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L'étude de la conscience est un sujet d'investigation fascinant avec un large champ d'applications et d'implications. Les processus de la conscience peuvent être divisés en deux composantes indépendantes quoiqu'intimement liées : l'état conscient et le contenu conscient. L'état conscient correspond aux processus de variation de la vigilance, tandis que le contenu conscient fait référence aux expériences sensorielles perçues et manipulées dans un espace conscient. Bien que la conscience soit un élément essentiel de la cognition humaine, qui conditionne ce que les gens vivent et peuvent se remémorer, la légitimité et le bien-fondé de l'analyse scientifique et rigoureuse des corrélats neuronaux de la conscience soulèvent encore des débats houleux. Dans la première partie de cette thèse, j'utilise un célèbre paradigme de conflit sensorimoteur pour identifier des corrélats neuronaux de l'émergence de la conscience. Les travaux initiés par Torstein Nielsen (Nielsen 1963) ont démontré que la majorité des traitements sensorimoteurs s'effectuent sans nécessiter une analyse consciente. L'émergence de phénomènes conscients apparaissant à partir d'un seuil subjectif de conflit sensori-moteur appelé point d'égalité subjective. A partir d'enregistrements électroencéphalographiques, effectués chez une population de sujets adultes, il est possible d'identifier des sources d'activités corticales indépendantes des intensités des stimulations sensorielles expérimentées et spécifiques de l'émergence d'une sensation perçue consciemment. Ainsi, j'ai pu démontrer que le précuneus était une structure centrale dans les processus qui transforment un conflit sensorimoteur en une expérience consciente. J'ai également étudié ce phénomène d'un point de vue développemental en examinant les performances comportementales et des enregistrements EEG recueillies chez l'enfant. Bien que le moment de la correction du mouvement et la qualité du tracé de la trajectoire étaient similaires aux données mesurées chez les sujets adultes, le seuil de conscience motrice s'est montré plus élevé et l'activité du cortex pariétal n'a pas été retrouvée. En revanche, l'aire motrice supplémentaire a été identiée comme un corrélat important de l'émergence d'une sensation consciente d'un conflit sensorimoteur chez l'enfant. Dans une seconde partie, mes travaux ont été consacrés à l'hypothèse audacieuse qu'une stimulation électrique du nerf vague pourrait modifier l'état de conscience d'un patient se trouvant dans un état végétatif depuis 15 ans. Nous rapportons les effets bénéfiques observés après cette thérapeutique expérimentale au niveau comportemental, clinique et neurophysiologiques. Les enregistrements EEG et les méthodes de mesure de connectivité fonctionnelle m'ont permis d'observer chez ce patient une augmentation du partage d'informations corticales particulièrement importante dans les régions pariétales. L'effet de la stimulation a été également confirmé par d'autres méthodes. L'imagerie métabolique a montré une augmentation généralisée de l'activité corticale et sous-corticale et les évaluations cliniques par la CRS-R ont montré une amélioration de l'état de conscience corrélée aux observations électroencéphalographiques. Ces changements induits par la stimulation du nerf vague sont prometteurs car les modifications cérébrales observées sont caractéristiques de l'amélioration des états de conscience chez les patients gravement cérébrolésés. L'ensemble de ces résultats suggèrent que le lobe pariétal constitue à la fois un corrélat important de l'état de conscience et du contenu conscient, faisant de cette région une composante essentielle de l'émergence de la conscience. De plus, nos résultats préliminaires suggèrent que la conscience peut être, au moins partiellement, restaurée. Cette découverte ouvre de toutes nouvelles perspectives pour le futur des recherches en neurosciences où, l'hypothèse d'une modulation de la plasticité cérébrale avait été oubliée / The study of consciousness is a fascinating topic of investigation with a wide field of applications and implications. Consciousness processes can be divided into two orthogonal though intimately linked components: the conscious state, that is the state of vigilance or arousal, and the conscious content which refers to the external inputs perceived and manipulated in a conscious space. Although consciousness represents the most important human dimension where people's personal events are continuously experienced and remembered, it is somewhat surprising that its underlying neural processes still sparks lot of debates. In the first part of this