Neural correlates of lexical and sublexical processes in reading

Brain and Language 89 (2004) 9–20 www.elsevier.com/locate/b&l

Neural correlates of lexical and sublexical processes in reading Sven Joubert,a,e,f,* Mario Beauregard,a,b Nathalie Walter,a Pierre Bourgouin,c Gilles Beaudoin,c Jean-Maxime Leroux,c Sherif Karama,a and Andre Roch Lecoursa,d a

e

Centre de Recherche, Institut universitaire de g eriatrie de Montr eal, Canada b D epartement de radiologie, Universit e de Montr eal, Canada c CHUM/Campus Notre-Dame, D epartement de radiologie, Montr eal, Canada d D epartement de Psychologie, Universit e de Montr eal, Canada Laboratoire de Neurophysiologie et Neuropsychologie, INSERM EMI-U 9926, Marseille, France f Service de Neurologie et Neuropsychologie, AP-HM Timone, Marseille, France Accepted 21 November 2003

Abstract The purpose of the present study was to compare the brain regions and systems that subserve lexical and sublexical processes in reading. In order to do so, three types of tasks were used: (i) silent reading of very high frequency regular words (lexical task); (ii) silent reading of nonwords (sublexical task); and, (iii) silent reading of very low frequency regular words (sublexical task). All three conditions were contrasted with a visual/phonological baseline condition. The lexical condition engaged primarily an area at the border of the left angular and supramarginal gyri. Activation found in this region suggests that this area may be involved in mapping orthographic-to-phonological whole word representations. Both sublexical conditions elicited significantly greater activation in the left inferior prefrontal gyrus. This region is thought to be associated with sublexical processes in reading such as grapheme-to-phoneme conversion, phoneme assembly and underlying verbal working memory processes. Activation in the left IFG was also associated with left superior and middle temporal activation. These areas are thought to be functionally correlated with the left IFG and to contribute to a phonologically based form of reading. The results as a whole demonstrate that lexical and sublexical processes in reading activate different regions within a complex network of brain structures. Ó 2003 Elsevier Inc. All rights reserved. Keywords: Lexical reading; Sublexical reading; HF words; LF words; Nonwords; Functional magnetic resonance imaging

1. Introduction Reading involves a series of cognitive processes which include visual analysis of letters, word forms and letter strings, conversion of graphemic word forms into corresponding phonological word forms, and access to the semantic representation of the words. In this context, dual-route cognitive models of reading suggest that single-word reading may be carried out in two different ways (i.e. Coltheart, Curtis, Atkins, & Haller, 1993; Lecours, 1996; Paap & Noel, 1991). According to these models, a direct lexical route is involved in converting the orthographic form of a word into its corresponding phonological whole-word form, and this may be done * Corresponding author. Fax: +49-178-9914. E-mail address: [email protected] (S. Joubert).

0093-934X/$ - see front matter Ó 2003 Elsevier Inc. All rights reserved. doi:10.1016/S0093-934X(03)00403-6

with or without intermediary access to the semantic representation of the word. The lexical route allows for irregular and regular words to be read, as their pronunciations have been memorized in their entirety. In contrast, an indirect sublexical route allows for the pronunciation of regular words or nonwords by means of specific grapheme-to-phoneme conversion (GPC)1 rules. The printed letter string is first segmented into its graphemic constituents (Joubert & Lecours, 2000), which are then converted into their phonemic correspondences by way of GPC rules (Lecours, 1996).

1 Abbreviations used: fMRI, functional magnetic resonance imaging; PET, positron emission tomography; HF words, high frequency words; LF words, low frequency words; GPC, grapheme-to-phoneme conversion; IFG, inferior frontal gyrus; AG, angular gyrus.

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The existence of separate lexical and sublexical processing mechanisms was fuelled by dissociations between the ability to read irregular words and nonwords in patients with acquired dyslexias. Indeed, patients suffering from acquired phonological dyslexia (Beauvois & Derouesne, 1979; Funnel, 1983; Southwood & Chatterjee, 2000) demonstrate a marked incapacity to read nonwords, while word reading remains relatively intact. One interpretation is that this type of dyslexia reflects a partial impairment of the sublexical processing route, while the lexical route remains relatively unaffected. In contrast, surface dyslexia is characterized by an incapacity to read irregular words and by a preserved ability to read regular words and nonwords (Behrmann & Bub, 1992; Coltheart, 1982; Shallice & Warrington, 1980). Surface dyslexics also produce many regularization errors by applying conventional GPC rules to irregular words (Shallice & McCarthy, 1985). This type of dyslexia has been thought to reflect an inability to access whole-word forms in the orthographic lexicon, and thus many words are assumed to be read by way of an intact sublexical system. These functional impairments are rarely clear-cut, however. Many patients with phonological dyslexia present with some lexical impairments, particularly in reading inflected words and function words, and all surface alexic patients read many high frequency irregular words correctly. Thus, the functional dissociation between lexical and sublexical processing based on clinical and experimental evidence has been a matter of debate for some time now (Humphrey & Evett, 1985; Plaut, McClelland, Seidenberg, & Patterson, 1996). Connectionnist models of reading, for instance, suppose that reading is based upon a single unitary process, and that there are no separate cognitive processes for reading words and pseudo-words (Plaut et al., 1996). Anatomoclinical methods have also brought valuable insight into the functional neuroanatomy of reading. In a seminal study, Dejerine (1892) described a patient who developed alexia with agraphia following a lesion to the left angular gyrus (AG). Dejerine suggested that this area was the site of the orthographic lexicon, and that this patient was therefore unable to access visual wholeword representations following an AG lesion. Overall, though, lesion studies of acquired dyslexias have not revealed consistent patterns of correlation between lesion sites and reading impairments. Acquired surface dyslexia, for example, has been associated with lesions to the left superior and middle temporal gyri and of the underlying white matter, and lesions to the left parietotemporal cortex and the deep gray matter of the left hemisphere (Black & Behrmann, 1994). These lesions, however, are usually extensive and heterogeneous, as they result from a variety of etiologies including craniocerebral trauma, intracerebral hemorrhage, tumors, and multifocal cortical degeneration. Acquired phono-

