Imaging findings associated with cognitive performance in primary lateral sclerosis and amyotrophic lateral sclerosis

Introduction: Executive dysfunction occurs in many patients with amyotrophic lateral sclerosis (ALS), but it has not been well studied in primary lateral sclerosis (PLS). The aims of this study were to (1) compare cognitive function in PLS to that in ALS patients, (2) explore the relationship between performance on specific cognitive tests and diffusion tensor imaging (DTI) metrics of white matter tracts and gray matter volumes, and (3) compare DTI metrics in patients with and without cognitive and behavioral changes. Methods: The Delis-Kaplan Executive Function System (D-KEFS), the Mattis Dementia Rating Scale (DRS-2), and other behavior and mood scales were administered to 25 ALS patients and 25 PLS patients. Seventeen of the PLS patients, 13 of the ALS patients, and 17 healthy controls underwent structural magnetic resonance imaging (MRI) and DTI. Atlas-based analysis using MRI Studio software was used to measure fractional anisotropy, and axial and radial diffusivity of selected white matter tracts. Voxel-based morphometry was used to assess gray matter volumes. The relationship between diffusion properties of selected association and commissural white matter and performance on executive function and memory tests was explored using a linear regression model. Results: More ALS than PLS patients had abnormal scores on the DRS-2. DRS-2 and D-KEFS scores were related to DTI metrics in several long association tracts and the callosum. Reduced gray matter volumes in motor and perirolandic areas were not associated with cognitive scores. Conclusion: The changes in diffusion metrics of white matter long association tracts suggest that the loss of integrity of the networks connecting fronto-temporal areas to parietal and occipital areas contributes to cognitive impairment

Monitoring different phonological parameters of sign language engages the same cortical language network but distinctive perceptual ones

The study of signed languages allows the dissociation of sensorimotor and cognitive neural components of the language signal. Here we investigated the neurocognitive processes underlying the monitoring of two phonological parameters of sign languages: handshape and location. Our goal was to determine if brain regions processing sensorimotor characteristics of different phonological parameters of sign languages were also involved in phonological processing, with their activity being modulated by the linguistic content of manual actions. We conducted an fMRI experiment using manual actions varying in phonological structure and semantics: (1) signs of a familiar sign language (British Sign Language), (2) signs of an unfamiliar sign language (Swedish Sign Language), and (3) invented nonsigns that violate the phonological rules of British Sign Language and Swedish Sign Language or consist of nonoccurring combinations of phonological parameters. Three groups of participants were tested: deaf native signers, deaf nonsigners, and hearing nonsigners. Results show that the linguistic processing of different phonological parameters of sign language is independent of the sensorimotor characteristics of the language signal. Handshape and location were processed by different perceptual and task-related brain networks but recruited the same language areas. The semantic content of the stimuli did not influence this process, but phonological structure did, with nonsigns being associated with longer RTs and stronger activations in an action observation network in all participants and in the supramarginal gyrus exclusively in deaf signers. These results suggest higher processing demands for stimuli that contravene the phonological rules of a signed language, independently of previous knowledge of signed languages. We suggest that the phonological characteristics of a language may arise as a consequence of more efficient neural processing for its perception and production

