Archives of Physical Medicine and Rehabilitation

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Archives of Physical Medicine and Rehabilitation 2015;96:1935-44

ORIGINAL RESEARCH

Add-on Effects of Repetitive Transcranial Magnetic

Stimulation on Subacute Aphasia Therapy: Enhanced
Improvement of Functional Communication and Basic
Linguistic Skills. A Randomized Controlled Study
Ilona Rubi-Fessen, MSc,a Alexander Hartmann, MD,a Walter Huber, PhD,b
Bruno Fimm, PhD,b Thomas Rommel, MD,a Alexander Thiel, MD,c Wolf-Dieter Heiss, MDd
From the aRehaNova Rehabilitation Hospital, Cologne, Germany; bDepartment of Neurology, RWTH Aachen University, Aachen, Germany; cDepartment
of Neurology and Neurosurgery, McGill University, Montreal, Canada; and dMax Planck Institute for Metabolism Research, Cologne, Germany.

Abstract
Objective: To determine to what extent repetitive transcranial magnetic stimulation (rTMS) combined with speech and language therapy
improves functional communication and basic linguistic skills of individuals with subacute aphasia.
Design: Randomized, blinded, and sham-controlled study.
Setting: Neurologic rehabilitation hospital.
Participants: Participants (NZ30) with subacute aphasia after stroke.
Interventions: During a 2-week treatment period, half of the participants received 10 sessions of 20-minute inhibitory 1-Hz rTMS over the right
inferior frontal gyrus (Brodmann area 45), and the other half received sham stimulation. Directly thereafter, all the participants underwent 45
minutes of speech and language therapy.
Main Outcome Measures: Aachen Aphasia Test, Amsterdam-Nijmegen Everyday Language Test (ANELT), a naming screening, and subscales of
the FIM, all assessed the day before and the day after treatment period.
Results: The participants who received real rTMS significantly improved with respect to all 10 measures of basic linguistic skills and functional
communication, whereas sham-treated participants significantly improved in only 6 of 10 measures (paired t tests, P<.05). There was a significant
difference in the gains made by the 2 groups on 5 of 10 measures including functional communication (ANELT) (repeated-measures analysis of
variance, P
.05).
Conclusions: For the first time, this study has demonstrated that basic linguistic skills as well as functional communication are bolstered by
combining rTMS and behavioral language therapy in patients with subacute aphasia.
Archives of Physical Medicine and Rehabilitation 2015;96:1935-44
ª 2015 by the American Congress of Rehabilitation Medicine

Aphasia is a common neurologic sequela of stroke that restricts
communicative abilities and quality of life. Recently, noninvasive
brain stimulation techniques such as repetitive transcranial mag-
netic stimulation (rTMS)dinducing changes in brain activity by
modulating cortical excitabilitydhave been used to optimize the
outcome of behavioral speech and language therapy (SLT).1-9
rTMS has been shown to improve language behavior in persons
with aphasia after stroke.1,2,10-16 In most of these studies,
Supported in part by the Walter and Marga Boll Foundation and the Wolf-Dieter Heiss-
Foundation.
Disclosures: none.
inhibitory rTMS is applied to the right hemisphere in order to
increase the language activity of the remaining left hemisphere
structures by suppressing competing right hemisphere language
activation.1,2,10-15 Although the discussion about processes un-
derlying successful aphasia recovery is still ongoing,3 functional
reintegration of preserved language-related areas of the left hemi-
sphere seems to provide an effective mechanism of language re-
covery17-20 in many, but not in all cases.3,21,22 Up to now, few
studies have investigated the influence of rTMS on the reorgani-
zation of language functions in the subacute stage of aphasia.23-29
Recent studies have combined rTMS with behavioral language

0003-9993/15/$36 - see front matter ª 2015 by the American Congress of Rehabilitation Medicine
http://dx.doi.org/10.1016/j.apmr.2015.06.017
1936 I. Rubi-Fessen et al

