Assessing early white matter predictors of syntactic abilities in post-stroke aphasia using HARDI-based tractography

La recherche de prédicteurs d’habilités langagières en aphasie post-accident vasculaire cérébral (AVC) basés sur la matière blanche a récemment vu un élan. Cela a été motivé par l’émergence du modèle à double-voie où des faisceaux de matière blanche dorsaux et ventraux jouent un rôle important dans le langage, ainsi que par l’avènement de la tractographie basée sur l’imagerie par résonance magnétique (IRM) de diffusion permettant l’étude in-vivo des faisceaux de matière blanche et de leurs propriétés structurelles. Les caractéristiques structurelles et la charge lésionnelle des faisceaux de matière blanche ont permis de prédire les troubles langagiers dans la phase chronique dans quelques études. Cependant, les prédicteurs aigus de matière blanche des habilités syntaxiques en aphasie post-AVC chronique sont méconnus. L’exploitation de la tractographie dans l’étude des faisceaux langagiers de matière blanche a été limitée par plusieurs défis méthodologiques, dont la difficulté de reconstruire des faisceaux ayant une architecture complexe. Des progrès méthodologiques ont été récemment introduits afin d’adresser ces limites, dont le plus important est la tractographie basée sur l’imagerie à haute résolution angulaire (« HARDI »). Cependant, la fiabilité test-retest de la reconstruction et des propriétés structurelles d’une approche de tractographie HARDI de pointe n’a pas encore été évaluée. Le premier article de cette thèse visait à évaluer la fiabilité test-retest de la reconstruction et des propriétés structurelles (anisotropie fractionnelle, FA; diffusivité moyenne, axiale et radiale, MD, AD, RD; nombre d’orientations de fibres, NuFO; volume du faisceau; longueur moyenne des « streamlines ») de faisceaux langagiers majeurs (arqué, inférieur fronto-occipital, inférieur longitudinal, unciné, AF, IFOF, ILF, UF) obtenus avec une approche de tractographie HARDI de pointe. La majorité des mesures de propriétés structurelles ont montré une bonne ou excellente fiabilité. Ces résultats ont des implications importantes pour l’utilisation d’une telle approche pour l’étude des faisceaux langagiers de matière blanche, car ils renforcent la confiance dans la stabilité des reconstructions et les propriétés structurelles obtenus avec la tractographie HARDI. Le second article de cette thèse visait à déterminer si et quelles propriétés structurelles (FA, AD, volume du faisceau), et la charge lésionnelle, de l’AF et l’UF gauches dans la phase aigüe (≤ 3 jours), obtenus avec l’approche de tractographie HARDI utilisée dans le premier article, prédisent les habilités syntaxiques dans le discours spontané en aphasie post-AVC chronique (≥ 6 mois). Des régressions multiples ascendantes ont révélé que le volume de l’AF prédit la production des verbes, la complexité des phrases et la complexité de la structure argumentale du verbe. Le volume de l’UF a amélioré la prédiction de cette dernière. Ces résultats indiquent que le volume semble être un bon prédicteur précoce des habilités syntaxiques dans le discours spontané en aphasie post-AVC chronique. Mis ensemble, les résultats de cette thèse soulignent l’utilité d’une approche de tractographie HARDI de pointe et son potentiel pour le développement futur de biomarqueurs précoces pouvant améliorer le pronostic de patients ayant une aphasie post-AVC chronique. Cela pourrait promouvoir l’optimisation des soins et le développement de thérapies pour le bienfait des patients et leurs familles.The search for white matter predictors of language abilities in post-stroke aphasia has gained momentum in recent years. This growing interest has been driven by the emergence of the dual-stream framework where dorsal and ventral white matter bundles play an important functional role in language, as well as the advent of diffusion magnetic resonance imaging (MRI)-based tractography which allows the in-vivo investigation of white matter bundles and their structural properties. Structural characteristics, as well as the lesion load, of white matter bundles have been previously found to predict language impairments in the chronic phase. However, little is known about acute white matter predictors of syntactic abilities in chronic post-stroke aphasia. Leveraging tractography to study white matter language bundles has been limited by several methodological challenges, such as the difficulty of reconstructing white matter bundles with a complex fiber architecture. A number of methodological advances have been introduced fairly recently to address these limitations, the most important of which is the advent of tractography based on High Angular Resolution Imaging (HARDI). However, the test-retest reliability of the reconstruction and structural properties of a state-of-the-art HARDI-based tractography pipeline has not been previously assessed. The first article of the present thesis aimed to assess the test-retest reliability of the reconstruction and structural properties (fractional anisotropy, FA; mean, axial, radial diffusivity, MD, AD, RD; number of fiber orientations, NuFO; bundle volume; mean length of streamlines) of major white matter language bundles (arcuate, inferior fronto-occipital, inferior longitudinal, and uncinate fasciculi, AF, IFOF, ILF, UF) obtained using a state-of-the-art HARDI-based tractography pipeline. Most measures of structural properties showed good to excellent test-retest reliability. These findings have important implications for the use of such a pipeline for the study of white matter language bundles, as they increase our confidence that the reconstructions and structural properties obtained from the tractography pipeline are stable and not due to random variations in measurement. The second article of the thesis aimed to determine whether and which structural properties (FA, AD, bundle volume), as well as the lesion load, of the left AF and UF in the acute phase post-stroke (≤ 3 days), obtained with the same state-of-the-art HARDI-based tractography pipeline used in the first article, predict syntactic abilities in connected speech in chronic post-stroke aphasia (≥ 6 months). Forward multiple regressions revealed that the left AF’s volume predicted the percentage of verbs produced, the structural complexity of sentences, as well as verb-argument structure complexity. The left UF’s volume improved the prediction of verbs with a complex argument structure. These findings indicate that the bundle volume may be a good early predictor of syntactic ability in connected speech in chronic post-stroke aphasia. Overall, the findings of this thesis highlight the usefulness of a state-of-the-art HARDI-based tractography approach and its potential for the future development of early biomarkers that could improve the prognosis and personalized care of patients with chronic post-stroke aphasia. This would promote the optimization of patient care and the development of therapies for the benefit of patients and their families

