Evidence suggests that high-level feedback plays an important role in visual perception by shaping the response in lower cortical levels (Sillito et al. 2006, Angelucci and Bullier 2003, Bullier 2001, Harrison et al. 2007). A notable example of this is reflected by the retinotopic activation of V1 and V2 neurons in response to illusory contours, such as Kanizsa figures, which has been reported in numerous studies (Maertens et al. 2008, Seghier and Vuilleumier 2006, Halgren et al. 2003, Lee 2003, Lee and Nguyen 2001). The illusory contour activity emerges first in lateral occipital cortex (LOC), then in V2 and finally in V1, strongly suggesting that the response is driven by feedback connections. Generative models and Bayesian belief propagation have been suggested to provide a theoretical framework that can account for feedback connectivity, explain psychophysical and physiological results, and map well onto the hierarchical distributed cortical connectivity (Friston and Kiebel 2009, Dayan et al. 1995, Knill and Richards 1996, Geisler and Kersten 2002, Yuille and Kersten 2006, Deneve 2008a, George and Hawkins 2009, Lee and Mumford 2003, Rao 2006, Litvak and Ullman 2009, Steimer et al. 2009). The present study explores the role of feedback in object perception, taking as a starting point the HMAX model, a biologically inspired hierarchical model of object recognition (Riesenhuber and Poggio 1999, Serre et al. 2007b), and extending it to include feedback connectivity. A Bayesian network that captures the structure and properties of the HMAX model is developed, replacing the classical deterministic view with a probabilistic interpretation. The proposed model approximates the selectivity and invariance operations of the HMAX model using the belief propagation algorithm. Hence, the model not only achieves successful feedforward recognition invariant to position and size, but is also able to reproduce modulatory effects of higher-level feedback, such as illusory contour completion, attention and mental imagery. Overall, the model provides a biophysiologically plausible interpretation, based on state-of-theart probabilistic approaches and supported by current experimental evidence, of the interaction between top-down global feedback and bottom-up local evidence in the context of hierarchical object perception.

No description available.

Fetal alcohol spectrum disorder is the leading cause of mental retardation in the western world. It is associated with learning and sensory deficits. Some of these deficits are a result of faulty neuronal plasticity. Previously our lab has used ferrets to demonstrate that alcohol exposure during the third trimester of human gestation results in impaired ocular dominance plasticity (ODP). Here we have transferred this model to mice. Mice, treated with 5 mg/kg of ethanol on postnatal days 5, 7 and 9, exhibit a lack of ODP plasticity after 10 days of monocular deprivation (MD) during the critical period of visual cortex plasticity, as seen by optical imaging of intrinsic signals. This deficit in ODP was rescued by treatment with a phosphodiesterase type 1 inhibitor (PDEi1), vinpocetine. This rescue did not occur after treatment with a PDEi4 (rolipram) or a PDEi5 (vardenafil) inhibitor alone. Interestingly when these drugs were given concurrently, ODP was rescued. To further explore the effect of early alcohol exposure on ODP, we used Visually Evoked Potentials to examine the potentiation and depression components of ODP. Ethanol exposed and saline control animals were MD for 5, 7 or 10 days during the critical period of the visual cortex. Here we saw that although saline animals exhibited a normal depression of contralateral eye responses and a potentiation of ipsilateral eye responses, ethanol animals exhibited only a depression of contralateral eye responses. Additional ethanol animals were then MD for 3 days to test for changes in the on-set of contralateral eye depression. Yet, these animals exhibited normal contralateral eye response changes. In conclusion early ethanol exposure disrupts only the potentiation of the ipsilateral eye inputs, while leaving the contralateral eye response depression in tact. This model provides a new approach to studying ODP after early alcohol exposure, opening the door for studies using transgenic animals to further elucidate the mechanisms behind these alcohol induced deficits.