therapy. Abo et al16 reported on the favorable effects of an after enrollment. Finally, 30 participants (nZ15 in each group)
inhibitory rTMS protocol and SLT in patients with chronic took part in the study. A participants’ flow diagram is shown
aphasia. These findings have been supported by other studies,26-28 in figure 1.
where a positive effect on naming and overall linguistic perfor-
mance was found by combining SLT and rTMS in patients with
subacute aphasia. In another study, Khedr et al29 observed Language data
enhanced language recovery of participants who received dual-
The day before and the day after the treatment period, each
hemisphere stimulation and SLT in comparison to sham-treated
participant was administered various language tests by a certified
participants with aphasia up to 12 weeks poststroke. By
speech and language therapist who was blinded to group alloca-
contrast, Seniów23 and Waldowski24 and colleagues found only
tion and not involved in behavioral therapy. One of the tests was
moderate benefits by combining rTMS with SLT in sub-
the AAT, which includes an evaluation of spontaneous language
acute aphasia.
production and 5 subtests: Token Test, repetition, written lan-
The strongest and most consistent effects of rTMS on language
guage, and naming, as well as auditory and written comprehen-
function were reported for picture naming.1,2,12-14 Even though the
sion. Severity of aphasia (profile height) was determined by
ultimate goal of language rehabilitation is to restore communi-
weighted T scores of all AAT subtests. In addition, a naming
cation in daily life, there is still limited knowledge about the in-
screening was administered, consisting of 60 items selected from
fluence of rTMS on functional communication.12-15 Thus, this
the Snodgrass and Vanderwart picture naming inventory.32 The
present study aims to determine how rTMS combined with SLT
Amsterdam-Nijmegen Everyday Language Test (ANELT)33 was
might improve both basic linguistic skills and functional
chosen to provide information about functional dimensions of
communication in individuals with subacute aphasia. This study
linguistic behavior. The ANELT is a valid instrument for assessing
partially incorporates previously published data27 but has been
functional communication34 and consists of 10 familiar daily life
expanded by including additional participants. Furthermore, re-
scenarios to which the participant has to respond verbally. Leaving
sults are reported from the full range of behavioral testing,
aside the B-scale, which measures motor speech skills, only the
including an additional test of naming and standardized assess-
semantic A-scale was analyzed to measure the effectiveness of
ments of functional communication.
conveying a message.
Functional communication (including verbal and nonverbal
communication) was further assessed by an internationally
Methods approved proxy-rating scale, the FIM.35 Items related to
communicative behavior (comprehension and expression) were
Participants used. The rating was performed by clinical employees (nursing
staff) who were neither involved in the study nor informed about
A total of 151 participants with first-ever stroke within the terri- study selection and group assignment.
tory of the left middle cerebral artery were recruited between 2008
and 2013 while they were inpatients in the RehaNova Rehabili-
tation Hospital in Cologne, Germany. Further inclusion criteria Neuroimaging and rTMS sessions
were as follows: (1) subacute aphasia with testability for the
According to group allocation, half of the participants (real
Aachen Aphasia Test (AAT)30; (2) poststroke period up to 16
stimulation/rTMS group) received 20 minutes of 1-Hz rTMS over
weeks (but most were 4e6wk poststroke); (3) right handedness as
the right triangular part of the inferior frontal gyrus (center of
measured by the Laterality Questionaire31; (4) German as the first
Brodmann area 45), whereas the other half of the participants
language; and (5) age between 55 and 85 years. Exclusion criteria
(sham group) received the same stimulation over the vertex. Both
were (1) prior symptomatic cerebrovascular accidents; (2)
groups were given an intensity of 90% of the individual resting
neurodegenerative or psychiatric disease; (3) epilepsy; and (4)
motor threshold. The resting motor threshold was defined as the
auditory or visual deficits that might impair testing.
minimum stimulator output that elicited a visible contraction on
Written consent was obtained from all subjects. The study
the first dorsal interosseus muscle of the unaffected hand in more
protocol was approved by the Ethics Committee of Cologne
than 5 of 10 stimulation trials. Stimulation parameters were in
University and the Federal Office for Radiation Protection
accordance with the guidelines suggested by Wassermann.36
(Salzgitter, Germany). Patients’ characteristics are shown in table 1.
Before stimulation, T1-weighted, diffusion-weighted, and T2
A total of 111 patients were excluded because they did not
fluid-attenuated inversion recovery MRI images were obtained to
meet the criteria. For 40 individuals, allocation to either real or
locate the optimal coil position. The respective brain areas were
sham stimulation was performed by a computer-generated allo-
stimulated using a Magstim Rapid2 stimulatora with a double 70-
cation sequence and concealed by means of consecutively
mm coil. The stimulation point was determined using reference
numbered sealed envelopes. Ten persons discontinued the study
lines defined on the reconstruction of the respective patient’s head
during initial magnetic resonance imaging (MRI) or withdrew
from the MRIs, which were then transferred to the patient’s head
(for details, see Weiduschat et al37). This method has an accuracy
List of abbreviations: of 10mm when compared with neuronavigated methods.
AAT Aachen Aphasia Test
ANELT Amsterdam-Nijmegen Everyday Language Test
ANOVA analysis of variance
Behavioral language therapy
MRI magnetic resonance imaging
rTMS sessions were immediately followed by 45 minutes of SLT
SLT speech and language therapy
conducted by an experienced speech and language therapist
rTMS repetitive transcranial magnetic stimulation
blinded to the participant’s group assignment. Above all, therapy

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Effects of transcranial magnetic stimulation on aphasia 1937

