126

J Neurol Neurosurg Psychiatry 1998;65:126–130

SHORT REPORT

Amnesia after a discrete basal forebrain lesion
Kazuo Abe, Maki Inokawa, Asako Kashiwagi, Takehiko Yanagihara

Department of
Neurology, Osaka
University Medical
School, 2–2
Yamadaoka, Suita,
Osaka 565, Japan
K Abe
T Yanagihara
Rehabilitation Unit,
Kyoritsuonsen
Hospital, Japan
M Inokawa
A Kashiwagi
Correspondence to:
Dr Kazuo Abe, Department
of Neurology, Osaka
University Medical School,
2–2 Yamadaoka, Suita, Osaka
565, Japan. Tel: 0081 6 879
3571; Fax: 0081 6 879 3579;
Email:
abe@neurol.med.osaka-u.ac.jp
Received 8 August 1997 and
in revised form 10 November
1997
Accepted 1 January 1998

Abstract
Destructive lesions of the basal forebrain
are often associated with memory impairment and this structure is thought to contribute to memory function by providing a
cholinergic input to critical structures
associated with memory such as the
hippocampus and amygdala. In previously
reported cases of amnesia associated with
damage in the basal forebrain, multiple
neuroanatomical regions were damaged,
and the critical lesion responsible for
amnesia has not been identified clearly.
We report a patient who developed primarily anterograde amnesia after clipping of
an unruptured anterior communicating
artery aneurysm. Postoperative magnetic
resonance imaging showed a discrete
lesion, centring in the right diagonal band
of Broca and including the anterior hypothalamus, septal nucleus, lamina terminalis, and paraterminal gyrus, and an
indiscrete patchy lesion in the corresponding area on the opposite side. The
nucleus basalis of Meynert was minimally
aVected and the diencephalon was not
damaged. Single photon emission computed tomography showed marked hypoperfusion in the midline frontobasal region
corresponding to the MRI lesion and
hypoperfusion in the hippocampus bilaterally. It is concluded that disconnection
of the pathway between the diagonal band
of Broca and the hippocampus contributed to memory impairment.
(J Neurol Neurosurg Psychiatry 1998;65:126–130)
Keywords: diagonal band of Broca; amnesia; time
tagging

The amnesic syndrome has been found in
patients with relatively discrete lesions in
several cerebral sites including (a) the medial
temporal lobes including the hippocampus, (b)
median thalamic nuclei, (c) anterior thalamic
nuclei, (d) basal forebrain, (e) fornix, (f) mammillary bodies, and (g) retrosplenial cortex.1–3
The basal forebrain has been considered to
contribute to memory function by way of the
pathways between nuclei of the diagonal band
or the septal nucleus and the hippocampal
region, thus providing a cholinergic input to
the hippocampus.1–4 In most previously reported cases of amnesia4–14 associated with

basal forebrain lesions, multiple neuroanatomically identified areas were damaged, and it has
been diYcult to identify the minimal lesion
necessary to produce an amnesic syndrome
except for patients in whom basal forebrain
lesions were relatively well circumscribed.4 5
We describe a patient who developed anterograde amnesia as the result of a discrete lesion
in the basal forebrain after clipping of an
unruptured anterior communicating artery
aneurysm.
Case report
A 61 year old right handed high school teacher,
who had taught science for more than 35 years
and had had good memory function, experienced a sudden onset of weakness in the right
upper and lower limbs in July 1993, but recovered the next day. He was admitted to a hospital elsewhere and underwent MRI, which
showed a small haemorrhage in the left
external capsule. He underwent cerebral angiography, which showed an aneurysm 5 mm in
diameter in the anterior communicating artery.
He underwent surgical clipping of the aneurysm one month later. Immediately after the
surgery, he developed disorientation and agitation. Although he became alert and oriented to
person and place one month after the operation, he remained disoriented to date. He
apparently had memory impairment at that
time, but the details are not known to us. He
had no motor or sensory deficits.
He visited the neurology outpatient service
of the Osaka University Hospital four months
after the operation. He was alert and did not
have any focal neurological deficits. He did not
seem to appreciate the graveness of his memory
impairment. His language comprehension and
expression were intact. He could repeat seven
digits and perform serial subtraction without
diYculty. He could learn five objects but could
recall only one of them after five minutes. During the interview, his recall was aided by cuing.
Recall of his remote personal history was relatively preserved but the dates were mixed up,
and he mistook recent personal episodes as
remote ones. He did not have confabulation
and remained silent when he could not answer
a question. An EEG showed no abnormality.
NEUROPSYCHOLOGICAL ASSESSMENT

