J. Neurol. Neurosurg. Psychiat., 1957, 20, 11.
LOSS OF RECENT MEMORY AFTER BILATERAL
HIPPOCAMPAL LESIONS
BY
WILLIAM BEECHER SCOVIILLE and BRENDA MILNER
From the Department of Neurosurgery, Hartford Hospital, and the Department of Neurology and Neurosurgery,
McGill University, and the Montreal Neurological Institute, Canada
In 1954 Scoville described a grave loss of recent
memory which he had observed as a sequel to
bilateral medial temporal-lobe resection in one
psychotic patient and one patient with intractable
seizures. In both cases the operations had been
radical ones, undertaken only when more conservative
forms of treatment had failed. The removals
extended posteriorly along the mesial surface of the
temporal lobes for a distance ofapproximately 8 cm.
from the temporal tips and probably destroyed the
anterior two-thirds of the hippocampus and hippocampal
gyrus bilaterally, as well as the uncus and
amygdala. The unexpected and persistent memory
deficit which resulted seemed to us to merit further
investigation. We have therefore carried out formal
memory and intelligence testing ofthese two patients
and also of eight other patients who had undergone
similar, but less radical, bilateral medial temporallobe
resections.* The present paper gives the results
of these studies which point to the importance of
the hippocampal complex for normal memory function.
Whenever the hippocampus and hippocampal
gyrus were damaged bilaterally in these operations
some memory deficit was found, but not otherwise.
We have chosen to report these findings in full,
partly for their theoretical significance, and partly as
a warning to others of the risk to memory involved
in bilateral surgical lesions of the hippocampal
region.
Operations
During the past seven years in an effort to preserve
the overall personality in psychosurgery some 300
fractional lobotomies have been performed, largely
on seriously ill schizophrenic patients who had failed
to respond to other forms of treatment. The aim in
these fractional procedures was to secure as far as
possible any beneficial effects a complete frontal
lobotomy might have, while at the same time avoiding
its undesirable side-effects. And it was in fact
found that undercutting limited to the orbital surfaces
of both frontal lobes has an appreciable
therapeutic effect in psychosis and yet does not cause
any new personality deficit to appear (Scoville,
Wilk, and Pepe, 1951). In view of the known close
relationship between the posterior orbital and mesial
temporal cortices (MacLean, 1952; Pribram and
Kruger, 1954), it was hoped that still greater
psychiatric benefit might be obtained by extending
the orbital undercutting so as to destroy parts of the
mesial temporal cortex bilaterally. Accordingly, in
30 severely deteriorated cases, such partial temporallobe
resections were carried out, either with or without
orbital undercutting. The surgical procedure
has been described elsewhere (Scoville, Dunsmore,
Liberson, Henry, and Pepe, 1953) and is illustrated
anatomically in Figs. 1 to 4. All the removals have
been bilateral, extending for varying distances along
the mesial surface of the temporal lobes. Five were
limited to the uncus and underlying amygdaloid
nucleus; all others encroached also upon the anterior
hippocampus, the excisions being carried back 5 cm.
or more after bisecting the tips ofthe temporal lobes,
with the temporal horn constituting the lateral edge
of resection. In one case only in this psychotic
group all tissue mesial to the temporal horns for a
distance of at least 8 cm. posterior to the temporal
tips was destroyed, a removal which presumably
included the anterior two-thirds of the hippocampal
complex bilaterally.
An equally radical bilateral medial temporal-lobe
resection was carried out in one young man (H. M.)
with a long history of major and minor seizures
uncontrollable by maximum medication of various
forms, and showing diffuse electro-encephalographic
abnormality. This frankly experimental operation
was considered justifiable because the patient was
totally incapacitated by his seizures and these had
proven refractory to a medical approach. It was
suggested because of the known epileptogenic qualities
of the uncus and hippocampal complex and
because of the relative absence of post-operative
* These further psychological examinations by one of the authors,
B. M., were made possible through the interest of Dr. Wilder Penfield.
11
WILLIAM BEECHER SCO VILLE AND BRENDA MILNER
.....+..*,;,...........................f. :.i
i.O,.r.FiG.
1.-Area removed bilaterally from the medial temporal lobes.demonstrating 5 cm. as well as 8 cm. removals through supra-orbital
trephines.
seizures in our temporal-lobe resections as compared
with fractional lobotomies in other areas. The
operation was carried out with the understanding
and approval of the patient and his family, in the
hope of lessening his seizures to some extent. At
operation the medial surfaces of both temporal lobes
were exposed and recordings were taken from both
surface and depth electrodes before any tissue was
removed; but again no discrete epileptogenic focus
was found. Bilateral resection was then carried out,
extending posteriorly for a distance of 8 cm. from
the temporal tips.