Table 1 Patient characteristics

Participant Stimulation Lesion Infarct

No. Group Sex Age (y) Duration (d) Aphasia* Severityy Fluency Locationz Volume (mm3)
1 Real F 59 49 Wernicke Moderate Fluent P 21,008
2 Real F 66 77 Anomic Mild Fluent Sc 10,376
3 Real F 59 43 Global Severe Nonfluent P 23,858
4 Real M 82 20 Wernicke Moderate Fluent Sc/A 44,481
5 Real F 73 60 Wernicke Severe Nonfluent Sc 13,910
6 Real F 70 17 Wernicke Severe Fluent P 16,060
7 Real M 75 56 Anomic Mild Fluent Sc 10,693
8 Real F 73 17 Broca Mild Nonfluent Sc 3,623
9 Real M 75 24 Wernicke Mild Fluent Sc 17,350
10 Real M 74 20 Wernicke Moderate Fluent P/A 76,302
11 Real F 58 31 Wernicke Moderate Fluent Sc 20,093
12 Real M 61 38 Global Moderate Nonfluent Sc/P 18,914
13 Real F 73 27 Anomic Mild Fluent P 26,823
14 Real F 55 45 Wernicke Severe Fluent P 26,909
15 Real F 66 88 Broca Moderate Nonfluent Sc/P 17,896
16 Sham M 60 46 Broca Mild Nonfluent P 30,904
17 Sham M 67 94 Broca Moderate Nonfluent Sc 16,415
18 Sham M 61 49 Global Severe Nonfluent Sc/A/P 90,829
19 Sham M 67 46 Wernicke Moderate Fluent A 38,976
20 Sham F 65 68 Broca Moderate Nonfluent Sc 3,652
21 Sham M 70 50 Global Severe Nonfluent Sc 11,060
22 Sham M 78 21 Anomic Mild Fluent A 21,929
23 Sham F 65 28 Wernicke Moderate Fluent Sc 6,260
24 Sham F 80 74 Wernicke Moderate Fluent A 13,521
25 Sham F 73 59 Wernicke Mild Fluent Sc/A 21,854
26 Sham F 83 20 Wernicke Mild Fluent P 16,202
27 Sham M 67 22 Anomic Moderate Fluent P 19,369
28 Sham F 73 37 Anomic Mild Fluent A 4,141
29 Sham M 66 70 Anomic Mild Fluent Sc/P 6,617
30 Sham M 69 47 Broca Moderate Nonfluent Sc MV
Abbreviations: A, anterior; F, female; M, male; MV, missing value; P, posterior; Sc, subcortical.
* Aphasia diagnosis according to AAT.
y
Severity according to AAT profile height.
z
A, P, and Sc part of left middle cerebral artery territory (see also supplemental fig S1, available online only at http://www.archives-pmr.org/).

focused on reactivation of word retrieval as required in tasks such
as oral and written picture naming, picture description, and
writing from memory. To ensure as much consistency of SLT and
treatment fidelity between subjects and across therapists as
possible, the treatment was conducted according to the following
principles: (1) main focus on oral naming; (2) preactivation of
word finding by receptive tasks (oral and written word-picture
matching); (3) application of increasing cues to support deliberate
lexical retrieval as validated by Abel et al38 for the German lan-
guage; (4) consolidation of successful verbal naming by additional
written naming (providing increasing written cues: initial
grapheme, initial syllable, word anagram, complete word); (5)
variation of training stimuli progressing from single object to
related action pictures as provided by the Everyday Life Activities
set39; and (6) exclusion of holistic or nonverbal facilitation
methods, or both, that might primarily involve right hemisphere
functions.40,41
All therapy plans were developed by the same experienced
speech and language therapist, who was blinded to group alloca-
tion and not involved in conducting the treatment. During the
course of the study, treatment was provided by a total of 7 speech
and language therapists, who were specifically introduced to the
principles above. The treatment of each participant was normally
performed by a single therapist. Training items were selected
according to type and severity of the individual aphasic symptoms
and extended after repeated correct naming performance.
Data analysis
All statistical analyses were conducted using SPSS (version 20b).
Independent-sample t tests were applied to identify group differ-
ences at baseline, and paired t tests were used to assess therapy
outcome for each group. To evaluate differences in language
improvement between groups, behavioral scores pre- and post-
treatment were analyzed using 2-way repeated-measures analysis
of variance (ANOVA), with the factors group and time. The
Kolmogorov-Smirnov test revealed normal distribution of age,
duration of disease, and behavioral data. Effect sizes were deter-
mined using partial h2 according to Cohen’s criteria.42 The level
of statistical significance was set at aZ5% for all t tests
and ANOVAs.

