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Improvement of language functions in a chronic nonfluent post-stroke aphasic patient following bilateral
sequential theta burst magnetic stimulation
ab

a

a

c

Jasmina Vuksanović , Milan B. Jelić , Sladjan D. Milanović , Katarina Kačar , Ljubica
de

Konstantinović

a

& Saša R. Filipović

a

Department of Neurophysiology, Institute for Medical Research, University of Belgrade,
Beograd, Serbia
b

Department for Philosophy (Psychology), State University of Novi Pazar, Novi Pazar, Serbia

c

Radiology Department, Special Hospital for Cerebrovascular Diseases “Sveti Sava”,
Belgrade, Serbia

Click for updates

d

Klinika za Rehabilitaciju “Dr Miroslav Zotović”, Belgrade, Serbia

e

Department of Rehabilitation, Faculty of Medicine, University of Belgrade, Belgrade,
Serbia
Published online: 03 Mar 2014.

To cite this article: Jasmina Vuksanović, Milan B. Jelić, Sladjan D. Milanović, Katarina Kačar, Ljubica Konstantinović &
Saša R. Filipović (2015) Improvement of language functions in a chronic non-fluent post-stroke aphasic patient following
bilateral sequential theta burst magnetic stimulation, Neurocase: The Neural Basis of Cognition, 21:2, 244-250, DOI:
10.1080/13554794.2014.890731
To link to this article: http://dx.doi.org/10.1080/13554794.2014.890731

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Neurocase, 2015
Vol. 21, No. 2, 244–250, http://dx.doi.org/10.1080/13554794.2014.890731

Improvement of language functions in a chronic non-fluent post-stroke aphasic patient following
bilateral sequential theta burst magnetic stimulation
Jasmina Vuksanovića,b, Milan B. Jelića, Sladjan D. Milanovića, Katarina Kačarc, Ljubica Konstantinovićd,e
and Saša R. Filipovića*
a

Department of Neurophysiology, Institute for Medical Research, University of Belgrade, Beograd, Serbia; bDepartment for Philosophy
(Psychology), State University of Novi Pazar, Novi Pazar, Serbia; cRadiology Department, Special Hospital for Cerebrovascular
Diseases “Sveti Sava”, Belgrade, Serbia; dKlinika za Rehabilitaciju “Dr Miroslav Zotović”, Belgrade, Serbia; eDepartment of
Rehabilitation, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

Downloaded by [Florida Atlantic University] at 10:44 01 February 2015

(Received 9 May 2013; accepted 27 December 2013)
In chronic non-fluent aphasia patients, inhibition of the intact right hemisphere (RH), by transcranial magnetic stimulation
(TMS) or similar methods, can induce improvement in language functions. The supposed mechanism behind this improvement is a release of preserved left hemisphere (LH) language networks from RH transcallosal inhibition. Direct stimulation
of the damaged LH can sometimes bring similar results too. Therefore, we developed a novel treatment approach that
combined direct LH (Broca’s area (BA)) stimulation, by intermittent theta burst stimulation (TBS), with homologue RH
area’s inhibition, by continuous TBS. We present the results of application of 15 daily sessions of the described treatment
approach in a right-handed patient with chronic post-stroke non-fluent aphasia. The intervention appeared to improve
several language functions, but most notably propositional speech, semantic fluency, short-term verbal memory, and verbal
learning. Bilateral TBS modulation of activation of the language-related areas of both hemispheres seems to be a feasible
and promising way to induce recovery in chronic aphasic patients. Due to potentially cumulative physiological effects of
bilateral stimulation, the improvements may be even greater than following unilateral interventions.
Keywords: aphasia; transcranial magnetic stimulation; rehabilitation; interhemispheric interaction; propositional speech;
verbal learning; semantic fluency; language; stroke

