The study of patient henry Molaison and what it taught us over past 50 years: Contributions to neuroscience

Bigya Shah; Raman Deep Pattanayak; Rajesh Sagar

doi:10.4103/0971-8990.153719

INSPIRATIONS FROM HISTORY

Year : 2014 | Volume : 19 | Issue : 2 | Page : 91-93

The study of patient henry Molaison and what it taught us over past 50 years: Contributions to neuroscience

Bigya Shah, Raman Deep Pattanayak, Rajesh Sagar
Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication

20-Mar-2015

Correspondence Address:
Raman Deep Pattanayak
Department of Psychiatry, A.I.I.M.S., New Delhi
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/0971-8990.153719

Abstract

This section provides a historical perspective and contributions from one of the most studied patients in neuroscience, Henry Molaison (1926-2008), known as H.M during his life to protect his privacy. The peculiar memory deficits seen after an experimental operation for intractable epilepsy led to some critical discoveries pertaining to memory organization in human brain.

Keywords: Henry Molaison, history, memory

How to cite this article:
Shah B, Pattanayak RD, Sagar R. The study of patient henry Molaison and what it taught us over past 50 years: Contributions to neuroscience. J Mental Health Hum Behav 2014;19:91-3

How to cite this URL:
Shah B, Pattanayak RD, Sagar R. The study of patient henry Molaison and what it taught us over past 50 years: Contributions to neuroscience. J Mental Health Hum Behav [serial online] 2014 [cited 2023 Jun 9];19:91-3. Available from: https://www.jmhhb.org/text.asp?2014/19/2/91/153719

"Studying how Henry forgot gave us a better understanding of how we remember"

(Suzzane Corkin, Prof of Behavioral Neuroscience, MIT author of "Permanent Present Tense")

In this section, we discuss about the legacy, contributions, and critical discoveries from one of the most studied patients in the history of neuroscience, Henry Molaison (H.M) during his life to protect his privacy.

After he underwent an experimental procedure for intractable epilepsy, Henry showed certain peculiar memory deficits. The understanding of memory and its anatomical substrates was still at a nascent stage at the time of his operation in early 1950s.

The Early Life of Henry Gustav Molaison: Henry Molaison (1926-2008)

Henry Molaison was born full term and had a normal early childhood (except for a minor head injury and a family history of seizures). At the age of 10, he started having petit mal seizures (almost daily) and at 15 years of age, also developed generalized tonic-clonic seizures. His family doctor referred the case to a neurosurgeon, Dr. William Scoville in view of inadequate control on medications. Dr. Scoville continued the medications (Records from 1946 - "to continue indefinitely" on Tabs Dilantin, Phenobarbital, Tridione, Mesantoin) with only some response. Repeated EEG studies did not find any localized area of origin in his brain. H.M. graduated from high school when he was 21 and later repaired electric motors and worked on a typewriter assembly line. His functioning continued to be affected by treatment refractory seizures (daily petitmal seizures and intermittent generalized seizures). ^[1],[2]

The 'Experimental' Procedure

Knowing that Henry's seizures had been progressing for a decade, Dr. Scoville in the year 1953 suggested an "experimental" operation (bilateral medial temporal lobe resection) hoping for control of medically intractable epilepsy and to improve the quality-of-life. ^[1],[2],[3] Henry would be the first patient - suffering from intractable epilepsy-to undergo this procedure (previously in schizophrenia with mixed results).

In early 1950s, the functions of amygdala and hippocampus (apart from smell) were not established, and these areas were often removed with temporal lobectomy. In case of H.M, however, a bilateral resection was planned, unlike earlier procedures which involved unilateral (either left or right) resection.