logical dyslexia, in turn, has been associated with lesions to the left medial frontal and posterior temporal gyri, as well as with lesions to the angular and supramarginal gyri (Black & Behrmann, 1994). Nonetheless, such lesions are also extensive, thus making it difficult to establish precise functional correlations. Furthermore, surface dyslexia and phonological dyslexia cannot be considered as syndromes with a single underlying cause. Rather, they are likely to result from lesions to a variety of functional levels. For instance, phonological dyslexia may result from lesions that affect the ability to combine letters into graphemes, to convert graphemes into phonemes, or to assemble phonemes into a final pronunciation. Interpretation of the anatomy of lesions must then clearly consider this heterogeneity of functional deficits. An other major drawback of anatomoclinical studies is that patients usually present a series of overlapping functional deficits rather than a single specific impairment, which makes it difficult to establish any solid relation between lesion and function. Finally, the loss of a function may not necessarily be due to damage to a specific brain region, but to the anatomical disconnection of certain regions of the brain (e.g., lesion to a pathway; Paulesu et al., 1996). Studies of functional brain imaging using 15 O positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are helpful and complementary alternatives for localizing brain areas involved in language processing. Functional neuroimaging studies have offered a valuable contribution to the study of single-word reading (for review, see Fiez & Petersen, 1998; Price, 1998, 2000). An important number of neuroimaging studies have attempted to determine the areas of brain activation that subserve word reading and to localize the visual word form area, yet to this day only a few studies have systematically explored differences between word and pseudoword reading (Fiez, Balota, Raichle, & Petersen, 1999; Herbster, Mintum, Nebes, & Becker, 1997; Horwitz, Rumsey, & Donohue, 1998; Rumsey et al., 1997). To our knowledge, no such study was carried out in French. Furthermore, in the few studies that have explored brain activation during pseudoword reading, pseudowords consisted generally of words in which only one letter had been changed, thus increasing the chances of resembling real words. The question of whether reading is subserved by two distinct processes or by a single unitary process has remained a matter of debate in the field of cognitive neuropsychology for over twenty years now. According to dual-route theory of reading, it is clear that a normal adult reader will rely almost principally upon a faster and more efficient whole word (lexical) reading strategy, while a more analytical rule-based form of reading (sublexical) involving conversion of graphemes to phonemes and phoneme blending remains essential in the acquisition of novel words.

S. Joubert et al. / Brain and Language 89 (2004) 9–20

Thus, relying upon dual-route cognitive models of reading, which assume that lexical and sublexical routes to reading represent functionally distinct processes, the purpose of the present fMRI study was to examine in a group of normal readers, whether lexical and sublexical reading are underlied by distinct brain regions. In order to test this hypothesis, three experimental conditions were used, one lexical and two sublexical conditions. The lexical condition consisted of extremely frequent words. The first sublexical condition consisted of nonwords that were made of low frequency sublexical units and did not resemble real words, while the second sublexical condition consisted of very rare regular words. All of these reading tasks were compared with a baseline condition involving consonant string viewing, along with the silent pronunciation of one or two of these consonants. Results of the present study show that the lexical condition consisting of very high frequency regular words produced several distinct peaks of activation in an area at the border of the left angular/supramarginal region, while the two sublexical tasks engaged primarily an area in the left prefrontal inferior cortex.

