Le grasset est l’une des articulations les plus complexes chez le cheval et est le siège d’une part importante des boiteries affectant le membre pelvien. Plus précisément, la majorité des chevaux présentant des signes de douleur localisée au grasset présenteraient une boiterie localisée dans l’articulation fémoro-tibiale médiale. Cette articulation peut être affectée par de nombreuses lésions comme de l’ostéoarthrose chez les chevaux âgés ou des lésions sous-chondrales d’apparence kystique, fréquemment diagnostiquées sur le condyle fémoral médial du grasset des jeunes chevaux sportifs mais également des poulains de manière précoce. En médecine humaine, des recherches se sont intéressées à l’évolution morphologique du genou avec l’âge et à sa maturation, mais également aux corrélations pouvant exister entre les caractéristiques morphologiques et la prévalence de pathologies telles que les ruptures de ligament croisé, l’ostéoarthrose ou l’ostéochondrite disséquante. Il a ainsi été montré que des corrélations existent entre l’étroitesse de l’espace intercondylaire fémoral et la prévalence de lésions d’ostéochondrite disséquante ou de rupture de ligament croisé antérieur. L’origine des lésions sous chondrales d’apparence kystique du condyle fémoral médial demeure, à ce jour, mal expliquée, notamment lorsque celles-ci surviennent très précocement, chez les très jeunes individus. L’évolution de la forme des os de l’articulation fémoro-tibiale avec l’âge et son impact biomécanique sur le développement de ces lésions doivent être évalués. Les objectifs de cette étude ont été de mesurer les paramètres morphologiques radiographiques du fémur distal et du tibia proximal de chevaux Thoroughbred en croissance, d’évaluer les variations de forme de l’espace intercondylaire du fémur avec l’âge, de confronter les paramètres morphologiques des individus sains avec ceux atteints de lésions sous-chondrales d’apparence kystique du condyle fémoral médial et de mesurer ces paramètres morphologiques prospectivement chez des jeunes poulains. Dans notre étude, des radiographies caudo-crâniales de grasset de jeunes Thoroughbreds (ie 3-20 mois), avec (n=53) et sans (n=183) lésions sous chondrales d’apparence kystique, provenant d'une banque de radiographies, ont été analysées; la forme de l’espace intercondylaire fémoral a été évaluée qualitativement sur des radiographies post-mortem de Thoroughbreds (n=53, âge 1-9 mois) provenant d'une étude antérieure ; finalement, des radiographies caudo-crâniales (n=94) ont été réalisées prospectivement sur des poulains Thoroughbreds âgés de 1 mois et analysées. Treize paramètres morphologiques portant sur l’aspect distal du fémur distal et l’aspect proximal du tibia ont été mesurés sur les radiographies réalisées in vivo, dont certains au niveau de la ligne articulaire fémorale (al) et de la fosse poplitée (pf). Chez les poulains sans lésion, la largeur et la hauteur des condyles fémoraux ont augmenté avec la maturation (p<0,0001), tandis que la largeur de l’espace intercondylaire a diminué (p<0,0001) au niveau articulaire. L'analyse qualitative de la forme a également révélé que l’espace intercondylaire rétrécissait distalement avec l'âge pour prendre une forme de Ω. Pour les poulains avec lésions la largeur des condyles fémoraux et la hauteur du condyle fémoral latéral ont aussi augmenté avec la maturation (p<0,003), mais aucun changement significatif n'a été observé pour la largeur du condyle fémoral médial au niveau de la fosse poplitée (pf), ou pour la hauteur ou la largeur de l’espace intercondylaire (al) avec la maturation. Dans les deux groupes, la largeur du plateau tibial a augmenté avec la maturation (p<0,0001), sans qu’aucun des autres paramètres tibiaux n’évolue. La largeur bicondylaire et la largeur de l’espace intercondylaire étaient plus grandes pour le membre gauche chez les poulains sains à tous les âges (p<0,01). Chez les poulains de 1 mois, le condyle fémoral médial était plus large à gauche (p<0,05). Cependant, la largeur du condyle fémoral médial à hauteur de l’articulation était plus grande du côté droit chez les poulains avec lésions, étant