Brain (1987), 110, 1631-1646

RETROSPLENIAL AMNESIA
by EDWARD VALENSTEIN, DAWN BOWERS, MIEKE VERFAELLIE,
KENNETH M. HEILMAN, ARTHUR DAYtfm/ROBERT T. WATSON

SUMMARY
A 39-year-old man developed retrograde and anterograde amnesia following haemorrhage from
an arteriovenous malformation situated near the splenium of the corpus callosum. MRI studies
demonstrated damage to the splenium, and to a region containing the retrosplenial cortex and the
cingulate bundle. The fornix was anterior and inferior to the site of maximal damage, but may have
been involved; the stria terminalis was probably spared. Structures known to be important in memory
but spared by the lesion included the hippocampus, thalamus, and basal forebrain. The retrosplenial
cortex receives input from the subiculum and projects to the anterior thalamus, thus providing an
alternative route between hippocampus and thalamus. Perhaps more importantly, medial temporal
structures involved in memory receive anterior thalamic input directly via the cingulate bundle and
indirectly through a relay in the retrosplenial cortex. We suggest that this thalamocortical portion
of Papez' circuit may be important in memory, and that lesions of the cingulum and retrosplenial
cortex may cause amnesia by disrupting this pathway.

INTRODUCTION

In 1977, Heilman and Sypert described a patient who developed severe amnesia in
association with the growth and removal of a pilocytic astrocytoma near the trigone
of the lateral ventricles. These authors postulated that the memory disturbance
was caused by involvement of the fornix bilaterally. They recognized that fornix
lesions in humans had not consistently been associated with amnesia; however,
they argued that, first, cases of alleged normal memory following fornix transection
were not well studied neuropsychologically and, secondly, lesions of the posterior
fornix interrupt connections between the fornix and thalamus that would be spared
by lesions of the columns of the fornix. Authors arguing against the importance
of the fornix in memory have discounted Heilman and Sypert's evidence on the
grounds that only surgical observation was available to document the extent of the
lesion, and that other structures, such as the temporal stem or the posterior
hippocampus, might have been involved by the tumour or by surgery (Horel, 1978).
We now report a patient with amnesia associated with haemorrhage from an
I Correspondence to: Dr Edward Valenstein, Department of Neurology, J. Hillis Miller Center, University of
Florida College of Medicine, Gainsville, FLA 32610, USA.

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(From the Department of Neurology and the Center for Neuropsychologica! Studies, University of
Florida College of Medicine, USA)

1632

E D W A R D VALENSTEIN AND OTHERS

CASE R E P O R T
On March 15, 1984, T.R., a 39-year-old right-handed college-educated accountant, awoke with a
severe headache. He was confused, and pyrexial, with a stiff neck and decreased memory. Lumbar
puncture yielded blood-stained CSF. He was transferred to the Shands Teaching Hospital, University
of Florida. His past medical history and family history were noncontributory. Nine months before
the onset of his illness he had moved from California to a responsible post in the offices of a large
corporation in Florida.
On admission (March, 15) his temperature was 38° C, and his blood pressure 118/90mmHg. He
had moderate meningism, was somnolent and orientated only for person. He recalled only 1 of 3
objects in 5 min, and had difficulty performing the serial 7s test. Spontaneous speech, comprehension
and repetition were normal. He had a right homonymous hemianopia, full extraocular movements
and normal pupillary responses. The rest of the cranial nerves were normal. He had no abnormal
motor signs or alteration in reflexes and pain sensation was intact.
Urine and blood studies, including clotting studies, were normal. A CT scan showed blood in the
ventricular system and an intracerebral haemorrhage just lateral to the splenium on the left (fig. 1).
An angiogram showed an arteriovenous malformation (AVM) both above and below the splenium
in the pericallosal cistern and the cistern of the velum interpositum, extending into the medial aspect
of the trigone of the left lateral ventricle (fig. 2). Feeding vessels arose from interhemispheric
branches of the left anterior and posterior cerebral arteries, and from choroidal branches of the left
posterolateral choroidal artery. He was treated with dexamethasone, cimetidine, phenytoin and
analgesics. He slowly became more alert. Repeat CT scans on March 21 and 29 demonstrated
disappearance of the intraventricular blood and partial resolution of the intracerebral haemorrhage.
There was slight ventricular enlargement.
Fifteen days after admission, he was alert and cooperative. He was orientated for place, person
and year, but was unsure of the month. He remembered 1 of 3 objects after distraction, but did not
recall the other 2 even with multiple choice. He had no recollection of the events of his illness, and
he was very uncertain about time relationships before his illness; for example, he could not remember
if he had moved to Florida before or after Christmas. Spontaneous speech was fluent, without errors,
and repetition and naming were normal. He made occasional errors on calculations, but right-left
orientation and finger naming were normal.
He had signs of a mild callosal disconnection. Although he made only occasional errors reading
aloud and reading comprehension for short commands was normal, he sometimes failed to read
correctly items in his left visual field. His writing was normal with his right hand; he made occasional
errors with his left hand, but could type correctly with the left hand the same sentences that he had
difficulty writing. He had some difficulty drawing with the left hand, but he was not apraxic with
either hand.

