Neural support of manual preference revealed by BOLD variations during right and left finger-tapping in a sample of 287 healthy adults balanced for handedness.

We have identified the brain areas involved in Manual Preference (MP) in 143 left-handers (LH) and 144 right-handers (RH). First, we selected the pairs of homotopic regions of interest (hROIs) of the AICHA atlas with significant contralateral activation and asymmetry during the right hand and the left hand Finger-Tapping (FT) both in RH and LH. Thirteen hROIs were selected, including the primary and secondary sensorimotor and premotor cortices, thalamus, dorsal putamen, and cerebellar lobule IV. In both groups, contralateral activations and ipsilateral deactivations were seen, with stronger asymmetries when the preferred hand was used. Comparing with different models for the prediction of MP, we found that the differences in activity during preferred hand minus non-preferred hand movement in 11 contralateral and/or ipsilateral hROIS were best at explaining handedness distribution. Two different mechanisms were identified: 1. Stronger contralateral activity of cortical and cerebellar motor areas during right hand movement, seen in both groups but modulated by handedness; 2. Stronger deactivation in ipsilateral areas during dominant hand movement in both groups, LH here mirroring RH. The present study thus demonstrates that handedness neural support is complex and not simply based on a mirrored organization of hand motor areas.

Intracortical Myelination of Heschl's Gyrus and the Planum Temporale Varies With Heschl's Duplication Pattern and Rhyming Performance: An Investigation of 440 Healthy Volunteers.

We investigated, in 445 healthy adults whose Heschl's gyrus (HG) gyrification patterns had been previously identified, how an in vivo MRI marker of intracortical myelination of HG and the planum temporale (PT) varied as a function of HG gyrification pattern and, in cases of duplication, of anatomical characteristics of the second HG (H2). By measuring the MRI T1/T2 ratio in regions of interest covering the first HG (H1), H2 in cases of common stem (H2CSD), or complete posterior duplication (H2CPD) and the PT, we showed that H1 had the highest T1/T2 values, while the PT had the lowest. The major impact of duplication was a decrease in both H1 and PT T1/T2 values in cases of left CPD. Concerning H2, the right and left T1/T2 values of right H2CSD were closer to those of H1, and those of left H2CPD were closer to those of PT. After adjusting for verbal skills, rhyming performance was not associated with T1/T2 values in left regions, but it decreased with increasing right PT T1/T2 values. These results reveal the existence of hemispheric differences in H2 myelination and underline the importance of neuroimaging markers of intracortical myelination for investigating brain structure-function relationships.

BIL&GIN: A neuroimaging, cognitive, behavioral, and genetic database for the study of human brain lateralization.

We report on a database, named BIL&GIN, designed for investigating the cognitive, behavioral, genetic, and brain morphological/functional correlates of hemispheric specialization. The database contains records from a sample of 453 adult participants enriched in left-handers (45%, N=205) as compared to the general population. For each subject, socio-demographic data, hand and eye laterality, family handedness, and cognitive abilities in the language, motor, visuo-spatial, and numerical domains have been recorded. T1-MRI and DTI data were also acquired, as well as resting-state functional MRI. Task-evoked functional MRI was performed in a sub-sample of 303 subjects (157 left-handers) using a customized functional battery of 16 cognitive tasks exploring the same three cognitive domains. Performances at the tasks executed in the magnet as well as post-acquisition debriefing were recorded. A saliva sample was obtained from the subjects of this sub-sample from which DNA was extracted. The BIL&GIN contains results of imaging data processing for each subject, namely maps of tissue (GM, WM, CSF) probability, cortical thickness, cortical surface, and diffusion parameters as well as regional values of these phenotypes for regions of both AAL and FreeSurfer parcellations. For the subjects who underwent FMRI, individual SPM contrast maps for each of the 8 runs were also calculated and included in the database, as well as corresponding BOLD variations in ROIs of the AAL and AICHA atlases, and Wilke's hemispheric functional lateralization index. The BIL&GIN data sharing is based on a collaborative model.

Relationships between hand laterality and verbal and spatial skills in 436 healthy adults balanced for handedness.

