Frontal and parietal areas have been shown to subtend different cognitive processes such as attentional orienting, decision making and access to consciousness, with bearing on visual performance. In spite of prior evidence supporting an implication of those regions in visual cognition, their contributions to the processing of low-contrast unmasked stimuli and the characteristic spatiotemporal activity patterns underlying them remain to be fully explored and causation is lacking. We here addressed a thorough exploration of such contributions in humans, with an emphasis on the dynamics of neural activity and visual performance enhancements as probed by patterns of noninvasive manipulation of local brain oscillatory activity. To this end, we tested in healthy participants the effects of either single pulses or short bursts of active vs. sham transcranial magnetic stimulation (TMS), delivered to the frontal eye field (FEF) and the intraparietal sulcus (IPS) prior to the presentation of a lateralized low-contrast near-threshold Gabor stimulus, on the visual discrimination and conscious detection of such stimulus. Our findings contribute to better substantiate the oscillatory basis of visual cognition and its associated behaviors and to set the stage for the development of novel therapies based on noninvasive manipulation of dysfunctional brain oscillatory activity.

Heritable ossification defects of the skull vault often present as enlarged parietal foramina (PFM), bilateral oval openings of the posterior parietal bones. Isolated PFM may originate from wider defects in infancy and usually show an autosomal dominant mode of transmission, offering unexplored genetic insights into the molecular pathways of calvarial development. Haploinsufficiency of the homeobox gene MSX2, located at 5q34-q35, underlies a fraction of PFM families but the locus can be excluded in others, indicating heterogeneity. The proximal 11p deletion syndrome (P11pDS), characterised by multiple exostoses (due to haploinsufficiency of EXT2), occasional mental retardation, and PFM, pointed to a second locus at 11p11-p12. The human orthologue of the mouse paired-like homeobox gene Alx4 was identified adjacent to EXT2. ALX4 was structurally characterised and heterozygous loss-of-function mutations were detected in association with skull vault defects in twenty-nine individuals from six families, including a new case of P11pDS. The calvarial phenotype of ALX4 mutations was almost indistinguishable from the MSX2-caused defects and ranged from a midline gap to non-penetrance, nevertheless typified by classical PFM; abnormal morphology of the dural septa was also observed. The mutation spectrum and the subtle genotype-phenotype correlations suggested haploinsufficiency as the predominant pathophysiological mechanism. Interestingly, Alx4^-/+ mice manifest polydactyly but no skull defects, illustrating species-specific dosage sensitivity. Two new MSX2 mutations were also ascertained, one of which segregated with PFM and clavicular hypoplasia. The potential contribution of ALX4 and MSX2 to premature fusion of the cranial sutures - craniosynostosis - was investigated, but no unequivocally pathogenic variants were found. To elucidate the functions of Alx4 and Msx2 in skull development, spatial expression analysis was performed in mouse embryos between embryonic days E12.5-E17. Transcripts of both Alx4 and Msx2 were seen in the early calvarial skeletogenic condensations and in later stages their expression displayed a more restricted pattern, overlapping minimally with the domains of mature bone. By assessing expression in embryonic heads of reciprocal knockout mice, activation of Alx4 was found to be independent of functional Msx2 and vice versa. Analysis of compound mutants demonstrated that the two loci exert roughly additive effects on the skull vault while protein interaction assays did not indicate any physiological interaction between Alx4 and Msx2. Hence, Alx4 and Msx2 appear to regulate proliferation, differentiation, or survival of osteoblast precursors and pre-osteoblasts through parallel pathways.

