeah, yeah. That's clear from the history, yeah.
Milner: I think that really happened. I was, you know, initially I was wanting not to get involved in the frontal lobes because everybody was talking about the frontal lobes.
Nadel: Right, right.
Milner: But then they fell out of fashion.
Nadel: (Nadel laughing). And that left it open for you.
Milner: I think and then we were getting so excited about technical things. It was so exciting to be having, you know, the recording of what was going on because before we thought we had to wait to, the fact that you could visualize the brain was incredible because we thought you had to wait for people to die and get their brains afterwards and obviously many things had happened between you testing them and them dying, you know. So it was...
Nadel: So the emergence of neuroimaging in general...
Milner: That was incredible.
Nadel: You would put that as...
Milner: I would put that as incredible.
Nadel: As incredibly important.
Milner: Yes, and I can still remember that human brain in action.
Nadel: Right. So one of the things that when people talk about the shift from kind of depending upon lesion data or post-mortem data to being able to image, right, that along with this shift in methodology...
Milner: Yes, that's right.
Nadel:...which has taken over the field, there has also been a shift in kind of the theories from thinking less about like a single structure...
Milner: A structure, that's right. That's right.
Nadel:...to more networks because the imaging.
Milner: That's right. That's right.
Nadel: That is, would you, I mean...
Milner: I agree with that.
Nadel: You agree with that. Yeah, yeah. And do you agree that that's a good outcome?
Milner: Oh of course it's a good outcome, yes.
Nadel: Exactly, alright.
Milner: Well, I believe the people before would have welcomed it so they didn't have the possibility.
Nadel: They didn't have the data. Yes, okay, alright. Alright. So that, so you...
Milner: There's no question about that.
Nadel: I had my questions written here. (Milner laughing). I want to make sure I at least ask you these questions. Okay, can you relate one personal story about interactions with colleagues that most exemplifies the world. Okay, the world of hippocampal research. So let's talk about from a sociological point of view.
Milner: I'm not in that, I never liked, I never liked social psychology. When I was at Cambridge, I never answered a question on it in my finals. I hate social psychology.
Nadel: So, let me give you some background here. (Milner laughing). So different fields in psychology of even within neuroscience acquire a certain reputation. This field is full of people who are very ambitious.
Milner: Yeah, yeah, you're right.
Nadel: This field is full of people who are really cooperative with each other. It's sort of usual.
Milner: Right, yes.
Nadel: And this field, people are at each other. You know, it varies right?
Milner: I suppose. I don't know that many fields.
Nadel: Okay. So you know the frontal lobe field with all of its characters and you know, important personalities and what they said and their theories and so on. The hippocampal world was a little different. And maybe you would...
Milner: Well it was maybe coming from rat work, right?
Nadel: Yes, a lot of it was the rat. So did you ever...
Milner: Because I always liked animal work.
Nadel: Right. So when you meet with the Mosers and you talk about things with them, I mean. Did you consider yourself...
Milner: I met them when?
Nadel: So you don't consider yourself to be part of the hippocampal world?
Milner: Oh no, no.
Nadel: Well we consider you to be a part of the hippocampal world. We claim you anyway. (Nadel laughing).
Milner: Well, yes well. No well I love the hippocampus, but I actually love the frontal lobes because when I came into psychology, into research and so on, and I was so tired of the fact that, I written it, everybody said, you know, the frontal lobes - man's hope for the future. Remember all that stuff. And it made me so sick, especially because I was seeing patients at the neuro having big unilateral frontal removals and showing really no, very little. And there was all this nonsense so, so...why was, why was I telling you that? That was...
Nadel: That you're part of the frontal world, not the hippocampal world, really.
Milner: Eh yes. The hippocampus, yes. That's right.
Nadel: Okay, we'll skip over that one. So then the last question of the questions I posed was if you were to speak to a young researcher now who was interested let's say in the hippocampus, but we can even leave that aside. What advice would you have for someone who's starting out their career now? What kind of problems should they look at? What, you know, where would you, what you tell them?