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arteriovenous malformation located between the splenium of the corpus callosum
and the trigone of the left lateral ventricle. For convenience, we have referred to
this area as the retrospinal region, although the actual retrosplenial cortex is
only one of the structures in this region. Neuroradiological studies in our case
demonstrate no lesions in the hippocampus, temporal stem, or stria terminalis, and
it is possible that the lesion did not involve the fornix. It unquestionably destroyed
the cingulate bundle and retrospinal cortex, structures that were also involved in the
case reported by Heilman and Sypert. These two structures have strong anatomical
connections with structures known to be important in memory, raising the possibility that lesions restricted to the retrosplenial area can be associated with amnesia.

RETROSPLENIAL AMNESIA

1633

R

FIG. 2. Anteroposterior subtraction view of a left
carotid angiogram, demonstrating the arteriovenous
malformation arising from posterior branches of the
anterior cerebral artery.

Visuospatial abilities were intact. With his right hand, he could draw a cube and a rudimentary map
of Florida, and could correctly indicate the location of major cities. He performed the cancellation task
normally with either hand. He had a partial right superior quadrantanopia to confrontation, and
variable left visual field extinction on bilateral simultaneous stimulation. He could accurately count
fingers on either side, and he could name colours in either visual field. Extraocular movements and
optokinetic nystagmus were normal, as was the remainder of his neurological examination.
On April 5 the AVM was removed through a left occipitoparietal craniotomy. After several
bridging veins along the interhemispheric fissure were divided, the left occipital lobe was retracted
laterally, exposing the splenium. The posterior pericallosal artery was followed to the AVM, which
was surrounded by an old haematoma. Using microdissection techniques the AVM was removed.
The fornix was not directly visualized during the operation.
He remained somnolent postoperatively. A CT scan showed intraventricular blood with increased
ventricular size. On April 6 ventriculostomy was performed. Three days later he was still somnolent,
but could name objects placed in his left hand and was not apraxic. He then became unresponsive.
The ventriculostomy continued to drain blood-stained CSF. He was treated for suspected meningitis,
although only one CSF culture was positive (anaerobic streptococcus). He gradually improved, and
by April 23 he was alert, but had a more extensive retrograde amnesia than preoperatively. He was
discharged on April 28. On June 15, formal visual field testing demonstrated a partial right superior
homonymous quadrantanopia. Eleven months after his haemorrhage he tried returning to work on
a limited basis, but he was unable to perform his previous work because of memory limitations.
Although improving, he has significant memory deficits 2 yrs after his haemorrhage.

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FIG. 1. Axial CT scan taken on the day after the
haemorrhage demonstrating an intracerebral haemorrhage medial to the trigone of the left lateral
ventricle, with extravasation into the ventricle.

1634

EDWARD VALENSTEIN AND O T H E R S

Neuropsychological testing

Follow-up testing
Tests performed 7 months after his haemorrhage showed improvement in his memory quotient
and paired associate learning. Twenty to 22 months after his haemorrhage, his full scale IQ had
increased to 125, but his memory quotient remained more than 20 points below his verbal IQ,
indicating isolated memory impairment. He recalled none of the logical memory stones on the
Wechsler memory test after a 30 min delay, and on the California Verbal Learning Test he recalled
only 3 of 16 words after distraction without delay, and zero of 16 with a 30 min delay, and his
performance on the Peterson-Peterson auditory consonant trigram memory task was at least as
impaired at 22 months as it had been 3 to 4 months after the haemorrhage.

