Neuropsychologia 41 (2003) 1330–1344

Deficits of memory, executive functioning and attention following
infarction in the thalamus; a study of 22 cases with localised lesions
Ysbrand D. Van der Werf a,∗ , Philip Scheltens b , Jaap Lindeboom c , Menno P. Witter a ,
Harry B.M. Uylings a,d , Jelle Jolles e
a Department of Anatomy and Embryology, Graduate School for Neurosciences Amsterdam, Research Institute Neurosciences

Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
b Department of Neurology, Alzheimer Center, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
c Department of Medical Psychology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
d Netherlands Institute for Brain Research, Amsterdam, The Netherlands
e Department of Biological Psychology, The Maastricht Brain and Behaviour Institute, Amsterdam, The Netherlands

Received 24 September 2001; received in revised form 28 January 2003; accepted 4 February 2003

Abstract
The thalamus plays a crucial role in memory, executive functioning and attention. It remains, however, unclear whether thalamic structures
have specific roles in each of these functions. We tested 22 cases of thalamic infarction, proven with MR imaging, using experimental and
established neuropsychological tests. We performed a lesion-overlap study in standardised stereotactic space of patients sharing a certain
deficit, corrected for the lesion distribution of patients without such deficits and determined the regions of interest using an atlas of the
human thalamus. We checked for additional, non-thalamic, damage and for deficient comprehension and perception that would preclude
interpretation of the results. Non-thalamic damage such as white matter lesions, hippocampal atrophy, sulcal widening and infarctions
occur significantly more often in patients aged over 60. The patients with additional damage overlapped to a major degree with those who
showed loss of orientation, or lack of comprehension of the test requirements. In the 10 patients judged ‘clean’, we observed a deficit of
episodic long-term memory with relative sparing of intellectual capacities and short-term memory when the mammillo-thalamic tract was
damaged. Lesions including the medial dorsal nucleus, midline nuclei and/or intralaminar nuclei accompany executive dysfunctioning.
Reduced simple processing speed and attention are associated with age, but not with a particular structure in the thalamus. Complex
attention deficits follow damage to the intralaminar nuclei.
We conclude that the analysis of structure–function relationships must take into account extra-structure damage which may explain
cognitive deficits. Separate thalamic structures are involved in memory, executive functioning and attention.
© 2003 Elsevier Science Ltd. All rights reserved.
Keywords: Diencephalon; Diencephalic amnesia; Amnesic syndrome; Executive functioning; Attention

1. Introduction
Studies of patients with thalamic damage show that the
thalamus plays a role in several aspects of cognition. Of
these, memory has always received the greatest attention
due to striking cases of diencephalic amnesia, i.e. severe
memory loss due to thalamic damage (Bogousslavsky,
Regli, & Uske, 1988; Castaigne et al., 1981; Ghidoni,
Pattacini, Galimberti, & Aguzzoli, 1989; Graff-Radford,
∗ Corresponding author. Present address: Department of Neuropsychology, Cognitive Neuroscience Unit, room 276, Montreal Neurological Institute, McGill University, 3801 Rue University, Montreal, Que., Canada
H3A 2B4. Tel.: +1-514-398-3372; fax: +1-514-398-1338.
E-mail address: ysbrand@bic.mni.mcgill.ca (Y.D. Van der Werf).

Damasio, Eslinger, Yamada, & Damasio, 1985; Neau &
Bogousslavsky, 1996; Partlow, Del Carpio-O’Donovan,
Melanson, & Peters, 1992; Rousseaux, 1994; Rousseaux
et al., 1986; Stuss, Guberman, Nelson, & Larochelle, 1988;
Wallesch, Kornhuber, Kunz, & Brunner, 1983). This memory deficit depends on damage to the medial and anterior portions of the thalamus (Graff-Radford, Tranel, Van
Hoesen, & Brandt, 1990; Von Cramon, Hebel, & Schuri,
1985); more precisely, the anterograde amnesia, reminiscent of that seen following hippocampal damage, in cases
with thalamic damage appears to follow lesions of the anterior thalamic nuclei or their afferent white matter bundle,
the mammillo-thalamic tract (Gentillini, De Renzi, & Crisi,
1987; Van Der Werf, Witter, Uijlings, & Jolles, 2000).
Severe deficits in executive functioning and attention

0028-3932/03/$ – see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0028-3932(03)00059-9

Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

have also been noted in thalamic patients, but it remains
unclear which structures are involved (Bogousslavsky
et al., 1988; Fukatsu, Fujii, Yamadori, Nagasawa, &
Sakurai, 1997; McGilchrist, Goldstein, Jadresic, & Fenwick,
1993; Miller, Cummings, McIntyre, Ebers, & Grode, 1986;
Pepin & Auray-Pepin, 1993; Sandson, Daffner, Carvalho,
& Mesulam, 1991; Van Der Werf et al., 1999).
We here present a study of 22 cases of thalamic infarction,
tested with a fixed battery of tests to allow comparison between cases. The selection of tests aimed to measure different aspects of memory, attention and executive functioning.
We obtained MRI scans from each patient and plotted the lesion sites both in standard stereotactic space and in an atlas
of the thalamus. This allowed us on the one hand to perform
an analysis of the overlap of infarctions in groups of patients
with similar symptoms and on the other hand, we were able
to describe the location of the regions of interest in terms
of nuclei and white matter tracts affected. We controlled
for infarctions in subcortical areas and white matter tracts
surrounding the thalamus, hippocampal atrophy and sulcal
widening, factors that would confound structure–function
relationships within the thalamus (De Groot et al., 2000;
Houx, Vreeling, & Jolles, 1991; Scheltens et al., 1992;
Visser et al., 1999). Similarly, we controlled for deficits of
basal cognitive abilities, such as vigilance and understanding. In doing so, we aimed to provide more information on
which thalamic structures are involved in executive functioning and attention, and to confirm previously established
structure–function relationships for memory (Van Der Werf
et al., 2000).

