Associations between lesion size, lesion location and aphasia in acute stroke

Background: The localization and organization of language has been an ongoing research interest ever since the early findings of Paul Broca. The emergence of neuroimaging the past 20 years has given us new insights on the anatomical and structural organization of the brain. Lesion studies on patients with aphasia can provide knowledge on where and how specific language functions are organized in the brain. Aims: The primary objective of the study was to investigate the relationships between aphasia severity, aphasic symptoms, lesion location and lesion volume in patients with left hemispheric stroke in the acute phase (within one week post-stroke). Using a voxel-based lesion-symptom mapping method (VLSM), we hypothesized that lesions associated with speech comprehension deficits mainly would involve regions within the posterior superior and middle temporal lobe, and lesions associated with speech production deficits would mainly be associated to the inferior frontal areas of the left hemisphere. Methods & procedures: Findings from diffusion-weighted magnetic resonance imaging (DWI-MRI) and patients’ scores from the Norwegian Basic Aphasia Assessment (NBAA) were used to investigate our research questions. We did a whole group analysis of descriptive statistics, lesion localization and lesion volume. We thereafter divided the patients into two groups based on their median scores on the NBAA, one high comprehension group and one low comprehension group. We used VLSM to investigate the associations between the patients’ lesions and the results from the NBAA. Outcomes & Results: Lesion volume was significantly associated with all subtest from the NBAA. Our initial analysis of the whole group showed that difficulties in naming was associated with lesions within the rolandic operculum. We also found that difficulties in repetition was associated with lesions within the rolandic operculum, and in addition, the superior temporal gyrus. In the group of patients with high comprehension scores lesions within Broca’s area, insula, the superior temporal gyrus (STG) and Heschl’s gyrus were found to be associated with difficulties with overall aphasia severity, repetition, naming, and reading out loud from the NBAA. Conclusions: Lesion volume is strongly associated with aphasia severity in the acute stages of stroke. Further, lesions within Broca’s area, the insula, the STG and Heschl’s gyrus were found to be crucial areas in language comprehension and production. This confirms current views that speech and language processes depend on the integrity of the entire network comprising both cortical structures and their interconnected fibre tracts

Arterial spin labelling shows functional depression of non-lesion tissue in chronic Wernicke’s aphasia

Behavioural impairment post-stroke is a consequence of structural damage and altered functional network dynamics. Hypoperfusion of intact neural tissue is frequently observed in acute stroke, indicating reduced functional capacity of regions outside the lesion. However, cerebral blood flow is rarely investigated in chronic stroke. This study investigated cerebral blood flow in individuals with chronic Wernicke’s aphasia and examined the relationship between lesion, cerebral blood flow and neuropsychological impairment. Arterial spin labelling cerebral blood flow imaging and structural MRIs were collected in 12 individuals with chronic Wernicke’s aphasia and 13 age-matched control participants. Joint independent component analysis (jICA) investigated the relationship between structural lesion and hypoperfusion. Partial correlations explored the relationship between lesion, hypoperfusion and language measures. Joint ICA revealed significant differences between the control and WA groups reflecting a large area of structural lesion in the left posterior hemisphere and an associated area of hypoperfusion extending into grey matter surrounding the lesion. Small regions of remote cortical hypoperfusion were observed, ipsilateral and contralateral to the lesion. Significant correlations were observed between the neuropsychological measures (naming, repetition, reading and semantic association) and the jICA component of interest in the WA group. Additional ROI analyses found a relationship between perfusion surrounding the core lesion and the same neuropsychological measures

Intervention orthophonique et neurobiologie du cerveau : apports de la neuroimagerie à la prise en charge de l’aphasie chronique

