BMC Neurology

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Case report

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Brain regions essential for improved lexical access in an aged
aphasic patient: a case report
Marcus Meinzer*1, Tobias Flaisch1, Jonas Obleser1,2, Ramin Assadollahi1,
Daniela Djundja1, Gabriela Barthel1 and Brigitte Rockstroh1
Address: 1University of Konstanz, Department of Psychology, Universitätsstr.10, P.O. Box 23, 78457 Konstanz, Germany and 2University College
London, Institute of Cognitive Neuroscience, 17 Queen Square, WC1N 3AR, London, Great Britain
Email: Marcus Meinzer* - marcus.meinzer@uni-konstanz.de; Tobias Flaisch - tobias.flaisch@uni-konstanz.de;
Jonas Obleser - j.obleser@ucl.ac.uk; Ramin Assadollahi - ramin.assadollahi@uni-konstanz.de; Daniela Djundja - daniela.djundja@unikonstanz.de; Gabriela Barthel - gabriela.barthel@uni-konstanz.de; Brigitte Rockstroh - brigitte.rockstroh@uni-konstanz.de
* Corresponding author

Published: 17 August 2006
BMC Neurology 2006, 6:28

doi:10.1186/1471-2377-6-28

Received: 22 February 2006
Accepted: 17 August 2006

This article is available from: http://www.biomedcentral.com/1471-2377/6/28
© 2006 Meinzer et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Background: The relationship between functional recovery after brain injury and concomitant
neuroplastic changes is emphasized in recent research. In the present study we aimed to delineate
brain regions essential for language performance in aphasia using functional magnetic resonance
imaging and acquisition in a temporal sparse sampling procedure, which allows monitoring of overt
verbal responses during scanning.
Case presentation: An 80-year old patient with chronic aphasia (2 years post-onset) was
investigated before and after intensive language training using an overt picture naming task.
Differential brain activation in the right inferior frontal gyrus for correct word retrieval and errors
was found. Improved language performance following therapy was mirrored by increased frontothalamic activation while stability in more general measures of attention/concentration and working
memory was assured. Three healthy age-matched control subjects did not show behavioral changes
or increased activation when tested repeatedly within the same 2-week time interval.
Conclusion: The results bear significance in that the changes in brain activation reported can
unequivocally be attributed to the short-term training program and a language domain-specific
plasticity process. Moreover, it further challenges the claim of a limited recovery potential in
chronic aphasia, even at very old age. Delineation of brain regions essential for performance on a
single case basis might have major implications for treatment using transcranial magnetic
stimulation.

Background
Aphasia, the loss of the ability to produce or comprehend
language, constitutes a frequent consequence of left hemispheric stroke. Within the aphasic syndrome, one of the
most frequent and disturbing syndromes is impaired lexical access (e.g. object naming). Even though patients may

succeed in retrieving words, semantic paraphasias
(misnaming) and neologisms (meaningless word creations) are frequently observed. Neurophysiological
changes accompanying recovery of function in aphasia
have remained controversial [1,2] Even though recently
two studies used functional magnetic resonance imaging
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(fMRI) to investigate overt language production in aphasia [3,4] the neural substrate for lexical access and its different types of errors has never been investigated.
Furthermore, recent efforts in aphasia treatment [5,6]
addressed naming performance by fascilitation or inhibition of brain regions using repetive transcranial magnetic
stimulation (rTMS). Therefore treatment may be
improved if brain regions involved in successful and failing word retrieval can be distinguished.
In the present study, brain activation during word
retrieval was examined by functional magnetic resonance
imaging in an 80 year old female patient with with
chronic aphasia (see methods). An overt-picture naming
task was designed and a temporal sparse-sampling procedure [7] realized to assess the activity pattern correlated
with correct responses and different error types. Such a
design allows to monitor the overt verbal response during
an off-phase of the scanner, while the hemodynamic
response is acquired after a short time delay. Furthermore,
post-hoc categorisation of different responses types (e.g.
correct word retrieval, semantic paraphasias, neologisms)
is permitted. In the present study patterns of brain activation were compared for correct responses and errors.
Moreover, if there was a difference of activation for errors
and correct word retrieval, this should be replicable by
comparing a patient's erroneous responses before therapeutic intervention to responses to the same items named
correctly after therapy.
Case presentation
We investigated an 80-year-old female patient with
chronic Wernicke's aphasia (duration >2 years) following
left hemispheric ischemic stroke (Fig. 1 shows the
patient's lesion) of the middle cerebral artery who demonstrated a severe word retrieval deficit. The patient was
tested before (T1) and after (T2) short-term intensive language training (Constraint-Induced Aphasia Therapy,
CIAT [8,9]), which comprises communicative languagegames with a focus on word retrieval and is scheduled for
three hours/day on ten consecutive days. Three healthy
right-handed female controls (aged 76, 80, 85 years)
underwent the same fMRI-paradigm twice within two
weeks.