Formal neuropsychological testing was performed several times over 36 months, and two
series are presented here, the one at the initial

127

Amnesia after a discrete basal forebrain lesion
Table 1

Neuropsychological assessment

MMSE
WAIS
VIQ
PIQ
Cancellation tasks (errors)
Rey-Osterrieth-copy
Token test (%)
Boston naming
Digit span
Forward
Backward
Wisconsin card sorting test
Category
Perseveration errors
Trail making test A
Trail making test B
Word fluency
Category
Letter head

Table 2

1994/2

1996/2

25

27

108
103
0
36
98
50

112
116
0
36
98
50

7
5

7
5

6
6
30”
55”

6
3
31”
48”

18
16

19
18

Memory assessment

WMS-R:
Verbal memory
Nonverbal memory
General memory
Attention/concentration
Delayed recall
Rey auditory verbal learning:
Maximum recall
After interference
Recognition (/50)
Work fluency (/min):
Letter head
Category
Benton visual retention:
Immediate
Errors
Corrects
Delay
Errors
Corrects
Paired verbal association (3 trials):
Related
Unrelated
Tower of Toronto (index)
Remote recall (%):
Items before operation
Recall
Recognition
Items after operation
Recall
Recognition
Remote autobiographical recall:
Recall
Recognition

1994/2

1996/2

69
104
77
92
65

82
108
90
89
78

9
0
40

11
2
44

13
12

14
14

6
5

8
6

13
2

8
4

4–6–8
0–0–0
18

5–7–8
1–2–2
16

94
100

98
100

3
8

8
15

70
100

80
100

evaluation in February 1994 and another 24
months later (tables 1 and 2).
First assessment
At the time of the first evaluation in February
1994, he was alert, cooperative, and oriented to
person and place. His verbal IQ and non-verbal
IQ fell within the normal range.15 The results of
the Wisconsin card sorting test,16 trail making
test,17 word fluency,18 and go/no go task17 to
measure the frontal lobe function were normal.
Performance on all other neuropsychological
measures fell within the normal range.
He obtained a verbal memory quotient of 69,
whereas the non-verbal memory quotient was
104 on the Wechsler memory scale-revised
(WMS-R).19 He clearly showed mismatch
between verbal and non-verbal memory function. He was able to repeat seven digits forward
and five digits backwards, indicating an intact
attention span.17 18 Although he could learn

Figure 1 Magnetic resonance image in February 1996,
30 months after surgery. A sagittal image (A) and two
coronal images (B, C) on the T2 weighted pulse sequence
show a discrete lesion located in the right basal forebrain
including the diagonal band of Broca, anterior
hypothalamus, and the lamina terminalis. Imaging was
carried out with a 1.5 Tesla superconducting system with a
spin echo method. The T2 weighted pulse sequence was
carried out by using the repetition time (TR) of 5000 ms
and the echoing time (TE) of 130 ms.

four out of 10 easy paired associates, he could
not learn any of the diYcult word pairs. He was
impaired on a word list learning task, recalling
no more than nine out of 15 words. Although
his recall of the word list dropped to zero after
performing an interfering word list, he had recognition of 40 out of 50 words presented in a

128

Abe, Inokawa, Kashiwagi, et al

Figure 2 Coronal section from the Haines neuroanatomical atlas indicates that the lesion was in the basal forebrain including the diagonal band of Broca,
anterior hypothalamus, and the lamina terminalis.

yes/no recognition paradigm.20 His recent nonverbal memory was relatively preserved. On the
visual reproduction portion of the WMS-R, he
obtained a non-verbal memory quotient of
104, which fell within the normal range.