PhD thesis, I took advantage from a well-known sensorimotor conflict paradigm, the Nielsen task, to investigate the neural correlates of the emergence of consciousness. Starting from the principle that much of motor processing occurs outside of awareness, I adapted the Nielsen paradigm to neurally investigate how the perception of a motor conflict in healthy subjects smoothly shifted along the unaware/aware state (i.e. point of subjective equality). Using EEG recordings, I then identify the brain sources which I consider the neural fingerprint of awareness. I found that the precuneus was critical for bringing the sensorimotor conflict into awareness. I also investigated this issue from a developmental perspective by examining the performance of healthy children. Although the timing of movement correction and the quality of movement trajectory in children was similar to adult subjects, motor awareness was shifted towards higher perception thresholds while parietal cortex activity was not found. Rather, children's response to conflict awareness was linked to SMA. After having addressed the topic of awareness in this first part, I will focus more on the second component, wakefulness. Usually these two components evolve together, however there are some pathological states in which they can be dissociated. It is the case for vegetative state patients who experience a state of wakefulness without awareness. In the second part of the thesis, I investigated the challenging hypothesis of a potential return to a conscious state, in a patient lying in a vegetative state for 15 years, after vagus nerve stimulation (VNS). We report beneficial effects of VNS including improved behavioural responsiveness and reinforced brain connectivity patterns as key signs of increased consciousness. The results showed an increase of information sharing a measure of functional connectivity particularly prominent across centro-posterior regions. Converging findings, coming from different methods, showed that VNS promoted the spread of cortical signals and metabolism which we found correlated with behavioural improvement as measured with the CRS-R scale. The VNS-induced changes are promising since they seem to follow an already known connectivity pattern characterizing state of consciousness improvements. Taken together, these findings indicate that the parietal lobe constitutes the neural correlate of both state and content-specific consciousness and suggest that this region is a "hot zone" for its emergence. Moreover, our first findings in a vegetative state patient also suggest that consciousness can be potentially repaired, thus opening the way to a new avenue of research in a domain where brain plasticity was underestimated

Afin d’effectuer un mouvement de la main, le système nerveux doit mettre en commun des informations issues de plusieurs sens : c’est l’intégration multisensorielle. Le cortex pariétal postérieur est une interface sensorimotrice qui est impliquée dans le processus d’intégration multisensorielle. Si cette région est endommagée, les patients présentent un trouble visuomoteur dénommé ataxie optique qui se caractérise par une difficulté à réaliser des mouvements visuellement guidés de la main. À ce jour, les mécanismes qui sous-tendent l’intégration multisensorielle pour l’action ne sont pas encore totalement connus. Le premier axe de ma thèse consiste à définir, chez les sujets sains, comment les informations visuelles et somatosensorielles sont intégrées pendant la planification d’un mouvement de pointage. Le deuxième axe s’intéresse aux troubles sensorimoteurs associés à l’ataxie optique qui permettent une meilleure compréhension des fonctions du cortex pariétal postérieur dans la planification motrice et le contrôle du mouvement. / To execute reach movements, the central nervous system needs to combine informationfrom different sensory modalities, a process knows as multisensory integration. Theposterior parietal cortex is a sensorimotor interface implicated in multisensory integrationprocesses. Patients with a damage to this region exhibit a visuomotor deficit called opticataxia. Patients with optic ataxia present difficulties in performing hand visually-guidedmovements. To date, the mechanisms underlying multisensory integration are still notfully understood. The first aime of my thesis is to determine how visual and somatosensoryinformation are integrated in healthy participants, during the planning of pointingmovements. I will then focus on the sensorimotor deficits observed in optic ataxia whichenable a better understanding of the functions of the posterior parietal cortex in motorplanning and online control.