significatif chez les femelles âgées de 7 mois ou plus (p=0,004). Ces résultats suggèrent une relation possible entre la morphologie du condyle fémoral médial et le développement de lésions sous chondrales d’apparence kystique, peut-être en créant des cinématiques/contraintes anormales au niveau du condyle fémoral médial en sa région axiale. Ces résultats justifient des études plus approfondies, par exemple au moyen de modalités d’imagerie tel que CT ou IRM en 3 dimensions qui permettraient de préciser et de multiplier les mesures. / The stifle is one of the most complex equine joints and is the site of a significant portion of hindlimb lameness. Many horses with stifle lameness have pain localized in the medial femorotibial joint compartment. The medial femoral condyle is the site most commonly affected by subchondral bone cysts in the stifle in young sport horses and the medial femorotibial joint compartment with osteoarthritis in older horses. Investigations of maturation and morphological evolution of the shape of the human knee with age and correlation with pathology has revealed shape associations with cruciate ligament rupture, osteoarthritis or osteochondritis dissecans. Specifically, the narrowness of the femoral intercondylar notch is associated with the occurrence of osteochondritis dissecans or anterior cruciate ligament rupture. It is now known that medial femoral condyle subchondral cyst-like lesions occur in foals as young as 2 months of age and their exact cause remains unknown. The modelling of the shape of the bones of the femorotibial joint during postpartum maturation may have biomechanical impact and affect development of these lesions. Our objective was to measure shape changes during the first 20 months of age in the distal femur and proximal tibia of Thoroughbred foals and determine if there was an association or difference in those with medial femoral condyle cysts. Caudocranial stifle radiographs retrieved from a radiographic bank of young Thoroughbreds (3-20 months), with (n=53) and without (n=183) subchondral cyst-like lesions were analyzed. In addition, caudocranial radiographs (n=94) were also taken prospectively in 1-month old Thoroughbred foals. Thirteen morphological parameters of the distal femur and proximal tibia were measured on these radiographs, including at the femoral articular line (al) and popliteal fossa (pf). The shape of the femoral intercondylar notch was also qualitatively assessed on post-mortem radiographs of Thoroughbred foals (n=53, age 1-9 months), acquired for a prior study. In foals without medial femoral condyle subchondral cyst-like lesions, femoral condyle width and height increased with maturation (p<0.0001), whereas the width of the intercondylar notch decreased (p<0.0001) at the articular level. The qualitative shape analysis also revealed that the intercondylar notch narrowed with age to an Ω shape. In foals with medial femoral condyle subchondral-cyst lesions, femoral condyle width and lateral femoral condyle height increased with maturation (p<0.003) but no significant changes were observed for the width of the medial femoral condyle at the popliteal fossa, its height, or the intercondylar notch width at the articular line level with maturation. In both groups, the tibial plateau width increased with maturation (p<0.0001), in contrast to other tibial parameters. The bicondylar width and intercondylar notch width were larger for the left limb of healthy foals in all ages (p<0.01). In one-month-old foals, the medial femoral condyle was larger on the left (p<0.05). However, the medial femoral condyle at the articular line was larger on the right side in foals with lesions, more specifically, in females older ≥ 7 months (p=0.004). These results suggest a possible relationship between the morphology of the medial femoral condyle and the development of lesions, possibly by creating abnormal kinematics/stresses in the axial region of the medial femoral condyle. Three-dimensional imaging modalities may allow for more precise and extensive measurements of the condyles with for instance evaluation of the curvature or of the thickness.