Results
The psychiatric findings bearing upon the treatment
of schizophrenia have already been reported
(Scoville and others, 1953). Briefly, it was found
that bilateral resections limited to the medial portions
of the temporal lobes were without significant therapeutic
effect in psychosis, although individual
patients (including the one with the most radical
removal) did in fact show some improvement. There
have been no gross changes in personality. This is
particularly clear in the case of the epileptic, nonpsychotic
patient whose present cheerful placidity
does not differ appreciably from his pre-operative
status and who, in the opinion of his family, has
shown no personality change. Neurological changes
in the group have also been minimal. The incidence
and severity of seizures in the epileptic patient were
sharply reduced for the first year after operation,
and although he is once again having both major and
minor attacks, these attacks no longer leave him
stuporous, as they formerly did. It has therefore
been possible to reduce his medication considerably.
As far as general intelligence is concerned, the
epileptic patient has actually improved slightly since
operation, possibly because he is less drowsy than
before. The psychotic patients were for the most
part too disturbed before operation for finer testing
of higher mental functions to be carried out, but
certainly there is no indication of any general
intellectual impairment resulting from the operation
in those patients for whom the appropriate test data
are available.
There has been one striking and totally unexpected
12
.:
.......
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LOSS OF RECENT MEMORY AFTER BILATERAL HIPPOCAMPAL LESIONS 13
/ 7e \FIG. 2.-Diagrammatic cross-sections of
iA . - }>i,/ \ human brain illustrating extent of
- -t ; ,57 ^ \ attempted bilateral medial temporal- - - ---- -- lobe resection in the radical operation.
.I - f- (For diagrammaticpurposes the resection
has been shown on one side only.)
A ~ \ BA
K, A
C ~~~~~yr -\ flU)CX ;g94 1_
*A< W b eJ ) C <S Bi::) 5
7< ~~~~~~~~~~~t7
-,
c, "t; ar " r paL-)t:
WILLIAM BEECHER SCOVILLE AND BRENDA MILNER
FIG. 3.-Post-operative skull radiograph with silver clip markers
outlining extent of bilateral resections limited to the uncus and
amygdala.
behavioural result: a grave loss of recent memory
in those cases in which the medial temporal-lobe
resection was so extensive as to involve the major
portion of the hippocampal complex bilaterally. The
psychotic patient having the most radical excision
(extending 8 cm. from the tips of the temporal lobes
bilaterally) has shown a profound post-operative
memory disturbance, but unfortunately this was not
recognized at the time because of her disturbed
emotional state. In the non-psychotic patient the
loss was immediately apparent. After operation this
young man could no longer recognize the hospital
staffnor find his way to the bathroom, and he seemed
to recall nothing of the day-to-day events of his
hospital life. There was also a partial retrograde
amnesia, inasmuch as he did not remember the
death of a favourite uncle three years previously,
nor anything of the period in hospital, yet could
recall some trivial events that had occurred just
before his admission to the hospital. His early
memories were apparently vivid and intact.
This patient's memory defect has persisted without
improvement to the present time, and numerous
illustrations of its severity could be given. Ten
months ago the family moved from their old house
to a new one a few blocks away on the same street;
he still has not learned the new address, though
remembering the old one perfectly, nor can he be
trusted to find his way home alone. Moreover, he
does not know where objects in continual use are
kept; for example, his mother, still has to tell him
where to find the lawn mower, even though he may
have been using it only the day before. She also
states that he will do the same jigsaw puzzles day
FIG. 4.-Post-operative skull radiograph with silver clip markers
outlining the extent of the bilateral resections including the anterior
hippocampal complex (approximately 6 cm. posterior to
the tip of the anterior temporal fossa).
after day without showing any practice effect and
that he will read the same magazines over and over
again without finding their contents familiar. This
patient has even eaten luncheon in front of one of us
(B. M.) without being able to name, a mere half-hour
later, a single item of food he had eaten; in fact, he
could not remember having eaten luncheon at all.
Yet to a casual observer this man seems like a
relatively normal individual, since his understanding
and reasoning are undiminished.
The discovery of severe memory defect in these
two patients led us to study further all patients in
the temporal-lobe series who were sufficiently cooperative
to permit formal psychological testing.
The operation sample included, in addition to the
two radical resections, one bilateral removal of the
uncus, extending 4 cm. posterior to the temporal
tips, and six bilateral medial temporal-lobe resections
in which the removal was carried back 5 or 6 cm.
to include also a portion of the anterior hippocampus;
in three of these six cases the temporal-lobe
resection was combined with orbital undercutting.
One unilateral case was also studied in which right
inferior temporal lobectomy and hippocampectomy
had been carried out for the relief of incisural
hemiation due to malignant oedema (Fig. 5). We
found some memory impairment in all the bilateral
cases in which the removal was carried far enough
posteriorly to damage the hippocampus and hippocampal
gyrus, but in only one of these six additional
cases (D. C.) did the memory loss equal in severity
that seen in the two most radical excisions. The
case with bilateral excision of the uncus (in which
the removal can have involved only the amygdaloid
14
LOSS OF RECENT MEMORY AFTER BILATERAL HIPPOCAMPAL LESIONS 15
N3,.
