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1.  Segregation of Lexical and Sub-Lexical Reading Processes in the Left Perisylvian Cortex 
PLoS ONE  2012;7(11):e50665.
A fundamental issue in cognitive neuroscience is the existence of two major, sub-lexical and lexical, reading processes and their possible segregation in the left posterior perisylvian cortex. Using cortical electrostimulation mapping, we identified the cortical areas involved on reading either orthographically irregular words (lexical, “direct” process) or pronounceable pseudowords (sublexical, “indirect” process) in 14 right-handed neurosurgical patients while video-recording behavioral effects. Intraoperative neuronavigation system and Montreal Neurological Institute (MNI) stereotactic coordinates were used to identify the localization of stimulation sites. Fifty-one reading interference areas were found that affected either words (14 areas), or pseudo-words (11 areas), or both (26 areas). Forty-one (80%) corresponded to the impairment of the phonological level of reading processes. Reading processes involved discrete, highly localized perisylvian cortical areas with individual variability. MNI coordinates throughout the group exhibited a clear segregation according to the tested reading route; specific pseudo-word reading interferences were concentrated in a restricted inferior and anterior subpart of the left supramarginal gyrus (barycentre x = −68.1; y = −25.9; z = 30.2; Brodmann’s area 40) while specific word reading areas were located almost exclusively alongside the left superior temporal gyrus. Although half of the reading interferences found were nonspecific, the finding of specific lexical or sublexical interferences is new evidence that lexical and sublexical processes of reading could be partially supported by distinct cortical sub-regions despite their anatomical proximity. These data are in line with many brain activation studies that showed that left superior temporal and inferior parietal regions had a crucial role respectively in word and pseudoword reading and were core regions for dyslexia.
PMCID: PMC3511309  PMID: 23226349
2.  Effect of Orthographic Processes on Letter Identity and Letter-Position Encoding in Dyslexic Children 
The ability to identify letters and encode their position is a crucial step of the word recognition process. However and despite their word identification problem, the ability of dyslexic children to encode letter identity and letter-position within strings was not systematically investigated. This study aimed at filling this gap and further explored how letter identity and letter-position encoding is modulated by letter context in developmental dyslexia. For this purpose, a letter-string comparison task was administered to French dyslexic children and two chronological age (CA) and reading age (RA)-matched control groups. Children had to judge whether two successively and briefly presented four-letter strings were identical or different. Letter-position and letter identity were manipulated through the transposition (e.g., RTGM vs. RMGT) or substitution of two letters (e.g., TSHF vs. TGHD). Non-words, pseudo-words, and words were used as stimuli to investigate sub-lexical and lexical effects on letter encoding. Dyslexic children showed both substitution and transposition detection problems relative to CA-controls. A substitution advantage over transpositions was only found for words in dyslexic children whereas it extended to pseudo-words in RA-controls and to all type of items in CA-controls. Letters were better identified in the dyslexic group when belonging to orthographically familiar strings. Letter-position encoding was very impaired in dyslexic children who did not show any word context effect in contrast to CA-controls. Overall, the current findings point to a strong letter identity and letter-position encoding disorder in developmental dyslexia.
PMCID: PMC3356879  PMID: 22661961
letter-string processing; letter-position encoding; letter-identity encoding; letter transposition; letter substitution; reading acquisition; dyslexic children
3.  ERP Characterization of Sustained Attention Effects in Visual Lexical Categorization 
PLoS ONE  2010;5(3):e9892.
As our understanding of the basic processes underlying reading is growing, the key role played by attention in this process becomes evident. Two research topics are of particular interest in this domain: (1) it is still undetermined whether sustained attention affects lexical decision tasks; (2) the influence of attention on early visual processing (i.e., before orthographic or lexico-semantic processing stages) remains largely under-specified. Here we investigated early perceptual modulations by sustained attention using an ERP paradigm adapted from Thierry et al. [1]. Participants had to decide whether visual stimuli presented in pairs pertained to a pre-specified category (lexical categorization focus on word or pseudoword pairs). Depending on the lexical category of the first item of a pair, participants either needed to fully process the second item (hold condition) or could release their attention and make a decision without full processing of the second item (release condition). The P1 peak was unaffected by sustained attention. The N1 was delayed and reduced after the second item of a pair when participants released their attention. Release of sustained attention also reduced a P3 wave elicited by the first item of a pair and abolished the P3 wave elicited by the second. Our results are consistent with differential effects of sustained attention on early processing stages and working memory. Sustained attention modulated early processing stages during a lexical decision task without inhibiting the process of stimulus integration. On the contrary, working memory involvement/updating was highly dependent upon the allocation of sustained attention. Moreover, the influence of sustained attention on both early and late cognitive processes was independent of lexical categorization focus.