Milner: Well you know, that's so funny, so funny. I wouldn't think of it in terms of problems so much as getting aware of different technologies. You see for me, I think that, not being in armchair psychology. No, I think it's learning different methodologies, including behavioral ones of course, but that, but electrophysiological is, what you could learn from what I call behavioral neuroscience as most people call cognitive neuroscience, to learn as, this sounds, I mean, this is what to me has been so exciting that you can look at the living brain in action. You don't have to wait for the patient to die...
Nadel: Right.
Milner:...20 years later and try to make some sense of the anatomy, that you got this correlation. I find this very very exciting and then idea if I was starting out. You have access to so much more information about the brain, the living brain of the patient you are studying.
Nadel: Right. Are you at all concerned about the high level of analysis that is required to understand those data. So let me, again let me give you some context. For my history class the other day, we were talking about statistics.
Milner: Who was?
Nadel: I was talking in my class the other day about statistics with my students, and I related to them that I was trained by somebody, Hebb, who believed in what he called the interocular test: if I can see it with my eyes, I believe it.
Milner: Did Hebb say that?
Nadel: Hebb said that.
Milner: I've never heard of that!
Nadel: Hebb was not a fan of high level statistics.
Milner: Oh no, I know. I know.
Nadel: Right. Basically, if I can't see it with my eyes, it's not that important. Now that's not true with neuroimaging data. What you can see with your eyes when you see it, you can't make any heads or tails of it.
Milner: No, no but I would never have said that.
Nadel: Ok so you feel differently about this.
Milner: Yes.
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.
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.
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.)
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.
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.
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.
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.
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.
I recently spent a month in Trondheim, during which time I sat down for interviews with May-Britt and Edvard Moser. Those interviews follow in the next few posts.
@Learning @cogneurophys some gems in there we take for granted now, but went against the grain or were simply unknown at the time. Remarkable opus. #prefrontalcortex #neuropsychology #HippocampusGurus #HippocampusHistory #neuroscience #cognitivepsych
I was recently contacted by a science writer who wanted to talk about the hippocampus and imagination. We just finished zoom chatting when I asked about her last name - Wickelgren. Did she know there was a famous psychologist -- yes, she said, that was my Dad. For those of you who don't know the history, Wayne Wickelgren was a renowned cognitive psychologist back in the 1950s and 1960s, who published some very insightful and before-its-time stuff on hippocampus. It's worth having a look.
HIPPOCAMPAL HISTORY TOUR PART 13: OZZIE STEWARD
#hippocampus #hippocampusHistory #HippocampusGurus
This entry from Oswald (Ozzie) Steward introduces another branch of the hippocampal tree -- those who were drawn to it as a model system, useful for studying pharmacology, physiology, and more. Already in the 1970s there were quite a few of these, and Ozzie was amongst the leaders. Some new names come up, and. a few old ones resurface. UC Irvine, where I spent about 5 years in the early 1980s, was already then, and continues to be now, a world center for brain research on learning and memory. Here's how Ozzie remembers it.
Oswald Steward's hippocampal reminiscences:
Something that makes me a bit different from many “hippocampologists” is that I have loved the hippocampus as a model system for studies of basic neuronal cell biology and synaptic growth and plasticity, not so much as an object of study in and of itself. Consequently, my contributions to understanding the hippocampus itself are perhaps more limited than others.
My fascination with the hippocampus began at the start of my second year in graduate school in the Department of Psychobiology at the University of California Irvine. I came to graduate school with a core interest in mechanisms of learning and memory, which had been seeded by my undergraduate advisor at the University of Colorado, Kurt Schlesinger. Kurt had been at North Carolina at the time the idea was advanced that memory might use the same basic mechanisms as genetic memory (DNA-RNA-protein). The North Carolina group was one of the first to report that blocking RNA synthesis impaired memory in mice and Kurt was working on this idea when I took my first course in “Biological Psychology” from him at the University of Colorado (my introduction to Neuroscience).