2. Method 2.1. Subjects Ten, healthy French-speaking male readers (mean age ¼ 26 years, SD ¼ 6 years; mean education ¼ 15.7 years, SD ¼ 2 years), participated in this study. Subjects had no history of neurological or psychiatric disorders, and were right-handed (mean ¼ 94%, SD ¼ 11; Edinburgh laterality quotient). None of the subjects had a history of learning disabilities. The study was approved by the Ethics Review Board of the CHUM, Campus Notre-Dame. Informed consent was obtained in writing from all subjects prior to the start of the scanning session. 2.2. Experimental design Subjects were trained on each task prior to being placed in the fMRI scanner with words and nonwords similar to those used in the experimental conditions. Subjects were specifically instructed not to move their tongues or lips during the tasks. All stimuli were presented as black lower-case letters on a light gray background. They appeared at a rate of 1.4 s, with an interstimulus rate of 0.5 s. The experiment consisted of three runs. In each run, subjects were presented four blocks of stimuli. Each block consisted of 30 stimuli. In the first run, the first and third blocks consisted of high frequency (HF) words, while the second and fourth blocks consisted of controls (consonant strings). In the second and third runs, the first and third blocks con-

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sisted of nonwords and low frequency (LF) regular words, respectively, while the second and fourth blocks consisted of controls. A resting period (blank screen for 12 s) was set between each block. Furthermore, a resting period of 38.4 s preceded the first block in each run. The order of the runs was counterbalanced, such that it was HF words/nonwords/LF words for half of the subjects, and nonwords/LF words/HF words for the other half of the subjects. Each run was separated by approximately 10 min. Stimuli were presented through goggles connected to a MR compatible video system (Resonance Technology, Van Nuys, CA, USA). Four different conditions were used in this study: (i) a control task consisting of viewing and silently pronouncing consonant strings; (ii) a lexical task involving the silent reading of HF regular words; (iii) a sublexical task involving the silent reading of nonwords; and, (iv) a second sublexical task consisting of reading silently LF regular words. All the words used in this study were taken from the Brulex computerized lexical database (Content, Mousty, & Radeau, 1990). The sublexical graphemic frequencies used to construct nonwords were taken from the Content and Radeau (1988) sublexical frequency tables. Pronounceable nonwords were matched to HF words for length, number of graphemes, number of phonemes, and number of syllables. Low frequency regular words were matched to HF words for length, number of graphemes, number of phonemes, number of syllables, N count (cf. the number of orthographic neighbors), and sublexical frequency. 2.2.1. Baseline condition Subjects were shown a series of five- and six-letter consonant strings which could not be read according to the conventional rules of the French language (i.e., xtpbn). They were instructed to passively view the letter strings and to silently read the letters in bold. The letter strings contained the same number of letters as the real words and nonwords. The consonants in bold that had to be read silently contained approximately the same number of phonemes as the real words and nonwords. This baseline task was designed so as to significantly reduce any activation that could be due to primary visual and pre-articulatory processes. The cognitive processes involved in such a task are primary visual processing, letter identification, and phono-articulatory programming. These processes were therefore controlled for when the baseline condition was contrasted with the word and nonword conditions. 2.2.2. High frequency regular word reading Subjects had to read silently a series of five- and sixletter HF regular words that were pronounceable according to the rules of the French language. The words were among the highest in frequency for their word length in the French language (mean frequency ¼ 45,600

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S. Joubert et al. / Brain and Language 89 (2004) 9–20

in a corpus of 26,500,000 words) (i.e., homme, coeur). Because they are so frequent in written language, reading these HF words is assumed to require a global, whole-word recognition. Processes involved in this type of reading include early visual processing, letter identification, access to the wordÕs orthographic representations, semantic processing, and phono-articulatory programming.

scan was performed in the same planes as the scan for anatomic localization and coregistration of images across subjects. Structural data were acquired via a T1-weighted 3D volume acquisition obtained using a gradient echo pulse sequence (TR ¼ 9.7 ms, TE ¼ 4 ms, Flip ¼ 12°, FOV ¼ 250 mm, Matrix ¼ 256
256). 2.4. Data analysis

2.2.3. Nonword reading Subjects had to read silently a series of five- and sixletter nonwords, composed of LH regular sublexical units which obeyed traditional grapheme-to-phoneme conversion rules. Average sublexical frequency was 620.63, and corresponded to the frequency of occurrence of sublexical units in a corpus of 30,000 words. Sublexical graphemic units consisted of single letters, bigrams, and trigrams. The nonwords were legal and pronounceable according to the rules of the French language (i.e., plaud, fosme). They did not resemble known words, thus avoiding the possibility of being read by analogy to real words. Nonwords are assumed to exert maximum demands on sublexical and phonological processes. Processes involved in this reading task include early visual processing, letter identification, conversion of graphemic representations (and possibly larger size units such as syllables) into corresponding phonological representations, and phono-articulatory programming.

Using the Statistical Parametric Mapping software (SPM96, Wellcome Department of Cognitive Neurology, UK), images for all subjects were realigned to correct for artifacts due to small head movements and normalized into an MRI stereotactic space. Images were then convolved in space with a three-dimensional isotropic gaussian kernel (4 mm FWHM) to improve the signal-to-noise ratio. For statistical analysis, the time series of the images were correlated with the delayed box-car function which approximates the activation patterns and a linear model for autocorrelated observations was applied voxelwise. Regional specific effects were assessed in terms of Z values. When comparing each experimental condition with the baseline condition, voxels were identified as significantly activated if they passed a height threshold set at P < :0005 (Z > 3:29).