Methods
Language performance of the patient outside of the scanner was evaluated by a standardised language test (Aachen
Aphasia Test, AAT [10]) and a naming test that included
150 items. Responses during the naming test were
required without time restriction, while the first response
of the patient was scored. To account for the potential
improvement of working-memory functions and more
general attentional processes after therapy two non-language tasks were administered: Visual working-memory

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was evaluated with the Benton Visual Retention Test [11].
More general attentional processes were assessed by a german non-verbal test of attention and concentration
(Alterskonzentrationstest, AKT [12]), which constitutes an
adaption of the D2 Test [13] and is specifically tailored to
assess attentional capacities of the elderly or aphasic subjects.
MRI was performed on a 1.5 Tesla scanner (Philips Intera)
at the Kliniken Schmieder in Allensbach. Functional MRI
stimulation consisted of two alternating blocked conditions (overt picture naming/passively viewing a fixation
cross; 5 consecutive stimuli for each condition, the
sequence of picture-naming blocks was fixed at both sessions while picture presentation during trials was randomized). Pictures were taken from an internet database
[14] and included 80 line drawings of objects, high name
agreement scores for all stimuli was assured (average
name agreement: 0.92 ± 0.09). Forty of these pictures
were included in the therapy material and trained once
daily. Stimuli were presented by a visor (VisuaStim, Resonance Technology, Inc.) for 3 seconds during which the
overt verbal response had to be performed (responses
were transmitted by a microphone, tape recorded and
transcribed after scanning). After a short delay (0.8 sec.) a
whole-brain functional MR volume was acquired (TR = 6
sec.; acquisition time TA = 2.2 sec.; 28 transversal slices,
slice-thickness: 4.5 mm; resolution: 3.6 × 3.6 mm, Field of
View = 230, acquisition matrix 64 × 64). Data was modeled using a finite impulse response function. A total of
160 functional whole brain volumes were acquired. No
overt response was required for the control condition (fixation).
Functional MRI post-processsing was performed using
Statistical Parametric Mapping (SPM2, Wellcome Department of Cognitive Neurology, London, UK) and included
standard slice-timing, realignment, normalization and
smoothing (9 × 9 × 12 mm3 Gaussian Kernel) routines.
Normalization in the patient included cost-function
masking to prevent distortion of the image due to the
lesion [15]. The design allowed post-hoc categorization of
the patient's responses as correct naming, semantic paraphasia or neologism, rendering it effectively into an eventrelated design due to the temporally sparse imaging
applied. To elucidate the differential neural contribution
to correct word retrieval and error types a total of 26 correct responses, semantic paraphasias and neologisms were
chosen from both sessions (13 from each session,
response types were matched for length, frequency, naming agreement, visual complexity within and between
response types). To assess the general activation pattern of
correct responses and error types we calculated basic contrasts comparing correct responses and error types to rest
(correct>fixation, semantic paraphasias>fixation, neolo-

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Figure
The
patient's
1
lesion: The figure shows the normalised T1-weighted structural magnetic resonance scan
The patient's lesion: The figure shows the normalised T1-weighted structural magnetic resonance scan. The left hemispheric
lesion includes the inferior parietal lobe, the superior temporal lobe, postcentral regions, the rolandic operculum, parts of the
insula and the inferior frontal gyrus (axial slices, left = left).