O potencial visual evocado (PVE) é um sinal elétrico de baixa intensidade originado no córtex visual em resposta a uma estimulação visual periódica. O potencial visual evocado de varredura é um procedimento de PVE modificado para medir acuidade visual de grades em pacientes pré-verbais e não-verbais. Este biopotencial está imerso em uma grande quantidade de ruído eletroencefalográfico e artefato relacionado ao movimento. A relação sinal-ruído tem um papel dominante na determinação de erros sistemáticos e estatísticos. O propósito deste estudo é apresentar um método baseado na transformada wavelet para filtrar e extrair o potencial evocado visual de varredura. Grades de luminância de onda senoidal moduladas em 6 Hertz foram usadas como estímulo para se determinar os limiares de acuidade. A amplitude e a fase da 2ª. harmônica (12 Hertz) do padrão de resposta foram analisadas usando-se a transformada rápida de Fourier após a filtragem por wavelet. O método da transformada wavelet discreta foi usado para decompor o PVE em coeficientes wavelet, determinando-se quais destes representavam uma atividade significativa. Em um passo seguinte somente os coeficientes relevantes foram considerados, zerando-se os demais e reconstruindo-se, assim, o sinal PVE. Isto resultou na filtragem das demais freqüências que foram consideradas ruído. Simulações numéricas e análises com dados de PVE humanos mostraram que este método forneceu maior relação sinal-ruído quando comparado com o método clássico dos mínimos quadrados recursivo (RLS) e ainda uma análise de fase mais apropriada / Visually evoked potential (VEP) is a very small electrical signal originated in the visual cortex in response to periodic visual stimulation. Sweep-VEP is a modified VEP procedure used to measure grating visual acuity in non-verbal and preverbal patients. This biopotential is buried in a large amount of electroencephalographic noise and movement related artifact. The signal-to-noise ratio (SNR) plays a dominant role in determining both systematic and statistic errors. The purpose of this study is to present a method based on wavelet transform technique for filtering and extracting steady-state sweep-VEP. Counter-phase sine-wave luminance gratings modulated at 6 Hertz were used as stimuli to determine sweep-VEP grating acuity thresholds. The amplitude and phase of the second-harmonic (12 Hertz) pattern reversal response were analyzed using the fast Fourier transform after the wavelet filtering. The wavelet transform method was used to decompose the VEP signal into wavelet coefficients by a discrete wavelet analysis to determine which coefficients yield significant activity at the corresponding frequency. In a subsequent step only significant coefficients were considered and the remaining was set to zero allowing a reconstruction of the VEP signal. This procedure resulted in filtering out other frequencies that were considered noise. Numerical simulations and analyses of human VEP data showed that this method has provided higher SNR when compared with the classical recursive least squares (RLS) method. An additional advantage was a more appropriate phase analysis showing more realistic second-harmonic amplitude value during phase brake

O córtex visual desempenha papel essencial no processamento de informação visual. A primeira região do córtex a receber estímulos visuais é o córtex visual primário (V1) e pode ser subdividida anatomicamente em seis camadas, onde cada camada contém diferentes tipos e números de neurônios. Entender a forma como a informação é processada entre as diferentes camadas envolve o estudo da dinâmica dos padrões coletivos de atividade neural quando a rede é exposta a diferentes situações e como esses padrões relacionam-se com a organização estrutural e funcional da rede cortical. Essa dinâmica é afetada por mecanismos de plasticidade sináptica, de maneira que modelos computacionais que busquem capturá-la devem incluir tais mecanismos. Neste trabalho foi construído um modelo computacional de uma rede neural com 4000 neurônios baseada em informações sobre a estrutura local das conexões em V1 disponíveis na literatura neurobiológica. O modelo contém características estruturais consideradas fundamentais tais como: proporção entre neurônios inibitórios e excitatórios e probabilidades de conexões entre neurônios de diferentes populações em diferentes camadas. Os neurônios foram descritos pelo modelo de Izhikevich, reproduzindo três classes eletrofisiológicas mais abundantes no córtex: neurônios de disparo regular, para os excitatórios; neurônios de disparo rápido e baixo limiar de disparo, para os inibitórios. A regra de plasticidade sináptica utilizada foi do tipo plasticidade dependente dos tempos dos disparos neuronais (STDP em inglês), que pode fortalecer ou enfraquecer a força da conexão entre dois neurônios dependendo dos instantes dos seus disparos. Foram utilizadas