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

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.

Full text

91
Journal of Mental Health and Human Behaviour ¦ September 2014 ¦ Volume 19 ¦ Issue 2 91
Inspirations from History
“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decits.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indenitely”
on Tabs Dilantin, Phenobarbital, Tridione, Mesantoin) with
onlysomeresponse.RepeatedEEGstudiesdidnotnd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.[1-3]Henrywouldbetherst
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,
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
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 decitsseenafter an experimental operationfor
intractable epilepsy led to some critical discoveries pertaining to memory organization in human brain.
Key words: Henry Molaison, history, memory
Address for correspondence: Dr. Raman Deep Pattanayak,
Department of Psychiatry, A.I.I.M.S.
E‑Mail: drramandeep@gmail.com
Access this article online
Quick Response Code:
Website:
www.jmhhb.org
DOI:
10.4103/0971-8990.153719
Abstract
[Downloaded free from http://www.jmhhb.org on Tuesday, June 1, 2021, IP: 103.213.125.242]

Shah, et al.: The study of patient Henry Molaison
92 Journal of Mental Health and Human Behaviour ¦ September 2014 ¦ Volume 19 ¦ Issue 2
92
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ndings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
specicnature.Hisamnesiawaspure–largelyunconfounded
byothercognitivedecits.[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decits
• 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 [2,4-9]:
• 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 indenitely.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
signicant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
rst 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
rst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decient.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,
[Downloaded free from http://www.jmhhb.org on Tuesday, June 1, 2021, IP: 103.213.125.242]

Shah, et al.: The study of patient Henry Molaison
93
Journal of Mental Health and Human Behaviour ¦ September 2014 ¦ Volume 19 ¦ Issue 2 93
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scienticpapers.[3,5-8]
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 rst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].
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.
Source of Support: Nil.Conict of Interest:Nonedeclared.
[Downloaded free from http://www.jmhhb.org on Tuesday, June 1, 2021, IP: 103.213.125.242]