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Formal neuropsychological testing was performed preoperatively, and several times during the
next 20 months (April 24, 1984; June, July, and October, 1984; November, 1985; January, 1986).
Details of the most comprehensive testing are given in the Appendix. We will first consider testing
performed preoperatively and within 4 months of surgery. During preoperative and early postoperative testing, he was alert, attentive, and socially appropriate. With the exception of an increase
in the span of his retrograde amnesia from 9 months preoperatively to 4 yrs postoperatively,
differences between preoperative and early postoperative testing were minimal.
On the Wechsler Adult Intelligence Scale—Revised (Wechsler, 1981), his verbal IQ was 118
preoperatively and 115 postoperatively; his memory quotient of 84 preoperatively was significantly
reduced compared with his verbal IQ. All language and language-related functions were intact, as
was performance on tasks associated with frontal-subcortical functions (i.e., Verbal Fluency (Benton,
1968; Lezak, 1976), Proverb Interpretations, Stroop, Visual-Verbal Test (Siegel, 1957)). The single
exception was poor performance on the Wisconsin Card Sorting test (Milner, 1963; Robinson ex al.,
1980): abnormal preoperative performance on this test was thought at the time to reflect difficulty in
remembering the categories that he was sorting.
In contrast to these preserved functions, he had a profound amnesia. Retrograde amnesia was
present at the onset of his illness. He could recall none of the events surrounding his illness, and he
thought he still worked in another state. His retrograde amnesia transiently increased postoperatively
to encompass more than 4 yrs: he did not remember the birth of his second child (aged 4 yrs),
believing he had only one child. His remote memory, however, appeared intact, as assessed by the
Albert Remote Memory Battery (Albert el al., 1979). At 6 months postoperatively, his retrograde
amnesia had shrunk back to a span of 9 to 12 months.
His anterograde amnesia was profound. For at least 6 months after the onset of his illness, he had
virtually no recall of episodic personal information. By lunch he could not recount reliably what he
had done that morning. When asked how he felt, he would say that he had improved dramatically
from the day before, that everything yesterday was a 'fog', and that he had now reached a 'new level
of consciousness and clarity'. Formal assessment of recent memory confirmed this clinical impression:
he was severely impaired across all verbal memory tasks, both with auditory and visual presentations.
Story recall of the Logical Memory stories from the Weschler Memory Scale—I (Wechsler, 1945)
was 6 immediately (average normal = 10), but zero after a 30 min delay (average normal = 8): no
information was recalled and there was no overt recognition that stories had previously been
presented. Paired associate learning from the Wechsler Memory Scale was impaired and none of the
hard associates were learned. Me was similarly impaired on word list learning tasks (California Verbal
Learning Test (Delis et al., 1983)), recalling no more than 5 of 16 words. After a 30 min delay, both
cued and free recall of the California word list were zero.
In contrast, he performed much better on nonverbal recent memory tasks, such as the Milner
facial memory task (Milner, 1968), and the Benton visual recognition task (Benton, 1974). Immediate
and delayed recall of the Rey Osterreith figure (Lezak, 1976), however, was abnormal.

RETROSPLENIAL AMNESIA

1635

DISCUSSION

Localization
Although T.R. has a classic amnesic syndrome, extensive neuroradiological
studies demonstrated that the lesions associated with his intracerebral haemorrhage
spared the areas classically associated with amnesia: there were no lesions seen in
the diencephalon (Victor et ah, 1971; Squire and Moore, 1979; Speedie and
Heilman, 1982, 1983; Graff-Radford et ai, 1984; von Cramon et ai, 1985;
Rousseaux et al., 1986) or basal forebrain (Whitehouse et ai, 1981; Alexander and
Freedman, 1983; Volpe and Hirst, 1983; Damasio et al., 1985; Hepler et ai,
1985), and both medial temporal lobes (Scoville, 1954; Scoville and Milner, 1957;
Cummings et al., 1984; Zola-Morgan et al., 1986) were free of evidence of a
destructive lesion. The small lucency in the anterior hippocampus on the left (see
fig. 3D) probably represents anomalous vessels: it remained lucent on T2 MRI
studies (spin echo sequence: 2000 ms pulse repetition time; 90 ms echo delay),
suggesting either calcium or blood, but it was not visible on the CT scan or

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T.R.'s amnesia is similar to the classic amnesic syndromes described with
bitemporal or diencephalic lesions (Butters and Miliotis, 1985). He had severe
anterograde amnesia: he initially was disorientated, and remembered very little
about daily events. His anterograde amnesia began to improve about 5 months
after the haemorrhage, so that by 7 months he was usually orientated as to place
and day, but even after 2 years he was unable to carry on the responsibilities of his
previous job, and performed poorly on standardized tests of recent memory. He
also demonstrated a circumscribed retrograde amnesia. Although he did well on
some tests of remote memory (the Albert Remote Memory test and the Florida
recent/remote memory battery), he had difficulty recalling with appropriate clarity
and specificity personal memories for events occurring in the past 4 years, as
demonstrated on a personal autobiographical test of memory. Finally, he had
remarkably intact general intellectual functions: there were no consistent deficits
on tests of'frontal lobe' function, and language, praxis, and visuospatial functions
that did not rely on memory were intact.
T.R.'s memory deficit was to some extent material-specific. Verbal tasks showed
a consistent deficit; while tests of nonverbal memory, except for the Rey-Osterreith
Complex Figure Test, were performed normally. Poor performance on the Rey
Osterreith Complex Figure task, however, is seen in both right and left hemispheredamaged patients. While T.R. had an abnormal rate of forgetting for verbal
material, the rate of forgetting for nonverbal material was not significantly different
from controls {see Appendix). The results are compatible with the proposal that
the predominantly left-sided lesion in this case affected verbal more than nonverbal
memory.
More detailed consideration of the results of neuropsychological testing of this
patient are to be reported separately.

