Neurofunctional reorganization to support semantic processing during aging : an fMRI study

Le langage est dans son ensemble bien préservé pendant le vieillissement (Meyer & Federmeier, 2010) tandis que la mémoire sémantique peut même s'améliorer (Kavé, Samuel-Enoch, & Adiv, 2009; Prinz, Bucher, & Marder, 2004; Salthouse, 2009; Verhaegen & Poncelet, 2013 ; Wingfield & Grossman, 2006), malgré de nombreux changements neurophysiologiques se produisant dans le cerveau (Grady, Springer, Hongwanishkul, McIntosh, & Winocur, 2006 ; Kemper & Anagnopoulos, 1989 ; Wingfield & Grossman, 2006). Cette thèse se concentre sur la préservation de la mémoire sémantique dans le vieillissement, « l'acte cognitif d'accéder aux connaissances stockées sur le monde » (Binder, Desai, Graves et Conant, 2009) à travers une tâche de jugement sémantique manipulant le contrôle sémantique avec deux niveaux de demande (faible et élevé) et deux types de relations sémantiques (taxonomique et thématique). Nous avons développé une nouvelle tâche variant les niveaux de demande (faible et élevé) chez 39 adultes jeunes et 39 adultes âgés. Plus précisément, les objectifs de notre étude étaient 1) d'identifier si le vieillissement affecte l'activité cérébrale liée à la mémoire sémantique conformément aux prédictions du modèle CRUNCH, à travers une tâche de jugement sémantique à deux niveaux d'exigences. 2) de combler le vide de la littérature sur l'existence et l'évolution des hubs sémantiques dans le vieillissement, à la lumière des théories single hub et dual-hub, en évaluant l'effet du vieillissement sur le rôle des lobes temporaux antérieurs (ATL) et du jonction temporo-pariétale (TPJ) en tant que représentations neuronales des centres sémantiques responsables respectivement du traitement taxonomique et thématique. Une soumission par rapport pré-enregistré (registered report) a été utilisée pour ce projet de recherche. Nos participants, adultes plus jeunes et plus âgés, étaient globalement appariés en termes de réserve cognitive, plus précisément en ce qui concerne le niveau d'éducation et comme le montrent les questionnaires évaluant l'engagement dans des activités cognitivement stimulantes, les tests MoCA et WAIS-III. Les résultats comportementaux ont confirmé que la tâche varie correctement la difficulté de la tâche puisque les taux d'erreur et les temps de réponse (RT) augmentent de manière linéaire avec l'augmentation des exigences de la tâche, à savoir dans la condition de forte demande. Nous avons constaté que la participation à des activités stimulantes sur le plan cognitif avait un impact positif à la fois sur les RT de référence et sur la précision. Nous n’avons pas observé de différence statistiquement significative dans la précision entre les participants jeunes et plus âgés, quelle que soit la condition. Nous avons constaté que des scores plus élevés aux tests WAIS-III et PPTT étaient positivement corrélés avec la précision chez les personnes âgées. En termes de RT, nous avons observé une différence statistiquement significative entre les participants jeunes et plus âgés pour la tâche et les conditions de référence, les adultes plus âgés étant plus lents à répondre en général. Les RT augmentent linéairement avec l'âge du participant. En tant que telle, la tâche de mémoire sémantique a réussi à a) manipuler la difficulté de la tâche sur deux niveaux d'exigences et b) démontrer une performance comportementale invariante selon l'âge pour le groupe plus âgé, comme l'exige le test du modèle CRUNCH (Fabiani, 2012 ; Schneider-Garces et al., 2010). Pour l'objectif n°1, les tests cruciaux du modèle CRUNCH, l'interaction IRMf groupe par difficulté, n'étaient pas cohérents avec les prédictions du modèle. Malgré nos résultats comportementaux, lorsque nous avons comparé directement la condition de faible demande avec la condition de forte demande, il n'y avait pas de différence statistiquement significative dans l'activation entre les conditions de faible et de forte demande. Nous n'avons pas non plus obtenu d'interaction entre tranche d'âge et difficulté. Nous avons obtenu des interactions significatives en comparant les conditions de demande faible et élevée avec la ligne de référence. Au niveau neuronal, indépendamment de l'âge, la tâche de jugement de similarité sémantique a activé un large réseau bilatéral fronto-temporo-pariétal. Pour l'objectif n°2 concernant l'effet de relation sémantique, le contraste de la condition taxonomique avec la condition thématique directement n'a pas trouvé d'activation robuste à un seuil corrigé. La condition taxonomique a donné des résultats intéressants par rapport à la condition de base. Sept groupes distincts dans le cortex fronto-temporo-pariétal ont été activés dans les deux hémisphères, y compris les lobes temporaux antérieurs (ATL) et la jonction temporo-pariétale gauche (TPJ). De plus, l'activation était significative dans le gyrus supérieur frontal gauche, le gyrus angulaire gauche (AG) et le gyrus frontal inférieur (partie orbitale) sur l'hémisphère droit. Cette découverte pourrait être en partie conforme à la théorie du double-hub, qui propose que les ATL bilatéralement et le TPJ agissent comme des hubs sémantiques. Bien que nous n'ayons pas trouvé d'activation significative dans les ATL pendant la condition taxonomique et dans le TPJ pendant la condition thématique, nous avons cependant constaté que dans la condition taxonomique parmi les sept clusters significativement activés, l'activation dans le gyrus frontal supérieur gauche était significativement corrélée avec la performance dans la condition taxonomique pour les deux groupes d'âge. L'activation dans le gyrus temporal moyen droit était également corrélée à l'amélioration des performances, mais cela n'était pas significatif dans le groupe plus âgé. En ce qui concerne la condition thématique, par contraste avec condition de référence, dix groupes distincts ont été activés, y compris la jonction temporo-pariétale (TPJ), alors que les ATL n'ont pas été activés de manière robuste pendant la condition thématique. Plus précisément, les régions activées comprenaient bilatéralement le gyrus angulaire, le gyrus temporal moyen, le gyrus frontal inférieur (partie triangulaire) et le gyrus frontal moyen. Nous visons à poursuivre des analyses supplémentaires pour explorer la relation entre les exigences de la tâche, le type de relation sémantique et la réorganisation neurofonctionnelle liée à l'âge. Cependant, ces résultats relatifs à la préservation avec l'âge des capacités à traiter les différentes relations sémantiques de mots sont associés à un certain nombre