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Neuroscience 183 (2011) 64 –70

TRANSCRANIAL DIRECT CURRENT STIMULATION OVER BROCA’S


REGION IMPROVES PHONEMIC AND SEMANTIC FLUENCY IN
HEALTHY INDIVIDUALS
Z. CATTANEO,* A. PISONI AND C. PAPAGNO et al., 2008), and there is evidence that tDCS may be
Department of Psychology, University of Milano-Bicocca, Italy effective in the treatment of pain syndromes and depres-
sion (e.g. Antal et al., 2010; Brunoni et al., 2010; for
reviews, see Lefaucheur et al., 2008; Lima and Fregni,
Abstract—Previous studies have demonstrated that transcra-
2008; Nitsche et al., 2009; Murphy et al., 2009; Utz et al.,
nial direct current stimulation (tDCS) can be proficiently used
to modulate attentional and cognitive functions. For instance,
2010).
in the language domain there is evidence that tDCS can Previous studies have shown tDCS to improve lan-
fasten picture naming in both healthy individuals and aphasic guage functions. For instance, anodal tDCS over both
patients, or improve grammar learning. In this study, we Wernicke’s area (Sparing et al., 2008) and the left dorso-
investigated whether tDCS can be used to increase healthy lateral prefrontal cortex (see Fertonani et al., 2010) re-
subjects’ performance in phonemic and semantic fluency sulted in shorter naming latencies in healthy subjects.
tasks, that are typically used in clinical assessment of lan- Similar results have been reported in aphasic patients after
guage. Ten healthy individuals performed a semantic and a
anodal tDCS over the left frontal cortex (Baker et al., 2010;
phonemic fluency task following anodal tDCS applied over
Broca’s region. Each participant underwent a real and a sham Fridriksson et al., 2011; see also Monti et al., 2008 for
tDCS session. Participants were found to produce more naming improvement in aphasic patients after cathodal
words following real anodal tDCS both in the phonemic and stimulation of Broca’s region). Anodal tDCS over Wer-
in the semantic fluency. Control experiments ascertained that nicke’s area has also been found to facilitate associative
this finding did not depend upon unspecific effects of tDCS learning as compared to sham stimulation in neurologically
over levels of general arousal or attention or upon partici- unimpaired individuals (Floel et al., 2008). These results
pants’ expectations. These data confirm the efficacy of tDCS
sum up with those obtained using transcranial magnetic
in transiently improving language functions by showing that
anodal stimulation of Broca’s region can enhance verbal stimulation (TMS) (for a review, see Devlin and Watkins,
fluency. Implications of these results for the treatment of 2007) and demonstrate that brain stimulation is effective in
language functions in aphasia are considered. © 2011 IBRO. modulating language functions, highlighting the potential
Published by Elsevier Ltd. All rights reserved. clinical applications of TMS and tDCS for language reha-
bilitation post-stroke. Indeed, TMS has allowed to clarify
Key words: tDCS, Broca’s region, verbal fluency, language the role of different subregions of the Broca’s area in
functions, aphasia rehabilitation.
