Brain & Language 119 (2011) 15

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Brain & Language

journal homepage: www.elsevier.com/locate/b&l

Cathodal transcranial direct current stimulation of the right Wernickes area

improves comprehension in subacute stroke patients
Dae Sang You, Dae-Yul Kim , Min Ho Chun, Seung Eun Jung, Sung Jong Park
Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

a r t i c l e

i n f o

Article history:
Accepted 7 May 2011

Keywords:
Stroke
Global aphasia
Transcranial direct current stimulation

a b s t r a c t
Previous studies have shown the appearance of right-sided language-related brain activity in righthanded patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate
excitability in the brain. Moreover, rTMS and tDCS have been found to improve naming in non-uent
post-stroke aphasic patients. Here, we investigated the effect of tDCS on the comprehension of aphasic
patients with subacute stroke. We hypothesized that tDCS applied to the left superior temporal gyrus
(Wernickes area) or the right Wernickes area might be associated with recovery of comprehension ability in aphasic patients with subacute stroke. Participants included right-handed subacute stroke patients
with global aphasia due to ischemic infarct of the left M1 or M2 middle cerebral artery. Patients were randomly divided into three groups: patients who received anodal tDCS applied to the left superior temporal
gyrus, patients who received cathodal tDCS applied to the right superior temporal gyrus, and patients
who received sham tDCS. All patients received conventional speech and language therapy during each
period of tDCS application. The Korean-Western Aphasia Battery (K-WAB) was used to assess all patients
before and after tDCS sessions. After intervention, all patients had signicant improvements in aphasia
quotients, spontaneous speech, and auditory verbal comprehension. However, auditory verbal comprehension improved signicantly more in patients treated with a cathode, as compared to patients in the
other groups. These results are consistent with the role of Wernickes area in language comprehension
and the therapeutic effect that cathodal tDCS has on aphasia patients with subacute stroke, suggesting
that tDCS may be an adjuvant treatment approach for aphasia rehabilitation therapy in patients in an
early stage of stroke.
2011 Elsevier Inc. All rights reserved.

1. Introduction
Aphasia is a disturbance of language caused by brain injury to
the left cerebral hemisphere (Jordan & Hillis, 2006). Stroke is the
most common cause of aphasia, and about 20% of stroke patients
develop aphasia (Naeser et al., 2005a).
Aphasia treatments include speech and language therapy and
pharmacologic therapy (Greener, Enderby, & Whurr, 2001; Walker-Batson et al., 2001), but several studies have found that these
treatments are not effective for patients with aphasia (Greener
et al., 2001; Lincoln et al., 1984). Therefore, there is a need for
new treatments that show greater improvements in patients with
aphasia.

Corresponding author. Address: Department of Rehabilitation Medicine, Asan

Medical Center, University of Ulsan College of Medicine, Asanbyeongwon-gil 86,
Songpa-gu, Seoul 138-736, South Korea. Fax: +82 2 3010 6964.
E-mail address: kysmart@amc.seoul.kr (D.-Y. Kim).
0093-934X/$ - see front matter 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.bandl.2011.05.002

Transcranial direct current stimulation (tDCS) and repetitive

transcranial magnetic stimulation (rTMS) are new approaches for
non-invasive brain stimulation that have been shown to modulate
excitability in the brain (Fitzgerald, Fountain, & Daskalakis, 2006;
Paulus, 2003). Among the advantage of tDCS over rTMS are increased patient comfort, a broader area of stimulation, simultaneous speech training, and fewer side effects. Cathodal tDCS has
been found to decrease cortical excitability, and anodal tDCS has
been found to increase excitability and to potentiate N-methylD-aspartate action (Liebetanz, Nitsche, Tergau, & Paulus, 2002;
Vines, Nair, & Schlaug, 2006). To date, tDCS has been utilized primarily to help stroke patients recover motor functioning, and tDCS
has been found to improve motor skills (Hummel et al., 2005).
The left superior temporal cortex has been associated with language processing and improved comprehension in patients with
aphasia (Price, 2000), but activation of the right hemisphere may
facilitate transcallosal disinhibition, which is less conducive to language recovery in right-handed acute post-stroke aphasia patients
(Winhuisen et al., 2005).

