Henry Gustav Molaison (1926-2008) was perhaps the best-known and most studied patient in the history of neuroscience. Henry became the subject of a scientific article which would become one of the most cited articles in the history of medical literature.

At around the age of ten, Henry began having epileptic seizures, which became more severe over time, compromising his health, school performance, and social life. As an adult, Henry’s ability to work and function independently were severely impaired by his seizures in spite of taking high doses of anticonvulsant medications. In an effort to alleviate Henry’s seizures, neurosurgeon William Beecher Scoville performed an experimental brain operation on Henry, then 27, to remove portions of his medial temporal lobes, including a large portion of the hippocampus, which may have been the source of his seizures.

The article showed that, while Henry’s seizures were reduced in frequency, he acquired unexpected amnesia after his surgery. Henry was a normal, intelligent young man who had no memory impairments prior to his surgery. His acquired amnesia, therefore, was attributed to the surgical removal of his medial temporal lobes. This would prove to be a medical breakthrough, since the neurological substrate of memory in the brain was unknown at the time of Henry’s operation.

Thanks to Henry’s willingness to undergo extensive scientific testing, the modern era of memory research essentially began with evidence from his case. He was unexpectedly unable to retain new information – a condition known as anterograde amnesia, which prevents the process of consolidation, which transfers short-term into long-term memories. Reminiscent of the main character in the movie Memento, Henry was able to hold information in his mind through rehearsal, but could not store that information in long-term memory. Therefore, for all practical purposes, Henry lived only in the present tense. For example, Henry could not recognize members of the hospital staff who cared for him extensively during his stay. In fact, from recorded interviews with Henry, it is clear that he could not remember what he had eaten for lunch on any given day, or identify the current President of the United States.

Prior to his death from respiratory failure on December 2, 2008 in a Connecticut nursing home at the age of 82, he was popularly known as Patient H.M., Henry M., or, simply H.M. Shortly before Henry’s death, his guardians authorized the release of audio recordings made of him in the early 1990s, which were made available online by National Public Radio. These audio recordings represented the first opportunity for the general public to hear his voice and poignantly captured the essence of his existence, which included discernable optimism and good will – all in spite of his profound surgery-induced memory impairments.

After Henry’s death, his full name was made publicly available and the story of his life was published by neuroscientist Suzanne Corkin, Ph.D., Professor of Neuroscience, Emerita, at the Massachusetts Institute of Technology, in her book, Permanent Present Tense: The Unforgettable Life of the Amnesic Patient, H.M., which details Henry’s remarkable contributions to neuroscience.

Henry’s profound memory impairment had an enormously negative impact on his quality of life. Although Henry’s semantic memory (conscious recollections of facts and general knowledge about the world) for the years before his surgery was preserved, especially that for major world events, he was unable to recall any autobiographical memories from that time. In spite of this, Henry’s personality, language, attention, intellectual abilities, and short-term memory all remained unaffected. In fact, based on tests performed ten months after his surgery, Henry’s IQ was above average. Interestingly, further testing revealed that Henry had a number of preserved learning and memory functions (including normal performance in motor skill learning, perceptual learning, and visuoperceptual priming), even while claiming he could not recall these learning experiences and, therefore, lacked that declarative knowledge (“knowing that”). This revealed, for the first time, that non-declarative or procedural learning (“knowing how”), which was normal in Henry, relied on memory circuits separate from those in the medial temporal lobe and that it did not require conscious memory processes.

Since brain imaging technology was not available at the time of Henry’s surgery, the nature and extent of his brain lesions could not be visualized until much later. Computerized tomography (CT) scans of Henry’s brain were first published in 1984, although they did not clearly reveal the nature and extent of tissue damage in his medial temporal lobes. Later, in the 1990s, magnetic resonance imaging (MRI) indicated that his lesions included most of the amygdaloid complex and entorhinal cortex, as well as a large portion of the hippocampal formation. These MRI scans, however, did not reveal the exact anatomical boundaries of the lesions in Henry’s medial temporal lobes.

After Henry’s death, his brain was donated to science and sent to The Brain Observatory at the University of California at San Diego, where, as part of Project HM, it could be expertly cut and simultaneously recorded in a series of high resolution neuroanatomical images. From these images, it was possible to construct a detailed microscopic level mapping and to make 3D measurements from a digital model of Henry’s brain.

