Neuropsychologia 46 (2008) 2292–2299 Contents lists available at ScienceDirect Neuropsychologia journal homepage: www.elsevier.com/locate/neuropsychologia The left fusiform area is affected by written frequency of words Alice M. Proverbio a,∗ , Alberto Zani b , Roberta Adorni a a Department of Psychology, University of Milano-Bicocca, Viale dell’Innovazione 10, 20126 Milan, Italy b Institute of Molecular Bioimaging and Physiology, CNR, Milano-Segrate, Milan, Italy article info Article history: Received 19 December 2007 Received in revised form 5 March 2008 Accepted 28 March 2008 Available online 10 April 2008 Keywords: VWFA Reading Language ERPs Visual route Developmental dyslexia Pure alexia abstract The recent neuroimaging literature gives conflicting evidence about whether the left fusiform gyrus (FG) might recognize words as unitary visual objects. The sensitivity of the left FG to word frequency might pro- vide a neural basis for the orthographic input lexicon theorized by reading models [Patterson, K., Marshall, J. C., & Coltheart, M. (1985). Surface dyslexia: Cognitive and neuropsychological studies of phonological reading. London: Lawrence Erlbaum]. The goal of this study was to investigate the time course and neural correlates of word processing in right-handed readers engaged in an orthographic decision task. Three hundred and twenty Italian words of high and low written frequency and 320 non-derived legal pseudo- words were presented for 250ms in the central visual field. ERPs were recorded from 128 scalp sites in 10 Italian University students. Behavioural data showed a word superiority effect, with faster RTs to words than pseudo-words. Left occipito/temporal N2 (240ms) was greater to high-frequency than low- frequency words and pseudo-words. According to the swLORETA inverse solution, the underlying neural source of this effect was located in the left fusiform gyrus of the occipital lobe (X = -29, Y = -66, Z = -10, BA19) and the right superior temporal gyrus (X = 51, Y = 6, Z = -5, BA22), which are probably involved in word recognition and semantic representation, respectively. Later frontal ERP components, LPN (300–350) and P3 (400–500), also showed strong lexical sensitivity, thus suggesting implicit semantic processes. The results shed some light on the possible neural substrate of visual reading disabilities such as developmental surface dyslexia or pure alexia. © 2008 Elsevier Ltd. All rights reserved. 1. Introduction One of the most debated issue in the recent neurolinguis- tic literature is whether a specialized area exists in the left occipito/temporal cortex devoted to the processing of alphabetic characters, the so-called visual word form area (VWFA) (Cohen & Dehaene, 2004; Cohen et al., 2000; Price & Devlin, 2003; Puce, Allison, Asgari, Gore, & McCarthy, 1996). Neurometabolic and MEG data (Flowers et al., 2004; Garrett et al., 2000; James, James, Jobard, Wong, & Gauthier, 2005; Pernet, Celsis, & Demonet, 2005; Polk et al., 2002; Tarkiainen, Helenius, Hansen, Cornelissen, & Salmelin, 1999) have shown that the middle part of the left fusiform gyrus is more responsive to letter-strings than other symbols (e.g. dig- its, ideograms, geometrical figures, colours). There is also much evidence that the VWFA has a role in developmental dyslexia, a dis- order of reading acquisition (Pugh et al., 2000; Salmelin, Helenius, & Service, 2000; Salmelin, Service, Kiesila, Uutela, & Salonen, 1996). In a magnetoencephalography study (Salmelin et al., 1996) Salmelin and coworkers found insufficient/atypical activation of the left infe- ∗ Corresponding author. Tel.: +39 02 64483755; fax: +39 02 64483706. E-mail address: mado.proverbio@unimib.it (A.M. Proverbio). rior temporal–occipital cortex in dyslexics viewing words. Simos et al. (2002) reported an enhancement of neural activity in the left occipito/temporal region in dyslexic children following remedial training. Furthermore, it seems that the VWFA shows a certain sublexical sensitivity to the orthographic regularities by which letters form words. While pronounceable pseudo-words activate the fusiform gyrus (Kuriki, Takeuchi, & Hirata, 1998), unpronounceable letter strings activate the left occipito-temporal/inferior-occipital sulci. Several fMRI data have shown that this region becomes more activated in response to poorly structured letter-strings (illegal letter-strings) than to well-structured ones (Cohen et al., 2002), and more activated in response to well-structured letter-strings that are words rather than legal pseudo-words (Kronbichler et al., 2004; Vigneau, Jobard, Mazoyer, & Tzourio-Mazoyer, 2005). Consis- tently, a review of neuroimaging studies (Mechelli, Gorno-Tempini, & Price, 2003) comparing brain activation in response to pseudo- words versus words showed greater activation to pseudo-words than to words in six out of nine studies in regions correspond- ing to or near the VWFA. The inverse relationship between word frequency and VWFA activation has been related to several neu- roimaging studies showing lower activation of object responsive areas in the ventral occipito-temporal cortex for more famil- 0028-3932/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2008.03.024