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gisms>fixation). To assess the differential neural substrate
of correct responses and error types contrasts included
correct responses versus semantic paraphasias (Correct>SP) and correct responses versus neologisms (Correct>Neo). Since the patient's performance improved after
therapy we compared activation elicited by 10 selected trials that were categorized as errors (7 neologisms, 3 semantic paraphasias) before therapy to activation elicited by
the same pictures after therapy, when the patient articulated a correct response. The general activation pattern
elicited by naming in the control group was calculated as
a fixed effects model (naming>fixation at T1). To assess
changes of activation between sessions in the control
group we compared naming before and after the two week
time interval (T2>T1). Maximally activated voxels within
significant clusters are reported. Anatomic localization
was conducted using the Talairach Demon software [16].

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right thalamus, right and left putamen and the anterior
cingulate gyrus (cluster threshold p < .05 corrected, k>50;
voxel threshold p < .01, uncorrected; Fig. 2c). Naming performance for controls was close to a ceiling effect at both
sessions (mean T1/T2: 71/72 correct responses, Tab. 3).
The fMRI activation pattern for naming compared to rest
(fixation) in controls was comparable to that described in
earlier studies using covert or overt picture naming tasks
(for review [17]). Picture naming activated a large bilateral network that included frontal, temporal and occipital
regions, the thalamus, basal ganglia and limbic structures
(Tab. 4). The strongest change of activation in the control
group was a decrease of activation in the left IFG at T2
(cluster threshold p < .01 corrected, k>50; voxel threshold
p < .001), no increased activation was evident even at a
lower threshold (voxel threshold p < .01).

Discussion
Written informed-consent has been obtained from all participants. The study was approved by the local ethics committee and in accordance with the Helsinki Declaration.

Results
We compared brain activation elicited by a total of 26 correct naming responses during the overt picture naming
task to 26 semantic paraphasias and 26 neologisms. Comparison of correct responses and error types during fMRI
yielded a differential activation pattern that was mainly
characterised by increased activation in the right inferior
frontal gyrus (IFG) for correct words compared to paraphasias and neologisms (Figure 2a+b; Tab. 1, cluster
threshold p < .05 corrected, k>50; voxel threshold p <
.001, uncorrected; the general activation pattern for correct responses, paraphasias and neologisms is described in
Tab. 2). Most interestingly, the difference between the
activation pattern of correct responses and error types was
more pronounced in the right IFG when responses were
semantically less related to the target picture (Fig. 2a+b:
words > semantic paraphasias > neologisms).
After a two week period of intensive language training [8]
the patient improved significantly in the profile score of a
standardised language test (Aachen Aphasia Test, AAT
[10]), which is an index of the general aphasia severity,
and the repeating subtest of the AAT. Naming performance during fMRI (pre/post: 13/23 correct responses; maximum 80) and the naming test outside of the scanner
(pre/post 22/44; maximum 150) almost doubled. No
improvement of visual working memory or attentional
functions were observed (Tab. 3). Improvement of language performance was mirrored by changed brain activation in the fMRI naming task: when we compared correct
responses after therapy that evolved from errors (thus, the
same pictures before and after treatment; T1/T2) significantly increased activation was evident in the IFG, the

This case-study constitutes the first report to elucidate the
neural substrate of correct word retrieval and error performance in aphasia. Differences between correct retrieval
and errors were observed mainly in right inferior frontal
areas. This was replicated after therapy: words correctly
produced at T2, but erroneous at T1, exhibited increased
activation in the right IFG and subcortical structures (right
thalamus, right and left putamen). The thalamus seems
crucially involved in semantic-lexical retrieval by mediating activity in frontal areas [18]. In the present case, this is
supported by the gradually increasing involvement of IFG
with increasing semantical relationship of responses to
the target picture. Furthermore, effective compensatory
activity of the right hemispheric IFG homologue during
naming performance may depend on intact function of
the left basal ganglia [6]. This would explain the increased
activation in the right and left putamen that was associated with correct word retrieval after therapy.
The contribution of the left or right hemisphere to the
recovery of language in aphasic patients following stroke
is controversially discussed in the literature, in particular,
activity in right hemispheric areas following stroke has
been attributed to "...the loss of active inhibition or competitive interaction of the homologous (left frontal) area,
or an inefficient dead-end strategy" [6,19]. Several functional imaging studies on naming in aphasic patients
showed no correlation between right hemispheric (frontal) activation and speech recovery [20-23], on the other
hand, there are reports that emphasize the importance of
right hemispheric areas to the recovery of function in
aphasia [24]. For example, Winhuisen et al. [25,26]
showed that deactivation of the right IFG using rTMS
interferred with performance during a semantic task in
aphasic patients, indicating an essential contribution of
this area to language recovery (at least in a subset of
patients) and results of Crosson et al. [27] support the