D.S. You et al. / Brain & Language 119 (2011) 15

Although naming improved after tDCS in stroke patients with

non-uent aphasia (Monti et al., 2008), little is known about the effects of tDCS on the recovery of comprehension from global aphasia after stroke.
Thus, we assessed whether activating the left superior temporal
gyrus or the suppressing the contralateral portion of Wernickes
area via tDCS could ameliorate the symptoms of aphasia, including
those related to comprehension capacity, in subacute stroke
patients.
2. Methods
2.1. Subjects
This was a single-center, prospective, double-blind, sham-controlled study. We evaluated 78 patients with subacute middle cerebral artery (MCA) ischemic infarct who were hospitalized in the
rehabilitation department of the Asan Medical Center, Seoul, Korea,
between April 2007 and May 2009. Magnetic resonance imaging
(MRI) was performed to conrm both the clinical diagnosis of
ischemic stroke and the lesion location. Patients with other types
of stroke (e.g., hemorrhagic) were not included to reduce the heterogeneity of the study population. We estimated the ischemic infarct volume for each subject to exclude major differences in
infarct size. The last diffusion-weighted MR images (DWI) were reviewed by a certied radiologist who was blinded to the study conditions. Areas of high signal intensity on DWI were considered
acute brain ischemic infarcts, and the volume of each infarct was
measured on DWI scans using the image analysis package of the
picture archiving communication system (PACS). The entire outline
of the infarct was drawn on each slice in which the infarct appeared, and the enclosed area was simultaneously calculated. The
infarct volume (V) was calculated according to the equation:
V = S  A, where S is the interval of the serial slices (0.5 cm) and
A is the enclosed area in square centimeters.
Patients with histories of previous stroke, seizure, multiple
stroke lesions, or with metal implants in the brain, were excluded,
as were those who were uncooperative with speech therapy. Patients taking Na+ or Ca2+ channel or NMDA receptor antagonists
were also excluded. Written informed consent was obtained from
all of the patients caregivers, and the experimental protocol used
for this study was approved by the Institutional Review Board of
Asan Medical Center. All patients were evaluated by a professional
speech and language pathologist using the Korean-Western Aphasia Battery (K-WAB) (Kim & Na, 2004). Patients were assigned to
aphasic classications based on their scores on four language subtests including spontaneous speech, auditory comprehension, repetition, and naming.

placement, while the cathode was placed over the contralateral

supraorbital region. Current was run through the brain and other
tissues of the head from the anodal to the cathodal electrode. In
cathodal tDCS, the cathode was placed over the right superior temporal gyrus, and level CP6 was used for placement symmetrical to
the left superior temporal gyrus, while the anode was placed over
the contralateral supraorbital region. In sham tDCS, the anode was
placed over the left superior temporal gyrus and the cathode was
placed on the contralateral supraorbital region. For this method,
the current was allowed to increase over the rst 30 s, decrease
to zero over the next 30 s, and remain at zero thereafter. During
each period of tDCS, patients received conventional speech and
language therapy from the same speech and language pathologist.
Conventional speech and language therapy, provided by trained
and qualied speech and language therapists, included tasks devoted to naming, comprehension, and increasing verbal output.
The therapy focused on picture-object selection; object naming,
recognition, and association; expression of feelings and opinions;
improving conversational skills; and gestural and non-verbal communication. All patients received the same protocol for up to 5 h
(30-min weekly therapy sessions for 2 weeks).