Copies of author's previously published articles inserted. / Includes bibliographies. / 3 v. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The aim of this thesis is to provide a comprehensive study of the cytology, innervation and blood supply of the pineal complex in Tiliqua rugosa, a large desert dwelling skink (family: Scincidae), commonly known as the sleepy or stumpy-tailed lizard. The study complements the physiological work already reported and expands the knowledge of the epithalamic region in lizards. Various histological techniques, at both light and electron microscopic levels, are utilised. / Thesis (Ph.D.)--University of Adelaide, Dept. of Anatomy and Histology, 1997

Copies of author's previously published articles inserted. / Includes bibliographies. / 3 v. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The aim of this thesis is to provide a comprehensive study of the cytology, innervation and blood supply of the pineal complex in Tiliqua rugosa, a large desert dwelling skink (family: Scincidae), commonly known as the sleepy or stumpy-tailed lizard. The study complements the physiological work already reported and expands the knowledge of the epithalamic region in lizards. Various histological techniques, at both light and electron microscopic levels, are utilised. / Thesis (Ph.D.)--University of Adelaide, Dept. of Anatomy and Histology, 1997

Thesis (M.S.)--Medical College of Ohio, 2004. / "In partial fulfillment of the requirements for the degree of Master of Science in Biomedical Sciences." Major advisor: Michael J. Dennis. Includes abstract. Document formatted into pages: iii, 62 p. Title from title page of PDF document. Includes bibliographical references (p. 57-61).

Thesis (Ph. D. in Psychology)--Vanderbilt University, Dec. 2008. / Title from title screen. Includes bibliographical references.

Locomotion requires visuospatial attention. However, the role and cortical control of visuospatial attention during locomotion remain unclear. Four experiments were conducted in this study to examine the role and cortical control of visuospatial attention during locomotion in healthy young adults. In the first experiment, we employed a visuospatial attention task at different phases of obstacle crossing during gait. The results suggested that toe-obstacle clearance was significantly reduced for the trailing limb when distraction interfered with visuospatial attention during the approaching phase of obstacle crossing. In the second experiment, subjects performed a visual Stroop task while approaching and crossing an obstacle during gait. The results for the second experiment indicated toe-obstacle clearance was significantly increased for the leading and trailing limbs. Taken together, it was found that different visual attention tasks lead to distinct modifications on obstacle crossing behaviors. In the third and fourth experiments, anodal transcranial direct current stimulation (tDCS) was applied over the right posterior parietal cortex (PPC) to examine the aftereffects on attention function and locomotor behavior. The results suggested that the orienting attention was significantly improved after anodal tDCS. In addition, the aftereffects of anodal tDCS potentially enhanced cognitive and motor performance while interacting with a challenging obstacle-crossing task in young healthy adults, suggesting that the right PPC contributes to attending visuospatial information during locomotion. This study demonstrated that visuospatial attention is critical for planning during locomotion and the right PPC contributes to this interplay of the neural processing of visuospatial attention during locomotion. This dissertation includes previously published and unpublished co-authored material.