Immediate and delayed recall of the Benton
visual retention test21 were moderately impaired. Memory for past public events was
examined using the method described by
Fukatsu et al12 and was within the normal range
for the 1950s to the 1980s. He showed a
limited period of retrograde amnesia for events
before his operation. With the help of his family, a list for personal autobiographical memory
was constructed with questions about significant personal events (for example, marriage,
death, children’s accomplishments). Although
he could recall almost all events, he could not
tag these events in sequence.
Follow up assessment
He was assessed in February 1996, 30 months
after surgery. He showed mild improvement in
memory performance, predominantly in nonverbal memory (tables 1 and 2). Immediate
and delayed recall of the Benton visual
retention test fell within the normal range.
Although his verbal memory quotient on the
WMS-R increased from 69 to 82, it remained
impaired compared with his non-verbal
memory quotient of 108. He achieved normal
maximal learning of a word list learning task,
but he continued to show severely impaired
delayed recall. On memory for past public
events and personal autobiography, he could
recall each event fairly well. However, he could
not arrange these events in sequence and mistook the latest event for one having occurred
years before.
NEUROIMAGING EXAMINATION

Figure 3 Single photon emission computed tomography
using 99mTc- d,l-hexamethylpropyleneamine oxime (99mTcHMPAO) 30 months after surgery. Scanning was carried
out 15 minutes after intravenous injection of 740 mBq
99mTc-HMPAO. An axial SPECT image parallel to the
orbitomeatal line (left) shows a defect (*) in the midline
expanding to both sides corresponding to the lesion on MR
I. Another axial image parallel to the hippocampus (right)
shows mild hypoperfusion bilaterally in the hippocampus
(arrows) but slightly more reduction on the left side.

Brain MRI with a 1.5 Tesla superconducting
system (General Electric), disclosed a small
discrete lesion in the basal forebrain slightly to
the right of the midline in February 1996 (fig
1). Mapping of the lesion by superimposing on
two schematic coronal sections from the
Haines neuroanatomical atlas23 indicated that
the lesion was in the basal forebrain including

Amnesia after a discrete basal forebrain lesion

the diagonal band of Broca, septal nucleus,
anterior hypothalamus, and the lamina terminalis (fig 2). There was an indiscrete patchy
lesion in the corresponding area on the
opposite side on the T2 weighted image (fig 2)
but this lesion was identified on only one slice.
The involvement of the nucleus basalis of
Meynert was minimal and neither the medial
temporal lobe nor diencephalon was damaged.
The orbitofrontal and cingulate cortex were
also spared. The appearance of the lesion on
the right side indicated the presence of
hemosiderin deposition. Single photon emission computed tomography (SPECT) using
99m
Tc-d, l-hexamethyl propyleneamine oxime
showed an area of hypoperfusion, below 40%
of the maximal isotope uptake in the cerebellum, in the midline frontobasal region expanding to both sides corresponding to the lesion on
the MR image (fig 3). In addition, the isotope
uptake in the hippocampus was below 50% of
the maximal isotope uptake in the cerebellum
bilaterally, but slightly more reduced on the left
side (fig 3).
Discussion
In summary, our patient showed (a) anterograde amnesia, (b) mild retrograde amnesia for
both semantic and personal episodic information, (c) benefit from cuing, and (d) defects
in the temporal tagging of information. The
clinical presentation was similar to the previously reported cases of amnesia after damage
to the basal forebrain and adjacent
structures.3 14 As reviewed previously,24 those
cases were mostly associated with a ruptured
anterior communicating artery aneurysm.
However, previously reported cases5–13 did not
have such a discrete lesion in the basal
forebrain as our patient, whose anterior
communicating artery aneurysm was unruptured.
Our patient could learn test items in the
memory evaluation batteries, but he had
diYculty in recall and could not develop a
proper time sequence for this information even
when he could recall. This was striking and was
diVerent from memory impairment described
in patients HM and DRB, whose failures were
in learning both types of information.25 26 The
availability of contextual memory is thought to
depend on the recording of separate information that is composed of a perceived
episode, computation, and recoding of the
relation between multiple components, and
time tagging of this information. Despite his
ability to learn information correctly, our
patient showed diYculty in his daily living.
This may be due to the diYculty in forming
time tagging of this information. Because cuing
markedly improved recall and recognition of
both anterograde and retrograde memories, his
amnesia with preserved cuing may be due to a
deficit in retrieval. This notion was supported
by the clinical finding and the result of the
Rey’s auditory verbal learning test.20
It is diYcult to ascertain the minimal lesion
necessary to cause the amnesic syndrome associated with a basal forebrain lesion, because of
the extent and variability of the previously