With a somewhat unimpressive academic pedigree, I was incredibly fortunate to be accepted into the graduate program at UCI, albeit not in the first round. I got a phone call from my future graduate advisor Carl Cotman several weeks after initial offers had gone out; the gist of his call was: “Well, our top candidates turned us down but you looked interesting a possible backup”. I didn’t really care whether I was first or dead last as long as I got an offer--UCI was my first choice.
My first-year project in Carl’s lab foreshadowed what has been a focus throughout my career—how synaptic activity regulates postsynaptic gene expression. Using the Aplysia abdominal ganglion, I tested whether synaptic activation would trigger increases in protein synthesis (incorporation of radioactive amino acids into protein) in a postsynaptic neuron (R2, the largest neuron in Aplysia). I didn’t get any useful data though; consequently, at least a few Aplysia Californica were spared from the species’ only predator (graduate student neuroscientists in Southern California collecting for experiments).
During my first year in graduate school, Gary Lynch carried out the very first experiment showing “sprouting” (growth of axons and synapses) in the hippocampus. His initial study was motivated by Geoff Raisman’s publication a year earlier showing electron microscopic (EM) evidence of new synapse formation on septal nucleus neurons after deafferenting lesions. Gary was fascinated by the idea of using histochemical markers for pathways, which could be readily deployed. He reasoned that AChE staining for the cholinergic septal projections to the hippocampus might reveal post-lesion growth if it occurred. Gary described the study to Walle J.H. Nauta during a visit to Irvine, and Nauta said “Well, good idea, but most good ideas don’t pan out”. This one did! The experiment was to lesion the entorhinal cortex (EC) and stain for AChE to reveal septo-hippocampal projections. The result was dramatic—huge increases in AChE in the dentate gyrus molecular layer that had been denervated by the EC lesion. You could hold the microscope slide up and see this by eye without a microscope!
That year, Gary visited Per Anderson and presented the data. Per’s comment was in essence—“Well this sprouting is interesting but the question is whether sprouting axons are functional.” And that’s where I came in. At Irvine, graduate students were accepted into one lab (in my case, Carl’s) but were required to do a second-year project in another lab. There was great excitement about the cholinergic sprouting, so I chose Gary’s lab where I would learn hippocampal neurophysiology to try to determine whether sprouted septal projections formed functional synapses. I didn’t get any useful data (is there a repeating theme here?). The synaptic physiology of the cholinergic pathway from the septum to the dentate gyrus was (is) too complex. But in the process of testing pathways to the dentate gyrus after unilateral EC lesions, I discovered that unilateral lesions of the EC triggered sprouting of a crossed pathway from the contralateral EC. This type of sprouting was unique in that it led to the re-establishment of synapses with dentate granule cells that were homologous with the ones that were lost. My dissertation research characterized this new form of sprouting.
Studies of reinnervation of the dentate gyrus and recovery of function were the focus of my research for the first decade of my career. During our EM studies of reinnervation, we discovered the selective location of protein synthetic machinery (polyribosomes) at individual spine synapses. This founded a field of research on protein synthesis at synapses that now involves numerous labs across the world. Later, the highly laminated structure of the hippocampus allowed definitive studies on localization of mRNAs in dendrites. And the highly laminated inputs to the hippocampus provided the model system for my subsequent studies showing that newly synthesized Arc mRNA was selectively targeted to active synapses.
What findings about the hippocampus other than mine most excited me? LTP and LTD—synaptic plasticity mechanisms consistent with Hebb’s postulates that could plausibly account for memory.
A personal story about interactions with colleagues: Many to choose from, but the one that stands out is my collaboration with William B. (Chip) Levy on “Hebbian” plasticity. Chip realized that my data on the convergence of a sparse (weak) crossed projection from the EC to the dentate gyrus with the ipsilateral (strong) projection provided an ideal model system (there it is again) to test synapse cooperativity in LTP and LTD. Chip gave up a tenure track position at UC Riverside to come to UVA to collaborate on this. We showed that high frequency stimulation of the weak crossed pathway did not lead to LTP, but pairing of ipsi- and contralateral stimulation produced robust LTP of the crossed pathway. Moreover, stimulation of the strong ipsilateral pathway alone actually produced LTD of the crossed pathway (heterosynaptic LTD). To the best of my knowledge, our first paper together (XX), was the first to use the term “Hebb synapse” (actually, we said “Hebb-like synapse”) to describe the phenomena. A follow-up paper together (Temporal contiguity requirements…)” remains one of my most highly cite papers. Chip and I also collaborated on the initial EM description of selective localization of polyribosomes at synapses.
