Neuropsychologia 50 (2012) 2645–2651

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Neuropsychologia

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Neurosc

Rome, I

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journal homepage: www.elsevier.com/locate/neuropsychologia

High frequency rTMS over the left parietal lobule increases non-wordreading accuracy

Floriana Costanzo a, Deny Menghini a, Carlo Caltagirone b,c, Massimiliano Oliveri b,d, Stefano Vicari a,n

a Department of Neuroscience, Bambino Ges �u Children’s Hospital, IRCCS, Rome, Italyb Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italyc Department of Neuroscience, University of Rome Tor Vergata, Rome, Italyd Department of Psychology, Faculty of Education Science, University of Palermo, Palermo, Italy

a r t i c l e i n f o

Article history:

Received 8 March 2012

Received in revised form

21 June 2012

Accepted 10 July 2012Available online 20 July 2012

Keywords:

Inferior parietal lobe

Superior temporal gyrus

Reading

Transcranial Magnetic Stimulation

32/$ - see front matter & 2012 Elsevier Ltd. A

x.doi.org/10.1016/j.neuropsychologia.2012.07

espondence to: Child Neuropsychiatry Unit, D

ience, Children’s Hospital Bambino Ges �u, Pi

taly. Tel.: þ39 6 68592475; fax: þ39 6 68592

ail address: stefano.vicari@opbg.net (S. Vicari

a b s t r a c t

Increasing evidence in the literature supports the usefulness of Transcranial Magnetic Stimulation

(TMS) in studying reading processes. Two brain regions are primarily involved in phonological decoding: the

left superior temporal gyrus (STG), which is associated with the auditory representation of spoken words,

and the left inferior parietal lobe (IPL), which operates in phonological computation. This study aimed to

clarify the specific contribution of IPL and STG to reading aloud and to evaluate the possibility of modulating

healthy participants’ task performance using high frequency repetitive TMS (hf-rTMS).

The main finding is that hf-rTMS over the left IPL improves non-word reading accuracy (fewer errors),

whereas hf-rTMS over the right STG selectively decreases text-reading accuracy (more errors).

These results confirm the prevalent role of the left IPL in grapheme-to-phoneme conversion. The non-

word reading improvement after Left-IPL stimulation provide a direct link between left IPL activa-

tion and advantages in sublexical procedures, mainly involved in non-word reading. Results indicate also

the specific involvement of STG in reading morphologically complex words and in processing the

representation of the text. The text reading impairment after stimulation of the right STG can be interpreted

in light of an inhibitory influence on the homologous area.

In sum, data document that hf-rTMS is effective in modulating the reading accuracy of expert readers

and that the modulation is task related and site specific. These findings suggest new perspectives for the

treatment of reading disorders.

& 2012 Elsevier Ltd. All rights reserved.

1. Introduction

Reading aloud is usually considered to involve the computa-tion of a target phonological code from orthographic (visual)input. The phonological code is translated into the sequence ofarticulatory gestures that underlie overt pronunciation. To somedegree, semantic (meaning) information may also contribute tothis computation (Graves, Desai, Humphries, Seidenberg, &Binder, 2010; Plaut, McClelland, Seidenberg, & Patterson, 1996).

Functional magnetic resonance imaging has revealed distrib-uted neural systems for mapping orthography directly to phonol-ogy: an anterior system, mainly located in the region of theinferior frontal gyrus, and two crucial posterior systems, one inthe occipito-temporal area (ventral stream) and one in theparieto-temporal area (dorsal stream) (Philipose et al., 2007;

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Price, 2000; Shaywitz, 2003; Turkeltaub, Eden, Jones, & Zeffiro,2002). All of these areas have been found to have a role in thereading process (Graves et al., 2010; Turkeltaub et al., 2002), andsome studies have investigated their specific contribution.

For example, it was found (Jobard, Crivello, & Tzourio-Mazoyer,2003; Price, 2000) that the anterior system is implicated in theoutput of phonological and articulatory as well as semantic aspectsof word reading. Recently, however, it was suggested (Graves et al.,2010; Hoeft et al., 2007) that in both expert readers and dyslexicsthe contribution of this system to reading is primarily due to theattention, working memory and executive processes required byreading than to orthographical–phonological mapping per se.