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(a)

correct responses > neologisms

(b)

correct responses > semantic paraphasias

(c)

words that evolved from errors (T2>T1)

3.17

4.42
z-scores

Figure
word
Differential
retrieval
2 activation
to (a) neologisms
for correctand
and(b)
erroneous
semanticresponses:
paraphasias
Increased activation in the right IFG was found comparing correct
Differential activation for correct and erroneous responses: Increased activation in the right IFG was found comparing correct
word retrieval to (a) neologisms and (b) semantic paraphasias. (c) Correct word retrieval at T2, but not at T1 (the same pictures, N = 10) yielded increased activation in the right IFG, the right thalamus and right and left putamen (left = left, all contrasts: cluster threshold p < .05, k>50, FWE-corrected; voxel threshold p < .01, uncorrected).

importance of right frontal areas in successful naming
therapy.

language functions, which makes the previous assumption unlikely.

In the present study we found gradually increased activation of right the IFG to be associated with better naming
performance, which emphasizes the importance of this
area for the recovery of naming performance in this particular patient. Still, language performance of the patient
was low and even though improvements were substantiated, the overall naming capacity was still severely disturbed after therapy, which in some way points to a
dysfunctional compensatory activation pattern. We can
only speculate about the effect of rTMS to the right IFG in
this patient and it might even be possible that inhibition
of this area fascilitates naming performance. On the other
hand, the results of the present case study show, that gradual involvement of the right IFG contributes to improved

We also substantiated additionally activated clusters in
left perilesional (precentral) areas for correct responses
compared to neologisms and sematic paraphasias (see
Tab. 1), that may be functionally as important as the right
hemispheric activation. However, in patients with primary progresssive aphasia [28] activation in precentral
areas was negatively correlated with performance during a
naming task using fMRI. The authors interpreted these
results as "a compensatory spread of language-related
neural activity or a failure to suppress activity in areas normally inhibited during language tasks". While to our
knowledge no studies found associations between precentral activation and semantic tasks, activation of the right
IFG has been implicated with semantic decisions by a

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Table 1: Differential brain activation of words and errors: Activation elicited by correct word-retrieval was compared to semantic
paraphasias (words > semantic errors) and neologisms (words > neologisms). Furthermore, we compared activation elicited by
erroneous responses (before therapy) to the same stimuli that were named correctly after therapy (correct trials > former errors; all
contrasts: cluster threshold p < .05, k>50, FWE-corrected; voxel threshold p < .01, uncorrected).

Hemi
Words > Neologisms

Words > Semantic Errors
Correct Trials > Former Errors (T2> T1)

R

L
L
L
R
R
L
R
R

Regions

BA

Z

k

x

y

z

Inferior frontal

47
45
46
6
9
4
45

4.74
4.51
4.19
4.01
4.00
3.81
3.78
4.31
4.24
3.94
4.11
4.08
3.92

1635

42
59
50
-50
-21
-50
59
30
27
9
42
27
9

28
19
42
-3
43
-4
18
-14
-9
-17
28
37
32

-19
21
20
47
39
44
18
9
-7
1
-17
-17
1

Middle frontal
Frontal (precentral)
Superior frontal
Frontal (precentral)
Inferior frontal
Putamen
Putamen
Thalamus
Inferior frontal*
Middle frontal
Limbic (anterior cingulate)

47
11
24

499
466
995
629
562

437

Hemi = Hemisphere; R = right, L = left; BA = Brodman Area; k = cluster extent; x/y/z = coordinates according to Talairach and Tournoux [36], Z
= z-scores of significant voxels within significant clusters are reported (p < .01, k>50, corrected).
* The right IFG activation for the contrast correct trials > former errors (42,28,-17) differs with regard to localization to that from the contrast
words vs. semantic errors, while the localization of the IFG related activation of this contrast and the contrast words vs. neologisms almost match
perfectly. This might be explained by the fact that the first contrast includes 7 neologisms (and 3 sematic paraphasias) that may "dominate" the
activation pattern.