phonological, semantic and syntactic processing (Choui-
nard et al., 2009; Devlin et al., 2003; Gough et al., 2005;
Transcranial direct current stimulation (tDCS) is a stimula- Romero Lauro et al., 2008; Nixon et al., 2004; Sakai et al.,
tion technique that can be used to modulate spontaneous 2002). TMS has also shed light on the functions of Wer-
cortical activity in the human brain (e.g. Been et al., 2007; nicke’s area: for instance, low-frequency repetitive TMS
Hamilton et al., 2011; Fregni and Pascual-Leone, 2007; (rTMS) over Wernicke’s area was found to speedup the
Miniussi et al., 2008; Nitsche et al., 2008; Paulus, 2003; response to a task tapping on native language perception
Priori, 2003; Utz et al., 2010, for reviews). The effects of in healthy volunteers (Andoh et al., 2006). Significant
stimulation depend on the polarity of the current flow, with shortening of picture naming latencies was observed after
brain excitability being usually increased by anodal tDCS single-pulse TMS over Wernicke’s area (Mottaghy et al.,
and decreased by cathodal tDCS (Liebetanz et al., 2002), 2006). In patients with chronic post-stroke aphasia, excit-
although the effects of cathodal tDCS are more controver- atory rTMS applied to the affected Broca’s area improved
sial (see for instance Monti et al., 2007). Crucially, the language skills (Szaflarski et al., 2011), and there is now
cortical excitability alterations can last for over an hour consistent evidence that suppressing the right-hemi-
after the end of stimulation (Nitsche and Paulus, 2001). In spheric Broca homologue through low frequency rTMS
the past few years, many studies have underlined the facilitate recovery of language functions in post-stroke
potential of tDCS as a clinical tool for rehabilitating specific aphasic patients (e.g. Barwood et al., in press; Weiduschat
attentional and cognitive functions in brain-damaged pa- et al., 2011; see Naeser et al., 2010, for a review).
tients (e.g. Hummel et al., 2006; Priori et al., 2009; Schlaug Here we investigated whether anodal tDCS over the
left inferior frontal gyrus (Broca’s region: left BA 44/45) can
*Corresponding author. Tel: ⫹39-02-64483843; fax: ⫹39-02-64483706. be used to increase verbal fluency in neurologically unim-
E-mail address: zaira.cattaneo@unimib.it (Z. Cattaneo).
Abbreviations: rTMS, repetitive TMS; tDCS, transcranial direct current paired individuals. Verbal fluency tasks are short tests in
stimulation; TMS, transcranial magnetic stimulation. which participants are asked to generate as many words
0306-4522/11 $ - see front matter © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.neuroscience.2011.03.058

64
Z. Cattaneo et al. / Neuroscience 183 (2011) 64 –70 65

as possible from a semantic category (e.g. words design- duration (approximately 10 min) of the tasks following stimulation,
ing “animals” or “fruits”) or beginning with a specific letter as suggested by previous evidence showing that 13 min of 1 mA
within a limited period of time, and are commonly used in tDCS stimulation over the motor cortex significantly increased
motor cortex excitability for up to 90 min after the end of stimula-
clinical practice to investigate the semantic and phonolog-
tion (Nitsche and Paulus, 2001). Current density (0.057 mA/cm2)
ical processes central to speech production (Lezak, 1995). was maintained below the safety limits (Poreisz et al., 2007). For
Earlier findings suggest that anodal tDCS over the left sham stimulation, the electrodes were placed in the same posi-
prefrontal cortex may improve performance in a letter cue tions as Broca’s tDCS. At the onset of both the real and sham
word generation task (Iyer et al., 2005), but no study so far stimulation the current was increased in a ramp-like fashion
has investigated the effect of anodal tDCS on semantic (Nitsche et al., 2003), eliciting a transient tingling sensation on the
fluency. scalp that faded over seconds, consistent with previous reports
(Nitsche et al., 2003). In both the real and the sham sessions,
Specifically, here we compared the effect of anodal
current was then turned off slowly over a few seconds (in the real
tDCS and sham tDCS over Broca’s region within the same tDCS session after 20 min of stimulation, in the sham session after
group of neurologically unimpaired subjects undergoing 30 s of stimulation), out of the field of view of the participants, a
both a phonemic and a semantic verbal fluency task. Al- procedure that does not elicit perceptions (Hummel et al., 2005;
though phonemic and semantic fluencies involve partially Nitsche et al., 2003). This procedure ensured that participants felt
different neural networks (e.g. Birn et al., 2010; Gourovitch the initial itching sensation at the beginning of tDCS, but pre-
et al., 2000), the inferior frontal gyrus is critically involved in vented any effective modulation of cortical excitability by tDCS.