\!T \%
FIo. 5.-Unilateral inferior horizontal
temporal lobectomy
extending a distance of 8 cm.
posterior to the tip of the
anterior temporal fossa. This
operation is performed for
incisural herniation of the
temporal lobes (Case 10).
and peri-amygdaloid areas) showed excellent memory
function. The unilateral operation, extensive as it
was, has caused no lasting memory impairment,
though some disturbance of recent memory was
noted in the early post-operative period (Scoville,
1954); we now attribute this deficit to temporary
interference with the functioning of the hippocampal
zone of the opposite hemisphere by contralateral
pressure.
The histories and individual test results for these
10 cases are reported below, and the Table summarizes
the principal findings. For purposes of
comparison the cases have been divided into three
groups representing different degrees of memory
impairment.
Group I: Severe Memory Defect
In this category are those patients who since
operation appear to forget the incidents of their
daily life as fast as they occur. It is interesting that
all these patients were able to retain a three-figure
number or a pair of unrelated words for several
minutes, if care was taken not to distract them in
the interval. However, they forgot the instant
attention was diverted to a new topic. Since in
normal life the focus of attention is constantly
a.
16 WILLIAM BEECHER SCOVILLE AND BRENDA MILNER
TABLE
CLASSIFICATION OF CASES
Approximate
Age at Bi- Extent of
Time of or Removal Time
Cases Folow- Sex Diagnosis Operation Uni- along between Wechsler Scale
up ~~~~~~~~~~~lateral Medial Operation
(yr.) ~~~~~~~~~Temporal and(yr.) ~~~~~~
~~~~~~~~~~~LobesTesting Intelli(cm.)
(mth.) gence Memory
Quotient Quotient
Group 1: Severe
Memory Defect
Case 1, H. M. 29 M Epilepsy Medial temporal B 8 20 112 67
Case 2, D. C. 47 M Paranoid Medial temporal and B 5 5 21 122 70
schizophrenia orbital undercutting
Case 3, M. B. 55 F Manic-depressive Medial temporal B 8 28 78 60
psychosis
Group II: Moderate
Memory Defect
Case 4, A. Z. 35 F Paranoid Medial temporal B 5 40 96 84
schizophrenia
Case 5, M. R. 40 F Paranoid Medial temporal and B 5 39 123 81
schizophrenia orbital undercutting
Case 6, A. R. 38 F Hebephrenic Medial temporal and B 4-5 47 Incomplete
schizophrenia orbital undercutting
Case 7, C. G. 44 F Schizophrenia Medial temporal B 5-5 41 Incomplete
Case 8, A. L. 31 M Schizophrenia Medial temporal B 6 38 Incomplete
Group III: No
Memory Defect
Case 9, I. S. 54 F Paranoid Uncectomy B 4 53 122 125
schizophrenia
Case 10, E. G. 55 F Incisural Inferior temporal U-Rt. 9 16 93 90
herniation lobectomy
changing, such individuals show an apparently
complete anterograde amnesia. This severe defect
was observed in the two patients having the most
radical bilateral medial temporal-lobe excisions (with
the posterior limit of removal approximately 8 cm.
from the temporal tips) and in one other case, a
bilateral 5 5 cm. medial temporal excision. These
three cases will now be described.
Case 1, H. M.-This 29-year-old motor winder, a high
school graduate, had had minor seizures since the age
of 10 and major seizures since the age of 16. The small
attacks lasted about 40 seconds, during which he would
be unresponsive, opening his mouth, closing his eyes, and
crossing both arms and legs; but he believed that he could
" half hear what was going on ". The major seizures
occurred without warning and with no lateralizing sign.
They were generalized convulsions, with tongue-biting,
urinary incontinence, and loss of consciousness followed
by prolonged somnolence. Despite heavy and varied
anticonvulsant medication the major attacks had increased
in frequency and severity through the years until the
patient was quite unable to work.
The aetiology of this patient's attacks is not clear.
He was knocked down by a bicycle at the age of 9
and was unconscious for five minutes afterwards, sustaining
a laceration of the left supra-orbital region. Later
radiological studies, however, including two pneumoencephalograms,
have been completely normal, and the
physical examination has always been negative.
Electro-encephalographic studies have consistently
failed to show any localized epileptogenic area. In the
examination of August 17, 1953, Dr. T. W. Liberson
described diffuse slow activity with a dominant frequency
of 6 to 8 per second. A short clinical attack was said to
be accompanied by generalized 2 to 3 per second spikeand-wave
discharge with a slight asymmetry in the central
leads (flattening on the left).
Despite the absence of any localizing sign, operation
was considered justifiable for the reasons given above.
On September 1, 1953, bilateral medial temporal-lobe
resection was carried out, extending posteriorly for a
distance of 8 cm. from the midpoints of the tips of the
temporal lobes, with the temporal horns constituting the
lateral edges of resection.
After operation the patient was drowsy for a few days,
but his subsequent recovery was uneventful apart from
the grave memory loss already described. There has
been no neurological deficit. An electro-encephalogram
taken one year after operation showed increased spikeand-wave
activity which was maximal over the frontal
areas and bilaterally synchronous. He continues to have
seizures, but these are less incapacitating than before.