1636

EDWARD VALENSTEIN AND OTHERS

FIG. 3. MRI scan taken 9 months after the haemorrhage. These T,-weighted images were taken using a spin
echo pulse sequence with a 500 ms pulse repetition time and a 30 ms echo delay. Sagittal (A), axial (B), and coronal
(C) views through the lesion. D, coronal view in the plane of the anterior portion of the hippocampus, demonstrating
a small lucency on the left (arrowed). This was one of serial 6 mm coronal cuts, and the abnormality was not seen
on any other section. This area also appeared lucent on T,-weighted images.

angiogram. Coronal sections at 6 mm intervals encompassing the entire extent of
the temporal lobes showed no other lesions. There were no lesions involving
neocortex and subcortical damage was confined to the site of the principal lesion,
plus a small lesion at the site of a temporary ventricular shunt in the right
dorsolateral frontal lobe.
The CT study (fig. 1), the angiogram (fig. 2) and the MRI studies (fig. 3) all
locate the pathology near the splenium of the corpus callosum. Two MRI scans,
performed 3 and 9 months after the onset of his deficit (and 2 and 8 months after
operation) demonstrated a defect in the splenium of the corpus callosum, and an

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C

RETROSPLENIAL AMNESIA

1637

Pathogenesis of T.R. 's amnesia
Damage to one or more of the above-mentioned structures is presumably responsible for T.R.'s amnesia. Memory loss sometimes occurs after section of the corpus
callosum (Dimond et al., 1977; Bentin et ai, 1984). This has been attributed
to associated damage to the fornix and/or the hippocampal commissure, or to
disconnection of the left hemisphere from the right medial temporal region in
patients with dysfunctional left medial temporal structures (associated with seizures) (Ross, 1980). The first mechanism might applv to our patient, and will be
discussed below. The second appears unlikely; there is little to suggest that our
patient's left hippocampus was dysfunctional, and even if it were, a small lesion in
the splenium would not be sufficient to disconnect the left hemisphere from the
right hippocampus. Patients with cerebral infarctions in the distribution of the left
posterior cerebral artery may also present acutely with amnesia (Geschwind and
Fusillo, 1966; Damasio and Damasio, 1983). These patients sometimes have lesions
in the splenium; however, when amnesic, they always have associated damage to
medial temporal structures (Damasio and Damasio, 1983). Although their lesions
often extend anteriorly to involve at least a portion of the hippocampus, they may
also involve the retrosplenial cortex and cingulum, and the mechanism of memory
loss may thus be similar to that in our patient.
Lesions of the bodies of the fornix (fig. 4, lesion 1) disconnect the hippocampus
from the septum, anterior thalamus and mamillary bodies. Fornix lesions in
monkeys produce mild memory impairment (Gaffan, 1974; Owen and Butler, 1981;
Moss et al., 1981; Carr, 1982; Bachevalier et al., 1985a, b). Fornix lesions in
humans have had variable effects on memory. There are reports of definite memory
impairment after surgical section (Sweet et al., 1959; Hassler and Riechert, 1957)
or trauma (Grafman et al., 1985), and there are also reports of normal memory
after surgical section (Dott, 1938; Cairns and Mosberg, 1951; Garcia Bengochea
et al., 1954) or destruction by tumour (Woolsey and Nelson, 1975). The reports of
normal memory have not included careful neuropsychological testing. Heilman
and Sypert (1977) also pointed out that surgical section of the columns of the fornix

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adjacent lesion posterolateral to the splenium, involving the cortex and subcortical
white matter between the splenium and trigone of the left lateral ventricle. This is
the location of the most posterior portion of the cingulate gyrus, which is composed
principally of the retrosplenial cortex. In the white matter deep to this cortex runs
the cingulate bundle. The neuroradiological studies lack the resolution to identify
with certainty whether certain small structures, such as the fornix and stria
terminalis, were damaged. In the ventricle, the fornix runs anterior and inferior to
the site of maximal damage, but may have been damaged, and the hippocampal
commissure, directly beneath the splenium may also have been involved. The stria
terminalis, adjacent to the caudate nucleus in the inferolateral wall of the lateral
ventricle, was lateral to the lesion, and was probably spared. There was no radiological or clinical evidence to suggest right hemisphere involvement.

1638

EDWARD VALENSTEIN AND OTHERS

(fig. 4, lesion 2) may spare memory because projections from the hippocampus
directly to the anterior thalamic nuclei and to the septal area leave the fornix before
the site of the lesion.
Since in both humans and animals, section of the fornix has been associated with
at most mild impairment of memory, it would be difficult to ascribe the severe
memory loss suffered by the patient of Heilman and Sypert (1977) to fornix lesions
alone. The lesion in their patient, however, also involved the retrosplenial cortex
and cingulum. It may be that combined lesions of the fornix and these latter areas
produce a more profound amnesia than lesions restricted to the fornix. Finally, it
should be kept in mind that while it is virtually certain that the cingulate bundle
and retrosplenial cortex were involved by T.R.'s lesion, we have no proof that the
fornix was affected. It is therefore possible that all the memory deficits in the
present case might need to be explained by factors other than fornix damage.
The retrosplenial cortex, architechtonically transitional between the allocortex
of the hippocampus, and the isocortex of the posterior cingulate cortex, lies in the
isthmus of the gyrus fornicatus between the subiculum-presubiculum and the
posterior cingulate cortex (area 23) (Vogt, 1976; Braak, 1980) (fig. 5). Anteriorly,
it is contained in the inferior bank of the posterior cingulate gyrus; posteriorly, it
extends onto the medial surface of the hemisphere, curves downwards behind the
splenium of the corpus callosum, and ends at the calcarine fissure.
The connections of the retrosplenial cortex have not been studied extensively in