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L’accident vasculaire cérébral (AVC) est une maladie débilitante qui a rendu des centaines de milliers de personnes handicapées. Les lésions du cortex moteur entraînent des déficiences motrices dont certaines sont permanentes. Le rat est le modèle animal le plus populaire dans la recherche sur les AVC. Il est capable de mouvements adroits d'atteinte et de préhension malgré un système moteur cortical beaucoup plus simple qui se compose de deux régions motrices des membres antérieurs, une plus grande région, l’aire caudale de la patte antérieure (CFA), considérée comme un équivalent du M1; et une plus petite, l’aire rostrale de la patte antérieure (RFA), considérée comme prémoteur. Leur contribution exacte à la production de mouvement, et leurs effets modulateurs sur le cortex moteur controlatéral ne sont pas clairs. L'effet des AVC sur les différentes modalités de mouvement et sur la réorganisation ipsi- et contralésionnelle n'a pas non plus été quantifié chez le rat. L'ensemble actuel d'expériences vise à établir l'impact de l'AVC ischémique sur les résultats comportementaux et les interactions corticales chez le rat. Dans le chapitre 1, le contexte scientifique et les connaissances actuelles de l’AVC comme trouble moteur du système nerveux central sont revus. Dans le chapitre 2, une relation entre les accidents vasculaires cérébraux de différentes tailles et les troubles du comportement et la récupération sur différentes modalités comportementales a été établie. Dans le chapitre 3, nous avons caractérisé les différences de retour moteur de deux régions corticales du membre antérieur et quantifié les effets modulateurs du cortex moteur du membre antérieur controlatéral sur ledit retour moteur. Enfin, nous avons quantifié la réorganisation du retour moteur et la modulation controlatérale suite à un accident vasculaire cérébral dans le cortex moteur des membres antérieurs au chapitre 4. Le chapitre 5 conclue la thèse avec une discussion générale et des orientations futures pour la recherche. Les résultats présentés ici établissent un lien clair entre les dommages aux sous-régions corticales et l'altération de domaines moteurs spécifiques. La caractérisation des différences dans les retours moteurs du CFA et du RFA ainsi que leurs interactions interhémisphériques ont confirmé leurs rôles distincts dans le contrôle moteur et établit une base pour des comparaisons avec les primates. Enfin, des preuves nouvelles et surprenantes de réorganisation bilatérale après un AVC ont été définies et caractérisées. / Stroke is a debilitating condition that has left hundreds of thousands of people disabled. Injury to the motor cortex leads to motor impairments, some of which are permanent. The rat is the most popular animal model in stroke research. It is capable of dexterous reach and grasp movements, despite having a much simpler cortical motor system, which consists of two forelimb motor regions; the larger area is the caudal forelimb area (CFA), thought to be an M1 equivalent, and the smaller one is rostral forelimb area (RFA), considered to be premotor. Neither their exact contribution to movement production nor modulatory effects on the contralateral motor cortex are clear. The effect of strokes on different movement modalities and the ipsi- and contralesional reorganization has not been quantified in the rat either. The current set of experiments set out to establish the impact of ischemic stroke on behavioral outcomes and cortical interactions in the rat. Chapter 1 introduces the scientific background and the present understanding of stroke as a motor disorder of the central nervous system. In Chapter 2, a relationship between strokes of various sizes and behavioral impairment and recovery on different behavioral modalities was established. In Chapter 3, we characterized the differences in motor outputs from two cortical forelimb regions and quantified the modulatory effects of the contralateral forelimb motor cortex on said motor outputs. Lastly, we quantified the reorganization of motor outputs and contralateral modulation following a stroke in the forelimb motor cortex in Chapter 4. Chapter 5 concludes the thesis with the general discussion and future directions. The results presented here establish a clear link between damage to cortical subregions and impairment to specific motor domains. Characterization of differences in motor outputs of the CFA and RFA as well as their interhemispheric interactions confirmed their distinct roles in motor control and lay the groundwork for comparisons to primates. Lastly, novel and surprising evidence of bilateral reorganization after stroke was defined and characterized.