1331

2. Methods
Neurologists from four academic centres in The Netherlands participated to recruit patients with thalamic stroke
from neurology clinics, rehabilitation clinics, academic hospitals and community hospitals. In the course of 4 years, 22
patients were included.
In all patients, the diagnosis of thalamic infarction was
made with the aid of structural brain images; in most cases,
high-resolution MR images were obtained with a 1.5 T machine using both T1- and T2-weighted images. In case 11,
no MR imaging could be performed due to the presence of
a pacemaker; the MRI of case 19 was discarded because of
motion artefacts. In these cases, CT scans were used to delineate the site of the lesion.
Table 1 shows demographic, personal and lesion characteristics of the group of patients studied.
2.1. Lesion localisation
Lesion sites were interpreted by two experienced neuroanatomists who were blind to the deficits of the patients. We plotted lesions in T1-weighted MR images of
a single subject’s brain, transformed into Talairach space
(Talairach & Tournoux, 1988), using software developed in
the Montreal Neurological Institute. The brain used forms
the template for the software package for Statistical Parametric Mapping (SPM’99). The template consists of 1-mm
isotropic voxels. After drawing, the lesions were smoothed
with a 2-mm FWHM kernel. This serves to take away

Table 1
Patient characteristics
Case

Sex

Age at testing

Infarction-test delay

Side of infarction

Formal education (year)

Handedness

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22

M
M
M
F
F
M
M
F
M
M
M
M
M
M
F
F
F
M
M
F
F
F

22
31
38
44
46
47
50
54
54
54
56
57
58
60
66
66
68
71
72
75
82
83

3 months
3 months
5 years
3 years and 5 months
3 months
3 months
7 months
4 years and 5 months
9 months
24 years
3–4 years
1 year and 6 months
1 year and 3 months
16–18 years
5–7 months
3 months
2 months
?
3 months
7 months
2 months
3 months

L
R
L
R
L
L
L
Bilateral venous thrombosis
Bilateral
Bilateral
L
L
Bilateral, L > R
R
R
Bilateral
R
Bilateral
L
R
L
L

10
15
9
11
10
15
>10
9
10
10
12
>10
>10
10
7
8
7.5
Unknown
Unknown
Unknown
9
Unknown

R
R
R
L
R
R
R
R
R
R
R
R
R
R
Ambidextrous
Ambidextrous
R
R
R
Ambidextrous
R
Ambidextrous

Abbreviations: M, male; F, female; L, left; R, right.

1332

Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

Fig. 1. Atlas of the human thalamus, used to map the site and extent of the infarctions (adapted from Morel et al., 1997). The slices shown are sections
perpendicular to the line connecting the anterior commissure and the posterior commissure. The distance in millimetres to the posterior commissure is
indicated. Abbreviations: Ant, anterior nuclei; IML, internal medullary lamina; LP, lateral posterior nucleus; MD, medial dorsal nucleus; Mid, Midline
nuclei; MTT, mammillo-thalamic tract; Pulv, Pulvinar; Rt, reticular thalamic nucleus; VA, ventral anterior nucleus; VL, ventral lateral nucleus; VP, ventral
posterior nucleus.

sharp edges of the drawing, minimises drawing inaccurities and the end result can be thought of a representing a
probability map of the lesion localisation. We classified the
infarctions according to the nuclei and white matter tracts
affected, using sections of the thalamus adapted from the
human thalamic atlas of Morel, Magnin, and Jeanmonod
(1997) (Fig. 1). Six coronal sections perpendicular to
the line connecting the anterior and posterior commissure were chosen, spaced 3.4 mm apart. The nomenclature
follows that of Morel et al. (1997) and Hirai and Jones
(1989).
The scans were scored by a single trained neurologist,
who was blind to the outcome of neuropsychological testing, using qualitative and quantitative rating scales for the
presence of cortical or subcortical abnormalities, i.e. other
infarcts, white matter lesions, hippocampal atrophy and sulcal widening (Scheltens et al., 1992, 1993). The reliability
of such ratings, e.g. for hippocampal atrophy, is fair to good,
especially when scores are collapsed into a dichotomous
score (present or absent atrophy; see Section 2.4) (Scheltens,
Launer, Barkhof, Weinstein, & Van Gool, 1995).
2.2. Neuropsychological assessment: tests used
To test the different memory-related functions, we used
a specially selected battery of tests following Jolles (1986)
and Jolles, Houx, Van Boxtel, and Ponds (1995), used for
large-scale experimental and clinical studies of neurocogni-

tion in middle-aged and elderly subjects (e.g. Bosma, Van
Boxtel, Ponds, Houx, & Jolles, 2000; De Groot et al., 2000;
Hofman, 2000; Moller et al., 1998; Van Boxtel et al., 1998,
2000). These addressed recall from short- and long-term
memory, recognition, executive abilities and speeded information processing. Table 2 gives an overview of the tests
used.
The Verbal Learning Task (VLT) was used to assess direct, delayed and recognition memory in the verbal modality (Brand & Jolles, 1985). Recognition was tested with a
list containing the 15 words encountered during the learning trials and 15 distractor words. Non-verbal memory was
assessed with the Rey Complex Figure Test (Meyers &
Meyers, 1995), Warrington’s Recognition Memory Test for
Faces (Warrington, 1984), and the Visual Association Test
(Lindeboom, 1989; Lindeboom, Schmand, Tulner, Walstra,
& Jonker, 2002; Rombouts et al., 1997). Memory interference was measured using a test for recall of word triplets
(Jolles, modified after Luria, 1966).
We measured attentional processes involving speeded information processing with the Brown–Peterson paradigm,
digit span backward and forward (Lindeboom & Matto,
1994), the Concentration-Endurance Test (d2 test) (Brickenkamp, 1981), Concept Shifting Test (Jolles et al., 1995; a
modification of the Trail Making Test, Reitan, 1958), the
Stroop test (Stroop, 1935) and the Paper and Pencil Memory Scanning Test (Brand & Jolles, 1987; Houx et al., 1991;
Jolles et al., 1995).

Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

1333

Table 2
Tests administered
Cognitive variable

Test used

Memory

VLT
Direct recall
Delayed recall
Delayed recognition
Rey
Direct recall
Delayed recall
Delayed recognition
VAT
RMTf
Word triplets

Operationalisation
Number of words remembered after five trials of 15 words
Number of words remembered after a 1-h interval
Number of words recognised (15 target words/15 distractor words)
Number of correctly drawn elements (of 36)
Number of correctly drawn elements (of 36)
Number of correctly recognised elements (of 24)
Number of correctly recalled visual associations (two series of 6)
Number recognised (of 50)
Number recalled

Attention and speeded processing

Digit span
Brown–Peterson paradigm
PPMST
Concept Shifting Task
Stroop
d2

Forward; backward
0-s delay; 3-s delay; 9-s delay; 18-s delay
% symbol subtest; 1–4 letter subtest
Zero, letter, digit and alternating conditions
Reading and color naming conditions
Total number of items crossed out; number of errors; total number
of items crossed out minus errors; consistency

Fronto-executive functions

WCST
ToL
Verbal category fluency
Stroop

Number of categories achieved; number of perseverative errors
Number of trials correct; number of trial correct in minimal sequence
Animals; professions
Interference condition

Intelligence and general abilities

GIT
DART
CST

Three-subtest version
Number of correctly pronounced words
20 items of personal and general knowledge

Abbreviations: CST, Concept Shifting Test; DART, Dutch Adult Reading Test; GIT, Groningen Intelligence Test; MCRT, Multiple Choice Reaction Time
Task; PMT, Prospective Memory Test; PPMST, Paper and Pencil Memory Scanning Test; RMTf, Recognition Memory Test for Faces; TMT, Trail Making
Test; VAT, Visual Association Test; VLT, Verbal Learning Task; WCST, Wisconsin Card Sorting Test.

Executive abilities were assessed with the Tower of London test (Maastricht version of the test devised by Shallice,
1982), a computerised version of the Wisconsin Card Sorting Test (Berg, 1948), verbal category fluency (Lezak, 1995)
and the colour–word interference condition of the Stroop
test (Stroop, 1935).
The short form of the Groningen Intelligence Test (GIT)
(Luteijn, 1966; Luteijn & Van Der Ploeg, 1983) was used
to obtain a measure of general intellectual functioning. The
Cognitive Screening Test, a Dutch modification of the Short
Portable Mental Status Questionnaire (Pfeiffer, 1975), was
used to obtain a measure of orientation and general knowledge.
2.3. Neuropsychological assessment: scoring
Two neuropsychologists scored the neuropsychological
and observational data (JJ and JL). At the time of this assessment, both were unaware of the nature or location of
the brain lesion. Before interpreting the results, the patients
were judged for their ability to use language, perceive and
comprehend the test instructions. The rationale for this was
that for patients who were unable to understand the procedure accurately or were unable to discern or hear the stimuli, a definite conclusion about memory or other functions
could not be based on the raw test data. Verbal memory

was indexed for immediate and delayed recall and delayed
recognition. A separate index for visual memory was used.
The patients were judged to have an amnesic syndrome if
they fulfilled the criteria of anterograde amnesia with spared
intellectual and attentional abilities (Van Der Werf et al.,
2000). We analysed memory performance further in terms
of ‘primacy’ and ‘recency’, measured as the recall of the
first and the last three words in the list, respectively, summed
over five trials. The number of words recalled from positions
4 to 12 in the list, summed over five trials was called ‘rest’.
Delayed recall and recognition were tested after an interval
of 1 h. Recall scores were expressed as total number of target words recalled, recognition scores were expressed as the
number of target words minus the number of false negatives
and false positives. The non-verbal recall score was the sum
of the scores of the Rey direct and delayed recall measure.
Impulsivity/inhibition was judged from behaviour during
the semi-structured interview preceding testing and from
behaviour during test performance, e.g. from inappropriate
or rash responses. Evidence for executive dysfunctions was
derived quantitatively from the Wisconsin Card Sorting
Test, the Tower of London test, the colour–word interference condition of the Stroop test, verbal category fluency
and qualitatively from the learning strategy used in the
verbal learning test. Attention and speed of information
processing were judged on the basis of speed and number

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Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

of errors on tests of simple and complex processing (Houx
& Jolles, 1993; Jolles, 1986; Jolles et al., 1995).
The two scoring neuropsychologists judged the performance of the patients per test variable and made use of behavioural observations made during the testing, described in
the test protocol by the testing neuropsychologist (YDvdW).
They used a formal scoring system in which the performance
per test or observational variable was scored as either normal
(scored as 0), mildly impaired (1), impaired (2) or strongly
deficient (3).
2.4. Structure–function analysis
From the drawings of the lesions in stereotactic space,
we established an overlap of regions affected in patients
with similar symptoms, using software developed in the
Montreal Neurological Institute. The degree of overlap between lesion sites does not necessarily reflect only those
areas implicated in the functional deficits, but may contain
areas that are damaged because of sharing arterial supply
with critical regions. Such ‘innocent bystander’ regions
may be excluded when the overlap plot of patients without a certain deficit is subtracted from the overlap plot
of patients who share that deficit. This method has been
used before in thalamic patients in determining the areas
associated with neglect (Karnath, Himmelbach, & Rorden,
2002). We formed subgroups of patients on the basis of the
neuropsychological scoring. We used Chi-squared analyses
to verify findings from the overlap/subtraction analysis and
to investigate further possible group differences (Pearson’s
χ 2 , SPSS for Microsoft Windows software, version 9.0). In
the analyses, we condensed the scores for test performance
into a dichotomy of no/mild impairments (score 0 or 1) and
evident impairments (score 2 or 3).