number of studies [25,26], which emphasizes its potential
importance during recovery of naming perfomance in
aphasic patients. Moreover, left precentral areas were not
activated when we compared correct trials vs. former
errors, which provides additional evidence for the importance of the right hemispheric IFG for improved task performance in this particular patient, rather than that of the
left precentral activation pattern.
One critical issue in this case report is the relatively small
number of improved responses during fMRI post-testing
compared to the baseline. Still, naming performance was
elicited under rigorous time constraints. Naming of the
pictures had to be performed within three seconds. This
might be an explanation for the relatively low number of
improved namings. Moreover, taking into account the relatively low number of correctly named pictures at the first
investigation (13/80) an increase by 10 correct namings
equals an improvement of 77%. Furthermore, not only
the number of correctly namind pictures increased, moreover, the number of neologisms halved (28/14) and the
number of semantic paraphasias increased (i.e. there were
more semantically related namings than before treatment). Therefore a closer look at the behavioral data during fMRI (obtained under rigorous time constraints)
reveals an overall increase of semantically improved naming attempts after treatment. An additional naming test
outside of the scanner without time restrictions was performed before and after treatment that included only
untrained items. We also found an increase of correct
naming responses of 83% (per/post: 24/44), when we

also scored self-corrections, this increase was even more
pronounced (31/63). Therefore, we are confident that
there was an actual improvement of naming performance
due to the treatment. This cannot merely be attributed to
the training of specific items, rather the generalization to
untrained items points to a general fascilitation of lexical
access.
Some methodological issues need to be discussed: First,
the most crital analysis (correct trials vs. former errors;
Tab. 1) was based on 10 items, which is a comaparably
week data basis. However, it has been shown convincingly
that especially in temporal sparse sampling fewer trials are
necessary to achieve the same power in brain activation
[7]. With respect to that, we were optimistic to achieve a
reliable activation pattern even with 10 trials per condition. In auditory fMRI, a recent study [29] replicated the
now well-established finding of left anterior STS activation with intelligible over unintelligble speech material
[30-32] on the basis of a mere 10 trials per condition.
Therefore, we feel that it was both justified and conclusive
to use even a comparably sparse data basis in performing
this revealing contrast of error trials which have been corrected in post-testing.
Second, aphasic patients generally fluctuate in their language performance and multiple baseline investigations
might be considered essential for the interpretation of
therapy induced effects. In the present case report we did
not assess the patient's performance during multiple baseline sessions for several reasons: First of all, the patient

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Table 2: General activation pattern of the patient during picture naming for different response types. Contrasts included correct
responses > fixation; semantic paraphasias > fixation; neologisms > fixation (cluster threshold p < .01, k>50, FWE-corrected; voxel
threshold p < .001, uncorrected).

Correct > Fixation
Region

Hemi

BA

x

y

SP > Fixation

z

Neo > Fixation

Z

x

y

z

Z

x

y

z

Z

36
-39

-86
-78

21
12

>8
4.4

36

-86

21

>11

-39

-79

-1

4.8
30

-83

-21

7.6

27

-86

35

>9

45
53

-81
-20

18
-1

>10
7.6

48

-29

1

6.8

-39
-30
-30

-47
-49
-47

47
61
49

4.0
5.7
5.1

-24

-4

-28

6.9

OCCIPITAL
Middle Occipital

Inferior Occipital
Fusiform Gyrus
Lingual Gyrus
Cuneus
Uncus

R
L
R
L
L
R
R
L
R
L

19
19
18
18
19
18
17
17
19
36

33

-89

21

>9

24
-18

-95
-98

19
19

>7
5.3

27
-21

-83
-90

-21
-3

6.3
5.2
-21
27
-24

-88
-86
-4

-3
35
-28

5.7
6.7
6.8

45
53
30
48
-65

-81
-21
19
-35
-3

18
-4
-36
5
0

7.7
6.0
6.6
6.2
5.4

-62

1

28

6.6

-53

38

1

4.2

36

-6

61

6.6

TEMPORAL
Middle Temporal
Superior Temporal

R
R
R
R
L

19
21
38
22
22

45

-81

18

>9

FRONTAL
Precentral
Inferior Frontal

Middle Frontal

R
L
R
L
L
R
R
L

4
6
13*
47
10
6
11

12

-31

71

7.4

39
-24

27
29

7
-6

5.1
5.7

45

48

20

4.6

-27

38

-4

4.9

PARIETAL
Postcentral
Inferior Parietal
Superior Parietal
Precuneus

R
L
L
L

3
40
7
7

12

-37

68

7.5

LIMBIC LOBE AND SUBCORTICAL STRUCTURES
Limbic (Uncus)