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1938
Fig 1 Consolidated Standards of Reporting Trials flow diagram. Abbreviation: rTMS, repetitive transcranial magnetic stimulation.
Results
Baseline characteristics
At baseline, the mean performance of the sham group was
quantitatively slightly better regarding all language measures
except for the AAT subtest written language. However,
independent-sample t tests did not reveal any significant group
differences with respect to age (mean age  SD: rTMS,
67.98.12y; sham, 69.66.67y), disease duration (mean time 
SD poststroke: rTMS, 41.4721.51d; sham, 48.7321.57d),
lesion size (mean volume  SD: rTMS, 23,21917,395mm3;
sham, 21,55222,369mm3), and aphasia severity (mean  SD
AAT profile height [T score]: rTMS, 50.527.15; sham,
51.607.71). Furthermore, for each language measure, Pearson
correlations between time postonset and language performance at
baseline were found to be insignificant, thus indicating no sig-
nificant association between lower baseline performance and
shorter duration of aphasia (table 2). Other characteristics such as
aphasia type (rTMS: anomic nZ3, Broca nZ2, Wernicke nZ8,
global aphasia nZ2; sham: anomic nZ4, Broca nZ4, Wernicke
nZ5, global aphasia nZ2), sex (rTMS: female nZ10, male nZ5;
sham: female nZ6, male nZ9), and lesion location (rTMS:
subcortical nZ6, posterior nZ5, mixed nZ4; sham: subcortical
nZ5, posterior nZ3, anterior nZ4, mixed nZ3), which might
I. Rubi-Fessen et al
influence therapy outcome, were sufficiently well balanced be-
tween the 2 groups (see table 1). Supplemental figure S1 (avail-
able online only at http://www.archives-pmr.org/) outlines the
method of defining lesion location.
Changes in language and communication
Table 3 lists the mean values of outcome measures at baseline and
posttreatment, SDs, and gains across time. Individual results for
all participants are listed in supplemental table S1 (available on-
line only at http://www.archives-pmr.org/).
Given the influence of behavioral therapy and spontaneous
recovery, both groups improved their language and communica-
tive skills during the 2 weeks of therapy. There was a significant
main effect of time on all measures: AAT profile score
(F1,28Z61.015, P<.000, partial s2Z.685), AAT Token Test
(F1,28Z11.120, PZ.002, partial s2Z.284), AAT repetition
(F1,28Z23.847, P<.001, partial s2Z.460), AAT written language
(F1,28Z25.647, P<.001, partial s2Z.478), AAT naming
(F1,28Z33.195, P<.001, partial s2Z.542), AAT comprehension
(F1,28Z21.404, P<.001, partial s2Z.433), naming screening
(F1,28Z17.775, P<.001, partial s2Z.388), ANELT A-scale
(F1,28Z43.632, P<.001, partial s2Z.609), FIM comprehension
(F1,28Z7.993, PZ.009, partial s2Z.222), and FIM expression
(F1,28Z9.164, PZ.005, partial s2Z.247).
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Effects of transcranial magnetic stimulation on aphasia 1939

Table 2 Comparison of sample characteristics and language baseline between groups

r (nZ30) Time
Sample Characteristics and Poststroke x
Language Tests Pre-Real Stimulation Pre-Sham Independent-Samples t Test* Language Baseline P*
Age (y) 67.98.12 69.606.67 t28Z.639, PZ.528
Time poststroke (d) 41.4721.51 48.7321.57 t28Z.924, PZ.363
Infarct volume (mm3) 23,21917,395 21,55222,369 t28Z.225, PZ.824
AAT profile heighty 50.527.15 51.607.71 t28Z.398, PZ.693 .500 .739
AAT subtest Token Testz 51.337.51 54.6711.46 t28Z.943, PZ.354 .238 .206
AAT subtest repetitionz 52.8010.35 53.139.18 t28Z.093, PZ.926 .038 .841
AAT subtest written languagez 50.537.01 48.877.17 t28Z.644, PZ.525 .061 .750
AAT subtest namingz 47.076.14 50.209.91 t28Z1.041, PZ.307 .024 .898
AAT subtest comprehensionz 48.535.30 51.0713.02 t28Z.698, PZ.494 .127 .504
Naming screeningx (0e60) 32.8718.43 39.2719.67 t28Z.920, PZ.366 .125 .509
ANELT A-scalex (10e50) 28.0011.48 29.6715.08 t28Z.340, PZ.736 .294 .115
FIM comprehensionx (1e7) 4.271.39 4.401.18 t28Z.283, PZ.779 .035 .853
FIM expressionx (1e7) 3.271.34 2.801.15 t28Z1.027, PZ.313 .202 .283
NOTE. Values are mean  SD or as otherwise indicated.
* Two-sided.
y
Weighted T scores.
z
T scores based on AAT norms for aphasia.
x
Raw score.