Psychological Examination.-This was performed on
April 26, 1955. The memory defect was immediately
apparent. The patient gave the date as March, 1953, and
his age as 27. Just before coming into the examining
room he had been talking to Dr. Karl Pribram, yet he
had no recollection of this at all and denied that anyone
had spoken to him. In conversation, he reverted constantly
to boyhood events and seemed scarcely to realize
that he had had an operation.
On formal testing the contrast between his good
general intelligence and his defective memory was most
striking. On the Wechsler-Bellevue Intelligence Scale he
achieved a full-scale I.Q. rating of 112, which compares
LOSS OF RECENT MEMORY AFTER BILATERAL HIPPOCAMPAL LESIONS 17
favourably with the pre-operative rating of 104 reported
by Dr. Liselotte Fischer in August, 1953, the improvement
in arithmetic being particularly striking. An extensive
test battery failed to reveal any deficits in perception,
abstract thinking, or reasoning ability, and his motivation
remained excellent throughout.
On the Wechsler Memory Scale (Wechsler, 1945) his
immediate recall of stories and drawings fell far below the
average level and on the " associate learning " subtest
of this scale he obtained zero scores for the hard word
associations, low scores for the easy associations, and
failed to improve with repeated practice. These findings
are reflected in the low memory quotient of 67. Moreover,
on all tests we found that once he had turned to a
new task the nature of the preceding one could no longer
be recalled, nor the test recognized if repeated.
In summary, this patient appears to have a complete
loss of memory for events subsequent to bilateral medial
temporal-lobe resection 19 months before, together with
a partial retrograde amnesia for the three years leading
up to his operation; but early memories are seemingly
normal and there is no impairment of personality or
general intelligence.
Case 2, D. C.-This 47-year-old doctor was a paranoid
schizophrenic with a four-year history of violent, combative
behaviour. Before his illness he had been practising
medicine in Chicago, but he had always shown
paranoid trends and for this reason had had difficulty
completing his medical training. His breakdown followed
the loss of a lawsuit in 1950, at which time he made a
homicidal attack on his wife which led to his admission
to hospital. Since then both insulin and electro-shock
therapy had been tried without benefit and the prognosis
was considered extremely poor. On May 13, 1954, at the
request of Dr. Frederick Gibbs and Dr. John Kendrick, a
bilateral medial temporal-lobe resection combined with
orbital undercutting was carried out at Manteno State
Hospital (W. B. S., with the assistance of Dr. John
Kendrick). The posterior limit of the removal was 5 cm.
from the sphenoid ridge, or roughly 5-5 cm. from the
tips of the temporal lobes, with the inferior horns of the
ventricles forming the lateral edges of resection. Recording
from depth electrodes at the time of operation showed
spiking from the medial temporal regions bilaterally with
some spread to the orbital surfaces of both frontal lobes,
but after the removal had been completed a normal
electro-encephalographic record was obtained from the
borders of the excision.
Post-operative recovery was uneventful and there has
been no neurological deficit. Since operation the patient
has been outwardly friendly and tractable with no return
of his former aggressive behaviour, although the paranoid
thought content persists; he is considered markedly
improved. But he too shows a profound memory disturbance.
At Manteno State Hospital he was described
as " confused ", because since the operation he had been
unable to find his way to bed and seemed no longer to
recognize the hospital staff. However, no psychological
examination was made there, and on November 29, 1955,
he was transferred to Galesburg State Research Institute
where he was interviewed by one of us (B. M.) on
January 12, 1956.
Psychological Findings.-This patient presented exactly
the same pattern of memory loss as H. M. He was courteous
and cooperative throughout the examination, and
the full-scale Wechsler I.Q. rating of 122 showed him to
be still of superior intellect. Yet he had no idea where he
was, explaining that naturally the surroundings were
quite unfamiliar because he had only arrived there for
the first time the night before. (In fact, he had been there
six weeks.) He was unable to learn either the name of the
hospital or the name of the examiner, despite being told
them repeatedly. Each time he received the information
as something new, and a moment later would deny
having heard it. At the examiner's request he drew a dog
and an elephant, yet half an hour later did not even
recognize them as his own drawings. On the formal tests
of the Wechsler Memory Scale his immediate recall of
stories and drawings was poor, and the memory quotient
of 70 is in sharp contrast to the high I.Q. level. As with
H. M., once a new task was introduced there was total
amnesia for the preceding one; in his own words, the
change of topic confused him. This man did not know
that he had had a brain operation and did not recall
being at Manteno State Hospital, although he had spent
six months there before the operation as well as six
months post-operatively. Yet he could give minute
details of his early life and medical training (accurately,
as far as we could tell).
Case 3, M. B.-This 55-year-old manic depressive
woman, a former clerical worker, was admitted to
Connecticut State Hospital on December 27, 1951, at
which time she was described as anxious, irritable, argumentative,
and restless, but well-orientated in all spheres.
Her recent memory was normal, in that she knew how
long she had been living in Connecticut and could give
the date of her hospital admission and the exact times of
various clinic appointments. On December 18, 1952, a
radical bilateral medial temporal-lobe resection was
carried out, with the posterior limit of removal 8 cm.
from the temporal tips. Post-operatively she was stuporous
and confused for one week, but then recovered
rapidly and without neurological deficit. She has become
neater and more even-tempered and is held to be greatly
improved. However, psychological testing by Mr. 1.
