Thu June 6, 2013
The Patient Who Let Us Peek Inside A Brain In 'Present Tense'
Originally published on Thu June 6, 2013 4:03 pm
In 1953, 27-year-old Henry Gustave Molaison underwent an experimental brain surgery in an attempt to alleviate his severe epileptic seizures. The surgery left him with a form of amnesia; he could remember many things from the past, but was unable to form new memories.
"He could tell us about where he was born, [that] his father's family was from Thibodaux, La., his mother came from Ireland," says neuroscientist Suzanne Corkin. "He talked about the towns in Hartford where he lived and about his specific neighbors. He knew the schools he attended, some of his classmates' names."
Corkin worked with and studied Molaison for almost 50 years, from 1962 until his death in 2008. She writes about how his case has helped scientists understand how memories are processed and stored in her new book Permanent Present Tense.
Her work with Molaison over those decades has taught us much of what we know about long-term memory. Corkin stresses that although his memory was almost nonexistent, Molaison was an intelligent man. This insight led to conclusions that intelligence and memory are not linked, that memory is compartmentalized, and that the ability to form new memories is localized to a specific part of the brain called the hippocampus and the surrounding cortex.
While Molaison is considered one of the most important case studies in the history of brain science, Corkin says that a sense of his celebrity was understandably lost on him.
"Every now and then I would tell him he was very famous and a lot of people knew about him in the world of scientists," Corkin says, " ... he would get this little sheepish grin and say, 'Oh, you know, isn't that nice.' You could see that it was heartwarming for him. But ... of course, as soon as he was distracted, he forgot."
On the signs of Molaison's intelligence
"We gave him IQ tests. In fact, he had an IQ test the day before his operation. A psychologist at the Hartford hospital had tested him. After his operation his IQ actually went up, which isn't a surprise because he wasn't having as many seizures. So we monitored his IQ over the years. We wanted to know that he maintained a particular level of intellectual ability. Aside from that, just talking to him in every day life, you knew you were talking to an intelligent person. Evidence of this is that he would spontaneously come up with very funny jokes. He had a wonderful sense of humor, and he would come up with little quips that were appropriate to a specific moment, nothing that he had made up before, rehearsed or he knew from his preoperative life.
"One day a postdoctoral fellow in my lab was testing Henry at the MIT clinical research center, they walked out of the testing room and the door slammed, and [one fellow] said, 'Oh, I think I've left my keys inside.' And Henry said, 'Well at least you'll know where to find them.' One of his favorite past times was doing crossword puzzles. He always had one at arm's reach and a pencil, and so I said, 'Henry, you are the puzzle king of the world,' and he said, 'I'm puzzling.' "
On short-term versus long-term memory
"Short-term memory is misunderstood and mislabeled by most of us. It's really just [what] you can remember for 30 seconds without distraction. It's the right now. It's the immediate present. It's what's on your radar screen now, not what was on five minutes ago or five minutes from now. So Henry's immediate memory was preserved. So if I said to him, 'Henry, I have this favorite plant, white petunias, that I like very much.' And then I'd ask him to say back [to me] what I had just said ... and he was able to do that. ... [But] if I said to him five minutes later, 'What is my favorite plant?' he would have no idea. So anything beyond 30 seconds falls into the domain of long-term memory."
On Molaison's later years
"He had to go to the bathroom a lot, so the nurses would take him and he would do what he had to do, and then 10 minutes later he would ask to go again, and they would say, 'Henry, you just went.' We learned from his full-body autopsy that he had colon cancer, and maybe this is why he had to go to the bathroom frequently. So yes, the later years of his life were sometimes unpleasant for him. At the same time, he had wonderful care in the nursing home. The aides really doted on him, and there were three in particular that they called 'The Island Ladies.' They were from Jamaica, and they loved Henry, and they called him their 'teddy bear,' and he had very caring people around him. His medical needs were for the most part met. So it was a mixed bag."
