ARTICLE IN PRESS

www.elsevier.com/locate/ynimg

YNIMG-03192; No. of pages: 12; 4C: 3, 4, 7

DTD 5

NeuroImage xx (2005) xxx – xxx

Word and non-word reading: What role for the Visual Word

Form Area?

M. Vigneau,a G. Jobard,a B. Mazoyer,a,b and N. Tzourio-Mazoyera,*

aGroupe d’Imagerie Neurofonctionnelle, UMR 6194, CNRS CEA, Universities of Caen and Paris 5, GIP Cyceron, BP 5229,

14074 Caen Cedex, FrancebMR Unit Caen University Hospital, Institut Universitaire de France, France

Received 3 January 2005; revised 1 April 2005; accepted 18 April 2005

The putative role of the so-called Visual Word Form Area (VWFA)

during reading remains under debate. For some authors, this region

is specifically involved in a pre-lexical processing of words and

pseudowords, whereas such specificity is challenged by others given

the VWFA involvement during both non-word reading and word

listening. Here, we further investigated this issue, measuring BOLD

variations and their lateralization with fMRI during word and non-

word reading, in order to evaluate the lexicality effect, and during

reading and listening of words, in order to evaluate the impact of

stimulus delivery modality on word processing networks. Region of

interest (ROI) analysis was first performed in three target areas: 1—

VWFA as defined by a meta-analysis of the word reading literature,

2—a middle temporal area (T2) found co-activated by both word

reading and listening, 3—an inferior occipital area (OI) belonging to

the unimodal visual cortex of the inferior occipital gyrus. VWFA

activity was found not different between word and non-word reading

but was more leftward lateralized during word reading due to a

reduction of activity in the VWFA right counterpart. A similar larger

leftward lateralization during word reading was also uncovered in the

T2 ROI but was related to a larger left side activity. Such a lexicality

effect was not observed in the OI ROI. By contrast, BOLD increases

during listening were restricted to the left VWFA and T2 ROIs.

Voxel-based analysis (SPM99) showed that semantic areas were more

active during word than non-word reading and co-activated by both

reading and listening, exhibiting a left lateralized activity in all tasks.

These results indicate that the left VWFA would be the place where

visual and verbal representations bind under the control of left

semantic areas.

D 2005 Elsevier Inc. All rights reserved.

Keywords: fMRI; Reading; Word; Fusiform, VWFA; Hemispheric special-

ization; Language

1053-8119/$ - see front matter D 2005 Elsevier Inc. All rights reserved.

doi:10.1016/j.neuroimage.2005.04.038

* Corresponding author. Fax: +33 231 470 222.

E-mail address: tzourio@cyceron.fr (N. Tzourio-Mazoyer).

Available online on ScienceDirect (www.sciencedirect.com).

Introduction

The past 10 years have witnessed the emergence of numerous

brain imaging studies aimed at uncovering the brain networks

involved while subjects are reading. A crucial question, inherited

from the neuropsychological models of reading, concerns the

existence of brain areas dedicated to the visual perception of

words. Acquisition of reading indeed relies on the readers’ capacity

to adequately identify complex visual stimuli at such a fine degree

that Fshirt_ must be discriminated from Fshift_ within a single

fixation of a few hundreds of milliseconds. Several brain regions

have been proposed as potential candidate areas in which such a

visual specialization for words could occur, such as Petersen’s

medial extra-striate region (Petersen et al., 1990), Howard’s

angular gyrus (Howard et al., 1992) or Cohen’s occipito-temporal

region (Cohen et al., 2000). Positive correlation between activation

within this latter region and reading skill in children has been

reported, but this correlation also extended to Howard’s angular

gyrus, suggesting that the occipito-temporal junction was not

necessarily the critical site for word reading specific process

(Shaywitz et al., 2002). Actually, since the involvement of the

angular gyrus in the visual identification of words remains both

unreplicated and contested (see Cohen et al. (2000) and Jobard et

al. (2003) for a critical review of these regions in reading), most

authors agree on the specificity of the occipito-temporal junction

for the visual identification of words. This region is situated in the

fusiform gyrus of the left hemisphere, lying in the ventral route for

object visual identification. Its activity does not seem to vary as a

function of visual-hemifield of presentation, indicating a conver-

gence of visual information in this area in order to identify

presented words (Cohen et al., 2000). Cohen et al. further refined

their investigations of this region they named FVisual Word Form

Area_ (VWFA) and showed that it is activated by word-like stimuli

(including pseudowords) but less so by consonant strings (Cohen

et al., 2002). The activation of this region has also been

demonstrated to be independent of word meanings (Dehaene et

al., 2002) and sensitive to priming even when the appearance of

letters was altered using different letter case (Dehaene et al., 2001;

ARTICLE IN PRESSM. Vigneau et al. / NeuroImage xx (2005) xxx–xxx2

Polk et al., 2002). These results would therefore indicate that the

VWFA processes words in an abstract enough fashion to strictly

ignore visual variations if letter identity is conserved.

Despite these converging findings, several issues remain so far

unanswered, for instance, the level of specialization exerted by the

VWFA. While some studies did find activation of this region

during word and word-like stimuli reading minus consonant string

reading (Cohen et al., 2002; Kiehl et al., 1999; Pammer et al.,

2004; Polk et al., 2002), many studies have also been unsuccessful

at replicating VWFA activation using word reading minus non-

word reading contrast (Beauregard et al., 1997; Binder et al., 2003;

Joubert et al., 2004; Price et al., 1996; Rees et al., 1999; Tagamets

et al., 2000).

In addition, as underlined by Price et al., the specialization of

the VWFA for the visual modality is still a matter of debate (Price

et al., 2003b). While Dehaene et al. reported no implication of the

VWFA during audition of words (Dehaene et al., 2002), other

studies showed its implication in tasks where subjects had to listen

to words and were not presented with visual materials (Booth et al.,

2002a,b; Price et al., 2003a). Dehaene et al. have objected that such

VWFA activation during word listening could be due to subjects

picturing in their minds words in their written form (Dehaene et al.,

2002). Currently, no clear answer has been brought concerning

these discrepant findings, and the existence of an area strictly

devoted to written language only (Cohen et al., 2002) remains an

open question.

In this debate, an important issue appears to have been

somewhat overlooked, namely, the hemispheric specialization.

Reading is indeed a cognitive activity during which a strong

interaction between visual and language networks must occur.

Interestingly, right hemisphere activations have been reported to be

smaller during word than during pseudo- or non-word reading,

while left hemisphere activity was similar during all conditions

(Tagamets et al., 2000). These findings indicate that hemispheric

lateralization, rather than increased activity at a given anatomical

localization, may be a good marker of the functional specialization

for words. Such left hemisphere specialization in right-handers has

been shown to be a fundamental element in the brain organization

for language that presides to the setting of regional specialization

(Tzourio-Mazoyer et al., 2004). Since the elements obtained solely

on the comparison of activation levels in the VWFA remain

contradictory, it seems interesting to evaluate whether or not

hemispheric lateralization could constitute the support of the

debated specialization of the VWFA for word reading.

In the present study, we used fMRI for a further investigation of

the neural networks of word reading as compared to either word

listening or non-word reading. We questioned the VWFA neural

activity in terms of region BOLD signal modulation and

lateralization during these different tasks using both an a priori

region of interest (ROI) analysis and a voxel-based whole brain

approach.

