Telômeros são complexos DNA-proteína presentes nas extremidades dos cromossomos. Os telômeros se encurtam a cada divisão celular, sendo o comprimento telomérico, portanto, considerado um biomarcador do envelhecimento celular. Esse encurtamento é vinculado a diversas doenças relacionadas à idade avançada. Na doença de Alzheimer (DA), têm sido associados com diversas vias fisiopatológicas, como a neuroinflamação e o estresse oxidativo, porém seus mecanismos ainda são pouco conhecidos. A maioria dos estudos sobre comprimento telomérico na DA é realizada em DNA leucocitário, pouco se sabendo sobre seu estado no sistema nervoso central. O lítio é um importante estabilizador de humor, com efeitos neuroprotetores amplamente evidenciados, mas pouco se sabe sobre seu efeito na manutenção do comprimento telomérico. O objetivo do presente estudo foi avaliar o efeito do tratamento crônico com lítio no comprimento telomérico em diferentes regiões cerebrais (córtex parietal, hipocampo e epitélio olfatório) de camundongos triplo transgênicos para DA (3xTg-AD) e selvagens. Dezoito animais transgênicos e 22 selvagens foram tratados por oito meses com ração contendo 1,0 g (Li1) ou 2,0 g (Li2) de carbonato de lítio/kg, ou ração padrão (Li0). O comprimento telomérico do DNA extraído destes tecidos foi quantificado por PCR em tempo real. O tratamento crônico com lítio foi associado a telômeros mais longos no córtex parietal (Li1, p=0,04) e hipocampo (Li2, p=0,02) dos camundongos 3xTg-AD comparados com os respectivos selvagens. Nossos achados sugerem que o tratamento crônico com lítio afeta a manutenção do comprimento telomérico, mas que a magnitude desse efeito depende da concentração de lítio ministrada e das características do tecido envolvido. Esse efeito foi apenas observado quando comparando os animais triplo transgênicos com os selvagens, indicando que a presença da patologia, no caso a DA, se faz necessária para a modulação do comprimento telomérico promovida pelo lítio / Telomeres are DNA-protein complexes present in the extremities of chromosomes. Telomeres shorten at each cell division, being the telomere length, therefore, considered a cell aging biomarker. This telomere shortening is associated to several age-related diseases. In Alzheimer\'s disease (AD), telomere length has been linked to several pathophysiological pathways, such as neuroinflammation and oxidative stress, though its mechanism are still poorly understood. Majority of studies regarding telomere length in AD are based in leucocyte DNA, with little information about its status in the central nervous system. Lithium is an important mood stabilizer, with neuroprotective effects widely evidenced, but little is known about its effects in telomere length maintenance. The objective of this present study was to evaluate the effect of chronical lithium treatment on telomere length in different brain regions (parietal cortex, hippocampus and olfactory epithelium) of wild type and triple transgenic mice model for AD (3xTg-AD). Eighteen transgenic and 22 wild type male mice were treated for eight months with chow containing 1.0g (Li1) or 2.0g (Li2) of lithium carbonate/kg, or standard chow (Li0). Telomere length of extracted DNA from theses tissues was quantified by real-time PCR. Chronic lithium treatment was associated with longer telomeres in the parietal cortex (Li1, p=0.04) and in the hippocampus (Li2, p=0.02)of 3xTg-AD compared with the respective wild type.Our findings suggest that chronic lithium treatment does affect telomere maintenance, but the magnitude of this effect depends on the working concentrations of lithium and characteristics of the involved tissue. This effect was only observed when comparing triple transgenic with wild type mice, suggesting that the presence of AD pathology was required for the lithium modulation of telomere length

