Discovering the Roots of Memory

By Olga Khazan

As a 95-year-old psychologist, Brenda Milner still remembers the “bad old days” of frontal lobotomies as a treatment for psychosis. In fact, her research provided some of the first evidence showing why such invasive brain operations could be harmful.

Milner, who teaches and conducts research at the Montreal Neurological Institute at McGill University in Quebec, is perhaps most known for her work with Henry Molaison, a patient formerly known as H.M.

Molaison had epilepsy and was treated by having specific regions of both his temporal lobes—the parts of the brain we now know are responsible for memory—removed in 1953 by William Beecher Scoville, a neurosurgeon at Hartford Hospital. The operation helped Molaison’s epilepsy but gave him anterograde amnesia, meaning he could not form memories of new events, though his working memory was unaffected.

Milner in 1965 (left) and today. (Courtesy of Brenda Milner and Meera Paleja)

Through her studies on H.M., Milner found that he could learn new motor tasks, but he had no memory of having done so. For example, he was able to draw a reflected image of a star by looking in a mirror, but he couldn’t remember practicing the skill over the course of days.

This discovery, as well as Milner’s future work, led to a greater scientific understanding of different types of memory

I talked with Milner by phone last week. What follows is a lightly edited transcript of our conversation.

How would you describe the field of neuropsychology?

I suppose it's the idea that as a psychologist, I'm a student of behavior, the scientific study of behavior. That’s my definition of experimental psychology. Where you make the leap into neuropsychology is by thinking that you should try to correlate these behavioral phenomena, such as memory or perception, with what is going on in the brain. And of course, before we knew so much about the brain, it was just speculation. But the more we found out about the brain, the more reasonable this approach seemed to be.

In World War II, you spent some time performing aptitude tests on fighter pilots and bomber pilots. What was that like?

In World War II, scientists in the U.K. were a reserved occupation; they couldn’t be drafted into the army. If I had gone into the arts, I would have been in uniform and maybe been in France. But scientists were considered brains that could be used at home, so I was in Cambridge. I had just completed my bachelor's degree in 1939 when war broke out. I had a scholarship from my college for two years research.

In Cambridge, we were very near a lot of airfields where planes were taking off and landing. It became very natural that our department was working on research that was relevant to the Airforce. What I had been interested to study, even before the war, was perception and what you do when you get conflicting information from different senses. Or what happens if you get sensations as you’re flying a plane that disagree with what your instruments are telling you. What we were doing in Cambridge—we were working with the Airforce to try to decide which of the incoming airmen who were going to be pilots, which of them should be directed to fly in bomber planes and which should be directed to fly in fighter planes.

Everybody had to trust their instruments, but there were many different tasks ... we were looking over the whole array of what these potential pilots had done on various tests. And of course it all depended on the needs of the moment. At the Battle of Britain, we needed fighter pilots, but later in the war, the emphasis was on bombing German cities. They were exciting years.

Did you face any sexism early in your career?

No, I’ve never seen any sexism. I didn't find it difficult. The Montreal Neurological Institute, when I went there, was a very authoritarian place. Dr. Penfield was a very dominant figure— when you were young and new there, you didn’t speak out of turn. It was hierarchical, but it was not sex discrimination.

The only gender discrimination I discovered was a structural one: When I was in high school, I decided I wanted to go to Cambridge University. There were very few women students at Oxford or Cambridge, and back then the women couldn’t go to the men’s colleges. In 1936, across the whole university and all three years it took to get your B.A., there couldn't be more than 400 women, and there were thousands of men. To get into one of these women’s colleges, there were very few places. And I had to get scholarships because I had no money. The situation that was competitive was structural in that there were so few women’s [places].

But [sexism] isn’t something I’m interested in as a topic. I enjoy men as companions. I work well with men.

How did you come to start working with H.M., the patient who suffered the memory loss?

I was working here with Dr. Wilder Penfield, who founded the Montreal Neurological Institute. In those days, we did not have MRIs. We had no way of looking into the brain, so the surgeon did not know what he was going to find until he opened up the brain.

We were undertaking planned removals of different parts of the brain for the treatment of epilepsy. The removal of part of one temporal lobe of the brain has now become a standard treatment for temporal lobe epilepsy worldwide. But the whole assumption is that the temporal lobe on the opposite side of the brain is functioning. You can get along with one kidney, one eye, one temporal lobe … but you can’t lose both sides because then you’ll have a handicap of some sort.

These patients with operations on the left hemisphere were having trouble remembering names or the gist of a story, which is a nuisance, but not a serious handicap. In patients that had operations on the right temporal lobe, they would be poor at remembering faces and places. This was the work I did for my PhD.