Materials and methods

Subjects

This study was approved by our local ethic committee. Twenty-

three healthy male volunteers aged 18–28 years (mean = 22.1 T2.5 years) took part in the study after they gave their informed

written consent. All subjects were right-handed as assessed by the

Edinburgh inventory questionnaire (Oldfield, 1971) (mean = 92.7 T12.5). All had a high level of education, reported French as their

mother tongue and were not familiar with the Finnish tongue. Two

groups were constituted, one including 13 volunteers who

performed both word (1 run) and non-word (3 runs) reading, the

other composed of 10 volunteers who performed both word

reading (1 run) and listening (1 run).

Experimental paradigm

Each run consisted in a block design alternating 4 blocks of 30 s

of stimulus presentation (either words or non-words) with 5 blocks

of cross fixation of equal duration. The reading and listening

blocks were both made up of 32 stimuli, each stimulus being

presented during 940 ms. Visual stimuli were projected in white

font onto a black screen, while auditory stimuli were delivered

through earphones. A special emphasis was put on the necessity for

subjects to try to read non-words as well as they would do for

words, despite their unfamiliar appearance. As an incentive for the

subjects to carefully attend to the stimuli, they were informed that

they would have to perform a recognition test for words and non-

words after the scanning session.

Word reading and listening

French words were extracted from the ?BrulexX data base

(Content et al., 1990). Half of these words were frequent and

highly imageable common nouns, 25% were non-conjugated verbs

and 25% were adjectives. The proportion of words describing

natural and manufactured objects was equated. Mean length of

these words was 6.5 (T1.8) letters. The word lists used in the

reading and listening conditions were matched for length, image-

ability and category.

Non-word reading

Non-words are letter assemblies that differ markedly from

pseudowords in terms of their orthographical construction. Pseudo-

words follow the orthographical rules of a given language and are

therefore quite similar to familiar words (any new word so far

unknown by the subject is indeed a pseudoword at first). Non-

words, on the contrary, violate these rules and can immediately be

identified as being meaningless. Here, we used three different types

of such orthographically illegal stimuli with a mean size identical

to that of words: 1—Consonant strings that contained a sequence

of letters randomly formed and extracted from the 20 consonants of

the alphabet (?vfgtjkpX, ?cvbbcxX); 2—Vowel strings that con-

tained a sequence of randomly formed vowels; 3—Finnish words

that can be considered as non-words for French subjects since they

differ so much in their structure, being formed of irregular

sequences of letters (?kiinnitaaX, ?vystyyaaX, ?ksoisperaX) and

sharing no morphological roots with French words. All Finnish

words used during this task resulted from the translation of French

words selected upon the same criteria as the French words used for

the reading condition.

Image acquisition

MRI experiments were performed using a GE Signa 1.5-T

Horizon Echospeed scanner (General Electric, BUC, France), each

starting with two anatomical acquisitions. First, a high-resolution

structural T1-weighted 3D volume (T1-MRI) was acquired using a

spoiled gradient recalled sequence (SPGR-3D, FOV = 256� 256�

ARTICLE IN PRESSM. Vigneau et al. / NeuroImage xx (2005) xxx–xxx 3

186 mm3, sampling = 0.94 � 0.94 � 1.5 mm3) providing detailed

anatomic images and used to define the location of the 32 axial

slices to be acquired during both the second anatomical acquisition

and functional sequences. The second anatomical acquisition

consisted in a double echo proton density/T2-weighted (PD-MRI/

T2-MRI) sequence (FOV = 256 � 256 � 121 mm3, sampling =

0.94 � 0.94 � 3.8 mm3). For each functional run (either reading or

listening), a time series of 50 EPI volumes was acquired (TR = 6 s,

TE = 60 ms, FA = 90-, sampling = 3.75 � 3.75 � 3.8 mm3).

Functional image pre-processing

The first five volumes of each functional run were discarded,

allowing for signal stabilization, and differences in slice

acquisition timing were corrected (SPM99). The sixth volume

of the run was considered as the reference functional volume

(fMRI0). For registration of fMRI0 onto the stereotactic Montreal

Neurological Institute (MNI) template, rigid (fMRI0 onto T2-MRI

and PD-MRI onto T1-MRI) and non-linear (T1-MRI onto the

MNI template) registration matrices were computed and then

combined. The registration of fMRI0 and T1-MRI volumes in the

MNI space was thereafter visually checked with the MPI Tool

software (Max-Planck Institute, Germany) and manually corrected

when necessary.

Then, each fMRI volume was registered onto the fMRI0volume (SPM99) and re-sampled in the MNI space using the

registration parameters calculated in the first procedure. Finally,

data were spatially smoothed with an 8-mm FWHM Gaussian

kernel, leading to an image smoothness of approximately 11 mm in

the 3 directions.

Image analysis

ROI analysis

ROIs definition. Our anatomical definition of the VWFA was

based on a meta-analysis of 16 neuroimaging studies that reported

27 activation peaks in this area during word reading (Jobard et al.,

2003). Accordingly, VWFA was defined as a sphere (Fig. 1)

centered on the average coordinates of these 27 activation peaks

(x = �44, y = �58, z = �15) and having a radius equal to the

Fig. 1. ROI approach: regions definition. Three areas were defined as

spheres having the same volume (radius r = 5 mm) centered into the MNI

space. The three regions are projected onto the average statistical map of the

23 subjects computed during word reading. The VWFA (black circle) was

estimated from the meta-analysis of neuroimaging studies of word reading

and defined as a sphere with center x = �44, y = �58, z = �15. The OI

centered (x = �42, y = �78, z = �10) was identified from the contrast of

word reading minus word listening and was located in the inferior occipital

gyrus (green circle). The T2 centered (x = �50, y = �44, z = �10) was

common to both the reading and listening task and was located in the

posterior part of the middle temporal gyrus (blue circle).

standard deviation of the set of peak-to-peak distances (r = 5

mm). In order to compute Functional Asymmetry Indices (FAI), a

right homologue of this VWFA ROI was defined by taking its

symmetric with respect to the MNI space y axis, i.e. a sphere

having the same radius (r = 5 mm) and centered at (x = 44, y =

�58, z = �15). First, we computed, from images containing

weighted signal BOLD estimate, individual BOLD variation in

both left and right VWFA and during each reading and listening

tasks. We used mask images corresponding to each region of

interest and within which voxels were to be assessed. Then, mean

left and right BOLD variations were obtained by averaging

individual BOLD variations. Finally, VWFA FAI were defined as

the difference between left and right BOLD values.

In order to better characterize the VWFA behavior in terms of

visual and/or verbal processing, BOLD variations were also

assessed in both a visual and a supramodal ROI. Two other pairs

of bilateral spherical regions of interest within the ventral route

were thus defined, having the same radius than the VWFA ROI:

one was located within the inferior occipital gyrus (OI), belonging

to unimodal visual cortex (center coordinates: x = T42, y = �78,

z = �10), the other was centered in the posterior part of the

middle temporal gyrus (T2) and corresponded to a peak of co-

activation of reading and listening to words (center coordinates:

x = T50, y = �44, z = �10) as evidenced by the conjunction

analysis in the present study (see below).

Statistical analysis. For each of the three ROIs, we used Student

paired t tests to assess the difference between word reading, non-

word reading and word listening on the three following variables of

interest: right ROI BOLD variations, left ROI BOLD variations and

functional asymmetry indices (FAI: left minus right ROI BOLD

variations). The effect of lexicality was investigated by comparing

word to non-word reading (i.e. Finnish words, consonant and vowel

strings) in the first group of subjects (N = 13). Then, in order to

evaluate the effect of the modality, we compared word reading with

word listening in the second group (N = 10).

Whole brain approach

The pre-processed functional MRI images were also analysed

with SPM99 (Friston et al., 1995). This statistical analysis

consisted of two stages: first, we computed individual BOLD

contrast maps of either reading or listening versus their reference

(cross fixation); in a second stage (group level), a statistical

analysis was performed for both mean BOLD variations and mean

asymmetry indices. Asymmetry indices were obtained by subtract-

ing BOLD values of one hemisphere from those of the homologous

hemisphere (i.e. left minus right for the left hemisphere and reverse

for the right counterpart).