2.3. Evaluation of aphasia

The effects of tDCS were evaluated before and after tDCS sessions using K-WAB (Shewan & Kertesz, 1980), a short but efcient
and sophisticated tool that classies patients according to recognized neurodiagnostic syndromes. One independent speech and
language pathologist, who was blinded to the type of intervention
performed, was used for these studies to measure patient outcomes. Diagnostic categories included Brocas aphasia and Wernickes aphasia. Patients were classied according to scores
obtained from four language subtests assessing spontaneous
speech, auditory verbal comprehension, repetition, and naming.
These four subtest scores are factored into the aphasia quotient
(AQ). Although WAB is recognized in academia as a reliable measurement for determining the severity of language impairment
(Brookshire, 2003), K-WAB has also been shown to be valid and
reliable for evaluating aphasia (Kim & Na, 2004). On the K-WAB,
spontaneous speech accounts for 20 points, auditory verbal comprehension for 200 points, repetition for 100 points, and naming
for 100 points. In calculating the AQ, spontaneous speech accounts
for 20 points, auditory verbal comprehension for 10 points, repetition for 10 points, and naming for 10 points. The nal score is calculated from the sum total of all four scores, multiplied by 2,
resulting in a possible total score of 100 points.

2.4. Statistical analysis

2.2. Transcranial direct current stimulation
tDCS was delivered by a battery-powered, constant-current
electrical stimulator (Phoresor II Auto Model PM850, IOMED, Salt
Lake City, UT) at 2-mA intensity using a pair of surface salinesoaked 35-cm2 sponge electrodes (5 cm  7 cm). Current was applied over 10 consecutive sessions, ve times a week for 2 weeks,
for 30 min per session. Study protocols for 2-week treatments were
developed in keeping with the Asan Medical Centers focus on early
rehabilitation and its policy of limiting stays to one month. At
2 mA, tDCS is considered a safe brain-stimulation technique that
is associated with relatively minor adverse effects (Iyer et al.,
2005). We used two different electrode montages including an anode and a cathode. In anodal tDCS, the anode was placed over the
left superior temporal gyrus, and level CP5 on the international 10/
20 EEG system was used for electroencephalogram electrode

All statistical analyses were performed using SPSS 14.0. For statistical analyses, Wilcoxon signed-rank tests were performed for
paired-comparisons of aphasia improvement within groups in response to tDCS conditions (anodal stimulation, cathodal stimulation, sham stimulation) before and after the tDCS stimulation. To
compare aphasia improvement among the three groups, we attempted to use repeated measures ANOVA. However, AQ and auditory verbal comprehension had normal distributions, while
spontaneous speech, repetition and naming did not. Therefore,
we utilized repeated measures ANOVA for AQ and auditory verbal
comprehension, using the factors intervention (anodal, cathodal,
sham tDCS) and time (pre, post), followed by post hoc tests using
the Bonferroni correction. The KruskalWallis test was used to assess improvements in spontaneous speech, repetition and naming.
A p-value < 0.05 was considered statistically signicant.

D.S. You et al. / Brain & Language 119 (2011) 15

cant improvements from baseline in AQ, spontaneous speech, and

auditoryverbal comprehension (p < 0.05) over the 2-week course
of the trial (Table 3).
In terms of auditory verbal comprehension, repeated measures
ANOVA showed a signicant effect of Time [F(1, 18) = 50.764;
p < 0.001] and Intervention  Time [F(2, 18) = 5.098; p = 0.018], in
the absence of a signicant effect of Intervention
[F(2, 18) = 1.483; p = 0.253]. Post hoc test shows cathodal tDCS
was signicant differences (cathodal tDCS vs. anodal tDCS,
p = 0.040; cathodal tDCS vs. sham tDCS, p = 0.037; anodal tDCS
vs. sham tDCS, p = 1.0) (Fig. 2). In terms of AQ, repeated measures
ANOVA showed a signicant effect of Time [F(1, 18) = 27.021;
p < 0.001] but did not show signicant differences of Intervention
[F(2, 18) = 0.789; p = 0.470], Intervention  Time [F(2, 18) = 0.657;
p = 0.530]. However, there were no signicant differences in spontaneous speech, repetition, and naming among three groups. No
patient showed any side effect of tDCS, such as seizure.
Fig. 1. Flow chart of patient recruitment and allocation.

