Remembering the man who couldn’t
Surgery left a patient known as H.M. unable to form memories. His digitized brain lets scientists study why.
If you know that a small, sea-horse-shaped structure deep in the brain called the hippocampus is crucial to committing new facts and skills to memory, you have not only your hippocampus to thank — you also owe a debt of gratitude to Henry Gustav Molaison.
Known to neuroscientists worldwide as H.M., Molaison is history’s most famous amnesiac patient. In 1953, surgeons attempted to treat his epilepsy by removing his hippocampus and surrounding brain tissue. The surgery reduced the frequency of his debilitating seizures, but it left him unable to make, store and retrieve memories for the last 55 years of his life.
H.M.’s brain has fascinated researchers for decades, even after Molaison’s passing in 2008. In death as in life, the man who was incapable of forming new memories continues to deepen scientists’ understanding of what it takes to make them.
A new study published this week clearly shows that after H.M.’s fateful surgery, portions of his hippocampus remained in both hemispheres of his brain. Until recently, when their presence was detected by magnetic resonance imaging, no remnants were thought to have existed.
H.M.’s surgical lesions and profound memory impairment have been crucial in characterizing the role of the hippocampus and its surrounding structures as key to the consolidation and storage of “declarative memory,” the type that is consciously learned and retrieved.
His lifetime as a research subject helped neuroscientists refine their understanding of memory as a complex and multilayered phenomenon served by many regions of the brain.
After Molaison went under the knife at the age of 27, his language and perceptual skills remained intact. He could also remember general aspects of his life before the surgery (though he was unable to recall specific events), and he could learn new motor skills.
But he was almost completely unable to remember events that occurred, or people he met, after the surgery. And despite the fact that he could improve a skill with training, he was incapable of recalling that he had ever been taught that skill in the first place.
Until his death at the age of 82, Molaison lived in a state of “permanent present tense,” the title of a book on his life and contributions to brain science written by MIT researcher Suzanne Corkin.
The one-of-a-kind brain was made famous by an article published in the Journal of Neurology, Neurosurgery and Psychiatry in 1957. The report became one of the most-cited studies in all of medical literature.
After H.M. died, his famous brain was removed and preserved in a formalin bath. Two months later, it was soaked in sucrose and glycerol to prevent shrinkage, wrapped in cotton and transported to the laboratory of neuroanatomist Jacopo Annese at UC San Diego. There, the brain was encased in gelatin and frozen.
In a continuous 53-hour procedure that was re- ported live via Twitter and webcast from Annese’s lab, H.M.’s brain was methodically sliced into 2,401 crosssections stretching from front to rear. Each 70-micron slice was photographed and digitized. The resulting images have been combined into a high-resolution, threedimensional model that will allow future researchers to conduct virtual dissections of their own.
The digital brain made its debut Tuesday in the journal Nature Communications. An initial analysis led by Annese confirms that remnants of H.M.’s hippocampus and some of the surrounding tissue were unexpectedly spared.
The early findings are notable for their consistency with previous imaging studies, said Brenda Milner, professor of neurosurgery at McGill University’s Montreal Neurological Institute and Hospital. “That’s reassuring,” said Milner, the first researcher to study H.M. and a coauthor of the 1957 paper. She was not involved with the latest effort.
Echoing Annese, Milner said it was possible that the bits of hippocampus left behind helped H.M. develop vague post-surgery memories of people and events he had seen repeatedly on television, including President Kennedy’s assassination, the 1969 moon landing and Liza Minnelli.
However, Corkin, who has studied H.M. for 46 years and participated in the new study, expressed doubt that the remnants of hippocampus were functional after the surgery. Having been robbed of incoming signals by the removal of the adjoining entorhinal cortex, the observed remains appeared to have atrophied.
More likely, she said, other parts of H.M.’s brain that were untouched by the surgery, including his entire cerebral cortex, may have afforded him some semblance of recall despite his profound amnesia.
The new images will help researchers explore the neurological basis for different kinds of memory, including those that shape our identities, allow us to learn new skills, interact socially and make plans, Corkin said.
“A lot of rich science will flow from this in the future,” she said.
The slides may also shed light on epilepsy, a condition marked by erratic and often disabling electrical storms in the brain. Though the disease is largely treated with medications, unresponsive cases are sometimes treated with modern-day versions of the surgery performed on H.M.
Corkin said the new slides may reveal a darker possibility: that the surgery that so dramatically changed H.M.’s life should never have been done. Scientists will probably comb his virtual brain to pinpoint where his seizures began.
H.M.’s surgeon, Dr. William Beecher Scoville, acknowledged before the procedure that electrodes sunk into H.M.’s brain failed to identify the hippocampus as the origin of his seizures. That they abated after surgery suggests that it somehow broke the chain of misfiring electrical signals anyway — though at a steep cost.
Annese said he had met the famous patient just once. Molaison was 80 and, having suffered several strokes, was no longer able to carry on a conversation. Annese said he would ask the patient, if he could, whether he understood how much he had helped to advance neuroscience. And, he said, he would ask if he was pleased with Annese’s work.