Der menschliche inferiore Parietallappen (IPC) gehört zum Assoziationskortex und spielt eine wichtige Rolle bei der Integration von somatosensorischen (taktilen), visuellen und akustischen Reizen. Bisher gibt es keine eindeutigen Informationen über den strukturellen Aufbau dieser Hirnregion. Parzellierungen anhand der Zytoarchitektur reichen von zwei (Brodmann 1909) bis sieben Subareale (Caspers et al. 2006). Homologien zwischen dem IPC des Menschen und Makaken-Affen sind weitestgehend unbekannt. In der vorliegenden Arbeit wurden der Aufbau und die Konnektivitäten des menschlichen IPC genauer untersucht. Dazu führte man eine konnektivitätsbasierte Parzellierung des IPC an 20 Probanden durch. Als Methode kam Diffusions-Tensor-Imaging (DTI) kombiniert mit probabilistischer Traktogra-phie zum Einsatz. Der IPC konnte anhand der Konnektivitäten in drei Subareale (IPCa, IPCm, IPCp) parzelliert werden. Diese besitzen in beiden Hemisphären eine ähnliche Größe und eine rostro-kaudale Anordnung. Die Parzellierung ist vergleichbar mit der des Makaken-IPC, bei dem ebenfalls eine Unterteilung in drei Areale (PF, PFG, PG) und eine rostro-kaudale Anordnung nachgewiesen werden konnte. Jedes Subareal des menschlichen IPC besitzt ein individuelles Konnektivitätsmuster. Beim Menschen als auch beim Makaken gibt es starke Verbindungen zum lateralen prämotorischen Kortex und zum superioren Parietallappen. Diese Gemeinsamkeiten lassen darauf schließen, dass strukturelle Eigenschaften im Laufe der Evolution erhalten geblieben sind. Allerdings sind beim Menschen auch Neuentwicklungen nachweisbar. Dazu gehören die deutlich hervortretenden Verbindungen zum Temporallappen. Möglicherweise haben sich diese erst während der Evolution entwickelt und sind beim Menschen als Teil des perisylvischen Sprachnetzwerkes an der Sprachbildung beteiligt. / The human inferior parietal cortex convexity (IPCC) is an important association area, which integrates auditory, visual and somatosensory information. However, the structural organization of the IPCC is a controversial issue. For example, cytoarchitectonic parcellations reported in the literature range from two to seven areas. Moreover, anatomical descriptions of the human IPCC are often based on experiments in the macaque monkey. In this study we used diffusion-weighted magnetic resonance imaging (dMRI) combined with probabilistic tractography to quantify the connectivity of the human IPCC, and used this information to parcellate this cortex area. This provides a new structural map of the human IPCC, comprising three sub-areas (IPCa, IPCm, IPCp) of comparable size, in a rostro-caudal arrangement in the left and right hemisphere. Each sub-area is characterized by a connectivity fingerprint and the parcellation is similar to the subdivision reported for the macaque IPCC (rostro-caudal areas areas PF, PFG, and PG). However, the present study also reliably demonstrates new structural features in the connectivity pattern of the human IPCC, which are not known to exist in the macaque. This study quantifies inter-subject variability by providing a population representation of the sub-area arrangement, and demonstrates substantial lateralization of the connectivity patterns of IPCC.

Telômeros são complexos DNA-proteína presentes nas extremidades dos cromossomos. Os telômeros se encurtam a cada divisão celular, sendo o comprimento telomérico, portanto, considerado um biomarcador do envelhecimento celular. Esse encurtamento é vinculado a diversas doenças relacionadas à idade avançada. Na doença de Alzheimer (DA), têm sido associados com diversas vias fisiopatológicas, como a neuroinflamação e o estresse oxidativo, porém seus mecanismos ainda são pouco conhecidos. A maioria dos estudos sobre comprimento telomérico na DA é realizada em DNA leucocitário, pouco se sabendo sobre seu estado no sistema nervoso central. O lítio é um importante estabilizador de humor, com efeitos neuroprotetores amplamente evidenciados, mas pouco se sabe sobre seu efeito na manutenção do comprimento telomérico. O objetivo do presente estudo foi avaliar o efeito do tratamento crônico com lítio no comprimento telomérico em diferentes regiões cerebrais (córtex parietal, hipocampo e epitélio olfatório) de camundongos triplo transgênicos para DA (3xTg-AD) e selvagens. Dezoito animais transgênicos e 22 selvagens foram tratados por oito meses com ração contendo 1,0 g (Li1) ou 2,0 g (Li2) de carbonato de lítio/kg, ou ração padrão (Li0). O comprimento telomérico do DNA extraído destes tecidos foi quantificado por PCR em tempo real. O