Although no significant main effect for group was found,
ANOVA statistical analyses demonstrated significant differences
in the interactions between group and time, thereby indicating
higher gains in the real stimulation group with respect to the
following measures: AAT profile score (F1,28Z8.91, PZ.006,
partial s2Z.239), AAT written language (F1,28Z4.84, PZ.036,
partial s2Z.147), AAT naming (F1,28Z8.23, PZ.006, partial
s2Z.240), AAT comprehension (F1,28Z4.66, PZ.040, partial
s2Z.143), and ANELT A-scale (F1,28Z4.19, PZ.050, partial
s2Z.130). Insignificant trends were found on AAT Token
Test (F1,28Z3.31, PZ.080, partial s2Z.106) and naming
screening (F1,28Z3.73, PZ.064, partial s2Z.117). No
significant interactions were found on AAT repetition and the
FIM ratings.
Figures 2 and 3 illustrate the interaction between group and
time of the linguistic and communicative measures. The interac-
tion effect for AAT profile height and AAT subtest naming
demonstrated a medium effect size. For all other measures besides
AAT subtest repetition and the FIM rating subscale expression, a
small to medium effect size was found. Supplemental appendix S1
(available online only at http://www.archives-pmr.org/) gives an
example for changes in functional communication.
Both at baseline and posttherapy, no significant differences
were found between the 2 groups (independent-sample t tests).

Table 3 Changes in language performance and functional communication

Real Stimulation nZ15 Sham nZ15
Paired t Paired t
Test (Pre Test (Pre
Language Test Pre- Post- Gain vs Post)* Pre Post Gain vs Post)*
y
AAT profile height 50.527.15 54.937.88 4.412.63 <.001 51.607.71 53.587.80 1.981.76 <.001
AAT Token Testz 51.337.51 54.739.26 3.403.48 .001 54.6711.46 55.6710.59 1.003.74 .159
AAT repetitionz 52.8010.35 55.739.09 2.933.81 .005 53.139.18 55.479.83 2.341.72 <.001
AAT written languagez 50.537.01 55.279.19 4.734.35 <.001 48.877.17 50.736.82 1.872.56 .007
AAT namingz 47.076.14 53.537.77 6.473.25 <.001 50.209.91 52.2710.89 2.074.73 .057
AAT comprehensionz 48.535.30 52.936.79 4.403.70 <.001 51.1312.98 52.6711.99 1.603.40 .045
Naming screening (0e60)x 32.8718.43 40.9318.59 8.078.67 .002 39.2719.67 42.2719.35 3.005.50 .023
ANELT A-scale (10e50)x 28.0011.48 34.2012.09 6.204.59 <.001 29.6715.08 32.9314.84 3.263.13 <.001
FIM comprehension (1e7)x 4.271.39 4.931.28 0.671.05 .013 4.401.18 4.601.40 0.200.56 <.094
FIM expression (1e7)x 3.271.34 3.801.21 0.530.83 .013 2.801.15 3.071.39 0.270.59 .052
NOTE. Values are mean  SD or as otherwise indicated.
* One-sided.
y
Weighted T scores.
z
T scores based on AAT norms for aphasia.
x
Raw score.

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1940 I. Rubi-Fessen et al

AAT Profile Height AAT Token Test AAT Repetition AAT Written Lang
60 60 60 60
58 58 58 58
56 56 56 56
54 54 54 54
Weighted T-scores

52 52 52 52

T-scores

T-scores
T-scores
50 50 50 50
48 48 48 48
46 46 46 46
44 44 44 44
42 42 42 42
40 40 40 40
Real Stimulation Sham Real Stimulation Sham Real Stimulation Sham Real Stimulation Sham

pre post p=.006 pre post p=.080 pre post p=.582 pre post p=.036

AAT Naming AAT Comprehension Naming Screening

60 60 50
58 58
56 56 45

54 54
40
52 Raw Score (0-60)
52
T-scores
T-scores

50 50 35
48 48
30
46 46
44 44
25
42 42
40 40 20
Real Stimulation Sham Real Stimulation Sham Real Stimulation Sham

pre post p=.006 p=.064

pre post p=.040 pre post

Fig 2 Language performance regarding pre- and posttreatment. The graphs show mean values at baseline and after a 2-week treatment for the
real stimulation group and sham group with respect to profile height of the AAT, AAT subtests, and naming screening. P values refer to group-by-
time interaction in 2-way repeated-measures ANOVAs. Error bars represent SEs of the mean. Abbreviations: Lang, language; post, posttreatment;
pre, pretreatment.

Fig 3 Communicative measures regarding pre- and posttreatment. Graphs show mean values at baseline and after a 2-week treatment for the
real stimulation group and sham group on A-scale of the ANELT, and subtests of the FIM. P values refer to group-by-time interaction in 2-way
repeated-measures ANOVAs. Error bars represent SEs of the mean. Abbreviations: post, posttreatment; pre, pretreatment.