Fruit rot caused by Aspergillus niger or Colletotrichum musae is an important post-harvest disease on orange, chilli and Cavendish banana fruits. The use of synthetic fungicides has been a traditional strategy for the management of the fruit rot disease, but these chemicals adversely affect human health and environment. Therefore, the objective of this study was to evaluate the effects of CaCl2 on in vitro hyphal growth and in vivo lesion inhibition. First, aqueous solutions of CaCl2 at three concentrations of 20, 40 and 60 mM were assessed for their inhibitory effect against hyphal growth in vitro. Next, mature fruits were immersed into a solution of 20 mM CaCl2 for 20 - 30 s, then inoculated by a pathogen suspension at the density of 106 conidia mL-1 and observed for 12 days. The results showed that 20 mM CaCl2 was the most effective concentration in antifungal assay to Aspergillus isolated from orange rot. The treatment of CaCl2 continued to gain efficacy on limiting lesions’ development on orange fruits until 12 days after inoculation (DAI). On chilli, CaCl2 at concentrations of 20 and 40 mM inhibited well on the growth of Aspergillus hyphae isolated from chilli rot. However, calcium treatment was not effective on chilli fruits. On Cavendish banana, solutions of CaCl2 at concentrations of 20, 40 and 60 mM highly limited fungal growth of Colletotrichum in vitro conditions. The application of CaCl2 solution could inhibit anthracnose lesion length of Cavendish banana variety, but its efficacy did not prolong until 6 DAI. In general, the good results were obtained from the 20 mM CaCl2 in almost all the studied assays. Management of rot diseases on fruits by employing 20 mM CaCl2 could be suitable to replace the current hazardous agro-chemicals. / Thối trái do nấm Aspergillus niger hay nấm Colletotrichum musae là bệnh sau thu hoạch thường gặp trên cam, ớt và chuối già. Thuốc trừ nấm tổng hợp là biện pháp truyền thống quản lý bệnh thối trái nhưng lại ảnh hưởng bất lợi đến sức khỏe con người và môi trường. Vì vậy, mục tiêu của nghiên cứu là đáng giá ảnh hưởng của CaCl2 đối với sự sinh trưởng in vitro của nấm và sự ức chế vết bệnh ở điều kiện in vivo. Đầu tiên, dung dịch CaCl2 ở các nồng độ 20, 40 và 60 mM được sử dụng để đánh giá khả năng ức chế sự sinh trưởng in vitro của nấm bệnh. Tiếp theo, trái trưởng thành được nhúng vào dung dịch CaCl2 20 mM trong 20 - 30 s, rồi lây nhiễm với huyền phù mầm bệnh ở mật số 106 bào tử mL-1 và quan sát đến 12 ngày. Kết quả cho thấy CaCl2 20 mM có hiệu quả ức chế tốt đối với nấm Aspergillus phân lập từ bệnh thối trái cam. CaCl2 tiếp tục thể hiện hiệu quả ức chế bệnh trên trái cam đến 12 ngày sau lây bệnh. Trên ớt, CaCl2 20 và 40 mM cho hiệu quả ức chế sự phát triển nấm Aspergillus phân lập từ bệnh thối trái ớt. Tuy nhiên, xử lý CaCl2 không mang lại hiệu quả mong đợi trên trái ớt. Trên chuối già, dung dịch CaCl2 ở các nồng độ 20, 40 và 60 mM ức chế tốt sợi nấm Colletotrichum trong điều kiện in vitro. Dung dịch canxi có thể ức chế vết bệnh thán thư trên chuối già, nhưng hiệu quả không kéo dài đến 6 ngày sau lây bệnh. Nhìn chung, các kết quả tốt đều đạt được khi xử lý bằng CaCl2 20 mM ở hầu hết các thí nghiệm. Việc kiểm soát bệnh thối trái bằng CaCl2 20 mM có thể thay thế cho hóa chất nông nghiệp độc hại hiện nay.

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Background Monteggia fractures and Monteggia-like lesions result after severe trauma and have high complication rates. Preliminary biomechanical studies suggested a correlation between ulnar fracture localization and clinical result. Objectives Key objective was to evaluate whether the site of the ulnar fracture can be correlated to clinical outcome after open reduction and internal stabilization. Methods In a retrospective, monocentric study 35 patients who underwent surgical treatment after suffering a Monteggia injury or Monteggia-like lesion were included. Fractures were classified according to Bado and Jupiter, the site of the fracture location at the proximal ulna and regarding the potential accompanying ligamentary injury. In a follow-up examination validated patient-reported outcome measures and functional parameters were evaluated. Furthermore, treatment strategy and complications were analysed. Results Mean patient age was 51.9 years (± 18.0). 69% were females (n = 24). Follow-up took place after 50.5 months (± 22.1). Fractures were classified according to Bado (I:2, II:27, III:4, IV:2). Bado II-fractures were further classified according to Jupiter (A:7, B:16, C:3, D:1). Cases were divided into subgroups depending upon the distance of the ulnar fracture site in respect to its distal endpoint (A: < 7 cm and B: > 7 cm). Average overall MEPS was 84.1 (± 19.0). Oxford elbow score and DASH were 37.2 (± 10.5) and 20.4 (± 20.5). Average extension capability reached − 7° (± 7.5). Mean flexion was 134.8° (± 19.7). Average pain according to visual analogue scale was 1.6 (± 1.9). We found no differences between the subgroups regarding the PROMs. Subgroup A displayed a worse extension capability (p = 0.027) and patients were significantly older (p < 0.01). Comparing patients with and without fracture of the radial head, we observed no differences. Patients with an accompanying injury of the coronoid process displayed higher pain levels (p = 0.011), a worse functionality (p = 0.027) and overall lower scoring in PROM. Conclusion The presented results suggest that in Monteggia fractures and Monteggia-like lesions, the localization of the ulna fracture can give a hint for its postoperative outcome. However, we could not confirm the hypothesis of an increasing instability in ulnar fractures located further distally (high severity of the potential ligamentous injury). Intraarticular fractures or injuries with a close relation to the joint have a worse prognosis, especially if the coronoid process is injured. Trial registration Registration was done with ClinicalTrials.gov under NCT05325268.