L’aphasie est un trouble acquis du langage entraînant des problèmes de communication pouvant toucher la compréhension et/ou l’expression. Lorsque l’aphasie fait suite à un accident vasculaire cérébral, une régression des déficits communicatifs s'observe initialement, mais elle peut demeurer sévère pour certains et est considérée chronique après un an. Par ailleurs, l’aphasie peut aussi être observée dans l’aphasie progressive primaire, une maladie dégénérative affectant uniquement le langage dans les premières années. Un nombre grandissant d’études s’intéressent à l’impact de la thérapie dans l’aphasie chronique et ont démontré des améliorations langagières après plusieurs années. L’hémisphère gauche semble avoir un rôle crucial et est associé à de meilleures améliorations langagières, mais la compréhension des mécanismes de plasticité cérébrale est encore embryonnaire. Or, l’efficacité de la thérapie dans l’aphasie progressive primaire est peu étudiée. À l’aide de la résonance magnétique fonctionnelle, le but des présentes études consiste à examiner les mécanismes de plasticité cérébrale induits par la thérapie Semantic Feature Analysis auprès de dix personnes souffrant d’aphasie chronique et d’une personne souffrant d’aphasie progressive primaire. Les résultats suggèrent que le cerveau peut se réorganiser plusieurs années après une lésion cérébrale ainsi que dans une maladie dégénérative. Au niveau individuel, une meilleure amélioration langagière est associée au recrutement de l’hémisphère gauche ainsi qu’une concentration des activations. Les analyses de groupe mettent en évidence le recrutement du lobule pariétal inférieur gauche, alors que l’activation du gyrus précentral gauche prédit l’amélioration suite à la thérapie. D’autre part, les analyses de connectivité fonctionnelle ont permis d’identifier pour la première fois le réseau par défaut dans l’aphasie. Suite à la thérapie, l’intégration de ce réseau bien connu est comparable à celle des contrôles et les analyses de corrélation suggèrent que l’intégration du réseau par défaut a une valeur prédictive d’amélioration. Donc, les résultats de ces études appuient l’idée que l’hémisphère gauche a un rôle prépondérant dans la récupération de l’aphasie et fournissent des données probantes sur la neuroplasticité induite par une thérapie spécifique du langage dans l’aphasie. De plus, l’identification d’aires clés et de réseaux guideront de futures recherches afin d’éventuellement maximiser la récupération de l’aphasie et permettre de mieux prédire le pronostic.Aphasia is an acquired language impairment leading to communication disorders which may affect comprehension and/or expression. When aphasia follows a stroke, major recovery of the communicative deficits is initially observed after the lesion, but for some the aphasia may remain severe and is considered to be chronic after a year. Furthermore aphasia can be observed in primary progressive aphasia, a degenerative disease only affecting language in the early years. The impact of therapy in chronic aphasia is the subject of growing literature in recent years and has shown language improvements after several years of therapy. The left hemisphere seems to have a crucial role and is associated with greater language improvements but our understanding of brain plasticity mechanisms is still lacking. In primary progressive aphasia, few studies have examined therapy effectiveness. Using functional magnetic resonance imaging, the aim of these studies was to examine therapy-induced brain plasticity mechanisms following Semantic Feature Analysis in ten participants suffering from chronic aphasia and one participant with primary progressive aphasia. The results suggest that brain reorganization is possible several years after injury and in degenerative disease. At the individual level, greater language improvement is associated with the recruitment of the left hemisphere and less activated areas. Group analysis shows the recruitment of left inferior parietal lobule, whereas the activation of left precentral gyrus predicts improved response to therapy. Functional connectivity analysis allowed for the first time the identification of the default-mode network in aphasia. Following therapy, the integration of this well-known network is comparable to that of the controls and the correlation analysis suggests that the default-mode network integration has a predictive value for improvement. Therefore, the results of these studies support the idea that the left hemisphere has a major role in the recovery of aphasia and provide evidence on therapy-induced neuroplasticity in aphasia. In addition, the identification of key areas and networks will guide future research in order to possibly maximize the recovery of aphasia and to better predict the prognosis

Cross-Linguistic Transfer (CLT) in Bilingual Speakers : Neural Correlates of Language Learning