Borganz in November, 1953, revealed a grave impairment
of recent memory; she gave the year as 1950 and
appeared to recall nothing of the events of the last three
years. Yet her verbal intelligence proved to be normal.
She was examined briefly by B. M. in April, 1955, at
which time she showed a global loss of recent memory
similar to that of H. M. and D. C. She had been brought
to the examining room from another building, but had
already forgotten this; nor could she describe any other
part of the hospital although she had been living there
continuously for nearly three and a half years. On the
Wechsler Memory Scale her immediate recall of stories
and drawings was inaccurate and fragmentary, and
delayed recall was impossible for her even with prompting;
when the material was presented again she failed to
recognize it. Her conversation centred around her early
WILLIAM BEECHER SCOVILLE AND BRENDA MILNER
life and she was unable to give any information about
the years ofher hospital stay. Vocabulary, attention span,
and comprehension were normal, thus confirming Mr.
Borganz' findings.
Group II: Moderately Severe Memory Defect
In this second category are those patients who can
be shown to re- some impression of new places
and events, alth. .gi they are unable to learn such
arbitrary new associations as people's names and
cannot be depended upon to carry out commissions.
Subjectively, these patients complain of memory
difficulty, and objectively, on formal tests, they do
very poorly irrespective of the type of material to be
memorized. 'Thefive remaining patients with bilateral
medial temporal-lobe removals extending 5 or 6 cm.
posteriorly from the temporal tips make up this
group. Only two of these patients were well enough
to permit thorough testing, but in all five cases
enough data were obtained to establish that the
patient did have a memory defect and that it was not
of the gross type seen in Group I. The individual
cases are reported below.
Case 4, A. Z.-This 35-year-old woman, a paranoid
schizophrenic, had been in Cor < icut State Hospital
for three years and extensiv o-shock therapy had
been tried without lasting be ''-'She was described as
tense, assaultative, and se Ay preoccupied. On
November 29, 1951, bilatc A medial temporal-lobe
resection was carried out under local anaesthesia, the
posterior limit of the removal being approximately 5 cm.
from the tips of the temporal robes. During subpial
resection of the right hippocanv-al cortex the surgeon
inadvertently went through the arachnoid and injured
by suction a portion of the right peduncle, geniculate, or
hypothalamic region with immediate development of
deep coma. The injury was visualized by extra-arachnoid
inspection. Post-operatively the patient remained in
stupor for 72 hours and exhibited a left spastic hemiplegia,
contracted fixed pupils, strabismus, and lateral
nystagmus of the right eye; vital signs remained constant
and within normal limits. She slowly recovered the use
of the left arm and leg and her lethargy gradually disappeared.
By the seventh post-operative day she could
walk without support and pupillary responses had
returned to normal. The only residual neurological
deficit has been a left homonymous hemianopia. Of
particular interest was the dramatic post-operative improvement
in her psychotic state with an early complete
remission of her delusions, anxiety, and paranoid behaviour.
At the same time she showed a retrograde
amnesia for the entire period of her illness.
This patient was discharged from the hospital nine
months after operation and is now able to earn her living
as a domestic worker. However, she complains that her
memory is poor, and psychological examination (April
27, 1955) three and a half years post-operatively confirms
this. But the deficit is less striking than in the three cases
reported above. This patient, for example, was able to
give the address of the house where she worked although
she had been there only two days, and she could even
describe the furnishings in some detail although she had
not yet learned the name of her employer. She was also
able to give an accurate, though sketchy, description of a
doctor who had spoken to her briefly that morning and
whom she had never seen before. However, she could
recall very little of the conversation.
Formal testing at this time showed her intelligence to
lie within the average range with no impairment of attention
or concentration. The Wechsler-Bellevue I.Q. rating
was 96. On the Wechsler Memory Scale her immediate
recall of stories was normal, but passing from one story
to the next was enough to make her unable to recall the
first one, though a few fragments could be recovered with
judicious prompting. She showed the same rapid forgetting
on the " visual retention" subtest, indicating that
the memory impairment was not specific to verbal
material. Finally, she was conspicuously unsuccessful on
the "associate learning " subtest, failing to master a
single unfamiliar word association. This examination as
a whole provides clear evidence of an impairment of
recent memory.
Case 5, M. R.-This 40-year-old woman, a paranoid
schizophrenic with superimposed alcoholism, had been a
patient at Norwich State Hospital for 11 years, receiving
extensive electro-shock therapy. Bilateral medial temporal-lobe
resection combined with orbital undercutting
was carried out on January 17, 1952, the posterior extent
of removal being roughly 5 cm. from the temporal tips.
The patient has shown complete remission of psychotic
symptoms and was discharged from the hospital on
September 16, 1954, to the care of her family.