Para-hippocal
Thalamus
Globus Pallidus
Putamen

R
R
L
L
L
R
R
L

38
34
36
20
36

-27

4

-33

4.5

-21
-30

-2
-19

-30
-29

4.8
4.9

12

-30
12
24
-15

-9
11

0
-11

-1

-28
-15

-25

-26
1

6.2

5.6
5.7

6.9
3.5

SP = semantic paraphasias, Neo = neologisms; Hemi = Hemisphere; R = right, L = left; BA = Brodman Area; x/y/z = coordinates according to
Talairach and Tournoux [36], Z = z-scores of significant voxels within significant clusters are reported (p < .001, k>50, corrected).
* The strongest activation in the cluster that includes the right IFG (total cluster size: k = 218, number of voxels located in the right IFG: k = 148)
was found in BA 13 (k = 31), closer inspection of this cluster revealed addional activation in BA 45 (29,26,4; Z = 5.0; k = 33), BA 46 (42, 30, 10; Z
= 4.8; k = 38) and BA 47 (42,26,1; Z = 4.4, k = 46). Therefore, a substantial part of Brodmann's Areas 45/47 are activated above baseline.
Additionally activated voxels were located in the insula (k = 22), the middle frontal gyrus (k = 45) and the superior temporal gyrus (k = 3).

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Table 3: Test performance of the patient and 3 healthy age-matched female controls. The patient was investigated before and after
intensive language therapy. For controls fMRI-scanning was repeated witin a 2-week interval.

Patient (80 years, 25 months post stroke)
Aachen Aphasia Test (* = significant according to AAT manual)
before therapy
47.5
27
88
38
44
90

AAT profile score
AAT Token Test (errors)
AAT repeating
AAT written language
AAT Naming
AAT comprehension

after therapy
48.9*
28
108*
39
51
88

Naming Test (no time limit)
150 items (all untrained)
correct responses
+ correct after self-correction

before therapy
24
+7

after therapy
44
+19

fMRI-Naming (before/after therapy)
80 items (40 trained)
trained items (40)
untrained items (40)
total

correct
8/14
5/9
13/23

SP
11/12
11/16
22/28

PP
3/7
4/3
7/10

Neo
10/6
18/8
28/14

no response
8/1
2/4
10/5

Benton Visual Retention Test
15 items
correct recognition

before therapy
11/15

after therapy
9/15

Alterskonzentrationstest (AKT)
before therapy
79 s
20

time to completion
correct responses (max.20)

after therapy
101 s
19

Healthy female controls (N = 3, all 씸)
fMRI Naming (80 items)
ID
1
2
3

age
76
80
85

correct at T1
74 (92.5%)
68 (85%)
70 (87.5%)

correct at T2
75 (93.75%)
69 (86.25%)
71 (88.75%)

SP = semantic paraphasia, PP = phonematic paraphasia, Neo = neologism

was in the late chronic stage of aphasia and major spontaneous improvement of language functions within short
time intervals are not to be expected [33]. This would be
different for the acute or post-acute stage, where spontaneous recovery and stronger fluctuations of behavioral
performance would call for multiple baselines in any case.
Furthermore, there is evidence that repeated scanning produces stable activation patterns, even in severe chronic
aphasia [34], in this study repeated scanning yielded a
decrement of activation, supposedly related to task famil-

iarity, rather than an increase of activation. Therefore, the
increase of activation found in the present report is
unlikely to be interpreted as the effect of the repeated
measurement. From a more pragmatic viewpoint we
chose not to asses stability in this 80-year old patient for
the following reasons: Since we used the same pictures for
pre-post assessment, repeated measures would have
familiarized the patient with the test materials and an
additional fMRI scan would have increased the stress
upon the patient, this was especially important in this 80year old lady. Furthermore, we included a gender and age-

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Table 4: General activation pattern of the control group comparing naming with baseline activation (naming > fixation) at the first
investigation (fixed effects model, N = 3; cluster threshold p < .01, k>50, FWE-corrected; voxel threshold p < .05 corrected).