tratamento crônico com lítio foi associado a telômeros mais longos no córtex parietal (Li1, p=0,04) e hipocampo (Li2, p=0,02) dos camundongos 3xTg-AD comparados com os respectivos selvagens. Nossos achados sugerem que o tratamento crônico com lítio afeta a manutenção do comprimento telomérico, mas que a magnitude desse efeito depende da concentração de lítio ministrada e das características do tecido envolvido. Esse efeito foi apenas observado quando comparando os animais triplo transgênicos com os selvagens, indicando que a presença da patologia, no caso a DA, se faz necessária para a modulação do comprimento telomérico promovida pelo lítio / Telomeres are DNA-protein complexes present in the extremities of chromosomes. Telomeres shorten at each cell division, being the telomere length, therefore, considered a cell aging biomarker. This telomere shortening is associated to several age-related diseases. In Alzheimer\'s disease (AD), telomere length has been linked to several pathophysiological pathways, such as neuroinflammation and oxidative stress, though its mechanism are still poorly understood. Majority of studies regarding telomere length in AD are based in leucocyte DNA, with little information about its status in the central nervous system. Lithium is an important mood stabilizer, with neuroprotective effects widely evidenced, but little is known about its effects in telomere length maintenance. The objective of this present study was to evaluate the effect of chronical lithium treatment on telomere length in different brain regions (parietal cortex, hippocampus and olfactory epithelium) of wild type and triple transgenic mice model for AD (3xTg-AD). Eighteen transgenic and 22 wild type male mice were treated for eight months with chow containing 1.0g (Li1) or 2.0g (Li2) of lithium carbonate/kg, or standard chow (Li0). Telomere length of extracted DNA from theses tissues was quantified by real-time PCR. Chronic lithium treatment was associated with longer telomeres in the parietal cortex (Li1, p=0.04) and in the hippocampus (Li2, p=0.02)of 3xTg-AD compared with the respective wild type.Our findings suggest that chronic lithium treatment does affect telomere maintenance, but the magnitude of this effect depends on the working concentrations of lithium and characteristics of the involved tissue. This effect was only observed when comparing triple transgenic with wild type mice, suggesting that the presence of AD pathology was required for the lithium modulation of telomere length

INTRODUÇÃO: A vivência de maus tratos na infância é apontada como um fator de risco para o desenvolvimento de comportamentos antissociais e traços psicopáticos. Estudos sugerem alterações estruturais de substância branca (SB) cerebral em vítimas de maus tratos, que podem estar subjacentes a sintomas psiquiátricos e dificuldades cognitivas. OBJETIVO: Investigar o comportamento social de adolescentes vítimas de maus tratos (A-VMT), através da comparação de suas habilidades sociais e traços de psicopatia com um grupo controle (GC), e de possíveis correlações destas medidas com os diferentes tipos de maus tratos e com o volume de SB cerebral. MÉTODO: Foram avaliados 67 A-VMT e 41 adolescentes do GC através do Questionário de Traumas na Infância (QUESI), da Psychopathy Checklist Youth Version (PCL-YV) e do Inventário de Habilidades Sociais para Adolescentes (IHSA). Também foram adquiridas imagens anatômicas cerebrais através de equipamento de ressonância magnética (1,5T Siemens Sonata) e realizadas análises de morfometria baseada em voxels (VBM). RESULTADOS: Os A-VMT apresentaram maior intensidade de traços psicopáticos e mais déficits de habilidades sociais que o GC. A negligência emocional foi a forma de maus tratos que mais influenciou a presença de traços de psicopatia e que mais associou-se a prejuízos de habilidades sociais específicas. O volume de SB de regiões do hemisfério esquerdo (giro angular, precuneus e lobo parietal inferior) correlacionouse negativamente com o fator afetivo da PCL:YV. Além disso, foram encontradas correlações positivas entre o volume de SB de regiões de hemisfério direito com fatores de psicopatia: o volume do lobo parietal superior direito