de réorganisations neurofonctionnelles. Celles-ci peuvent être spécifiques au traitement de différentes relations sémantiques et de différentes demandes de tâches. Il reste à déterminer si cette réorganisation est induite par les changements structurels du cerveau avec l'âge, ou par l'utilisation accrue de telles relations sémantiques tout au long de la trajectoire de la vie.Language overall is well preserved in aging (Meyer & Federmeier, 2010) whereas semantic memory may even improve (Kavé, Samuel-Enoch, & Adiv, 2009; Prinz, Bucher, & Marder, 2004; Salthouse, 2009; Verhaegen & Poncelet, 2013; Wingfield & Grossman, 2006), despite numerous neurophysiological changes taking place in the brain (Grady, Springer, Hongwanishkul, McIntosh, & Winocur, 2006; Kemper & Anagnopoulos, 1989; Wingfield & Grossman, 2006). The present study focuses on the preservation of semantic memory in aging, the ‘cognitive act of accessing stored knowledge about the world’ (Binder, Desai, Graves, & Conant, 2009) by means of a semantic judgment task manipulating semantic control with two demand levels (low and high) and two types of semantic relations (taxonomic-thematic). We used a novel task that varied task demands (low versus high) in 39 younger and 39 older adults. More specifically, the aims of this study was 1) to identify whether aging affects the brain activity subserving semantic memory in accordance with the CRUNCH predictions, through a semantic judgment task with two levels of demands (low and high). 2) To bridge the gap in the literature on the existence and evolution of semantic hubs in aging, in light of the dual and single-hub theories, by evaluating the effect of aging on the role of the Anterior Temporal Lobes (ATLs) and the Temporo-parietal junction (TPJ) as neural representations of the semantic hubs responsible for taxonomic and thematic processing, respectively. A submission by registered report was opted for this research project. Our participants, younger and older adults, were overall matched in regards to level of education and as shown in questionnaires assessing engagement in cognitively stimulating activities, MoCA and WAIS-III tests. The behavioral results confirmed that the task was successful in manipulating task difficulty, with error rates and RTs increasing with increasing task demands, namely in the high-demand condition. We found that engaging in cognitively stimulating activities impacted positively on both baseline RTs and accuracy and that higher scores on the WAIS-III and the PPTT tests were positively correlated with accuracy in older adults. There was no statistical difference in accuracy between younger and older participants regardless of the condition, so there was no age effect in accuracy. In terms of RTs, there was a statistically significant difference between younger and older participants for both the task and the baseline conditions, with older adults being slower to respond in general. RTs increased the more the participant’s age increased, which is in line with findings in the literature. As such, the semantic memory task was successful in a) manipulating task difficulty across two levels of demands and b) demonstrating age-invariant behavioural performance for the older group, as requires to test the CRUNCH model (Fabiani, 2012; Schneider-Garces et al., 2010). For objective no 1, the crucial test of CRUNCH model, the fMRI age group by task demand interaction was not found. We did not find statistically significant interaction neither between task demands and age group for RTs or accuracy, nor in regards to brain activation. At the neural level, independently of age, the semantic similarity judgment task activated a large network including bilateral inferior frontal, parietal, supplementary motor, temporal and occipital brain regions, which correspond overall with the semantic network, as suggested in the literature. Region of interest analyses demonstrated task demand effect in these regions, most notably in the left and right inferior frontal gyrus, the left posterior middle temporal gyrus, the posterior inferior temporal gyrus and the pre-frontal gyrus, regions which are typically associated with semantic control requirements. We did not find any significant interactions between task demands and activation in the regions of interest either. Several possible reasons may justify the lack of findings as predicted by the CRUNCH hypothesis. For objective no 2 in regards to the semantic relation effect, the contrast of the taxonomic with the thematic condition directly did not produce any robust activation at a corrected threshold. The taxonomic condition yielded interesting results when contrasted with the baseline one. Seven distinct clusters in the fronto-temporo-parietal cortex were activated across the two hemispheres, including the anterior temporal lobes (ATLs) and the left temporo-parietal junction (TPJ). Additionally, activation was significant in the left frontal syperior gyrus, the left angular gyrus (AG) and the inferior frontal gyrus (orbital part) on the right hemisphere. This finding could be partly in line with the dual-hub theory, that proposes that the ATLs bilaterally and the TPJ act as semantic hubs. Though we did not find the expected double dissociation e.g., significant activation in the ATLs during the taxonomic condition only and in the TPJ during the thematic condition only, we found however that in the taxonomic condition among the seven significantly activated clusters, activation in the left superior frontal gyrus was significantly correlated with performance in both age groups. Activation in the right middle temporal gyrus was also correlated with improved performance, but this was not significant in the older group. During the thematic condition, when contrasted with baseline, ten distinct clusters were activated, including the temporo-parietal junction (TPJ), whereas the ATLs were not robustly activated during the thematic condition. We aim to pursue additional analyses to explore the relation between task demands, type of semantic relation and age-related neurofunctional reorganization. However, these results in relation to the preservation with age of the abiliites to process the different semantic word relations is associated with a number of neurofunctional reorganizations. These can be specific to the processing of different semantic relations and different task demands. Whether this reorganization is induced by the structural changes in the brain with age, or by the enhanced use of such semantic relations along the trajectory of life is still under exploration