On Molaison's postmortem scan
"The scans were beautiful. They were much clearer than what you could see in a living person, partly because we scanned him for so long. You can't scan a living person for hours and hours. But the other thing that made them so spectacular was that there was no movement. If you or I go into an MRI scanner we're still breathing, and our heart is beating, and we might have a twitch in our right shoulder. And all of this makes you move and makes your brain move. Of course [after he died] Henry didn't have a heart rate or respiration, and we scanned him for a long time. So we could see individual structures much more clearly. We could see the spaces in his brain much more clearly. We could see they were enlarged because he had dementia. We could see the white matter was thin, the telephone lines were thin in certain places. We could see the dura, the outside covering of the brain. Much more detail from the postmortem scans."
On whether it was frustrating to work with Molaison
"The only thing that was a teeny bit annoying for researchers was if they heard the same story over and over and over again. So, you know, we used to pick him up at his nursing home and drive him up to MIT and then take him home again, and these car rides were a couple of hours. There were certain billboards along the way that [would] evoke the same story over and over again. Howard Eichenbaum had a funny experience where he had a coffee cup from McDonald's in his car and every time Henry looked at this, he talked about his friend named so-and-so McDonald, and so after a while Howard got so sick of listening to the story that he put the coffee cup under his seat. But, you know, it was just funny. It wasn't frustrating or annoying. It was amusing. And this was Henry being Henry. This is what he did. So we just accepted it."
TERRY GROSS, HOST:
This is FRESH AIR. I'm Terry Gross. A lot of what we know about memory is based on studying a now-famous patient named Henry Molaison. In 1953, he underwent experimental brain surgery that was intended to alleviate his extreme epileptic seizures. The surgery left him with a form of amnesia. He could remember many things from the past, but was unable to form new memories.
His unusual condition made him a rich subject for neuroscientists investigating the nature of memory. My guest, Suzanne Corkin, is a neuroscientist who worked with and studied Molaison from 1962 until his death in 2008. Her new book, "Permanent Present Tense," is about Henry Molaison - or HM, as he's known among scientists - and how his case helped scientists understand how memories are processed, stored and retrieved.
Corkin heads the Corkin Lab at MIT, where she's professor of neuroscience emerita. Let's start with a brief excerpt of a recording she made of her interviewing Henry Molaison in 1992.
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SUZANNE CORKIN: Do you know what you did yesterday?
HENRY MOLAISON: No, I don't.
CORKIN: How about this morning?
MOLAISON: I don't even remember that.
CORKIN: Could you tell me what you had for lunch today?
MOLAISON: I don't know, to tell you the truth.
GROSS: Suzanne Corkin, welcome to FRESH AIR. So that excerpt of your interview with Henry gives us a sense of his amnesia. So he couldn't remember - he couldn't make new memories, but how much could he remember about what happened to him before the surgery?
CORKIN: So he had rather rich mental representations covering the period from his birth, 1926, up to August '53, when he had the operation. But the quality of these preoperative memories was severely compromised. He lacked specific episodes, specific autobiographical memories, and instead, what he retained was the gist of his preoperative life.
GROSS: So it was hard to really find out about his past by talking to him, even though he still had some memories of his past.
CORKIN: Right. He could tell us about - you know, he knew where he was born, his father's family came from Thibodaux, Louisiana, his mother's came from Ireland. He talked about the towns in Hartford where he lived, and about his specific neighbors. He knew the schools he attended, some of his classmates' names and, you know, the kinds of things he did for fun.
So he had quite a lot of memories, but none of them were unique episodes.
GROSS: In that little interview excerpt, when you asked him, I think it was, like, what did you have for lunch or breakfast today? And he says I don't know, he sounds, like, almost, like, surprised, like, hmm, gee, I don't know that.
GROSS: Was he confused a lot of the time, because he couldn't remember? Or did he not even have the cognitive ability to be thinking about whether he remembered or not?
CORKIN: Oh, he - first of all, I want to emphasize that he was a very intelligent man. His IQ was above average. And he actually had very good insight about his memory impairment. He knew he had a bad memory, but, you know, if you asked him a question, he thought about it and tried to answer. And if he couldn't, he didn't make up something fanciful. He just said I don't remember. He was matter-of-fact about it.
But he had very good insight. He knew, you know, he had an operation, that something didn't go quite right and that he had a poor memory.