correlacionou-se com características interpessoais e o do giro pré-central com o fator antissocial. CONCLUSÃO: Os A-VMT apresentaram déficits do comportamento social quando comparados ao GC. O volume de SB de áreas cerebrais envolvidas no processamento de informações sociais e reconhecimento de emoções se correlacionou com traços específicos da psicopatia. A vivencia de maus tratos na infância pode contribuir para déficits na cognição social, o que por sua vez, pode predispor esta vulnerável população a alguns comportamentos antissociais / Introduction: Child maltreatment is considered a risk factor for the development of antisocial behaviors and psychopathic traits. Studies suggest that specific white matter tracts may be vulnerable to child maltreatment and their alterations can be associated with psychiatric symptoms and cognitive deficits. Aim: Compare social skills and psychopathic traits between maltreated adolescents (MTA) and a control group, as well as their possible correlations with different types of maltreatment and white matter volumes.. Method: The sample was composed by 67 MTA and 41 youths from the CG. Brain images were acquired by magnetic resonance imaging equipment (1,5T Siemens Sonata) for voxel-based morphometry analyses. The clinical evaluation was carried out using Childhood Trauma Inventory (CTQ), Social Skills Inventory for Adolescents (SSIA) and The Hare Psychopathy Checklist: Youth Version (PCL:YV). Results: MTA presented more psychopathic traits and social skills deficits than the CG. Emotional neglect was the only maltreatment subtype with significant effect on psychopathic traits, and it was correlated with specific social skills deficits. The white matter volumes of left hemisphere regions (angular gyrus, precuneus and inferior parietal lobe) were negatively correlated with PCL:YV affective factor scores. Moreover, positive correlations between white matter volume of right hemisphere areas (superior parietal lobe and precentral gyrus) and specific psychopathic traits (antisocial and interpersonal) were found. Conclusion: MTA presented social deficits when compared to CG. The white matter volume of brain areas associated with social information processing and emotion recognition was correlated with specific psychopathic traits. Child maltreatment may contribute to social cognition deficits and predispose this vulnerable population to psychopathic traits

L’utilisation d’outils est un trait définitoire du genre Homo. Il est donc fondamental de mieux connaître les bases cognitives et cérébrales nous permettant d’utiliser des outils. Les modèles cognitivistes actuels expliquent l’utilisation d’outils à travers l’hypothèse de l’activation d’une mémoire gestuelle (i.e., engrammes gestuels ou visuo-kinétiques, ou connaissances sensorimotrices sur la manipulation ; voir Rothi, Ochipa, & Heilman, 1991 ; Buxbaum, 2001) ? Cette hypothèse ne permet toutefois pas de comprendre l’utilisation d’outils nouveaux. Une hypothèse alternative a été établie, suggérant que toute situation d’utilisation d’outils (familiers et nouveaux) requière un raisonnement technique (e.g., Osiurak & Badets, 2016). Ce type de raisonnement, qui impliquerait le lobe pariétal inférieur gauche, nous permettrait de formuler l’action mécanique et d’évaluer les propriétés physiques des outils et des objets. Dans le cadre de cette hypothèse, l’une des finalités de cette thèse était de mieux comprendre les troubles d’utilisation d’outils chez des patients cérébro-lésés. Le présent travail s’est également porté sur l’investigation de la cognition numérique. Par ce terme, nous ne faisons pas uniquement référence au calcul mental ou à l’arithmétique. Nous englobons également ce que Dehaene et Cohen (1995) ont nommé code analogique dans leur Modèle du Triple Code. Ce code stockerait les représentations des quantités numériques au sein des lobes pariétaux. Autrement dit, il contiendrait le sens du nombre (Dehaene, 1997) permettant d’associer une étiquette symbolique (e.g., chiffre arabe) à la quantité correspondante. Au quotidien, ce serait grâce à ces représentations que nous pourrions comparer ou estimer la numérosité des ensembles d’objets. L’objectif principal de cette thèse