Aphasia is a common consequence of strokes affecting
structures in the language-dominant (usually left) cerebral
hemisphere (Dronkers & Larsen, 2001). Most patients show
some degree of spontaneous recovery of language function,
typically during the first 2–3 months following a stroke
(Laska, Hellblom, Murray, Kahan, & Von, 2001).
However, the amount of recovery varies greatly (Lazar &
Antoniello, 2008) and a number of patients are left with
lasting impairment of language functions in spite of receiving speech therapy (Kelly, Brady, & Enderby, 2010).
Language recovery after stroke is critically dependent
on the degree and pattern of compensatory plastic changes
in cerebral hemispheres taking place in the post-stroke
period (Thompson, 2000). Noninvasive brain stimulation
(NBS) interventions, such as transcranial magnetic
stimulation (TMS) and transcranial direct current stimulation (tDCS), can be used to promote plastic changes in
brain recovery (Miniussi et al., 2008). In relation to the
language system, there is an evidence that such interventions can have a positive impact on a number of language
functions in both healthy individuals and aphasic patients
(Hamilton, Chrysikou, & Coslett, 2011; Mylius, Zouari,
Ayache, Farhat, & Lefaucheur, 2012; Schlaug, Marchina,
& Wan, 2011).
*Corresponding author. Email: sasa.filipovic@imi.bg.ac.rs
© 2014 Taylor & Francis

Most of the published NBS studies in post-stroke
aphasia have been based on a widely accepted view that
for the long-term recovery of language, a reactivation of
undamaged network areas of the ipsilateral hemisphere is
more efficient than the involvement of homologue contralateral regions (Heiss & Thiel, 2006). Decreased activity in
contralesional areas following an inhibitory NBS treatment
should cause interhemispheric transcallosal inhibition
toward the lesioned side to diminish, thus permitting activity in lesioned or perilesioned areas to increase, which
eventually should lead to improvement in language functions. An alternative option, a direct facilitation of the
lesioned and perilesioned areas, has been tried in only a
handful of cases (e.g. Baker, Rorden, & Fridriksson, 2010)
due to various safety and methodological issues, the most
important ones being risk of seizures and exact determination of the area to stimulate. Even so, it is still unknown
whether direct stimulation of the lesioned hemisphere
coupled with inhibition of homologue contralateral areas
might bring similar or even greater effects.
Moreover, verbal memory and verbal learning are
usually impaired together with language loss in aphasia
(Burgio & Basso, 1997; Schouten, Schiemanck, Brand, &
Post, 2009). However, the effects of NBS on verbal

Neurocase

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memory and learning in chronic aphasic patients have not
been investigated in detail yet.
Therefore, we developed a TMS-based treatment procedure designed to inhibit the right Broca’s area homologue (BAh) and subsequently to facilitate Broca’s area
(BA). The procedure was developed in keeping with the
hypothesis of a maladaptive right hemisphere (RH) overactivation in chronic aphasia patients and a need to promote the reappearance of functions in the left hemisphere
(LH) to achieve proper language recovery. In this study,
we report the effects of 15 consecutive daily applications
of the treatment on language deficits and verbal memory in
a right-handed patient with chronic non-fluent aphasia.

Methods
Case history
The patient was a 63-year-old monolingual Serbian-speaking right-handed man with 12 years of formal education
who worked as a telecommunication technician before his
stroke. Seventeen months before participation in this
study, he suffered an ischemic stroke in the left middle
cerebral artery territory, which caused damage in the left
frontotemporoparietal white matter but with relative sparing of cortical gray matter (Figure 1). The stroke left him
with right hemiparesis and severe non-fluent aphasia (one
monosyllabic word phrase length in spontaneous and/or
on-demand language production). During the first 2
months following the stroke, he had an initial rehabilitation program, including speech and language therapy, at a
specialized residential rehabilitation facility. This was
R

L

245

followed by fairly regular physiotherapy sessions at a
community medical center. He has regained considerable
mobility of his right limbs, and at the time he entered the
study, he had only mild right hemiparesis. His modified
Rankin scale score was 3, and average Medical Research
Council (MRC) score (across all muscle groups) for the
right upper limb was 1.9. However, his speech has recovered poorly and he presented with severe non-fluent aphasia, which was little different than it was in the acute phase.
The patient had not had previous strokes or transient
ischemic attacks. Twenty years earlier, he suffered an
injury of the right hip for which he had a metal prosthesis
implanted. The metal in his hip prevented carrying out
MRI scanning.
Here, we present results of the language function and
verbal memory assessments, first carried out a few days
before the first (initial) TMS treatment session (baseline test
– T0), and from two retests. One retest (T1) was within a
week of completing the TMS treatment (i.e. 4 weeks following the T0), and another retest (T2) took place 2 months later.
The study was approved by the local Ethics Committee and
the patient gave his written informed consent.
Language function assessment
For language function assessment, the Boston Naming
Test (BNT) (Kaplan, Goodglass, & Weintraub, 1983) and
several subtests of the Boston Diagnostic Aphasia
Examination (BDAE) (Goodglass & Kaplan, 1983) were
used. To limit the strain on the patient, the selection of
BDAE subtests was limited to propositional speech
(Cookie Theft picture description task), repetition, auditory comprehension, and semantic verbal fluency (number
of animal names generated within a 2-min period).
Verbal memory and learning assessment