2.2.4. Low frequency regular word reading Subjects had to read silently a series of five- and sixletter very LF words that were pronounceable according to the rules of the French language. These words were among the lowest in frequency for their word length in the French language (mean frequency ¼ 35.42 out of a corpus of 23,500,000) (i.e., sonar, tango). Because of their very low frequency and their regular pronunciation, these words are also thought to exert maximum demands on sublexical phonological processes. We assume that semantic access may occur in this condition but via a sublexical route to reading. Processes involved in this type of reading include early visual processing, letter identification, grapheme-to-phoneme conversion, semantic processing, and phono-articulatory programming (see Fig. 1).

3.1. Significant activation during HF word, nonword, and LF word reading

2.3. Image acquisition and scanning Scanning was performed on a 1.5 T system (Magnetom Vision, Siemens Electric, Erlangen). Twenty-eight slices (5 mm thick) were acquired every 6.4 s in an inclined axial plane, aligned with the AC–PC axis. The T2* weighted functional images were acquired using an echo-planar (EPI) pulse sequence (TR ¼ 0.8 s, TE ¼ 54 ms, Flip ¼ 90°, FOV ¼ 215 mm, Matrix ¼ 128
128). Following functional scanning, a high-resolution structural

3. Results

Relative to the visual/phonological control condition, silent reading of HF words (lexical task) produced significant blood oxygenation level dependent (BOLD) signal increases in the following regions (see Fig. 2 and Table 1): (i) an area at the margin of the left angular gyrus and the left supramarginal gyrus (Brodmann area-BA 39/ 40), near the posterior superior temporal gyrus. As seen in Table 1, three different peaks of activation were found in this region; (ii) the left inferior frontal gyrus (BA 44, 47); (iii) the visual striate cortex bilaterally (BA 17); (iv) the middle frontal cortex bilaterally (BA 9); (v) the right superior temporal gyrus (BA 22/42); (vi) the right cuneus (BA 18, 19); and, (vii) the right lingual gyrus (BA 19). Silent reading of nonwords (sublexical task) produced significant BOLD activation in the following areas: (i) the inferior frontal cortex bilaterally (BA 44, 45, 47). As seen in Table 1, four different peaks of activation were found in the left IFG; (ii) the border of the left angular gyrus and the supramarginal gyrus (BA 39/40); (iii) the left superior temporal gyrus (BA 22/42); (iv) the left middle temporal gyrus (BA 21); (v) the lingual gyrus bilaterally (BA 19); (vi) the left and right precentral gyri (BA 6); (vii) the left middle frontal cortex (BA 9); (viii) the left medial frontal gyrus (BA 8); and, (ix) the right

S. Joubert et al. / Brain and Language 89 (2004) 9–20

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Fig. 1. Schematic description of the different cognitive processes involved in the present subtraction paradigm.

Fig. 2. Regions showing activated voxels when the brain activity associated with silent reading of HF words (lexical condition), nonwords (sublexical condition), and LF words (sublexical condition) was contrasted with that of viewing and silently pronouncing consonant strings. In this figure, the left side of the brain appears on the left and the right side on the right. The images display activity above a significance threshold of P > :0005. Areas of activation are represented in red and yellow (yellow colors denote greater activation and higher levels of significance). In this figure, note particularly the greater spatial extent of the BOLD signal increases in the left inferior prefrontal region in silent reading of nonwords and LF words.

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S. Joubert et al. / Brain and Language 89 (2004) 9–20

Table 1 Identification of blood oxygenation level dependent (BOLD) signal increases in subjects when the brain activity associated with silent reading of HF words, nonwords, and LF words were contrasted with that associated with viewing and pronouncing consonant strings Region (Brodmann area)

Significant activation (at P < :0005) HF words > consonant strings x

L Inferior frontal gyrus (44) L Inferior frontal gyrus (45) L Inferior frontal gyrus (47) R Inferior frontal gyrus (45/47) L Angular gyrus /SMG (39/40)

L Superior temporal gyrus (22/42) R Superior temporal gyrus (22/42) R Superior temporal gyrus (22) L Middle temporal gyrus (21) L Inferior temporal gyrus (20/36) L Inferior temporal gyrus (36) R Inferior temporal pole (21/20) L Fusiform gyrus (37) L Occipital gyrus (17) R. Occipital gyrus (17) L Lingual gyrus (18)

y

Nonwords > consonant strings

LF words > consonant strings x

z

Z

x

)47 )38

12 10

18 16

3.77 3.71

)47

6

14

4.36

)40

32

3

4.08

4.39 3.90 4.56 4.85

3.84 3.54 3.44

3.92 6.46 4.37 3.86 4.10

7 )3 )6 1

32 26 23

17 )5 )2 )3 32

32 24 26 24

)53 )57 )49

22 28 14 26 )49

)45 )47 )38 55

)40 )43 )36

)45 )47 )50 54 )43 )55

)24

3

3.87

)50

)35

14

4.94

59

)12

14

4.02

59

1

3

4.00

)27 )29 40 47 )38

)37 )1 8 )10 )45

)16 )28 )30 )13 )16

4.83 4.66 4.53 4.18 4.18

11 10

)76 )76

)9 5

4.66 3.47

13 4 11

)78 )90 )90

20 20 24

5.26 4.74 4.00

)47

)63

)31

5.10

61

)35

3

y

)86 )80

11 9

Z

4.09

)59

)8 3

z

)12

)6

R Cuneus (18) R Cuneus (19)

