Codage de l'identité et de la position lors du traitement de séquences de lettres : normo-lecteur versus dyslexique. Etude comportementale chez l'enfant et étude en IRMf chez l'adulte

L'acte de lire représente une activité devenue parfaitement automatique et constitue un outil permettant de s'inscrire et de participer au monde social et culturel qui nous entoure. L'acquisition de la lecture requiert un apprentissage long et laborieux. Il repose sur la capacité des lecteurs à identifier correctement des stimuli visuels complexes à un degré tel qu'ils doivent pouvoir distinguer " lion " et " loin " ou " foin " en une seule et unique fixation. Par conséquent, le codage de l'identité et de la position de la lettre est crucial dans l'identification visuelle des mots. Ce travail de thèse s'inscrit dans ce cadre de recherche et présente deux objectifs principaux. Premièrement, nous voulions explorer la façon dont le codage de l'identité et la position de la lettre est modulé par le contexte orthographique au cours de l'acquisition de la lecture et dans le cadre de la dyslexie de développement. Les participants réalisaient une tâche de comparaison de séquences de lettres dans laquelle ils devaient juger si deux suites de lettres présentées successivement et brièvement étaient identiques ou différentes. L'identité et la position des lettres étaient manipulées par le biais d'une substitution ou d'une transposition de deux lettres au sein de la séquence. Des non-mots, des pseudo-mots et des mots ont été utilisés comme stimuli pour étudier les effets lexicaux et sub-lexicaux sur l'encodage des lettres. Les résultats montrent que le traitement orthographique (codage de l'identité et de la position des lettres) et la représentation lexicale sont soumis à des changements développementaux et sont altérés chez les enfants dyslexiques. Un trouble de l'empan visuo-attentionnel (VA), i.e. une capacité VA réduite, chez ces enfants dyslexiques permet de rendre compte de ces perturbations. Deuxièmement, nous voulions explorer, en utilisant l'IRMf, les substrats neurobiologiques du codage de l'identité et de la position des lettres en contexte non-mot chez des adultes normo-lecteurs et dyslexiques. Les normo-lecteurs montrent une forte activation dans les régions pariétales et l'aire occipito-temporale ventrale (VOT) en condition de substitution de lettres, tandis que ces activations sont absentes chez les dyslexiques. Chez les normo-lecteurs, la condition de transposition de lettres active un réseau cortical plus limité, incluant l'aire VOT, laquelle n'est pas activée chez les participants dyslexiques. Ces résultats conduisent à mieux le rôle des régions pariétales et VOT dans la phase précoce du traitement visuel des mots en lecture et dans le cadre de la dyslexie développementale.With time and practice, reading becomes a fully automatized activity that acts as an essential tool for our insertion in the social and cultural world around us. The acquisition of reading is long and laborious and relies on the readers' capacity to properly identify complex visual stimuli at such a fine degree that 'causal' must be discriminated from 'casual' within a single fixation. Consequently, letter-identity and letter-position encoding are crucial for visual identification of words. This thesis work fits into this research framework and investigates two main issues. First, we aimed to explore how letter-identity and letter-position encoding are modulated by letter context during reading acquisition and in developmental dyslexia. A letter-string comparison task was administered to participants who had to judge whether two successively and briefly presented letter strings were identical or different. Letter-position and letter-identity were manipulated through the transposition or substitution of two letters. Non-words, pseudo-words, and words were used as stimuli to investigate sub-lexical and lexical effects on letter encoding. Results show that orthographic processing (letter-identity and letter-position encoding) and lexical representations are subject to developmental changes and are strongly impaired in dyslexic children. A disorder of visuo-attention (VA) span, i.e. a reduced VA capacity, in these dyslexic children might account for this deficit. Secondly, using fMRI, we investigated the neurobiological substrates of letter-position and letter-identity encoding in non-word context in normal and dyslexic adults. Healthy readers activate the parietal and ventral occipito-temporal (VOT) areas in the substitution condition, while dyslexics do not. In healthy readers, the transposition condition activates a more limited cortical network including VOT area, which was not activated in dyslexic participants. These findings provide new insights on the role of parietal and VOT regions in the early phase of visual word processing in reading and developmental dyslexia

L'orthographe grammaticale au collège: une approche sociodifférenciée.

National audienceCette étude vise à préciser les difficultés en orthographe grammaticale de collégiens de 6e scolarisés en réseaux de réussite scolaire (RRS). Un texte de 64 mots a été dicté à 341 élèves dans trois collèges sociodifférenciés, permettant d'évaluer le marquage de l'accord en nombre (singulier, pluriel) du verbe avec le sujet, et du nom et de l'adjectif dans le groupe nominal. Les résultats montrent la fragilité du marquage du pluriel pour tous les élèves, quelle que soit la catégorie grammaticale, et cette difficulté est beaucoup plus grande dans le collège le moins favorisé

Analysis of Variance in Neuroreceptor Ligand Imaging Studies

Radioligand positron emission tomography (PET) with dual scan paradigms can provide valuable insight into changes in synaptic neurotransmitter concentration due to experimental manipulation. The residual t-test has been utilized to improve the sensitivity of the t-test in PET studies. However, no further development of statistical tests using residuals has been proposed so far to be applied in cases when there are more than two conditions. Here, we propose the residual f-test, a one-way analysis of variance (ANOVA), and examine its feasibility using simulated [11C]raclopride PET data. We also re-visit data from our previously published [11C]raclopride PET study, in which 10 individuals underwent three PET scans under different conditions. We found that the residual f-test is superior in terms of sensitivity than the conventional f-test while still controlling for type 1 error. The test will therefore allow us to reliably test hypotheses in the smaller sample sizes often used in explorative PET studies

