A Fascinating Brain, in Death as in Life

by Guy McKhann, M.D.

December 8, 2009

As I sit here writing this column, I am watching a live feed on my computer from the laboratory of Dr. Jacopo Annese, director of the Brain Observatory program at the University of California, San Diego. As outlined in the article “H.M. Recollected,” Dr. Annese is making the initial slices of the brain of Henry Molaison, or H.M., a process that may take up to 30 hours. In the background, on the screen, is Dr. Suzanne Corkin, a professor of behavioral neuroscience at MIT, who oversaw much of the care and study of H.M. during the last 46 years of his life.

First of all, why all the attention to H.M.? As described in the San Diego Union-Triube article, H.M. was 10 years old when he began having epileptic seizures, episodes that gradually became worse and eventually left him unable to live on his own. The attempt to treat H.M.’s epilepsy resulted in far fewer seizures, but it also affected his memory in ways that neuroscientists have been studying ever since.

In the early 1950s, surgery for epilepsy was being developed, primarily by Dr. Wilder Penfield at the Montreal Neurological Institute. Then, as now, surgery was used for patients for whom anticonvulsants were ineffective. The idea behind this approach is that if you can find and remove the area in the brain where the abnormal activity starts, the seizures could be lessened, or even cured. To find this focus of abnormal activity, careful recordings were, and are, done, both from the surface of the skull and from electrodes placed within the brain. Often the abnormal focus was in the temporal lobe on one side of the brain. The surgery was then done to remove that part of the temporal lobe.

In 1953, Dr. William Scoville, who had trained with Dr. Penfield, studied H.M., considering him a candidate for epilepsy surgery. There was a major difference between H.M. and many other epilepsy patients: He had foci of abnormal activity in both temporal lobes, and both temporal lobes became the targets of Dr. Scoville’s surgery. After surgery, H.M. had a very peculiar memory pattern. He could learn new information for a brief period of time, but he could not store that information in his long-term memory. For example, Dr. Corkin could walk into his room and say, “Good morning, today is Sunday,” and H.M. would reply, “Today is Sunday.” But then Dr. Corkin could go out of the room for a few minutes, return, and H.M. would have no recollection of her having been there before or of what she had said.

The surgery resulted in the removal, on both sides, of most of a neuronal structure called the hippocampus. Observations of H.M., and other patients in whom the hippocampus is damaged on both sides, led to the realization that these neuronal structures are vital for converting short-term memories to storage as long-term memories.
Imagine an hourglass that you turn over so that the sand can run from one chamber to the other. The sand funnels through the narrow part between the two larger chambers. The hippocampus is like that funnel part of the timer; new memories have to flow through it to get to long-term storage. If the funnel is broken or blocked, that vital step in the consolidation of memories never occurs.

H.M. was the first well-studied person with this pattern of memory dysfunction, though there have been others since. Certain viral infections of the brain or brain damage after a cardiac arrest can result in similar problems. But H.M.’s lesions were discrete and sharply focal. Further, Dr. Corkin followed H.M. closely and knew how his memory may or may not have been changing.

The other aspect of H.M.’s story is how his brain is being studied. About a year before H.M.’s Dec. 2, 2008, death, Dr. Corkin gathered a group of experts to discuss how his brain should be studied and what questions should be asked. As a result of that meeting, Dr. Annese was chosen to be responsible for performing the initial studies. Dr. Annese has set up a unique system for preserving the brain, cutting it in ultra-thin slices (the process I am watching now) and then processing those slices with various stains. Many of the slices will be kept frozen for future studies.

Digitized slices will be available on the Web so that investigators around the world can share in the findings, make suggestions and interpretations, and, if qualified, contribute techniques from their own studies. All this information will be stored in supercomputers, which will allow H.M.’s brain to be compared with normal brains handled in the same way. H.M. was an inadvertent contributor to brain science during his life time, and his contributions continue after his death. This is the ultimate in giving one’s brain to science.

I am pleased to add that the Dana Foundation has had an active role in this process, funding the meeting Dr. Corkin organized and the setting up of Dr. Annese’s laboratory.