Word reading relative to cross fixation contrast was computed

in the whole group of subjects (N = 23). Word versus non-word

contrasts were calculated in the first group (N = 13), namely, word

reading minus non-word reading and non-word reading minus

word reading in order to test an effect of lexicality. In the second

group (N = 10), we computed the conjunction of reading and

listening of words to identify neural networks common to both

modalities and word reading minus word listening in order to

uncover areas dedicated to the visual processing of words.

Statistical threshold was set at 0.001 uncorrected for multiple

comparisons (z score > 3.22), leading to a threshold at 0.00001

uncorrected for the conjunction analysis (0.001 for each map

entering the conjunction analysis).

ARTICLE IN PRESSM. Vigneau et al. / NeuroImage xx (2005) xxx–xxx4

Results

ROI analysis

VWFA

Plots of individual values (Fig. 2) show that all subjects (N = 23)

presented a BOLD signal increase in the left VWFA during word

reading when compared to the cross fixation reference condition,

whereas 19 subjects out of 23 activated its right counterpart. On

average, the VWFA showed a significant signal increase during

word reading (t = 6.7, P < 0.001 and t = 4.8; P < 0.001 for the left

and right sides, respectively) together with a significant leftward

signal lateralization (FAI = 0.009 T 0.018, P = 0.02). Similar

findings were observed in the sub-group of 13 subjects, although

their average FAI failed to reach significance (Table 1).

During non-word reading, mean BOLD variations did not differ

with the type of non-word (Finnish words, consonants or vowels).

This lack of difference led us to pool these three reading

conditions, subsequently referred to as Fnon-words_. Significant

Fig. 2. For each ROI, individual value was obtained by averaging BOLD values co

increase within the VWFA excepted for 4 subjects in the right region. Within bo

excepted one in the right. The left T2 was activated for 22 subjects out of 23, whi

These results demonstrated the robustness of both the functional implication and

activations during non-word reading were observed in both

hemispheres with no significant asymmetry (Table 1).

Contrasting word with non-word reading did not show any

difference in the left VWFA, while a trend for a larger signal

increase during non-word as compared to word reading was

observed in the right counterpart. This led to a significant larger

leftward asymmetry for word relative to non-word reading.

In the other sub-group, a bilateral increase was observed during

reading (as in the first group), but the listening task led to a

nonsignificant left hemisphere increase together with a signal

decrease on the right. Direct comparison between the two modal-

ities shows larger bilateral signal increase during word reading. A

leftward lateralization was present during both word reading and

listening, with no significant difference between the two conditions.

OI area

All subjects presented a BOLD signal increase in the left OI

ROI, and all but one in its right counterpart, resulting in a

significant bilateral signal increase during word reading taking the

mputed within each voxel (SPM99). All subjects showed a bilateral BOLD

th the left and right OI, a signal increase was detected for all the subjects

le the right region accounted for a signal increase for 15 subjects out of 23.

anatomical location of each region of interest.

ARTICLE IN PRESS

Table 1

ROI approach: average BOLD variations and mean asymmetry indices computed in the VWFA, the occipital inferior (OI) and middle temporal (T2) regions of

interest

VWFA OI T2

Mean (SD) P value Mean (SD) P value Mean (SD) P value

Lexicality effect (N = 13)

Word reading

Left 0.03 (0.020) *** 0.04 (0.015) *** 0.011 (0.005) ***

Right 0.021 (0.014) *** 0.029 (0.01) *** 0.0055 (0.005) **

Asymmetry indices 0.009 (0.016) 0.07 0.011 (0.015) * 0.0056 (0.006) **

Non-word reading

Left 0.029 (0.015) *** 0.046 (0.01) *** 0.0077 (0.005) ***

Right 0.025 (0.013) *** 0.033 (0.011) *** 0.0057 (0.003) ***

Asymmetry indices 0.004 (0.016) 0.36 0.013 (0.014) ** 0.002 (0.005) 0.2

Words–non-words

Left 0.001 (0.011) 0.57 �0.005 (0.01) * 0.003 (0.004) **

Right �0.004 (0.009) 0.08 �0.004 (0.012) 0.08 �2.10–4 (0.004) 0.91

Asymmetry indices 0.005 (0.009) ** �0.001 (0.009) 0.52 0.0032 (0.005) **

Modality effect (N = 10)

Word reading

Left 0.019 (0.013) ** 0.032 (0.015) *** 0.007 (0.005) **

Right 0.01 (0.016) 0.11 0.017 (0.013) ** �0.001 (0.005) 0.3

Asymmetry indices 0.009 (0.021) 0.17 0.015 (0.014) ** 0.008 (0.007) **

Word listening

Left 0.008 (0.014) 0.09 �0.006 (0.013) 0.17 0.0062 (0.006) *

Right �0.004 (0.011) 0.26 �0.004 (0.015) 0.37 0.0015 (0.006) 0.47

Asymmetry indices 0.012 (0.014) * �0.002 (0.004) 0.30 0.0047 (0.005) *

Reading– listening

Left 0.011 (0.009) ** 0.038 (0.022) *** 0.0008 (0.007) 0.85

Right 0.014 (0.019) 0.06 0.021 (0.02) ** �0.0025 (0.01) 0.33

Asymmetry indices �0.003 (0.029) 0.68 0.017 (0.012) ** 0.0033 (0.006) 0.12

Univariate t tests were used to assess the significance of mean BOLD variation and mean functional asymmetry indices (left bold value minus right) during

each condition (word reading, non-word reading and word listening). Paired t tests were calculated to evaluate an effect of the lexicality (words–non-words)

and of the modality (reading– listening). *P � 0.05 **P < 0.01 ***P < 0.001.

M. Vigneau et al. / NeuroImage xx (2005) xxx–xxx 5

group as a whole (Fig. 2; t = 12.4 P < 0.001 and t = 12.5; P <

0.001 for the left and right regions, respectively).

A significant leftward asymmetry was present during word as

well as during non-word reading (Table 1). Comparing non-word to

word reading revealed larger bilateral signal increase in favor of non-

words. However, no difference in terms of asymmetry was observed.

In the second group (N = 10), significant activation was

observed during word reading in both the left and right OI, together

with a significant leftward asymmetry. On the opposite, word

listening elicited nonsignificant BOLD signal decreases in the

same areas and a nonsignificant rightward asymmetry. Accord-

ingly, leftward asymmetry during word reading was significantly

higher than during word listening.

T2 area

All subjects but one presented a BOLD increase in the left T2

area, and 15 out of 23 in the contralateral homologue (Fig. 2).

Whole group analysis revealed a significant activation during word

reading as compared to cross fixation on the left, while a trend for

significance was present on the right (N = 23; left t = 8 P < 0.001;

right t = 1.9; P = 0.06).

Comparing word to non-word reading showed significant larger

left T2 BOLD activity during word reading, leading to a leftward

asymmetry significantly larger during word than non-word reading

(Table 1).

Significant BOLD increase was detected during both reading

and listening tasks in the left hemisphere, leading to a significant

leftward asymmetry. One should note that left and right BOLD

signal variations, and asymmetry indices for the T2 area, were

equivalent in both modalities.

Whole brain approach

Word reading minus cross fixation (N = 23)

Word reading activated the bilateral ventral stream, the

cluster of activity being centered on the inferior occipital gyri

and extending from the inferior temporal to the anterior fusiform

gyri, including a peak located within the VWFA coordinates on

the left. A second cluster of activity was detected in the

posterior part of the left middle and superior temporal gyri, as

well as in their right counterparts although of a smaller extent

(Table 2, Fig. 3a).