)6 )10

13 17

)57 )90

3 15

3.87 5.47

6 6

)86 )82

31 41

4.61 3.51

)22 11

47 51

34 25

Z

4.11 4.18

L Cerebellum R Cerebellum

L Precentral gyrus (6) R Precentral gyrus (6) L Middle frontal gyrus (9) R Middle frontal gyrus (9) L Medial/Frontal gyrus (8)

z

4.24

)67 )76

7 )7

3.58 3.55

R Lingual gyrus (18) R Lingual gyrus (19) R Cuneus (18)

y

3.86 4.17

18 29 6 25 )4 8 )13

)86 )82 )76 )30 12 20 43

)36 )44 )21 )26 50 45 32

4.29 4.14 3.60 3.58 4.37 4.44 3.83

)6

26

43

4.26

Stereotaxic coordinates are derived from the human brain atlas of Talairach and Tournoux (1988) and refer to medial-lateral position (x) relative to midline (positive ¼ right), anterior–posterior position (y) relative to the anterior commissure (positive ¼ anterior), and superior–inferior position (z) relative to the commissural line (positive ¼ superior). Designations of Brodmann areas (BA) are also based on this atlas.

cerebellum. Most widespread activation was found in the left inferior frontal gyrus (see Fig. 2 and Table 1). Finally, silent reading of LF words (sublexical task) induced significant foci of activation in the following regions: (i) the left and right inferior frontal gyri (BA 45,47). As seen in Table 1, three different peaks of activation were found in the left IFG; (ii) the superior temporal gyrus bilaterally (BA 22/42); (iii) the inferior temporal gyrus bilaterally (BA 20, 21, 36); (iv) the left fusiform gyrus (BA 37); (v) the right lingual gyrus (BA

18); (vi) the right cuneus (BA 18); and, (vii) the left cerebellum. The most widespread activation was found in the left inferior frontal gyrus. No significant activation was found in the left angular/supramarginal gyrus (see Fig. 2 and Table 1). 3.2. Lexical vs. sublexical conditions Direct comparisons of the magnitude of BOLD response were also carried out between silent reading of

Table 2 Identification of blood oxygenation level dependent (BOLD) signal increases in subjects when the brain activity associated with silent reading of HF words, nonwords, and LF words were contrasted with each other (direct contrasts) Region (Brodmann area)

R Inferior frontal gyrus (45/47)

HF words > nonwords

Nonwords > HF words

HF words > LF words

x

x

x

y

z

Z

y

z

Z

)52

14

2

3.44

)45 )48 57

28 16 16

)6 )8 22

4.02 3.33 3.28

y

z

Z

LF words > HF words

Nonwords > LF words

LF words > nonwords

x

x

y

x

y

)41

)49

32

3.32

)48

)41

56

3.15 )50

)35

14

3.87

)47 59 55

)24 )24 1

12 19 3

2.81 4.33 3.68

6 )47

)74 )61

19 )31

3.64 3.70

y

z

Z

)55

10

28

4.31

25

16

)6

3.75

31

22

3

3.46

L Angular gyrus/ SMG (39/40)

z

Z

L Superior temporal gyr (22/42)

R Superior temporal gyr (22) L Inferior temporal gyr (20/36) L Fusiform gyrus (37) R Cuneus (18) L Cerebellum R Cerebellum

L Precentral gyrus (6) R Precentral gyrus (6) L Medial/Frontal gyrus (8)

)22 25

)47 50

)41 )30

6 4

)21 )28

14 32

4.49 4.89

2.91 3.79

)22

)41

)14

5.17

)43

)57

4

4.72

)47 18

)57 )70

)27 )17

4.76 4.61

25

)51

)27

4.57

18

)80

)29

2.97

)43

)1

45

2.93

)3

32

42

2.93

z

Z

S. Joubert et al. / Brain and Language 89 (2004) 9–20

L Inferior frontal gyrus (44) L Inferior frontal gyrus (45) (47)

Significant differences (at P < :005)

Stereotaxic coordinates are derived from the human brain atlas of Talairach and Tournoux (1988) and refer to medial–lateral position (x) relative to midline (positive ¼ right), anterior–posterior position (y) relative to the anterior commissure (positive ¼ anterior), and superior–inferior position (z) relative to the commissural line (positive ¼ superior). Designations of Brodmann areas (BA) are also based on this atlas.