The relationship between manual laterality and cognitive skills remains highly controversial. Some studies have reported that strongly lateralised participants had higher cognitive performance in verbal and visuo-spatial domains compared to non-lateralised participants; however, others found the opposite. Moreover, some have suggested that familial sinistrality and sex might interact with individual laterality factors to alter cognitive skills. The present study addressed these issues in 237 right-handed and 199 left-handed individuals. Performance tests covered various aspects of verbal and spatial cognition. A principal component analysis yielded two verbal and one spatial factor scores. Participant laterality assessments included handedness, manual preference strength, asymmetry of motor performance, and familial sinistrality. Age, sex, education level, and brain volume were also considered. No effect of handedness was found, but the mean factor scores in verbal and spatial domains increased with right asymmetry in motor performance. Performance was reduced in participants with a familial history of left-handedness combined with a non-maximal preference strength in the dominant hand. These results elucidated some discrepancies among previous findings in laterality factors and cognitive skills. Laterality factors had small effects compared to the adverse effects of age for spatial cognition and verbal memory, the positive effects of education for all three domains, and the effect of sex for spatial cognition.

What is right-hemisphere contribution to phonological, lexico-semantic, and sentence processing? Insights from a meta-analysis.

To evaluate the relative role of left and right hemispheres (RH) and describe the functional anatomy of RH during ortholinguistic tasks, we re-analyzed the 128 papers of a former left-hemisphere (LH) meta-analysis (Vigneau et al., 2006). Of these, 59 articles reported RH participation, providing 105 RH language contrasts including 218 peaks compared to 728 on the left, a proportion reflecting the LH language dominance. To describe inter-hemispheric interactions, in each of the language contrasts involving both hemispheres, we distinguished between unilateral and bilateral peaks, i.e. having homotopic activation in the LH in the same contrast. We also calculated the proportion of bilateral peaks in the LH. While the majority of LH peaks were unilateral (79%), a reversed pattern was observed in the RH; this demonstrates that, in contrast to the LH, the RH works in an inter-hemispheric manner. To analyze the regional pattern of RH participation, these unilateral and bilateral peaks were spatially clustered for each language component. Most RH phonological clusters corresponded to bilateral recruitment of auditory and motor cortices. Notably, the motor representation of the mouth and phonological working memory areas were exclusively left-lateralized, supporting the idea that the RH does not host phonological representations. Right frontal participation was not specific for the language component involved and appeared related to the recruitment of attentional and working memory areas. The fact that RH participation during lexico-semantic tasks was limited to these executive activations is compatible with the hypothesis that active inhibition is exerted from the LH during the processing of meaning. Only during sentence/text processing tasks a specific unilateral RH-temporal involvement was noted, likely related to context processing. These results are consistent with split-brain studies that found that the RH has a limited lexicon, with no phonological abilities but active involvement in the processing of context.

Large-scale plurimodal networks common to listening to, producing and reading word lists: an fMRI study combining task-induced activation and intrinsic connectivity in 144 right-handers.

We aimed at identifying plurimodal large-scale networks for producing, listening to and reading word lists based on the combined analyses of task-induced activation and resting-state intrinsic connectivity in 144 healthy right-handers. In the first step, we identified the regions in each hemisphere showing joint activation and joint asymmetry during the three tasks. In the left hemisphere, 14 homotopic regions of interest (hROIs) located in the left Rolandic sulcus, precentral gyrus, cingulate gyrus, cuneus and inferior supramarginal gyrus (SMG) met this criterion, and 7 hROIs located in the right hemisphere were located in the preSMA, medial superior frontal gyrus, precuneus and superior temporal sulcus (STS). In a second step, we calculated the BOLD temporal correlations across these 21 hROIs at rest and conducted a hierarchical clustering analysis to unravel their network organization. Two networks were identified, including the WORD-LIST_CORE network that aggregated 14 motor, premotor and phonemic areas in the left hemisphere plus the right STS that corresponded to the posterior human voice area (pHVA). The present results revealed that word-list processing is based on left articulatory and storage areas supporting the action-perception cycle common not only to production and listening but also to reading. The inclusion of the right pHVA acting as a prosodic integrative area highlights the importance of prosody in the three modalities and reveals an intertwining across hemispheres between prosodic (pHVA) and phonemic (left SMG) processing. These results are consistent with the motor theory of speech postulating that articulatory gestures are the central motor units on which word perception, production, and reading develop and act together.

