Substrats neuronaux du traitement visuel et sémantique des mots dans le vieillissement normal : apports de la MEG

Bien que l’on ait longtemps considéré que les substrats cérébraux de la mémoire sémantique (MS) demeuraient intacts au cours du vieillissement normal (VN), en raison d’une préservation de la performance des personnes âgées à des épreuves sémantiques, plusieurs études récentes suggèrent que des modifications cérébrales sous-tendant le traitement sémantique opèrent au cours du vieillissement. Celles-ci toucheraient principalement les régions responsables des aspects exécutifs du traitement sémantique, impliqués dans les processus de recherche, de sélection et de manipulation stratégique de l’information sémantique. Cependant, les mécanismes spécifiques régissant la réorganisation cérébrale du traitement sémantique au cours du VN demeurent méconnus, notamment en raison de divergences méthodologiques entre les études. De plus, des données de la littérature suggèrent que des modifications cérébrales associées au vieillissement pourraient également avoir lieu en relation avec les aspects perceptifs visuels du traitement des mots. Puisque le processus de lecture des mots représente un processus interactif et dynamique entre les fonctions perceptuelles de bas niveau et les fonctions de plus haut niveau tel que la MS, il pourrait exister des modifications liées à l’âge au plan des interactions cérébrales entre les aspects perceptifs et sémantiques du traitement des mots. Dans son ensemble, l’objectif de la présente thèse était de caractériser les modifications cérébrales ainsi que le décours temporel du signal cérébral qui sont associés au traitement sémantique ainsi qu’au traitement perceptif des mots en lien avec le VN, ainsi que les relations et les modulations entre les processus sémantiques et perceptifs au cours du VN, en utilisant la magnétoencéphalographie (MEG) comme technique d’investigation. Dans un premier temps (chapitre 2), les patrons d’activation cérébrale d’un groupe de participants jeunes et d’un groupe de participants âgés sains ont été comparés alors qu’ils effectuaient une tâche de jugement sémantique sur des mots en MEG, en se concentrant sur le signal autour de la N400, une composante associée au traitement sémantique. Les résultats démontrent que des modifications cérébrales liées à l’âge touchent principalement les structures impliquées dans les aspects exécutifs du traitement sémantique. Une activation plus importante du cortex préfrontal inférieur (IPC) a été observée chez les participants jeunes que chez les participants âgés, alors que ces derniers activaient davantage les régions temporo-pariétales que les jeunes adultes. Par ailleurs, le lobe temporal antérieur (ATL) gauche, considéré comme une région centrale et amodale du traitement sémantique, était également davantage activé par les participants âgés que par les jeunes adultes. Dans un deuxième temps (chapitre 3), les patrons d’activation cérébrale d’un groupe de participants jeunes et d’un groupe de participants âgés sains ont été comparés en se concentrant sur le signal associé au traitement perceptif visuel, soit dans les 200 premières millisecondes du traitement des mots. Les résultats montrent que des modifications cérébrales liées à l’âge touchent le gyrus fusiforme mais aussi le réseau sémantique, avec une plus grande activation pour le groupe de participants âgés, malgré une absence de différence d’activation dans le cortex visuel extrastrié entre les deux groupes. Les implications théoriques des résultats de ces deux études sont ensuite discutées, et les limites et perspectives futures sont finalement adressées (chapitre 4).While it has long been assumed that the organization of the brain network underlying semantic processing remains intact in normal aging, mainly due to older adults’ intact behavioral performance on semantic tasks, several recent studies suggest that brain changes underlying semantic processing operate during aging. These changes appear to affect mainly the brain regions responsible for the executive aspects of semantic memory (SM), involved in semantic search and selection processes, as well as the strategic manipulation of semantic knowledge. However, the specific mechanisms underlying cerebral reorganization of semantic processing in normal aging are not well understood, partly because of methodological differences among studies. Recent literature also suggests that brain changes may be observed in relation to visual perceptual aspects of word processing in older adults. Since reading words is a dynamic interactive process between low-level perceptual functions and higher-order processes such as semantic processing, there may be age-related changes in terms of brain interactions between perceptual and semantic aspects of word processing. The general aim of this thesis was to characterize the cortical changes and the time course of brain signal associated with semantic and perceptual processing of words, as well as the modulations between semantic and perceptual processes in normal aging, using magnetoencephalography (MEG) as the investigative method. Firstly (Chapter 2), the patterns of brain activation of two groups of healthy younger and older adults were compared relative to a semantic task participants carried out during MEG acquisition, by focusing on the signal around the N400, a component associated with semantic processing. The results indicate that brain changes associated with normal aging mainly affect structures involved in the executive aspects of semantic processing. Greater activation was observed in prefrontal cortex for younger relative to older adults, while the latter group of participants activated the temporoparietal region to a greater extent than young adults. Moreover, the left anterior temporal lobe (ATL), considered to be a central and amodal region of semantic processing, was also more activated by older than younger participants. Secondly (Chapter 3), specific patterns of brain activation of younger and healthy older adults were compared in relation to visual perceptual processing, by focusing on the 200 first milliseconds of cortical signal during word processing. The results show that the age-related brain changes affect the fusiform gyrus, as well as the semantic network, with greater activation found in these regions in the group of older participants relative to younger participants, while no difference in activation of the visual extrastriate cortex was found between groups. The theoretical implications of the results of these two studies are discussed. Finally, limitations of this thesis and future perspectives are addressed (Chapter 4)