In the parietal cortex, two bilateral activation peaks were

observed, one in the superior parietal and angular gyri, the other

centered on the inferior parietal gyri.

In the frontal lobe, a premotor network was identified in-

cluding the pre-SMA and bilateral activation of the precentral

gyrus. Within the inferior frontal gyrus, the pars triangularis,

opercularis and orbitaris were activated on the left, while it

was limited to the pars triangularis and orbitaris on the

right.

Within the activated areas, computation of FAI allowed to

detect a network of left-lateralized areas. In the frontal lobe, it

included the upper part of the precentral gyrus (x = �52, y = �6,

ARTICLE IN PRESS

Table 2

Activation peaks identified during word reading compared to cross fixation in the whole group of 23 subjects

Anatomical localization N voxels Stereotactic coordinates z scores P corrected

x y z

Occipito-temporal cortex

L inferior occipital 3950 �42 �78 �10 Inf 0.000

L VWFA �48 �62 �14 6.25 0.000

L anterior fusiform �38 �46 �22 6.20 0.000

L superior temporal �62 �48 16 4.25 0.234

L middle temporal �60 �36 �2 4.18 0.293

R lingual 2119 26 �88 �6 7.51 0.000

R inferior occipital 42 �76 �12 7.28 0.000

R anterior fusiform 38 �46 �22 5.52 0.001

R inferior temporal 50 �62 �4 5.10 0.008

R superior temporal sulcus 60 �42 10 3.90 0.606

R middle temporal 68 �44 �2 3.66 0.863

R middle occipital 47 32 �74 26 4.07 0.405

Parietal cortex

L superior parietal 904 �28 �64 50 5.76 0.000

L angular gyrus �56 �60 42 4.31 0.196

L middle occipital �26 �70 26 3.30 0.995

L inferior parietal 28 �54 �42 48 3.44 0.976

R superior parietal 433 38 �62 58 5.68 0.000

R angular gyrus 32 �56 46 4.60 0.068

R inferior parietal 64 54 �46 48 3.49 0.960

Frontal cortex

L precentral 5192 �50 2 36 6.15 0.000

L postcentral �56 �8 40 5.52 0.001

L superior precentral �48 0 56 5.29 0.003

L IFG pars opercularis �40 26 �4 5.09 0.008

L IFG pars orbitaris �48 38 �6 4.59 0.070

L IFG pars triangularis �50 26 20 4.45 0.119

L inferior precentral �64 4 22 4.24 0.245

R precentral 3579 58 12 44 5.74 0.000

R IFG pars triangularis 44 28 �2 5.65 0.001

R IFG pars triangularis 58 28 26 5.32 0.003

R superior precentral 46 2 58 4.79 0.031

R IFG pars orbitaris 54 34 �10 4.78 0.032

R middle frontal 42 18 56 3.74 0.780

R SMA 1302 8 12 54 5.80 0.000

R inferior precentral 26 68 4 18 3.58 0.919

R middle frontal orbitaris 25 32 58 �10 3.83 0.683

Cerebellum

R vermis 106 2 �58 �34 4.34 0.173

R pallidum 214 18 6 4 4.23 0.255

R thalamus 128 �2 �32 0 4.00 0.482

L putamen 160 �22 �2 8 3.77 0.755

Statistical threshold was set at P < 0.001 uncorrected for multiple comparisons, and coordinates of activation peaks are given into the MNI stereotactic space

(L: left, R: right, VWFA: Visual Word Form Area, IFG: inferior frontal gyrus, SMA: supplementary motor area).

M. Vigneau et al. / NeuroImage xx (2005) xxx–xxx6

z = 52, z score = 4.28) and the pars triangularis of the inferior

frontal gyrus (x = �46, y = 26, z = 12, z score = 3.45). In the

occipito-temporal network, it consisted of the anterior part of the

fusiform gyrus (x = �46, y = �40, z = �12, z score = 4.53) and

inferior occipital gyrus (x = �44, y = �76, z = �14, z score =

4.93). In the parietal lobe, this left asymmetry was restricted to the

angular gyrus (x = �20, y = �56, z = 22, z score = 5.35).

Word reading minus non-word reading (N = 13)

This comparison revealed three clusters of activation, all

located in the left hemisphere. In the temporal cortex, activation

was observed in the middle part of the middle temporal gyrus,

along the ventral side of the superior temporal sulcus. Within the

parietal lobe, one activation peak was detected in the angular gyrus

whereas, in the frontal lobe, one peak was uncovered in the pars

orbitaris of the inferior frontal gyrus (Table 3, Fig. 3a).

Non-word reading minus word reading (N = 13)

In the left hemisphere, two large activation peaks centered on

the inferior parietal and superior parietal gyri, respectively,

extending ventrally to the supramarginal gyrus, were detected

together with an activation of the middle occipital gyrus. The

ARTICLE IN PRESS

Fig. 3. (a, b) Whole brain approach: group results. Statistical maps of z

scores computed on the basis of mean BOLD variations (in red) and mean

asymmetry indices (in blue) for various contrasts. Volumes were thresh-

olded at P < 0.001 uncorrected for multiple comparisons and P <

0.000001 uncorrected for the conjunction analysis. Activated areas are

projected onto the average MRI of the 23 subjects normalized into the

MNI stereotactic space.

M. Vigneau et al. / NeuroImage xx (2005) xxx–xxx 7

precentral gyrus was the seat of two foci of activation: one in its

upper part, at the junction with the superior frontal sulcus, the other

in the lower part of the gyrus, posterior to the pars opercularis of

the inferior frontal gyrus. A small peak was also observed within

the posterior part of the fusiform gyrus, however, this region

elicited a deactivation during word reading (Table 3, Fig. 3a).

In the right hemisphere, the activation pattern included a cluster

centered on the superior occipital gyrus and extending dorsally to

the superior parietal gyrus and frontally to the inferior parietal

gyrus, above the supramarginal gyrus. An inferior occipital

activation, at the junction with the middle temporal gyrus, was

also detected.

Computation of asymmetry indices revealed a rightward

asymmetry in the superior occipital gyrus (x = 32, y = �74, z =

44, z score = 4.69) and precuneus (x = 12, y =�56, z = 28, z score =

4.35), while a leftward asymmetry was present in the supramarginal

gyrus (x = �62, y = �28, z = 40, z score = 3.95).

Conjunction of word reading and listening (N = 10)

Activations common to both reading and listening tasks

included a left hemisphere cluster centered along the posterior

and middle parts of the superior temporal sulcus and straddling the

middle temporal gyrus. In the right hemisphere, a symmetrical

although smaller activated area was detected (Table 4, Fig. 3b).

In the frontal cortex, activation peaks were observed in both

hemispheres but with a larger extent on the right. In the precentral

gyrus, bilateral activations were situated at the level of the

precentral sulcus duplication, close to the middle frontal gyrus.

In the pars triangularis of the inferior frontal gyrus, a cluster was

detected in its lower part within the right hemisphere, while it was

located dorsally on the left.

Computation of FAI demonstrated a leftward asymmetry in the

posterior temporal network extending from the posterior part of the

superior temporal gyrus (x = �62, y = �48, z = 20, z score = 5.13)

along the posterior end of the superior temporal sulcus (x = �54,

y = �50, z = 6, z score = 5.30).

Reading minus listening of words (N = 10)

In the bilateral occipito-temporal cortex, a large activation was

observed during word reading as compared to word listening. It

was centered on the inferior occipital gyrus and extended towards

the posterior ventral stream including the inferior temporal and

fusiform gyri. In the right hemisphere, two activation clusters were

also identified in superior parietal and postcentral gyri (Table 4,

Fig. 3b).