Le cortex pariétal postérieur (PPC) est une structure clé de l’intégration sensori-motrice qui forme, avec les structures frontales auxquelles il est connecté, des réseaux pariéto-frontaux aux fonctions spécifiques. Il est ainsi impliqué dans la planification et le contrôle des mouvements de préhension visuo-guidés mais aussi dans le contrôle de l’attention spatiale. L’atteinte fonctionnelle du membre supérieur et la négligence spatiale sont deux conséquences fréquentes et invalidantes après un accident vasculaire cérébral (AVC). Dans ces deux situations, il est démontré que la connectivité cérébrale des réseaux pariéto-frontaux est modifiée au sein de l’hémisphère lésé, mais aussi vers et au sein de l’hémisphère non-lésé. Par ailleurs, ces modifications semblent impliquées dans la genèse et/ou les mécanismes de récupération de la négligence spatiale et de la déficience motrice. Cependant, la spécificité des modifications de connectivité du PPC controlésionnel reste partiellement méconnue, en particulier si on considère les régions fonctionnelles spécialisées qui y ont été identifiées chez le sujet sain. Ces dernières incluent notamment les parties antérieure et postérieure du sillon intra-pariétal (respectivement aIPS et pIPS) et le cortex pariéto-occipital supérieur (SPOC). Les objectifs de ce travail étaient (1) d’étudier les modifications de la connectivité intra- et inter-hémisphérique de ces trois zones chez des patients post-AVC comparativement à un groupe de sujets contrôles sains, (2) de déterminer les liens de la connectivité avec la sévérité des déficiences motrices et visuo-spatiales, et enfin (3) de juger de l’effet de la modulation du PPC sur ces dernières.Dans un premier temps, nous avons mesuré, au repos, la connectivité des réseaux pariétofrontaux au sein de l’hémisphère controlésionnel en utilisant une technique de stimulation magnétique transcrânienne à impulsion double (ppTMS). La deuxième étude s’est intéressée aux aspects fonctionnels (IRM fonctionnelle de repos) et structurels (mesure de la fraction d’anisotropie sur des séquences de diffusion) de la connectivité intra- et inter-hémisphérique du PPC controlésionnel. Nous avons enfin analysé l’effet de la modulation inhibitrice du PPC controlésionnel (rTMS en mode thetaburst continu (cTBS)) sur les paramètres du mouvement de pointage avec le membre supérieur parétique.La première étude a mis en évidence une hyperexcitabilité des connexions pariéto-frontales chez les patients négligents lorsque la stimulation conditionnante concernait le SPOC, ce d’autant plus que la négligence péripersonnelle était sévère. La connectivité aIPS-M1 n’était pas différente entre sujets hémiparétique et contrôles, et le degré de déficience motrice n’était pas lié aux données de connectivité. Le travail d’imagerie a montré que la connectivité fonctionnelle et structurelle du PPC controlésionnel était altérée chez les patients, au sein de l’hémisphère controlésionnel mais aussi vers l’hémisphère lésé, de manière différente selon les sites du PPC. Les données de connectivité fonctionnelle montraient des liens avec la sévérité de la négligence spatiale mais peu avec celle de la déficience motrice. Enfin, l’inhibition du PPC controlésionnel par un protocole de cTBS pourrait améliorer l’excitabilité de M1 du coté lésé et certains paramètres spatiaux et temporels du mouvement de pointage. Les patients post-AVC présentaient donc des modifications étendues de connectivité cérébrale du PPC controlésionnel, à la fois intra- et inter-hémisphériques. Alors que des liens entre connectivité et négligence ont été mis en évidence, il n’existait que peu de relation avec la déficience motrice, probablement parce qu’elle est déterminée par un nombre important d’autres facteurs. Enfin, ce travail ouvre de nouvelles pistes d’évolution des stratégies de modulation par les techniques de stimulation cérébrale non-invasives en post-AVC. / The posterior parietal cortex (PPC) is a key structure for sensorimotor integration. It forms with the frontal areas to which it is connected the parieto-frontal networks that have specialized functions. It is involved in the planning and online control of visually-guided prehension but also in the control of spatial attention. Upper limb impairment and spatial neglect are two frequent and disabling consequences of stroke. In these two deficiencies, it has been shown that cerebral connectivity in the parieto-frontal networks is modified within the lesioned hemisphere, but also towards and within the non-lesioned hemisphere due to an imbalance in the interhemispheric influences between parietal areas. Furthermore, these modifications seem to be involved in the genesis and/or the recovery of spatial neglect and motor deficiency. However, the changes in connectivity remain partly unknown, especially if we consider the different PPC functional areas identified in healthy subjects in the PPC (anterior and posterior parts of the intraparietal sulcus (respectively aIPS and pIPS) and the superior parieto-occipital cortex (SPOC)). The aims of the present work were (1) to study the modifications of intra- and interhemispheric cerebral connectivity of these 3 PPC areas in post-stroke patients vs healthy controls, (2) determine the relationship between connectivity data and the severity of motor and visuo-spatial deficiencies, and (3) study the effect of a modulation of the PPC on these deficiencies.We first assessed the connectivity of parieto-frontal networks within the contralesional hemisphere using a paired-pulse transcranial magnetic stimulation protocol (ppTMS). In a second study, we addressed the functional (resting state fMRI) and structural (fractional anisotropy on diffusion weighted imagery) intra- and interhemispheric connectivity of the contralesional PPC. We finally study the effect of an inhibitory modulation of the contralesional PPC (continuous theta-burst stimulation (cTBS)) on reaching parameters with the paretic upper limb in stroke patients.In the first study, we demonstrated an hyperexcitability of parieto-frontal connections in neglect patients when the conditioning stimulus was applied over the SPOC, especially when peripersonal neglect was severe. Connectivity between the aIPS and M1 was not different between patients and healthy controls and the severity of motor deficiency was not associated with connectivity. The neuroimaging study revealed that functional and structural connectivity from the contralesional PPC was altered in stroke patients, within the contralesional hemisphere but also to the lesioned hemisphere, in different ways depending on the PPC site considered. Functional connectivity showed some relationships with neglect severity but almost not with motor deficiency. Finally, the inhibition of the contralesional PPC lead by a cTBS protocol may increase lesioned M1 excitability and some spatiotemporal parameters of pointing movements.In conclusion, post-stroke patients showed wide modifications of cerebral connectivity of the contralesional PPC, both within the contralesional and toward the lesioned hemisphere. Whereas we identified links between connectivity and neglect severity, relationships were poorer with motor deficiency, certainly since this last is determined by several other factors. Finally, this work puts light on new perspectives of modulation protocols using non-invasive brain stimulation in stroke patients.