était de rapprocher, tant au niveau cognitif que cérébral, ces deux domaines d’intérêt que sont l’utilisation d’outils et la cognition numérique. En effet, nous avons remarqué que ces deux capacités nécessitaient toutes deux un processus commun d’estimation de la magnitude (i.e., magnitude des propriétés physiques et magnitude des quantités numériques). En outre, au niveau cérébral, elles nécessitent l’activation de régions communes dans le lobe pariétal. Pour penser ce lien, nous nous sommes appuyés sur la théorie de la magnitude (ATOM) formulée par Walsh (2003). Celui-ci postule que toutes les magnitudes, c’est-à-dire toutes les dimensions qui peuvent être décrites par des relations « plus que/moins que », soient traitées au sein d’un système commun et unique dans le lobe pariétal droit (Bueti & Walsh, 2009). Nous avons supposé que la magnitude des propriétés physiques pourrait être traitée dans ce système au même titre que les magnitudes discrètes (e.g., numérosité) et continues (e.g., temps, espace). Nos résultats ont mis en évidence un trouble de l’utilisation d’outils nouveaux chez les patients LBD, sans difficultés apparentes pour estimer les propriétés physiques. Les patients RBD étaient déficitaires dans toutes les conditions évaluant la cognition numérique, contredisant les prédictions issues du TCM. Ces patients étaient également en difficulté pour estimer la longueur mais pas le poids. Comme des associations entre estimation de la longueur et du poids, et entre estimation de la longueur et cognition numérique ont été observées dans les différents groupes, nous suggérons que le système de magnitude soit divisé en sous-systèmes. Fait étonnant, nous avons trouvé une association entre utilisation d’outils et calcul approximatif chez les patients LBD supposant une tentative de compensation de l’utilisation par le calcul. Finalement, il semble que l’utilisation d’outils et la cognition numérique reposent sur des mécanismes neurocognitifs distincts, puisque les différents types de magnitudes ne paraissent pas être traités au sein d’un système commun et unique. / Tool use is a defining feature of the genus Homo. It is therefore fundamental to better understand the cognitive and cerebral bases that allow us to use tools. The current cognitivist models explain tool use through the hypothesis of an activation of gestural memories (i.e., gestural or visuo-kinetic engrams, or sensorimotor knowledge of manipulation; see Rothi, Ochipa, & Heilman, 1991; Buxbaum, 2001). This theory is unable to explain the use of novel tools. An alternative hypothesis suggests that any situation of tool use (familiar and new) requires technical reasoning (e.g., Osiurak & Badets, 2016). This reasoning, involving the left inferior parietal lobe, would enable to formulate the mechanical action and to evaluate the physical properties of tools and objects. One of the aims of this thesis was to better understand the tool use disorders in brain-damaged patients, within the framework of the technical reasoning hypothesis. This work has also focused on the investigation of numerical cognition. By this term we refer to mental arithmetic and math, but also to analogical code (see the Triple Code Model, Dehaene & Cohen, 1995). It corresponds to the representation of numerical quantities, stored in the parietal lobes. In other words, this code would contain the sense of number (Dehaene, 1997) to associate a symbolic label (e.g., Arabic digits) with the corresponding quantity. In everyday life, this representation would be critical to compare or estimate the numerosity of object sets.The main objective of this thesis was to explore, at cognitive and cerebral levels, whether links exist between both fields of interest that are tool use and numerical cognition. Indeed, we noticed that both capacities need a common process of magnitude estimation (i.e., physical properties and numerical quantity). In addition, at the cerebral level, they require the activation of common regions in the parietal lobe. We relied on the Theory Of Magnitude (ATOM) formulated by Walsh (2003). It postulates that all magnitudes, namely the dimensions described by “more than/less than” relationships (e.g., Is this stick