3. Results
3.1. Thalamic lesions
Of the 22 patients studied, 15 had unilateral lesions and
7 had lesions falling in the thalamus of both hemispheres.
The latter type of infarction was more or less symmetrical
in three cases, but four cases had lesions that were larger on
one side or in different locations on each side. Table 3 lists
the nuclei affected and Fig. 2 illustrates the location, size
and shape of the lesions.
Recurring patterns occurred in the distribution of lesions:
eight patients showed an elongated lesion in the rostral thalamus, seen on coronal view (Fig. 3A). This lesion was bilateral and symmetrical in patients 9 and 18, bilateral and
asymmetrical in patients 10 and 20, and left-sided unilateral in patients 5, 12, 14 and 19. This type of infarction
causes a lesion typically reaching the third ventricle ventral
in the thalamus and coursing obliquely in the dorsolateral
direction, thereby intersecting the MTT and often causing

Fig. 2. Lesion sites of the patients, drawn in the atlas of the human
thalamus. Patient 8 is not shown because her lesion was not the result
of an infarction, but due to a venous thrombosis of the sinus rectus.
Unilateral lesions are shown in the top diagram, bilateral lesions in the
lower diagram. Left and right in the drawing correspond to the actual site
of the infarction.

damage to the adjacent ventral IML and MD. Lesions of
this type arise from embolisms or ruptures of the polar or
tuberothalamic artery (Bogousslavsky, Regli, et al., 1988).
In four patients, a small lacunar infarct appears in the lateral internal medullary lamina or the lateral part of the MD,
approximately halfway the rostro-caudal extent of the thalamus (Fig. 3B). Cases 10, 13, 14 and 20 show such an infarction, either alone or in combination with other lesions
in the thalamus. This type of lesion interferes with the integrity of the nuclei contained in the lateral IML, mainly the
central lateral nucleus. This type of lesion typically occurs
after an occlusion of the small arterioles of the paramedian
artery.
Cases 2 and 4 had lesions encompassing the ventral part
of the thalamus at a middle level bordering the third ventricle (Fig. 3C). This type of lesion lies in the region of the
parafascicular and centre médian nuclei that together form
the caudal IML. Again, this type of lesion follows vascular
problems in the territory of the paramedian artery.
Cases 3, 6, 7, 11, 17 and 21 show lesions located laterally
and caudally in the thalamus, encompassing the lateral posterior nucleus, pulvinar or reticular nucleus (Fig. 3D). Such

Table 3
Lesion localisation of the patients included in this study
Age

1a
2a
3a
4a
5a
6

22
31
38
44
46
47

7a
8a

50
54

9a
10a
11
12a
13
14
15

54
54
56
57
58
60
66

16
17a
18
19
20
21

66
68
71
72
75
82

22

83

Ant

MTT

MD

Mid

IML

VA

L
R

L

R

L

VL

LP

VP

L
L

L

R
L

L/R
L/R

L/R

L

L
L

L

L

L
L

L
L

L/R
L

Rt

R
L

Sinus rectus
thrombosis
L/R
L

Pulv

L/R
L/R

L/R
L

L

L

R
L

L
L/R
R
R

R

R

L
R

L>R
R

L/R
L
R

L
L
R

L/R
L

L>R
L
L

R

L>R

L
L

L

L

L

White matter lesions

Hippocampal
atrophy (grade)

Sulcal widening

Other lesions

No
No
No
No
No
VR spaces in basal Ganglia
and frontal white matter
VR spaces in basal Ganglia
VR spaces

No
No
No
No
No
I

No
No
No
No
No
Diffuse, lightly

Temporal cyst L
None
None
None
None
Pontine infarct

No
No

No
No

None
Cerebellar infarct

No
No
No
No
Periventricular + subcortical
VR spaces
Parieto-occipital

No
No
No
No
No
II–III
I–II

No
Fitting with age
No
No
Fitting with age
Temporal
Occipital

No
Periventricular ‘caps’
Diffuse periventricular
Periventricular
No
No

I
No
II
Unclear
II–III
III

Frontal
No
Fitting with age
Diffuse
Diffuse
Fitting with age

Diffuse

II

Temporal

None
None
Old temporal cortex infarct L
None
Basal Ganglia lacunar infarcts
None
Claustrum L/R, capsula
interna R infarct
Occipital cortex infarct R
None
Basal ganglia lacunar infarcts
Temporo-occipital infarct R
Hypothalamic infarct R
Caudate R, pallidum R,
pontine infarcts
Claustrum infarct R

Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

Case

Abbreviations: Ant, anterior nuclei; IML, internal medullary lamina; LP, lateral posterior nucleus; MD, medial dorsal nucleus; Mid, Midline nuclei; MTT, mammillo-thalamic tract; Pulv, Pulvinar; Rt,
reticular thalamic nucleus; VA, ventral anterior nucleus; VL, ventral lateral nucleus; VP, ventral posterior nucleus; L, left-sided lesions; R, right-sided lesions; VR, Virchow–Robin.
a Patients judged ‘clean’, i.e. without significant pathology apart from the thalamic lesion.

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Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

Fig. 3. (A) T2-weighted coronal MR scan of patient 10 showing a bilateral infarction of the tuberothalamic artery. The arrowheads point at the liquor-filled
lacunes. Left and right are inverted, following radiological convention. (B) T1-weighted coronal MR scan of patient 13 showing a left-sided infarction
in the lateral part of the medial dorsal nucleus and/or the internal medullary lamina, arising from an embolism in the paramedian artery (arrow). (C)
T2-weighted axial MR image of patient 2 showing a recent right-sided medial infarction of the paramedian artery (arrow). (D) Turbo Inversion Recovery
axial MR scan of patient 17, showing a right-sided ventral posterior thalamic infarction (arrow) of the posterior choroidal artery.

lesions would follow occlusions in the posterior choroidal
or principal inferolateral arteries.
3.2. Other brain damage
Eleven cases showed evidence of pathology unrelated
to the thalamic lesion. These included gross abnormalities
like other infarctions or severe hippocampal atrophy, or
subtle changes such as diffuse cortical atrophy, seen as
sulcal widening (Fig. 4A–D). Some of the findings may be
asymptomatic and congruent with older age, such as the
presence of Virchow–Robin Spaces (e.g. cases 7 and 14) or
periventricular white matter caps (case 17). Hippocampal
atrophy of grade II, I or 0 is regarded as asymptomatic in
the age group of 75 and older. In case 1, a cyst located
in the temporal cortex was found that was judged asymptomatic. Case 8 was excluded from further analysis because

she had a venous thrombosis in the thalamus instead of an
infarction. Table 3 shows the occurrence of white matter
lesions, hippocampal atrophy, global cortical atrophy and
evidence of other lesions as judged from visual inspection of the MR images. The table shows that most of the
cases judged ‘clean’, i.e. without significant extra-thalamic
damage, were 60 years of age or younger. Chi-squared
analysis on the presence of significant pathology in the
patients confirmed this skewed distribution (χ 2 = 10.145,
P = 0.01).
3.3. Neuropsychological data
Ten patients showed impaired understanding of the test instructions, had an impairment of reasoning or formal thought
processes, had perceptual problems or visuo-constructive deficiencies that would hamper the interpretation of the test

Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

1337

Fig. 4. (A) T1-weighted coronal MR image of patient 6 showing a right posterior thalamic infarction (arrow). Note the pontine infarction (arrowhead).
(B) T1-weighted coronal MR image of patient 22. The left sided tuberothalamic artery infarction is indicated with an arrow. Note the pronounced cortical
atrophy (arrowhead). (C) T2-weighted MR image of patient 20, showing the medial thalamic infarction extending into the hypothalamus (arrow). The
arrowhead indicates the grade III hippocampal atrophy. (D) T2-weighted MR scan of patient 15, showing the bilateral parieto-occipital subcortical white
matter hyperintensities (arrowheads).

of memory and executive functioning. The conclusion of
impaired understanding was made by the two scoring neuropsychologists, at the time of scoring blind to the imaging
data of the patients.
Patients were excluded from interpretation of the memory
test scores on the basis of any of the following: scores of
2 or 3 on language, perception or visuo-construction; an
orientation score below 17; an IQ score of more than one
standard deviation below the mean (i.e. 85 or lower). The
latter criterium was not applied for case 3 since he is a
non-native Dutch speaker which lowered his IQ score. This
left a group of 12 patients judged sufficiently cognitively
adequate (i.e. sufficiently able to use language, perceive the
test stimuli, understand the instructions, etc.). This is shown
in Table 4.
From this group of 12 selected patients, 10 also fulfilled
the criterium of having no significant additional brain damage. The neuropsychological test results of all patients included in this study are given in Table 5.

3.3.1. Memory
In the whole group of patients, memory performance varied from intact to severely impaired. The verbal recall, verbal
recognition and visual recall impairments were distributed
randomly over both age groups (younger than 60 or 60 and
older) and over the two groups of patients, those judged
‘clean and cognitively adequate’ and those not (χ 2 = 1.316,
P = 0.251 and χ 2 = 1.473, P = 0.225, respectively, for
the verbal recall scores).
In the ‘clean and cognitively adequate’ group, consisting
of 10 patients, three cases matched the criteria for an amnesic syndrome. Of these, cases 9 and 10 showed a memory
deficit in both the verbal and non-verbal modality, whereas
in case 12 the deficit was observed only in verbal memory
tasks. The other cases showed either mild or no memory
problems. In the remaining group of patients, those with
extra-thalamic lesions and/or a lack of cognitive adequacy,
cases 15, 18 and 20 had memory problems compatible with
an amnesic syndrome. Cases 19 and 22 had a dense amnesia

1338

Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

Table 4
Prerequisites for interpretation of performance on the tests of memory, speeded processing, attention and executive deficits
Case

Language
skills (0–3)

Orientation (1–20)

Understanding (0–3)

IQ

Perception (0–3)

Visuo-construction
(0–3)

1a
2a
3a,b
4a
5a
6a
7a
8
9a
10a
11
12a
13
14
15
16
17a
18
19
20
21a
22b

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0

19.5
18
18
No data
17
19.5
18.5
19
No data
19
18
18
20
19
19.5
20
20
7
15
6
20
16

0
0
1
0
1
0
0
2
0
1
2
0
2
0
2
2
0
2
2
2
1
2

103
114
79
107
103
114
132
110
93
119
86
114
No data
58
56
No data
114
No data
68
No data
100
61

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
0
0
0
0
0
0

0
0
0
0
0
0
0
2
0
0
0
0
0
2
2
2
0
3
No data
No data
0
3

Use of language, orientation, understanding, perception and visuo-construction are scored on the basis of consensus between two independent neuropsychologists on a scale of 0 (normal) to 3 (severely impaired). Orientation is measured with the CST, a Dutch modification of the Short Portable Mental
Status Questionnaire (Pfeiffer, 1975). IQ is measured with the short version of the Groningen Intelligence Test (GIT; Luteijn, 1966).
a Patient judged ‘cognitively adequate’, i.e. sufficiently oriented and able to understand the tests, enabling the experimenters to validly interpret the
test results.
b Non-native speaker.

Table 5
Neuropsychological test performance after an infarction in the thalamus
Case

1a
2a
3a
4a
5a
6
7a
8
9a
10a
11
12a
13
14
15
16
17a
18
19
20
21
22

Recall verbal

0
1
0
0
2
0
2
0
3
3
2
3
2
3
3
2
0
3
3
3
0
3

Recognition
verbal

0
2
0
0
2
0
0
0
3
3
0
3
1
1
3
0
0
3
No data
3
0
0

Visual
memory

2
1
2
1
2
0
0
1
3
3
2
0
2
2
3
3
0
3
3
3
0
3

Amnesic
syndrome

No
No
No
No
No
No
No
No
Yes
Yes
No
Yes, verbal
No
No
Yes
No
No
Yes
Insufficient data
Yes
No
Insufficient data

Test results are scored qualitatively from 0 (intact) to 3 severely impaired.
a Patient judged both ‘clean’ and ‘cognitively adequate’.

Fronto-executive functions

Speeded information
processing

Planning

Impulsivity/inhibition

Simple

Complex

2
2
2
2
2
1
0
2
3
2
1
1
1
3
3
2
0
3
3
3
2
2

2
2
2
2
2
0
2
1
2
0
0
0
0
0
0
0
0
3
3
2
0
2

2
0
0
2
2
0
0
0
0
0
2
2
2
3
3
1
2
3
3
3
2
3

0
0
0
2
2
1
0
2
2
2
0
1
2
3
3
1
0
3
3
No data
2
2

Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

1339

Table 6
Profile of memory performance
Case

Primacy
(0–15)

Recency
(0–15)

Rest (0–45)

Delayed recall
(0–15)

Recognition
(0–15)

Non-verbal
recall (0–72)