The first posterior ventral reading system is particularlyimportant in skilled, fluent reading (i.e. rapid and automaticreading) and encompasses portions of the occipital and temporallobes, such as the middle and inferior temporal gyrus and thefusiform gyrus (Visual Word Form Area, VWFA) (Cohen et al.,2000; Vinckier et al., 2007). In opaque orthographies (e.g. English)word reading is mainly associated with increased activation alongthis ventral pathway (Das, Padakannaya, Pugh, & Singh, 2011).

F. Costanzo et al. / Neuropsychologia 50 (2012) 2645–26512646

The second posterior dorsal reading system encompassesportions of the parietal lobe, specifically the left inferior parietallobe (L-IPL), including the angular and the supramarginal gyri,and portions of the temporal lobe, such as the left superiortemporal gyrus (L-STG). In transparent orthographies (e.g. Italian)adult proficient readers showed increased activation in phonolo-gically tuned areas along this dorsal pathway during word read-ing (Das et al., 2011). Although this dorsal system as a whole isconsidered crucial in mapping the visual percept of print onto thesounds (phonology) of spoken language (Shaywitz, 2003), con-verging lines of evidence suggest a distinct role for the L-IPL andthe L-STG. Indeed, these areas are crucial for the application ofphonological rules but at a different level of analysis (Graves et al.,2010; Jobard et al., 2003).

L-IPL damage has been linked to impairment in mapping fromsublexical phonological to grapheme representations (Alexander,Friedman, Loverso, & Fischer, 1992; Roeltgen, Sevush, & Heilman,1983). Its activity has also been related to the process ofconverting spelling-to-sound rather than to stored visual words(Price & Mechelli, 2005; Pugh et al., 2001; Pugh, Mencl, Shaywitz,et al., 2000) and has been associated with low bigram frequencyin word reading (Graves et al., 2010). Although evidence supportsinvolvement of an IPL sub-region (i.e. the angular gyrus) in visualword recognition when participants focus on the meaning of theword (Demonet, Price, Wise, & Frackowiak, 1994; Devlin,Matthews, & Rushworth, 2003; Mummery, Patterson, Hodges, &Price, 1998), functional distinction within the IPL sub-regions isstill a matter of debate (Stoeckel, Gough, Watkins, & Devlin, 2009)and IPL is usually considered to be involved in sequentialcomputations and in transforming letters to sounds in word ornon-word reading (Jobard et al., 2003).

As concerns the left superior temporal cortex, its activation hasbeen found associated with both lexical-semantic analysis (e.g.Helenius, Salmelin, Service, & Connolly, 1998; Pylkkanen,Feintuch, Hopkins, & Marantz, 2004; Vartiainen, Aggujaro, et al.,2009) and phonological analysis (e.g. Helenius et al., 1998; Rugg,1984; Wydell, Vuorinen, Helenius, & Salmelin, 2003). Convergingevidence supports a key role for the posterior L-STG in the whole-word representation of words (Graves, Grabowski, Mehta, &Gupta, 2008) and in reading morphologically complex words(Zweig & Pylkkanen, 2009), but it is still unclear whether itscontribution is limited to the sound form of the word (lexicalphonology) or whether it is also involved in word meaning(lexical semantics). The posterior L-STG is sensitive to lexicalphonology and this seems to be modality-independent, because itwas activated during both reading aloud and word repetitiontasks (Price, Winterburn, Giraud, Moore, & Noppeney, 2003).Furthermore, the posterior L-STG is thought to be involved mainlyin the processing of context, particularly when sentences arelinked (Vigneau et al., 2006), in establishing the sequentialcoherence of the representation constructed from the text(Jobard, Vigneau, Mazoyer, & Tzourio-Mazoyera, 2007) and duringtext comprehension (Crinion, Lambon-Ralph, Warburton,Howard, & Wise, 2003; Wydell et al., 2003). In sum, there is noconsensus on the functional role of the IPL and STG on the degreeof linguistic and lexical complexity employed in reading tasks.