long enough to reach a given place?), are processed within a common and unique system, in the right parietal lobe (Bueti & Walsh, 2009). We assumed that the magnitude of physical properties could be processed in this system as well as the discrete (e.g., numbers) and continuous (e.g., time, space) magnitudes. Our results highlighted a disorder of novel tool-use in LBD patients, who nevertheless had no difficulty in estimating physical properties. The RBD patients were impaired in all conditions assessing the numerical cognition, refuting the predictions derived from TCM. They were also impaired in the estimation of the length but not of the weight. As associations between estimation of length and of weight, and between estimation of length and numerical cognition have been observed in the different groups, we suggest that the magnitude system be divided into subsystems. Surprisingly, we found an association between tool use and approximate calculation in LBD patients assuming an attempt to compensate tool use by calculation. Finally, it seems that tool use and numerical cognition rely on distinct neurocognitive mechanisms since the different types of magnitudes might not be processed within a common and unique system of magnitude

INTRODUÇÃO: A vivência de maus tratos na infância é apontada como um fator de risco para o desenvolvimento de comportamentos antissociais e traços psicopáticos. Estudos sugerem alterações estruturais de substância branca (SB) cerebral em vítimas de maus tratos, que podem estar subjacentes a sintomas psiquiátricos e dificuldades cognitivas. OBJETIVO: Investigar o comportamento social de adolescentes vítimas de maus tratos (A-VMT), através da comparação de suas habilidades sociais e traços de psicopatia com um grupo controle (GC), e de possíveis correlações destas medidas com os diferentes tipos de maus tratos e com o volume de SB cerebral. MÉTODO: Foram avaliados 67 A-VMT e 41 adolescentes do GC através do Questionário de Traumas na Infância (QUESI), da Psychopathy Checklist Youth Version (PCL-YV) e do Inventário de Habilidades Sociais para Adolescentes (IHSA). Também foram adquiridas imagens anatômicas cerebrais através de equipamento de ressonância magnética (1,5T Siemens Sonata) e realizadas análises de morfometria baseada em voxels (VBM). RESULTADOS: Os A-VMT apresentaram maior intensidade de traços psicopáticos e mais déficits de habilidades sociais que o GC. A negligência emocional foi a forma de maus tratos que mais influenciou a presença de traços de psicopatia e que mais associou-se a prejuízos de habilidades sociais específicas. O volume de SB de regiões do hemisfério esquerdo (giro angular, precuneus e lobo parietal inferior) correlacionouse negativamente com o fator afetivo da PCL:YV. Além disso, foram encontradas correlações positivas entre o volume de SB de regiões de hemisfério direito com fatores de psicopatia: o volume do lobo parietal superior direito correlacionou-se com características interpessoais e o do giro pré-central com o fator antissocial. CONCLUSÃO: Os A-VMT apresentaram déficits do comportamento social quando comparados ao GC. O volume de SB de áreas cerebrais envolvidas no processamento de informações sociais e reconhecimento de emoções se correlacionou com traços específicos da psicopatia. A vivencia de maus tratos na infância pode contribuir para déficits na cognição social, o que por sua vez, pode predispor esta vulnerável população a alguns comportamentos antissociais / Introduction: Child maltreatment is considered a risk factor for the development of antisocial behaviors and psychopathic traits. Studies suggest that specific white matter tracts may be vulnerable to child maltreatment and their alterations can be associated with psychiatric symptoms and cognitive deficits. Aim: Compare social skills and psychopathic traits between maltreated adolescents (MTA) and a control group, as well as their possible correlations with different types of maltreatment and white matter volumes.. Method: The sample was composed by 67 MTA and 41 youths from the CG. Brain images were acquired by magnetic resonance imaging equipment (1,5T Siemens Sonata) for voxel-based morphometry analyses. The clinical evaluation