Untersuchungen zur semantischen Integration beim auditiven Sprachverständnis

Bisherige Bildgebungsstudien haben gezeigt, dass die Integration semantischer Information in den Satzkontext mit einer Aktivierung links-hemisphärischer frontotemporaler Hirnregionen assoziiert ist [1]. Die Aktivierungsmuster werden dabei in Abhängigkeit von der Schwierigkeit der semantischen Integration moduliert, wobei der Grad der Prädizierbarkeit des finalen Nomens eine große Rolle spielt. Um diesen zu variieren, wurden Sätze mit erwarteten, unerwarteten, semantisch inkorrekten und Pseudowort-Endungen experimentell im Rahmen einer lexikalischen Entscheidungsaufgabe verglichen. Bisherige Bildgebungsstudien haben dieses Paradigma vornehmlich visuell präsentiert [1]. Im Gegensatz dazu wurde in dieser Studie die semantische Integration beim auditiven Sprachverständnis untersucht. Die vorliegenden Ergebnisse deuten darauf hin, dass sowohl der Gyrus frontalis inferior als auch der Gyrus temporalis medius Kernreale für die semantische Integration beim auditiven Sprachverständnis darstellen. Die Konnektivitätsanalysen liefern zudem Hinweise darauf, dass diese Hirnregionen Teil eines fronto-temporalen Netzwerkes sind, das auf eine erhöhte Schwierigkeit beim Abruf und der Integration semantischer Information reagiert. Insgesamt zeigt sich ein Effekt der Integrationsschwierigkeit sowohl in den Verhaltenseffekten, als auch in den Hirnaktivierungen und der überregionalen Konnektivität. Das verwendetet Paradigma ist damit ein valides Instrument für die Untersuchung der semantischen Integration beim auditiven Sprachverständnis. Referenzen: [1] Baumgaertner, A., C. Weiller, and C. Buchel, Event-related fMRI reveals cortical sites involved in contextual sentence integration. Neuroimage, 2002. 16(3), S. 736-45.:1 Einführung und theoretischer Hintergrund 1 1.1 Modelle zur Sprachverarbeitung – vom 19. Jahrhundert bis zur Gegenwart 2 1.2 Aktuelle Befunde zur semantischen Sprachverarbeitung 6 1.2.1 Der Gyrus frontalis inferior 7 1.2.2 Der Gyrus temporalis medius 8 1.2.3 Temporofrontale Interaktionen beim Sprachverständnis 9 1.3 N400 und BOLD-Signal als funktionelle und anatomische Korrelate der Sprachverarbeitung 10 1.4 Einordnung der vorliegenden Studie 11 2 Aufgabenstellung 15 3 Material und Methoden 16 3.1 Versuchspersonen 16 3.2 Funktionelle Magnetresonanztomographie 16 3.3 Durchführung und Versuchsaufbau 17 3.3.1 Stimuli 17 3.3.2 Experimentelles Design 19 3.3.3 Messparameter 20 3.3.4 fMRT-Experiment 20 3.4 Datenauswertung 22 3.4.1 Verhaltensdaten 22 3.4.2 fMRT-Daten 23 4 Ergebnisse 29 4.1 Verhaltensdaten 29 4.1.1 Fehlerraten 29 4.1.2 Reaktionszeiten 31 4.2 fMRT-Daten 33 4.2.1 Haupteffekte 33 4.2.2 Differentielle Effekte 38 4.2.3 Psychophysiologische Interaktionen 48 5 Diskussion 53 5.1 Verhaltensdaten 53 5.1.1 Fehlerraten 53 5.1.2 Reaktionszeiten 54 5.2 fMRT-Daten 55 5.2.1 Diskussion der Haupteffekte und der differentiellen Effekte 55 5.2.2 Diskussion der PPI Ergebnisse 64 5.3 Fazit und Ausblick 68 6 Zusammenfassung 70 7 Literaturverzeichnis 75 8 Anhang 8

Application of diffusion tensor imaging in the evaluation of possible side effects of adjuvant chemotherapy on the brain in female breast cancer patients