GROSS: So his amnesia was the result of surgery that was performed on him as a young man in an attempt to stop the terrible epileptic seizures he was having. Would you describe the surgery that was performed on him?
CORKIN: Oh, sure. It was done in 1953, at the Hartford Hospital, by William Beecher Scoville. The way the operation began was that Scoville drilled two holes in Henry's skull, each an inch-and-a-half in diameter and five inches apart. And he used these holes as the entranceway to Henry's brain. He operated first on one side, and then the other.
What he did was to insert a brain spatula, or a retractor, to lift up the frontal lobe on the side where he was operating. The frontal lobes are right behind your forehead. And when he did that, he could then see into the tip of the temporal lobe. The temporal lobes are just behind the frontal lobes. Before they did any - removed any brain tissue, they did EEG recordings from this area in question, the middle - the inner part of the temporal lobe.
The reason that they did that was to see if they could find a specific epileptic focus, a place where the seizures were starting. If they could, they would take that out, first on one side and then the other, and presumably Henry's seizures would stop. Well, they didn't find that specific focus. So then Scoville went ahead and did what he called a, frankly, experimental operation, taking out what we now know are critical memory structures in the inner part of the temporal lobe.
GROSS: And what are they called?
CORKIN: So what he took out was, first of all, the head of the hippocampus, and then the amygdale - which is actually not a memory area, it's an area that's specialized for emotions - and then some cortex right around the hippocampus that we now know is also important for memory, called the perirhinal and the parahippocampal cortices.
GROSS: And so with these parts of his brain removed and with Henry unable to form new memories, why did that make him such a good candidate for research about how memory works? I mean, after all, his memory no longer worked. So...
CORKIN: Right, that's a good point. Well, actually, his dedication to research brought about an epiphany in the science of memory. His case launched the modern era of memory research. And I can highlight three major scientific contributions, if you would like.
CORKIN: First of all, he was living proof that you can be a very intelligent person and still have a terrible memory. His IQ was consistently above average for decades after the operation, and what this tells us is that memory is processed by specialized brain circuits. Memory is compartmentalized.
And the second thing he showed us is that the ability to form new memories is localized to a specific part of the brain, the hippocampus and the surrounding cortex. Before Henry, we didn't understand that the hippocampus and the cortex around it are essential for the establishment of long-term memory.
And the third contribution was the discovery that there are different kinds of memory with different addresses in the brain. So Brenda Milner provided the first evidence of this dissociation in 1962, and since then, thousands of researchers have fleshed out this idea of multiple memory circuits.
GROSS: So let's take these one at a time. You say that Henry showed that you can be intelligent, but have a very bad memory - or in his case, kind of no memory, no memory of any new - no ability to retain any new memories. So what were the signs of his intelligence? How could you even measure that?
CORKIN: Oh, well, we gave him IQ tests. In fact, he had had an IQ test before his operation, the day before his operation. A psychologist at the Hartford Hospital had tested him. And after his operation, his IQ actually went up. That's not a surprise, because he wasn't having as many seizures.
And so we monitored his IQ over the years, because, you know, we wanted to know that he maintained a particular level of intellectual ability. And - but actually, aside from that, just talking to him in everyday life, you knew you were talking to an intelligent person. One evidence of this is that he would just spontaneously come up with very funny jokes.
He had a wonderful sense of humor, and he would come up with little quips that were appropriate to a specific moment that, you know, nothing he had made up before, rehearsed, or he knew from his preoperative life, which tells me...
GROSS: Can you think of an example?
CORKIN: Oh, I have lots of examples. So one day a postdoctoral fellow in my lab was testing Henry at the MIT Clinical Research Center. They walked out of the testing room and the door slammed. And Harvey Sager(ph) said, oh, I think I've left my keys inside. And Henry said, well, at least you'll know where to find them.
And then another - one time - one of his favorite pastimes was doing crossword puzzles. You know, he always had one at arm's reach, and a pencil. And so I said, Henry, you are the puzzle king of the world. And he said: I'm puzzling.
GROSS: So when the parts of his brain, when the hippocampus was removed from his brain, he lost his ability to make new memories.
