H.M. BIOGRAPHY

Patient H.M. is recognized as the most studied individual in the history of modern neuroscience. His fame as a medical patient was on account of the exceptional severity, purity, and persistence of his memory impairment. Participating in hundreds of tests and assessments, he contributed to a unique anthology of behavioral data that continues to influence theories on the organization of memory in the human brain today.


1926 H.M. is born on February 26 in Manchester, Connecticut, as an only child of working-class parents.


1933 At the age of 7, H.M. is hit by a bicycle and remains unconscious for approximately 5 minutes. He starts having petit mal epileptic seizures three years later. Both his bicycle accident and paternal history of epilepsy have been mentioned in connection with his convulsions.


1943 H.M. has his first generalized epileptic seizure on his sixteenth birthday. Despite intensive anticonvulsant medication, his seizures increase in frequency and severity over time. On average, he has one generalized seizure per week and as many as ten petit mal seizures per day.


1947 Due to his severe epilepsy, H.M. drops out of high school for a total of two years. He graduates at the age of 21. After high school, H.M. works on an assembly line and as a motor-winder. Because the risk of having an epileptic seizure limits him in the type of job he can perform, H.M. is not able to follow in his father's footsteps of being an electrician as he is expected to.


1953 By the age of 27, H.M.'s seizures are so severe that he is no longer able to work and maintain a normal life. The neurosurgeon William Beecher Scoville offers to perform an experimental operation at Hartford Hospital in Hartford, Connecticut, in an effort to reduce his debilitating seizures. On September 1, Scoville resects a large part of H.M.'s hippocampus, a structure with an unknown function at the time, and adjacent structures in the medial temporal lobe (MTL). As anticipated, H.M.'s epileptic seizures reduce considerably in frequency. However, an unexpected side-effect becomes apparent consequent to the surgery: H.M. is unable to form any new memories, a condition known as anterograde amnesia.


1957 Scoville and Milner publish details of H.M.'s surgery and its unexpected consequences. Scoville stresses the danger of temporal lobectomies and calls attention to the importance of the hippocampus for the formation of memories.


1962 Milner tests H.M.'s ability to learn a visuomotor skill, which later becomes a key experiment for memory research. H.M. is asked to trace the outline of a star with a pencil by looking at the reflection of the star and his hand in a mirror. After several practice trials, he shows significant improvement in performance indicating that learning took place. Yet, he does not remember the practice sessions. This experiment is the first to demonstrate that there are two distinct types of memory: explicit (knowing what) and implicit (knowing how).


1966 Drachman and Arbit report that H.M.'s short-term memory span is unimpaired as long as he rehearses the information in his mind. However, he is not able to transform these short-term memories into stable long-term memories.


1967 The consequences of the surgery force H.M. to live under constant care. He lives with both his parents until his father dies in 1967. After his father's death, H.M. and his mother live by themselves and H.M. starts working at a rehabilitation center for the next 10 years.


1973 Richards studies whether H.M.'s memory impairment affects his perception of time. He finds that for time intervals less than 20 seconds, H.M.'s perception of time is the same as that of individuals without memory loss. Past 20 seconds, H.M.'s sense of time greatly differs. According to calculations, H.M. perceives one hour as 3 minutes, one day as 15 minutes, and one year as 3 hours.


1974 H.M. and his mother move to live with a relative, who is a psychiatric nurse and can take care of him. His mother is admitted to a nursing home in 1977 and dies four years later at the age of 94.


1980 Anatomical details of the removed structures are limited to drawings made by Scoville at the time of the surgery until in 1997 the first magnetic resonance images (MRI) of H.M.'s brain are published by Corkin and colleagues. These scans show that the lesion is less extensive than originally indicated by Scoville.


1997 From 2002 to 2004, H.M. participates in several MRI scans. Observations from these images regarding the lesion location and brain changes related to aging are published in 2006.


2008 H.M. passes away on December 2 of respiratory failure at the age of 82. His brain is preserved by Dr. Jacopo Annese and his team at The Brain Observatory. Post-mortem examination allows for a precise documentation of the brain lesion, enabling researchers to substantiate neuropsychological observations from the past five decades with histopathological evidence. High resolution MRI scans of the brain are taken before the autopsy. These are the first reported images of the brain post-mortem. A 3-D model estimating the geometry of the lesion is created from the scans. The autopsy is conducted at the Massachusetts General Hospital in Boston and the brain is extracted without significant damage.


2009 On February 14, the brain of patient H.M. is transported to The Brain Observatory at UC San Diego. In December, the brain is frozen and sliced whole into 2,401 hair-thin sections (70 microns) during one uninterrupted procedure. This unprecedented event is broadcast live on the web and viewed by thousands of researchers and non-scientists. The boxes containing the slices are taped and tied to shelves as an earthquake precaution. One by one, they are transferred into cryogenic vials for long-term preservation.


2010 The whole brain is reconstructed into a virtual 3-D model from images taken during the cutting procedure. Novel neuroanatomical protocols and computer-assisted microscopy techniques are created in order to publish a web accessible map of the brain at cellular resolution to enable collaboration, free brain exploration, and morphometric projects based on crowd-sourcing. Selected sections are stained and subsequently digitized at 20x-40x magnification to visualize cellular detail.


References
Corkin, S., Amaral, D. G., Gonzales, R.G., Johnson, K.A., & Hyman, B.T. (1997). H.M.'s medial temporal lobe lesion: Findings from magnetic resonance imaging. The Journal of Neuroscience, 17 (10), 3964-3979.
Drachman, D.A. & Arbit, J. (1966). Memory and the hippocampal complex. II. Is memory a multiple process? Archives of Neurology, 15, 52-61.
Milner, B. (1962). Physiologie de l'Hippocampe, Passouant, P., ed. (Paris: Centre National de la Recherche Scientifique), pp. 257-272.
Milner, B., Corkin, S., & Teuber, H.-L. (1968). Further analysis of the hippocampal amnesic syndrome: 14-year follow-up study of H.M. Neuropsychologia, 6, 215-234.
Richards, W. (1973). Time reproductions by H.M. Acta Psychologia, 27, 279-282.
Sagar, H.J., Cohen, N.J., Corkin, S., & Growdon, J.H. (1985) Dissociations among processes in remote memory. Annals of the New York Academy of Science, 444, 533-535.
Salat, D.H., van der Kouwe, A.J.W., Tuch, D.S., Quinn, B.T., Fischl, B., Dale, A.M., and Corkin, S. (2006). Neuroimaging H.M.: A 10-year follow-up examination. Hippocampus, 16, 936-945.
Scoville, W.B. & Milner,B. (1957). Loss of recent memory after bilateral hippocampal lesions. Journal of Neurology, Neurosurgery, and Psychiatry, 20, 11-21.
Squire, L.R. (2009). The legacy of patient H.M. for neuroscience. Neuron, 61, 6-9.