[pt] Em aproximadamente um terço dos pacientes com epilepsia, a cirurgia é única forma de intervenção para diminuição dos impactos ou término das crises. Em pacientes sem um foco lesional na imagem por ressonância magnética, essa intervenção depende de outros métodos investigativos, que nem sempre estão prontamente disponíveis. Nesses casos, métodos avançados de pós-processamento e de sequências de imagens podem ajudar a detectar lesões. O objetivo dessa revisão sistemática foi resumir a disponibilidade e taxas de sucesso dessas técnicas. De acordo com as diretrizes PRISMA, usando as bases de dados PubMED, Web of Science, PsycNET e CENTRAL, uma busca por artigos foi conduzida até o dia 12 de janeiro de 2021. No total, a busca retornou 4.024 artigos, com 49 permanecendo após a revisão. Vinte e cinco artigos usaram alguma forma de voxel-based morphometry, 14 usaram machine learning e 10 usaram técnicas avançadas de MRI. Apenas um artigo descreveu um estudo prospectivo. A taxa de detecção de lesões variou bastante entre estudos, com técnicas de machine learning demonstrando taxas mais consistentes, todas acima de 50 por cento em grupos de pacientes com imagem negativa. Isso pode ser útil em centros onde outros métodos investigativos, como PET, SPECT, MEG ou sEEG não estão prontamente acessíveis. / [en] In approximately one third of patients with epilepsy, surgery is the only form of intervention to diminish seizure burden or achieve seizure freedom. In patients without a lesional focus on MRI, surgical intervention depends on other investigative methods, not always readily accessible. Advanced MRI postprocessing and acquisition methods may help with lesion localization in those cases. The aim of this systematic review was to summarize the availability and success rate of such MRI techniques. In accordance with the PRISMA guidelines, using PubMED, Web of Science, PsycNET, and CENTRAL, a search for papers was performed until the 12th of January of 2021. In total, the search returned 4,024 papers, of which 49 remained after revision. Twenty-five used a form of voxelbased morphometry, 14 used machine learning techniques, and 10 used advanced MRI sequences not commonly part of the standard MRI-protocol. Only one paper described a prospective study. The lesion detection rate greatly varied between studies, with machine learning techniques showing a more consistent rate, all above 50 percent in MRI-negative groups. This could be particularly helpful in center where other investigative methods, including PET, SPECT, MEG and stereo EEG are not readily available.