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FIG. 4. Semidiagrammatic representation of Papez' circuit, indicating the position of the retrosplenial area in
this circuit. I and 2 indicate sites of hypothetical lesions discussed in the text. A = anterior nuclei of thalamus;
AL = anterior limbic region; CB = cingulate bundle; CC = corpus callosum; Cing = cingulate cortex; DM = dorsomedial thalamic nucleus; F = fornix; Hip = hippocampus (D = dentate, CA = Ammon's horn, S = subiculum);
MB = mamillary bodies; PHG = parahippocampal gyrus; PR/PA = presubiculum and parasubiculum; RS = retrosplenial cortex; SE = septum.

RETROSPLENIAL

AMNESIA

1639

Fio. 5. The extent of the retrosplenial cortex on the medial aspect of the cerebral hemisphere is indicated by
cross-hatching. Inset shows a partial coronal section at the level indicated by the dotted line. CC = corpus callosum.
Spl = splenium.

primates, but it is clear from observations in various species that retrosplenial
cortex is richly connected both to the anterior thalamic nuclei and to medial
temporal structures. In the rabbit, the principal projections of the anteromedial
and anterodorsal thalamic nuclei are to the granular retrosplenial cortex, while the
anteroventral nucleus projects principally to the agranular retrosplenial cortex
(Robertson and Kaitz, 1981; Jones, 1985). The lateral dorsal thalamic nucleus
(considered to be one of the anterior thalamic nuclei) projects strongly to the
cingulate cortex, agranular retrosplenial cortex, and presubiculum and parasubiculum (Jones, 1985). It has been demonstrated in monkeys and rodents that
the retrosplenial cortex has reciprocal connections with subiculum and presubiculum and projects back to the anterior and lateral dorsal thalamus (Domesick,
1972; Rosene and Van Hoesen, 1977; Sorensen, 1980, Schwerdtfeger and Sarvey,
1983; Vogt and Miller, 1983). The fibres connecting the retrosplenial cortex with
the thalamus and medial temporal lobe structures are carried in the cingulate bundle
(Mufson and Pandya, 1984).
A lesion of the retrosplenial cortex and underlying cingulate bundle would
therefore interrupt an alternative pathway from hippocampus to anterior thalamus
(via the retrosplenial cortex). Perhaps more importantly,' such a lesion would also
interrupt input from the anterior and lateral dorsal thalamic nuclei to retrosplenial
cortex and medial temporal lobe (fig. 4). This lesion might substantially disrupt
communication between the anterior thalamus and hippocampus, and thus may
have an effect similar to lesions in either of the structures that it disconnects.

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Calcarine fissure
Parahippocampal gyms

1642

EDWARD VALENSTEIN A N D OTHERS

ACKNOWLEDGEMENTS
This investigation was supported by the Memory Disorders Clinic Grant, State of Florida.

REFERENCES
AGGLETON JP, MISHKIN M (1983) Memory impairments following restricted medial thalamic lesions

DAMASIO AR, GRAFF-RADFORD NR, ESLINGER PJ, DAMASIO H, KASSELL N (1985) Amnesia following

basal forebrain lesions. Archives of Neurology, Chicago, 42, 263-271.
DELIS D, KRAMER J. OBER B, KAPLAN E (1983) The California Verbal Learning Test: Administration
and Interpretation. Preliminary Manual. New York: Life Sciences Associates.
DIMOND SJ, SCAMMELL RE, BROUWERS EYM, WEEKS R (1977) Functions of the centre section (trunk)

of the corpus callosum in man. Brain, 100, 543-562.
DOMESICK VB (1972) Thalamic relationships of the medial cortex in the rat. Brain, Behavior and

Evolution, 6, 457^83.

Downloaded from http://brain.oxfordjournals.org/ at University of Birmingham on January 30, 2015