versões diferentes dessa regra de plasticidade para sinapses excitatórias (STDPe) e inibitórias (STDPi). Foram simuladas situações com e sem plasticidade e alterando o tipo de neurônio inibitório presente na rede. Para cada uma, três protocolos de estimulação da rede foram utilizados: 1 estimulação por trens de disparos poissonianos aplicada a neurônios da camada 4 (simulando entradas talâmicas) e aplicada aleatoriamente aos neurônios da rede como ruído de fundo; 2 - pulsos aplicados a neurônios da camada 4 simulando estimulação visual com barras luminosas com diferentes orientações angulares; 3 - similar ao segundo protocolo, porém, estimulando a rede com dois pulsos alternantes de diferentes ângulos. Os parâmetros do modelo foram ajustados para que a atividade neural tivesse baixas frequências de disparos coerentes com dados experimentais. Esse ajuste foi mais fácil nos casos em que os neurônios inibitórios eram do tipo FS e havia STDPi. Os resultados mostraram que, de modo geral, os neurônios do tipo LTS contribuem para a formação de atividade síncrona na rede e este efeito foi amplificado com a STDPe. Para todos os protocolos, a STDPe aumentou a frequência média de disparos da rede e, para o segundo experimento, apesar da seletividade à orientação dos neurônios não ter sido alterada significativamente, houve mudanças visíveis na formação de assembleias funcionais. A competição da atividade dos neurônios no experimento 3 na presença da STDPe foi intensificada fortalecendo respostas funcionais de neurônios que não respondiam a ambos os estímulos. O balanço entre os dois tipos de regra de STDP manteve o equilíbrio entre as forças das conexões excitatórias e inibitórias. / The visual cortex plays essential role in the processing of visual information. The first region of the cortex that receives visual stimuli is the primary visual cortex (V1) or striate cortex, which can be anatomically divided into six layers, where each layer has different types and numbers of neurons. Understanding the way in which information is processed by the different layers involves the study of the dynamics of collective patterns of neural activity when the network is exposed to different situations, and how these patterns are related with the structural and functional organization of cortical network. This dynamics is affected by mechanisms of synaptic plasticity, so computational models which seek to capture it should include them. In this project a computational model of a neural network was built with 4000 neurons based on information on local connectivity in V1 from the neurobiological literature. The model has realistic structural characteristics such as the proportion between inhibitory and excitatory neurons and the connection probabilities among neurons from different populations of different layers. Neurons were described by the Izhikevich model, reproducing the three most abundant electrophysiological classes in cortex: RS, for the excitatory ones; FS and LTS, for the inhibitory neurons. The synaptic plasticity rule used was spike-timing dependent plasticity (STDP), whereby the synaptic strength between two neurons can increase or decrease depending on the timing of their spikes. Were used different versions of this plasticity rule to synapses made by excitatory neurons (STDPe) and by inhibitory neurons (STDPi). Different scenarios were simulated with and without plasticity and changing the type of inhibitory neuron present in the network. For each configuration, three network stimulation protocols were used: 1 - stimulation applied to layer 4 neurons (simulating thalamic inputs) modeled by Poissonian spike trains and background noise applied to all network neurons modeled in a similar manner; 2 - pulses applied to layer 4 neurons simulating visual stimulation with light bars at different angular directions; 3 - similar to the second protocol, however, stimulating the network with two alternating pulses of different angles. The parameters of the model were adjusted so that neural activity had low spike frequencies consistent with experimental data. This adjustment was easier in cases where inhibitory neurons were of FS type and had STDPi. The results showed that, in general, LTS neurons contribute to the formation of synchronous activity in the network and this effect was amplified with the insertion of STDPe. For all protocols, the STDPe increased the average firing frequency of the network. For Experiment 2, although the orientation selectivity of the neurons did not change significantly, there have been noticeable changes in the formation of functional assemblies. The competition of the activity of neurons in Experiment 3 in the presence of STDPe strengthened functional responses of neurons that do not respond to both stimuli. The balance between the two types of STDP rule maintained the equilibrium between excitatory and inhibitory connections.

