In 1953, Henry Gustav Molaison of Hartford, CT, was 27. After undergoing a brain operation to correct seizures - which involved the removal of his hippocampus and surrounding tissue - he was left unable to form new memories, although his personality, language and intellectual ability remained intact.
"Patient H.M.," as he became known worldwide, lived for another 55 years, during which his willingness to undergo test after test contributed enormously to our understanding of human memory and the role of the hippocampus, in particular.
H.M.'s inability to form new "declarative memories" became the catalyst for over 50 years of scientific discoveries, resulting in thousands of published papers that have shaped basic understanding of how memory works.
At the time, around the 1950s, scientists believed that memory was distributed throughout the brain.
H.M. could learn new skills but not remember doing so
H.M.'s contribution changed all that and helped scientists discover that memory comprises at least two systems - declarative memory and motor learning.
Declarative memory helps us record names, faces and new experiences and stores them until we consciously retrieve them. This system uses the medial temporal areas of the brain and the hippocampus.
Motor learning uses other brain systems and happens more subconsciously. This is why people who have not ridden a bike for years can just get on one and ride off as if they had never stopped.
So for H.M., while he could learn new skills, he could not remember doing so. He was constantly surprised that he knew how to do something or that it was easier to learn than he was expecting. What he did not realize is that he had learned it already.
As technology improved over the years, and MRI scans were introduced, it was possible to look in more detail at the impact of the 1953 surgery on H.M.'s brain. However, the full extent could not be properly assessed while he was alive.
Postmortem study of H.M.'s brain released, including 3D model
Now, thanks to a detailed postmortem study of his brain, scientists around the world will finally see a detailed neurological picture of a case that has come to define modern studies of human memory.
Study leader and neuroanatomist Dr. Jacopo Annese, of the University of California San Diego and Brain Observatory, also in San Diego, and colleagues have published their work in the journal Nature Communications.
In the open paper, they describe how they used histological sectioning, which involves making stained slides of thin slices of brain tissue, and digital 3D construction, to reveal a microscopic anatomical model of H.M.'s brain.
The level of sampling and image quality is a significant advance over the MRI scans that were taken while H.M. was alive.
The work started in 2009, when Dr. Annese and his team dissected H.M.'s brain into 2,401 thin tissue slices and preserved them cryogenically in serial order.
While they prepared each slice, the team also recorded a series of digital images of the surface and archived them. This was used to create the microscopic 3D model of the whole brain.
The 1953 operation on H.M.'s brain did not fully remove hippocampus
Of particular interest are the detailed 3D measurements of the medial temporal lobe region, where H.M.'s hippocampus and some of the lobe structures were removed in the 1953 operation.
The reconstruction shows that the operation had not fully removed the hippocampus but had left, as the authors note, "a significant amount of residual hippocampal tissue with distinctive cytoarchitecture."
Dr. Annese says:
"Our goal was to create this 3D model so we could revisit, by virtual dissection, the original surgical procedure and support retrospective studies by providing clear anatomical verification of the original brain lesion and the pathological state of the surround areas of HM's brain."
The study also reveals something that had not been seen before: a small, circumscribed lesion in the left orbitofrontal cortex. Dr. Annese suggests this lesion was most likely created in the 1953 operation.
In 2012, a study of young recruits at the Swedish Armed Forces Interpreter Academy in Uppsala, found that learning languages helps parts of the brain to grow, including the hippocampus and three areas of the cerebral cortex. The researchers said their findings suggest learning languages could be a good way to keep the brain in shape.