Lexical selection in spoken word production among Arabic-French bilinguals : a language-specific or nonspecific process?

Tableau d'honneur de la Faculté des études supérieures et postdorales, 2014-2015L’objectif principal de ce mémoire est d’étudier la nature du processus de sélection lexicale chez des bilingues tardifs modérément compétents et locuteurs de deux langues lexicalement distantes : l’Arabe tunisien (AT) et le Français. Dans un premier temps, une base de données psycholinguistique en AT a été créée aux fins du contrôle convenable de variables psycholinguistiques dans la sélection des stimuli en AT. Cette première étude avait aussi pour but de mettre à disposition des chercheurs intéressés par le traitement du langage en Arabe une ressource psycholinguistique nécessaire. Dans la deuxième et principale étude, des bilingues AT-Français ont effectué une tâche d’interférence image-mot dans deux contextes expérimentaux différentes : unilingue (Expérience 1) ou bilingue (Expérience 2). Nos résultats suggèrent que le traitement lexical chez les bilingues est dynamique et modulé par un nombre de facteurs incluant, mais non limités à, la compétence langagière et le contexte langagier de l’expérimentation.The main aim of this master’s thesis was to investigate the nature of the lexical selection process among late moderately proficient bilinguals whose two languages are lexically distant: Tunisian Arabic (TA) and French. As a first step, a psycholinguistic normative database in TA was created to enable proper control of several psycholinguistic variables in the selection of TA stimuli. This first study also aimed to provide researchers interested in Arabic language processing with a much-needed psycholinguistic resource for a spoken variety of Arabic. In the second and main study, TA-French moderately proficient bilinguals performed a picture-word interference task in two different language settings: monolingual (Experiment 1) and bilingual (Experiment 2). Our findings suggest that bilingual lexical processing is dynamic and modulated by a variety of factors including, but not limited to, language proficiency and experimental language setting

Bilingual lexical selection as a dynamic process:evidence from Arabic-French bilinguals