Esta pesquisa pretendia estabelecer um mapa espaço temporal das respostas de vernier no córtex visual humano. O uso do potencial visual provocado de varredura (PVPv) proporciona medidas eficientes e sensíveis dos limiares de vernier com os quais se pode começar a examinar as respostas corticais de vernier no âmbito dos parâmetros espaço temporais. As respostas de vernier foram avaliadas em relação à hipótese de que os sinais retinianos provenientes das células ganglionares da via magnocelular e não da via parvocelular compõem o input neural para córtex que é utilizado para gerar as respostas de vernier (tarefas de localização de alta precisão Lee et a., 1990; Lee et al., 1995). Métodos: As respostas de vernier no córtex humano foram medidas por meio do potencial visual provocado de varredura (PVPv). Quebras de vernier foram introduzidas em grades de ondas quadradas de produzindo colunas verticais intercaladas de barras estáticas e móveis. Medidas binoculares da acuidade vernier foram feitas em grades de alto contraste (64%) em função de 3 frequências temporais (3, 6 e 15 Hz) e 2 frequências espaciais (1 e 8 c/g). Medidas utilizando grades de baixo contraste foram feitas em função de 3 frequências temporais (3, 6 e 10Hz) e 3 frequências espaciais (1, 2 e 8c/g) em ambos os protocolos (alto e baixo contraste) as medidas foram feitas utilizando o PVPv. Foi utilizado o sistema POWER DIVA que utiliza a metodologia dos mínimos quadrados recursivos para extrair a amplitude e fase da resposta nos harmônicos selecionados da frequência do estímulo. Foram analisados o primeiro (1F1) e o segundo (2F1) harmônicos neste estudo. Com base em estudos anteriores, assume-se que o primeiro componente harmônico refere-se às respostas ao estímulo de vernier, e o segundo às respostas ao movimento relativo dos elementos do estímulo. Esta hipótese foi testada por meio da utilização de protocolos controle para ambos os arranjos de estímulos (alto e baixo contraste) em que foram utilizados os mesmos parâmetros, porém com deslocamentos entre as barras completamente simétricos (elementos da grade jamais se alinhavam). O sistema POWER DIVA calcula para cada segundo de janela de análise (bin) a amplitude local. A amplitude média do ruído nos 10 bins de análise é utilizada para calcular a razão sinal ruído para cada bin. Apenas sinais com razão sinal ruído maior que 3 foram considerados resposta. A média vetorial de 8 tentativas para cada condição de estímulo foi utilizada para determinar os limiares.Resultados: Os dados são consistentes com dados psicofísicos anteriores, especialmente os dados de Bradley & Skottun (1987) que demonstraram decréscimo significativo nos limiares de vernier com o aumento da frequência espacial. Os limiares eletrofisiológicos de vernier obtidos com o presente trabalho mostraram-se paralelos aos dados psicofísicos em função das frequências espaciais em ambos os protocolos. Os limiares no 1F1 também demonstraram redução significativa com o aumento da frequência temporal em altas frequências espaciais / The research was directed at establishing a spatiotemporal map of human cortical vernier responses. The use of swept-parameter, steady state visual evoked potential (sweep VEP, or sVEP) provides efficient and sensitive measurement of vernier thresholds with which to begin to examine cortical vernier responses over the spatio-temporal parameter space. The vernier responses were evaluated in relation to the hypothesis that the magnocellular (M) but not parvocellular (P) ganglion cell retinal output forms the neural input to cortex that is used to derive vernier (high precision localization task - Lee et al., 1990; Lee et al., 1995). Methods: Human cortical vernier responses were measured using the sweep visual evoked potential (sVEP). Vernier offsets are introduced into a square wave grating producing interleaved vertical columns of moving and static bars. Binocular measurements of the vernier acuity were made using high contrast (64%) gratings as a function of 3 temporal frequencies (TF = 3, 6 and 15 Hz) and 2 spatial frequencies (SF = 1 and 8 c/g). Measurements were also made at low contrast (8%) as a function