Neuroimaging supports the representational nature of the earliest human engravings.

The earliest human graphic productions, consisting of abstract patterns engraved on a variety of media, date to the Lower and Middle Palaeolithic. They are associated with anatomically modern and archaic hominins. The nature and significance of these engravings are still under question. To address this issue, we used functional magnetic resonance imaging to compare brain activations triggered by the perception of engraved patterns dating between 540 000 and 30 000 years before the present with those elicited by the perception of scenes, objects, symbol-like characters and written words. The perception of the engravings bilaterally activated regions along the ventral route in a pattern similar to that activated by the perception of objects, suggesting that these graphic productions are processed as organized visual representations in the brain. Moreover, the perception of the engravings led to a leftward activation of the visual word form area. These results support the hypothesis that these engravings have the visual properties of meaningful representations in present-day humans, and could have served such purpose in early modern humans and archaic hominins.

Mental calculation in a prodigy is sustained by right prefrontal and medial temporal areas.

Calculating prodigies are individuals who are exceptional at quickly and accurately solving complex mental calculations. With positron emission tomography (PET), we investigated the neural bases of the cognitive abilities of an expert calculator and a group of non-experts, contrasting complex mental calculation to memory retrieval of arithmetic facts. We demonstrated that calculation expertise was not due to increased activity of processes that exist in non-experts; rather, the expert and the non-experts used different brain areas for calculation. We found that the expert could switch between short-term effort-requiring storage strategies and highly efficient episodic memory encoding and retrieval, a process that was sustained by right prefrontal and medial temporal areas.

Intra-hemispheric intrinsic connectivity asymmetry and its relationships with handedness and language Lateralization.

Asymmetry in intra-hemispheric intrinsic connectivity, and its association with handedness and hemispheric dominance for language, were investigated in a sample of 290 healthy volunteers enriched in left-handers (52.7%). From the resting-state FMRI data of each participant, we derived an intra-hemispheric intrinsic connectivity asymmetry (HICA) matrix as the difference between the left and right intra-hemispheric matrices of intrinsic correlation computed for each pair of the AICHA atlas ROIs. We defined a similarity measure between the HICA matrices of two individuals as the correlation coefficient of their corresponding elements, and computed for each individual an index of intra-hemispheric intrinsic connectivity asymmetry as the average similarity measure of his HICA matrix to those of the other subjects of the sample (HICAs). Gaussian-mixture modeling of the age-corrected HICAs sample distribution revealed that two types of HICA patterns were present, one (Typical_HICA) including 92.4% of the participants while the other (Atypical_HICA) included only 7.6% of them, mostly left-handers. In addition, we investigated the relationship between asymmetry in intra-hemispheric intrinsic connectivity and language hemispheric dominance, including a potential effect of handedness on this relationship, thanks to an FMRI acquisition during language production from which an hemispheric functional lateralization index for language (HFLI) and a type of hemispheric dominance for language, namely leftward, ambilateral, or rightward, were derived for each individual. There was a significant association between the types of language hemispheric dominance and of intra-hemispheric intrinsic connectivity asymmetry, occurrence of Atypical_HICAs individuals being very high in the group of individuals rightward-lateralized for language (80%), reduced in the ambilateral group (19%) and rare in individuals leftward-lateralized for language (less than 3%). Quantitatively, we found a significant positive linear relationship between the HICAs and HFLI indices, with an effect of handedness on the intercept but not on the slope of this relationship. These findings demonstrate that handedness and hemispheric dominance for language are significantly but independently associated with the asymmetry of intra-hemispheric intrinsic connectivity. These findings suggest that asymmetry in intra-hemispheric connectivity is a variable phenotype shaped in part by hemispheric lateralization for language, but possibly also depending on other lateralized functions.

Descriptive anatomy of Heschl's gyri in 430 healthy volunteers, including 198 left-handers.