Transcranial Magnetic Stimulation (TMS) has proven useful forinvestigating the causal relationship between activation of brainregions and behaviour and its role in the study of readingprocesses is increasingly evident in the literature (Braet &Humphreys, 2006; Duncan, Pattamadilok, & Devlin, 2009;Liederman et al., 2003; Nakamura et al., 2006; Skarratt &Lavidor, 2006; Stoeckel et al., 2009). These studies have focusedon the ‘‘virtual patient’’ approach (Pascual-Leone, Walsh, &Rothwell, 2000). In fact, low frequency repetitive TMS (rTMS),single-pulse TMS and paired-pulse TMS have been used to disrupt

reading at different levels (accuracy or speed) by interfering withdifferent reading areas, such as the occipito-temporal cortices(Duncan et al., 2009; Laycock, Crewther, Fitzgerald, & Crewther,2009; Liederman et al., 2003; Skarratt & Lavidor, 2006) and theparietal lobe (Braet & Humphreys, 2006).

On the contrary TMS can be used to improve cognitiveprocesses by modulating cortical excitability according to severalstimulation parameters (Brignani, Manganotti, Rossini, &Miniussi, 2008; Guse, Falkai, & Wobrock, 2010; Maeda, Keenan,Tormos, Topka, & Pascual-Leone, 2000). Indeed, high frequencyrTMS trains (Z5 Hz, hf-rTMS) applied before a task is executedare used to transiently enhance the excitability of the underlyingcortex (Peinemann et al., 2004; Rothkegel, Sommer, & Paulus,2010). Although hf-rTMS has not yet been used to study reading,language studies have documented an ameliorative effect onlinguistic-related tasks, including picture naming (Cappa,Sandrini, Rossini, Sosta, & Miniussi, 2002; Cotelli et al., 2011,2006; Cotelli, Manenti, Cappa, Zanetti, & Miniussi, 2008), oralword associations (Bridgers & Delaney, 1989) and digit span(Duzel, Hufnagel, Helmstaedter, & Elger, 1996).

We believe that the benefits derived from applying hf-rTMSover language-related areas might also extend to other linguisticprocesses, such as reading. To verify this hypothesis, we appliedhf-rTMS to adult normal readers to study its effect on theperformance of a reading aloud task. Although the number oferrors made by regular readers is minimal, their performance (interms of reading latency or errors) can also be affected in alanguage with transparent orthography, such as Italian. Forexample they can show greater difficulty in case of complex thansimple letter–sound conversion rules or in low-frequency word ornon-word than high-frequency word reading (Arduino & Burani,2004; Burani, Barca, & Ellis, 2006; Burani, Marcolini, De Luca, &Zoccolotti, 2008).

In order to verify a potential beneficial effect of hf-rTMS onadult expert reading, we applied 5 Hz-rTMS over two critical sitesof the dorsal reading pathway, the L-IPL and the L-STG thataccording to the literature are crucial for mapping print to soundsin transparent orthographies, such as Italian (Das et al., 2011). Wealso wanted to verify the differential effect of the stimulated brainareas on reading aloud performance by applying hf-rTMS off-lineprior to word, non-word and text reading.

As the increased activity of the L-IPL was found to beassociated with grapheme–phoneme conversion (Alexanderet al., 1992; Graves et al., 2010; Jobard et al., 2003; Roeltgenet al., 1983), we expected that stimulation of this site wouldprimarily affect isolated non-word reading performance, nothigh-frequency word or text reading performance. Differently,since L-STG specifically supports access to whole-word phonolo-gical forms (Graves et al., 2008) and to morphologically complexwords (Jobard et al., 2007; Zweig & Pylkkanen, 2009), weexpected that the stimulation of this site would primarily affectword and text reading performance rather than non-word readingperformance.

Because the contribution of the right IPL and the right STG toreading processes is still unclear (Graves et al., 2008; Peng et al.,2003; Vartiainen, Aggujaro, et al., 2009; Vartiainen, Parviainen, &Salmelin, 2009; Zweig & Pylkkanen, 2009), we decided to inves-tigate the specific role of each hemisphere in reading.