of 3 temporal frequencies (3, 6 and 10Hz) and 3 spatial frequencies (1, 2 and 8c/g) using the sVEP. The POWER DIVA system uses the recursive least squares to extract the response amplitude and phase at selected harmonics of the stimulus frequency. We analyzed the evoked potentials at the first (1F1 fundamental) and second (2F1) harmonics. Based on prior research, we take the 1F1 component to be the specific response to the periodic vernier onset/offset, while the 2F1 component reflects local relative motion responses. We checked this assumption by also measuring sVEPs using a motion control protocol in which equivalent displacement amplitudes were presented in and identical stimulus array, but with the displacements being completely symmetrical alternations between two states of misalignment (grating elements were never aligned). To ensure that the amplitude data used for the regression and extrapolation to threshold is really a response to stimulus instead of noise, POWER DIVA calculates, for each 1-second analysis window (time bin), a local noise amplitude. The mean noise amplitude across 10 analysis bins is used to calculate the signal to noise ratio for each time bin. Only signals with a signal to noise ratio > 3 were considered as a response. The vector average of at least 8 trials was used to determine thresholds. Results: The data are consistent with some comparable prior psychophysical data, especially data from Bradley & Skottun (1987) who showed significant decrease in the vernier thresholds with the increase of spatial frequency. Our cortical (sVEP) vernier thresholds paralleled the psychophysical data as a function of SF in both protocols. The 1F1 (vernier) thresholds also exhibited a significant decrease with increase of temporal frequency at high SF

The mammalian visual system develops to perform many complex tasks that allow us to perceive the natural world. These tasks rely on a dense network of synaptic connections transporting visual information both to and within visual cortex (V1). The laminar organization and functional properties of visual cortical neurons are largely conserved across mammals, and the mouse has been adopted as a model organism to study the development of this cortical circuit. Neurons in each cortical layer must find the correct synaptic partners for the optimal receipt, transfer, and processing of information. The molecular cues guiding the development of these connections, however, are largely unknown. In this thesis, I identify and then examine the role of molecular factors important for synapse formation in layer 2/3 (L2/3) of visual cortex. L2/3 neurons are highly interconnected and fire selectively to a refined set of visual stimuli. The developmental refinement of these visual preferences has been shown to occur in the week following eye opening, corresponding with a period of intense synapse formation and dynamic gene expression in mouse V1. In Chapters II–IV, I use the TU-tagging technique to identify molecular factors enriched L2/3 neurons before and after eye opening and identify several candidate genes with potential functions in synapse formation. In Chapter V, I examine the function of cell adhesion molecules nectin-1 and nectin-3, identified here as enriched in L2/3 visual cortex at eye opening, and previously shown to interact across synaptic junctions. I focus mainly on the effect of nectin-3 (having post-synaptic localization in hippocampus) on post-synaptic dendritic spine densities in developing L2/3 cortical neurons. I show that nectin-3 knockdown further increases spine densities after eye opening, while overexpressing a full length or truncated nectin-3 protein reduces spine densities. I conclude that nectin-3 may have a role in synapse formation following eye opening, and propose a mechanism describing the effects observed. Here, I describe a unique approach for understanding how cell-type specific connections are formed in visual cortex, beginning with the spatiotemporal examination gene expression and followed by the spatiotemporal manipulation of a single gene. This dissertation includes previously published co-authored material.