was carried out using Childhood Trauma Inventory (CTQ), Social Skills Inventory for Adolescents (SSIA) and The Hare Psychopathy Checklist: Youth Version (PCL:YV). Results: MTA presented more psychopathic traits and social skills deficits than the CG. Emotional neglect was the only maltreatment subtype with significant effect on psychopathic traits, and it was correlated with specific social skills deficits. The white matter volumes of left hemisphere regions (angular gyrus, precuneus and inferior parietal lobe) were negatively correlated with PCL:YV affective factor scores. Moreover, positive correlations between white matter volume of right hemisphere areas (superior parietal lobe and precentral gyrus) and specific psychopathic traits (antisocial and interpersonal) were found. Conclusion: MTA presented social deficits when compared to CG. The white matter volume of brain areas associated with social information processing and emotion recognition was correlated with specific psychopathic traits. Child maltreatment may contribute to social cognition deficits and predispose this vulnerable population to psychopathic traits

Der menschliche inferiore Parietallappen (IPC) gehört zum Assoziationskortex und spielt eine wichtige Rolle bei der Integration von somatosensorischen (taktilen), visuellen und akustischen Reizen. Bisher gibt es keine eindeutigen Informationen über den strukturellen Aufbau dieser Hirnregion. Parzellierungen anhand der Zytoarchitektur reichen von zwei (Brodmann 1909) bis sieben Subareale (Caspers et al. 2006). Homologien zwischen dem IPC des Menschen und Makaken-Affen sind weitestgehend unbekannt. In der vorliegenden Arbeit wurden der Aufbau und die Konnektivitäten des menschlichen IPC genauer untersucht. Dazu führte man eine konnektivitätsbasierte Parzellierung des IPC an 20 Probanden durch. Als Methode kam Diffusions-Tensor-Imaging (DTI) kombiniert mit probabilistischer Traktogra-phie zum Einsatz. Der IPC konnte anhand der Konnektivitäten in drei Subareale (IPCa, IPCm, IPCp) parzelliert werden. Diese besitzen in beiden Hemisphären eine ähnliche Größe und eine rostro-kaudale Anordnung. Die Parzellierung ist vergleichbar mit der des Makaken-IPC, bei dem ebenfalls eine Unterteilung in drei Areale (PF, PFG, PG) und eine rostro-kaudale Anordnung nachgewiesen werden konnte. Jedes Subareal des menschlichen IPC besitzt ein individuelles Konnektivitätsmuster. Beim Menschen als auch beim Makaken gibt es starke Verbindungen zum lateralen prämotorischen Kortex und zum superioren Parietallappen. Diese Gemeinsamkeiten lassen darauf schließen, dass strukturelle Eigenschaften im Laufe der Evolution erhalten geblieben sind. Allerdings sind beim Menschen auch Neuentwicklungen nachweisbar. Dazu gehören die deutlich hervortretenden Verbindungen zum Temporallappen. Möglicherweise haben sich diese erst während der Evolution entwickelt und sind beim Menschen als Teil des perisylvischen Sprachnetzwerkes an der Sprachbildung beteiligt.:1. Einleitung 1.1. Der inferiore Parietalkortex 1.2. Konnektivitätsbasierte-Parzellierung durch Diffusions-Tensor-Bildgebung 1.3. Motivation 1.4. Überblick 2. Methoden 2.1. Theoretische Grundlagen 2.1.1. Magnet-Resonanz-Bildgebung 2.1.2. Diffusionsgewichtete Magnet-Resonanz-Tomographie 2.1.3. Diffusions-Tensor-Bildgebung 2.1.4. Traktographie in der weißen Substanz 2.1.5. Parzellierungsmethoden 2.2. Datenerfassung 2.3. Datenverarbeitung 2.4. Parzellierung des IPC 2.4.1. Definition der Analyseregion 2.4.2. Bestimmung der Startvoxel 2.4.3. Probabilistische Traktographie 2.4.4. Clustering 2.4.5. Populationskarte 2.4.6. Statistische Auswertung der Parzellierungsergebnisse 2.5. Analyse der Konnektivitäten des IPC 2.5.1. Berechnung der Konnektivitäten 2.5.2. Statistische Auswertung der Konnektivitäten 3. Ergebnis 3.1. Definition der Analyseregion 3.2. Analyse der Parzellierung 3.3. Statistische Auswertung der Parzellierung 3.4. Zusammenfassung der Parzellierungsergebnisse 3.5. Populationskarte aller Probanden 3.6. Statistische Auswertung weiterer Eigenschaften 3.6.1. Schwerpunkte der Areale 3.6.2. Größe der Areale 3.7. Analyse der Konnektivitäten 3.8. Statistische Auswertung der Konnektivitäten 3.9. Vergleich der linken und rechten