Psychological Examination.-This was performed on
April 29, 1955. Tests showed this woman to be of
superior intelligence, with a full-scale I.Q. rating of 123
on the Wechsler Scale. However, she complained of poor
memory, adding that she could remember faces and " the
things that are important ", but that, to her great embarrassment,
she forgot many ordinary daily happenings.
Upon questioning she gave the year correctly but did
not know the month or the day. She knew that she
had had an operation in 1952 but did not recognize the
surgeon (W. B. S.) nor recall his name. Formal testing
revealed the same pattern of memory disturbance as
A. Z. had shown, and the memory quotient of 81 compares
most unfavourably with the high I.Q. rating. In
conversation, she reverted constantly to discussion of her
work during the years of depression and showed little
knowledge of recent events.
Case 6, A. R.-This 38-year-old woman had been in
hospital for five years with a diagnosis of hebephrenic
schizophrenia. Before operation she was said to be noisy,
combative, and suspicious, and electro-shock therapy
had caused only transient improvement in this condition.
On May 31, 1951,bilateral medial temporal-lobe resection
combined with orbital undercutting was carried out, the
posterior limit of removal being slightly less than 5 cm.
from the bisected tips of the temporal lobes. After
operation the patient gradually became quieter and more
18
LOSS OF RECENT MEMORY AFTER BILATERAL HIPPOCAMPAL LESIONS 19
cooperative and on September 29, 1952, she was discharged
to her home. There have been no neurological
sequelae.
Psychological Examination.-This was performed in
April, 1955. Examination revealed a hyperactive woman,
too excited and talkative for prolonged testing. She
showed a restricted span of attention but scores on verbal
intelligence tests were within the dull normal range.
Moreover, she appeared to recall some recent happenings
quite well. Thus, she knew that her daughter had caught
a 7 o'clock train to New York City that morning to buy
a dress for a wedding the following Saturday. She could
also describe the clothes worn by the secretary who had
shown her into the office. However, on formal testing
some impairment of recent memory was seen, although
unlike the other patients in this group she did succeed
on some of the difficult items ofthe " associate learning "
test. As with A. Z. and M. R., the deficit appeared most
clearly on tests of delayed recall after a brief interval
filled with some other activity. Thus, on the " logical
memory " test she gave an adequate version ofeach story
immediately after hearing it, but passing from one story
to the next caused her to forget the first almost completely;
similar results were obtained for the recall of
drawings. We conclude that this patient has a memory
impairment identical in type to that of the other patients
in this group, but somewhat milder. It is interesting that
she had a relatively small excision.
Case 7, C. G.-This 44-year-old schizophrenic woman
had been in the hospital for 20 years without showing any
improvement in her psychosis. On November 19, 1951,
bilateral medial temporal-lobe resection was carried out
under local anaesthesia, the posterior limit of removal
being 5-5 cm. from the tips of the temporal lobes. There
was temporary loss of consciousness during the resection
but the patient was fully conscious at the end of the
procedure and post-operative recovery was uneventful.
There has been no neurological deficit. She is considered
to be in better contact than before but more forgetful.
This patient was examined at Norwich State Hospital
in April, 1955, and although she was too distractible for
prolonged testing, it was possible to show that she remembered
some recent events. For example, she knew
that she had been working in the hospital beauty parlour
for the past week and that she had been washing towels
that morning. Yet formal memory testing revealed the
same deficit as that shown by A. Z. and M. R., though
less extensive data were obtained in this case.
Case 8, A. L.-This 31-year-old schizophrenic man
had been a patient at Norwich State Hospital since
October, 1950. He had first become ill in August, 1950,
demonstrating a catatonic type of schizophrenia with
auditory and visual hallucinations. On January 31, 1952,
bilateral medial temporal-lobe resection combined with
orbital undercutting was carried out, the removal extending
posteriorly for a distance of 6 cm. along the mesial
surface of the temporal lobes. Recovery was uneventful
and no neurological deficit ensued. The patient has been
more tractable since the operation but he is still subject
to delusions and hallucinations. He is said to have a
memory defect. When interviewed by B. M. in April,
1955, he was found to be too out of contact for extensive
formal testing. However, he was able to recall the examiner's
name and place of origin 10 minutes after hearing
them for the first time, and this despite the fact that the
interval had been occupied with other tasks. He could
also recognize objects which had been shown to him
earlier in the interview, selecting',-m correctly from
others which he had not seen befc But his immediate
recall of drawings and stories was "aulty and these were
forgotten completely once his attention was directed to
a new topic.
In this patient we stress the negative findings: despite
his evident psychosis he did not show the severe memory
loss typical of the patients in Group 1. Yet the brief
psychological examination and the hospital record both
indicate some impairment of recent memory, though no
reliable quantitative studies could be made.
Group III: No Persistent Memory Defect
Case 9, I. S.-This 54-year-old woman had a 20-year
history of paranoid schizophrenia, with auditory hallucinations
and marked emotional lability. She had
attempted suicide on several occasions. On November 16,
1950, six months after admission to a state hospital, a
bilateral medial temporal lobectomy was carried out
under local anaesth .ia with sectioning of the tips of the
temporal lobes and suction removal of the medial
portion, extending ) cm. to include the uncus and
amygdala. Thus thiu a conservative bilateral removal,
sparing the hipj. ampal region. The operation
was complicated by acciJ1ental damage to the midbrain
from the electrocautery, causing the patient to give a
convulsive twitch wi.:ch was followed by coma and
extensive rigidity. After operation she was somnolent
for a time with continuing rigidity, more marked on the
left side than on the right. Vital signs were normal. She
required traction to prevent flexure spasm contractures.