What would I tell a young researcher interested in the hippocampus to focus on now? Focus on questions, not a particular structure or system. If the hippocampus is a good model to answer fundamental questions, great! But whatever model system you use, develop deep knowledge of structure, connections, and function. New discoveries that stand the test of time and scrutiny are based on a solid foundation.
#hippocampus #hippocampusHistory #hippocampusGurus
HIPPOCAMPAL HISTORY TOUR PART 12: Charan Ranganath...part 2
What would tell a young researcher interested in the hippocampus to focus on now?
Think bigger–in terms of the brain, in terms of tasks, and in terms of models or theories.
There is a paradigm shift on the horizon. The idea that we can understand (at the computational or functional levels) the hippocampus as a module, independent of its connections, is untenable. Menno Witter’s detailed neuroanatomy, for instance, has made it very clear that the functions of the entorhinal cortex are inextricably linked with the hippocampus, such that you cannot understand one without the other. And the entorhinal cortex is the master hub of the brain, interacting with other major hubs, such as the prefrontal, perirhinal, and parahippocampal cortex, as well as subcortical areas like the amygdala. Then we can talk about neuromodulatory inputs like dopamine, cortisol, estrogen, etc. All this means that the computational environment of the hippocampus, by extension, its functions will be volatile and context dependent.
Moreover, the idea of the hippocampus as storing static “engrams” that are simply passed on to the cortex to reinstate memories is becoming increasingly untenable. We know that hippocampal representations are subject to substantial updating, but also they are dramatically modulated on the fly. A hippocampal “memory” of the same experience can be used for different purposes, and the representational space that you see in the hippocampus can look totally different depending on one’s goals or task context.
This brings us to the computational level. All the functions assigned to the hippocampus–which include everything from statistical learning and transitive inference to forming hyper-specific, pattern-separated memories–are computationally incompatible. They cannot be done by a single brain region. We can’t understand the hippocampus in isolation–we have to understand it in the context of dynamic interactions with other brain areas. That means we need to understand the characteristics of the animal’s environment (in a broad sense, not simply in terms of spatial geometry), its prior knowledge, and its goals. Trying to understand the hippocampus by asking people to memorize words in a word list, stretch out bird necks, or chasing fruit loops in an empty box is going to tell us nothing beyond what it does in those degenerate contexts.
If the goal is to understand episodic memory, we need to study events that have the complexity and timescale of events in the real world, and we need to consider how humans understand events in real time. If the goal is to understand navigation in a meaningful sense, we need to study navigation to a goal, in an animal with knowledge of its environment. If we want to understand the relationship between synaptic plasticity and forgetting, we need to study an animal that has more than two meaningful events in its lifetime, because retaining memories means maintaining robust connections amidst a daily barrage of interference.
So I think we need to study tasks that have a larger spatiotemporal scale, and think about the brain in terms of dynamic large-scale networks, and develop large-scale models that bridge these levels. This is going to be hard work and not for the faint of heart.
If you want me to get specific, one big opportunity that is waiting to be grabbed is to understand gating and regulation of information flow in the hippocampus. Right now, there’s a widespread implicit assumption that whenever hippocampal cells are active, that the neural activity is somehow behaviorally relevant. That assumption is probably wrong. For instance, we don’t think that the visual cortex is doing meaningful stuff when you sit around in the dark. Why should we assume that the hippocampus is constantly being consulted in the service of encoding and retrieval? There’s compelling evidence to suggest that, in fact, we don’t use the hippocampus constantly, and that a lot of what people see in hippocampal activity is just housekeeping. So, we need to understand when and how the hippocampus is brought in and out of action to serve behavior.
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