The study was a single-blind experiment: the individual subjects
both tasks (see Costafreda et al., 2006, for a review). were not informed about the type of stimulation they received
Hence, we expect anodal tDCS over this region to signif- while the experimenter knew it (see Fertonani et al., 2010, for a
icantly improve word generation following both semantic similar procedure). The order of the Sham and Real sessions was
and phonological cues. A spatial detection task was also counterbalanced across participants.
administered after stimulation to exclude that possible ef-
Verbal fluency. The experimental task consisted of Verbal
fects of anodal tDCS on verbal fluency depended in fact Fluency, both on phonemic and semantic cue, taken from Novelli
upon unspecific effects of tDCS over levels of general et al. (1986).
arousal or attention. Finally, a further experiment was car-
● Phonemic (letter) fluency: each subject was asked to gen-
ried on different healthy volunteers to rule out possible erate as many distinct words as he/she could, beginning with
confounding effects due to participants’ expectations. a specific letter (the letters “P,” “F,” “L” and “G”) in a period
of 1 min. Participants were instructed not to provide proper
EXPERIMENT 1 nouns (such as Paul or Paris) or use the root of a word more
than once (e.g. bed, bedroom . . .) and not to provide the
Method same word twice (perseverative error). The usual letters for
Italian are F, P, L. According to the Corpus and Frequency
Participants. Ten neurologically unimpaired individuals
Lexicon of Written Italian (COLFIS, see http://www.istc.cnr.it/
(four Males, mean age 23.6 years, SD⫽3.2) took part in the
material/database/colfis/index_eng.shtml), approximately
experiment. All participants were native Italian speaker under-
the same number of words are available for the letter F
graduate students; they were naive as to the experimental proce-
(mean frequency1⫽43.00) and P (mean frequency⫽43.07).
dure, and the purpose of the study. All subjects were right-handed
Hence, the letter G (mean frequency⫽35.73) was chosen in
(as assessed by means of the Edinburgh Inventory Questionnaire,
order to have a letter for which approximately the same
Oldfield, 1971) and with normal or corrected-to-normal vision.
number of words than the letter L (mean frequency⫽34.47)
They had no history of chronic or acute neurologic, psychiatric, or
is available.
medical disease; no family history of epilepsy; no current preg-
● Semantic (categorical) fluency: each subject was asked to
nancy; no cardiac pacemaker; no previous surgery involving im-
give as many exemplars belonging to a given category
plants to the head (cochlear implants, aneurysm clips, brain elec-
(“Fruits,” “Animals,” “Car brands and names,” “Musical in-
trodes); and did not take acute or chronic medication. Written
struments”) as possible in 1 min. They were instructed not to
informed consent was obtained from all participants. The experi-
ment was approved by the local ethical committee of the Univer- provide the same word twice, nor use the same family (i.e.
sity of Milano-Bicocca and subjects were treated in accordance “dog,” “puppy,” etc). The usual categories for Italian are
with the Declaration of Helsinki. brands of cars, animals and fruits. Musical instruments were
chosen in order to have a category matching brands of cars
tDCS. tDCS was delivered by a battery driven, constant in terms of difficulty (see Hodges et al., 1995).
current stimulator (Eldith, Neuroconn, Ilmenau, Germany) through
The total number of words generated excluding errors was
a pair of saline-soaked sponge electrodes (7 cm⫻5 cm:35 cm2)
recorded. All ratings were reviewed by a trained psychologist
kept firm by elastic bands. The excitability enhancing anodal
(A.P.).