UVOD: Karcinom dojke je najčešće dijagnostikovana maligna bolest u ženskoj populaciji, čineći četvrtinu svih maligniteta širom sveta a vodeći je uzrok smrtnih ishoda povezanih sa malignitetom kod žena. Ovaj entitet predstavlja heterogenu bolest koju čine molekularni i histološki podtipovi od kojih svaki ima jedinstvenu etiologiju, prezentaciju i prognozu. Sa novijim terapijskim protokolima i dijagnostičkim algoritmima koji za rezultat daju produžen životni vek ovih pacijentkinja, kognitivni problemi koji se javljaju kao rezultat primene hemioterapije kod ove grupacije postaju veliki predmet interesovanja. Upotrebom difuzionog tenzorskog imidžinga, kao savremene MR metode u detekciji promena strukture puteva bele moždane mase, može se steći uvid u eventualne podležuće mikrostrukturalne promene na čijoj se osnovi razvija kognitivna disfunkcija. CILJ: Izvršiti poređenje integriteta projekcionih, asocijativnih i komisuralnih puteva bele moždane mase preterapijski i nakon završetka hemioterapije. Izvršiti poređenje stepena mikrostrukturalnog oštećenja u zavisnosti od vremena proteklog od završetka hemioterapije. Proceniti značaj DTI parametara frakcione anizotropije, radijalne, aksijalne i srednje difuzivnosti u detekciji mikrostrukturalnih promena nastalih kao posledica neurotoksičnog dejstva adjuvantne hemioterapije. MATERIJAL I METODE: Istraživanje je uključivalo 32 ispitanice sa hirurški odstranjenim karcinomom dojke kod kojih je u celosti sproveden planirani MR protokol snimanja pre i nakon završetka adjuvantne hemioterapije sa prosečnim vremenom između snimanja od 290 dana. Pregledi ispitanica su vršeni na aparatu za magnetnu rezonancu, jačine magnetnog polja 1.5 T (SIEMENS Magnetom Aera, Erlangen, Nemačka) u Centru za imidžing dijagnostiku Instituta za onkologiju Vojvodine. Snimanje je rađeno prema multisekvencionalnom i multiplanarnom protokolu, koji podrazumeva DTI aksijalne tomograme (20 enkodiranih pravaca, b vrednosti = i 1000 s2/mm, TR=8000 ms, TE=83 ms, FA=90°, debljina preseka 3 mm, razmak između preseka 3.3 mm, FOV 230 x 230 mm, NEX 3, matriks 128 x 128, sa tri ponavljanja), T2W TSE aksijalne tomograme (TR=4100 ms, TE=107ms, FA=150°, debljina preseka 5 mm, razmak 5.5 mm, FOV 220x164 mm, matriks 384x288), FLAIR aksijalne tomograme (TR=9000ms,TI=2500ms, TE=127ms, debljina preseka 5 mm, razmak 5.5 mm, FOV 220x164 mm, matriks 384 x 288 ), 3D T1 MPRAGE sagitalne tomograme (TR=1640ms, TI=1100 ms, TE=2.75 ms, FA=15°, debljina preseka 1 mm, matriks 288x264). Postprocesing je vršen u nekoliko koraka koristeći dcm2nii softver i FSL v6.0 softverski paket. Analiza mapa frakcione anizotropije, radijalne, aksijalne i srednje difuzivnosti koje su uvršćene u upareni Studentov T test, vršena je koristeći TBSS metodu koja je deo FSL softverskog paketa. Ekstrakcija podataka regiona od interesa iz skeletonizovanih mapa vršena je koristeći ENIGMA DTI protokol. Korelacije između procentualnih razlika u parametrima anizotropije i vremena proteklog između dva snimanja kao i drugih kliničkih parametara dobijene su Pirsonovim korelacionim testom. REZULTATI: Na diferencionim mapama TBSS analize statistički značajne razlike između prvog i drugog snimanja (P<0.05) u parametru radijalne difuzivnosti uočene su dominantno u gornjoj koroni radijati obostrano a detektabilne su i u prednjoj koroni radijati obostrano, gornjem longitudionalnom fascikulusu obostrano, telu korpus kalozuma, cingulumu sa leve strane, levoj kapsuli interni kao i levom uncinatnom fascikulusu. Što se tiče srednje difuzivnosti, statistički značajne razlike uočene su dominantno u gornjoj koroni radijati obostrano kao i levom gornjem longitudionalnom fascikulusu a detektabilne su i u telu korpus kalozuma, cingulumu sa leve strane, prednjoj koroni radijati obostrano kao i u levom prednjem kraku kapsule interne. Ekstrakscijom ROI vrednosti regija od interesa definisanih DTI ENIGMA protokolom, statistički značajne razlike izmešu prvog i drugog snimanja u parametru radijalne difuzivnosti (RD) nađene su u prednjoj i srednjoj koroni radijati obostrano, gornjoj koroni radijati, cingulumu, gornjem fronto-okcipitalnom fascikulusu desno i donjem fronto-okcipitalnom fascikulusu obostrano, posteriornom kraku kapsule interne desno, forniksu, kao i u kolenu kaloznog tela. U slučaju aksijalne difuzivnosti (AD) statistički značajne razlike nađene su u prednjoj koroni radijati, cingulumu, desnom kortiko-spinalnom traktu, kao i splenijumumu korpus kalozuma. Što se tiče srednje