in monkeys. Experimental Brain Research, 52, 199-209.
AGGLETON JP, MISHKIN M (1985) Mamillary-body lesions and visual recognition in monkeys.
Experimental Brain Research, 58, 190-197.
ALBERT MS, BUTTERS N, LEVIN J (1979) Temporal gradients in the retrograde amnesia of patients
with alcoholic KorsakofT s disease. Archives of Neurology, Chicago. 36, 211-216.
ALEXANDER MP, FREEDMAN M (1983) Amnesia after anterior communicating artery aneurysm
rupture. Neurology, Cleveland, 33, Supplement 2, 104.
BACHEVALIER J, PARKINSON JK, MISHKIN M (1985a) Visual recognition in monkeys: effects of
separate vs combined transection of fomix and amygdalofugal pathways. Experimental Brain
Research, 57,554-561.
BACHEVALIER J, SAUNDERS RC, MISHKIN M (1985ft) Visual recognition in monkeys: effects of transection of fomix. Experimental Brain Research, 57, 547-553.
BENTIN S, SAHAR A, MOSCOVITCH M (1984) Intermanual information transfer in patients with lesions
iii the trunk of the corpus callosum. Neuropsychologia, 22, 601-611.
BENTON AL (1968) Differential behavioral effects in frontal lobe disease. Neuropsychologia, 6, 53-60.
BENTON AL (1974) Revised Visual Retention Test. Fourth edition. New York: Psychological Corporation.
BRAAK H (1980) Architectonics of the Human Telencephalk Cortex. Berlin: Springer.
BUTTERS N, MILIOTIS P (1985) Amnesic disorders. In: Clinical Neuropsychology. Second edition.
Edited by K.M. Heilman and E. Valenstein. New York and Oxford: Oxford University Press,
pp. 403-451.
CAIRNS H, MOSBERG WH (1951) Colloid cyst of the third ventricle. Surgery, Gynecology and Obstetrics,
92, 545-570.
CARR AC (1982) Memory deficit after fomix section. Neuropsychnlngia, 20, 95-98.
CRAMON DY VON, HEBEL N, SCHURI U (1985) A contribution to the anatomical basis of thalamic
amnesia. Brain, 108, 993-1008.
CUMMINGS JL, TOMIYASU U, READ S, BENSON DF (1984) Amnesia with hippocampal lesions after
cardiopulmonary arrest. Neurology, Cleveland, 34, 679-681.
DAMASIO AR, DAMASIO H (1983) The anatomic basis of pure alexia. Neurology, Cleveland, 33, 15731583.
DAMASIO AR, VAN HOESEN GW (1983) Emotional disturbances associated with focal lesions of the
limbic frontal lobe. In: Neuropsvchologv of Human Emotion. Edited by K.M. Heilman and P.
Satz. New York: Guilford Press, pp. 85-110.

RETROSPLENIAL AMNESIA

1643

Dorr NM (1938) Surgical aspects of the hypothalamus. In: The Hypothalamus: Morphological,
Functional, Clinical and Surgical Aspects. Edited by W. E. Le G. Clark, J. Beattie, G. Riddoch
and N. M. Dott. Edinburgh: Oliver and Boyd, pp. 131-185.
GAFFAN D (1974) Recognition impaired and association intact in the memory of monkeys after
transection of the fornix. Journal of Comparative and Physiological Psychology, 86, 1100-1109.
GARCJA BENGOCHEA F, DE LA TORRE O, ESQUIVEL O, VIETA R, FERNANDEZ C (1954) The section of

the fornix in the surgical treatment of certain epilepsies: a preliminary report. Transactions of
the American Neurological Association, 79, 176-178.
GESCHWIND N, FUSILLO M (1966) Color-naming defects in association with alexia. Archives of
Neurology, Chicago, 15, 137-146.
GRAFF-RADFORD NR, ESLINGER PJ, DAMASIO AR, YAMADA T (1984) Nonhemorrhagic infarction of

GRAFF-RADFORD NR, DAMASIO H, YAMADA T, ESLINGER PJ, DAMASIO AR (1985) Nonhaemorrhagic

thalamic infarction: clinical, neuropsychological and electrophysiological findings in four anatomical groups defined by computerized tomography. Brain, 108, 485-516.
GRAFMAN J, SALAZAR AM, WEINGARTNER H, VANCE SC, LUDLOW C (1985) Isolated impairment of

memory following a penetrating lesion of the fornix cerebri. Archives of Neurology, Chicago, 42,
1162-1168.
HASSLER R, RIECHERT T (1957) Uber einen Fall von doppelseitiger Fornicotomie bei sogenannter
temporaler Epilepsie. Ada Neurochirurgica, 5, 330-340.
HEILMAN KM, SYPERT GW (1977) Korsakoff's syndrome resulting from bilateral fornix lesions.
Neurology, Minneapolis, 27, 490—493.
HEPLER DJ, OLTON DS, WENK GL, COYLE JT (1985) Lesions in nucleus basalis magnocellularis

and medial septal area of rats produce qualitatively similar memory impairments. Journal of
Neuroscience, 5, 866-873.
HOREL JA (1978) The neuroanatomy of amnesia: a critique of the hippocampal memory hypothesis.
Brain, 101,403-445.
JONES EG (1985) The Thalamus. New York: Plenum Press.
LEZAK MD (1976) Neuropsychological Assessment. New York: Oxford University Press.
MAIR WGP, WARRINGTON EK, WEISKRANTZ L (1979) Memory disorder in Korsakoff's psychosis: a
neuropathological and neuropsychological investigation of two cases. Brain, 102, 749-783.
MILNER B (1963) Effects of different brain lesions on card sorting: the role of the frontal lobes.
Archives of Neurology, Chicago, 9, 90-100.
MILNER B (1968) Visual recognition and recall after right temporal-lobe excision in man. Neuropsychologia, 6, 191-209.
MILNER B, TEUBER H-L (1968) Alteration of perception and memory in man: reflections on methods.
In: Analysis of Behavioural Change. Edited by L. Weiskrantz. New York and London: Harper
and Row, pp. 268-375.
MISHKIN M, SPIEGLER BJ, SAUNDERS RC, MALAMUT BL (1982) An animal model of global amnesia.