electrode was placed over the Broca’s region, while the cathodal
In each session (Real and Sham tDCS) subjects were asked
electrode was placed over the right supraorbitary region. This
to perform the phonemic fluency for two letters and the semantic
montage has been successfully used in previous tDCS studies
fluency for two categories. For the same subject, different letters
(e.g. deVries et al., 2010; Iyer et al., 2005). The Broca’s region (left
and categories were used in the two experimental sessions. Spe-
BA 44/45) was localised according to the 10 –20 EEG system as
cifically, half of the participants were presented with the letters “G”
the crossing point between T3-Fz and F7-Cz. This localization
and “F” in the first tDCS session and with the letters “P” and “L” in
method has been used before in tDCS studies (e.g. Monti et al.,
2008), and the reliability of localizing a desired cortex region using the second tDCS session; the other half were presented with the
the 10 –20 system has been empirically demonstrated (Herwig et 1
The mean frequency for each letter has been computed by averaging
al., 2003). Stimulation intensity was set at 2 mA; the duration of the total frequency for all nouns, adjectives and verbs in the infinite
stimulation was 20 min. Twenty minutes of stimulation at 2 mA are form starting with that specific letter as reported in the COLFIS data-
expected to induce long-lasting effects fully covering the overall base.
66 Z. Cattaneo et al. / Neuroscience 183 (2011) 64 –70

5 min from the end of the tDCS stimulation, the visual detection
control task was administered. The control task took approxi-
mately 5 min.

Results
Verbal fluency. Analyses were performed on the mean
number of words generated excluding errors in the Phonemic
Fluency (averaged number of words for each letter) and in the
Semantic Fluency (averaged number of words for each category).
Fig. 1 shows the mean number of words produced in the Semantic
Fluency and in the Phonemic Fluency in the Real and Sham tDCS
session, respectively.
A repeated measures ANOVA was carried out on the mean
number of words generated with Task (Semantic vs. Phonemic
fluency) and stimulation condition (Sham vs. Real) as within-
Fig. 1. Mean number of words (average for one letter or category) subjects variables. The ANOVA revealed both a main effect of
produced in Phonemic Fluency and in Semantic Fluency in Experi- task, F(1,9)⫽11.18, P⫽0.009, n2⫽.55 and a main effect of stim-
ment 1 (tDCS delivered over Broca’s region). Participants produced ulation condition, F(1,9)⫽42.05, P⬍0.001, n2⫽.83. The type of
significantly more words in the Semantic than in the Phonemic fluency. task by stimulation interaction was not significant, F(1,9)⫽3.68,
Real tDCS significantly enhanced Verbal Fluency regardless of type of P⫽0.09, n2⫽.29. The main effect of task was due to the number
task (phonemic vs. semantic). Error bars depict⫾SEM. of words produced in the Semantic Fluency condition (mean num-
ber of words⫽19.33, SD⫽3.68) being overall higher than the total
reversed order. Similarly, half of the participants were presented number of words produced in the Phonemic Fluency condition
with the categories “Fruits” and “Car brands and names” in the first (mean number of words⫽14.98, SD⫽3.49), which is a well-known
tDCS session and with the categories “Animals” and “Musical result. The main effect of stimulation condition was due to real
instruments” in the second tDCS session. In each session, the tDCS enhancing subjects’ performance (mean number of words
order of presentation of each of the two letters and of each of the produced⫽18.93, SD⫽3.24) compared to the sham tDCS condi-
two categories was also randomised and counterbalanced across tion (mean⫽15.38, SD⫽2.89).
participants. The order in which the Phonemic and the Semantic
verbal fluency tasks were administered was counterbalanced Control experiment. Mean response latencies for correct
across subjects; for each subject, the order followed in the first responses in the Control experiment are reported in Fig. 2. Anal-
session was reversed in the second session. Crucially, all letters yses on the mean reaction times for correct responses in the
and categories were employed the same number of times in the Control experiment demonstrated that response latencies did not
Sham and Real tDCS conditions. significantly differ following sham tDCS (mean RT⫽332.5 ms,
SD⫽15.0) vs. real tDCS (mean RT⫽340.5, SD⫽34.9), t(6)⫽.85,
Control task. Seven participants also performed a spatial P⫽0.43.