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Effects of transcranial magnetic stimulation on aphasia
Fig 4 Group differences regarding gains in language performance between pre- and posttreatment. The bracket symbol indicates a significant
difference between the gains of both groups; P values from ANOVA group-by-time interaction. Error bars represent SEs of the mean. Abbreviations:
COMP, comprehension; NAM, naming; REP, repetition; Stim, stimulation; TT, Token Test; WRIT, written language.
However, post hoc analyses within groups across baseline and
posttherapy (paired t tests) revealed significant improvements for
all 10 measures for the real stimulation group (see table 3). In the
sham group, significant improvements were found for 6 of 10
measures: AAT profile height, AAT repetition, AAT written lan-
guage, AAT comprehension, naming screening, and ANELT.
Furthermore, the gain between baseline and posttreatment per-
formance for almost all measures was higher (fig 4) in the real
stimulation group than in the sham group.
The differences in the gain between the 2 groups are plotted in
figure 4. Here, only the AAT subtests are given, because their T
scores can be compared with the general performance of the
aphasia population.
Discussion
The present sham-controlled study investigates the effect of
inhibitory rTMS combined with SLT on recovery from subacute
aphasia and provides detailed behavioral data about changes of
basic linguistic skills and functional communication after a 10-day
treatment period. A relatively short treatment period of SLT
combined with rTMS led to significantly higher gains in basic
linguistic skills (AAT profile score, AAT subtests Token Test,
written language, naming, and comprehension) and in functional
communication (ANELT) for the real stimulation group as
opposed to the sham group.
rTMS and language therapy in subacute aphasia
To date, only a few other group studies have combined rTMS and
SLT during the subacute stage of aphasia. Using a design similar
to our study, Seniów23 found no significant add-on effect for a 3-
week inhibitory rTMS protocol combined with SLT in persons
with subacute aphasia with respect to naming, repetition, and
comprehension. In both the aforementioned study and the present
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1941
study, rTMS stimulation was directed at the pars triangularis of the
right inferior frontal gyrus with the aim of enhancing residual
language function of the damaged left hemisphere. The negative
outcome of Seniów might have been caused by different methods
of placing the rTMS coil. As demonstrated previously, the surface
distance measurement method,37 which we used in the present
study, is superior to the 10e20 method used by Seniów in local-
izing the inferior frontal gyrus. The importance of localizing the
target area within the inferior frontal gyrus has recently been
outlined.13,43 The variable effect of rTMS on language functions
may also be attributed to differences in behavioral testing or
treatment. In the present study, written language was explicitly
used during aphasia therapy. Given the high linguistic specificity
of reading and writing, this may have led to strong left hemisphere
enhancement, leading specifically to improvement of written
language functions.
Improvements across different language functions
and communication
Although rTMS has been shown to enhance picture naming,1,2,12-14
the current study has found additional significant add-on effects
with respect to the AAT subtests of auditory and written
comprehension, reading and writing, and for functional
communication as measured by the ANELT. For the commu-
nicative items of the FIM, no significant add-on effect was
found even though the real stimulation group showed significant
enhancements on the FIM subscales of comprehension and
expression. By contrast, the sham group showed only quanti-
tative yet insignificant improvements.
Apart from naming, the most significant effects were found for
written language processing, which might be related to content
and methods of behavioral therapy. The training focused on active
oral and written word-finding rather than on passive imitation of
verbal stimulation. These characteristics of the behavioral therapy
might also be responsible for the lack of difference between the 2
1942
groups with respect to repetition, which was not part of the par-
ticipants’ therapy plans.
A transfer of linguistic skills into everyday communication
was not specifically trained during the 2-week period. Neverthe-
less, communicative functions improved as well, which most
likely reflects a generalization effect. Generalization of semantic
and phonologic treatment effects in poststroke aphasia on func-
tional communication has been described by Doesborgh et al.44
They conclude that improvement in basic language functions
transfers to improvement in functional communication skills. With
respect to chronic aphasia, it was also shown that rTMS without