Neural changes associated with semantic processing in healthy aging despite intact behavioral performance

Semantic memory recruits an extensive neural network including the left inferior prefrontal cortex (IPC) and the left temporoparietal region, which are involved in semantic control processes, as well as the anterior temporal lobe region (ATL) which is considered to be involved in processing semantic information at a central level. However, little is known about the underlying neuronal integrity of the semantic network in normal aging. Young and older healthy adults carried out a semantic judgment task while their cortical activity was recorded using magnetoencephalography (MEG). Despite equivalent behavioral performance, young adults activated the left IPC to a greater extent than older adults, while the latter group recruited the temporoparietal region bilaterally and the left ATL to a greater extent than younger adults. Results indicate that significant neuronal changes occur in normal aging, mainly in regions underlying semantic control processes, despite an apparent stability in performance at the behavioral level

A MEG study of the neural substrates of semantic processing in semantic variant primary progressive aphasia

Despite a well-documented pattern of semantic memory (SM) impairment, the patterns of brain activation during semantic processing in svPPA still remain poorly understood. The current study aimed to investigate the neural substrates of residual semantic processing in the context of this significant but selective SM impairment, through the case study of one svPPA patient. One svPPA patient (EC) and six elderly controls carried out a general-level semantic categorization task (biological and manufactured objects) while their brain activity was recorded using magnetoencephalography (MEG). Despite similar behavioral performance, EC showed hyperactivation of the left inferior temporal gyrus (ITG) and right anterior temporal lobe (ATL) relative to controls. This suggests that periatrophic regions within the ATL region may support preserved semantic abilities in svPPA. These results thus contribute to our understanding of the brain regions which are recruited to compensate for bilateral atrophy of the ATL and ensure residual semantic processing in svPPA

Functional changes in the cortical semantic network in amnestic mild cognitive impairment

Semantic memory impairment has been documented in older individuals with amnestic Mild cognitive impairment (aMCI), who are at risk of developing Alzheimer’s disease (AD), yet little is known about the neural basis of this breakdown. The main objective of this study was to investigate the brain mechanisms associated with semantic performance in patients with aMCI. Method: A group of aMCI patients and a group of healthy older controls carried out a semantic categorization task while their brain activity was recorded using magnetoencephalography (MEG). During the task, participants were shown famous faces and had to determine whether each famous person matched a given occupation. The main hypotheses were that: (i) semantic processing should be compromised for aMCI patients, and (ii) these deficits should be associated with cortical dysfunctions within specific areas of the semantic network. Results: Behavioural results showed that aMCI participants were significantly slower and less accurate than control participants at the semantic task, corroborating previous reports. Additionally, relative to controls, a significant pattern of hyperactivation was found in the aMCI group within specific regions of the semantic network, including the right anterior temporal lobe and inferior prefrontal cortex. Conclusions: Abnormal functional activation within key areas of the semantic network suggests that it is compromised early in the disease process. Moreover, this pattern of increased activation in aMCI was positively associated with grey matter integrity in specific areas, but was not associated with any specific pattern of atrophy, suggesting that functional hyperactivation may precede atrophy of the semantic network in aMCI

The cognitive and neural expression of semantic memory impairment in mild cognitive impairment and early Alzheimer's disease.

International audienceSemantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge