Neurophilosophy

An interview with Suzanne Corkin

SUZANNE Corkin is a professor of behavioural neuroscience at the Massachusetts Institute of Technology who worked with the famous amnesic patient H.M. for more than 45 years. I interviewed her at the annual meeting of the Society for Neuroscience in San Diego last month, for this article I wrote for The Dana Foundation. We talked about her work with H.M., and about the project to examine his brain now that he has died, which was partly funded by Dana. The transcript of our conversation is below.

How long did you work with H.M.? Did he ever know who you were? What was he like? 

I started working with H.M. in 1962 when I was a graduate student [with Brenda Milner], and I’m still working with him. In a way he did remember me – he didn’t think I was a stranger, he always thought I was his friend from high school. But he never knew who I really was.

He was always very polite, and those who knew him say exactly the same thing. I’ve talked to a few of his classmates, and they all said he was very quiet and kept himself to himself. He may have been like that because of his epilepsy. Perhaps he was afraid of having a seizure and embarrassing himself. But his father was also a quiet person, so maybe he had part of this in his genes. 

It wouldn’t be an exaggeration to say that he has contributed more to our understanding of memory than anyone else.

Yes, more than any other patient, and he’s probably contributed more than all of the scientists who’ve studied him put together. I’d tell him that from time to time – I’d say “You know, you’re really famous for doing all these tests.” He’d act sheepish and smile, but then of course he’d forget what I said.

What do you think we’ll learn from Project H.M.?

The obvious thing it will tell us is exactly where his lesion was, and it’s extent. That’s important in relation to any preserved memory he had – like motor skill learning, which we believe is heavily dependent on the striatum. So we’d like to know what his caudate and putamen are like. Priming depends on cortical areas mainly, so what is his cortex like? Also, we want to know about the perirhinal and parahippocampal cortices, which are adjacent to the hippocampus, and which we know from studies in monkeys and fMRI are critical for different kinds of memory.

Another thing we will learn is the correspondence between an MRI in life and the acid test of the brain, because MRI isn’t perfect. If we have these comparisons to make between the in vivo scan and autopsy we’ll know how accurate the MRI scan is. That’ll be a good lesson, because so few autopsies are performed.

If researchers study patients with brain lesions, they should try to get autopsies when they die. They should ask the patient and their family for a brain donation when the person’s still alive. As good as MRI is, it’s not perfect, and it’s important to establish a correlation between brain and behaviour – if you’re doing a lesion study, it’s important to know exactly where the lesion is, and the only way to do that is to get an autopsy, and that’s not done commonly.

Didn’t H.M. have dementia when he died? Do you think it was related to Alzheimer’s? The disease starts in the medial temporal lobes, but his were missing.

Yes, it starts in the entorhinal cortex, which he didn’t have. H.M. was hypertensive, and it wasn’t treated. He also had many mini-strokes throughout his brain, and my guess is that he had vascular dementia, or what’s called vascular cognitive impairment. But we won’t know until we get the tissue from Jacopo [Annese, director of The Brain Observatory]. There are different stains that can be done to rule in or rule out different types of dementia. The neuropathologists will find out more.

How easy is it to distinguish between the degeneration that occured because of normal, age-related processes and the damage done during the surgery?

Damaging a part of the brain leads to retrograde degeneration, so that’s something that we want to look at. We’d like to look at the connectivity in the MRI scans, but the autopsied brain is where you get to the truth. If we know the anatomy, we can look at the degeneration.

With H.M., there’s the question of the mammillary bodies, which the hippocampus projects to. In monkeys, the mammillary bodies atrophy after hippocampal damage, but the neuropathologist who looked at H.M.’s said he thought they look pretty good. We’ll know more eventually, especially when we get some controls.

All old people get plaques and tangles, but what’s different about somebody with Alzheimer’s Disease is that they have many more. If you look at a piece of tissue from a healthy, aged person, and compare it with the brain of a patient who had Alzheimer’s, you’ll find a greater density of plaques in the Alzheimer’s brain.

You found that H.M. could remember the layout of his old apartment and that he could draw an accurate floor plan of it.

The interesting thing is that he moved to that house after his operation. For all intents and purposes he didn’t remember anything on a day-to-basis – like what he had for breakfast or lunch – so it’s quite astonishing that he moved into this house after his operation, lived there for years and was able to draw a floor plan, not just once, but on many different occasions.

I included drawings he did at two different times in my 2002 paper for Nature Reviews Neuroscience. Before I published it, I thought I’d better find out if they were accurate. Beforehand, I showed it to a distant relative he lived with for a while, and she said that it was right. But I was still a little uneasy, so I contacted the current owner of the house, and the really funny thing was that he makes floor plans for a living. He emailed me back a floor plan of his house, and only one thing had changed – they’d taken out a partition between the kitchen and dining room, but everything else was the same. He’d got it right, but he didn’t remember that he had spent most of life in that house.

How was that possible when his entorhinal cortex was missing? 

There were parts of the spatial memory network that Henry was clearly missing, like the hippocampus and entorhinal cortex, but he still had other parts, like all the cortical areas. I tried to get him to do a map following test at the clinical research center. I gave him a map and said “We’re here, and I want you to find your way over to there,” and he couldn’t do it at all.

So his spatial memory was very impaired, but he could do certain tasks from the Weschler Intelligence Scale. I showed him a card with a pattern of red and white blocks, and he could duplicate the pattern when I gave him the right number of blocks. He was above average on that. So spatial ability is not monolithic – he was very good at that, and could develop cognitive maps of some sort, but was terrible at finding his way around. The house he lived in was small, with one floor, and he could find his way from the living room into the kitchen or into his bedroom. He was walking these routes many times every single day, so it was prolonged non-declarative learning over time.

Can you tell me a bit about the book you’re writing?

It doesn’t have a title yet, but it’ll come out next year. It has 14 chapters, organized in chronological order, each containing something about H.M.’s life. The first chapter is about before his operation, the second about the surgery, and then there’s a chapter on  Penfield and Milner. It has science embedded in it too, of course, so it’s an intermixing of that and his life. There is one heavy duty chapter, about the cellular and molecular bases of memory – H.M. inspired all that work, but his brain can’t really tell us anything about it.

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