Orientador: Idelmo Rangel Garcia Júnior / Banca: Osvaldo Magro Filho / Banca: Paulo Sérgio Perri de Carvalho / Banca: Daniela Ponzoni / Banca: Luís Antônio Violin Pereira / Resumo: Devido a sua micro-arquitetura de composição cortical, baixo padrão de reabsorção e a possibilidade de obtenção de grande quantidade de tecido ósseo, o osso da calota craniana se destaca como uma das principais áreas doadoras para grandes reconstruções de maxilas atróficas para posterior reabilitação com próteses implanto-suportadas. O objetivo desse estudo foi de observar e mensurar, através de avaliação histológica e histométrica, os eventos celulares que ocorrem na interface de união do enxerto onlay de osso parietal na maxila de 10 pacientes, após um período de 6 meses de incorporação. As biópsias foram realizadas no momento da instalação dos implantes osseointegráveis. A área de contato ósseo representou 78,75% e a de contato conjuntivo em fase de remodelação 21,25%. A região de união conjuntiva entre o enxerto ósseo com o leito receptor apresentou osso neoformado (41,26%), medula (36,06%), tecido osteóide (15,86%) e tecido conjuntivo (6,80%). Em todas as amostras houve uma boa incorporação do enxerto ao leito receptor, com atividade osteogênica ativa e ausência de células inflamatórias. / Abstract: Because of its micro-architecture of cortical composition, low standard of absorption and the possibility to obtain large amount of bone tissue, the calvarial bone is highlighted as a good donor area for large reconstructions of atrophic jaw for subsequent rehabilitation with implant-supported prosthesis. The aim of this study was to observe and measure through histological and histometric evaluation, the cellular events that occur at the interface of union from onlay parietal bone graft on the maxilla of 10 patients, after a period of 6 months of incorporation. The biopsies were performed at the time of installation of osseointegrated implants. The bone contact area represented 78.75% and connective contact 21.25%. The region of connective union between the bone graft to the maxillae presented new bone formation (41.26%), marrow bone (36.06%), osteoid tissue (15.86%) and connective tissue (6.80%). All samples had good graft incorporation to the receptor bed with osteogenic activity and absence of inflammatory cells. / Doutor