succeeding SLT may support the transfer of specific linguistic
skills to communicative abilities.13-15 Medina et al15 demonstrated
improved functional communication after applying rTMS, and
they attributed these effects to enhanced lexical-semantic access.
Although we observed the strongest add-on effect on naming, we
did not find a correlation between any naming task and the applied
communicative assessment, the ANELT A-scale. Apparently,
communicative transfer cannot be limited merely to improved
lexical retrieval.
The role of left Broca’s area in lexical retrieval and its rele-
vance for picture naming have been investigated in numerous
studies in subjects with and without aphasia.45,46 Furthermore,
imaging studies have reported activation of the left Broca’s area in
phonologic and syntactic language tasks, both in receptive and
expressive modalities.47-49 Thus, the left Broca’s area and espe-
cially its more anterior parts (Brodmann area 45) seem to act like
a bottleneck for a wide range of language functions, integrating
lexical-semantic, phonologic, and syntactic information from the
ventral and dorsal stream of language processing.49-51 Therefore,
reintegrating left Broca’s area into language processing apparently
leads to improvements across linguistic tasks and modalities.27
This positive effect might be enhanced during the early period
of aphasia, which is characterized by increased neuronal recruit-
ment in the inferior frontal gyrus of the undamaged right hemi-
sphere.17 Reducing this overactivation of the right hemisphere by
inhibitory rTMS within the first months poststroke might trigger
left hemisphere activation not only of Broca’s area but of the
whole residual distributed neural network of language within the
left hemisphere, resulting in the observed generalization of lin-
guistic skills to functional communication.
Study limitations
Although we could show the add-on effect of an inhibitory rTMS
protocol on recovery from aphasia in a comparatively large cohort
of patients with subacute aphasia, our study has limitations. The
study design did not allow differentiation between language
improvement resulting from behavioral therapy or from sponta-
neous recovery. Implementing language-independent control tasks
in the assessment battery would support the differentiation be-
tween language-specific training effects and overall spontaneous
recovery. However, most of our participants were included about
4 to 6 weeks poststroke. Up to this point, most of the spontaneous
recovery should have taken place, and further improvement might
be more related to language therapy.52 Another limiting factor is
the heterogeneity of our sample with respect to lesion size, lesion
location, and the type and severity of aphasia. These character-
istics were relatively evenly distributed between our 2 experi-
mental groups; former studies, however, have shown that
especially lesion location could have an influence on language
recovery supported by rTMS.11,12 Future studies should
I. Rubi-Fessen et al
incorporate larger and carefully matched samples to allow
detailed analyses of different subgroups and the application of
consistent behavioral therapy tailored to the type and severity of
aphasia. Finally, we do not have information about the stability of
the observed advantages, because participants were not followed
up beyond the immediate posttreatment period. However, studies
of chronic aphasia provide first evidence that language benefits
observed after administration of rTMS may remain stable or even
increase after several month post-rTMS.1,10-13 Even so, the early
advantages observed in the real rTMS group suggest that this
approach coupled with SLT is a promising and encouraging
beginning tool of rehabilitation.
Conclusions
The present study delivers further evidence that combining 1-Hz
rTMS with SLT leads to significant add-on treatment effects in the
subacute stage of aphasia. As indicated by the results, the outcome
of behavioral therapy is enhanced not only for a variety of basic
linguistic skills but also for functional communication. Longitu-
dinal studies are required to evaluate the long-term stability of
these benefits.
Suppliers
a. Magstim Rapid2 stimulator; The Magstim Company Ltd.
b. SPSS version 20; IBM Corp.
Keywords
Aphasia; Language therapy; Rehabilitation; Transcranial magnetic
stimulation
Corresponding author
Ilona Rubi-Fessen, MSc, RehaNova Rehabilitation Hospital,
Ostmerheimerstr. 200, 51109 Cologne, Germany. E-mail
address: rubi-fessen@rehanova.de.
Acknowledgments
We thank the speech and language therapists of the RehaNova
Rehabilitation Hospital, Cologne, Germany, for their assistance in
performing the speech and language therapy.
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Effects of transcranial magnetic stimulation on aphasia
Supplemental Fig S1 Definition of lesion location: The vascular
territory of the middle cerebral artery (MCA) was defined following
standard vascular territory maps. The cortical region was the total of