129

reported lesions. There are only two patients in
the literature who had a relatively well circumscribed lesion.4 5 Damasio et al4 described a
patient (case 1) who had haematomas in the
left gyrus rectus and midline septal nuclei, who
subsequently underwent surgical clipping of
the ruptured left anterior cerebral artery aneurysm. The extent of the lesion was delineated
by CT. Another patient described by Morris et
al5 had a low grade glioma near the posterior
extent of the right gyrus rectus involving the
lamina terminalis and developed severe amnesia postoperatively. Postoperative MRI showed
a discrete lesion involving the right diagonal
band of Broca, preoptic area, anterior hypothalamus, lamina terminalis, and paraterminal
gyrus. There are some similarities and dissimilarities among these two cases and ours.
Damasio et al found a mismatch between
auditory-verbal and non-verbal memories as
we did. On the other hand, the patient
described by Morris et al had a lesion predominantly on the right side, but did not have such
a mismatch. Our patient also had a lesion
mostly to the right of the midline on MRI, but
possessed an area of profound hypoperfusion
in the midline frontobasal region expanding to
both sides on SPECT. He showed better
performance on the non-verbal memory
examination than the verbal one. As the
projection of the diagonal band to the hippocampus is predominantly ipsilateral, his lesion
should have aVected the projection to the right
hippocampus. He showed complete right
handedness by the handedness inventory27 and
had no family history of left handedness or
childhood events that might be associated with
anomalous lateralisation of cognitive function.
At the present time, there is no clear explanation for better performance on the non-verbal
memory examination despite the more extensive lesion in the right basal forebrain on MRI
examination. One possibility is that the left
hippocampus was functionally more impaired
in our patient, as the SPECT examination suggested. Another possibility is the presence of
hemispheric asymmetry for retrieval of episodic memory. According to Tulving et al, there
was increased blood flow in the right prefrontal
cortex at the time of retrieval of episodic
memory.28 They concluded that the left prefrontal cortex was more involved in retrieval of
episodic memory.29 Although their finding was
confined to the cerebral cortex, it is possible
that the retrieval of information may involve
the pathway from the basal forebrain to
amygdala or hippocampus and then to the prefrontal cortex, and time tagging of information
may be more reflected in verbal or episodic
memory. Further case analyses would be
necessary to confirm or rule out this possibility.
Summarising these three patients who had
discrete lesions in the basal forebrain, the critical anatomical lesion may be confined to the
nuclei of the diagonal band. Although other
possibilities cannot be entirely dismissed, the
primary underlying aetiology of amnesia resulting from a lesion in the basal forebrain thus
seems to be disconnection of the critical
bidirectional connections between the nuclei of