GROSS: Does that mean that memories are stored in the hippocampus?
CORKIN: No, probably not. In order to consolidate and store new memories, there's important conversations that go on between the hippocampus and the cortex. And eventually your semantic knowledge, your general knowledge of the world, your vocabulary, goes, is - becomes represented in the cortex, and you don't need the hippocampus any longer. And that's why he could retrieve his general knowledge of the world.
He could talk about World War II and the stock market crash and various presidents and celebrities from before his operation. What he couldn't do was to remember specific episodes, as I said. And what this tells us is that this kind of information, even from before the operation, still requires the hippocampus for retrieval. It doesn't move upstairs to the cortex to be protected.
GROSS: So old and new memories need the participation of the hippocampus.
CORKIN: That's right. All new memories need the hippocampus, and old ones, to be - if you're retrieving a specific event, a unique event, you also need the hippocampus for that. If you're retrieving some general knowledge like what was the name of your elementary school, it's already stored in the cortex and you don't need your hippocampus for that.
GROSS: If you're just joining us, my guest is neuroscientist Suzanne Corkin, and her new book is called "Permanent Present Tense: The Unforgettable Life of the Amnesiac Patient HM." Let's take a short break here, and then we'll talk about what you learned from Henry and from studying his amnesia. This is FRESH AIR.
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GROSS: If you're just joining us, my guest is neuroscientist Suzanne Corkin, and she runs a neuroscience lab at MIT, where she's a professor emerita of neuroscience. We're talking about her new book, "Permanent Present Tense," which is about the decades she spent studying the brain and the person Henry Molaison, who in 1953 at the age of 27 underwent experimental brain surgery to treat his epilepsy and it resulted in amnesia. He was unable to form new memories.
And over the decades she studied, to the extent that she could, how his brain operated, what its limitations were after the surgery, and it led to revelations about memory. And he's actually considered the most famous and most important patient in neuroscience history.
So when we were talking earlier, you said one of the things that neuroscientists learned from Henry was that there are different kinds of memory. And so let's start with what you learned from Henry about the difference between long-term and short-term memory and how they work.
CORKIN: So short-term memory is misunderstood and mislabeled by most of us. It's really just what you can remember for about 30 seconds without distraction. It's the right now. It's the immediate present. It's what's on your radar screen now, not what was on, you know, five minutes ago or five minutes from now.
So Henry, his immediate memory was preserved. So if I said to him, Henry, you know, I have this favorite plant, white petunias, that I like very much, and then I asked him to say back to me what I had just said, he was able to do that. He could encode information and repeat it immediately, but he couldn't consolidate it and store it.
So if I said to him, you know, five minutes later, what was my favorite plant, he would have no idea. So anything beyond 30 seconds falls into the domain of long-term memory. Normal people have no trouble making this transition from short-term to long-term memory. If their short-term memory capacity is exceeded, they just naturally recruit their long-term memory. But Henry couldn't do that. So he could only remember things for about 30 seconds.
GROSS: So what does that tell you about brain circuitry?
CORKIN: Oh, it tells you that short-term memory is probably - this immediate memory is probably localized in the cortex and cortical areas where it's, you know, you encode it and you retrieve it right away, and that long-term memory requires these structures removed in Henry, the hippocampus and its neighbors.
GROSS: And another thing that you learned from studying Henry is that although he couldn't keep new memories, he was able to learn some new things. Like when he got older and he needed a walker, he was able to learn how to use that walker. When he and his mother, who took care of him, moved to a new home, he was eventually able to learn his way around the home.
So how do you explain that he was able to learn some new things but he couldn't - you know, on the other hand he had no ability to make new memories?
CORKIN: Right, so the explanations for those two observations are different. In terms of his ability to learn the walker, he acquired a motor skill, motor skills; several motor skills are required to use a walker efficiently. And so for motor skills, we know from a lot of work done in our laboratory and others that they depend on other structures in the brain, the striatum, which is under the frontal lobes, and the cerebellum, and motor cortex, several areas in the brain.