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Made available in DSpace on 2016-03-15T19:40:03Z (GMT). No. of bitstreams: 1 Ana Clara Portela Hara.pdf: 1185473 bytes, checksum: 98af56b10b63f07c120ba7122a299358 (MD5) Previous issue date: 2013-08-06 / The human visual attention and cognitive processes involved still arouse interest in investigations and have gaps. Perform a reading task or look for a parking spot are common actions of our day-to-day life that require the recruitment of our visual attentional system. The present study aimed to investigate the influence of Transcranial Direct Current Stimulation (tDCS) over Posterior Parietal Cortex (PPC) in the performance of visuospatial attention tasks, such as Bisection of Lines test and Visual Search test in young healthy volunteers. In order to analyze differences and similarities between different types of stimulation (anodic and cathodic simulation) as well as the pseudoneglect phenomenon, participated 21 young adults of which 90.47% female, 95.23% with incomplete higher education; right handed and with a mean age of 22.66 ± 3.04 (mean ± standard deviation). The results showed that participants were faster in the second assessment compared to baseline for both tasks. In addition, volunteers were faster in the Line Bisection test when the large lines was at left. Another important finding of the study was the longer fixation time in the left visual hemifield when faced with larger lines on the left in the Line Bisection Task. Furthermore, similar results when there are target to the left or right was find in the Visual Search test. Was also observe an increase in fixation time on right hemifield after cathodal stimulation in the Visual Search test compared to baseline. Therefore, these findings come against pseudoneglect phenomenon, as well as inhibition of the right posterior parietal cortex with the Transcranial Direct Current Stimulation can have induced a decrease in this phenomenon. The present study brought important contributions to the understanding of pseudoneglect phenomenon, and showed that tDCS can be an important tool for research and future intervention possibilities. / A atenção visual humana e os processos cognitivos nela envolvidos ainda despertam interesse em investigações e apresentam lacunas. Realizar uma tarefa de leitura ou procurar uma vaga no estacionamentosão ações comuns do nosso dia-a-dia que exigem o recrutamento do nosso sistema atencional visual. O presente trabalhoteve como objetivo investigar a influência da Estimulação Transcraniana por Corrente Contínua em Córtex Parietal Posterior (CPP) no desempenho de tarefas de atenção visuoespacial, tais como Bissecção de Linhas e Busca Visual, em jovens saudáveis; a fim de analisar diferenças e semelhanças entre os diferentes tipos de estimulação (anódica, catódica e placebo), bem como o fenômeno pseudonegligência. Participaram do estudo 21 adultos jovens, sendo 90,47% do sexo feminino; 95,23% com ensino superior incompleto; destros e com idade média de 22,66 ±3,04 (média±desvio-padrão). Os resultados mostraram que na Tarefa de Bissecção de Linhas os participantes foram mais rápidos na segunda avaliação em comparação com a linha de base. Além disso, os voluntários foram mais rápidos quando diante das linhas Maiores à Esquerda. Outro achado importante do estudo foi o maior tempo de fixação visual em hemicampo esquerdo quando diante de linhas maiores à esquerda. Quanto aos resultados encontrados na Tarefa de Busca Visual, os participantes apresentaram maior número de acertos quando os alvos apareceram em hemicampo esquerdo. Além disso, independentemente da localização do alvo, seja em hemicampo esquerdo ou hemicampo direito, o tempo de fixação foi maior à esquerda. Outro achado significativo foi o aumento no tempo de fixação em hemicampo direito após estimulação catódica na tarefa Busca Visual em comparação com a linha de base. Tais achados apontam para o fenômeno pseudonegligência, assim como a inibição do CPP direito por meio da ETCC pode ter induzido a diminuição de tal fenômeno. O presente estudo trouxe importantes contribuições no entendimento da pseudonegligência, assim como demonstrou ser uma importante ferramenta de investigação sobre o fenômeno e com possibilidades futuras de intervenção.

Recollection, the process by which an item provokes the retrieval of associated information stored in the brain, is a key component of recognition memory. It is explored in this thesis through the use of a paradigm designed to allow the neural correlates of amount recalled to be identified through parametric fMRI analysis. A series of experiments were carried out during the development and optimisation of this paradigm in order to ensure that the various demands of this analysis were met. Subsequently this paradigm was applied during an fMRI experiment which provided data from both the encoding and retrieval stages of recollection.Whilst the development work was chiefly concerned with producing a suitable task design for the parametric fMRI analysis, these experiments provided some interesting results in their own right. The task design, which required participants to associate multiple item types within a story context, showed that there are significant differences in the frequency with which different stimuli are recollected. Participants were found to be particularly poor at recollecting faces whilst words were also shown to be recollected less frequently than either object or animal picture stimuli. A possible explanation for these differences may be related to the picture superiority effect although eye-tracking data collected from these experiments demonstrates large differences in viewing behaviour between different target stimulus types which is not correlated with later recall success. The amount of time participants spend engaging with the highly contextual scene item does predict later recall success.The fMRI analysis (Chapter 5) carried out during the encoding and retrieval stages of recollection found a variety of regions exhibiting a positive linear relationship with recollection at both these stages. This result provides support for the cortical reinstatement hypothesis of recollection despite the fact that the hippocampus only showed parametric modulation of activity during retrieval. It is proposed that parahippocampal activity during encoding and retrieval supports the recollection of contextual information whilst the same pattern of activity in parietal regions related to recollection may reflect the reinstatement of the global image of the story created during the encoding task.