This study describes the gyrification patterns and surface areas of Heschl's gyrus (HG) in 430 healthy volunteers mapped with magnetic resonance imaging. Among the 232 right-handers, we found a large occurrence of duplication (64 %), especially on the right (49 vs. 37 % on the left). Partial duplication was twice more frequent on the left than complete duplication. On the opposite, in the right hemisphere, complete duplication was 10 % more frequent than partial duplication. The most frequent inter-hemispheric gyrification patterns were bilateral single HG (36 %) and left single-right duplication (27 %). The least common patterns were left duplication-right single (22 %) and bilateral duplication (15 %). Duplication was associated with decreased anterior HG surface area on the corresponding side, independently of the type of duplication, and increased total HG surface area (including the second gyrus). Inter-hemispheric gyrification patterns strongly influenced both anterior and total HG surface area asymmetries, leftward asymmetry of the anterior HG surface was observed in all patterns except double left HG, and total HG surface asymmetry favored the side of duplication. Compared to right-handers, the 198 left-handers exhibited lower occurrence of duplication, and larger right anterior HG surface and total HG surface areas. Left-handers' HG surface asymmetries were thus significantly different from those of right-handers, with a loss of leftward asymmetry of their anterior HG surface, and with significant rightward asymmetry of their total HG surface. In summary, gyrification patterns have a strong impact on HG surface and asymmetry. The observed reduced lateralization of HG duplications and anterior HG asymmetry in left-handers highlights HG inter-hemispheric gyrification patterns as a potential candidate marker of speech lateralization.

Heschl's gyrification pattern is related to speech-listening hemispheric lateralization: FMRI investigation in 281 healthy volunteers.

This study investigates the structure-function relationships between the anatomy of Heschl's gyri (HG) and speech hemispheric lateralization in 281 healthy volunteers (135 left-handers). Hemispheric lateralization indices (HFLIs) were calculated with Wilke's method from the activations obtained via functional magnetic resonance imaging while listening to lists of words (LIST). The mean HFLI during LIST was rightward asymmetrical, and left-handers displayed a trend toward decreased rightward asymmetry. The correlations between LIST BOLD contrast maps and individual HFLIs demonstrated that among the cortical areas showing significant asymmetry during LIST, only phonological regions explained HFLI variability. Significant positive correlations were present among the left HG, supramarginal gyri, and the anterior insula. Significant negative correlations occurred in the mid-part of the right superior temporal sulcus. Left HG had the largest functional activity during LIST and explained 10% of the HFLI variance. There was a strong anatomo-functional link in the HG: duplication was associated with a decrease in both the surface area of the anterior HG and HG functional activity. Participants with a single left HG exhibited leftward anatomical and functional asymmetry of HG, but participants with a left duplication lost either anatomical and/or functional leftward asymmetries. Finally, manual preference was related to HG anatomy, but not to HG functional asymmetries measured during LIST. The anatomical characteristics of left-handers (lower occurrence of right HG duplication and a smaller surface area of the right first HG) thus appeared to be unrelated to variations in speech lateralization with handedness.

Between-hand difference in ipsilateral deactivation is associated with hand lateralization: fMRI mapping of 284 volunteers balanced for handedness.

In right-handers (RH), an increase in the pace of dominant hand movement results in increased ipsilateral deactivation of the primary motor cortex (M1). By contrast, an increase in non-dominant hand movement frequency is associated with reduced ipsilateral deactivation. This pattern suggests that inhibitory processes support right hand dominance in right-handers and raises the issues of whether this phenomenon also supports left hand preference in left-handers (LH), and/or whether it relates to asymmetry of manual ability in either group. Thanks to the BIL&GIN, a database dedicated to the investigation of hemispheric specialization (HS), we studied the variation in M1 activity during right and left finger tapping tasks (FTT) in a sample of 284 healthy participants balanced for handedness. An M1 fMRI localizer was defined for each participant as an 8 mm diameter sphere centered on the motor activation peak. RH exhibited significantly larger deactivation of the ipsilateral M1 when moving their dominant hand than their non-dominant hand. In contrast, LH exhibited comparable ipsilateral M1 deactivation during either hand movement, reflecting a bilateral cortical specialization. This pattern is likely related to left-handers' good performances with their right hand and consequent lower asymmetry in manual ability compared with RH. Finally, inter-individual analyses over the whole sample demonstrated that the larger the difference in manual skill across hands, the larger the difference in ipsilateral deactivation. Overall, we propose that difference in ipsilateral deactivation is a marker of difference in manual ability asymmetry reflecting differences in the strength of transcallosal inhibition when a given hand is moving.

Picture naming without Broca's and Wernicke's area.

Lexical and semantic retrieval was investigated in normal volunteers with PET by comparing picture confrontation naming and verb generation related to the same pictures. Conjunction analysis of the naming and verb generation uncovered a common network including the occipito-temporal ventral pathway for object recognition, and the bilateral anterior insula, SMA and precentral gyrus for coordination, planning and overt word production. Naming and verb generation highlighted two different patterns: verb generation showed specific implication of Broca and Wernicke's areas, whereas naming specifically relied on the primary visual areas, the right fusiform and parahippocampal gyri and the left anterior temporal region. These results indicate that speech does not necessarily involve the Wernicke-Broca's language network and testify that naming relies on an early developmental language network.

Cortical networks for working memory and executive functions sustain the conscious resting state in man.

The cortical anatomy of the conscious resting state (REST) was investigated using a meta-analysis of nine positron emission tomography (PET) activation protocols that dealt with different cognitive tasks but shared REST as a common control state. During REST, subjects were in darkness and silence, and were instructed to relax, refrain from moving, and avoid systematic thoughts. Each protocol contrasted REST to a different cognitive task consisting either of language, mental imagery, mental calculation, reasoning, finger movement, or spatial working memory, using either auditory, visual or no stimulus delivery, and requiring either vocal, motor or no output. A total of 63 subjects and 370 spatially normalized PET scans were entered in the meta-analysis. Conjunction analysis revealed a network of brain areas jointly activated during conscious REST as compared to the nine cognitive tasks, including the bilateral angular gyrus, the left anterior precuneus and posterior cingulate cortex, the left medial frontal and anterior cingulate cortex, the left superior and medial frontal sulcus, and the left inferior frontal cortex. These results suggest that brain activity during conscious REST is sustained by a large scale network of heteromodal associative parietal and frontal cortical areas, that can be further hierarchically organized in an episodic working memory parieto-frontal network, driven in part by emotions, working under the supervision of an executive left prefrontal network.

Weak language lateralization affects both verbal and spatial skills: an fMRI study in 297 subjects.

The present study reappraised the relationship between hemispheric specialization strength and cognitive skills in a sample of 297 individuals including 153 left-handers. It additionally assessed the interaction with manual laterality factors, such as handedness, asymmetry of hand motor skills, and familial sinistrality. A Hemispheric Functional Lateralization Index (HFLI) for language was derived from fMRI. Through mixture Gaussian modeling, three types of language hemispheric lateralization were defined: typical (left hemisphere dominance with clear positive HFLI), ambilateral (no dominant hemisphere with HFLI values close to 0), and strongly-atypical (right-hemisphere dominance with clear negative HFLI values). Three cognitive scores were derived from 12 tests covering various aspects of verbal and spatial cognition. Compared to both typical and strongly-atypical participants, those ambilateral for language production had lower performances in verbal and non-verbal domains, indicating that hemispheric specialization and cognitive skills are related in adults. Furthermore, this relationship was independent from handedness and asymmetry for motor skills, as no interaction was observed between these factors. On the other hand, the relationship between familial sinistrality and cognitive skills tended to differ according to language lateralization type. In contrast to previous reports in children, in the present adult population, we found no linear correlation between HFLI and cognitive skills, regardless of lateralization type.

The neural correlates of highly iconic structures and topographic discourse in French Sign Language as observed in six hearing native signers.