130

Abe, Inokawa, Kashiwagi, et al

the diagonal band and the hippocampus. This
idea is supported by the result of SPECT
showing a lesion in the basal forebrain and
reduction of blood perfusion in the hippocampus bilaterally. It is also possible that amnesia
caused by a lesion in the basal forebrain with
interference of the medial temporal function
may develop impairment in the time tagging of
information.
We obtained written informed consent to report on this patient.
1 Aaral DG. Memory anatomical organisation of candidate
brain regions. In: Mountcastle FP, Geiger SR, eds.
Handbook of physiology. Section 1. The nervous system. Vol V.
Higher function of brain. Part I. Bethesda, MD: American
Psychological Society, 1987:211–94,
2 Aggleton JP. Anatomy of memory. In: Yanagihara T,
Petersen RC, ed. Memory disorders: research and clinical
practice. New York: Marcel Dekker, 1991:23–62.
3 Von Cramon DY, Hebel N, Schuri U. A contribution to the
anatomical basis of thalamic amnesia. Brain 1985;108;993–
1008.
4 Damasio AR, GraV-Radford NR, Eslinger PJ, et al. Amnesia
following basal forebrain lesions. Arch Neurol 1985;42:263–
71.
5 Morris MK, Bowers D, Chatterjee A, et al. Amnesia following a discrete basal forebrain lesion. Brain 1992;115:1827–
47.
6 Lindqvist G, Norlen G. KorsakoV’s syndrome after
operation on ruptured aneurysm of the anterior communicating artery. Acta Psychiatr Scand 1966;42:24–36.
7 Talland GA, Sweet WH, Ballantine HT. Amnestic syndrome
with anterior communicating artery aneurysm. J Nerv
Ment Dis 1967;114:137–60.
8 Logue V, Durnard M, Pratt RTC, et al. The quality of survival after rupture of an anterior communicating artery
aneurysm. Br J Psychiatry 1968;114:137–60.
9 Gade A. Amnesia after operations on aneurysms of the
anterior communicating artery. Surg Neurol 1982;18:46–9.
10 Volpe BT, Hirst W. Amnesia following the rupture and
repair of an anterior communicating artery aneurysm. J
Neurol Neurosurg Psychiatry 1983;46:704–9.
11 Alexander MP, Freedman M. Amnesia after rupture of an
anterior communicating artery aneurysm. Neurology 1984;
34:752–7.

12 Parkin AJ, Leng NRC, Stanhope N, et al. Memory
impairment following ruptured aneurysm of the anterior
communicating artery. Brain Cogn 1988;7:231–43.
13 Phillips S, Sangalang V, Sterns G. Basal forebrain infarction.
A clinicopathologic correlation. Arch Neurol 1989;44:
1134–8.
14 Vilkki J. Amnestic syndromes after surgery of anterior communicating artery aneurysms. Cortex 1985;21:431–44.
15 Wechsler D. Wechsler adult intelligence scale - revised.
Anglicised revision. Sidcup: Psychological Corporation,
1986.
16 Milner B. Some eVects of frontal lobectomy in man. In:
Warren JM, Akert K, ed. The frontal granular cortex and
behavior. New York: McGraw - Hill, 1964:313–34.
17 Lezak MD. Neuropsychological assessment. 3rd ed. Oxford:
Oxford University Press, 1995.
18 Hirono N, Yamadori A, Kameyama M, et al. Spinocerebellar degeneration (SCD): cognitive disturbances. Acta Neurol Scand 1991;84:226–30,
19 Wechsler D. Wechsler memory scale - revised manual. San
Antonio, TX: The Psychological Corporation, 1991.
20 Taylor LB. Localization of cerebral lesions by psychological
testing. Clin Neurosurg 1969;16:269–87.
21 Benton AL, Spreen O. Visual memory test: the simulation of
mental incompetence. Arch Gen Psychiatry 1961;4:79–83.
22 Fukatsu R, Fujii T, Sati M, et al. Influence of age on long
term memory. Clin Neurol 1994;34:777–81. (In Japanese.)
23 Haines DE. Neuroanatomy: an atlas of structures, sections, and
systems. 4th ed. Baltimore: Williams and Wilkins, 1995.
24 Yanagihara T. Memory disorder in cerebral vascular disease.
In: Yanagihara T, Petersen RC, ed. Memory disorders:
research and clinical practice. New York: Marcel Dekker,
1991:l97–226.
25 Scoville WB, Milner B. Loss of recent memory after bilateral
hippocampal lesions. J Neurol Neurosurg Psychiatry 1957;
20:11–21.
26 Damasio AR, Eslinger PJ, Damasio H, et al. Multimodal
amnesic syndrome following bilateral temporal and basal
forebrain damage. Arch Neurol 1985;42:252–9.
27 Briggs GG, Nebes RD. Patterns of hand preference in a student population. Cortex 1975;11:230–8.
28 Tulving E, Kapur S, Markowitsch HJ, et al. Neuroanatomical correlates of retrieval in episodic memory: auditory sentence recognition. Proc Natl Acad Sci 1994;91:2012–5.
29 Tulving E, Kapur S, Fergus I, et al. Hemispheric encoding/
retrieval asymmetry in episodic memory: positron emission
tomography findings. Proc Natl Acad Sci 1994;91:2016–20.