2. Methods

2.1. Experimental design

A group of 10 normal readers performed three reading tasks (reading aloud

words, non-words and text) in seven experimental conditions: following 5 Hz-rTMS

over the IPL and STG (target sites) bilaterally (left and right hemisphere); following

F. Costanzo et al. / Neuropsychologia 50 (2012) 2645–2651 2647

5 Hz-rTMS over the vertex (control site); in two conditions without rTMS (no-TMS

or baseline). The experiment was carried out in two daily sessions (one for each

hemisphere stimulated). Accuracy (number of errors) and speed (onset reaction

times – RTs – for word and non-word reading; number of syllables read in the text

per second—syll/s) were the reading measure.

2.2. Subjects

The study included 10 participants (6 women, aged 20–43 years, mean ¼

29 years). All were right-handed (LQ range ¼ þ65 to þ88) according to the

Oldfield Inventory (Oldfield, 1971), native Italian speakers with normal or

corrected-to-normal vision and a university-level education. None had any form

of reading disability, a personal history of neurological disease or a family history

of epilepsy (according to self-report). Pre-screening established that none of the

participants performed pathologically on the Italian clinical tests for dyslexia

(Judica & De Luca, 2005; Sartori, Job, & Tressoldi, 1995) and all had normal IQs

(range 99–107) according to the Progressive Matrices Test (Raven, 1938). All gave

their written informed consent prior to participating in the TMS experiment and

were screened according to TMS application guidelines (Rossi, Hallett, Rossini, &

Pascual-Leone, 2009, 2011). They were paid for their participation and were free to

leave the experiment at any time. The study was approved by the Santa Lucia

Foundation Research Ethics Committee.

2.3. Stimuli

Stimulus materials consisted of seven sets of 30 words (15 trisyllabic and

15 disyllabic) with high frequency in Italian written texts, 30 non-words (15

trisyllabic and 15 disyllabic) created by rearranging the character-string of real

word items, and texts about 600 syllables long.

The words in each set were matched for Italian written word frequency,

number of letters and syllables, bigram frequency (according to CoLFIS, http://

www.istc.cnr.it/material/database/colfis/) and mean onset RTs (Barca, Burani, &

Arduino, 2002). Texts were derived from an Italian novel (‘‘Marcovaldo ovvero le

stagioni in citt�a’’ by Calvino, 1966) each consisted of approximately the first 600

syllables in chapters 2, 7, 11, 15, 16, 19, 20, arranged similarly to an existing Italian

clinical test for dyslexia (Judica & De Luca, 2005).

Piloting refined the sets of words, non-words and texts derived from an

original list of nine sets of words and non-words and fourteen texts. A behavioural

pre-test was conducted with a different group of 10 native Italian speakers (five

women) to determine whether any putative TMS effects could be due to

insufficient matching of psycholinguistic factors in the absence of TMS. The

selected sets showed no difference for speed measures (onset RTs) or accuracy

level (number of errors).

Words and non-words were written in black Chicago font 24 and presented

individually at the centre of a 1500 iMac monitor with a grey background by

presentation software PsyScope (version XB53). Each item appeared for 1000 ms

following a central fixation point, which lasted 250 ms. The onset time of subjects’

vocal response was recorded; a 500 ms pause preceded the next trial. Each text

was presented for the entire duration of reading and was written single-spaced in

black Times New Roman 9.5 font on a white sheet of A4 paper.

The stimulus material for the return-to-baseline control task, used to ensure

the return to the pre rTMS stimulation state, consisted of eleven sets of 30 low-

frequency words (15 trisyllabic and 15 disyllabic), matched for Italian written

word frequency, number of letters and syllables, bigram frequency (according

to CoLFIS, http://www.istc.cnr.it/material/database/colfis/) and mean onset RTs

(Barca et al., 2002).

To verify the return to the pre-stimulation state after the 60 min pause, low

frequency words were adopted as control. Indeed, low frequency words reading

would involve both whole-word phonological forms (Graves et al., 2008),

supported by the activation of L-STG, and sublexical procedures (Burani et al.,

2006), supported by the activation of L-IPL.

As piloting refined the sets of words, there was no difference in speed (total

time in sec) or accuracy level (number of errors) between sets. Words were

presented together; they were arranged in 15-item columns, written single-

spaced in black Times New Roman 12 font on a white sheet of A4 paper.