Left hemisphere damage is a frequent cause of aphasia. Analyses of deviant linguistic behaviors provide valuable information about the functional architecture of language. Correlating specific language difficulties with damage to the brain helps shed light on the relationships between language and the neural substrate. The aim of this Ph.D. thesis is to contribute to the understanding of the neural correlates of sentence comprehension, based on behavioral and neuroimaging evidence from aphasia. A substantial amount of research based on lesion-symptom mapping has been devoted to this issue, but several issues remain to be clarified. To consider just an example, lesion-symptom mapping studies have systematically linked the posterior regions of the left hemisphere to sentence comprehension. Surprisingly, however, the same studies failed to provide similarly strong evidence for prefrontal regions, contradicting the results of previous neuropsychological investigations that clearly supported the critical role of these regions in sentence processing. To date, there are enough controversial issues on sentence processing as to warrant reconsideration of available evidence. The present project focused on the neural correlates of the mechanisms involved in thematic role assignment and in the processing of morphosyntactic features. This is because both sets of mechanisms are critical for sentence interpretation both in comprehension and in production. The first step of the project consisted of a systematic literature review and meta-analysis of lesion-symptom investigations of sentence processing (study 1 – Chapter 1). The literature search yielded 43 studies eligible for review, of which 27 were used in the meta-analysis. The main goal was to identify the correlates of thematic role assignment and of morphosyntactic processing. Thematic role assignment errors correlated mainly with damage in the left temporo-parietal regions, and morphosyntactic errors mainly with damage in the prefrontal regions. However, careful consideration of the reviewed and meta-analyzed studies shows that conclusions are biased under several aspects. Data on thematic deficits are based almost exclusively on sentence comprehension, and data on morphosyntactic deficits on sentence production. Furthermore, even the very few studies that evaluated both impairments did so in distinct linguistic contexts, or in different response modalities. In addition, studies that focused on one set of mechanisms did not consider the possibility that performance on their dimension of interest was influenced by damage to the other. For example, studies focusing on thematic comprehension administered thematic foils, but not morphosyntactic foils. Therefore, the neurofunctional correlates emerging from the meta-analysis and the review may offer a biased and/or partial view. As a first attempt at overcoming these limitations, a lesion study on native speakers of Italian with post-left stroke aphasia was conducted (study 2 – Chapter 2) to clarify the neural substrates of morphosyntactic and thematic processes in comprehension. Experimental stimuli consisted of simple declarative, semantically reversible sentences presented in the active or passive voice. In an auditory sentence comprehension task, participants were asked to match a sentence spoken by the computer to the corresponding picture, that had to be distinguished from a thematic, a morphosyntactic or a lexical-semantic foil. Thirty-three left brain-damaged individuals (out of an initial sample of 70) were selected because they fared normally on lexical-semantic foils, but poorly on morphosyntactic (n=15) and/or thematic (n=18) contrasts. Voxel-based Lesion Symptom Mapping (VLSM) analyses retrieved non-overlapping substrates. Morphosyntactic difficulties were uninfluenced by sentence voice and correlated with left inferior and middle frontal damage, whereas thematic role reversals were more frequent on passives and correlated with damage to the superior and middle temporal gyrus and to the superior occipitolateral cortex. Both correlations persisted after covarying for phonological short-term memory. When response accuracy to passive vs active sentences in the presence of thematic foils was considered, portions of the angular and supramarginal gyrus were retrieved. They could provide the neural substrate for thematic reanalysis, that is critical for comprehending sentences with noncanonical word order. However interesting and strong, these results were obtained by considering just one sentence type (declaratives) and by relying on basic neuroimaging data. To go beyond these limitations, the final step of the project relied on more comprehensive behavioral analyses and more advanced neuroimaging techniques (study 3 – Chapter 3). The SCOPRO (Sentence Comprehension and PROduction) language battery was developed, that focuses on thematic and morphosyntactic processes and allows assessing these processes in a variety of reversible sentences in both comprehension and production. SCOPRO was administered to 50 neurotypical subjects (to assess applicability and establish cutoff levels) and 27 aphasic participants (native Italian speakers with left post-stroke aphasia). Of the latter, 21 were included in an MRI-based lesion-symptom mapping study. Results obtained in comprehension tasks were correlated with neuroimaging data (structural T1 and DWI). Lesion maps, disconnectome maps, tract disconnection probability and personalized deterministic tractography data demonstrated the involvement of grey and white matter. Thematic role reversals correlated to cortical damage in the left angular gyrus. They also correlated to cortical damage in the left supramarginal gyrus when controlling for single-word processing in a voxel-based disconnectome-symptom mapping analysis. Thematic errors were associated also with underlying white matter damage. Correlating the probability of tract disconnections and personalized deterministic tractography with thematic role performance involved the left arcuate fasciculus. The posterior segment was associated with thematic role reversals, even after controlling for morphosyntactic and single-word processing. The anterior segment was linked to accuracy on thematic roles when single-word processing was used as a covariate. The long segment also correlated with the level of thematic role performance, but the correlation was no longer present when morphosyntactic performance was used as a covariate. SCOPRO can be used not only to assess language processes in a broad sense (e.g., morphosyntactic vs thematic), but also to look into more detailed issues. Contrasting accuracy on declarative and comparative sentences is an interesting case in point. Both sentence types express reversible relations, but only declaratives require thematic role mapping. Hence, contrasting results between the two could help distinguish the correlates of role mapping from those of reversibility per se. The supramarginal gyrus was damaged in participants who fared poorly in both declaratives and comparatives but, interestingly, the aphasics with selective thematic difficulties had suffered damage to the posterior division of the middle temporal gyrus and to the angular gyrus, whereas those with selective difficulties on comparatives presented with lesions in the parietal and central opercular cortex. Clearly, these results are preliminary and require further investigation. It is unanimously accepted that sentence processing involves a large-scale network including frontal, temporal and parietal cortices and the underlying white matter pathways. The main contribution of the present project is that it allows articulating more detailed hypotheses on the role played by some components of the network during sentence comprehension. Results tie left frontal regions to morphosyntactic processing, posterior temporal regions to the retrieval of verb argument structure, and a posterior-superior parietal area to thematic reanalysis. Preliminary observations also suggest that different neural substrates could be involved in processing reversibility as such and when more specifically implemented in thematic roles. Further studies exploiting detailed behavioral tools like the SCOPRO battery and sophisticated neuroimaging techniques in larger samples will lead to a better understanding of language functions and their processing in the brain.

Die Stimme ist reich an grundlegenden Kommunikationselementen: Sie transportiert Sprache, sowie auch paralinguistische Informationen, wie den emotionale Zustand und die Identität des Sprechers. Im Vergleich zur Sprach- und Emotionsverarbeitung ist die Stimmerkennung bei weitem weniger gut erforscht. Dies ist erstaunlich, angesichts der allgegenwärtigen Relevanz der stimmbasierten Personenerkennung. Ein Ansatz neue Erkenntnisse zur Stimmerkennung zu erlangen, ist die Untersuchung von Personen, die ein selektives Defizit in der Stimmerkennung aufweisen. Dieses Defizit wird Phonagnosie bezeichnet. In der vorliegenden Dissertation untersuche ich Personen, bei denen Phonagnosie nach einer Hirnschädigung aufgetreten ist (i.e. erworbene Phonagnosie) und Personen, bei denen Phonagnosie entwicklungsbedingt und nicht durch eine offensichtliche Hirnschädigung bedingt ist (i.e. entwicklungsbedingte Phonagnosie). Die zugrunde liegenden kognitiven, neuro-funktionalen und neuro-anatomischen Mechanismen der Phonagnosie habe ich detailliert mit Hilfe von umfangreichen Verhaltensuntersuchungen sowie funktionaler und struktureller Magnetresonanztomographie charakterisiert. Die Ergebnisse der Dissertation bereichern das derzeitige Stimmerkennungsmodel durch: (i) Neue Erkenntnisse darüber welche Gehirnregionen notwendig sind, um eine Stimme zu erkennen. (ii) Und durch die empirische Bekräftigung der Annahme, dass Stimmerkennung ein mehrstufiger kognitiver Prozess ist, der verschiedene Subformen der Phonagnosie bedingt. Darüber hinaus tragen neue wissenschaftliche Erkenntnisse zur Stimmerkennung maßgeblich dazu bei, praktische Anwendungsbereiche wie klinische Therapieprogramme und künstliche Stimmerkennungprogramme weiterzuentwickeln. / The voice contains elementary social communication cues: it conveys speech, as well as paralinguistic information pertaining to the emotional state or the identity of the speaker. In contrast to neuroscientific research on vocal-speech and vocal-emotion processing, voice-identity processing has been less explored. This seems surprising, given the day-to-day significance of person recognition by voice. A valuable approach to unravel how voice-identity processing is accomplished is to investigate people who have a selective deficit in voice recognition. Such a deficit has been termed phonagnosia. In the present dissertation, I investigate phonagnosia following brain damage (i.e. acquired phonagnosia), as well as phonagnosia cases without apparent brain lesion (i.e. developmental phonagnosia). I in-depth characterise the underlying cognitive, neural-functional, and neuro-anatomical mechanisms of phonagnosia by means of comprehensive behavioural testing as well as functional and structural magnetic resonance imaging. The findings of this dissertation inform the current model of voice-identity processing by (i) delivering novel evidence of brain regions that crucially contribute to voice-identity processing, and by (ii) emphasising the multistage nature of voice-identity processing. We showed that dysfunction at different cognitive stages results in behaviourally distinct phonagnosia sub-types. Generally, advanced scientific knowledge about voice-identity processing as provided in the current dissertation also propels practical applications such as clinical treatment programs and artificial voice-recognition systems.