Within these clusters of activation, a small leftward asymmetry

was detected in the inferior occipital gyrus, posterior to the inferior

temporal gyrus (x = �46, y = �76, z = �4, z score = 3.77).

Discussion

Using an ROI analysis based on an a priori definition of the

VWFA (Jobard et al., 2003), we have shown here that this area was

involved to a similar degree during all reading tasks and activated

in every subject’s left hemisphere during word reading. This first

evidence argues for the robustness of the VWFA functional

implication during word reading. However, no difference was

found in the left VWFA activity between word and non-word

reading despite the enhanced statistical power provided by such an

a priori focal approach, which questions the reality of the

categorical specialization previously proposed for this area.

Actually, several other studies have failed to uncover significant

difference in VWFA activity between word and non-word reading

(Cohen et al., 2003; Mayall et al., 2001; Perani et al., 1999). In

fact, in Cohen’s latter study, a slight increase was even found for

consonant strings as compared to word reading, a phenomenon

ascribed to more attention given to consonants according to the

authors. Overall, if the left VWFA specialization is to be held in

terms of variation of activity related with category specificity, the

lack of difference between word and non-word reading found in

the present study, as well as in some others, would rather suggest

an extent of this specificity for all stimuli containing letters.

In our ROI approach, however, one region did show a trend for

a difference between word and non-word reading, namely, the right

homologue of the VWFA, that was more recruited by non-words

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Table 3

Lexicality effect: activation peaks identified for word minus non-word reading and for the reverse contrast

Anatomical localization N voxels Stereotactic coordinates z scores P corrected

x y z

Word reading > non-word reading (N = 13)

L angular 25 �64 �60 26 3.87 0.651

L IFG pars orbitaris 33 �50 38 �4 3.50 0.965

L middle temporal 22 �68 �46 �2 3.38 0.991

Non-word reading > word reading (N = 13)

Occipital cortex

L middle inferior occipital 75 �38 �80 6 3.49 0.960

R middle inferior occipital 184 40 �80 4 4.29 0.207

R calcarine 30 14 �68 14 3.67 0.850

Occipito-parietal cortex

L superior parietal 718 �20 �74 44 5.02 0.011

L inferior parietal 595 �52 �36 44 5.00 0.013

L supramarginal �60 �28 36 3.4 0.984

R superior occipito-parietal 1181 30 �72 42 4.92 0.018

R inferior parietal 38 �44 42 3.99 0.495

R supramarginal 50 �32 44 3.92 0.919

Temporal cortex

L posterior fusiform 27 �32 �54 �12 3.79 0.729

Frontal cortex

L precentral 107 �50 4 22 4.39 0.145

L precentral 100 �30 �12 66 3.81 0.703

L superior frontal �22 �8 60 3.63 0.884

Cerebellum

R vermis 37 6 �34 �20 4.25 0.238

Statistical threshold was set at P < 0.001 uncorrected for multiple comparisons. The word minus non-word contrast was masked by the word reading minus

fixation map (P < 0.05 uncorrected) and the reverse contrast by non-word minus fixation contrast. Coordinates of activation peaks are given into the MNI

stereotactic space (L: left, R: right, IFG: inferior frontal gyrus).

M. Vigneau et al. / NeuroImage xx (2005) xxx–xxx8

than by words. This observation is in agreement with the finding of

Tagamets et al. (2000) who found no difference between words and

consonant strings in the left occipito-temporal region (at coor-

dinates very similar to that of the VWFA ROI of the present study),

while its right counterpart was more activated by consonants than

by words.

The dissimilar behaviors of the left and right VWFA led us to

compute asymmetry indices in order to search for a more reliable

manifestation of specialization for word-like stimuli, and indeed,

we so uncovered a larger functional asymmetry index favoring the

left hemisphere VWFA during word than non-word reading. This

finding suggests that the visual specialization for words may in fact

operate through the dynamics of the interaction between left and

right VWFA rather than rely on the regional variation of activity in

the left VWFA alone. Such a dynamic inter-hemispheric mecha-

nism has been recently proposed by Poremba et al. for the

perception of species-specific calls in the monkey (Poremba et al.,

2004). These authors indeed showed that species-specific calls

elicited more activation in the left superior temporal gyrus (STG)

than in its right counterpart, while other types of sounds did not

(e.g. environmental, human voices, scrambles monkey calls. . .).However, when monkeys had been submitted to comissurectomy,

this asymmetry disappeared, indicating that the leftward FAI

observed in the intact monkeys was the result of a reduced activity

in the right STG under left-hemisphere control. A similar

mechanism could account for the greater left lateralization during

word reading as compared to the reading of non-words observed in

our study or of consonants as in Tagamets et al. study. As a matter

of fact, since BOLD signal variations were extremely similar in the

left VWFA during all reading conditions, the left predominant FAI

during word reading appears to be largely due to a reduced activity

of the right hemisphere VWFA homologue during this task as

compared to non-word reading. Reduced activity in the right

VWFA during word as compared to non-word reading could be

triggered by active suppression mechanisms stemming from the

left hemisphere when subjects read words.

Our results, combined with Poremba’s observations, indicate

that this inter-hemispheric shift initiated in the left VWFA

constitutes a critical step in the stream going from visual analysis

up to verbal semantic integration. Such a hypothesis is supported

by the analysis of activity of the visual and semantic ROIs of the

ventral route during the presentation of words and non-words. On

the one hand, significant leftward asymmetry was present in the

visual OI area during both word and non-word reading, without

any difference due to lexicality. This is consistent with studies

reporting a leftward dedication of visual areas during the

processing of graphical features of letter assemblies conveying

meaning or not (Kuriki et al., 1998; Pugh et al., 1996; Uchida et al.,

1999). On the other hand, larger leftward asymmetry due to larger

left hemisphere activity increase was observed in the T2 semantic

area during word than non-word reading. Thus, the VWFA seems

to be a place where the language-specificity of the stimulus is

tagged through a reduced activity of the right hemisphere, routing

further processing towards semantic areas.

As a matter of fact, semantic areas are specifically targeted

during word reading as compared to non-word reading. A larger

activity in the posterior temporal areas, as well as in the pars

orbitaris of the inferior frontal gyrus, such as uncovered by the

ARTICLE IN PRESS

Table 4

Modality effect: activation peaks identified by the conjunction of word listening and word reading and areas more activated during word reading than word

listening

Anatomical localization N voxels Stereotactic coordinates z scores P corrected

x y z

Listening and reading of words: conjunction (N = 10)

Temporal cortex

L superior temporal sulcus 582 �54 �46 8 6.97 0.000

L middle temporal �50 �44 4 6.81 0.000

L superior temporal �64 �48 18 6.25 0.000

L inferior temporal 2 �64 �52 �14 4.80 0.046

R superior temporal sulcus 241 60 �42 10 5.85 0.000

R middle temporal 72 �38 0 4.93 0.027

R middle temporal 2 68 �34 �4 4.86 0.036

Frontal cortex

L precentral 12 �48 0 50 4.94 0.026

L IFG pars triangularis 3 �58 32 10 4.95 0.024

L SMA 35 �6 6 56 5.56 0.001

L SMA 8 �6 �4 66 5.15 0.010

R precentral 283 60 �4 46 7.40 0.000

R precentral 56 10 44 6.95 0.000

R IFG pars triangularis 122 38 32 0 5.81 0.000

R IFG pars triangularis 3 50 20 24 4.82 0.042

Cerebellum

L cerebellum 7 �30 �66 �28 5.25 0.006

Word reading > word listening (N = 10)