2.4. Transcranial Magnetic Stimulation

TMS was carried out using a MagStim Super Rapid stimulator (Magstim,

Whitland, UK) with a figure-of-eight coil that was 70 mm in diameter. Stimulation

consisted of 10 rTMS trains of 50 stimuli at 5-Hz frequency (stimulation time,

10 s); stimuli were delivered at 100% of the motor threshold. There was an interval

of 30 s between each train. For each participant, the resting motor threshold was

defined as the lowest stimulator output that elicited a visible motor twitch in the

contralateral first dorsal interosseus (FDI) muscle in at least 5 out of 10 trials

(Rossini et al., 1994) and ranged 47–59% of stimulator output. The coils were

placed tangential to the skull with the handle pointing backward parallel to the

midline over P3 and P4 and over P5 and P6 of the extended version of the 10–20

EEG system.

In the control condition, the coil was placed over the vertex as a control region

not involved in the reading tasks.

2.5. Procedure

The main experiment included three different reading tasks: reading aloud

word and non-word sets (each set was randomly presented on a computer screen)

and reading aloud texts (presented on a sheet of paper). For the first two tasks the

presentation software recorded vocal onset delay (RTs in ms) as a measure of

reading speed (only RTs of correct responses were analysed); all responses were

recording by a portable recorder and digitised with the GOLDWAVE program

[Ver 5.12 (Goldwave Inc., St Johns, NL, Canada), http://www.goldwave.com] at

44.1 kHz.

A blinded experimenter recorded the number of errors, that is, one point for

every letter substitution (errors that involved consonant or vowel sound changes,

omissions, position changes or additions) and a half point for every self-correction

and hesitation (delay greater than 2000 ms), as a measure of reading accuracy.

No more than one point error was given for the same word. For texts, speed was given

by the number of syllables read per second (syll/s) and accuracy by the error score

(one point per letter substitution; a half a point for self-correction and hesitation).

The entire experiment was carried out in two daily sessions, that is, one for

each hemisphere stimulated. One session covered three experimental conditions

(no-TMS and the two target sites) and the other one, four experimental conditions

(no-TMS, the two target sites and the control site).

The order of the experimental conditions was counterbalanced across subjects

and the assignment of sets of words, non-words and texts to each condition was

randomly distributed.

With the exception of the no-TMS condition, that is, without TMS, the reading

tasks were administered immediately after the rTMS stimulation. The participants,

who were seated in a comfortable chair in a silent room, performed the reading

tasks in fixed order (words, non-words and text) for about 6 min. Before the new

condition, a 60 min interval elapsed after which they performed a return-to-

baseline control reading task to ensure they had returned to the pre rTMS

stimulation state. The return-to-baseline control task consisted of reading a set

of 30 low frequency words (15 disyllabic and 15 trisyllabic) on a sheet paper.

Before the experiment started, each subject read four initial sets of 30 low

frequency words; the mean of their errors and speed constituted their basal

return-to-baseline word reading accuracy and speed. The measures (accuracy and

speed) obtained in the return-to-baseline control tasks were then compared to the

basal mean return-to-baseline measures of word reading (accuracy and speed)

obtained in the first four sets of return-to-baseline control task.

If the participant’s performance in each return-to-baseline control task was

within one standard deviation of the basal condition, the experiment was

continued; if not, another 40 min interval elapsed before the new return-to-

baseline control task was administered. Overall, each experimental session lasted

from 2 to 4 h.

2.6. Statistical analysis

The mean baseline, that is, the average between the participants’ performance

in the two no-TMS conditions, one per each daily session, was entered as control

condition in all analyses. RTs beyond two standard deviations of the individual

means for each condition were omitted with the assumption that these responses

may have involved attentional lapses, blinks, etc.

Repeated measure ANOVAs were performed on each reading measure: errors,

RTs and syll/s. Condition (L-IPL, R-IPL, L-STG, R-STG, vertex, and mean baseline)

and Task (word, non-word and text – in the case of errors; word and non-word –

in the case of RTs; text in the case of syll/s) were the independent factors. The

sphericity assumption was not violated, as verified by Mauchly’s sphericity test.

Post hoc analyses by means of Fisher’s LSD test were performed to characterise the

significant effects. Partial eta squares (Zp2) and Cohen’s d (d) have been reported as

effect size measures.