4. Discussion

3. Results
We evaluated 78 MCA ischemic infarct patients, 33 of whom
met our inclusion criteria. These 33 patients had left M1 or M2
MCA infarct and were not taking pharmacological drugs, which
may affect brain modulation. All patients were randomized into
cathodal (n = 11), anodal (n = 10), and sham (n = 12) tDCS groups.
Within the groups, four, three, and ve subjects, respectively,
dropped out of our study before it was completed. Seven patients
were discharged early, three patients refused tDCS therapy due
to uncomfortable sensations, and two patients were unable to receive speech and language therapy due to their sleep habits. Thus,
21 patients completed the study (Fig. 1).
All 21 patients were diagnosed with global aphasia caused by a
left subacute MCA ischemic infarct. All patients were right handed.
No differences in gender, age, educational status, time of poststroke onset, and ischemic infarct volume were found among the
three groups (Table 1). Baseline values in the three groups did
not differ signicantly (Table 2). The three groups showed signi-

This study was designed to examine the effects of tDCS on patients with global aphasia following a subacute stroke. During
the comprehension of speech, Wernickes area receives polymodal
information and processes these data to select an appropriate word
(Seltzer & Pandya, 1994). Thus, dysfunctions in Wernickes area
have been associated with comprehension disabilities. To improve
comprehension ability, we therefore stimulated the superior temporal gyrus CP5 in the left hemisphere or CP6 in the right hemisphere, as identied in the 10/20 EEG system (Okamoto et al.,
2004).
We found that cathodal tDCS over the right superior temporal
areas of subacute patients with global aphasia showed signicantly
greater improvements in auditory verbal comprehension than anodal tDCS or sham tDCS over the left superior temporal areas. This
nding suggests that suppression of the right intact hemisphere
with cathodal tDCS is more effective than activation of the left
lesional hemisphere with anodal tDCS when tDCS is used to treat
aphasia. This nding, however, disagrees with previous results,
showing anodal tDCS over the left hemisphere improved language
processing in healthy subjects (Floel, Rosser, Michka, Knecht, &

Table 1
Biographical information and lesion description.
Patient number

Lesion size (cm3)

Sex

Age (year)

Education (year)

Post-stroke onset

Lesion location

1
2
3
4
5
6
7

F
M
F
F
M
F
M

62
60
78
65
66
80
82

12
12
9
9
16
9
6

22
29
20
18
30
23
31

PST, SM, AG
PF, IL
PF, AP, PST
PST
PF, IL, PST
CR, IB
PF, IL, AP

Cathodal group

8
9
10
11
12
13
14

M
F
M
F
F
M
M

65
48
78
65
76
80
49

16
12
16
9
9
8
12

22
36
20
35
20
34
23

PF, AP, PH
PF, IL, AP
PST
PF, IL
BG, CR
PF, IL, AF
PF

86
98
37
87
45
110
70

Sham group

15
16
17
18
19
20
21

M
F
M
M
M
M
F

71
72
55
49
75
58
64

16
6
12
14
9
16
12

38
16
18
22
35
30
18

PF, IL
PF, IL
PF, IL, AP
PF, AP, SM, AG
PF, AP
PF, AP
SM, AG

82
38
71
74
101
93
43

Anodal group

39
78
91
49
83
34
99

PST: posterior superior temporal gyrus, SM: supramarginal gyrus, AG: angular gyrus, PF: posterior frontal lobe, IL: insular lobe, AP: anterior parietal lobe, CR: corona radiata,
IB: internal border zone, PH: putamen hemorrhage transformation, BG: basal ganglia.