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HF words (lexical task), nonwords (sublexical task) and LF words (sublexical task). As seen in Table 2, both sublexical conditions elicited significantly more intense activation (in terms of Z score magnitude) in the left and right inferior frontal gyri than the lexical condition. Thus, with respect to the left hemisphere, nonword reading activated BA 45 and 47 significantly more than HF word reading, while LF word reading activated BA 44 significantly more than HF word reading. In the right hemisphere, greater activation was found in BA 47 during both nonword and LF word reading than during HF word reading. In contrast, silent reading of HF words did not activate any area of the brain significantly more than reading nonwords or LF words. When comparing nonwords with LF words, nonwords elicited significantly greater activation in left angular gyrus/supramarginal gyrus (BA 39/40) than LF words. Significant differences were also found in the left precentral gyrus (BA 6), the left medial frontal gyrus (BA 8), and the right cerebellum. Silently reading LF words, on the other hand, resulted in a significantly greater activation of the superior temporal gyrus bilaterally (BA 22/42) than nonword reading. Significant differences were also found in the left cerebellum and the right cuneus (BA 18).

4. Discussion Cognitive models have proposed detailed descriptions of the processes inherent to reading, yet very little is known about the underlying correlates of these models. With respect to this question, anatomoclinical studies have allowed some insights into the localization of reading deficits caused by acquired brain damage, but as previously mentioned, lesions are often extensive and heterogeneous, thus making it difficult to establish precise functional anatomical correlations. Therefore, the purpose of the present fMRI study was to better circumscribe the brain regions that subserve lexical and sublexical processes in reading. Based on neuropsychological and anatomoclinical evidence, the central presumption of this paper was that the lexical and sublexical routes are subserved by different regions of the brain. Based on DejerineÕs theory (1892), we could expect the lexical condition would elicit significant activation in the left AG. However, eventhough reading high frequency words is presumed to require lexical processing while low frequency word and nonword reading are thought to solicit primarily sublexical processes, they are not assumed to do so in an all or none fashion, as was postulated by early modular cognitive models of reading. Hence, all three experimental conditions were chosen because they were considered to require preferential although not selective engagement of one type of processing over another.

In the present experiment, the lexical condition activated primarily an area at the border of the left angular and supramarginal gyri when contrasted with the control condition: three different peaks of activation were found in that area and two were unique to that condition. Areas of brain activation that were unique to both sublexical conditions included the left and right frontal gyri (BA 45/ 47) and the left superior temporal gyrus (BA 22/42). The present results are now discussed in light of previous neuroimaging and neuropsychological data. 4.1. Neural substrate of the orthographic lexicon Several recent studies have found activation during word reading in the left posterior inferior temporal cortex (i.e. fusiform gyrus), and this area has been recently hypothesized to be a candidate site of the visual word form (Cohen et al., 2000; Pugh et al., 2000) and part of a semantic route to naming (Price et al., 1994). Support for this idea also stems from lesion data. In pure alexia, often referred to as ‘‘letter-by-letter reading’’ or alexia without agraphia, patients can write words but cannot read what they have just written, yet they can spell out words quite well and often use this strategy to produce a correct prononciation. They usually do not present any other language deficits. Typically, pure alexia has been associated with lesions to the inferior temporo-occipital region including the lingual gyrus and sometimes extending into the fusiform gyrus (e.g. Dejerine, 1892). Taken together, these data suggest that the left fusiform gyrus may represent a candidate site for the orthographic lexicon. In the present study however, neither the HF word nor the nonword condition resulted in any changes in activity in the left fusiform gyrus. This may be due to the fact that the baseline task, which required letter identification, was subtracted from each experimental condition, thus eliminating any possible confounding activation due to early letter processing. In our view, the left inferior occipito-temporal cortex is most likely involved in detecting the complex attributes of letters and letter strings, rather than reflecting the neural substrate of the orthographic lexicon. Thus, the results of the present study do not support the notion of a visual word form in an area of the left ventral infero-temporal route connecting visual associative areas with left temporoparietal areas and possibly left prefrontal areas and involved in highly automatized lexical semantic processing in reading (Price et al., 1994; Pugh et al., 2000). On the other hand, different data suggest that the critical substrate of the orthographic lexicon may be at an area at the border of the left angular/supramarginal gyrus. For instance, Dejerine (1892) described a patient who developed pure alexia (without agraphia) following a stroke which resulted in a lesion to the left lingual and fusiform gyri, and of the ventral part of the splenium of