So that tells us that these are independent of declarative memory, what he couldn't do. Now, in terms of drawing the floor plan of the house, this is much harder to explain because this was declarative memory. This wasn't motor skill learning. He could sit down and consciously draw the floor plan. Now, this is something he really shouldn't have been able to do because he moved into that house after his operation, and yet he could - he learned the floor plan and even - he could still draw it even after he moved out of that house, which is even more astonishing.
So how did he do this? Well, this was a small bungalow and he spent a lot of his life there, in the house, and of course on a daily basis he would walk from one room to another, living room to the kitchen, living room to the bathroom, his bedroom to the kitchen or the dining room, et cetera.
And so he had - in terms of the way we talk about an experiment, he had many, many learning trials with respect to the layout of this house. He locomoted from one room to another to another constantly. So over, you know, days, weeks, months, years, he established a cognitive map of his house.
GROSS: So you say that you think this memory was established through repetition and routine, but if you gave him the same thing to eat for lunch every day and then asked him what did you have for lunch today, hours later, he probably wouldn't have remembered that, right?
CORKIN: No, because each day is a different episode. But there are other examples of things that he could learn - that he learned as a result of repetition. One of his - he watched a lot of television because he spent a lot of time at home, and one of his favorite programs was "All in the Family," with Archie Bunker being a not-PC individual.
And I think that he just captured Henry's fancy. And Henry watched this. There were reruns that were shown, I think, every day of the week. So he watched these programs a lot. And so over time he learned that Archie Bunker called his son-in-law Meathead.
Now, this is astonishing, that Henry, who for all practical purposes in everyday life remembered nothing, would know what Archie Bunker called his son-in-law, and yet is was something that was salient for him. He might have thought it was funny. It just captured his fancy. And because he heard it over and over and over again, it stuck with him.
GROSS: So as a scientist, when there's like an outlier here, like his ability to remember that Archie Bunker called his son Meathead, or his ability to remember where the bedroom was where he lived, is it - it must be like baffling at first, like this is disproving - unless you come up with a good answer, this is like disproving your theory.
CORKIN: That's right.
GROSS: So it's kind of like interesting and upsetting at the same time. I mean how do you deal with something that contradicts what you're finding and you have to come up with an explanation for it?
CORKIN: Well, what I did was to look at his brain, look at MRI scans of his brain, and try and explain it that way. Now, we know that he had a little bit of preserved memory tissue next to the hippocampus. I told you that the part of the perirhinal and parahippocampal cortex was removed, but the back two centimeters of these areas on both sides of his brain were intact.
We know from experiments in monkeys that the damage has to include the perirhinal cortex in order to produce an amnesia in the monkey that is as severe as HM's. So we know that these areas are important for memory. Obviously they weren't sufficient to sustain his memory in everyday life, but they still are memory areas.
And in addition to that, his cerebral cortex was intact. So he recruited these known memories, plus his well-functioning cortex, and was able to, you know, encode and store tiny bits of information. I mean he also knew things like, for example, that Julie Andrews was famous for singing on Broadway, that Lee Harvey Oswald assassinated the president, that Liza Minnelli was a movie star, actress and a dancer too.
He had these tiny little scraps of information about celebrities. Now, compared to healthy people his age, his performance was disastrous, but the fact that he could remember - could give accurate distinguishing information about any of these people was really extraordinary. And, you know, again he didn't learn it the same way that you or I would.
He learned it very slowly, by exposure over time, and probably there was an emotional component to the things he remembered, that something was very pleasing or very sad like the Kennedy assassination.
GROSS: Suzanne Corkin will be back in the second half of the show. Her new book about Henry Molaison and what his case taught her and other neuroscientists about memory is called "Permanent Present Tense." I'm Terry Gross and this is FRESH AIR.
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GROSS: This is FRESH AIR. I'm Terry Gross, back with neuroscientist Suzanne Corkin. She worked with and studied one of the most famous patients in the history of neuroscience, Henry Molaison. His case helped neuroscientists understand how memories are formed, stored and retrieved. Molaison had experimental surgery to alleviate his extreme epileptic seizures in 1953. The surgery left him with a form of amnesia, unable to create new memories. Corkin studied Molaison from 1962 until his death in 2008 and continues to study his preserved brain. Corkin heads the Corkin Lab at MIT and is the author of a new book about Molaison called "Permanent Present Tense."