D.S. You et al. / Brain & Language 119 (2011) 15

Table 2
Changes in Scores on the Korean-Western Aphasia Battery for the Three Groups: Before and After Intervention.
Pre-treatment
a

Post-treatment
Repetition
2
12
6
8
0
2
0

Naming
7
2
0
8
0
0
0

AQ
20.4
11.6
8.6
27.6
12.2
2.4
0.4

SSa
5
4
7
9
4
2
1

AVCb
129
81
19
110
67
34
17

Repetitionc
24
26
26
14
3
4
0

Namingc
20
12
2
25
4
2
2

AQc
31.8
24.6
22
33.8
15.4
8.2
3.8

91
114
54
80
46
3
75

10
16
10
0
0
0
11

0
0
9
0
0
0
8

21.2
18.6
19.2
12
4.6
0.4
19.4

5
15
7
4
2
2
5

141
164
90
108
56
74
117

11
40
23
3
2
0
21

6
47
22
0
0
0
20

27.6
63.8
32
19.4
10
11.4
30

29
42
49
92
71
52
66

4
0
0
0
0
11
2

0
0
0
0
0
7
0

11.8
4.2
5
9.2
9.2
12.8
7

7
5
2
0
7
3
2

70
62
57
108
107
58
58

39
50
0
4
7
11
4

7
28
0
0
0
7
3

30.2
31.8
9.8
11.6
26.2
15.4
19.2

Patient number
1
2
3
4
5
6
7

SS
4
2
3
8
3
0
0

AVC
106
48
14
83
62
20
3

Cathodal group

8
9
10
11
12
13
14

5
2
5
2
0
0
4

Sham group

15
16
17
18
19
20
21

4
0
0
0
1
2
0

Anodal group

SS: spontaneous speech, AVC: auditory verbal comprehension, AQ: aphasia quotient.
a
Maximum score of 20.
b
Maximum score of 200.
c
Maximum score of 100.

Table 3
Treatment outcomes according to the Korean-Western Aphasia Battery: Scores of the
three groups before and after Intervention.
Anodal tDCS
(n = 7)

Cathodal tDCS
(n = 7)

Sham tDCS
(n = 7)

SS
Pre-treatment
Posttreatment

3.0(0.0, 4.0)
4.0(2.0, 7.0)a

2.0(0.0, 5.0)
5.0(2.0, 7.0)a

0.0(0.0, 2.0)
5.0(2.0, 7.0)a

AVC
Pre-treatment
Posttreatment

48.0 (14.0, 83.0)

67.0(19.0, 110.0)b

75.0(46.0, 91.0)
108.0(74.0, 141)b,c

52.0(42.0, 71.0)
62.0(58.0, 107.0)b

Repetition
Pre-treatment
Posttreatment

2.0(0.0, 8.0)
14.0(3.0, 26.0)

10.0(0.0, 11.0)
11.0(2.0, 23.0)

0.0(0.0, 4.0)
7.0(4.0, 39.0)

Naming
Pre-treatment
Posttreatment

0.0(0.0, 7.0)
4.0(0.0, 16.0)

0.0(0.0, 8.0)
6.0(0.0, 22.0)

0.0(0.0, 0.0)
3.0(0.0, 7.0)

AQ
Pre-treatment
Posttreatment

11.6(2.4,20.4)
22.0(8.2, 31.8)b

18.6(4.6, 19.4)
27.6(11.4, 32.0)b

9.2(5.0, 11.8)
19.2(11.6, 30.2)b

Data presented as median (25%, 75% range)

SS: Spontaneous speech, AVC: auditoryverbal comprehension, AQ: Aphasia
quotient
a
p < 0.05 vs. pre-treatment (Wilcoxon signed rank test).
b
p < 0.05 vs. pre-treatment (Repeated measures ANOVA)
c
p < 0.05 vs. anodal and sham (Repeated measures ANOVA), p value by Bonferroni correction