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the corpus callosum. The same patient suffered a lesion to the left angular gyrus four years later, and developed alexia with agraphia. Oral language remained relatively intact. Dejerine suggested that the patientÕs first occipitotemporal lesion prevented the normal transmission of visual information from the left and right occipital areas to the angular gyrus (this would account for the fact that the patient could write but nor read what he had just written). Dejerine also concluded that the patientÕs second lesion resulted in a disruption of the visual word form, making it impossible to access the global visual representations of words. This study was the first to clearly account for the involvement of the left angular gyrus in reading. Further evidence comes from surface dyslexia. Although clearly distinguishable from the type of alexia reported by Dejerine (1892), surface dyslexia is a disorder which is thought to reflect a disruption of visual whole word representations. Typically, most irregular words are read using conventional grapheme–phoneme conversion rules (i.e. pint is read as mint), which results in so-called regularization errors. Regular words and nonwords, however, are read remarkably well. This type of dyslexia, which shows an evident dissociation between impaired irregular word reading and the preserved ability to read regular words and nonwords, is thought to reflect an impairment of the lexical route and a preservation of grapheme–phoneme conversion rules. Consistent with DejerineÕs theory, the common areas that seem to be involved in surface dyslexia are the left supramarginal and angular gyri, along with the deep gray matter of the left hemisphere and the left posterior superior and middle temporal gyri (Black & Behrmann, 1994). Other evidence of the localization of the left AG/ SMG comes from recent neuroimaging studies. In a PET investigation by Howard et al. (1992), subjects repeated heard spoken words. When compared with visual and auditory baselines, word reading produced significant activation in the left posterior middle temporal gyrus. The area activated in this study was on the margin of the AG, the presumed site of the orthographic lexicon according to Dejerine (1892). In a follow-up study by the same group, Price et al. (1994) compared reading aloud and silent viewing of words. Both tasks significantly activated similar regions for both exposure durations, corroborating their previous results (Howard et al., 1992). In another neuroimaging investigation (PET) by Menard, Kosslyn, Thompson, Alpert, and Rauch (1996), when activation was associated with passive viewing of pictures, crosshairs, or Xs baseline conditions was subtracted from that associated with silent word reading, the left angular gyrus and BrocaÕs area were found to be activated. According to the authors, these data support the idea that a ‘‘word form area’’ is near the margin of the AG. Finally, Horwitz et al. (1998) examined reading in a group of normal

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readers and in a group of impaired dyslexic readers. The authors found a strong connectivity between the left angular gyrus and other left-hemisphere regions, including the posterior inferior temporo-occipital cortex, suggesting a prominent role of the left AG in reading. Furthermore, the left AG was found to be functionally disconnected from other brain areas in dyslexic readers, thus indicating that a disconnection syndrome between the left AG and other left-hemisphere language areas can underlie various forms of dyslexia. In summary, all of these neuroimaging studies suggest that the neural substrate of the visual orthographic lexicon is found in the left angular/supramarginal region. In the present study, the lexical condition produced three peaks of activation in an area at the border of the left angular/supramarginal region when compared with the baseline condition. The stimuli used in the lexical condition, very HF regular words, were specifically selected so as to exert maximum demands on the orthographic route to reading, and hence the visual orthographic lexicon (Lecours, 1996). Our results thus clearly suggest that this area may be involved in processing highly lexicalized visual representations of words. The left angular/supramarginal region presumably acts as an associative multimodal turntable and is involved in mapping whole-word orthographic-to-phonological representations in reading, a role specific to the left hemisphere. When direct contrasts were carried out between the lexical and sublexical tasks (see Table 2), however, the lexical condition did not activate any brain region significantly more than nonword or LF regular word reading, including the left AG/SMG. This is likely to reflect the relative degree of difficulty of each condition: Reading very familiar HF words is much less demanding in terms of processing than reading very low frequency regular words or words that do not exist. 4.2. Activation in the left inferior prefrontal cortex Several foci of activation were found in the left inferior prefrontal cortex (BA 45, 47). First, greatest BOLD signal activation was found in the left inferior prefrontal gyrus during silent reading of both nonwords and LF words. Second, the nonword and LF word conditions yielded significant activation in Brodman area 45 but reading HF words did not produce any activation in this same area. There are several implications to these results. From a functional perspective, a commonly held view is that this prefrontal region plays an important role in semantics (Demb et al., 1995; Menard et al., 1996; Petersen, Fox, Posner, Mintum, & Raichle, 1988). In a fMRI study by Demb et al. (1995), greater activation was found in the left inferior prefrontal region (BA 45, 46, 47) during semantic encoding relative to nonsemantic encoding, regardless of task difficulty. These authors suggested that this cortical region is part of a semantic executive system involved in