There was slow improvement over the ensuing two
months, with some residual clumsiness and spasticity of
gait. For a time the patient's mental state was worse
than before operation, but within three months she had
improved markedly, with increased gentleness, diminished
auditory hallucinations, and no depression. She ultimately
showed the best result of all the cases in this series
and was discharged from the hospital five months after
operation.
This patient was re-examined on May 11, 1956. She
shows a complete remission of her former psychotic
behaviour and is living at home with her husband and
leading a normal social life. Her hallucinations have
ceased. Upon neurological examination she shows some
25% residual deficit, manifested chiefly by spastic incoordination
of gait and similar but less marked incoordination
ofthe arms. The deep leg reflexes are increased
to near clonus, but there is no Babinski sign. Arm
reflexes are moderately increased and abdominal reflexes
absent. Smell is completely lost but all other sense
modalities are intact and other cranial nerves normal.
Psychological Findings.-The patient was examined
psychologically in April, 1955. From the standpoint of
WILLIAM BEECHER SCOVILLE AND BRENDA MILNER
memory, this patient presents a complete contrast to the
cases reported above, obtaining excellent scores for both
immediate and delayed recall of stories, drawings, and
word associations, and describing accurately episodes
from the relatively early post-operative period. The
memory quotient of 125 is consistent with the I.Q. level
of 122, and both would be classed as superior. This is so
despite prolonged psychosis, intensive electro-shock
therapy, and brain-stem damage of undetermined extent.
Case 10, E. G.-This 55-year-old woman developed
malignant oedema after removal of a huge, saddle-type
meningioma from the right sphenoid ridge; the pupils
were dilated, she lost consciousness, and vital signs began
to fail. A diagnosis of incisural hippocampal herniation
was made, and, as a life-saving measure, unilateral nondominant
inferior temporal lobectomy was carried out,
with deliberate resection of the hippocampus and hippocampal
gyrus to a distance of 9 cm. from the tip of the
temporal lobe. (The operative procedure is illustrated
in Fig. 5.) Vital signs improved immediately and consciousness
gradually returned, but for a few weeks the
patient showed a disturbance ofrecentmemory resembling
that seen in our bilateral cases. However, follow-up
studies in April, 1955, 16 months after operation, showed
no residual memory loss. Both immediate and delayed
recall were normal and the memory quotient of 90 was
completely consistent with the I.Q. level of 93. Neurological
examination at this time showed a left homonymous
visual field defect with macular sparing but no
other deficit.
Discussion
The findings in these 10 cases point to the importance
of the hippocampal region for normal memory
function. All patients in this series having bilateral
medial temporal-lobe resections extensive enough
to damage portions of the hippocampus and hippocampal
gyrus bilaterally have shown a clear and
persistent disturbance of recent memory, and in the
two most radical excisions (in which the posterior
limit ofremoval was at least 8 cm. from the temporal
tips) the deficit has been particularly severe, with no
improvement in the two or more years which have
elapsed since operation. These observations suggest
a positive relationship between the extent of destruction
to the hippocampal complex specifically and
the degree of memory impairment. The correlation
is not perfect, since D. C., who had only a 5-5 cm.
removal, showed as much deficit as did the two cases
of most radical excision. Moreover, in the absence
of necropsy material we cannot be sure of the exact
area removed.
In all these hippocampal resections the uncus and
amygdala have also ofcourse been destroyed. Nevertheless
the importance of the amygdaloid and periamygdaloid
region for memory mechanisms is open
to question, considering the total lack of memory
impairment in the bilateral uncectomy case (I. S.),
in which a 4 cm. medial-temporal lobe removal was
made. But not enough is known of the effects of
lesions restricted to the hippocampal area itself to
permit assessment of the relative contributions of
these two regions. This is a question on which
selective ablation studies in animals could well shed
important light, but unfortunately the crucial experiments
have yet to be done (Jasper, Gloor, and
Milner, 1956).
The role of the hippocampus specifically has been
discussed in some clinical studies. Glees and
Griffith (1952) put forward the view that bilateral
destruction ofthe hippocampus in man causes recentmemory
loss and mental confusion, citing in support
of this a somewhat unconvincing case of Grunthal
(1947) and also a case of their own in which the
hippocampus, the hippocampal and fusiform gyri,
and 75% of the fornix fibres had been destroyed
bilaterally by vascular lesion, but in which the rest
of the brain appeared normal at necropsy. Interestingly
enough, the amygdaloid nuclei were found
to be intact as were the mamillary bodies. This
patient showed marked anterograde and retrograde
amnesia.