Occipito-temporal cortex

L inferior occipital 1194 �42 �78 �10 6.95 0.000

L middle occipital �30 �90 2 4.15 0.321

L anterior fusiform �38 �48 �20 3.37 0.989

R lingual 968 24 �88 �6 5.27 0.004

R inferior occipital 42 �78 �16 5.24 0.004

R inferior temporal 48 �62 �4 4.24 0.243

R middle occipital 86 32 �76 26 4.28 0.214

R fusiform 26 38 �44 �22 3.98 0.509

Parietal cortex

L superior parietal 48 �26 �64 52 3.75 0.77

R superior parietal 132 36 �62 58 3.99 0.495

Frontal cortex

L postcentral 11 �36 �12 32 3.39 0.986

L postcentral 13 �50 �10 26 3.21 0.999

R postcentral 130 48 �10 32 3.93 0.566

R thalamus 10 24 �32 14 3.98 0.5

Conjunction analysis statistical threshold was set at P < 0.00001 uncorrected. The word reading minus listening map was thresholded at P < 0.001

uncorrected and masked by the word reading minus fixation contrast (P < 0.05 uncorrected). Coordinates of activation peaks are given into the MNI

stereotactic space (L: left, R: right, IFG: inferior frontal gyrus, SMA: supplementary motor area).

M. Vigneau et al. / NeuroImage xx (2005) xxx–xxx 9

whole brain analysis of our study, has been consistently docu-

mented (Cappa et al., 1998; Herbster et al., 1997; Petersen et al.,

1990; Sakurai et al., 2000). These areas are known to be involved

in semantic processing (Chee et al., 2000; Grossman et al., 2002;

Heim et al., 2002; Jennings et al., 1998; Perani et al., 1999)

(Bookheimer et al., 1995; Cappa et al., 1998; Petersen et al., 1988;

Poldrack et al., 1999; Price et al., 1994, 1996, 1997; Warburton et

al., 1996; Wise et al., 1991, 2001). The present study builds upon

these previous findings, showing that activity in these fronto-

temporal areas is leftward lateralized and that the recruitment of

posterior temporal areas is modality-independent. A greater

involvement of lexico-semantic regions for words than non-words

could be in apparent contradiction with the ones of Mechelli and

Paulesu showing a greater involvement of these areas in a

pseudoword versus word reading comparison (Mechelli et al.,

2002; Paulesu et al., 2000). However, since pseudowords follow

the orthographical rules of a given language, they are visually quite

similar to familiar words, and this similarity may suffice in

engaging lexico-semantic networks. In contrast, since non-words

can immediately be identified as being meaningless letters

assemblies, non-words visual configuration may be too remote

from one of the words to trigger these networks.

By contrast, the bilateral ventral route activations were, as

expected, specific of the visual modality during word processing,

although the anterior part of the fusiform gyrus was activated by

word listening as well. Interestingly, within the left ventral route,

the posterior part of the fusiform gyrus showed a larger BOLD

variation for non-words than words reading. In his recent findings,

Cohen observed a medial occipito-temporal activation during word

reading but not for spoken words, leading to propose that this more

medial region would be the real Visual Word Form Area (Cohen et

al., 2004). Because our temporal coordinates were very close to

ARTICLE IN PRESSM. Vigneau et al. / NeuroImage xx (2005) xxx–xxx10

Cohen’s (x = �36, y = �60, z = �12 in Cohen’s study; x = �32,

y = �54, z = �12 in our study), we could hypothesize that this

region would be in fact a better candidate for the VWFA than the

one we chose (which could then correspond to the Left Inferior

Temporal Multimodal Area). Actually, since our left temporal

region elicited a deactivation during word reading, it seems

unlikely to coincide with Cohen’s VWFA.

The superior parietal cortices recruited only in presence of

visual stimuli were also more activated by non-words than by

words. These findings attest the visuo-spatial processing special-

ization of these bilateral parieto-occipital areas, which is further

reinforced by the observation of their rightward lateralization

during non-word reading.

That non-word reading (as compared to word reading) yielded a

larger activation of the phonological networks may help explaining

some of the discrepant results in the literature concerning left

VWFA activity during reading. One could indeed hypothesize

during reading the existence in the VWFA of a process that would

run until completion for words but would be interrupted for non-

words. In the present study, the larger activity observed in

phonological areas during non-word reading can be taken as an

indication that the subjects did complete the non-word reading

task. This may be the case because we emphasized, during the

instruction period, the obligation for the subjects to read the entire

stimuli and to attend non-words as much as words, despite their

unfamiliar structure. Accordingly, networks allowing the grapho-

phonemic conversion necessary to access to pronunciation were

more activated during non-word reading. The pars opercularis of

the IFG and the supramarginal gyrus that are part of the articulatory

loop (Fiez, 1997; Fiez et al., 1999; Paulesu et al., 1993; Poldrack et

al., 1999), together with the precentral and the superior temporal

gyri constituting an auditory–motor coordination system at work

during syllables (Wildgruber et al., 2001) and phoneme articulation

(Bookheimer et al., 2000), were indeed more activated by non-

word reading. This confirms that subjects did process the non-

words, making possible that results of previous studies showing

larger activity during word than non-word reading originated from

an early interruption of non-word reading processes.

Every visual stimulus being associated with a phonological

output in this experiment, we could conjecture that the same

activity is elicited in the left VWFA as long as a phonological

output per se is required. Nevertheless, if the pronunciation aspect

was critical in the activation of the VWFA, its activity should be

somewhat modulated by the ease with which this assembly is

affected. In the case of consonant strings reading, the reported

subjects’ efforts to read out these stimuli being greater, a BOLD

difference would then be expected in the VWFA, compared to

more easily assembled stimuli. This pattern of results is not the one

we observe in this experiment. We believe the equivalent degree of

activation in the VWFA for all stimuli reflects the engagement of a

similar visual processing for both words and non-words aimed at

identifying familiar visual units as described by Warrington and

Shallice (1980). On the contrary though, the greater inter-hemi-

spheric balance in favor of the left seems to characterize

specifically the activity taking place during word reading.

We have shown that activity during word reading is charac-

terized by both a leftward shift in the VWFA and the recruitment of

integrative semantic areas. Therefore, the VWFA role seems to be

critical within the stream of verbal visual processing, binding

visual and verbal representation of words. This view is consistent

with a role for this region in identifying, on the basis of letters

abstract identities, these units that can easily be bound to a verbal

representation, may the latter be lexical or pre-lexical. As such, in

the framework of reading, we would predict the involvement of the

VWFA in all reading tasks, with a left asymmetry being observed

only when the identification of these visual units can lead to the

activation of a known verbal unit. In this study, we showed that this

left asymmetry was observed during real word reading and not

during non-word reading purportedly because their visual form can

be bound to a semantic representation. Although we did not

address this issue in the present study, previous results reporting

leftward lateralization of the VWFA during pseudoword reading

indicate that this binding may also occur for pre-lexical units (such

as graphemes, syllables or morphemes) and would constitute a

critical step of visual identification necessary for an access through

a grapho-phonological route.

Whether or not the VWFA could play a similar role for other

kind of visual stimuli remains an open issue. Price et al. have

indeed demonstrated the VWFA implication during picture naming

(Price and Devlin, 2003), questioning its specificity for verbal

material. In the same vein, leftward asymmetry of VWFA activity

has been observed during mental imagery (or perception) of

pictures of objects as compared to non-objects (Mazard et al., in

press). Based on these evidences, we suggest that the VWFA could

truly act the same way on pictures as it does for words.