Breitenstein, 2008; Fregni et al., 2005) in comparing that cathodal

tDCS is more effective than anodal tDCS. Moreover, previous results reported that cathodal tDCS applied to the intact brain cortex
(i.e. the left lesional frontotemporal areas or Brocas region) of

aphasic patients with chronic non-uent post-stroke conditions

improved picture-naming but that anodal tDCS applied to the same
area was ineffective (Monti et al., 2008).
Although we could not exactly explain the effect of tDCS on
improvements in aphasia, our ndings suggest that it is associated
with interhemispheric transcallosal disinhibition (Thiel et al.,
2006). Application of inhibitory rTMS (1 Hz) to the anterior portion
of the right side of Brocas area signicantly improved the ability of
chronic global aphasia patients to name pictures (Naeser et al.,
2005a, 2005b). In addition, application of rTMS to the right hemisphere has been reported to improve language processing by inhibiting corticomotoneuronal excitability (Martin et al., 2004). These
ndings may suggest that inhibitory neuromodulatory stimulation
of the contralesional Wernickes area reduces cortical excitability
of this area, thereby improving comprehension by relaxing the
transcallosal inhibition of the lesional Wernickes area. However,
a mechanism called transcallosal or interhemispheric inhibition
was most evident in motor aphasia associated with the inferior
frontal gyrus. Since the comprehension of language involves more
complex mechanisms than spontaneous speech, our results are
likely not due to transcallosal inhibition alone.
The improvements in aphasia we observed may also have been
due to the left superior temporal area stimulated by anodal tDCS
being rendered ineffective due to necrosis secondary to the ischemic infarct. This hypothesis is supported by our nding that four
patients with superior temporal gyrus were in the anodal group,
whereas one patient with a lesion in the superior temporal gyrus
was in the cathodal group. Further studies are needed to understand the effect of tDCS on recovery from aphasia.
tDCS has after-effects that extend beyond the period of stimulation, and the maximum duration of a single tDCS session has been
reported to be about 90 min (Hummel et al., 2006; Uswatte, Taub,
Morris, Barman, & Crago, 2006). We conducted 10 consecutive
stimulations because we hypothesized that consecutive stimulations would be more effective than a single stimulation. We found
that 10 consecutive stimulations were effective, suggesting that
tDCS may have a cumulative effect.

D.S. You et al. / Brain & Language 119 (2011) 15

Fig. 2. AVC LS means scores for the cathodal, anodal, and sham tDCS groups before
and after tDCS. Improvements were signicantly greater in the cathodal than in the
anodal and sham tDCS groups. AVC: auditory verbal comprehension, LS: least
squares, CI: condence interval. p < 0.05 vs anodal and sham (repeated measures
ANOVA).

This study has several limitations. The number of patients with

small and there was a probability of spontaneous recovery.
Although we controlled for nonspecic effects by using a sham
tDCS group, all three groups showed improvements in language
skills over 2 weeks, making it difcult to precisely identify the effect of tDCS on aphasia. Improvements in comprehension in the
cathodal group also do not rule out the possible effects of spontaneous recovery, since comprehension usually shows greater
improvement than speech during recovering from global aphasia
(Kenin & Swisher, 1972). In addition, other comorbidities, such as
depression, may have affected patient attitudes toward speech
therapy, thus affecting K-WAB results. Furthermore, the
5 cm  7 cm sponge electrodes that were placed over the posterior
superior temporal lobes may cover far more territory than the
lobes, suggesting that other brain tissue may be involved in recovery from aphasia. Finally, unwanted changes in excitability may
have occurred under the reference electrodes on the forehead,
changes that may also affect recovery from aphasia.
5. Conclusion
This is the rst study to show that application of contralesional
cathodal tDCS during speech therapy in subacute global aphasia
stroke patients with left MCA ischemic infarct results in improvements in comprehension. Cathodal tDCS over the right Wernickes
area, combined with speech therapy, was more effective than
speech therapy alone, suggesting that inactivation of contralesional neural overactivity is therapeutic. Our ndings suggest that tDCS
may provide an adjuvant treatment approach for aphasia rehabilitation therapy in patients in the early stages of stroke.
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