Le but de cette thèse est d'étudier les corrélats comportementaux et neuronaux du transfert inter-linguistique (TIL) dans l'apprentissage d’une langue seconde (L2). Compte tenu de nos connaissances sur l'influence de la distance linguistique sur le TIL (Paradis, 1987, 2004; Odlin, 1989, 2004, 2005; Gollan, 2005; Ringbom, 2007), nous avons examiné l'effet de facilitation de la similarité phonologique à l’aide de la résonance magnétique fonctionnelle entre des langues linguistiquement proches (espagnol-français) et des langues linguistiquement éloignées (persan-français). L'étude I rapporte les résultats obtenus pour des langues linguistiquement proches (espagnol-français), alors que l'étude II porte sur des langues linguistiquement éloignées (persan-français). Puis, les changements de connectivité fonctionnelle dans le réseau langagier (Price, 2010) et dans le réseau de contrôle supplémentaire impliqué dans le traitement d’une langue seconde (Abutalebi & Green, 2007) lors de l’apprentissage d’une langue linguistiquement éloignée (persan-français) sont rapportés dans l’étude III. Les résultats des analyses d’IRMF suivant le modèle linéaire général chez les bilingues de langues linguistiquement proches (français-espagnol) montrent que le traitement des mots phonologiquement similaires dans les deux langues (cognates et clangs) compte sur un réseau neuronal partagé par la langue maternelle (L1) et la L2, tandis que le traitement des mots phonologiquement éloignés (non-clang-non-cognates) active des structures impliquées dans le traitement de la mémoire de travail et d'attention. Toutefois, chez les personnes bilingues de L1-L2 linguistiquement éloignées (français-persan), même les mots phonologiquement similaires à travers les langues (cognates et clangs) activent des régions connues pour être impliquées dans l'attention et le contrôle cognitif. Par ailleurs, les mots phonologiquement éloignés (non-clang-non-cognates) activent des régions usuellement associées à la mémoire de travail et aux fonctions exécutives. Ainsi, le facteur de distance inter-linguistique entre L1 et L2 module la charge cognitive sur la base du degré de similarité phonologiques entres les items en L1 et L2. Des structures soutenant les processus impliqués dans le traitement exécutif sont recrutées afin de compenser pour des demandes cognitives. Lorsque la compétence linguistique en L2 augmente et que les tâches linguistiques exigent ainsi moins d’effort, la demande pour les ressources cognitives diminue. Tel que déjà rapporté (Majerus, et al, 2008; Prat, et al, 2007; Veroude, et al, 2010; Dodel, et al, 2005; Coynel, et al ., 2009), les résultats des analyses de connectivité fonctionnelle montrent qu’après l’entraînement la valeur d'intégration (connectivité fonctionnelle) diminue puisqu’il y a moins de circulation du flux d'information. Les résultats de cette recherche contribuent à une meilleure compréhension des aspects neurocognitifs et de plasticité cérébrale du TIL ainsi que l'impact de la distance linguistique dans l'apprentissage des langues. Ces résultats ont des implications dans les stratégies d'apprentissage d’une L2, les méthodes d’enseignement d’une L2 ainsi que le développement d'approches thérapeutiques chez des patients bilingues qui souffrent de troubles langagiers.The purpose of this thesis was to study the behavioral and neural correlates of Cross-linguistic Transfer effects (CLT) at the word level, in second language learning. Moreover, given that language distance has an impact on CLT, (Paradis, 1987, 2004, Odlin, 1989, 2004, 2005, Gollan, 2005, Ringbom, 2007), two distinct language pairs were examined: Close language pairs (Spanish-French) and distant language pairs (Persian-French). This thesis comprises three studies. In study I, Spanish speakers and in study II Persian speakers were trained for lexical learning until consolidation level. Cognates (phonologically and semantically similar words), Clangs (phonologically similar words with different meanings), and Non-cognate-non-clangs (semantically similar words), were presented in a picture naming task. Accuracy rates and response times as well as event-related fMRI BOLD responses to each word category were measured. Simple and direct contrasts with phonologically similar and phonologically distant words were performed. Thus, Study I reports the results of close languages (Spanish-French) and Study II, reports the results of distant languages (Persian-French). The neurocognitive processing of language learning was further investigated in terms of networks using functional connectivity analysis in distant languages (Persian-French) and the results are reported in Study III. The Results with the General Linear Model analysis show that with close language pairs (French-Spanish), the processing of phonologically similar words (cognates and clangs) relies upon a shared L1-L2 language specific neural areas, whereas processing of phonologically distant words (non-clang-non-cognates), activates L1 language processing areas, but also relies upon working memory, attentional, and processing structures. However, with distant language pairs (French-Persian), even phonologically similar words (cognates and clangs) activate areas known to be involved in attentional processing and cognitive control. Moreover, phonologically distant words (non-clang-non-cognates) also activate areas involved in working memory and executive function processing structures. Thus, the factor of L1-L2 cross-linguistic distance appears to modulate the executive load imposed to the system, on the basis of the degree of phonological overlap between L1-L2 items; thus in order to compensate for more effortful processing demands, the system recruits executive function supporting structures. The results of the connectivity analysis show that, in line with literature (Majerus, et al., 2008; Prat, et al., 2007; Veroude, et al., 2010; Dodel, et al., 2005; Coynel, et al., 2009), when the language proficiency is low, there is enhanced functional connectivity between and within language specific and other cognitive processing (working memory, attentional and cognitive control) networks. However, as proficiency increases, integration values (functional connectivity) decrease. This reflects that language tasks become less effortful and demand less cognitive resources. The results of this dissertation contribute to a better understanding of CLT effects on L2 learning, both in regards to different word types and L1-L2 language distance. These results have implications with regards to L2 learning and teaching strategies and approaches as well as with regards to the development of data-driven therapy approaches in the case of language break down in bilingual population