difuzivnosti (MD), kod ENIGMA DTI protokola ekstrakcije ROI vrednosti, statistički značajne rezlike nađene su u prednjoj i gornjoj koroni radijati, u cingulumu obostrano, splenijumu korpus kalozuma i forniksu, kao i u donjem fronto-okcipitalnom fascikulusu obostrano. Statistički značajne razlike u vrednostima frakcione anizotropije (FA) nađene su u telu korpus kalozuma, gornjoj i srednjoj koroni radijti izraženije levo, kapsuli eksterni sa desne strane, forniksu, posteriornom kraku capsule interne obostrano, retro-lentikularnom segmentu kapsule interne levo. Nakon primenjene Bonferoni korekcije za višestruka poređenja statistički značajne razlike dobijene su za FA u kapsuli eksterni desno, za RD u inferiornom fronto-okcipitalnom fascikulusu, izraženije sa desne strane kao i u kolenu kaloznog tela, dok je za MD verifikovana značajna razlika samo u inferiornom fronto-okcipitalnom fascikulusu. Značajne korelacije procentualnih razlika vrednosti frakcione anizotropije (FA) sa vremenom izmeđi dva snimanja nađene su dominanatno u gornjoj koroni radijati obostrano a evidentne su i prednjoj koroni radijati sa desne strane, posteriornoj koroni radijati sa leve strane i posteriornom kraku kapsule interne sa desne strane kao i donjem fronto-okcipitalnom fascikulusu. U slučaju radijalne difuzivnosti (RD) značajne korelacije nađene su u prednjoj koroni radijati sa desne strane, u manjoj meri i u posteriornoj koroni radijati sa leve strane kao i u gornjoj koroni radijati obostrano. Kod srednje difuzivnosti (MD) korelacije procentualnih razlika sa vremenom između dva snimanja nađene su u prednjem kraku kapsule interne sa leve strane kao i kortiko-spinalnom traktu sa desne strane. Za razlike u aksijalnoj difuzivnosti (AD) značajne korelacije sa intervalom između dva snimanja nađene su u cingulumu sa leve strane kao i u nešto manjoj meri u prednjem kraku kapsule interne sa leve strane. ZAKLJUČAK: Kod bolesnica sa karcinomom dojke nakon sprovedene adjuvantne hemioterapije dolazi do značajnih promena DTI parametara koji ukazuju na postojanje mikristrukturalnih oštećenja, odnosno smanjenja integriteta puteva bele moždane mase, procesom koji je potencijalno reverzibilnog karaktera, pri čemu se određen stepen reverzibilnosti ispoljava već u prvoj godini nakon završetka hemioterapije.Mikrostrukturalna oštećenja bele moždane mase nakon sprovedene adjuvantne hemioterapije bila su najizraženija u uncinatnom fascikulusu, kapsuli eksterni i korpus kalozumu, pri čemu je radijalna difuzivnost pouzdaniji parametar u detekciji mikrostrukturalnog oštećenja u odnosu na frakcionu anizotropiju, srednju difuzivnost i aksijalnu difuzivnost, što ukazuje na oštećenje mijelinskog omotača kao najverovatniji mehanizam mikrostrukturalnog oštećenja. Difuzioni tenzorski imidžing je vijabilna metoda za ispitivanje integriteta puteva bele moždane mase, odnosno procenu mikrostrukturalnog oštećenja, što kod bolesnica sa karcinomom dojke može igrati značajnu ulogu u patogenezi poremećaja kognitivnih funkcija.INTRODUCTION: Breast cancer is the most common form of cancer in the female population, accounting for one fourth of malignancies, while being the leading cause of cancer-related deaths in women. Breast cancer represents a heterogenic disease with molecular and histologic subtypes which have distinct etiologies, presentation and prognosis. With the advancement of diagnostic and therapy protocols resulting in better overall survival of these patients, cognitive problems occurring after chemotherapy are becoming a field of rising interest. The use of diffusion tensor imaging, as a novel MRI method in the detection of white matter structural abnormalities, could give insight into the potential underlying microstructural alterations that play a role in the pathogenesis of cognitive dysfunction. OBJECTIVE: Compare the integrity of brain white matter tracts before and after the administration od adjuvant