3. Results

3.1. Return-to-baseline control task

Word reading accuracy and speed in the return-to-baselinecontrol tasks was within 1 SD of the basal condition for eachparticipant and condition, with the exception of two cases.Specifically, one participant showed a reading speed of 1.7 SD ofthe basal speed after L-STG stimulation; a second participantshowed a reading accuracy of �1.3 SD of the basal accuracy after

F. Costanzo et al. / Neuropsychologia 50 (2012) 2645–26512648

R-IPL stimulation. For these participants, a 40 min extra-timeinterval was necessary to return to the pre-stimulation state.

3.2. Main experiment

3.2.1. Reading accuracy

Analysis on errors revealed a main effect of Task [F(2,18) ¼ 8.57;p ¼ 0.002; Zp

2¼ 0.49]; specifically, significantly fewer errors were

found in word reading than non-word reading (p ¼ 0.002;d ¼ �1.11 ) and text (p o 0.001; d ¼ �1.2) reading. The analysisalso revealed a main effect of Condition [F(5,45) ¼ 3.51; p ¼ 0.009;Zp

2¼ 0.28]: regardless of which task was performed, fewer errors

were found with L-IPL stimulation than all other conditions (allp o 0.05, d range ¼ �0.29 to �1.44), with the exception of theL-STG condition (p ¼ 0.32; d ¼ �0.51); significantly more errorswere found with R-STG stimulation than with L-IPL (p o 0.001,d ¼ 1.43) and R-IPL (p ¼ 0.005; d ¼ 0.44) stimulation, but not thanthe other conditions (all p ¼ n.s., d range ¼ 0.43–0.95).

Finally, a significant Task � Condition interaction emerged[F(10,90) ¼ 2.86; p ¼ 0.004; Zp

2¼ 0.24). Post hoc comparisons

revealed no significant difference between conditions in theword-reading task (all p ¼ n.s. d range ¼ 0.0–0.14); however, adifference emerged in the non-word and in the text reading tasks.Specifically, fewer errors were found with L-IPL stimulation thanthe other conditions in non-word reading (all p o 0.05;d range ¼ �0.79 to �1.96), whereas more errors were foundwith R-STG stimulation than the other conditions (all p o 0.001;d range ¼ 0.72–1.21) in text reading (Fig. 1). Notably, no

Fig. 1. Mean errors for the three tasks. Mean errors when reading words, non-

words and text for each experimental condition: after hf-rTMS over the left

inferior parietal lobule (L-IPL), the left superior temporal gyrus (L-STG), the right

inferior parietal lobule (R-IPL), the right superior temporal gyrus (R-STG) and the

vertex (CZ), and in the no-TMS conditions (baseline). Standard errors are

represented in the figure by the error bars attached to each column. Fewer errors

were found after L-IPL stimulation compared to the other conditions in non-word

reading whereas more errors were found after R-STG stimulation compared to the

other conditions in text reading. No differences emerged between the two control

conditions (CZ and baseline).

Table 1Mean reaction times (standard deviation) on the reading tasks in each experimental c

Task L-IPL L-STG R-IPL

Worda 554 (48) 555 (49) 534 (56

Non-worda 659 (48) 644 (92) 632 (89

Textb 6.13 (0.90) 6.26 (0.93) 6.16 (0.

Mean reaction times on the word, non-word and text reading tasks after hf-rTMS over t

right inferior parietal lobule (R-IPL), the right superior temporal gyrus (R-STG), the verte

between conditions.a Milliseconds.b Syllables per second.

differences emerged between the mean baseline and vertex eitherin the main effect of Condition or in the interaction effect ofTask � Condition, thus indicating the absence of unspecificeffects related to rTMS per se.

3.2.2. Reading speed

Analysis of RTs revealed a significant main effect of Task[F(1,9) ¼ 29.4; p o 0.001; Zp

2¼ 0.78], with word onset (mean

RTs 554.37 7 16 ms) shorter than non-word onset (mean RTs644.57 7 22 ms). Neither the Condition [F(5,45) ¼ 1.9; p ¼ 0.10;Zp

2¼ 0.18] nor the interaction Task � Condition [F(5,45) ¼ 1;

p ¼ 0.42; Zp2¼ 0.16] effect was significant.