The anterior temporal lobes support residual comprehension in Wernicke’s aphasia

Wernicke’s aphasia occurs following a stroke to classical language comprehension regions in the left temporoparietal cortex. Consequently, auditory-verbal comprehension is significantly impaired in Wernicke’s aphasia but the capacity to comprehend visually presented materials (written words and pictures) is partially spared. This study used fMRI to investigate the neural basis of written word and picture semantic processing in Wernicke’s aphasia, with the wider aim of examining how the semantic system is altered following damage to the classical comprehension regions. Twelve participants with Wernicke’s aphasia and twelve control participants performed semantic animate-inanimate judgements and a visual height judgement baseline task. Whole brain and ROI analysis in Wernicke’s aphasia and control participants found that semantic judgements were underpinned by activation in the ventral and anterior temporal lobes bilaterally. The Wernicke’s aphasia group displayed an “over-activation” in comparison to control participants, indicating that anterior temporal lobe regions become increasingly influential following reduction in posterior semantic resources. Semantic processing of written words in Wernicke’s aphasia was additionally supported by recruitment of the right anterior superior temporal lobe, a region previously associated with recovery from auditory-verbal comprehension impairments. Overall, the results concord with models which indicate that the anterior temporal lobes are crucial for multimodal semantic processing and that these regions may be accessed without support from classic posterior comprehension regions

Structural and effective connectivity of lexical-semantic and naming networks in patients with chronic aphasia