Assuming that binding of visual and verbal representations

occurs in the VWFA would also explain reports of activity in this

area during word listening as observed by previous authors (Booth

et al., 2002a,b; Price et al., 2003a), as well as in the present study.

In this context, we believe that the left asymmetry observed in the

VWFA during word reading (caused by a small increase of activity

during word listening, but mainly by a large decrease in the right

VWFA) originates from top–down afferences from left semantic

areas. In the case of word listening, the use in most of these studies

of concrete stimuli with high imagery values makes it plausible for

the subjects to proceed to an automatic binding between their

meaning and a top–down activation of their visual attributes. That

auditory presentation of concrete word definitions (leading to the

construction of a mental image) as compared to that of abstract

word definitions (preventing the emergence of a visual representa-

tion) elicits activation of an area encompassing the left VWFA

(Mellet et al., 1998) further supports the idea that this area is the

place where visual and verbal representations are linked.

In conclusion, the so-called VWFA should not be considered as

an area devoted to written language only but rather as a place

where visuo-verbal associations occur, which makes it critical for

the acquisition of reading skills.

Acknowledgments

The authors are grateful to Fabrice Crivello, Marc Joliot and

Guy Perchey for their help in data acquisition and analysis. M.

Vigneau is supported by a grant from the CEA and the Basse-

Normandie Regional Council.

References

Beauregard, M., Chertkow, H., Bub, D., Murtha, S., Dixon, R., Evans, A.,

1997. The neural substrates for concrete, abstract, and emotional word

lexica: a positron emission tomography. J. Cogn. Neurosci. 9, 441–461.

ARTICLE IN PRESSM. Vigneau et al. / NeuroImage xx (2005) xxx–xxx 11

Binder, J.R., McKiernan, K.A., Parsons, M.E., Westbury, C.F., Possing,

E.T., Kaufman, J.N., Buchanan, L., 2003. Neural correlates of

lexical access during visual word recognition. J. Cogn. Neurosci. 15,

372–393.

Bookheimer, S.Y., Zeffiro, T.A., Blaxton, T., Gaillard, W., Theodore, W.,

1995. Regional cerebral blood flow during object naming and word

reading. Hum. Brain Mapp. 3, 93–106.

Bookheimer, S.Y., Zeffiro, T.A., Blaxton, T.A., Gaillard, W., Theodore,

W.H., 2000. Activation of language cortex with automatic speech tasks.

Neurology 55, 1151–1157.

Booth, J.R., Burman, D.D., Meyer, J.R., Gitelman, D.R., Parrish, T.B.,

Mesulam, M.M., 2002a. Functional anatomy of intra- and cross-modal

lexical tasks. NeuroImage 16, 7–22.

Booth, J.R., Burman, D.D., Meyer, J.R., Gitelman, D.R., Parrish, T.B.,

Mesulam, M.M., 2002b. Modality independence of word comprehen-

sion. Hum. Brain Mapp. 16, 251–261.

Cappa, S.F., Perani, D., Schnur, T., Tettamanti, M., Fazio, F., 1998. The

effects of semantic category and knowledge type on lexical–semantic

access: a PET study. NeuroImage 8, 350–359.

Chee, M.W.L., Weekes, B., Lee, K.M., Soon, C.S., Schreiber, A., Hoon,

J.J., Chee, M., 2000. Overlap and dissociation of semantic processing of

Chinese characters, English words, and pictures: evidence from fMRI.

NeuroImage 12, 392–403.

Cohen, L., Dehaene, S., Naccache, L., Lehericy, S., Dehaene-Lambertz,

G., Henaff, M.A., Michel, F., 2000. The visual word form area:

spatial and temporal characterization of an initial stage of reading in

normal subjects and posterior split-brain patients. Brain 123 (Pt. 2),

291–307.

Cohen, L., Lehericy, S., Chochon, F., Lemer, C., Rivaud, S., Dehaene, S.,

2002. Language-specific tuning of visual cortex? Functional properties

of the visual word form area. Brain 125, 1054–1069.

Cohen, L., Martinaud, O., Lemer, C., Lehericy, S., Samson, Y., Obadia, M.,

Slachevsky, A., Dehaene, S., 2003. Visual word recognition in the left

and right hemispheres: anatomical and functional correlates of

peripheral alexias. Cereb. Cortex 13, 1313–1333.

Cohen, L., Jobert, A., Le, B.D., Dehaene, S., 2004. Distinct unimodal and

multimodal regions for word processing in the left temporal cortex.

NeuroImage 23, 1256–1270.

Content, A., Mousty, P., Radeau, M., 1990. Brulex, une base de donnees

lexicales informatisee pour le francais ecrit et parle. Annee Psychol. 90,

551–566.

Dehaene, S., Naccache, L., Cohen, L., Bihan, D.L., Mangin, J.F.,

Poline, J.B., Riviere, D., 2001. Cerebral mechanisms of word

masking and unconscious repetition priming. Nat. Neurosci. 4,

752–758.

Dehaene, S., LeClec’H, G., Poline, J.B., LeBihan, D., Cohen, L., 2002. The

visual word form area: a prelexical representation of visual words in the

fusiform gyrus. NeuroReport 13, 321–325.

Fiez, J.A., 1997. Phonology, semantics, and the role of the left inferior

prefrontal cortex. Hum. Brain Mapp. 5, 79–83.

Fiez, J.A., Balota, D.A., Raichle, M.E., Petersen, S.E., 1999. Effects of

lexicality, frequency, and spelling-to-sound consistency on the func-

tional anatomy of reading. Neuron 24, 205–218.

Friston, K.J., Holmes, A.P., Poline, J.B., Grasby, P.J., Williams, S.C.,

Frackowiak, R.S., Turner, R., 1995. Analysis of fMRI time-series

revisited. NeuroImage 2, 45–53.

Grossman, M., Koenig, P., DeVita, C., Glosser, G., Alsop, D., Detre, J.,

Gee, J., 2002. Neural representation of verb meaning: an fMRI study.

Hum. Brain Mapp. 15, 124–134.

Heim, S., Opitz, B., Friederici, A.D., 2002. Broca’s area in the human brain

is involved in the selection of grammatical gender for language

production: evidence from event-related functional magnetic resonance

imaging. Neurosci. Lett. 328, 101–104.

Herbster, A.N., Mintun, M.A., Nebes, R.D., Becker, J.T., 1997. Regional

cerebral blood flow during word and nonword reading. Hum. Brain

Mapp. 5, 84–92.

Howard, D., Patterson, K., Wise, R., Brown, W.D., Friston, K., Weiller, C.,

Frackowiak, R., 1992. The cortical localization of the lexicons. Positron

emission tomography evidence. Brain 115 (Pt. 6), 1769–1782.

Jennings, J.M., McIntosh, A.R., Kapur, S., Zipursky, R.B., Houle, S., 1998.

Functional network differences in schizophrenia: a rCBF study of

semantic processing. NeuroReport 9, 1697–1700.

Jobard, G., Crivello, F., Tzourio-Mazoyer, N., 2003. Evaluation of the dual

route theory of reading: a metaanalysis of 35 neuroimaging studies.

NeuroImage 20, 693–712.

Joubert, S., Beauregard, M., Walter, N., Bourgouin, P., Beaudoin, G.,

Leroux, J.M., Karama, S., Lecours, A.R., 2004. Neural correlates of

lexical and sublexical processes in reading. Brain Lang. 89, 9–20.

Kiehl, K.A., Liddle, P.F., Smith, A.M., Mendrek, A., Forster, B.B., Hare,

R.D., 1999. Neural pathways involved in the processing of concrete and

abstract words. Hum. Brain Mapp. 7, 225–233.