More recently Milner and Penfield (1955) have
described a memory loss similar in all respects to
that shown by our patients, in two cases ofunilateral
partial temporal lobectomy in the dominant hemisphere.
In one case the removal was carried out in
two stages separated by a five-year interval, and the
memory loss followed the second operation only, at
which time the uncus, hippocampus, and hippocampal
gyrus alone were excised. Although these
authors had carried out careful psychological testing
in over 90 other cases of similar unilateral operation,
only in these two cases was a general memory loss
found. To account for the unusual deficit, they have
assumed that there was in each case a pre-operatively
unsuspected, but more or less completely destructive
lesion of the hippocampal area of the opposite hemisphere.
The unilateral operation would then deprive
the patient of hippocampal function bilaterally, thus
causing memory loss. The present study provides
strong support for this interpretation.
Memory loss after partial bilateral temporal
lobectomy has been reported by Petit-Dutaillis,
Christophe, Pertuiset, Dreyfus-Brisac, and Blanc
(1954) but in their patient the deficit was a transient
one, a finding which led these authors to question
the primary importance of the temporal lobes for
memory function. However, their temporal lobe
removals were complementary to ours in that they
destroyed the lateral neocortex bilaterally but spared
the hippocampal gyrus on the right and the uncus
and hippocampus on the left. It therefore seems
likely that the memory loss was due to temporary
20
LOSS OF RECENT MEMORY AFTER BILATERAL HIPPOCAMPAL LESIONS 21
interference with the functioning of the hippocampal
system, which later recovered.
We have stated that the loss seen in patients with
bilateral hippocampal lesions is curiously specific to
the domain of recent memory; neither in our cases
nor in those of Milner and Penfield was there any
deterioration in intellect or personality as a result
of hippocampal resection. It appears important to
emphasize this, since Terzian and Dalle Orc (1955)
have described gross behavioural changes (affecting
memory, perception, and sexual behaviour) after
bilateral temporal lobectomy in man; they consider
these changes comparable to Kluver and Bucy's
(1939) findings after radical bilateral temporal lobectomy
in the monkey. But Terzian and Ore included
not only the uncal and hippocampal areas, but also
the lateral temporal cortex in their bilateral removal.
In contrast to the grossly deteriorated picture they
describe, we find that bilateral resections limited to
the mesial temporal region cause no perceptual disturbance,
even on visual tests known to be sensitive
to unilateral lesions of the temporal neocortex
(Milner, 1954).
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. But the hippocampus has a strong
and orderly projection to the mamillary bodies
(Simpson, 1952), and as early as 1928 Gamper
claimed that lesions of the mamillary bodies were
commonly found in amnesic states of the Korsakoff
type. Moreover, Williams and Pennybacker (1954)
have carried out careful psychological studies of
180 patients with verified intracranial lesions and
find that a specific deficit in recent memory is most
likely to occur when the lesion involves the mamillary
region. It is possible, then, that when we have
two interrelated structures (hippocampus and mamillary
bodies) damage to either can cause memory
loss, a point which has been emphasized by Jasper
and others (1956). In view of these findings it is
interesting that sectioning the fornix bilaterally, and
thereby interrupting the descending fibres from the
hippocampus, appears to have little effect on behaviour
(Dott, 1938; Garcia Bengochea, De la
Torre, Esquivel, Vieta, and Fernandez, 1954),
though a transient memory deficit is sometimes seen
(Garcia Bengochea, 1955).
To conclude, the observations reported herein
demonstrate the deleterious effect of bilateral surgical
lesions of the hippocampus and hippocampal
gyrus on recent memory. The relationship between
this region and the overlying neocortex in the temporal
lobe needs further elucidation, as does its
relationship to deeper-lying structures.
Summary
Bilateral medial temporal-lobe resection in man
results in a persistent impairment of recent memory
whenever the removal is carried far enough posteriorly
to damage portions of the anterior hippocampus
and hippocampal gyrus. This conclusion is
based on formal psychological testing of nine cases
(eight psychotic and one epileptic) carried out from
one and one-half to four years after operation.
The degree of memory loss appears to depend on
the extent of hippocampal removal. In two cases
in which bilateral resection was carried to a distance
of 8 cm. posterior to the temporal tips the loss was
particularly severe.
Removal of only the uncus and amygdala bilaterally
does not appear to cause memory impairment.
A case of unilateral inferior temporal lobectomy
with radical posterior extension to include the major
portion of the hippocampus and hippocampal gyrus
showed no lasting memory loss. This is consistent
with Milner and Penfield's negative findings in a
long series of unilateral removals for temporal-lobe
epilepsy.
The memory loss in these cases of medial temporal-lobe
excision involved both anterograde and
some retrograde amnesia, but left early memories
and technical skills intact. There was no deterioration
in personality or general intelligence, and no
complex perceptual disturbance such as is seen after
a more complete bilateral temporal lobectomy.
It is concluded that the anterior hippocampus and
hippocampal gyrus, either separately or together,
are critically concerned in the retention of current
experience. It is not known whether the amygdala
plays any part in this mechanism, since the hippocampal
complex has not been removed alone, but
always together with uncus and amygdala.
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