Memory
interference

1a
2a
3a
4a
5a
6
7a
8
9a
10a
11
12a
13
14
15
16
17a
18
19
20
21
22

12
15
12
12
12
11
13
14
1
7
8
13
7
5
11
10
14
2
5
0
13
1

7
0
11
10
5
9
7
4
8
11
10
9
4
7
6
8
11
2
7
2
12
8

25
27
25
23
11
22
16
24
12
10
11
6
8
11
9
20
22
2
8
0
24
10

7
6
9
11
6
9
8
8
0
0
6
0
0
4
2
4
11
0
No data
0
9
2

14
10
15
15
12
14
13
12
8
8
14
0
8
9
7
13
14
No data
No data
3
12
12

17.5
26
29
31
35
42.5
47
30.5
4.5
18
14
55
21
20
8.5
5.5
38
No data
17.5
No data
38
7

None
Proactive
Global
No data
Proactive
None
Proactive
Global
No data
None
Global
Retroactive
Proactive
No data
Global
Global
No data
No data
None
Global
Global
Global

a Patients judged both ‘clean’ and ‘cognitively adequate’.

presumably caused by an amnesic syndrome, but clouding
of consciousness precluded such a diagnosis.
Table 6 presents a closer look at the memory performance
of the patients. It shows that two of the patients judged ‘clean
and cognitively adequate’ with an amnesic syndrome (cases
9 and 10) had low primacy scores (1 and 7, respectively)
and variable recency scores of verbal learning. Such a pattern indicates a failure to encode new verbal stimuli. In contrast, the patients in this group who did not have an amnesic
syndrome all had good primacy scores (12 or higher). Interestingly enough, case 12 who had an amnesic syndrome
in the verbal modality only, did show a high primacy score.
In view of his markedly deficient delayed recall and recognition scores, his memory deficit seems more a problem of
rapid forgetting than of deficient encoding. His deficit cannot be attributed to retrieval problems and, therefore, remains compatible with an amnesic syndrome. In addition,
this case was the only one to show retroactive interference
in the word triplets test.
In the group of patients that were judged to have additional lesions and/or cognitive dysfunctions precluding test
administration, four of five patients with a probable amnesic
syndrome (cases 18, 19, 20 and 22) had the same profile of
low primacy scores. Case 15, on the other hand, showed a
relatively good primacy score.
3.3.2. Frontal-like dysfunctions
Executive dysfunctions frequently characterised our thalamic patients and were found regardless of whether the patients were considered ‘clean and cognitively adequate’ and
regardless of age (χ 2 = 0.069, P = 0.793 and χ 2 = 2.006,

P = 0.157, respectively). Impulsivity or disinhibition on
the other hand, appeared to cluster in the group of patients
considered ‘clean and cognitively adequate’ but showed no
relationship with age. This was confirmed by statistical analysis (χ 2 = 2.933, P = 0.087 and χ 2 = 0.188, P = 0.665,
respectively). Executive deficits could be associated with severe memory disorders (e.g. case 9) or be encountered alone
(e.g. case 8).
3.3.3. Speeded information processing
These functions were tested both with simple and complex
information processing tests and included aspects of attention. Speeded information processing is frequently impaired
in patients with thalamic lesions. Here too, the deficits were
found regardless of whether or not the cases were judged
‘clean and cognitively adequate’ (for the simple tasks: χ 2 =
1.473, P = 0.225; for the complex tasks: χ 2 = 2.291,
P = 0.130). Impairments on tasks of simple speed, however, tended to cluster with the group of patients aged 60
or older (χ 2 = 4.197, P = 0.040). Complex attentional
deficits, on the other hand, did not show a relationship with
age (χ 2 = 1.683, P = 0.195).
3.4. Structure–function relationships
3.4.1. Overlap/subtraction analysis
As an initial screening, we performed the overlap and subtraction image analysis on the group of subjects with any
kind of memory problem (scores of >2 on any of the memory variables: verbal recall, verbal recognition, visual memory, and/or amnesic syndrome, see Table 6) minus the group

1340

Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

Fig. 5. Amnesic syndrome corresponds to lesions of the MTT. The figure shows the degree of overlap of lesions of patients with an amnesic syndrome,
corrected for the lesion distribution of patients who do not show such deficits, in the in the group of 10 ‘clean’ patients. The data are displayed on a
template in standardised space (z = −2) (Scheltens et al., 1995). The image is thresholded between P = 0.4 and 0.82.

of people without memory problems (scores of <2 on all
of the memory variables). This analysis shows that memory problems may occur after lesion of different widespread
areas of the thalamus. The subtraction of the area damaged in subjects without memory problems from that of
patients with, does not reveal a single area of high probability (not shown). To analyse further the involvement of
thalamic structures in specific functions, we made separate overlap/subtraction plots for the amnesic syndrome,
for simple and complex speeded processing, for impulsivity/disinhibition and deficits of executive functioning. For
the overlap of areas associated with the amnesic syndrome
minus the overlap of the lesions of patients without, two regions emerged in the left and right ventral anterior thalamus,
coinciding with the location of the mammillo-thalamic tract,
or MTT (P = 0.52 and 0.46, respectively). When the analysis was restricted to the patients judged ‘clean’, a single
circumscribed region emerged with high probability (P =
0.82; Fig. 5; Table 7). The peak lies in the left thalamus,
due to the lesion distribution of the three patients that contribute to this overlap; in cases 9 and 10, the lesion damaged
the thalamus on both sides, in case 12 the lesion was found
in the left thalamus only. The probability does not reach 1,
because one patient (case 5) did not show an amnesic syndrome in spite of left unilateral damage in the region of

the MTT. Statistical analysis confirmed that the clustering
of an amnesic syndrome with lesions of the MTT in the
group of 10 selected patients was significant (χ 2 = 6.429,
P = 0.011).
For deficits of executive functioning, there was no single
region in the thalamus that shows a high degree of association with the deficits. Rather, two areas showed up with
equal likelihood of involvement (P = 0.40 and 0.39) in the
group of ‘clean’ patients only: these are a right medial ventral region corresponding to the ventral MD, midline nuclei
and medial intralaminar nuclei, and a region lying ventrally
and anteriorly in the left thalamus. At first glance, this area
seems to correspond to that found for the amnesic syndrome,
but it lies lateral, posterior and dorsal to it, and, therefore,
would correspond to the anterior portion of the intralaminar
nuclei that is located adjacent to the MTT (Fig. 6; Table 7).
For complex speeded processing, a peak indicating a probability of involvement of 0.69 arose in the left ventral anterior
portion of the thalamus, with the same coordinates as the
presumed ventral intralaminar peak found for executive dysfunctioning. This was evident in the group of ‘clean’ patients
only. For impulsivity/inhibition and simple speeded processing, no overlaps were found with probabilities greater than
0.35 in either the groups of ‘clean’ patients or all patients
(not shown).