Analysis of syll/s in text reading revealed no significant effectof Condition [F(5,45) ¼ 1.28; p ¼ 0.29; Zp

2¼ 0.12], with a mean of

6.11 7 0.12 syll/s between conditions. Detailed RT measures foreach task and condition are provided in Table 1.

4. Discussion

The present study was aimed at determining whether applying5 Hz-rTMS over the L-IPL and L-STG would enhance reading aloudin normal readers. We found that reading abilities are modifieddifferently by hf-rTMS depending on the brain area stimulated.

In particular, L-IPL stimulation has a specific role in non-wordreading. Converging evidence documents the role of the L-IPL insequential computations and in grapheme transduction in non-word reading (Alexander et al., 1992; Pugh, Mencl, Shaywitz, et al.,2000; Roeltgen et al., 1983). Support for involvement of theparietal lobe network in the serial mechanism of non-word readingalso comes from neurobiological studies (Jobard et al., 2003; Pughet al., 2001), simulation evidence (Valdois et al., 2006) and clinicalreports. Indeed, it has been found that damage of the left angularand supramarginal gyri is associated with the selective impairmentof grapheme-to-phoneme conversion (Friedmann, Ween, & Albert,1993; Greenwald, 2001). However, the ameliorative effect on non-word reading after L-IPL facilitation may be particularly valid fortransparent orthographies as Italian. Readers in any orthographysimilarly adopt grapheme to phoneme assembly in novel-word ornon-word reading but some brain areas are more highly activateddepending on the transparency of the orthography (Das et al.,2011; Paulesu et al., 2000; Simon, Bernard, Lalonde, & Rebaı, 2006).Specifically, the anterior part of the interior frontal gyrus is morestrongly activated in English readers than in Italian readers duringnon-word reading (Paulesu et al., 2000). It is possible that deep-orthography readers recruit more areas involved in naming andsemantic processing to resolve orthographic ambiguity than trans-parent-orthography readers. Conversely, since L-IPL facilitationdirectly improves non-word reading in our readers, it could bethat transparent-orthography readers take higher advantage fromareas’ activation linked to grapheme to phoneme assembly thandeep-orthography readers. The issue of a direct comparison

ondition.

R-STG CZ Baseline

) 546 (52) 567 (55) 566 (56)

) 641 (69) 653 (86) 638 (60)

92) 5.92 (0.96) 6.18 (0.88) 6.02 (0.74)

he left inferior parietal lobule (L-IPL), the left superior temporal gyrus (L-STG), the

x (CZ), and in the no-TMS conditions (baseline). No significant differences emerged

F. Costanzo et al. / Neuropsychologia 50 (2012) 2645–2651 2649

between transparent- and deep-orthographies on non-word read-ing after L-IPL needs further investigation.

An opposite result emerged after facilitation of the R-STG;indeed, poorer accuracy was found, especially in text reading. Weexpected an effect of the L-STG, because studies have reportedinvolvement of the posterior L-STG in whole-word representa-tions of words (Graves et al., 2008), in reading morphologicallycomplex words (Zweig & Pylkkanen, 2009) and in processing therepresentation constructed from the text (Jobard et al., 2007).Nevertheless, we only found a strong effect of interference in textreading after R-STG stimulation. Our data on the interfering effecton reading accuracy for the right hemisphere can be interpretedin light of research findings documenting higher right-hemi-sphere activity in individuals with reading disorders. In particular,evidence shows that in subjects with reading disabilities theposterior regions of the right hemisphere are more activated thanthose of the left hemisphere (Eden et al., 2004; Pugh, Mencl,Jenner, et al., 2000; Shaywitz et al., 2004, 2002; Simos, Breier,Fletcher, Bergman, & Papanicolaou, 2000). Furthermore, areversed asymmetry in the temporo-parietal region (R 4 L) wasconfirmed in poor readers as they listened to pairs of sentences(Rumsey et al., 1994). In a recent study (Rimrodt et al., 2009) onneural activity in reading and comprehension of words andsentences, dyslexics showed increased right superior temporalgyrus activation compared with controls. Also, in both dyslexicsand controls reading accuracy was negatively correlated withright superior temporal lobe activation. Accordingly, data on theassociation between right-hemisphere activity and reduced read-ing performance might explain our finding of an interfering effecton reading after facilitation of the R-STG. It is possible that thenegative outcome after stimulation of the right STG comes fromthe interhemispheric competitive effect, with right STG having aninhibitory influence on the homologous area. How it is wellknown, rTMS can induce homeostatic-like effects. The after-effects of rTMS do not occur in isolation but the brain interactswith the changes that occur on a target area (Ridding & Rothwell,2007). The variation of excitability is compensated by a reorga-nisation of activity in other areas, particularly contra lateral areas(Lee et al., 2003). Moreover, we cannot exclude that an ameliora-tive effect with L-STG stimulation may be detected with a greatersample size.