Using non-invasive stimulation of the undamaged brain to guide the identification of lesion sites that predict language outcome after stroke

Disrupting the neural activity in the left anterior supramarginal gyrus (SMG) or opercular part of the left inferior frontal gyrus (pOp) with repetitive transcranial magnetic stimulation (TMS) has been demonstrated to cause a transient slowing of response times during phonologically more than semantically demanding tasks. Likewise, a wealth of functional magnetic resonance imaging (fMRI) studies have shown increased activation in SMG and/or pOp for phonological relative to semantic processing. Here I set out to investigate whether, and how frequently, stroke damage to SMG and/or pOp results in persistent phonological processing impairments in a large sample of 262 right-handed English-speaking adults, who were tested at least 1 year after a left-hemisphere stroke. In Experiment I, I compared the effect of damage to different parts of SMG and pOp that were defined by regions of interest from either TMS or fMRI studies of phonological processing in neurologically-normal individuals. I found that the incidence of phonological processing impairments was predicted significantly better by the presence or absence of damage to SMG and pOp regions defined by TMS studies than SMG and pOp regions defined by fMRI studies. Moreover, the discriminatory power (for segregating patients with and without phonological abilities) of the TMS sites was not improved further when combined with the fMRI sites. In Experiment II, I adapted the borders of the TMS SMG and pOp regions to include the surrounding grey and white matter where the presence or absence of stroke damage was consistently associated with the presence or absence of phonological processing impairments. The presence or absence of damage to these new TMS-guided regions was able to explain the incidence of phonological impairments better than the original TMS regions, even in a new sample of patients that was entirely independent of the region identification process. In Experiment III, I showed that damage to the TMS-guided regions accounted for the incidence of phonological impairments substantially better than damage to an alternative set of regions derived from voxel-based lesion-deficit mapping techniques that search the whole brain for areas that are most frequently damaged in those with phonological impairments. However, the best classification accuracy was observed when the analysis took into account a combination of regions from TMS-guided and voxel-based lesion-deficit mapping approaches. In Experiment IV, I investigated the nature of the functional impairment caused by SMG or pOp lesions and found that damage to either region impaired covert and overt phonological processing abilities more than semantic processing abilities, as predicted by prior TMS and fMRI studies of neurologically-normal subjects. Finally, the behavioural effects of damage were remarkably similar (i.e. no statistically significant differences) for both TMS-guided sites (i.e. pOp and SMG). In conclusion, the fact that damage to the TMS-guided SMG and pOp regions impaired phonological processing abilities years after stroke onset, suggests that these regions are critical for accurate phonological processing (both overt and covert) and that other brain areas are not typically able to fully compensate for the contribution that these regions make to language processing. More broadly, the results illustrate how non-invasive stimulation of the undamaged brain can be used to guide the identification of regions where brain damage is likely to cause persistent behavioural effects. By combining these regions of interest with those derived from other lesion-deficit mapping approaches, I was not only able to explain the presence, but also the absence, of phonological processing impairments in a large cohort of patients