Le but de cette thèse est d’investiguer l’organisation fonctionnelle du contrôle cognitif au sein du cortex préfrontal latéral dans la schizophrénie. Chez le sujet sain, Koechlin et coll. (Science, 2003) ont montré que le cortex préfrontal latéral était structuré en une cascade de processus de contrôle allant des régions antérieures aux régions postérieures, intégrant respectivement les informations épisodiques (événements antérieurs) et contextuelles (le contexte immédiat de l’action) au choix de l’action en réponse à un stimulus externe. En utilisant le paradigme expérimental de Koechlin et coll. en IRM fonctionnelle, nous avons investigué l’architecture fonctionnelle du contrôle cognitif au sein du cortex latéral préfrontal chez 15 patients schizophrènes et 14 sujets contrôles appariés. Dans une première étude, nous avons trouvé que les patients schizophrènes présentaient un déficit sélectif du contrôle contextuel associé à une hypoactivation des régions postérieures préfrontales, expliquant la désorganisation du discours et du comportement observés chez ces patients. Par ailleurs, les patients schizophrènes hyperactivaient leurs régions rostrales du cortex préfrontal latéral pendant le contrôle des informations de nature épisodique, ce que nous avons interprété comme une tentative de compensation infructueuse des dysfonctions du contrôle contextuel. Dans une seconde étude, nous avons montré que les patients schizophrènes présentaient également une perturbation du traitement top-down des informations de nature épisodique, liée à une dysconnectivité des régions rostrales vers les régions caudales du cortex préfrontal latéral. / The goal of this thesis is to investigate the functional organization of cognitive control within the LPFC in schizophrenia. We used a model postulating that cognitive control is functionally organized within the lateral prefrontal cortex (LPFC) as a cascade of representations ranging from premotor to anterior LPFC regions according to stimuli, the present perceptual context, and the temporal episode in which stimuli occur. Using functional magnetic resonance imaging, we investigated the functional architecture of cognitive control within the LPFC in 15 schizophrenic patients and 14 matched healthy controls. In a first study, we found that immediate contextual signals insufficiently bias the caudal LPFC activity required to select the appropriate behavioral representation. This specific deficit could thus alter the internal consistency of schizophrenic patients’ behavior. To compensate for this weakening of contextual influence, schizophrenic patients may inefficiently use temporal episodic information through higher activation in rostral LPFC regions. In a second study, we showed that schizophrenic patients inappropriately process episodic information flow along a rostro-caudal axis within the LPFC. This top-down episodic control dysfunction could lead to a disruption of episodic memory that could account for the patients’ difficulties in organizing their behavior across time. All the results argue in favor of both dysfunctional specialization and integration within the LPFC in schizophrenia.