detection task after completion of the fluency tasks. In each trial,
a fixation point was presented in the middle of the screen together
with two empty squares (measuring approximately one degree of EXPERIMENT 2
visual angle), appearing one to the left and one to the right of the
fixation point and on the same horizontal axis, for 1 s. After Although there is evidence that participants cannot distinguish
fixation, a cross (target) appeared either in the left or in the right between Real and Sham stimulation condition when 1 mA tDCS
square. Participants had to indicate, as fast as possible, whether using 5⫻5 cm2 electrodes (current density⫽0.04 mA/cm2) is used
the target appeared in the left or in the right square by pressing (Gandiga et al., 2006), in our experiment 2 mA tDCS was applied
with the right index finger a left key, and with the right middle finger and 5⫻7 cm2 electrodes were used (current density⫽0.057 mA/
a right key, respectively. Reaction times and accuracy were re- cm2). Given these differences in current intensity and density, we
corded for each trial. The control task consisted of 200 trials (1 min cannot exclude that at least some of our participants may have
rest was given after 100 trials). been able to distinguish between Sham and Real stimulation, this
knowledge possibly affecting their performance. In order to control
Procedure. Subjects were seated in front of a computer for this possibility, a new group of neurologically unimpaired par-
screen, in a normal-lightened and silent room. Before starting the
experiment, participants were instructed about the tasks they
would have to perform. Participants who performed the control
experiment were also presented with a few experimental trials in
order to familiarise themselves with the task. After the instructions,
a cartoon movie (with no audio) was projected on the PC com-
puter, and subjects were told to watch it. The tDCS stimulation
was started concurrently with the beginning of the video. The
cartoon movie was the same for each subject and for the two
tDCS sessions. This was done in order to reduce inter-subjects
variability with participants being exposed to the same visual
experience. Verbal fluency was administered after the end of the
tDCS stimulation. After 18 min from the beginning of the stimula-
tion, the cartoon movie was stopped and subjects were told that in
2 min they would have to perform the task. The first fluency task
was administered within 1 min from the end of the tDCS stimula-
tion; the second fluency task was administered within 1 min from Fig. 2. Participants’ mean response latencies (correct responses
the end of the first verbal fluency. In all cases, the two tasks were only) in the control experiment. Reaction times did not significantly
completed within 5 min from the end of the tDCS stimulation. After differ between Real tDCS and Sham tDCS. Error bars depict⫾SEM.
Z. Cattaneo et al. / Neuroscience 183 (2011) 64 –70 67

ticipants was tested. In these participants, anodal tDCS was Analyses on the mean reaction times for correct responses in
applied over the right-hemisphere homologue of the Broca’s the Control spatial detection experiment demonstrated that re-
region. If participants’ verbal fluency in the sham and real tDCS sponse latencies did not significantly differ following sham tDCS
sessions of Experiment 1 depended on their capacity to distin- (mean RT⫽318.6 ms, SD⫽55.8) vs. real tDCS (mean RT⫽323.5,
guish between the two stimulations, then this knowledge should SD⫽50.3), t(7)⫽.85, P⫽0.42.
also affect fluency scores when the homologue of Broca’s
region is stimulated.
DISCUSSION
Method
Our results show that anodal tDCS over Broca’s region
Participants. Eight right-handed neurologically unimpaired (compared to sham stimulation) significantly improved
individuals (three Males, mean age 23.8 years, SD⫽3.5) took part participants’ performance in both semantic and phone-
in Experiment 2. None of them had participated in Experiment 1.