Kuriki, S., Takeuchi, F., Hirata, Y., 1998. Neural processing of words in the

human extrastriate visual cortex. Cogn. Brain Res. 6, 193–203.

Mayall, K., Humphreys, G.W., Mechelli, A., Olson, A., Price, C.J., 2001.

The effects of case mixing on word recognition: evidence from a PET

study. J. Cogn. Neurosci. 13, 844–853.

Mazard, A., Laou, L., Joliot, M., Mellet, E., in press. Neural impact of the

semantic content of visual mental images and visual percepts. Cognit.

Brain Res.

Mechelli, A., Penny, W.D., Price, C.J., Gitelman, D.R., Friston, K.J.,

2002. Effective connectivity and intersubject variability: using a

multisubject network to test differences and commonalities. Neuro-

Image 17, 1459–1469.

Mellet, E., Tzourio, N., Denis, M., Mazoyer, B., 1998. Cortical anatomy of

mental imagery of concrete nouns based on their dictionary definition.

NeuroReport 9, 803–808.

Oldfield, R.C., 1971. The assessment and analysis of handedness: the

Edinburgh inventory. Neuropsychologia 9, 97–113.

Pammer, K., Hansen, P.C., Kringelbach, M.L., Holliday, I., Barnes, G.,

Hillebrand, A., Singh, K.D., Cornelissen, P.L., 2004. Visual word

recognition: the first half second. NeuroImage 22, 1819–1825.

Paulesu, E., Frith, C.D., Frackowiak, R.S., 1993. The neural correlates of

the verbal component of working memory. Nature 362, 342–345.

Paulesu, E., McCrory, E., Fazio, F., Menoncello, L., Brunswick, N., Cappa,

S.F., Cotelli, M., Cossu, G., Corte, F., Lorusso, M., Pesenti, S.,

Gallagher, A., Perani, D., Price, C., Frith, C.D., Frith, U., 2000. A

cultural effect on brain function. Nat. Neurosci. 3, 91–96.

Perani, D., Cappa, S.F., Schnur, T., Tettamanti, M., Collina, S., Rosa, M.M.,

Fazio, F., 1999. The neural correlates of verb and noun processing—A

PET study. Brain 122, 2337–2344.

Petersen, S.E., Fox, P.T., Posner, M.I., Mintun, M., Raichle, M.E., 1988.

Positron emission tomographic studies of the cortical anatomy of single-

word processing. Nature 331, 585–589.

Petersen, S.E., Fox, P.T., Snyder, A.Z., Raichle, M.E., 1990. Activation of

extrastriate and frontal cortical areas by visual words and word-like

stimuli. Science 249, 1041–1044.

Poldrack, R.A., Wagner, A.D., Prull, M.W., Desmond, J.E., Glover, G.H.,

Gabrieli, J.D., 1999. Functional specialization for semantic and

phonological processing in the left inferior prefrontal cortex. Neuro-

Image 10, 15–35.

Polk, T.A., Stallcup, M., Aguirre, G.K., Alsop, D.C., D’Esposito, M.,

Detre, J.A., Farah, M.J., 2002. Neural specialization for letter

recognition. J. Cogn. Neurosci. 14, 145–159.

Poremba, A., Malloy, M., Saunders, R.C., Carson, R.E., Herscovitch, P.,

Mishkin, M., 2004. Species-specific calls evoke asymmetric activity in

the monkey’s temporal poles. Nature 427, 448–451.

Price, C.J., Devlin, J.T., 2003. The myth of the visual word form area.

NeuroImage 19, 473–481.

Price, C.J., Wise, R.J.S., Watson, J.D.G., Patterson, K., Howard, D.,

Frackowiak, R.S.J., 1994. Brain activity during reading. The effect of

exposure duration and task. Brain 117, 1255–1269.

Price, C.J., Wise, R.J., Frackowiak, R.S., 1996. Demonstrating the implicit

processing of visually presented words and pseudowords. Cereb. Cortex

6, 62–70.

ARTICLE IN PRESSM. Vigneau et al. / NeuroImage xx (2005) xxx–xxx12

Price, C.J., Moore, C.J., Humphreys, G.W., Wise, R.J., 1997. Segregating

semantic from phonological processes during reading. J. Cogn. Neuro-

sci. 9, 727–733.

Price, C.J., Gorno-Tempini, M.L., Graham, K.S., Biggio, N., Mechelli, A.,

Patterson, K., Noppeney, U., 2003a. Normal and pathological reading:

converging data from lesion and imaging studies. NeuroImage 20

(Suppl. 1), S30–S41.

Price, C.J., Winterburn, D., Giraud, A.L., Moore, C.J., Noppeney, U.,

2003b. Cortical localisation of the visual and auditory word form areas:

a reconsideration of the evidence. Brain Lang. 86, 272–286.

Pugh, K.R., Shaywitz, B.A., Shaywitz, S.E., Constable, R.T., Skudlarski, P.,

Fulbright, R.K., Bronen, R.A., Shankweiler, D.P., Katz, L., Fletcher,

J.M., Gore, J.C., 1996. Cerebral organization of component processes in

reading. Brain 119 (Pt. 4), 1221–1238.

Rees, G., Russell, C., Frith, C.D., Driver, J., 1999. Inattentional blindness

versus inattentional amnesia for fixated but ignored words. Science 286,

2504–2507.

Sakurai, Y., Momose, T., Iwata, M., Sudo, Y., Ohtomo, K., Kanazawa, I.,

2000. Different cortical activity in reading of Kanji words, Kana words

and Kana nonwords. Brain Res. Cogn Brain Res. 9, 111–115.

Shaywitz, B.A., Shaywitz, S.E., Pugh, K.R., Mencl, W.E., Fulbright,

R.K., Skudlarski, P., Constable, R.T., Marchione, K.E., Fletcher, J.M.,

Lyon, G.R., Gore, J.C., 2002. Disruption of posterior brain systems

for reading in children with developmental dyslexia. Biol. Psychiatry

52, 101–110.

Tagamets, M.A., Novick, J.M., Chalmers, M.L., Friedman, R.B., 2000. A

parametric approach to orthographic processing in the brain: an fMRI

study. J. Cogn. Neurosci. 12, 281–297.

Tzourio-Mazoyer, N., Josse, G., Crivello, F., Mazoyer, B., 2004. Inter-

individual variability in the hemispheric organization for speech.

NeuroImage 21, 422–435.

Uchida, I., Kikyo, H., Nakajima, K., Konishi, S., Sekihara, K., Miyashita,

Y., 1999. Activation of lateral extrastriate areas during orthographic

processing of Japanese characters studied with fMRI. NeuroImage 9,

208–215.

Warburton, E.A., Wise, R.J.S., Price, C.J., Weiller, C., Hadar, U., Ramsay,

S., Frackowiak, R.S.J., 1996. Noun and verb retrieval by normal

subjects. Studies with PET. Brain 119, 159–179.

Warrington, E.K., Shallice, T., 1980. Word-form dyslexia. Brain 103,

99–112.

Wildgruber, D., Ackermann, H., Grodd, W., 2001. Differential contribu-

tions of motor cortex, basal Ganglia, and cerebellum to speech motor

control: effects of syllable repetition rate evaluated by fMRI. Neuro-

Image 13, 101–109.

Wise, R., Chollet, F., Hadar, U., Friston, K.J., Hoffner, E., Frackowiak,

R.S.J., 1991. Distribution of cortical networks involved in word

comprehension and word retrieval. Brain 114, 1803–1817.

Wise, R.J.S., Scott, S.K., Blank, S.C., Mummery, C.J., Murphy, K.,

Warburton, E.A., 2001. Separate neural subsystems within FWernicke’s

area_. Brain 124, 83–95.