no / To investigate the underlying nature of the effects of transcranial magnetic stimulation (TMS) on speed perception, we applied repetitive TMS (rTMS) to human V5/MT+ following adaptation to either fast- (20 deg/s) or slow (4 deg/s)-moving grating stimuli. The adapting stimuli induced changes in the perceived speed of a standard reference stimulus moving at 10 deg/s. In the absence of rTMS, adaptation to the slower stimulus led to an increase in perceived speed of the reference, whilst adaptation to the faster stimulus produced a reduction in perceived speed. These induced changes in speed perception can be modelled by a ratio-taking operation of the outputs of two temporally tuned mechanisms that decay exponentially over time. When rTMS was applied to V5/MT+ following adaptation, the perceived speed of the reference stimulus was reduced, irrespective of whether adaptation had been to the faster- or slower-moving stimulus. The fact that rTMS after adaptation always reduces perceived speed, independent of which temporal mechanism has undergone adaptation, suggests that rTMS does not selectively facilitate activity of adapted neurons but instead leads to suppression of neural function. The results highlight the fact that potentially different effects are generated by TMS on adapted neuronal populations depending upon whether or not they are responding to visual stimuli. / BBSRC

Made available in DSpace on 2016-03-15T19:40:41Z (GMT). No. of bitstreams: 1 Rita dos Santos de Carvalho Picinini.pdf: 1897105 bytes, checksum: 40db215aab8bca0781df1d15de88b3d3 (MD5) Previous issue date: 2009-01-27 / Fundo Mackenzie de Pesquisa / Different mathematical skills have been investigated over time and, with the advance of neuroimaging techniques, such as PET (Positron Emission Tomography) and fMRI (functional Magnetic Resonance), central components of arithmetical processing have been identified in the parietal and the pre-frontal cortices. Besides the advances of the neuroimaging techniques, other techniques such as non-invasive brain modulation have also been studied such as the transcranial magnetic stimulation (TMS) and the transcranial direct current stimulation (TDCS) in the involvement of cognitive functions in the area of calculation. This study aimed at investigating the impact of anodal TDCS applied over the left dorsolateral pre-frontal cortex (LDLPFC), right parietal cortex (RPC), left parietal cortex (LPC) while the subject was performing multiplication operations. Fifteen healthy volunteers, students of psychology, aged between 18 and 30 years old, have held subtests of the WAIS III and the multiplication task. The results showed that the anodal TDCS over the RPC improved the performance of men regarding the number of rightness. The influence of TDCS on volunteers who had worse performance took place not on complex tasks, but simple arithmetical ones. Besides, the influence of TDCS on volunteers who had better performance was in complex tasks, not simple ones. These results show that the effects of the TDCS on a certain function depend on the baseline values of each volunteer. The other stimulation conditions over the LDLPFC and LPC did not show any significant results. The TDCS can bring a beneficial effect in calculation tasks, depending on the intensity, polarity, time and location of stimulation, resulting in the increased or diminished cortex excitability. / Diferentes habilidades matemáticas vêm sendo investigadas ao longo dos tempos e, com o avanço das técnicas de neuroimagem, como PET (Tomografia por emissão de Pósitrons) e fMRI (ressonância magnética funcional) componentes centrais no processamento aritmético vêm sendo identificados em córtex parietal e pré-frontal. Além do avanço das técnicas de neuroimagem, outras técnicas como de modulação cerebral não-invasiva também vêm sendo estudadas, como Estimulação Magnética Transcraniana (EMT) e a Estimulação Transcraniana por Corrente Contínua (ETCC) no envolvimento das funções cognitivas com a área de cálculo. Este estudo teve como objetivo investigar o impacto da ETCC anódica quando aplicada no Córtex Pré-Frontal Dorsolateral (CPFDLE), Córtex Parietal Direito (CPD), Córtex Parietal Esquerdo (CPE) no desempenho em operações de multiplicação. Quinze voluntários saudáveis, estudantes de psicologia, com faixa etária entre 18 e 30 anos, realizaram subtestes do WAIS III e a tarefa de multiplicação. Os resultados desse estudo mostraram que a ETCC anódica aplicada no CPD melhorou o desempenho dos homens em relação ao número de acertos. A influência da ETCC em participantes com pior desempenho em Aritmética se deu em tarefa simples de multiplicação, mas não complexa, ao passo que a influência da ETCC em participantes com melhor desempenho em Aritmética se deu em tarefa complexa de multiplicação, mas não em simples. Tais resultados sinalizam que os efeitos da estimulação em uma determinada função dependem dos valores de linha de base de cada participante As outras condições de estimulações, CPFDLE e CPE não resultaram em efeitos significativos. A ETCC pode produzir um efeito benéfico em tarefas de cálculo, dependendo da intensidade, polaridade, tempo e localização da estimulação, podendo resultar em aumento ou diminuição na excitabilidade do córtex.

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