When you start your research on Henry - on the patient known as HM - it was before there were MRIs, you couldn't image his brain.
GROSS: And, you know, modern neurology was in its very early stages then. So when MRIs and then FMRIs were developed, how did that change the nature of your research and what questions you were able to ask?
CORKIN: Yeah, it changed drastically. It was wonderful to finally be able to see inside a human brain. Initially what we knew about his lesion was the surgeon's estimate at the time of the operation. And his guess was that he removed eight centimeters of brain tissue from the tip of the temporal lobe going back on both sides. Now, with the advent of MRI, structural MRI, we knew that the eight centimeters was a gross overestimate and in fact his removal is 5.4 centimeters on the right side and 5.1 centimeters on the left. So this, I mean this just opened up a whole new world.
Now, when - after he died we did high resolution MRI scanning the night he died for nine hours with his brain still inside his skull, and then 10 weeks later after his brain had been removed and preserved, we scanned again in a very powerful magnet. So now we know even more from the postmortem scans about his brain than we did from the envivo, the scans we did during his life.
GROSS: Why were you able to do more high-powered scanning after he died?
CORKIN: What we used was two strong magnets, one was a three Tesla magnet and one was a seven Tesla magnet. When we scanned him when he was alive, we only used a 1.5 Tesla magnet because we were afraid that something bad might happen with a stronger magnet. Specifically, he had two clips in his brain that had been left behind by the surgeon intentionally to stop bleeding, and we were afraid that in a stronger magnet - the three Tesla or seven Tesla - that these would heat up or possibly move and we didn't want to risk that.
GROSS: Sure. Yeah. I mean when you get a regular MRI, they always tell you to take off anything - metal that you're wearing.
CORKIN: Exactly. Now, I have established before we did the scanning in the 1.5 Tesla magnet that the clips were safe. I had consulted actually a partner of Scoville and he referred me to the company that made the clips. So I went to great pains to make sure that it was going to be safe in the 1.5 scanner. It probably would've been in the three Tesla of scanner also, but we just didn't want to take a chance.
GROSS: Later in life, Henry developed Alzheimer's disease. And how is dementia different for Henry than amnesia was? Because one of the things that happens with Alzheimer's is that you lose recent memories...
GROSS: ...and you can't make new ones. Yet you know, dementia is different than amnesia.
CORKIN: Yes. It's true that he became demented later in his life. We don't know whether he had Alzheimer's disease or some other kind of dementia. We did see in scans late in his life that he had small strokes scattered throughout his brain, in gray matter, the neurons in the brain, and also in white matter, which are the telephone lines that connect different brain areas, so it's likely that he had vascular dementia caused by hypertension. Now, in addition, he may also have Alzheimer's as well, and we will only know the answer to this, we will know definitively what kind of dementias he had when we examine the brain - the brain tissue - and stain it for these different kinds of dementias.
Now, the difference between Henry and people with dementia is that Henry's amnesia was pure. His other - his intellectual functions were preserved. His lexical and semantic language processing was normal. His perception was normal. He didn't have any psychiatric disorders. So this distinguishes him pre-dementia from people who have dementia because patients with Alzheimer's and other kinds of dementia have a double whammy. They have Henry's damage, they have damage to the inner part of their temporal lobes, just like Henry did, but in addition they also have damage throughout their cortex. And that's why dementia is much more catastrophic than a pure amnesia such as Henry's.
GROSS: So in writing about Henry, you write that, you know, most of the time he was living in the moment because he couldn't make new memories so there wasn't, you know, a lot of past - as out of the distant past - for him to live in. And as a result of that, or maybe as a result of that, he was usually calm. He was in good spirits. He wasn't plagued by the kind of, you know, worries about the future and the past, and what did I say, and did I do that wrong that plague most of us. But when the dementia set in, did his mood change? Was he more agitated or more worried?