Brain atrophy and white matter hyperintensities are independently associated with plasma neurofilament light chain in an Asian cohort of cognitively impaired patients with concomitant cerebral small vessel disease

Introduction: Plasma neurofilament light chain (NfL) is a potential biomarker for neurodegeneration in Alzheimer's disease (AD), ischemic stroke, and non-dementia cohorts with cerebral small vessel disease (CSVD). However, studies of AD in populations with high prevalence of concomitant CSVD to evaluate associations of brain atrophy, CSVD, and amyloid beta (Aβ) burden on plasma NfL are lacking. Methods: Associations were tested between plasma NfL and brain Aβ, medial temporal lobe atrophy (MTA) as well as neuroimaging features of CSVD, including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds. Results: We found that participants with either MTA (defined as MTA score ≥2; neurodegeneration [N]+WMH−) or WMH (cut-off for log-transformed WMH volume at 50th percentile; N−WMH+) manifested increased plasma NfL levels. Participants with both pathologies (N+WMH+) showed the highest NfL compared to N+WMH−, N−WMH+, and N−WMH− individuals. Discussion: Plasma NfL has potential utility in stratifying individual and combined contributions of AD pathology and CSVD to cognitive impairment

Validation of low-dose lung cancer PET-CT protocol and PET image improvement using machine learning

PURPOSE: To conduct a simplified lesion-detection task of a low-dose (LD) PET-CT protocol for frequent lung screening using 30% of the effective PETCT dose and to investigate the feasibility of increasing clinical value of low-statistics scans using machine learning. METHODS: We acquired 33 SD PET images, of which 13 had actual LD (ALD) PET, and simulated LD (SLD) PET images at seven different count levels from the SD PET scans. We employed image quality transfer (IQT), a machine learning algorithm that performs patch-regression to map parameters from low-quality to high-quality images. At each count level, patches extracted from 23 pairs of SD/SLD PET images were used to train three IQT models - global linear, single tree, and random forest regressions with cubic patch sizes of 3 and 5 voxels. The models were then used to estimate SD images from LD images at each count level for 10 unseen subjects. Lesion-detection task was carried out on matched lesion-present and lesion-absent images. RESULTS: LD PET-CT protocol yielded lesion detectability with sensitivity of 0.98 and specificity of 1. Random forest algorithm with cubic patch size of 5 allowed further 11.7% reduction in the effective PETCT dose without compromising lesion detectability, but underestimated SUV by 30%. CONCLUSION: LD PET-CT protocol was validated for lesion detection using ALD PET scans. Substantial image quality improvement or additional dose reduction while preserving clinical values can be achieved using machine learning methods though SUV quantification may be biased and adjustment of our research protocol is required for clinical use

Head-to-head comparison of amplified plasmonic exosome Aβ42 platform and single-molecule array immunoassay in a memory clinic cohort

Background: Various blood biomarkers reflecting brain amyloid‐β (Aβ) load have recently been proposed with promising results. However, to date, no comparative study among blood biomarkers has been reported. Our objective is to examine the diagnostic performance and cost effectiveness of three blood biomarkers on the same cohort. Methods: Using the same cohort (n=68), we compared the performance of the single‐molecule array (Simoa)‐Aβ40 and Aβ42, Aβ42/Aβ40 and the amplified plasmonic exosome (APEX)‐Aβ42 blood biomarkers using amyloid PET as the reference standard. We also determined the extent to which these blood tests can reduce the recruitment cost of clinical trials by identifying Amyloid positive (Aβ+) participants. Results: Compared to Simoa biomarkers, APEX‐Aβ42 showed significantly higher correlations with amyloid PET retention values and excellent diagnostic performance (sensitivity=100%, specificity=93.3%, AUC=0.995). When utilized for clinical trial recruitment, our simulation showed that pre‐screening with blood biomarkers followed by a confirmatory amyloid PET imaging would roughly half the cost (56.8% reduction for APEX‐Aβ42 and 48.6% for Simoa‐Aβ42/Aβ40) as compared to the situation where only PET imaging is used. Moreover, with a 100% sensitivity; APEX‐Aβ42 pre‐screening does not increase the required number of initial participants. Conclusions: With its high diagnostic performance, APEX is an ideal candidate for Aβ+ subject identification, monitoring, primary care screening, and could efficiently enrich clinical trials with Aβ+ participants while halving recruitment costs

What approach to brain partial volume correction is best for PET/MRI?

Many partial volume correction approaches make use of anatomical information, readily available in PET/MRI systems but it is not clear what approach is best. Seven novel approaches to partial volume correction were evaluated, including several post-reconstruction methods and several reconstruction methods that incorporate anatomical information. These were compared with an MRI-independent approach (reblurred van Cittert ) and uncorrected data. Monte Carlo PET data were generated for activity distributions representing both 18F FDG and amyloid tracer uptake. Post-reconstruction methods provided the best recovery with ideal segmentation but were particularly sensitive to mis-registration. Alternative approaches performed better in maintaining lesion contrast (unseen in MRI) with good noise control. These were also relatively insensitive to mis-registration errors. The choice of method will depend on the specific application and reliability of segmentation and registration algorithms