In: Alzheimer's Disease: A Report of Progress in Research. Aging, Volume 19. Edited by S.
Corkin, K. L. Davis, J.H. Growdon, E. Usdin and R.J. Wurtman. New York: Raven Press,
pp. 235-247.
Moss M, MAHUT H, ZOLA-MORGAN S (1981) Concurrent discrimination learning of monkeys after
hippocampal, entorhinal, or fornix lesions. Journal of Neuroscience, 1, 227-240.
MUFSON EJ, PANDYA DN (1984) Some observations on the course and composition of the cingulum
bundle in the rhesus monkey. Journal of Comparative Neurology, 225, 31-43.
OWEN MJ, BUTLER SR (1981) Amnesia after transection of the fornix in monkeys: long-term memory
impaired, short-term memory intact. Behavioural Brain Research, 3, 115-123.
PENFIELD W, MILNER B (1958) Memory deficit produced by bilateral lesions in the hippocampal zone.
Archives of Neurology and Psychiatry, Chicago, 79, 475—497.

Downloaded from http://brain.oxfordjournals.org/ at University of Birmingham on January 30, 2015

the thalamus: behavioral, anatomic, and physiologic correlates. Neurology, Cleveland, 34, 14—
23.

1644

EDWARD VALENSTEIN AND OTHERS

ROBERTSON RT, KAITZ SS (1981) Thalamic connections with limbic cortex. I. Thalamocortical
projections. Journal of Comparative Neurology, 195, 501-525.
ROBINSON AL, HEATON RK, LEHMAN RAW, STILSON DW (1980) The utility of the Wisconsin Card

Sorting Test in detecting and localizing frontal lobe lesions. Journal of Consulting and Clinical
Psychology, 48, 605-614.
ROSENE DL, VAN HOESEN GW (1977) Hippocampal efferents reach widespread areas of cerebral
cortex and amygdala in the rhesus monkey. Science, 198, 315-317.
Ross ED (1980) Sensory-specific and fractional disorders of recent memory in man. II. Unilateral
loss of tactile recent memory. Archives of Neurology, Chicago, 37, 267-272.
ROUSSEAUX M, CABARET M, LESOIN F, DEVOS P, DUBOIS F, PETIT H (1986) Bilan de I'amnesie des

TEUBER H-L, CORKIN S, TWITCHELL TE (1976) A study of cingulotomy in man. In: Psychosurgery.

An Appendix to a report to the National Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research. US Department of Health, Education, and Welfare
Publication no. (OS) 77-0002.
VICTOR M, ADAMS RD, COLLINS GH (197!) The Wcrnicke-Korsakojf Syndrome: A Clinical and

Pathological Study of 245 Patients, 82 with Post-Mortem Examinations. Philadelphia: F. A. Davis
and Oxford: Blackwell.
VOGT BA (1976) Retrosplenial cortex in the rhesus monkey: a cytoarchitectonic and Golgi study.
Journal of Comparative Neurology, 169, 63-97.
VOGT BA, MILLER MW (1983) Cortical connections between rat cingujate cortex and visual, motor,
and postsubicular cortices. Journal of Comparative Neurology, 216, 192-210.
VOLPE BT, HfRST W (1983) Amnesia following the rupture and repair of an anterior communicating
artery aneurysm. Journal of Neurology, Neurosurgery and Psychiatry, 46, 704-709.
WECHSLER D (1945) A standardized memory scale for clinical use. Journal of Psychology, 19,
87-95.
WECHSLER D (1981) Wechsler Adult Intelligence Scale—Revised. Manual. Cleveland, OH: Psychological Coporation.
WHITEHOUSE PJ, PRICE DL, CLARK AW, COYLE JT, DELONG MR (1981) Alzheimer disease: evidence

for selective loss of cholinergic neurons in the nucleus basalis. Annals of Neurology, 10,
122-126.
WOOLSEY RM, NELSON JS (1975) Asymptomatic destruction of the fornix in man. Archives of
Neurology, Chicago, 32, 566-568.

Downloaded from http://brain.oxfordjournals.org/ at University of Birmingham on January 30, 2015