Given the difficulty in predicting outcomes in persons with stroke-induced aphasia (PWA), neuroimaging-based biomarkers of recovery could provide invaluable predictive power to stroke models. However, the neural patterns that constitute beneficial neural organization of language in PWA remain debated. Thus, in this work, we propose a novel network theory of aphasia recovery and test our overarching hypothesis, i.e., that task-specific language processing in PWA requires the dynamic engagement of intact tissue within a bilateral network of anatomically-segregated but functionally and structurally connected language-specific and domain-general brain regions. We first present two studies in which we examined left frontotemporal connectivity during different language tasks (i.e., picture naming and semantic feature verification). Results suggest that PWA heavily rely on left middle frontal gyrus (LMFG)-driven connectivity for tasks requiring lexical-semantic processing and semantic control whereas controls prefer models with input to either LMFG or left inferior frontal gyrus (LIFG). Both studies also revealed several significant associations between spared tissue, connectivity and language skills in PWA. In the third study, we examined bilateral frontotemporoparietal connectivity and tested a lesion- and connectivity-based hierarchical model of chronic aphasia recovery. Between-group comparisons showed controls exhibited stronger left intra-hemispheric task-modulated connectivity than did PWA. Connectivity and language deficit patterns most closely matched predictions for patients with primarily anterior damage whereas connectivity results for patients with other lesion types were best explained by the nature of the semantic task. In the last study, we investigated the utility of lesion classification based on gray matter (GM) only versus combined GM plus white matter (WM) metrics. Results suggest GM only classification was sufficient for characterizing aphasia and anomia severity but the GM+WM classification better predicted naming treatment outcomes. We also found that fractional anisotropy of left WM association tracts predicted baseline naming and treatment outcomes independent of total lesion volume. Finally, results of a preliminary multimodal prediction analysis suggest that combined structural and functional metrics reflecting the integrity of regions and connections comprise optimal predictive models of behavior in PWA. To conclude this dissertation, we discuss how multimodal network models of aphasia recovery can guide future investigations.2020-10-23T00:00:00

Changes of right-hemispheric activation after constraint-induced, intensive language action therapy in chronic aphasia: fMRI evidence from auditory semantic processing

The role of the two hemispheres in the neurorehabilitation of language is still under dispute. This study explored the changes in language-evoked brain activation over a 2-week treatment interval with intensive constraint induced aphasia therapy (CIAT), which is also called intensive language action therapy (ILAT). Functional magnetic resonance imaging (fMRI) was used to assess brain activation in perilesional left hemispheric and in homotopic right hemispheric areas during passive listening to high and low-ambiguity sentences and non-speech control stimuli in chronic non-fluent aphasia patients. All patients demonstrated significant clinical improvements of language functions after therapy. In an event-related fMRI experiment, a significant increase of BOLD signal was manifest in right inferior frontal and temporal areas. This activation increase was stronger for highly ambiguous sentences than for unambiguous ones. These results suggest that the known language improvements brought about by intensive constraint-induced language action therapy at least in part relies on circuits within the right-hemispheric homologs of left-perisylvian language areas, which are most strongly activated in the processing of semantically complex language

Increased Functional Connectivity in the Default Mode Network in Mild Cognitive Impairment: A Maladaptive Compensatory Mechanism Associated with Poor Semantic Memory Performance

Semantic memory decline and changes of default mode network (DMN) connectivity have been reported in mild cognitive impairment (MCI). Only a few studies, however, have investigated the role of changes of activity in the DMN on semantic memory in this clinical condition. The present study aimed to investigate more extensively the relationship between semantic memory impairment and DMN intrinsic connectivity in MCI. Twenty-one MCI patients and 21 healthy elderly controls matched for demographic variables took part in this study. All participants underwent a comprehensive semantic battery including tasks of category fluency, visual naming and naming from definition for objects, actions and famous people, word-association for early and late acquired words and reading. A subgroup of the original sample (16 MCI patients and 20 healthy elderly controls) was also scanned with resting state functional magnetic resonance imaging and DMN connectivity was estimated using a seed-based approach. Compared with healthy elderly, patients showed an extensive semantic memory decline in category fluency, visual naming, naming from definition, words-association, and reading tasks. Patients presented increased DMN connectivity between the medial prefrontal regions and the posterior cingulate and between the posterior cingulate and the parahippocampus and anterior hippocampus. MCI patients also showed a significant negative correlation of medial prefrontal gyrus connectivity with parahippocampus and posterior hippocampus and visual naming performance. Our findings suggest that increasing DMN connectivity may contribute to semantic memory deficits in MCI, specifically in visual naming. Increased DMN connectivity with posterior cingulate and medio-temporal regions seems to represent a maladaptive reorganization of brain functions in MCI, which detrimentally contributes to cognitive impairment in this clinical population