Figure 1. CT scan, carried out a week after the stroke, showed
ischemic lesions in the left basal ganglia, extending into periventricular and supraventricular white matter, with hemorrhagic
transformation within the area of lentiform nucleus, but with
relative sparing of the cortical gray matter. Sides are positioned
according to medical imaging convention; the left side of the
brain is on the right image side.

The Rey Auditory Verbal Learning Test (RAVLT) (Lezak,
Howieson, & Loring, 2004) was used for verbal memory
and learning assessment. The test consists of two parallel
sets of 15-noun lists (A and B). First, list A was presented
five times in a row, each time followed by free recall,
(A1, A2, A3, A4, A5), then, list B (interference) was
presented followed by free recall (B1). After a 20-min
interval, the subject was asked to recall list A (A6), and
finally, after another 20-min delay, A list was recalled
again (A7). For all recall tasks, the number of correct
words recalled from the presented word list (either A or
B) was taken as the task’s score. Several different sets of
stimuli (i.e. lists A and B) were used to eliminate the
effects of repetition on the test.
TMS treatment protocol
TMS was applied through a 70-mm-diameter figure-of-eight
coil using Magstim Rapid magnetic stimulator (Magstim,

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246

J. Vuksanović et al.

Whitland, UK). The treatment intervention consisted of the
so-called theta burst stimulation (TBS) (Huang, Edwards,
Rounis, Bhatia, & Rothwell, 2005) in which bursts consisting of 3 TMS pulses given at 50-Hz rate are repeated every
200 ms (i.e. with frequency of 5 Hz). The TMS pulse
intensity was set to be at 80% of the active motor threshold
(AMT) obtained from the RH. The AMT for the RH primary
motor cortex was established according to published criteria
(Rothwell et al., 1999). Due to the stroke, the AMT values for
the LH were too high to be used. Two types of TBS were
used: (1) facilitatory intermittent TBS (iTBS), consisting of
2-s trains of TBS followed by 8-s rest, which was repeated 20
times for a total of 200 s (i.e. 600 pulses); and (2) inhibitory
continuous TBS (cTBS), consisting of a 40-s train of uninterrupted TBS (i.e. 600 pulses). First, the cTBS was delivered
over RH BAh, and then immediately after, iTBS was delivered over LH BA. For scalp projections of the BA and the
BAh, F7 and F8 sites of the 10–20 International EEG electrode positioning system (Klem, Luders, Jasper, & Elger,
1999) were used; the two sites were found to correspond
reliably enough with pars triangularis of the inferior frontal
gyrus (Brodman area 45) (Koessler et al., 2009; Okamoto
et al., 2004), the cortical region that forms a part of the BA
and the BAh, respectively. Prior studies of TMS in aphasia
showed that enhancements of language ability were associated specifically with stimulation of the pars triangularis
area (e.g. Naeser et al., 2011).

Results
Language functions
The BNT score at the baseline (T0) was 17, considerably
below the published norms (Tombaugh & Hubiey, 1997).
Following the TMS treatment, it increased slightly to 19 at

T1 and increased again to 21 at T2. However, major
improvement was observed in some of the BDAE subtests
that were used (Table 1), particularly in propositional
elicited speech. The number of words per longest phrase,
which was a meager 2 at T0, increased to 6 at T1, with
further increase to 8 at T2. The mean number of words per
sentence increased as well, from only 2 at T0 to 6 at T2.
The number of sentences dramatically increased also, from
only 3 at T0 to 10 at T1, with slight decrease to 8 at T2. In
addition, the performance on semantic verbal fluency task
increased, particularly at T2 where it was 10, a 100%
higher than at T0 where it was only 5. In addition to
these results, auditory comprehension was generally
improved. The number of discriminated words increased
from 49 at T0 to 65 at T1, followed by a slight decrease to
54 at T2. The number of correct commands performed
increased from 8 at T0 to 14 at both T1 and T2.