Our ability to learn relies on the potential of neuronal networks to change through experience. The primary visual cortex (V1) has become a popular system for studying how experience shapes cortical neuronal networks. Experience-dependent plasticity in V1 has been extensively studied in young animals, revealing that experiences in early postnatal life substantially shape neuronal activity in the developing cortex. In contrast, less is known about how experiences modify the representation of visual stimuli in the adult brain. In addition, adult experience-dependent plasticity remains largely unexplored in neurodevelopmental disorders. To address this issue, we established a two-photon calcium imaging set-up, suitable for chronic imaging of neuronal activity in awake-behaving mice. We implemented protocols for the reliable expression of genetically encoded calcium indicators (GCaMP6), for the implantation of a chronic cranial window and for the analysis of chronic calcium imaging data. This approach enables us to monitor the activity of hundreds of neurons across days, and up to 4-5 weeks. We used this technique to determine whether the daily exposure to high-contrast gratings would induce experience-dependent changes in V1 neuronal activity. We monitored the activity of putative excitatory neurons and of three non-overlapping populations of inhibitory interneurons in layer 2/3 of adult mice freely running on a cylindrical treadmill. We compared the results obtained from mice that were exposed daily to either a high-contrast grating or to a grey screen and characterized their neuronal response properties. Our results did not reveal significant differences in neuronal properties between these two groups, suggesting a lack of stimulus-specific plasticity in our experimental conditions. However, we did observe and characterize, in both groups, a wide range of activity changes in individual cells over time. We finally applied the same method to investigate impairments in experience-dependent plasticity in a mouse model of intellectual disability (ID), caused by synaptic GTPase-activating protein (SynGAP) haploinsufficiency. SynGAP haploinsufficiency is a common de novo genetic cause of non-syndromic ID and is considered a Type1 risk for autism spectrum disorders. While the impact of Syngap gene mutations has been thoroughly studied at the molecular and cellular levels, neuronal network deficits in vivo remain largely unexplored. In this study, we compared in vivo neuronal activity before and after monocular deprivation in adult mutant mice and littermate controls. These results revealed differences in baseline network activity between both experimental groups. These impairments in cortical neuronal network activity may underlie sensory and cognitive deficits in patients with Syngap gene mutations.

L'imagerie par résonance magnétique fonctionnelle (IRMf) permet d'examiner l'organisation fonctionnelle du cerveau humain de manière non-invasive et chez les sujets sains. L'implémentation de cette technique chez des primates non-humains représente un progrès important dans les neurosciences des systèmes. D'une part, l'IRMf singe permet la réduction et le raffinement des protocoles invasifs impliquant des primates non humains, en révélant les régions d'intérêts dans lesquelles les approches focales invasives, électrophysiologiques ou anatomiques, devraient être menées. D'un autre côté, les connaissances acquises avec ces approches invasives peuvent être transposées plus aisément à l'homme, une fois que les homologies et différences interspécifiques ont été identifiées au travers de protocoles d'IRMf menées en parallèle chez les primates humains et non- humains. La 1ère partie de cette thèse présente les approches conventionnelles d'étude des fonctions cérébrales. Nous montrons que des études invasives chez l'animal demeurent nécessaires pour comprendre les mécanismes neuronaux qui sous-tendent nos fonctions cognitives, malgré le progrès des techniques d'investigation chez l'homme. Suit une revue sur l'évolution des techniques d'IRMf singe et certaines de ses réalisations majeures comme pont dressé entre les études non-invasives menées chez l'homme et les études invasives réalisées chez l'animal, notamment en ce qui concerne notre compréhension des mécanismes neuronaux permettant la saisie manuelle d'objets sous contrôle visuel. Purement méthodologique, la fin de cette 1ère partie décrit l'animalerie et la plate-forme d'IRM à Toulouse et expose les jalons de l'implémentation de l'IRMf chez le singe macaque vigile. La 2ème partie de la thèse présente les 4 études que nous avons menées en IRMf singe. La 1ère étude modélise la réponse hémodynamique chez le singe, un outil indispensable à l'analyses de données d'IRMf, acquises dans les études suivantes. La 2ème étude traite de l'organisation visuotopique du cortex visuel dorsal des primates, et y décrit un nouvel assemblage d'aires visuotopiques chez 2 animaux, grâce à l'usage de nouvelles techniques de stimulation visuelle et d'analyse de champ récepteurs. Ces résultats apportent un point de vue neuf sur l'organisation