CORKIN: Yes, he was. He complained more about loud noises in his nursing home. He complained that someone had stolen his pillow that belonged to his father and he was very, very upset about that. On one occasion he said that his mother was coming to visit and there was no place for her to sit and that was upsetting to him.
GROSS: She was long dead by then.
CORKIN: Yeah. She was dead by then. Yeah. And in addition, he has to go to the bathroom a lot. And so the nurses would take him and he would do what he had to do and then, you know, 10 minutes later he'd ask to go again. And they would say, well, Henry, you know, you just went. And we learned from his full body autopsy that he had colon cancer and maybe this is why he had to go the bathroom frequently. So there, yes, the later years of his life were sometimes unpleasant for him. At the same time, he had wonderful care in the nursing home. The aides really doted on him, and there were three in particular who they called the island ladies, they were from Jamaica, and they loved Henry and they called him their teddy bear. So he, you know, he had very caring people around him and, you know, his medical needs were for the most part met. So you know, it was a mixed bag in his later life.
GROSS: My guest is neuroscientist Suzanne Corkin, author of "Permanent Present Tense." We'll talk more after a break.
This is FRESH AIR.
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GROSS: My guest is neuroscientist Suzanne Corkin, author of the new book "Permanent Present Tense," about what she and other neuroscientists learned from the case of Henry Molaison. In 1953, experimental brain surgery left Molaison with a form of amnesia. He was unable to create new memories. Corkin worked with and studied him from 1962 until his death in 2008.
When you got the call that Henry died, you felt his loss as a person, but as a scientist you wanted to preserve his brain so you could continue to do research. What did you have to do immediately to make sure that his brain was preserved well enough so that you could conduct the research you wanted to conduct?
CORKIN: So the first thing we had to do was to get his body up to Mass General as quickly as possible. And for that trip we had delivered ice packs to the - cooling packs to the nursing home, which they had in the freezer or the fridge, and they immediately wrapped his head in these ice packs to preserve the brain. So he rode up to Mass General in a hearse with ice packs on his head.
GROSS: So they were - you and the nursing home were prepared for the fact that his death could be imminent.
CORKIN: Absolutely. Actually, for quite a few years before. We started planning exactly what we would do in 2002, so we had seven years of planning. You know, you can't set up a whole bunch of research procedures on the spur of the moment and you can't make sure that you get his body up to Mass General as quickly as possible unless you planned ahead of time. So then, you know, we knew what we were going to do. And as luck would have it, everything went off without a hitch. There were a million things that could have gone wrong and nothing did. So he was there in a timely fashion. He was in the scanner just under four hours from the time he died. We scanned him for nine hours that night. The next morning his body went to the morgue. Autopsy went off very smoothly and then the brain was preserved. So thanks to a lot of planning by a lot of people, it was very successful.
GROSS: So you explained that you were able to do a more high-powered scanning of his brain after he died because you were able to use a more high-powered magnet in the MRI.
GROSS: So what could you see with that more high-powered MRI that you couldn't have seen before?
CORKIN: Well, it was, it was - the scans were beautiful. They were much clearer than you can see in a living person, partly because we scanned him for so long. I mean you can't scan a living person for hours and hours. But the other thing that made them so spectacular was that there was no movement. If you or I go into an MRI scanner, we're still breathing and our heart is beating and we might have, you know, a twitch in our right shoulder, and all of this makes you moved and your brain move. Of course, Henry didn't have a heart rate or respiration and we scanned him for a long time, so we could see the structures in his brain much more - individual structures much more clearly. We could see the spaces in his brain much more clearly and we could see that they were enlarged because he had dementia. We could see that the white matter was thin, the telephone lines was thin in certain places. We could see the dura, the outside covering of the brain, so much more detail from the postmortem scans.
In addition, in the MRI scans during his life, there were a few areas where we weren't sure where the lesion ended, what the demarcation of the lesion was. And so with the high-resolution MRI scans later, we could make a clear determination of exactly where the lesion ended and where the preserved tissue began.
GROSS: And then you preserved Henry's brain for further study.
GROSS: How did you preserve it and what use do you want to put it to?