Table 7
Peak values from the overlap/subtraction analysis
Function

X

Y

Z

Probability

Corresponding structure

Amnesia—all patients

−6
8
−6
−7
5
−8

−9
−11
−9
−10
−19
−10

−1
1.5
−2
0
−1
1

0.5135
0.4644
0.8195
0.6935
0.4025
0.3852

Left MTT
Right MTT
Left MTT
Left vIML
Right vIML/MD
Left vIML

Amnesia—clean patients
Complex speed—clean patients
Executive dysfunctioning—clean patients

X, Y and Z coordinates of local maxima are given in stereotactic space. Only overlaps with P > 0.35 are shown.

Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

1341

Fig. 6. Executive disorders correspond to damage to the ventral IML and ventral MD/midline. Shown in the figure is the degree of overlap of lesions
in patients with executive dysfunction, corrected for the lesion distribution of patients without such deficits, within the group of 10 ‘clean’ patients. The
data are displayed on a template in standardised space (z = +1) (Scheltens et al., 1995). The degrees of overlap are thresholded between P = 0.1 and
0.42. Note the more lateral and dorsal position of the anterior thalamic peak, compared to Fig. 5.

3.4.2. Case-wise description of the data
In the group of 10 patient judged ‘clean and cognitively
adequate’, all three cases that showed memory deficits so
severe as to qualify as an amnesic syndrome, had sustained
damage to the MTT. In cases 9 and 10, the damage to the
MTT was found on both sides; in case 12, the lesion was
found on one side only. One case, however, which had unilateral damage to the MTT showed memory problems but
not strong enough to fulfil the criteria of an amnesic syndrome (case 5). In the remaining 12 patients, a similar picture
emerged although definite conclusions could not be drawn
due to the structural pathological or cognitive factors complicating test interpretation. Thus, patients 18 and 20 had
lesions encompassing the MTT and were diagnosed with an
amnesic syndrome. Patients 19 and 22 had also sustained
damage to their MTT and suffered from a dense amnesia,
although they were too disoriented to obtain sufficient test
results for a diagnosis of an amnesic syndrome. Patient 15
did not have a lesion encompassing the MTT, a finding that
would not agree with the fact that her memory deficit might
lead to the diagnosis of an amnesic syndrome. Nevertheless,
at closer observation, the profile of her memory performance
was characterised by a good primacy score compared to her
recency score, as evident from Table 7. Apparently, her severe memory deficits are not so much a result of an amnesic
syndrome but due to a lack of efficient use of memory strategies. This would be the result of her extensive white matter
lesions and additional infarcts.
The executive deficits were at first sight not found to be
strongly related to the site of the infarction in the thalamus.
They could be observed after large anterior lesions (e.g. case
5), middle lesions (e.g. case 4) or large posterior lesions (e.g.
case 3). Since executive dysfunctions were so frequent and
seemingly a-specific, we decided to look at the cases that did
not display signs of deficits on these measures, to see if they
had a common denominator. There were five cases without
gross defects in the performance on tasks of executive func-

tions. These had lesions falling postero-laterally (cases 6, 11
and 17), a small lesion lying anteriorly without interfering
with the IML and barely touching the MD (case 12) or a
small lesion falling in the lateral MD (case 13). These five
lesions, thus, tended to either avoid the main masses of the
MD, midline nuclei and the lateral part of the IML, or be so
small as to affect only a small portion of these nuclei.
No relation between the attentional or information processing deficits and damage to thalamic structures was
apparent. These seemed to be scattered over the group
regardless of whether the lesions were found anterior, posterior, lateral or medial. Four cases showed no evidence of
such deficits; these had lesions falling posteriorly (cases 3,
6 and 7) or in the ventral midline (case 2).

4. Discussion
We aimed to find relationships between thalamic structures and memory, executive functions and attention. We
performed a lesion-overlap and subtraction study in stereotactic space to investigate associations between thalamic
structures and cognitive functions across our group of subjects, followed by a case-wise analysis of the pattern of
deficits in each subject. A clear relationship between a specific kind of memory disorder, i.e. the amnesic syndrome,
and structural damage to the MTT was found. No such simple relationships showed up for executive functioning and
attention.
It proved necessary to distinguish between patients with
pure lesions of the thalamus and those in which additional
damage obscured the interpretation of test results; the association between functional deficits and structural damage in
our image analysis was invariably higher when considering
only the pure cases of thalamic damage.
The occurrence of such subtle additional brain lesions in
older age is a common phenomenon and explains a large

1342

Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

proportion of the differences between subjects. Indeed, the
variance in cognitive capacities increases with older age,
causing structure–function relationships between e.g. thalamic volume and performance on cognitive tasks in healthy
subjects to attain significance in young subjects only (Houx
& Jolles, 1993; Van Der Werf et al., 2001).
The data confirm our previous finding that no single
area in the thalamus appears to account for memory problems in the broad sense of the word (Van Der Werf et al.,
2000). Damage to several and distinct areas contribute to
amnesia, although the nature of the memory deficit may
be different. These areas include large areas in the anterior
and medial parts of the thalamus, including the anterior
nuclei, MD, midline and intralaminar stuctures. Posterior
and lateral lesions can evolve without any memory problem, showing some degree of functional specificity in the
thalamus. When considering memory problems consistent
with an amnesic syndrome, however, only one area proved
to associate highly: a ventral area that overlaps the location
of the MTT. It has to be noted that this peak spreads into
the adjacent sector of the ventral MD and IML. It cannot be
ruled out that these lesions contribute to the development of
an amnesic syndrome. The data would, therefore, concord
with the views of Graff-Radford et al. (1990) and Aggleton
and Brown (1999), who state that a combined lesion to the
MTT and adjacent IML white matter carrying fibres from
the medial temporal lobe cortices to the MD is necessary
for the development of a dense amnesia, characterised by
both deficient recall and recognition. According to Aggleton
and Brown (1999), damage to the MD and afferent fibres
carried in the IML alone would be sufficient to produce
a recognition deficit. The cases that had IML and/or MD
lesions but no damage to the MTT/anterior nuclei (cases
1, 4, 6 and 16), however, did not have such recognition
deficits. The claim of a role for the MD in recognition
memory can, therefore, not be supported on the basis of our
data, nor those of other reports of lesions in the MD with
spared recognition (Edelstyn, Jenkinson, & Sawyer, 2002;
Kritchevsky, Graff-Radford, & Damasio, 1987).
One case had a lesion to the left MTT, which was not associated with an amnesic syndrome (case 5). Memory problems were unmistakable and strong but the deficits of this
patient were not as severe as those seen in patients with
typical dense amnesias following thalamic damage. Instead,
she showed a deterioration of strategic abilities hampering
memory performance, as indicated by the combination of
a depression of recall scores with relatively intact recognition scores. The profile is, therefore, more reminiscent of a
frontal amnesia. In this case, the lesion was confined to the
left thalamus only and the right side might have been able to
provide some compensation. At present, however, this case
remains an anomaly.
Executive deficits frequently follow thalamic lesions. An
interpretative problem here is that most tests used to determine the integrity of the executive functions draw on several
functions: they require the subject to perform set shifting or

