Light on fading memory
(appeared on 29th Jan 2014)

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New light may be shed on the working of the brain and memory, says S.Ananthanarayanan.

Much of the brain’s internal mechanism is hidden from view, as intense probing of a living brain is dangerous. What is known has been come by through tentative excisions, clinical records and animal studies. The functions of the major parts of the brain are thus only broadly known, including an organ called the hippocampus, located deep within the brain, which is associated with memory and spatial cognition. But studies of the hippocampus have been limited to findings derived from non-invasive imaging, like MRI, to supplement the symptoms that appeared in one classic case of brain surgery that affected the hippocampus.

Jacopo Annese, Natalie M. Schenker-Ahmed, Hauke Bartsch, Paul Maechler, Colleen Sheh, Natasha Thomas, Junya Kayano, Alexander Ghatan, Noah Bresler, Matthew P. Frosch, Ruth Klaming and Suzanne Corkin, working at San Diego and MIT, USA, now report, in Nature Communications, the creation of a 3-D model of derived from the post mortem examination of the brain of the same patient of brain surgery, after his death in 2008.

The Hippocampus

The hippocampus is a short, tube-like structure, a major component of the brain of humans and other vertebrates. Mammals have a pair of hippocampi, one on each side of the brain. The name, hippocampus, is derived from the Greek for seahorse, which the organ resembles. The organ is known to play an important part in consolidating short term memory into long term memory and in spatial navigation. In Alzheimer’s disease, where there is loss of memory and disorientation, the hippocampus is one of the first parts of the brain that is damaged.

In respect of the ‘spatial’ role, specific parts of the hippocampi of laboratory mice are known to become active when they pass particular places. In monkeys the activity is known to start when the monkey looks at particular places. Similar findings are reported in humans patients of epilepsy, who had implants in the hippocampus to identify the part that was involved in seizures. These findings indicate that the hippocampus has ‘place cells’ or forms a cognitive map, or a representation of the physical environment that helps navigation. In London, taxi drivers have to pass a strict examination of knowledge of the shortest route to different parts of the city. A study has shown that taxi drivers have larger hippocampi than others and also that the most experienced drivers have the largest of all.

In respect of the role in memory formation, it has been found that the hippocampus is involved in forming new memories. As there is a hippocampus in each hemisphere of the brain, it is found that damage to only one of them leaves memory formation almost unaffected. But damage to both affects formation of new memories and sometimes memories that were formed before the damage occurred. This could extend many years back but some older memories still remain. Persistence of older memories indicates that over time, memories are recorded in other parts of the brain too. But damage to the hippocampus does not affect some kinds of memory. For instance, if a patient with hippocampus damage were to learn to play the violin, she would retain the new skill, although she would forget how she went about learning!

Patient HM

Much of the understanding of the functions of the hippocampus has come from the case of Henry Gustav Molaison (February 26, 1926 – December 2, 2008), who came to be known as Patient H.M. While there had been long reluctance to perform surgical procedures on the brain to attempt cures of psychiatric or other conditions, these were tentatively attempted and after 1935, the procedure of lobotomy, or the scraping away of parts of the front of the brain had become popular. In 1953, a similar procedure was performed on patient HM, in an attempt to cure him of severe epileptic seizures. At the age of 27, HM was treated by William Beecher Scoville, a neurosurgeon, who localized the source of the seizures at parts of the brain and carried out surgical removal of the parts, to control the seizures.

The surgery involved most of the hippocampus and also other parts of the brain and the relevant feature is the complete record, with sketches, that Scoville maintained. The surgery was successful in controlling the seizures but seriously affected HM’s memory of new experiences. He also had moderate loss of older memories, entirely of events in the two years before surgery and partly till eleven years earlier. But he could learn new motor skills and till his death, age 81, could solve crossword puzzles with clues that referred to pre-1953 knowledge. He could even form new memories, where the memory amounted to modifying a pre-1953 record.

The detailed record of the surgery and the long term observation of the patient have led to most of the new knowledge about the working of the memory in humans. While the nature of memory loss and also the kind of memory that was retained helped refine theories of memory function, detailed imaging of HM’s brain, using probes like MRI, in the 1990s, revealed that there were more areas of the brain that had been damaged. But it was not clear if there were also recent, age related changes and the picture began to become cloudy, as to what areas affected memory and which areas were not, in fact, responsible.

When HM died, in 2008, his brain became available for anatomical study and in 2009, a team led by Dr Jacopo Annese, Director of the Brain Observatory, San Diego, acquired a large number of brain slices for analysis. The paper now published in Nature Communications is the result of reconstructing a microscopic anatomical model of HM’s brain, a procedure that was not possible while he was alive.


The objective of the exercise, Dr Annese and others say in the paper, was to reconstruct a 3-D model of HM’s brain, through high resolution images, so that Scoville’s original procedure could be revisited, through ‘virtual dissection’. The procedure was a 53 hour-long collection of 2,401 digital images, and corresponding sections, which were studied microscopically. The result was a 3-D model which enables computer based study of HM’s brain from any orientation. The whole procedure was also video recorded and broadcast, for scientific scrutiny and public engagement.

The model so created is found, the authors tentatively state, that HM’s brain had a good portion of the hippocampus intact and also reveals the details to re-enact the surgery performed, at a level of clarity that is significantly higher than what was shown by MRI scans. “The findings constitute new evidence that may help elucidate the consequences of H.M.’s operation in the context of the brain’s overall pathology…................During life, H.M. was the best-known and possibly the most studied patient in modern neuroscience; the availability of a large and organized collection of slices and digital anatomical images through the whole brain provides an unprecedented opportunity for collaborative and retrospective studies to continue,” the authors say.

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