However, the selective involvement of the STG in text readingindicates a functional role of the STG in sentence processingrather than in single word or non-word processing. This evidenceis consistent with the results of studies supporting major involve-ment of the STG in establishing the sequential coherence of partof a text (Crinion et al., 2003; Jobard et al., 2007; Vigneau et al.,2006; Vingerhoets et al., 2003) than in phonological analysis(e.g. Helenius et al., 1998; Rugg, 1984; Wydell et al., 2003).

The lack of improvement in word reading after hf-rTMS overthe L-STG can be explained from a neuroanatomical perspective.Although L-STG has a documented role in word reading (Graveset al., 2008; Price et al., 2003) the posterior ventral readingsystem, that is the middle and inferior temporal gyrus and thefusiform gyrus (VWFA) (Cohen et al., 2000; Dehaene, Cohen,Sigman, & Vinckier, 2005; Vinckier et al., 2007), could be theneural circuits more involved in high-frequency word reading inadult readers than L-STG (Helenius et al., 1998). Further studiesand with a larger number of participants are needed to investi-gate this hypothesis by extending to other brain regions and toother tasks the effect of hf-rTMS in reading. However, sinceparticipants made approximately zero errors, a ceiling effectmight have prevented a clear demonstration of TMS facilitation.

Our results document a TMS effect on accuracy but not speed.A greater effect on accuracy than RTs has also been confirmed byother studies using different TMS paradigms. In particular,

interference with dorsal visual areas (VT5/MTþ) by rTMS andpaired-pulse TMS demonstrated that word discrimination accu-racy (Laycock et al., 2009) and non-word naming accuracy weredisrupted (Liederman et al., 2003).

In sum, the present results show that hf-rTMS is effective inmodulating (i.e. improving or worsening) the reading accuracy ofexpert readers and that the modulation is strictly task and sitespecific. Moreover, the participants’ amelioration in accuracy aftera left but not a right stimulation could be in line with a veryrecent study (Turkeltaub et al., 2012) which demonstrated that,enhancing left lateralisation in a reading brain area (posteriortemporal cortex), by a non-invasive brain stimulation technique(transcranial direct current stimulation) improves reading effi-ciency in adults without dyslexia.

Two potential limitations of this study warrant mention.One has to do with the lack of a navigational system, which isfunctional to improve anatomical localisation of the target sitesby providing stereotaxic information. A second limitation relatesto the reading task order. A fixed order of task presentation waschosen because the small subjects’ number does not allowus to counterbalance both for condition and task order. Never-theless, a possible interfering effect on results related to the fixedorder of task presentation would need further examination in afuture study.

Although preliminary, present findings suggest new perspec-tives for the treatment of reading disorders. As hf-rTMS has beensuccessfully adopted in remediating patients with aphasia anddegenerative linguistic disorders (Cotelli et al., 2011, 2006, 2008;Finocchiaro et al., 2006), it could also be used with dyslexicpopulations (Frye, Rotenberg, Ousley, & Pascual-Leone, 2008).Indeed, although functional imaging studies are still rare indyslexic individuals following rehabilitative cognitive training(Temple et al., 2003), the existing research highlights the sig-nificant effects on neural activity after treatment (Odegard, Ring,Smith, Biggan, & Black, 2008; Shaywitz et al., 2004). Futurestudies are needed to develop hf-rTMS methods to supportcognitive training for the remediation of reading difficulties indyslexic individuals.

Acknowledgements

We thank S. Torriero and E. Lo Gerfo for their assistance incollecting data.

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