The nature of the lexical selection process in bilingual spoken word production is one of the pending questions of research on bilingualism. According to one view this competitive process is language-specific, while another holds that it is language-nonspecific (i.e., lexical competition is cross-linguistic). In recent years, research on bilingual language production has seen the rise of a third view that postulates that lexical selection is in fact dynamic and may function as language-specific or nonspecific depending on a number of factors. The aim of the present study was to investigate the lexical selection process among moderately proficient bilinguals whose two languages are typologically distant: Tunisian Arabic and French. The picture-word interference task was used in two experiments where moderately proficient Tunisian Arabic (L1)-French (L2) bilinguals were asked to name pictures in their L2 while ignoring auditory distractors (semantic, phono-translation, phonological, or unrelated) in their L2 (Experiment 1) or their L1 (Experiment 2). Thus, the language context was entirely monolingual in Experiment 1 and bilingual in Experiment 2. In Experiment 1, only a phonological facilitation effect was observed. In Experiment 2, interference was found in the phono-translation, semantic, and phonological conditions. Taken together, these results indicate that cross-language competition occurs among moderately proficient Tunisian Arabic-French bilinguals only in a bilingual context (Experiment 2) as indexed by the phono-translation interference effect observed. Our findings are in line with the recent hypothesis that lexical selection is a dynamic process modulated by factors like language similarity, language proficiency, and the experimental language context

Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer’s disease: a behavioral and neuroimaging study

The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer’s disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions

Test-Retest Reliability of Diffusion Measures Extracted Along White Matter Language Fiber Bundles Using HARDI-Based Tractography

High angular resolution diffusion imaging (HARDI)-based tractography has been increasingly used in longitudinal studies on white matter macro- and micro-structural changes in the language network during language acquisition and in language impairments. However, test-retest reliability measurements are essential to ascertain that the longitudinal variations observed are not related to data processing. The aims of this study were to determine the reproducibility of the reconstruction of major white matter fiber bundles of the language network using anatomically constrained probabilistic tractography with constrained spherical deconvolution based on HARDI data, as well as to assess the test-retest reliability of diffusion measures extracted along them. Eighteen right-handed participants were scanned twice, one week apart. The arcuate, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculi were reconstructed in the left and right hemispheres and the following diffusion measures were extracted along each tract: fractional anisotropy, mean, axial, and radial diffusivity, number of fiber orientations, mean length of streamlines, and volume. All fiber bundles showed good morphological overlap between the two scanning timepoints and the test-retest reliability of all diffusion measures in most fiber bundles was good to excellent. We thus propose a fairly simple, but robust, HARDI-based tractography pipeline reliable for the longitudinal study of white matter language fiber bundles, which increases its potential applicability to research on the neurobiological mechanisms supporting language

The role of the left anterior temporal lobe for unpredictable and complex mappings in word reading

The anterior temporal lobes (ATLs) have been consistently associated with semantic processing which, in turn, has a key role in reading aloud single words. This study aimed to investigate (1) the reading abilities in patients with the semantic variant of primary progressive aphasia (svPPA), and (2) the relationship between gray matter (GM) volume of the left ATL and word reading performance using voxel-based morphometry (VBM). Three groups of participants (svPPA, Alzheimer’s Disease, AD and healthy elderly adults) performed a reading task with exception words, regular words and pseudowords, along with a structural magnetic resonance imaging scan. For exception words, the svPPA group had a lower accuracy and a greater number of regularization errors as compared to the control groups of healthy participants and AD patients. Similarly, for regular words, svPPA patients had a lower accuracy in comparison with AD patients, and a greater number of errors related to complex orthography-to-phonology mappings (OPM) in comparison to both control groups. VBM analyses revealed that GM volume of the left ATL was associated with the number of regularization errors. Also, GM volume of the left lateral ATL was associated with the number of errors with complex OPM during regular word reading. Our results suggest that the left ATL might play a role in the reading of exception words, in accordance with its role in semantic processing. Results further support the involvement of the left lateral ATL in combinatorial processes, including the integration of semantic and phonological information, for both exception and regular words