On August 25, 1953, Dr. Scoville operated to remove the bilateral (a) Inner part of the temporal pole; (b) most of the amygdaloid complex; (c) hippocampal complex, except for about 2 cm at the back; (d) parahippocampal gyrus-entorhinal, perirhinal, and parahippocampal cortices-except for 2 cm at back. ^[2],[3]

Living in Thirty Seconds

Soon after the operation, it was noticed that Henry was unable to form new memories. He was perpetually "trapped in the moment," unable to recall anything beyond 30 s. Scoville, along with Milner (who would work on H.M case for several years), described this postoperative loss of recent memory in his 1957 paper ^[3] with the following conclusion.
"The findings reported herein have led us to attribute a special importance to the anterior hippocampus and hippocampal gyrus in the retention of new experience" (p. 21). ^[3]

Henry lived for 55 years without acquiring any new declarative memories. His surgery, however, left intact other circuits that supported his nondeclarative memory, so he could learn new motor skills and acquire conditioned responses.

One of the unique features of H.M.'s memory loss was its specific nature. His amnesia was pure-largely unconfounded by other cognitive deficits. ^{[1],[2],[4],[5]}

Henry's short-term memory was intact; whereas he failed to convert short-term memories into long-term memories
Forgot new experiences after operation and inability to form new memories
His semantic memory for prior to operation was intact (recalled historical facts, recognized relatives, good vocabulary) and had intact procedural memory
The episodic memory prior to operation showed deficits
Performance on digit span was intact
His IQ was above average
His language, reasoning, and perceptual capacities were normal. (exceptions were impaired olfactory function, caused by the operation, and cerebellar symptoms, a side effect of Phenytoin).

Critical Discoveries from Henry Molaison's Case

The cognitive psychological and behavioral studies, and in ensuring decades, the structural and functional neuroimaging studies of patient H.M. have led to some major breakthroughs in understanding of how memories are formed and organized in human brain. Following is a summary of some of the critical insights gained ^{[2],[4],[5],[6],[7],[8],[9]} :

Fractionation of memory into short-term and long-term memory processes, each part being mediated by a specialized memory circuit. It became evident from a series of cognitive tests that short-term memory is the immediate present. Its capacity is limited and fades immediately unless (a) We rehearse it or (b) convert it into a form that can be retained in long-term memory. Henry was able to use rehearsal but unable to convert short-term memories into long-term memories
Duration of short-term memory - Henry could easily and accurately perform the task when there was no delay between stimuli, however, the ability to differentiate between stimuli became harder as the gap between them got longer beyond 30 s. At 60 s, it was just a random performance. The abrupt breakdown in Henry's performance between 30 s and 60 s showed that the duration of short-term memory lasted <60 s
Concept of semantic and episodic memory as being distinctly organized in brain - In case of H.M., most details of unique events were lost (episodic, autobiographical memory), but general knowledge of the world is preserved (semantic memory), indicating that the anatomical substrates for these two forms of memory were distinct. We now know that the medial temporal-lobe structures are engaged in the initial encoding, storage, and retrieval of both kinds of memories. Then, during the process of consolidation, semantic memories become permanently established in the cortex while episodic, autobiographical-memory traces continue to depend on medial temporal-lobe structures indefinitely. Thus, the removal of this tissue from Henry's brain left him devoid of autobiographical memories
Recognizing that learning can take place without awareness (nondeclarative memory) was one of the most significant advances. Henry learnt to use a walker. Milner introduced the idea that some memory processes were not hippocampus-dependent by showing that H.M.'s error scores decreased across 3 days of testing on a motor skill-learning task, that is, mirror tracing. This discovery constituted the first experimental demonstration of preserved learning in amnesia. The "nondeclarative memory" typically was not impaired in Henry's case. Milner's view was further strengthened by the touch-guided maze test, which was first demonstration within a single experiment, of impaired declarative learning (failure to learn the correct route) with preserved procedural - nondeclarative - learning (improving the motor skill) ^[7]
A healthy hippocampus is essential for vividly recounting the details (recollection), but that it is not essential for simply recognizing a face, without identifying it or placing it in a context (familiarity)
Henry was able to produce conditioned responses in eye blink conditioning experiment, which helped to speculate that the conditioned memory, which was intact, was not mediated by medial temporal lobe
The brain circuit responsible for odor detection (this bottle contains an odor) and odor intensity discrimination (this odor is stronger) is separate from the circuit that supports odor discrimination (this smells like cloves). Henry could not do latter. We now know that odor discrimination takes place in the front part of the parahippocampal gyrus, the amygdala, and the cortex around the amygdale
Henry's spatial memory-declarative memory for spatial locations-was deficient. It established the importance of the hippocampus for spatial learning. However, after a few days, he could accurately draw the map of the house where he lived, means that other brain areas took over the job of encoding and storing that rich spatial information. This task depended on the parahippocampal gyrus, part of which remained in Henry's brain on both sides. Hence, on rare occasions, he somehow compensated for the devastating effect of his hippocampal damage by mobilizing preserved brain structures and networks.