mic fluency. Overall participants generated more words
The same criteria that were used to select participants in Exper-
iment 1 were also applied to Experiment 2. Written informed following semantic cues (i.e. the name of a category)
consent was obtained from all participants, with the approval of than phonological cues (i.e. a letter), in line with previ-
the local ethical committee of the University of Milano-Bicocca; ous evidence (Gollan et al., 2002; Grogan et al., 2008;
subjects were treated in accordance with the Declaration of Novelli et al., 1986), but the effect of tDCS over the
Helsinki. Broca’s region was comparable in the two tasks. Al-
Task and procedure. Task, procedure and tDCS parame- though one might argue that the effects we obtained
ters were the same as in Experiment 1, the only difference being may depend—at least in part— on non-specific effects of
the position of the electrodes on the scalp: the excitability enhanc- tDCS over levels of general arousal or attention, this
ing anodal electrode was placed over the right-hemisphere homo- possibility was ruled out by a control experiment dem-
logue of Broca’s region, while the cathodal electrode was placed
onstrating that response latencies in a spatial attention
over the left supraorbitary region. The homologue of Broca’s
region in the right-hemisphere was localized according to the task were similar following real and sham tDCS over
10 –20 EEG system. Broca’s region. Accordingly, previous studies have con-
sistently shown that tDCS over frontal regions during
Results language tasks did not directly affect attention (see Fer-
Analyses were performed as in Experiment 1. Fig. 3 shows the tonani et al., 2010; Monti et al., 2008). Finally, although
mean number of words produced in the Semantic Fluency and in some participants may have been aware of the differ-
the Phonemic Fluency in the Real and Sham tDCS session, ence between Real and Sham tDCS, this possible
respectively. A repeated measures ANOVA carried out on the knowledge did not affect their performance, as demon-
mean number of words generated with task (Semantic vs. Pho- strated by the lack of difference in fluency scores be-
nemic fluency) and stimulation condition (Sham vs. Real) as with- tween Real and Sham tDCS when Broca’s homologue in
in-subjects variables, only revealed a main effect of task,
F(1,7)⫽37.66, P⬍0.001, n2⫽.84. Neither the effect of stimulation
the right-hemisphere was stimulated (Experiment 2).
condition, F(1,7)⫽.007, P⫽0.94, n2⫽.001, nor the interaction type Large evidence suggests that phonemic and semantic
of task by stimulation condition, F(1,7)⫽.35, P⫽0.57, n2⫽.05, fluency involve partially different neural networks (e.g. Birn
reached significance. The main effect of task depended on par- et al., 2010; Grogan et al., 2009; Gourovitch et al., 2000;
ticipants producing overall more words in the Semantic Fluency Heim et al., 2008; Perani et al., 2003). In particular, se-
condition (mean⫽18.75, SD⫽4.15) than in the Phonemic Fluency mantic fluency compared to phonemic fluency is associ-
condition (mean⫽13.44, SD⫽3.61), resembling Experiment 1’s
ated to a greater activation of the left inferior temporal lobe,
findings.
reflecting the site of stored information being retrieved (e.g.
Mummery et al., 1996; Gourovitch et al., 2000; Heim et al.,
2008). Nonetheless, the inferior frontal gyrus is likely to
subserve common processes critical for both semantic and
phonemic tasks (for a review, see Costafreda et al., 2006),
as also suggested by the case of patients with frontal
lesions showing deficits in both situations (Baldo and Shi-
mamura, 1998; Schwartz and Baldo, 2001). Moreover,
there is evidence suggesting that semantic facilitation is
pervasive in word retrieval processes, even in the letter-
fluency task (e.g. Schwartz et al., 2003) and consistent
findings on healthy adults point to a specific role of the left
inferior frontal gyrus for semantic judgment (e.g. Devlin et
al., 2003; McDermott et al., 2003). Our results support the
importance of the inferior frontal gyrus in verbal fluency
Fig. 3. Mean number of words produced in Phonemic Fluency and in and points to the Broca’s region as a critical candidate for
Semantic Fluency in Experiment 2 (tDCS delivered over the right- tDCS stimulation in rehabilitation protocols aiming to im-
hemisphere homologue of Broca’s region). As in Experiment 1, par- prove language functions in patients.
ticipants produced significantly more words in the Semantic than in the
Phonemic fluency. No difference in performance was observed be-
Indeed, verbal fluency tests have been largely used to
tween the Real tDCS and the Sham tDCS sessions. Error bars assess language related and executive control processes
depict⫾SEM. in several neural disorders, ranging from traumatic brain
68 Z. Cattaneo et al. / Neuroscience 183 (2011) 64 –70

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(Accepted 27 March 2011)


(Available online 6 April 2011)