Region

Hemisphere

BA

k

x

y

z

Z

Left
Left
Left
Right
Left
Right
Right
Right
Left
Left
Left
Left
Left
Right
Left
Right
Right
Right
Right
Left

6
4
44
18
18
4
6

6112

-53
-50
-55
22
-22
55
46
61
-30
-24
-22
-26
-40
30
-16
2
8
18
8
-28

-3
-10
10
-91
-97
-5
-8
-27
27
15
-68
-67
-31
36
37
-5
1
-6
-15
-18

26
41
5
14
10
17
28
1
-10
-11
38
24
3
-15
4
61
68
68
6
-8

>13
>9
>8
>13
>12
>12
>11
>7
7.09
5.91
6.91
5.69
6.23
6.19
5.53
5.42
5.37
5.33
5.30
5.14

Frontal (precentral)

Middle Occipital
Parietal (precentral)
Frontal (precentral)
Middle Temporal Gyrus
Inferior Frontal Gyrus
Parietal (Precuneus)
Occipital (Precuneus)
Superior Temporal Gyrus
Middle Frontal Gyrus
Limbic Lobe (anterior cingulate)
Medial Frontal Gyrus
Superior Frontal Gyrus
Thalamus (Medial Dorsal Nucleus)
Basal Ganglia (Putamen)

47
47
7
31
41
11
32
6
6
6

11466
4597

373
513
110
111
59
247

107
77

Hemi = Hemisphere; R = right, L = left; BA = Brodman Area; k = cluster extent; x/y/z = coordinates according to Talairach and Tournoux [36], Z
= z-scores of significant voxels within significant clusters are reported (p < .05, k>50, FWE-corrected).

matched control group that evidenced no increased activation. This shows stability of the activation pattern
induced by the paradigm across time.

Conclusion
We conclude that improvement in various language tasks
is supported by improved communication within a larger
functional cortical network that includes right hemispheric fronto-thalamic areas. This communication might
be mediated by spared left basal ganglia functions. Moreover, the crucial impact of right hemispheric (frontal)
areas for correct word retrieval evident in the present case
supports the potential role of contralateral homologue
brain areas in the recovery from aphasia [35].
The findings reported gain significance insofar as they
reflect functional changes that are specific both to treatment and to the language domain: First, age-matched controls did not show changes in performance or increased
brain activation, which allows to link changes observed in
the patient to the treatment supplied. Second, the patient
did not improve in less domain-specific measures of brain
functioning: performance in both non-language specific
tests did not improve after therapy. This ties the changes
in brain activation even closer to therapy-induced recovery of language performance. Still, evidence suggests that
there is considerable variablility in areas responsible for
recovery of language functions in aphasia and the results
of the present study are based on a single patient. There-

fore, the findings from this case report might not generalize and replication in a larger sample is necessary.
Although based on data of a single patient, the global
behavioral improvement after short-term intensive treatment [8,9] challenges the claim of a limited recovery
potential in chronic aphasia, even at very old age. This
encourages further study of both therapy effectiveness and
brain plasticity in aphasia-therapy, where elder patients
form the rule rather than an exception. Furthermore,
delineation of brain regions essential for language performance in aphasia on a single case basis, might be of
major relevance to future treatment efforts using rTMS
[5,6].

Competing interests
The author(s) declare that they don't have any competing
interests.

Authors' contributions
MM conceived and conducted the study, analysed the data
and drafted the manuscript. TF, JO and RA were involved
in the implementation of the fMRI design and set-up. TF
and JO also provided their expertise in data analysis. DD
and GB were responsible for diagnostic assessment and
conducted therapy. BR, TF and JO participated in the discussion and final revision of the manuscript. MM, TF and
JO revised the initial submission. All authors read and
approved the final version of the manuscript.

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Acknowledgements
We thank T. Elbert and C. Herbert for helpful comments on the final version of the draft. This work was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant RO 805/11-4) and the Kuratorium Zentrales
Nervensystem (ZNS, Grant 2001013).

22.
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