Subsequent Life after Operation Till Death (2008)

Postoperatively, H.M.'s petit and grand mal attacks continued at a reduced frequency. Henry's parents continued to take care of him, and after their death, Lillian Herrick took over the care when he was 48 years. After her death, Henry stayed in a long-term care facility founded by Lillian Herrick's family. Researchers from MIT and other places continued to seek understanding of various aspects of his cognitive functioning and neural correlates. Henry gradually became known within the neuroscience community, with references to him as H.M. appearing in psychology and neuroscience textbooks and scientific papers. ^{[3],[5],[6],[7],[8]}

After 75 years of age, his physical health deteriorated (due to intermittent seizures, hypertension, vascular dementia-like brain changes, osteoporosis, sleep apnea) and he became fully dependent on a wheelchair to move from place to place. On December 2, 2008 at age of 82 years, he died at 5:30 pm.

For the first time, Henry's name was made public, and with the conservator's permission, Henry's brain was donated to Mass. General and MIT.
"Henry's intact brain was examined by the Neuropathologist at Mass General, scanned by investigators in the Mass General Martinos Center, and cut into 70-μ slices at the University of California, San Diego (UCSD). This brain will be the centerpiece in the Digital Brain Library Project at UCSD". ^[9]

A three-dimensional reconstruction of Henry's brain using magnetic resonance imaging data has been done as part of "Project H.M." in brain observatory project. ^[10] His case inspired hundreds of other researchers to investigate various kinds of amnesia and memory disorders, using different approaches with non-human primates and other animals.

Ethical Issues

Several ethical aspects arise pertaining to the use of a controversial experimental procedure with bilateral resection. It is possible that with frequent seizures, Henry's life would be shortened without the operation. However, the current life, though long, rendered him incapable of forming new memories.

To conclude, Henry's case helped to launch a fertile period of research in memory organization aimed at delineation of the cognitive and neural processes of the memory formation.

References

1.	Squire LR. The legacy of patient H.M. for neuroscience. Neuron 2009 15;61:6-9.
2.	Corkin S. Permanent Present Tense: The Unforgettable Life of the Amnesic Patient. New York: H.M. Basic Books; 2013.
3.	Scoville WB, Milner B. Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 1957;20:11-21.
4.	Corkin S. What′s new with the amnesic patient H.M.? Nat Rev Neurosci 2002;3:153-60.
5.	Moscovitch M. Memory before and after H.M.: An impressionistic historical perspective. In: Zeman A, Kapur N, Jones-Gotman M, editors. Epilepsy and Memory. Oxford: Oxford University Press; 2012. p. 19-50.
6.	Corkin S, Amaral DG, González RG, Johnson KA, Hyman BT. H. M.′s medial temporal lobe lesion: Findings from magnetic resonance imaging. J Neurosci 1997;17:3964-79.
7.	Milner B. Brenda Milner. In: Squire LR, editor. The History of Neuroscience in Autobiography. Vol. 2. San Diego: Academic Press; 1998. p. 276-305.
8.	Schmolck H, Kensinger EA, Corkin S, Squire LR. Semantic knowledge in patient H.M. and other patients with bilateral medial and lateral temporal lobe lesions. Hippocampus 2002;12:520-33.
9.	Annese J, Schenker-Ahmed NM, Bartsch H, Maechler P, Sheh C, Thomas N, et al. Postmortem examination of patient H.M.′s brain based on histological sectioning and digital 3D reconstruction. Nat Commun 2014;5:3122.
10.	Project HM. The Brain Observatory. Available from: http://www.thebrainobservatory.ucsd.edu/hm. [Last accessed on 2014 Dec 01].s