PMCID: PMC2845638  PMID: 20361039
4.  Testing for the Dual-Route Cascade Reading Model in the Brain: An fMRI Effective Connectivity Account of an Efficient Reading Style 
PLoS ONE  2009;4(8):e6675.
Neuropsychological data about the forms of acquired reading impairment provide a strong basis for the theoretical framework of the dual-route cascade (DRC) model which is predictive of reading performance. However, lesions are often extensive and heterogeneous, thus making it difficult to establish precise functional anatomical correlates. Here, we provide a connective neural account in the aim of accommodating the main principles of the DRC framework and to make predictions on reading skill. We located prominent reading areas using fMRI and applied structural equation modeling to pinpoint distinct neural pathways. Functionality of regions together with neural network dissociations between words and pseudowords corroborate the existing neuroanatomical view on the DRC and provide a novel outlook on the sub-regions involved. In a similar vein, congruent (or incongruent) reliance of pathways, that is reliance on the word (or pseudoword) pathway during word reading and on the pseudoword (or word) pathway during pseudoword reading predicted good (or poor) reading performance as assessed by out-of-magnet reading tests. Finally, inter-individual analysis unraveled an efficient reading style mirroring pathway reliance as a function of the fingerprint of the stimulus to be read, suggesting an optimal pattern of cerebral information trafficking which leads to high reading performance.
PMCID: PMC2724737  PMID: 19688099
5.  Early diagnosis of Alzheimer's disease using cortical thickness: impact of cognitive reserve 
Brain  2009;132(8):2036-2047.
Brain atrophy measured by magnetic resonance structural imaging has been proposed as a surrogate marker for the early diagnosis of Alzheimer's disease. Studies on large samples are still required to determine its practical interest at the individual level, especially with regards to the capacity of anatomical magnetic resonance imaging to disentangle the confounding role of the cognitive reserve in the early diagnosis of Alzheimer's disease. One hundred and thirty healthy controls, 122 subjects with mild cognitive impairment of the amnestic type and 130 Alzheimer's disease patients were included from the ADNI database and followed up for 24 months. After 24 months, 72 amnestic mild cognitive impairment had converted to Alzheimer's disease (referred to as progressive mild cognitive impairment, as opposed to stable mild cognitive impairment). For each subject, cortical thickness was measured on the baseline magnetic resonance imaging volume. The resulting cortical thickness map was parcellated into 22 regions and a normalized thickness index was computed using the subset of regions (right medial temporal, left lateral temporal, right posterior cingulate) that optimally distinguished stable mild cognitive impairment from progressive mild cognitive impairment. We tested the ability of baseline normalized thickness index to predict evolution from amnestic mild cognitive impairment to Alzheimer's disease and compared it to the predictive values of the main cognitive scores at baseline. In addition, we studied the relationship between the normalized thickness index, the education level and the timeline of conversion to Alzheimer's disease. Normalized thickness index at baseline differed significantly among all the four diagnosis groups (P < 0.001) and correctly distinguished Alzheimer's disease patients from healthy controls with an 85% cross-validated accuracy. Normalized thickness index also correctly predicted evolution to Alzheimer's disease for 76% of amnestic mild cognitive impairment subjects after cross-validation, thus showing an advantage over cognitive scores (range 63–72%). Moreover, progressive mild cognitive impairment subjects, who converted later than 1 year after baseline, showed a significantly higher education level than those who converted earlier than 1 year after baseline. Using a normalized thickness index-based criterion may help with early diagnosis of Alzheimer's disease at the individual level, especially for highly educated subjects, up to 24 months before clinical criteria for Alzheimer's disease diagnosis are met.
PMCID: PMC2714060  PMID: 19439419
Early Alzheimer's disease; individual diagnosis; mild cognitive impairment; magnetic resonance imaging (MRI); cognitive reserve

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