to access semantic knowledge, but may also tap memory,
working memory and attentive processes. Executive functioning as such can, therefore, not be ascribed solely to the
integrity of the prefrontal cortices, but also make use of
other areas. This can be appreciated in functional imaging
variants of the tests used here, for instance in the Wisconsin Card Sorting Test (Berman et al., 1995), the Stroop test
(Taylor, Kornblum, Lauber, Minoshima, & Koeppe, 1997)
and the Tower of London test (Baker et al., 1996) that activate parietal, temporal and occipital cortices in addition to
prefrontal areas. This is reflected in the absence of a strong
association between a restricted thalamic structure and executive deficits. Rather, two areas have moderate degrees of
association as seen from the overlap of subjects showing
substantial deficits on the executive tasks: these are a ventral
anterior region including the ventral IML adjacent to, but
lateral and dorsal to the MTT, and a more posterior region
in the ventral medial part of the MD that might also include
part of the adjacent midline nuclei and IML. This indicates
that diverse areas in the thalamus might account for executive deficits, but that the combination of lesioned structures
likely contains the ventral IML or the ventral MD. In accord with this, Mennemeier and coworkers (Mennemeier,
Fennell, Valenstein, & Heilman, 1992; Mennemeier et al.,
1997) have published a detailed analysis of a case with a
small but strategically located infarction encompassing the
left ventral IML and MD, and described deficits of executive
aspects of memory.
Deficits of simple speeded processing and attention do not
seem to be associated with a certain structure in the thalamus.
This might be caused by the fact that inattention is a general
feature of thalamic lesions, irrespective of where the damage is found. This would follow the findings of Castaigne
et al. (1981) and Rousseaux (1994), who noted that a loss of
attention was a common denominator in patients with thalamic infarctions. Rather, performance on simple tasks of
attention tended to be associated with increasing age across
the whole group of patients. This indicates that in higher
age, processes of attention become more vulnerable to disruption due to thalamic lesions. This would fit with correlation data in both healthy and diseased subjects, showing
that age-related volume decreases of the thalamus correlate with reduced simple speeded processing (Van Der Werf
et al., 2001). More complex forms of attention, as measured
here with the same tests for simple speeded processing but
with more complex demands, appear to be related to an area
in the ventral IML, similar to that associated with executive
dysfunctions.
The following remarks on subject selection and interpretation of the data are warranted: our study group likely
suffered from an inclusion bias, i.e. patients with evident
cognitive impairments were probably more likely to be
included, whereas patients with asymptomatic thalamic infarctions may have gone relatively unnoticed. Although not
necessarily corrupting the structure–function relationships
found here, this might lead to an overestimation of the

Y.D. Van der Werf et al. / Neuropsychologia 41 (2003) 1330–1344

likelihood that any thalamic infarction leads to cognitive
deficits. Our data, nevertheless, do indicate which are the
regions where infarctions remain ‘silent’ in terms of specific
cognitive deficits; infarctions falling laterally or posteriorly
in the thalamus seem unrelated to both memory problems
and executive dysfunctioning. In addition, infarctions of
limited size that fall in the MD do not necessarily result
in memory or executive dysfunctions. This indicates that
a critical mass of tissue in the MD needs to be damaged
before functioning is disturbed, agreeing with a previously
published report of normal memory and frontal functions
despite a small lesion to the MD (Kritchevsky et al., 1987).
Such reports of asymptomatic thalamic infarctions would
increase further our understanding of the relationship between thalamic structures and cognition.
The present investigation of thalamic involvement in
cognition focused on memory, executive functions and
cognition; other functions, such as those in the domain of
language, were not addressed. Given the fact that none of
the subjects in the study was excluded from the analyses
because of inadequate language skills, we are confident
that we did not miss any cognitive deficits that might be
mediated by language disturbances.
In conclusion, our study: (a) shows that in studies of
patients with thalamic damage, special attention needs to
be paid to the occurrence of additional brain damage that
might influence the cognitive outcome in these patients.
This, sometimes subtle, damage occurs especially in patients aged 60 and older; (b) confirms that dense memory
deficits compatible with the criteria of an amnesic syndrome
are associated with lesions of the MTT; (c) suggests that
executive deficits cannot be attributed as readily to lesions
of a certain structure in the thalamus, but may arise from
combined lesioning of several structures including the MD,
IML and midline nuclei; (d) shows that simple attentional
deficits seem a rather general trait of thalamic lesions and
occur more frequently with higher age, whereas complex attentional processes draw upon structures overlapping those
associated with executive processes.

Acknowledgements
This study was supported by a grant from The Netherlands
Organisation for Scientific Research (NWO), Grant Number 970-10-012. The help of Drs. W.J.H.J. Smeets and H.J.
Groenewegen for lesion localisation and of Drs. Barkhof,
Boiten, Gonera, Haaxma and Weerts for referral of patients
is gratefully acknowledged.

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