chemotherapy in breast cancer patients. Compare the extent of microstructural damage in correlation with the time period since the completion of chemotherapy. Evaluate the significance of fractional anisotropy, radial diffusivity, axial diffusivity and mean diffusivity in the detection of microstructural alterations as a result of neurotoxic effects of adjuvant chemotherapy. MATERIAL AND METHODS: The study included 32 subjects with surgically treated breast cancer, in which the complete planned MRI protocol was performed before and after the administration of adjuvant chemotherapy, with a mean time interval of 290 days between two scans. The MRI scans were performed on a 1.5 T MRI scanner (SIEMENS Magnetom Aera, Erlangen, Germany) in the Centre for diagnostic imaging of the Institute for Oncology of Vojvodina. Scanning was done using a multi sequence and multi planar protocol, which included DTI axial slices (20 encoded directions, b value = 1000 s2/mm, TR=8000 ms, TE=83 ms, FA=90°, slice thickness 3 mm, gap 3.3 mm, FOV 230 x 230 mm, NEX 3, matrix 128 x 128, with 3 repetitions), T2W TSE axial slices (TR=4100 ms, TE=107ms, FA=150°, slice thickness 5 mm, gap 5.5 mm, FOV 220x164 mm, matrix 384x288), FLAIR axial slices (TR=9000ms,TI=2500ms, TE=127ms, slice thickness 5 mm, gap 5.5 mm, FOV 220x164 mm, matrix 384 x 288 ), 3D T1 MPRAGE sagital slices (TR=1640ms, TI=1100 ms, TE=2.75 ms, FA=15°, slice thickness 1 mm, matrix 288x264). Post processing was performed in several steps using dcm2nii software and the FSL v6.0 software package. Analysis of maps of fractional anisotropy, radial diffusivity, axial diffusivity and mean diffusivity which were incorporated into the paired Student T test was performed using the TBSS method. Extraction of ROI values from skeletonized maps was done using the ENIGMA DTI protocol. Correlations between percentual differences in anisotropy parameters and time between two scans as well as other clinical parameters were obtained using Pearson’s correlation test. RESULTS: Analysis of TBSS maps showed significant changes in radial diffusivity (RD) (P<0.05) between two scans mainly on both sides of the superior corona radiata, while changes were also detectable bilaterally in the superior longitudional fasciculus, body of the corpus callosum, left cingulum, left internal capsule and lef uncinate fasciculus. Mean diffusivity values were significantly different mostly in the superior corona radiata bilaterally and left anterior corona radiata, with apparent changes evident in the body of the corpus callosum, left cingulum, anterior corona radiata bilaterally as in the left anterior limb of the internal capsule. Extraction of ROI values via the ENIGMA DTI protocol showed statistically significant changes in radial diffusivity in the anterior and superior corona radiata bilaterally, cingulum, right superior fronto-occipital fasciculus, inferior fronto-occipital fasciculus bilaterally, posterior limb of the right internal capsule, fornix and genu of the corpus callosum. In the parameter of axial diffusivity, significant changes were detected in the anterior corona radiata, cingulum, right cortico-spinal tract and splenium of the corpus callosum. Changes in values of mean diffusivity were significant in the anterior and superior corona radiata bilaterally, cingulum bilaterally, splenium of the corpus callosum, fornix and inferior fronto-occipital fasciculus bilaterally. Statistically significant changes in fractional anisotropy values were evident in the body of the corpus callosum, superior and mean corona radiata more on the left side, right external capsule, fornix, posterior limb of the internal capsule bilaterally. After the Bonferroni correction for multiple comparisons, changes in FA persisted in the right external capsule, inferior fronto-occipital fasciculus for RD more pronounced on the right, as well as the body of the corpus callosum, with