"Highly iconic" structures in Sign Language enable a narrator to act, switch characters, describe objects, or report actions in four-dimensions. This group of linguistic structures has no real spoken-language equivalent. Topographical descriptions are also achieved in a sign-language specific manner via the use of signing-space and spatial-classifier signs. We used functional magnetic resonance imaging (fMRI) to compare the neural correlates of topographic discourse and highly iconic structures in French Sign Language (LSF) in six hearing native signers, children of deaf adults (CODAs), and six LSF-naïve monolinguals. LSF materials consisted of videos of a lecture excerpt signed without spatially organized discourse or highly iconic structures (Lect LSF), a tale signed using highly iconic structures (Tale LSF), and a topographical description using a diagrammatic format and spatial-classifier signs (Topo LSF). We also presented texts in spoken French (Lect French, Tale French, Topo French) to all participants. With both languages, the Topo texts activated several different regions that are involved in mental navigation and spatial working memory. No specific correlate of LSF spatial discourse was evidenced. The same regions were more activated during Tale LSF than Lect LSF in CODAs, but not in monolinguals, in line with the presence of signing-space structure in both conditions. Motion processing areas and parts of the fusiform gyrus and precuneus were more active during Tale LSF in CODAs; no such effect was observed with French or in LSF-naïve monolinguals. These effects may be associated with perspective-taking and acting during personal transfers.

Neuroanatomy: tool for functional localization, key to brain organization.

The article by Devlin and Poldrack reminds researchers in the functional neuroimaging domain of the importance of anatomical expertise for functional activation localization. In line with this article, we highlight that macroscopic neuroanatomy should not be considered solely as a landmark system but also as one of the foundations of the functional organization of the brain.

Impact of modality and linguistic complexity during reading and listening tasks.

Reading and understanding speech are usually considered as different manifestations of a single cognitive ability, that of language. In this study, we were interested in characterizing the specific contributions of input modality and linguistic complexity on the neural networks involved when subjects understand language. We conducted an fMRI study during which 10 right-handed male subjects had to read and listen to words, sentences and texts in different runs. By comparing reading to listening tasks, we were able to show that the cerebral regions specifically recruited by a given modality were circumscribed to unimodal and associative unimodal cortices associated with the task, indicating that higher cognitive processes required by the task may be common to both modalities. Such cognitive processes involved a common phonological network as well as lexico-semantic activations as revealed by the conjunction between all reading and listening tasks. The restriction of modality-specific regions to their corresponding unimodal cortices was replicated when looking at brain areas showing a greater increase during the comprehension of more complex linguistic units than words (such as sentences and texts) for each modality. Finally, we discuss the possible roles of regions showing pure effect of linguistic complexity, such as the anterior part of the superior temporal gyrus and the ventro-posterior part of the middle temporal gyrus that were activated for sentences and texts but not for isolated words, as well as a text-specific region found in the left posterior STS.

Meta-analyzing left hemisphere language areas: phonology, semantics, and sentence processing.

The advent of functional neuroimaging has allowed tremendous advances in our understanding of brain-language relationships, in addition to generating substantial empirical data on this subject in the form of thousands of activation peak coordinates reported in a decade of language studies. We performed a large-scale meta-analysis of this literature, aimed at defining the composition of the phonological, semantic, and sentence processing networks in the frontal, temporal, and inferior parietal regions of the left cerebral hemisphere. For each of these language components, activation peaks issued from relevant component-specific contrasts were submitted to a spatial clustering algorithm, which gathered activation peaks on the basis of their relative distance in the MNI space. From a sample of 730 activation peaks extracted from 129 scientific reports selected among 260, we isolated 30 activation clusters, defining the functional fields constituting three distributed networks of frontal and temporal areas and revealing the functional organization of the left hemisphere for language. The functional role of each activation cluster is discussed based on the nature of the tasks in which it was involved. This meta-analysis sheds light on several contemporary issues, notably on the fine-scale functional architecture of the inferior frontal gyrus for phonological and semantic processing, the evidence for an elementary audio-motor loop involved in both comprehension and production of syllables including the primary auditory areas and the motor mouth area, evidence of areas of overlap between phonological and semantic processing, in particular at the location of the selective human voice area that was the seat of partial overlap of the three language components, the evidence of a cortical area in the pars opercularis of the inferior frontal gyrus dedicated to syntactic processing and in the posterior part of the superior temporal gyrus a region selectively activated by sentence and text processing, and the hypothesis that different working memory perception-actions loops are identifiable for the different language components. These results argue for large-scale architecture networks rather than modular organization of language in the left hemisphere.

Word and non-word reading: what role for the Visual Word Form Area?

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.