Verbal memory and learning
All scores, apart from the delayed recall task score (A7),
increased after the TMS treatment, at T1 (Figure 2).
Unfortunately, due to time restrictions imposed on the
patient by sudden family problems, we were not able to
carry out a planned verbal memory evaluation at T2.
The total number of correct words recalled immediately after the first reading of list A (A1) increased from 2
at T0 to 4 at T1. Verbal learning improved proportionally
more. At the end of the learning curve, following the fifth
presentation of the list A (A5), the patient was able to
correctly recall only five list A words at T0, but this
increased by 100%, to 10 at T1. The total number of
correct words recalled across the first five trials (∑A1–5)
increased from 25 at T0 to 32 at T1 (a 28% increase

Table 1. Primary outcome measures, Boston Naming Test (BNT) and selected Boston Diagnostic Aphasia
Examination (BDAE) scores, before (T0), a week after (T1), and 2 months after (T2) the TMS treatment.
Testing material

T0

T1

T2

BNT score (max = 60)
BDAE scores:
(1) Semantic verbal fluency
(2) Spontaneous speech (Cookie Theft picture description)
Longest number of words per phrase length
Mean number of words per phrase length
Number of sentences
Articulatory agility (max = 8)
(3) Auditory comprehension
Word discrimination (max = 72)
Commands (max = 15)
Complex ideational material (max = 12)
(4) Repetition
Single words (max = 10)
High probability sentences (max = 8)
Low probability sentences (max = 8)

17

19

21

5

6

10

2
2
3
4

6
5
10
5

8
6
8
7

49
8
6

65
14
7.5

54
14
7.5

7
7
2

9
8
4

10
8
4

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35

T0
T1

(a)

247
10

(b)

10
8
30
8
6
25
6
4
4

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20
2
2
15
0

0
A1

A5

A5−A1

ΣA1–5

0
New Words New Words
during B during A6 and A7

Figure 2. Results of the Rey Auditory Verbal Learning Test (RAVLT) before (T0) and after (T1) the TMS treatment. (a) Verbal learning
and memory indices. The number of correct words recalled from the relevant word list (A or B) was taken as the task’s score. The
A1 score was used as a measure of short-term memory. The A5 score, the A5−A1 score difference, and the sum of scores across A1 to A5
(∑A1–5), were used as measures of verbal learning. The first three measures refer to the left Y-axis, the fourth measure refers to the right
Y-axis. (b) Numbers of non-list words during list B recall and during 6th and 7th recall of A list.

compared to T0). The learning score (rA5−rA1 difference)
increased also, from 3 at T0 to 6 at T1 (a 100% increase
compared to T0). The patient’s retrieval of list B words
(B1) increased also, from 0 at T0 to 4 at T1. Long-term
retention (A6) improved slightly, from 3 at T0 to 4 at T1.
However, delayed recall (A7) did not change and
remained 4 throughout.
Regarding the derivative measures, the number of
intrusions of list A words into list B recall stayed low, it
was 1 at T0 and at T1, signaling a low level of proactive
interference effect. On the other hand, the number of
intrusions of list B words into A6 remained 0 throughout,
indicating consistent lack of retroactive interference effect.
In keeping with the latter, the A6 score, as an indirect
indicator of retroactive interference, remained relatively
stable across the testing sessions.
In addition, qualitative analyses of B1, A6 and A7
answers, showed that the patient, in an attempt to retrieve
existing words from the lists, produced many new non-list
words that shared either phonological or semantic features
with the existing words; e.g. a non-list word children as a
semantic analog to the list word parent; a non-list word
arm (ruka in Serbian [pronounced as rookah]) as a phonological analog to the list word river (reka in Serbian
[pronounced as rekah]). This tendency increased after the

TMS treatment (at T1) for both, list A and list B words,
but was considerably more expressed for list A words
(Figure 2b).
Discussion
Increased activation of RH regions, homologue to the
lesioned LH language areas, typically encountered in
chronic aphasic post-stroke patients, was found to be not
only associated with unsuccessful or deficient recovery of
language performance (Crosson et al., 2007; Saur &
Hartwigsen, 2012) but also supposed to strongly inhibit
activity in the remaining language-related LH structures
(Heiss & Thiel, 2006).
Several reports have been published on the beneficial
effects of NBS treatments on the language functions of
chronic aphasic patients (reviewed in Hamilton et al.,
2011; Mylius et al., 2012; Schlaug et al., 2011).
However, all attempts so far have used unilateral application of either TMS or tDCS; in most cases the undamaged
RH was targeted with inhibitory protocols, while in only a
handful of cases a direct modulation of LH structures was
attempted.
In this report, we present the results of an NBS treatment, applied in a bilateral sequential and potentially

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J. Vuksanović et al.