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Tecnologia, Departamento de Engenharia Mecânica, 2006. / Submitted by Diogo Trindade Fóis (diogo_fois@hotmail.com) on 2009-11-13T17:01:39Z No. of bitstreams: 1 2006_Daniel Vieira Soares.pdf: 2805065 bytes, checksum: 108054ac551f281ccc978083e86d7a00 (MD5) / Approved for entry into archive by Tania Milca Carvalho Malheiros(tania@bce.unb.br) on 2009-11-16T14:16:56Z (GMT) No. of bitstreams: 1 2006_Daniel Vieira Soares.pdf: 2805065 bytes, checksum: 108054ac551f281ccc978083e86d7a00 (MD5) / Made available in DSpace on 2009-11-16T14:16:56Z (GMT). No. of bitstreams: 1 2006_Daniel Vieira Soares.pdf: 2805065 bytes, checksum: 108054ac551f281ccc978083e86d7a00 (MD5) Previous issue date: 2006-11-10 / Este trabalho tem como objetivo extender o modelo de turbulência k − w proposto por Bredberg (2002), originalmente desenvolvido para escoamentos isotérmicos nos quais ocorram gradientes adversos de pressão, para simular os efeitos da variação de massa específica do fluido exclusivamente devida à presença de gradientes de temperatura - situações de alto interesse industrial - implementando-o em uma nova versão do código acadêmico TURBO-2D, de resolução temporal semi-implícita seqüencial, e discretização espacial via elementos finitos P1-IsoP2. O desenvolvimento da extensão ao modelo k − w é baseado na metodologia empregada por Munhoz da Cruz (1989) na resolução numérica de escoamentos dilatáveis, incluindo termos nas equações do modelo de turbulência referentes aos efeitos de variações térmicas do fluido, assunto pouco explorado por modelos de turbulência de baixo-Reynolds. Quatro casos teste foram escolhidos para a validação do modelo, devido aos bons resultados da literatura disponíveis: dois casos teste isotérmicos com separação da camada limite, o canal divergente de Driver e Seegmiller (1985) e a colina abrupta de Loureiro et. al (2005), e dois casos de camada limite térmica, um com convecção forçada, o caso do escoamento sobre placa plana fortemente aquecida de Ng (1981), e outro com convecção natural, de Tsuji e Nagano (1988), possibilitando uma análise mais profunda sobre a influência da dilatação térmica do fluido sobre as características turbulentas do escoamento. Os resultados obtidos foram comparados aos de simulações com o modelo k−E implementado no código TURBO-2D, extensivamente validado por Soares e Fontoura Rodrigues, (2004) e (2005), utilizando as leis de parede logarítmica clássica (velocidade) e de temperatura de Cheng e Ng (1982), de Mellor (1966), de Nakayama e Koyama (1984) e de Cruz e Silva Freire (1998) e (2002), para velocidade e temperatura, com dados experimentais e de outras simulações numéricas disponíveis na literatura. __________________________________________________________________________________________ ABSTRACT / The main goal of this work is to extend the K − W turbulence model proposed by Bredberg (2002), originally developed in order to simulate turbulent isothermal flows in which adverse pressure gradients occur, to simulate the effects of density variations exclusively due to the presence of thermal gradients - cases vastly applied in industry - implementing in a new version of the academic code TURBO-2D, with sequential semi-implicit time resolution and spatial discretization via P1/IsoP2 finite elements. The development of the K − W model extension is based in the work of Munhoz da Cruz (1989), to numerically solve thermal flows including extra terms in the turbulence quantities equations, derived from the influence of density variations on the fluid motion. Such study is rarely treated by low-Reynolds RANS turbulence models. Four test cases were selected to validate the model implementation, due to the good results available in the literature: two isothermal cases with boundary-layer separation, the divergent channel of Driver and Seegmiller (1985) and the steep hill of Loureiro et. al (2005), and two thermal boundary-layer cases, the forced convection over a strongly heated wall of Ng (1981), and the natural convection boundary layer of Tsuji and Nagano (1988), which makes possible to perform a deeper analysis of the density variation influence over the turbulent flow characteristics. The simulations results were compared to other simulations with the K − E turbulence model implemented in the code TURBO-2D, extensively tested and validated by Soares and Fontoura Rodrigues (2004) and (2005), using the classic log-law for velocity, the temperature log-law of Cheng and Ng (1982), the velocity laws of the wall of Mellor (1966) and of Nakayama and Koyama (1984), and the velocity and temperature laws of the wall of Cruz and Silva Freire (1998 and 2002, respectively), and compared to the experimental data and results from other simulations, available in the literature.