all cortical gray matter regions within the MCA territory, and it was
subdivided along the central sulcus into an anterior and posterior MCA
territory. All white matter within the MCA territory, as well as the
basal ganglia and thalamus, was included in the subcortical MCA
territory (see supplemental fig S1 for clarification of vascular territory
borders). This basically corresponds to the typical vascular occlusion
syndromes causing aphasia: Rolandic and pre-Rolandic artery occlu-
sions (anterior M2 branches of the MCA) causing predominantly
expressive aphasia syndromes and the posterior M2 branches (arteria
gyri angularis and arteria supramarginalis) mainly causing sensory
aphasia syndromes, while occlusion of the deep M1 segment perfo-
rators causes subcortical infarcts and the related aphasia symptoms.
www.archives-pmr.org
1944.e1
Supplemental Appendix S1 Clinically
Relevant Differences
Patient’s example of the ANELT
Assessing the ANELT, the investigator presents 10 everyday
communicative situationsdfor example, a doctor’s visit. The pa-
tient’s task is to produce an adequate verbal reaction. The level of
communicative effectiveness is determined by the adequacy with
which relevant information is communicated (A-scale). Five levels
of ability are differentiatedd“not at all” (1 point), “a little” (2
points), “medium” (3 points), reasonable” (4 points), and “good”
(5 points)dwith a maximum of 50 points.
Example (see audio files)
Examiner: Wir sind in einem Geschäft und sie möchten einen
Fernseher kaufen. Ich bin die Verkäuferin: “Was kann ich für Sie
tun, gnädige Frau?“ (You are in a store and want to buy a tele-
vision. I am the salesperson here: Can I help you?)
ANELT pretreatment (scored 3 points)
Participant: Ja was haben Sie denn Schönes da für mich. In den ..
den neuen.. Fer. Fernsehen, haben sie da schon welche, die ganz
neu.. die geneust..ach.. die geneu.die neusten schon gesehen
haben? (Roughly translated [errors intended]: What do you have
nice for me? In the.. the new.. tele..television, do you have of
them, which are very new.. the newe.. oh.. the new.. the newest
already have seen?)
ANELT posttreatment (scored 4 points)
Participant: Ja ich brauche neues Fernsehen. Sie müssen mal mir
ein schönes zeigen, was gefällt ihnen das am Besten für mich -
und wie teuer kostet das? (Roughly translated [errors intended]:
Yes, I need new television. You have to show me a nice one, what
do you like best for me - and how expensive costs that?)
 1944.e2
Supplemental Table S1 Behavioral changes in basic language skills and functional communication
AAT Naming ANELT FIM
Token Test Written Compre- Compre-
Profile (Reversed)y Repetition Language Naming hension Screening A-Scale Expression hension
Participant Height* (Max 50) (Max 150) (Max 90) (Max 120) (Max 120) (Max 60) (10e50) (1e7) (1e7)
No. Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post
1 46.38 52.29 10 24 70 88 37 65 80 103 88 99 57 59 24 39 5 5 4 4
2 63.14 66.07 46 47 146 147 86 85 88 106 84 100 46 54 34 46 2 3 4 5
3 43.45 44.65 15 15 71 54 15 20 12 45 59 73 22 30 19 20 2 3 5 5
4 54.71 57.75 18 18 146 146 65 82 40 63 65 62 9 28 19 22 2 2 2 3
5 45.11 49.40 17 23 97 120 15 20 51 78 49 75 38 32 19 18 2 2 5 5
6 35.98 43.10 9 6 0 59 10 32 0 31 49 46 9 8 19 25 3 3 4 4
7 56.97 65.02 39 48 141 147 64 82 90 100 96 100 46 56 48 50 4 5 5 5
8 55.72 63.75 36 45 130 138 75 87 89 106 77 98 56 59 38 48 5 5 7 7
9 55.74 63.37 44 48 140 146 53 77 65 102 83 99 35 53 44 48 3 4 3 4
10 46.93 49.01 6 13 125 128 22 24 36 62 52 55 22 38 17 27 3 3 3 4
11 49.60 56.49 24 39 111 128 53 74 51 95 80 92 28 54 30 41 2 5 3 6
12 49.33 49.83 29 30 124 125 36 32 20 26 61 84 3 4 14 20 2 3 4 4
13 58.82 62.68 26 33 145 143 75 83 99 111 93 94 49 56 47 49 6 6 7 7
14 43.60 45.99 10 12 78 90 16 29 14 43 77 80 18 27 24 31 4 4 4 7
15 52.30 54.48 37 41 123 123 43 55 77 88 82 96 55 56 24 29 4 4 4 4
16 55.18 59.57 50 50 99 110 47 61 90 111 114 113 54 60 40 44 2 2 7 7
17 52.68 51.59 50 45 83 92 57 53 50 57 105 108 39 48 17 18 2 2 6 6
18 35.81 36.81 5 10 5 15 0 0 0 0 47 44 0 0 10 10 1 1 4 4
19 48.42 51.94 14 17 127 132 47 63 19 55 36 52 18 15 12 15 3 3 3 3
20 48.79 48.67 15 15 122 121 22 22 79 75 44 51 41 39 18 24 2 2 3 3
21 36.83 41.50 6 14 33 68 0 12 0 0 34 54 0 0 10 10 1 1 3 2
22 61.19 64.73 45 50 136 145 69 76 111 110 96 102 60 60 49 49 5 5 5 6
23 51.12 53.63 23 19 135 142 17 29 83 93 61 69 40 39 42 44 3 3 5 5
24 51.13 53.23 20 24 131 135 44 56 73 81 62 71 37 39 25 33 4 4 4 5
25 55.69 56.45 14 13 148 150 60 54 49 56 65 48 30 42 26 35 3 3 4 4
26 56.58 56.02 34 34 136 138 52 55 106 96 64 74 53 54 45 47 3 5 4 5
27 54.37 55.99 38 40 123 125 56 63 84 95 107 109 55 60 45 48 4 4 5 5
28 56.58 60.11 30 35 144 147 60 69 89 95 90 95 49 49 43 43 3 4 3 3
29 63.37 65.43 50 50 135 136 77 80 110 116 111 110 59 60 47 50 4 5 5 6
30 46.26 48.03 16 26 80 97 43 45 50 51 54 64 54 51 16 24 2 2 5 5
www.archives-pmr.org

Abbreviation: Max, maximum.

I. Rubi-Fessen et al
* Weighted T scores.
y
Raw scores for all other subtests of AAT, ANELT, and FIM.