Test-retest reliability of diffusion measures extracted along white matter language fiber bundles using HARDI-based tractography

High angular resolution diffusion imaging (HARDI)-based tractography has been increasingly used in longitudinal studies on white matter macro- and micro-structural changes in the language network during language acquisition and in language impairments. However, test-retest reliability measurements are essential to ascertain that the longitudinal variations observed are not related to data processing. The aims of this study were to determine the reproducibility of the reconstruction of major white matter fiber bundles of the language network using anatomically constrained probabilistic tractography with constrained spherical deconvolution based on HARDI data, as well as to assess the test-retest reliability of diffusion measures extracted along them. Eighteen right-handed participants were scanned twice, one week apart. The arcuate, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculi were reconstructed in the left and right hemispheres and the following diffusion measures were extracted along each tract: fractional anisotropy, mean, axial, and radial diffusivity, number of fiber orientations, mean length of streamlines, and volume. All fiber bundles showed good morphological overlap between the two scanning timepoints and the test-retest reliability of all diffusion measures in most fiber bundles was good to excellent. We thus propose a fairly simple, but robust, HARDI-based tractography pipeline reliable for the longitudinal study of white matter language fiber bundles, which increases its potential applicability to research on the neurobiological mechanisms supporting language

Des objets sans sens : connaissances concrètes et démence sémantique.

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The role of the hippocampus in the semantic variant of primary progressive aphasia : a resting‐state fcMRI study

The goal of the study was to determine whether the semantic variant of primary progressive aphasia (svPPA) affects the intrinsic connectivity network anchored to left and right anterior hippocampus, but spares the posterior hippocampus. A resting‐state functional connectivity MRI (rs‐fcMRI) study was conducted in a group of patients with svPPA and in controls, using a seed‐to‐voxel approach. In comparison to controls, massively reduced connectivity was found in the anterior hippocampus, mainly the left one, for svPPA patients but not in the left or right posterior hippocampus. In svPPA, the anterior hippocampus showed reduced functional connectivity with regions implicated in the semantic memory network. Significant correlation was also found between the functional connectivity strength of the left anterior hippocampus and the ventromedial cortex, and performance in semantic tasks. These findings indicate that the functional disconnection of the anterior hippocampus may be a promising in vivo biomarker of svPPA and illustrate the role of this hippocampal subregion in the semantic memory system

Differential language network functional connectivity alterations in Alzheimer's disease and the semantic variant of primary progressive aphasia

Patients with Alzheimer's disease (AD) and semantic variant primary progressive aphasia (svPPA) can present with similar language impairments, mainly in naming. It has been hypothesized that these deficits are associated with different brain mechanisms in each disease, but no previous study has used a network approach to explore this hypothesis. The aim of this study was to compare resting-state functional magnetic resonance imaging (rs-fMRI) language network in AD, svPPA patients, and cognitively unimpaired elderly adults (CTRL). Therefore, 10 AD patients, 12 svPPA patients and 11 CTRL underwent rs-fMRI. Seed-based functional connectivity analyses were conducted using regions of interest in the left anterior temporal lobe (ATL), left posterior middle temporal gyrus (pMTG) and left inferior frontal gyrus (IFG), applying a voxelwise correction for gray matter volume. In AD patients, the left pMTG was the only key language region showing functional connectivity changes, mainly a reduced interhemispheric functional connectivity with its right-hemisphere counterpart, in comparison to CTRL. In svPPA patients, we observed a functional isolation of the left ATL, both decreases and increases in functional connectivity from the left pMTG and increased functional connectivity form the left IFG. Post-hoc analyses showed that naming impairments were overall associated with the functional disconnections observed across the language network. In conclusion, AD and svPPA patients present distinct language network functional connectivity profiles. In AD patients, functional connectivity changes were restricted to the left pMTG and were overall less severe in comparison to svPPA patients. Results in svPPA patients suggest decreased functional connectivity along the ventral language pathway and increased functional connectivity along the dorsal language pathway. Finally, the observed connectivity patterns are overall consistent with previously reported structural connectivity and language profiles in these patients