fonctionnelle de la voie visuelle dorsale et ouvrent de nombreuses perspectives pour les comparaisons entre espèces. La 3ème étude cartographie le réseau d'aires corticales impliqué dans le traitement du flux optique chez les primates non humains et le compare à celui décrit récemment chez l'homme. Grâce à la réplication d'une étude réalisée chez l'homme, nous avons confirmé chez 3 macaques l'implication de zones précédemment identifiées par des enregistrements électrophysiologiques. Nos résultats révèlent de nouvelles zones corticales impliquées dans le traitement du flux optique, dessinant l'image d'un réseau cortical partageant de nombreuses similitudes, mais ayant également des différences frappantes, avec celui documenté dans le cerveau humain. En résumé, l'ambition de cette thèse est double : (1) fournir des recommandations pour la mise en place de techniques IRMf chez le singe, tirées de notre propre expérience et (2) exposer les résultats d'un ensemble d'études que nous avons menées avec cette approche, traitant de l'organisation visuotopique du cortex visuel dorsal et de son implication dans le traitement du mouvement visuel. En plus d'apporter une perspective nouvelle sur l'organisation fonctionnelle du cortex visuel chez les primates non humains, ces études illustrent la contribution de l'IRMf singe comme pont entre études électrophysiologiques chez les primates non humains et études d'imagerie fonctionnelle chez l'homme. / Functional magnetic resonance imaging (fMRI) allows addressing the functional organization of the human brain with minimal invasiveness and in healthy individuals. The implementation of that technique in non-human primates represents an important achievement in systems neuroscience. On the one hand, monkey fMRI contributes to the reduction and refinement of invasive approaches in non-human primates, by revealing the regions of interest in which focal electrophysiological and/or anatomical investigations should be carried out. On the other hand, the knowledge acquired with such invasive approaches can be more safely transposed to humans, once inter-species homologies and differences have been identified through the use of similar fMRI protocols in human and non-human primates. The first part of this thesis reviews the most common approaches that have been used to study brain functions, either in humans or in non-human primates. It is shown that despite progresses in the human approaches, invasive studies in monkeys remain necessary for understanding the neuronal mechanisms underlying cognitive functions. Then follows a description of the evolution of the monkey fMRI techniques and some of its achievements in bridging the gap between non-invasive human studies and invasive animal studies, notably for deciphering the neural mechanisms supporting visually-guided grasping. The end of this first part is purely methodological. It undertakes the description of the monkey facilities and the MR platform in Toulouse, and details the necessary milestones for conducting fMRI research in macaque monkeys. The second part of the thesis presents the 4 studies we have conducted with monkey fMRI. The first study is a preparatory experiment for characterizing the monkey hemodynamic response function, which is a prerequisite for proper analysis of subsequent monkey fMRI data. The second study addresses the visuotopic organization of the primate dorsal visual cortex with a novel technique of wide-field (80°) phase-encoded visual stimulation, coupled with a state of the art surface-based analysis of population receptive fields. The results obtained in 2 animals uncover a new cluster of visuotopic areas in the posterior parietal cortex of the macaque monkey, bringing a fresh view to the functional organization of this piece of cortex and opening a promising avenue for inter-species comparisons. The third study unveils the cortical network involved in optic flow processing in non-human primates and it compares this network to that recently described in humans. To that end, we replicated in macaque monkeys an experiment previously conducted in human subjects with optic flow stimuli that are either consistent or inconsistent with egomotion. Besides confirming the involvement of areas previously identified through electrophysiological recordings, our results reveal new cortical areas involved in the processing of optic flow, drawing the picture of a network sharing many similarities, but also striking differences, with that documented in the human brain. In summary, the ambition of this thesis is two-fold: (1) providing guidelines for setting-up monkey fMRI techniques, drawn from our own experience and (2) exposing a set of studies we have conducted with this approach, dealing with the visuotopic organization of the dorsal visual cortex and its involvement in the processing of visual motion. Besides bringing a fresh view to the functional organization of the dorsal visual pathway in non-human primates, these studies illustrate how monkey fMRI bridges the gap between electrophysiological studies in non-human primates and functional imaging studies in humans.