infarctus thalamiques restreints—6 cas. Cortex, 22, 213-228.
SCHWERDTFEGER WK, SARVERY JM (1983) Connectivity of the hilar region of the hippocampal
formation in the rat. Journal fur Hirnforschung, 24, 201-207.
SCOVILLE WB (1954) The limbic lobe in man. Journal of Neurosurgery, 11, 64-66.
SCOVILLE WB, MILNER B (1957) Loss of recent memory after bilateral hippocampal lesions. Journal
of Neurology, Neurosurgery and Psychiatry, 20, 11-21.
SIEGEL SM (1957) Discrimination among mental defective, normal, schizophrenic, and brain damaged
subjects of the Visual-Verbal concept formation test. American Journal of Mental Deficiency, 62,
338-343.
SQUIRE LR, MOORE RY (1979) Dorsal thalamic lesion in a noted case of human memory dysfunction.
Annals of Neurology, 6, 503-506.
SORENSEN KE (1980) Ipsilateral projection from the subiculum to the retrosplenial cortex in the
guinea pig. Journal of Comparative Neurology, 193, 893-911.
SPEEDIE LJ, HEILMAN KM (1982) Amnestic disturbance following infarction of the left dorsomedial
nucleus of the thalamus. Neuropsychologia, 20, 597-604.
SPEEDIE LJ, HEILMAN KM (1983) Anterograde memory deficits for visuospatial material after infarction of the right thalamus. Archives of Neurology, Chicago, 40, 183-186.
SWEET WH, TALLAND GA, ERVIN FR (1959) Loss of recent memory following section of fornix.
Transactions of the American Neurological Association, 84, 76-82.

RETROSPLENIAL

1645

AMNESIA

ZOLA-MORGAN S, SQUIRE LR (1986) Memory impairment in monkeys following lesions limited to
the hippocampus. Behavioral Neuroscience, 100, 155-160.
ZOLA-MORGAN S, SQUIRE LR, AMARAL DG (1986) Human amnesia and the medial temporal region:
enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. Journal of Neuroscience, 6, 2950-2967.
(Received October 9, 1986. Revised March 17, 1987. Accepted April 13, 1987)

APPENDIX

Date of testing

4/2/84

6-7/84

11/85-1/86

Time after haemorrhage
Time after surgery

18 days
(preop.)

3—4mos
2-3 mos

20-22 mos
19-21 mos

General intelligence
WAIS-R
Verbal IQ
Performance IQ
Full Scale IQ

118
86
101

115

127
115
125

84
34'
3/6*
5/5
9/9
6
0"
6
5

80
35*
4/6*
4/5
8/9
6
0**
7
4

101
26*
5/6
4/5
7/9
8
0**
7
5

9/14
0/14*
6/21*
1*

4/14*
2/14*
10/21*
0**

9/14

5
7**
19**
1"
4**
0"
2**

4
5**
23**
0**
5**
0**
0**

100%
100%
40%*
80%

100%
100%
60%
73%

—
—
—

100%
67%*
53%*
47%*

Memory
Wechsler Memory Scale
Memory quotient (MQ)
VIQ-MQ difference
Information
Orientation
Mental Control
Stories, immediate
Stories, delay
Digit span forward
Digit span backward
Visual Reproduction
Immediate
30min delay
Paired Associates
No. of hard items learned
Recent verbal memory
Word Lists (California)
Trial 1 (total 16 words)
Trial 5 (total 16 words)
Total trials 1-5
Free recall: immediate
Cued recall: immediate
Free recall: 30min delay
Cued recall: 30min delay
Peterson-Peterson words (visual presentation)
Immediate
20 s, no distraction
20 s, with distraction
4 s, predistraction delay
Peterson-Peterson CCC (auditory presentation)
Immediate
3s
9s
18s

16/21
4

5
• « • •

34* •
3**
8*
0"
4**

—
—
100%
75%
40%
33%

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SUMMARY OF NEUROPSYCHOLOGICAL TEST RESULTS

E D W A R D VALENSTEIN AND O T H E R S

Date of testing
Verbal rate of forgetting
5min
Ih
24 h
5d
Kimura Recurring Words

Remote memory
Albert Remote Memory (1920s-1970s)
Public events recognition
Event recall .
Face recognition
Florida recent/remote (1974-1984)
Recognition
Recall
Personal autobiographical (1980-1984)
Frontal and miscellaneous
Wisconsin Card Sorting
Controlled Verbal Fluency
Shipley Abstraction score
Luria tasks:
Contrasting motor programs
Go-no go motor programs
Recursive writing of 'mn'
WAIS similarities (scaled scores)
Boston naming

6-7/84

90%
73%"
70%"
50%"
38

45
9/12
13/15

47
9/12

34(pc = 75)
2(pc<25)
2(pc<25)

34(pc = 75)
16(pc<25)
0(pc<25)

11185-1/86

9/12

77% (WNL)
63%"
56%
60%

—
—
—

65%
44%
58%

—

85%
80%
4/10 (chance = 20%)

95
—
—

ABNL
85th pc
—

Nl
75th pc
36/40

95
—

100%
100%
WNL
iS
100%

—
—
18
100%

—
—
IX

* > 1 SD from the means of normal controls: " > 2 SD from the means of normal controls: — = test not performed on that
date: pc = percentile; WNL = within normal limits; ABNL = abnormal: Nl = normal.

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Memory, recent, nonverbal
Kimura Recurring Figures
Milner Facial Memory
Benton Visual Recognition
Rey Osterreith Figure
Copy (score, pc)
Immediate recall pc
Delayed recall pc
Nonverbal rate of forgetting
lOmin
Ih
24 h
5d

412184

M i l l

1646