Postmortem of famous brain explains why its owner couldn't learn

Patient H.M. was missing part of the hippocampus, which is involved in creating memories.

By slicing up and reconstructing the brain of Henry Gustav Molaison, researchers have confirmed predictions about a patient that has already contributed more than most to neuroscience.

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No big scientific surprises emerge from the anatomical analysis, which was carried out by Jacopo Annese of the Brain Observatory at the University of California, San Diego, and his colleagues, and published today in Nature Communications¹. But it has confirmed scientists’ deductions about the parts of the brain involved in learning and memory.

“The confirmation is surely important,” says Richard Morris, who studies learning and memory at the University of Edinburgh, UK. “The patient is a classic case, and so the paper will be extensively cited.”

Molaison, known in the scientific literature as patient H.M., lost his ability to store new memories in 1953 after surgeon William Scoville removed part of his brain — including a large swathe of the hippocampus — to treat his epilepsy. That provided the first conclusive evidence that the hippocampus is fundamental for memory. H.M. was studied extensively by cognitive neuroscientists during his life.

After H.M. died in 2008, Annese set out to discover exactly what Scoville had excised. The surgeon had made sketches during the operation, and brain-imaging studies in the 1990s confirmed that the lesion corresponded to the sketches, although was slightly smaller. But whereas brain imaging is relatively low-resolution, Annese and his colleagues were able to carry out an analysis at the micrometre scale.

Fine detail

Using the most modern neuropathological technologies, the researchers cut the brain into 2,401 razor-thin slices, and stained everythirtieth slice to reveal the details of each cell and its projections. They used the slices to create a three-dimensional computer model of the area of the brain around the excision.

The results confirmed that the residue of the posterior hippocampus that was suspected to have survived the operation did exist, and that it was a little larger than anticipated. Because it was disconnected from other anatomical structures in the circuitry involved in consolidating long-term memories — including the entorhinal cortex, which the results show to have been almost completely excised — it could not have rescued H.M.’s condition. The results also showed expected damage to the cerebellum caused by the anti-epileptic drug phenytoin, which he was required to take throughout his life, as well as other damage typical of ageing.

The slicing operation — all 53 hours of it — was shown live in a webcast. Directors of a UK theatre company were among the viewers and went on to write and produce the play 2401 Objects, an exploration of H.M.’s life that was critically acclaimed at the 2011 Edinburgh Festival.

Annese et al.