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physiologically cumulative manner, in a chronic non-fluent aphasic patient. We aimed to explore whether this
novel approach could bring about improvement in language performance similar or even greater than improvements that have been reported for unilateral NBS
treatments. Our expectation that in this patient, with dominantly subcortical lesions and relatively preserved left
inferior frontal cortical regions, the TMS treatment aimed
at suppressing BAh on the RH and stimulating BA would
result in improved language skills and verbal memory
performance and was confirmed by the outcome results.

Language functions
The patient showed improvement in almost all measures of
language functions tested (Table 1), but most notably in
naming, semantic verbal fluency, auditory comprehension
of commands, and most of all in elicited propositional
speech.
Naming improvement has been one of the most consistent findings of NBS studies in chronic post-stroke nonfluent aphasia regardless of the approach adopted, inhibition of the RH (Barwood et al., 2011; Hamilton et al.,
2010; Martin et al., 2009; Naeser et al., 2005, 2010), or
stimulation of the lesioned LH (Baker et al., 2010;
Szaflarski et al., 2011). The magnitude of our patient’s
naming improvement 2 months after the TMS treatment
was rather modest, but similar to the magnitudes of
improvement reported within the similar window of time
following NBS treatment in the former studies.
Interestingly, although a high correlation between BNT
scores and achievements on semantic fluency tests was
found to generally exist in patients with lesions in the
left inferior frontal gyrus (Stuss et al., 1998), in our patient
semantic fluency improved much more than naming. At 2
months after TMS treatment it was 100% better than preTMS. Similar dissociation between significant improvement in semantic fluency (although of much smaller magnitude than in our patient) and negligible improvement in
naming was found by Szaflarski et al. (2011) in eight
chronic post-stroke aphasic patients following 10 days of
unilateral iTBS over fMRI localized BA. The results may
suggest that in chronic aphasia the two linguistic domains,
the externally driven one (i.e. naming) and the dominantly
internally driven one (i.e. fluency), differ in their susceptibility for the TMS-treatment-induced functional plasticity.
Whether or not it is a more general feature of chronic nonfluent aphasia is an issue that may be investigated further.
Auditory comprehension of commands increased considerably as well. It went from only 53.3% of maximal
score pre-TMS to 93.3% (almost 100% improvement)
immediately post-TMS and remained at the same level 2
months after. Similar improvement, but of notably lesser
magnitude, was reported for their patients by Naeser et al.

(2010) and Barwood et al. (2011), 2–3 months following
RH 1-Hz repetitive TMS (rTMS).
Finally, the most prominent improvement was
observed in elicited propositional speech during picture
description. Following the TMS treatment, the longest
phrase length during storytelling (Cookie Theft picture)
improved four-fold, while the mean number of words per
sentence and number of sentences increased three-fold.
This finding is in line with recent reports of patients with
non-fluent aphasia, following LH stroke, who experienced
significant benefits in elicited propositional speech after
receiving 10 sessions of inhibitory 1-Hz rTMS over the
intact right BAh (Barwood et al., 2011; Hamilton et al.,
2010; Martin et al., 2009). However, in all of those studies, patients improved noticeably more modestly in comparison to the patient in our study.
It is of note that in several domains, most notably in
elicited propositional speech, semantic fluency, and auditory comprehension of commands, our patient improved
considerably more than patients in other NBS studies,
which targeted either right BAh or left BA. The difference
may well be due to the differences in extent and location
of the cerebral lesion, relative preservation of left inferior
frontal regions, or duration of aphasia, or a combination of
all of them (Lazar & Antoniello, 2008). However, an
alternative explanation could be that combined stimulation
of LH language areas and inhibition of their right-sided
homologues, achieved by bilateral physiologically potentially cumulative neuromodulatory treatment in our study,
was behind the greater magnitude of the language recovery effects. Using functional imaging, Heiss, Kessler,
Thiel, Ghaemi, and Karbe (1999) showed that efficient
restoration of language functions was usually achieved
only if left temporal areas were preserved and could be
reintegrated into the functional network. Similarly, Martin
et al. (2009), reported that a “good responder” patient, one
whose naming and phrase length in propositional speech
significantly improved, showed notable post-rTMS
increase in LH peri-lesional activation on fMRI.
Therefore, we may presume that in our patient, suppression of the RH BAh coupled with direct facilitation of BA
managed to promote quite substantial activation of the
dominant hemisphere language network important for lexical retrieval and syntactic production, as well as language
comprehension.
Verbal memory and learning
In addition to improvements in language functions, the
beneficial effect of the TMS treatment in our patient was
seen also in short-term verbal memory and verbal learning.
In healthy adults, LH facilitatory anodal tDCS was shown
to be able to improve verbal learning (Flöel, Rösser,
Michka, Knecht, & Breitenstein, 2008). Our results suggest that NBS may have the potential to improve verbal