A research team, led by neuroanatomist Jacopo Annese, Ph.D., Founder and Director of The Brain Observatory, and Matthew Frosch, M.D., Ph.D., Director of Neuropathology Service at Massachusetts General Hospital, performed histological sectioning and digital 3D reconstruction of Henry’s brain. Project H.M., funded by the National Science Foundation, Dana Foundation, National Eye Institute, and National Institute of Mental Health, clearly delineated the exact anatomical locations of Henry’s brain lesions for the first time.

The findings, published online in Nature Communications, were based on 2,401 digital images of Henry’s brain, which was cut in an uninterrupted 53-hour procedure that was streamed live on the internet on the one-year anniversary of Henry’s death. “I didn’t sleep for three days,” said Dr. Annese. “It was probably the most engaging, most exciting thing I’ve ever done,” he said.

The results show that there was complete removal of Henry’s anterior hippocampus and most of his entorhinal cortex, although a substantial portion of presumably non-functional hippocampal tissue remained. “These initial results confirm what we already knew about the size and shape of Henry’s brain lesions,” said Dr. Corkin. In addition, there was a near-complete removal of the amygdala, which may explain Henry’s dampened expression of emotions, poor motivation, lack of initiative, and inability to identify internal states such as pain, hunger, and thirst. Moreover, the results showed that Henry had a small lesion in the left frontal lobe of unknown origin that had never previously been identified. Whether this newly discovered frontal lobe lesion had any influence on Henry’s behavior is currently unknown.

Also noteworthy was the visualization of atrophy of the cerebellum, which had been previously identified via brain imaging and which Henry acquired as a side effect of long-term use of Dilantin, part of Henry’s seizure management both before and after his surgery. Lastly, the results also showed that Henry had diffuse damage to deep white matter (insulation for parts of brain cells) underlying the removed medial temporal lobes, which appeared to be a recent age-related phenomenon attributable to medical conditions, including hypertension.

Henry Molaison lived solely in the present tense for 55 years, during which time he taught us more about memory and the brain than we had ever thought possible. By all accounts, Henry enjoyed participating in the research being conducted on him and expressed happiness, saying: “What they find out about me helps them to help other people.”

Undoubtedly, Henry’s contributions to neuroscience will never be forgotten, but rather will last forever. “Henry’s disability, a tremendous cost to him and his family, became science’s gain,” said Dr. Corkin.

References

Annese J, Schenker-Ahmed NM, Bartsch H, Maechler P, Sheh C, Thomas N, Kayano J, Ghatan A, Bresler N, Frosch MP, Klaming R, & Corkin S (2014). Postmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction. Nature communications, 5 PMID: 24473151

Buchen L (2009). Famous brain set to go under the knife. Nature, 462 (7272) PMID: 19940891

Corkin S. (2013). Permanent Present Tense: The Unforgettable Life of the Amnesic Patient, H.M. Jackson, TN: Basic Books.

Corkin S (2002). What’s new with the amnesic patient H.M.? Nature reviews. Neuroscience, 3 (2), 153-60 PMID: 11836523

Corkin S, Amaral DG, González RG, Johnson KA, & Hyman BT (1997). H. M.’s medial temporal lobe lesion: findings from magnetic resonance imaging. The Journal of neuroscience : the official journal of the Society for Neuroscience, 17 (10), 3964-79 PMID: 9133414

Corkin S, Amaral DG, González RG, Johnson KA, & Hyman BT (1997). H. M.’s medial temporal lobe lesion: findings from magnetic resonance imaging. The Journal of neuroscience : the official journal of the Society for Neuroscience, 17 (10), 3964-79 PMID: 9133414

Hughes, V. (2014, January 28). After death, H.M.’s brain uploaded to the cloud. National Geographic RSS. Retrieved February 2, 2014.

Newhouse, B. (2007, February 24). H.M.’s brain and the history of memory. National Public Radio. Retrieved February 2, 2014.

SCOVILLE WB, & MILNER B (1957). Loss of recent memory after bilateral hippocampal lesions. Journal of neurology, neurosurgery, and psychiatry, 20 (1), 11-21 PMID: 13406589

Thomson, H. (2014, January 28). Neuroscience’s most famous brain is reconstructed. New Scientist RSS. Retrieved February 2, 2014.

Image via Oliver Sved / Shutterstock.