CORKIN: Well, it was originally preserved in formaldehyde, and then it went to San Diego for cryo-embedding, freezing and the cutting. One year after he died, Jacopo Annese's lab at UCSD cut the brain into 2,401 slices; each one is 70 microns thick. That's about as thick as a human hair. And so now the brain is stored there. And our plans, immediate plans, are to conduct the neuropathological examination. What this means is staining the tissue with different stains to determine what kind of dementia he had. And then from then on, different researchers will be able to ask specific research questions about their favorite part of the brain - be it the temporal lobe or the cerebellum or the mammillary nuclei or whatever. So it will be - a committee has been set up that will review protocols for further research, and a brain bank will supply the necessary tissue to different investigators. So you know, it's almost, you know, endless possibilities of the things we could continue to learn from his brain. So his contribution continues.
GROSS: Can you explain why his brain is more valuable now to neuroscientists, now that it's sliced, than it would have been had you tried to preserve it as an intact brain?
CORKIN: Oh, because now you can look much more closely at individual cells. So these very - these thin 70 micron slices of tissue can be placed, can be mounted on slides, and they can be placed under a microscope. And you can count neurons; you can estimate the density of neurons in area A, B or C. And you can also track the integrity of the white matter tracks throughout the brain. There's just an awful lot more information we can get area by area. So it's a goldmine.
GROSS: Now, I know you needed permission in order to preserve his brain and slice the brain for further study. Whose permission did you get? I mean, was Henry himself legally capable of giving permission?
CORKIN: Yes, that's a good question. In 1992, Henry signed a brain donation form donating his brain to Mass General Hospital and MIT. His conservator, his court-appointed conservator, also signed the brain donation form at that time. And of course gave his consent after Henry died, as well. I have been in contact with the conservator extensively and the night Henry died I called him and told him what happened.
And told him what we were going to do in terms of the scanning and the autopsy and he was fine with that. He consented to that. And he's very supportive of everything we do.
GROSS: Did Henry, with his amnesia, comprehend that he was actually very, very important to neuroscientists who were studying memory and that his brain was very important to neuroscientists?
CORKIN: Alas, no. He didn't. Every now and then I would tell him that he was very famous and a lot of people knew about him in the world scientists and people who were not scientists and students. And he would just, you know, sort of give this little sheepish grin and say, oh, you know, isn't that nice. You could see that it was heartwarming for him. But he didn't have a lot to say about it.
And of course, as soon as he was distracted, he forgot.
GROSS: So in the years that you worked with Henry and studied him, was it ever frustrating because, due to his amnesia, he was unable to create new memories? And certainly couldn't remember who you were, though he had this vague sense that you were familiar to him.
CORKIN: It wasn't frustrating to be around him. You know, we all accepted the fact that he didn't really know who we were and that he didn't remember what happened, you know, in the past. But, you know, you just interact with him as a normal person. We would have conversations. We would exchange ideas. We would talk about, you know, now we're going to go down the hall and have lunch or whatever. Or, you know, what's your favorite food.
And he could talk about that. So a lot of things to talk about with him. The only thing that was a teeny bit annoying for researchers was if they heard the same story over and over and over again. So, you know, we used to pick him up at his nursing home and drive him up to MIT and then take him home again.
And these car rides were a couple of hours. So there were certain billboards along the way that invoke the same story over and over again. Or Howard Eichenbaum had a funny experience where he had a cup - coffee cup - from McDonald's in his car and every time Henry looked at this he talked about his friend named So-and-So McDonald.
And so after a while, Howard got so sick of listening to the story he'd just put the coffee cup under his seat. But, you know, it was just funny. It wasn't frustrating and it wasn't annoying; it was just amusing. And this was Henry being Henry. This is what he did. And so, you know, we just accepted it.
GROSS: Suzanne Corkin, thank you so much.
CORKIN: Thank you, Terry.
GROSS: Suzanne Corkin is the author of the new book "Permanent Present Tense." You can read an excerpt on our website freshair.npr.org. Coming up, rock critic Ken Tucker reviews the new album by Jason Isbell, a former guitarist for the Drive-By Truckers. This is FRESH AIR. Transcript provided by NPR, Copyright NPR.