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the retrieval of semantic information. Activation in this area has also been correlated with the specific semantic difficulty of a task (Gabrieli, Poldrack, & Desmond, 1998). In the present study, although one could argue that both sublexical tasks could activate a semantic search, it seems unlikely that this semantic network would be significantly more activated in these two sublexical conditions than in the lexical HF word condition. Thus, in our view, activation in the left inferior prefrontal cortex does not reflect activation of a semantic network. Although the inferior prefrontal cortex has been associated with retrieval of semantic information, it may be also involved in specific forms of sublexical and phonologically based processing (‘‘sounding out the words’’). Indeed, in a study by Sergent, Zuck, Levesque, and MacDonald (1992), greater activation was found in the left inferior prefrontal gyrus (BA 45, 46) during phonological judgements than during semantic judgements on visually presented words. In another study by Pugh et al. (1996), a phonological task, which consisted of a nonword rhyme judgement task, also produced robust activation in this prefrontal area. Based on their findings, these authors (Pugh et al., 1996) suggested that the left inferior prefrontal gyrus is a candidate site for the mapping of graphemic strings to phonemic strings. Similarly, in the present study, nonword reading and LF word reading both yielded significant widespread activation in the left inferior prefrontal gyrus, suggesting that this area is involved in a rule-governed sublexical conversion code. Silent reading of nonwords and LF words also significantly activated the left superior temporal gyrus when contrasted with baseline consonant strings. Silent reading of HF words, on the other hand, did not engage these areas when contrasted with controls. This brain area may be functionally correlated with left prefrontal areas during phonological processing. Therefore in the present study, we suggest that activation in this area relates to phonological coding mechanisms (grapheme-to-phoneme correspondence, phoneme blending) associated with nonword and LF word reading. In an interesting study by Fiez et al. (1999), PET was used to investigate the neural substrates of three factors that affect reading performance: lexicality (word vs. nonword), frequency, and consistency (spelling-tosound correspondence). Comparisons between reading and visual fixation indicate that a left inferior frontal region shows an effect of consistency: inconsistent words produced more robust activation than consistent words and LF words produced more activation than high frequency words in this brain region. In a region located near the border of the IFG (BA44/45) and the insula, significantly greater activation was found for LF inconsistent words than for other types of words. Finally, a region of the left superior temporal gyrus was more active when subjects read low-frequency than when they

read HF words. Reading words and nonwords also activated the same regions, but different patterns of activation within this network of regions were found for the various conditions. The left inferior frontal region was thought to contribute to orthographic to phonological transformation and other phonological tasks. In another PET study by Herbster et al. (1997), reading irregular words and nonwords activated a region of the left inferior frontal cortex including BA 44 and 47. Reading aloud HF regular/consistent and LF irregular/inconsistent words also activated the left fusiform gyrus when contrasted with ‘‘zero-order speak’’ (subjects repeated a same word as each letter string was presented), while nonwords did not activate this region at all. A direct contrast between regular word and nonword reading showed significantly greater activation in the left fusiform gyrus during regular word reading and significantly greater activation in the left IFG during nonword reading. The authors concluded that the increased activation in this region for LF irregular word and nonword tasks reflects increased processing in the phonological system while the left fusiform gyrus is important for processing the meaning of words. In the present study, LF and HF words were regular and had a consistent spelling-to-sound correspondence. Our results differ from those of previous studies in that significant activation in the left IFG was found for consistent LF, and to a lesser extent, consistent HF words. This was not the case in the aforementioned studies (Fiez et al., 1999; Herbster et al., 1997). In our view, regular words with very low frequency counts are seldom encountered and we suggest that they require greater reliance upon sublexical and phonologically based mechanisms than very HF words. More robust activation found in the left IFG for LF regular words and nonwords supports the idea that this region may be specifically involved in distinct sublexical mechanisms, namely grapheme–phoneme correspondence and phonological assembly (assembling the phonemes into a correct pronunciation). Sublexical reading mechanisms also call for greater involvement of short-term phonological memory than a lexically based reading system: The phonemes of a nonword or a very LF regular word must be maintained in working memory before being assembled into a final pronunciation. According to a recent interpretation of the phonological loop, a component of working memory, the phonological loop plays a critical role in learning the phonological forms of new words (Baddeley, Gathercole, & Papagno, 1998). Its role would be to store unfamiliar sound patterns, while more permanent sound records are being established. Thus, the phonological loop plays a primary role in learning novel words, while retaining sequences of familiar words remains secondary. It is thus plausible that short-term verbal memory processes involved in the decoding of nonwords may also account for IFG activation.

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Consistent with this idea, the left IFG is known to be involved in various aspects of working memory (cf. Bunge, Klingberg, Jacobsen, & Gabrieli, 2000).

5. Conclusions In this study, activation related to ÔcentralÕ processes in reading was differentially distributed within a network of posterior temporo-parietal, inferior prefrontal and middle, and superior temporal regions. The HF word condition engaged primarily an area at the border of the left angular and supramarginal gyri, while both LF word and nonword sublexical conditions elicited significantly greater activation in the left inferior prefrontal and left superior temporal regions. We suggest the left AG/supramarginal region represents a candidate site for the visual orthographic lexicon, while the left IFG and left middle/superior temporal regions may call for a sublexical phonologically based form of processing that includes GPC conversion, phonological retrieval, and phoneme blending.

Acknowledgments We thank the subjects who participated in this study, the technicians of the fMRI unit at the CHUM (Centre hospitalier de lÕUniversite de Montreal), Campus NotreDame, for their help in scanning volunteers. This work was supported by funds from lÕInstitut universitaire de geriatrie de Montreal, and by a grant from FCAR (Fonds pour la Formation de Chercheurs et lÕAide a la Recherche) to Sven Joubert.

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