A year or two later, we encountered two patients who had a severe memory impairment after a unilateral removal—a type of removal that we thought was safe.

So we had these two unacceptable results. You have to understand that operating on someone to control epilepsy is intended to improve their quality of life; it's not acceptable to make the quality of life worse. We said, “how can we account for this?”

We speculated that these two patients had damage on the unoperated side. So when Dr. Penfield made his removal on the left side, he was depriving the patient of the function of those structures in both hemispheres. Twelve years later, one of these patients died and we got the brain and confirmed that hypothesis.

We reported that finding at the American Neurological Association meeting in 1953, and in the audience, there was the surgeon, Dr. William Scoville from Hartford, Conn. He read the abstracts, he called Dr. Penfield and said, "I think what you and Dr. Milner are describing is what I've seen in my patient who had a similar operation."

That patient was H.M. Dr. Scoville invited me down to Hartford to study that patient because Dr. Penfield and I had made so much of this memory disorder.

I started going down to MIT and studying H.M. down there. It was easier to bring him to Boston than to Montreal. We got H.M. to Montreal just once. It's tricky bringing an amnesic patient with seizures across the border.

So what was H.M.’s problem, specifically?

Temporal lobes create memories. (Wikimedia Commons) 

He had epilepsy, and it had been resistant to all medication. He did not have temporal lobe epilepsy. Dr. Scoville had been doing surgery on the brains of patients within the bad old days of frontal lobotomy for psychosis. He was disenchanted with it, he didn’t like the effects. But then he read that maybe if he did surgery on the temporal lobe, instead of the frontal lobe, maybe that would help. But the difference here was that he was deliberately operating on both hemispheres. We were doing unilateral procedures.

Then, H.M. was this patient who had had these seizures from an early age, he’d been treated with every kind of medication that was available in the day. Dr. Scoville thought maybe this operation [on both sides of the brain] would be useful in this desperate case of H.M. And he agreed to it, and the operation was carried out. And after that, though, there was this huge memory impairment.

You mentioned that he could learn how to do something perfectly, but he could never remember having done it.

He couldn’t learn a poem or something like that or the route to the bathroom, but he could improve a motor skill. In this case, it was trying to follow the outline of a star on a piece of paper when it’s reflected in a mirror. If you only see your hand in the mirror, you really make a mess of it at first. We all do. That’s normal. The beautiful thing was that H.M. showed this improvement toward the end. He was doing this drawing on the table, and he did this beautiful drawing, and he said, “that’s funny, it looks like it would be difficult, but it looks as though I’ve done it quite well.”

He was so amazed because he had absolutely no recollection of the 30 trials of this he’d done over three days. So the motor learning systems were still intact in him. When you have a patient who doesn’t remember anything, the challenge isn’t to show if he’s forgetful—that’s obvious. The challenge is to show if he can learn anything at all.

The most exciting moment in my research was that. I had not predicted this.

How did your peers react to that discovery?

This was the early 1950s, and people were doing research on animals or with graduate student volunteer subjects.

So some said, "Well this is one peculiar case, who knows what else is going on in this person's brain? You’re claiming that these structures are so important for memory, and we don’t have an animal model.”

The important thing was to get an animal model, from monkeys ideally, in whom these temporal lobe structures had been damaged and then you could show a comparable equivalent impairment.

And it took about 17 years before there was an animal model, and then once we had that, everyone was really excited about the human findings.

What do you think is your most enduring breakthrough?

In terms of what has attracted attention and continues to, I suppose this evidence of the importance of the hippocampus [a structure in the temporal lobe] in memory processes. And in terms of all the work it's generated all over the world, that’s the most important thing.

When I began this work, memory was not a fashionable topic in psychology. I didn't go into neuropsychology with the intention of working on memory. But when you have a patient in their 20s complaining of memory problems, you feel that this is something you have to investigate. It was a long time before these findings became accepted, and after that people became interested in memory.

Now, people are living to much older ages than they used to. As you live longer, your memory does get worse. It’s an older population, so people are now talking about these things as things they experience themselves.

What is your advice to other scientists or young academics?

Don't be afraid to change your field. It's very hard, you get enthusiasms growing up, and you think it's something you want to do. I really wanted to do mathematics, but I wasn’t a great mathematician. Don't be afraid to change fields, even very radically. I changed very radically. I think sometimes people feel very frightened and they get caught doing something they don’t enjoy or they’re not particularly good at. It's really important to be ready to make a bold change.

 

This article available online at:

http://www.theatlantic.com/health/archive/2014/03/discovering-the-roots-of-memory/284295/