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Neurocase
learning in post-stroke aphasic patients as well. At the end
of the TMS treatment, two of the three indices of verbal
learning improved by 100% in comparison to the baseline.
It is of note that following the TMS treatment, the
tendency for producing new non-list words increased in
our patient. In an attempt to retrieve existing words from
the list, the patient also produced many non-list words that
shared either phonological or semantic features with the
list words. It is already known that word representations
are interrelated within semantic memory; the associations
are not formed only semantically, but also based on phonology/orthography and morphology (e.g. Frost, Deutsch,
Gilboa, Tannenbaum, & Marslen-Wilson, 2000;
Slowiaczek & Hamburger, 1992). Ability to use these
associations seemed to be lost in our patient before the
TMS treatment, but apparently has been reestablished
following the treatment. Besides being of interest per se,
the finding may provide a clue for explaining the other
beneficial effects of the TMS treatment in our patient.
Concluding remarks
Retrieval of language material, through pre-existing
semantic and non-semantic associative links, generally
tends to cause the spread of activation from cue item to
other items, increasing their probability to be retrieved. In
normal circumstances, this is counterbalanced by activity
of various intrinsic and extrinsic inhibitory mechanisms
that reduce the level of activation for inappropriate
responses, preventing them from achieving a threshold to
be overtly expressed. However, it can be speculated that in
aphasic patients the activity of the inhibitory mechanisms
within language-related cortical areas is increased, well
over the limits required for normal linguistic functioning,
and effectively interferes with a patient’s ability to recover
premorbid lexical competences. By combining reduction
of RH transcallosal inhibition with direct LH facilitation,
the TMS treatment seems to have induced weakening of
inhibitory activity within our patient’s LH BA, which
allowed him to gain easier availability of lexical units
within his mental lexicon. This in turn led not only to
the increased number of non-list words in delayed retrieval
conditions but also to improvements in language functions, particularly propositional speech and semantic
fluency.
There is of course a possibility that observed improvements may have been caused by concomitant speech and
language therapy. However, it has to be noted that the
patient had speech and language therapy for 3 weeks
before starting with TMS, but in spite of that his preTMS scores were quite low. In contrast, scores on several
language tests increased dramatically after TMS treatment.
The presented results are from one patient only and
thus cannot be easily generalized. Moreover, there was no
control for possible placebo effects of the TMS

249

procedures. However, the data obtained suggest that in
patients with LH strokes but with relatively preserved
LH cortical structures, the NBS-induced suppression of
the RH BAh followed by facilitation of BA has potential
to promote strong functional activation of previously dormant language networks in the dominant hemisphere. This
LH language areas’ activation seems to be able to bring
about not only improvements in lexical retrieval and syntactic production of aphasic patients but also improvements in their language comprehension and verbal
learning. Further placebo-controlled studies on larger
number of patients are required to confirm this hypothesis.
Acknowledgments
The authors would like to express their gratitude to Ms Ivana
Avramović, Ms Irena Avramović, Dr Aleksandra Jeremić, and Dr
Aleksandra Dragin, for their help in data collection, to Ms
Natalija Radivojević for her help in data interpretation, and to
Dr Denis Collins for his help in finalization of the manuscript.

Funding
This study was supported by the Ministry for Education, Science
and Technological Development of Republic of Serbia [grant
number 175012].

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