O potencial visual evocado (PVE) é um sinal elétrico de baixa intensidade originado no córtex visual em resposta a uma estimulação visual periódica. O potencial visual evocado de varredura é um procedimento de PVE modificado para medir acuidade visual de grades em pacientes pré-verbais e não-verbais. Este biopotencial está imerso em uma grande quantidade de ruído eletroencefalográfico e artefato relacionado ao movimento. A relação sinal-ruído tem um papel dominante na determinação de erros sistemáticos e estatísticos. O propósito deste estudo é apresentar um método baseado na transformada wavelet para filtrar e extrair o potencial evocado visual de varredura. Grades de luminância de onda senoidal moduladas em 6 Hertz foram usadas como estímulo para se determinar os limiares de acuidade. A amplitude e a fase da 2ª. harmônica (12 Hertz) do padrão de resposta foram analisadas usando-se a transformada rápida de Fourier após a filtragem por wavelet. O método da transformada wavelet discreta foi usado para decompor o PVE em coeficientes wavelet, determinando-se quais destes representavam uma atividade significativa. Em um passo seguinte somente os coeficientes relevantes foram considerados, zerando-se os demais e reconstruindo-se, assim, o sinal PVE. Isto resultou na filtragem das demais freqüências que foram consideradas ruído. Simulações numéricas e análises com dados de PVE humanos mostraram que este método forneceu maior relação sinal-ruído quando comparado com o método clássico dos mínimos quadrados recursivo (RLS) e ainda uma análise de fase mais apropriada / Visually evoked potential (VEP) is a very small electrical signal originated in the visual cortex in response to periodic visual stimulation. Sweep-VEP is a modified VEP procedure used to measure grating visual acuity in non-verbal and preverbal patients. This biopotential is buried in a large amount of electroencephalographic noise and movement related artifact. The signal-to-noise ratio (SNR) plays a dominant role in determining both systematic and statistic errors. The purpose of this study is to present a method based on wavelet transform technique for filtering and extracting steady-state sweep-VEP. Counter-phase sine-wave luminance gratings modulated at 6 Hertz were used as stimuli to determine sweep-VEP grating acuity thresholds. The amplitude and phase of the second-harmonic (12 Hertz) pattern reversal response were analyzed using the fast Fourier transform after the wavelet filtering. The wavelet transform method was used to decompose the VEP signal into wavelet coefficients by a discrete wavelet analysis to determine which coefficients yield significant activity at the corresponding frequency. In a subsequent step only significant coefficients were considered and the remaining was set to zero allowing a reconstruction of the VEP signal. This procedure resulted in filtering out other frequencies that were considered noise. Numerical simulations and analyses of human VEP data showed that this method has provided higher SNR when compared with the classical recursive least squares (RLS) method. An additional advantage was a more appropriate phase analysis showing more realistic second-harmonic amplitude value during phase brake