changes only in the inferior fronto-occipital fasciculus for MD. Significant correlations of percentual differences of FA values and time elapsed between two scans were found dominantly in the anterior right corona radiata, posterior left corona radiata, left posterior limb of internal capsule, right posterior limb of internal capsule and inferior fronto-occipital fasciculus. Alterations in RD values correlated significantly with time elapsed between two scans in the anterior right corona radiata, posterior left corona radiata and superior corona radiata bilaterally. Time correlation with alterations in MD values were present in the anterior limb of the internal capsule on the left side and the cortico-spinal tract on the righ side. Percentual differences in values of AD corellated with the time interval between two scans in the left cingulum and to a lesser extent in the anterior limb of the internal capsule on the left. CONCLUSION: Female patients with breast cancer show significant alterations in DTI parameters after adjuvant chemotherapy, which represent micstrostuctural abnormalities or loss of integrity of white matter tracts in a process that is potentially reversible, with a degree of reversibility evident in the first year after completion of chemotherapy. Mictrostructural alterations of brain white matter after adjuvant chemotherapy were most prominent in the uncinate fasciculus, external capsule and corpus callosum, with radial diffusivity (RD) being a more sensitive parameter of microstructural damage compared to fractional anisotropy (FA), mean diffusivity (MD) and axial diffusivity (AD), which indicates myelin sheath abnormalities as a dominate mechanism of microstructural damage. Diffusion tensor imaging is a viable method for studying white matter tracts and evaluating microstructural damage, which could play a significant role in the pathogenesis of cognitive function disorder

Exploring semantic memory organization using a proactive interference paradigm

Several decades of research into semantic memory have yielded two main perspectives as to how semantic memory may be organized. One hypothesis is that information is stored according to taxonomical categories (e.g., animals, objects); the other hypothesis suggests that information is stored according to featural attributes (e.g., functional and perceptual properties). Using a proactive interference (PI) paradigm, this study aimed to investigate these two hypotheses by contrasting the impact of categorical and featural cues on patterns of PI effects (i.e., buildup and release). Using the same stimuli and task, while examining recall performance and intrusion errors when featural and categorical information were opposed, allowed for a direct measure of the contribution of these two types of information for semantic organization. To explore semantic organization across the lifespan, 20 healthy younger and 20 healthy older participants were tested. Given that semantic memory deficits frequently occur in Alzheimer's disease (AD), the performance of the healthy older participants was also compared to 16 participants with AD to examine differences in semantic organization of featural and categorical information in individuals for whom there is a potential breakdown of semantic memory. All groups showed expected PI effects when stimuli were categorically cued. Participants also showed a release from PI when the featural cue changed (but the category remained the same). An unexpected release from PI effect was found in the featural PI continued condition in which the featural cue remained the same (e.g., USED FOR TRANSPORTATION) but there was an implicit switch in category (e.g., from OBJECTS to ANIMALS). The results are discussed in terms of the implications for the categorical and featural hypotheses of semantic memory organization

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)