Hemisphäre 4. Diskussion 4.1. Zwei oder drei Regionen: Welche Parzellierung ist am geeignetsten für den IPC? 4.2. Welche Konnektivitäten charakterisieren den IPC? 4.3. Vergleich von Mensch und Makaken 4.3.1. Homologien in der Parzellierung des IPC 4.3.2. Homologien in den Konnektivitäten des IPC 4.4. Funktionelle Bedeutung der IPC Parzellierung 4.4.1. Der IPC des Makaken 4.4.2. Der IPC des Menschen 4.5. Anmerkung zu den Methoden 4.5.1. Definition der Analyseregion 4.5.2. Auflösung der Diffusions-Tensor-Bildgebung 4.5.3. Traktographie Artefakte 4.6. Zusammenfassung 5. Anhang 5.1. Glossar 5.2. Abkürzungsverzeichnis 5.3. Detaillierte Abbildung der Ergebnisse 6. Danksagung 7. Zusammenfassung der Arbeit 8. Literaturverzeichnis 9. Publikation 10. Eigenständigkeitserklärung 11. Lebenslauf / The human inferior parietal cortex convexity (IPCC) is an important association area, which integrates auditory, visual and somatosensory information. However, the structural organization of the IPCC is a controversial issue. For example, cytoarchitectonic parcellations reported in the literature range from two to seven areas. Moreover, anatomical descriptions of the human IPCC are often based on experiments in the macaque monkey. In this study we used diffusion-weighted magnetic resonance imaging (dMRI) combined with probabilistic tractography to quantify the connectivity of the human IPCC, and used this information to parcellate this cortex area. This provides a new structural map of the human IPCC, comprising three sub-areas (IPCa, IPCm, IPCp) of comparable size, in a rostro-caudal arrangement in the left and right hemisphere. Each sub-area is characterized by a connectivity fingerprint and the parcellation is similar to the subdivision reported for the macaque IPCC (rostro-caudal areas areas PF, PFG, and PG). However, the present study also reliably demonstrates new structural features in the connectivity pattern of the human IPCC, which are not known to exist in the macaque. This study quantifies inter-subject variability by providing a population representation of the sub-area arrangement, and demonstrates substantial lateralization of the connectivity patterns of IPCC.:1. Einleitung 1.1. Der inferiore Parietalkortex 1.2. Konnektivitätsbasierte-Parzellierung durch Diffusions-Tensor-Bildgebung 1.3. Motivation 1.4. Überblick 2. Methoden 2.1. Theoretische Grundlagen 2.1.1. Magnet-Resonanz-Bildgebung 2.1.2. Diffusionsgewichtete Magnet-Resonanz-Tomographie 2.1.3. Diffusions-Tensor-Bildgebung 2.1.4. Traktographie in der weißen Substanz 2.1.5. Parzellierungsmethoden 2.2. Datenerfassung 2.3. Datenverarbeitung 2.4. Parzellierung des IPC 2.4.1. Definition der Analyseregion 2.4.2. Bestimmung der Startvoxel 2.4.3. Probabilistische Traktographie 2.4.4. Clustering 2.4.5. Populationskarte 2.4.6. Statistische Auswertung der Parzellierungsergebnisse 2.5. Analyse der Konnektivitäten des IPC 2.5.1. Berechnung der Konnektivitäten 2.5.2. Statistische Auswertung der Konnektivitäten 3. Ergebnis 3.1. Definition der Analyseregion 3.2. Analyse der Parzellierung 3.3. Statistische Auswertung der Parzellierung 3.4. Zusammenfassung der Parzellierungsergebnisse 3.5. Populationskarte aller Probanden 3.6. Statistische Auswertung weiterer Eigenschaften 3.6.1. Schwerpunkte der Areale 3.6.2. Größe der Areale 3.7. Analyse der Konnektivitäten 3.8. Statistische Auswertung der Konnektivitäten 3.9. Vergleich der linken und rechten Hemisphäre 4. Diskussion 4.1. Zwei oder drei Regionen: Welche Parzellierung ist am geeignetsten für den IPC? 4.2. Welche Konnektivitäten charakterisieren den IPC? 4.3. Vergleich von Mensch und Makaken 4.3.1. Homologien in der Parzellierung des IPC 4.3.2. Homologien in den Konnektivitäten des IPC 4.4. Funktionelle Bedeutung der IPC Parzellierung 4.4.1. Der IPC des Makaken 4.4.2. Der IPC des Menschen 4.5. Anmerkung zu den Methoden 4.5.1. Definition der Analyseregion 4.5.2. Auflösung der Diffusions-Tensor-Bildgebung 4.5.3. Traktographie Artefakte 4.6. Zusammenfassung 5. Anhang 5.1. Glossar 5.2. Abkürzungsverzeichnis 5.3. Detaillierte Abbildung der Ergebnisse 6. Danksagung 7. Zusammenfassung der Arbeit 8. Literaturverzeichnis 9. Publikation 10. Eigenständigkeitserklärung 11. Lebenslauf