L’intégration de stimulations provenant de modalités sensorielles différentes nous offre des avantages perceptifs tels qu’une meilleure discrimination et une accélération des temps de réponse (TR) face aux évènements environnementaux. Cette thèse a investigué les effets de la position spatiale de stimulations visuelles et tactiles sur le gain de redondance (GR), qui correspond à une réduction du temps de réaction lorsque deux stimulations sont présentées simultanément plutôt qu’isolément. La première étude a comparé le GR lorsque les mêmes stimulations visuotactiles sont présentées dans une tâche de détection et une tâche de discrimination spatiale. Les stimulations étaient présentées unilatéralement dans le même hémichamp ou bilatéralement dans les hémichamps opposés. Dans la tâche de détection, les participants devaient répondre à toutes les stimulations, peu importe leur localisation. Les résultats de cette tâche démontrent que les stimulations unilatérales et bilatérales produisent un GR et une violation du modèle de course indissociables. Dans la tâche de discrimination spatiale où les participants devaient répondre seulement aux stimulations présentées dans l’hémichamp droit, les TR aux stimulations bilatérales étaient moins rapides. Nous n’avons pas observé de différence entre le GR maximal obtenu dans l’une ou l’autre des tâches de cette étude. Nous concluons que lorsque l’information spatiale n’est pas pertinente pour accomplir la tâche, les stimulations unilatérales et bilatérales sont équivalentes. La manipulation de la pertinence de l’information spatiale permet donc d’induire une altération du GR en fonction de la localisation des stimulations. Lors d’une seconde étude, nous avons investigué si la différence entre les gains comportementaux résultants de l’intégration multimodale et intramodale dépend de la configuration spatiale des stimulations. Les résultats montrent que le GR obtenu pour les conditions multimodales surpasse celui obtenu pour les stimulations intramodales. De plus, le GR des conditions multimodales n’est pas influencé par la configuration spatiale des stimulations. À l’opposé, les stimulations intramodales produisent un GR plus important iii lorsque les stimulations sont présentées bilatéralement. Nos résultats suggèrent que l’intégration multimodale et intramodale se distinguent quant au GR qu’ils produisent et quant aux conditions nécessaires à cette amélioration. La troisième étude examine le rôle du corps calleux (CC) dans l’observation du GR obtenu pour les stimulations multimodales et intramodales lorsque celles-ci sont présentées unilatéralement et bilatéralement. Quatre patients ayant une agénésie congénitale du corps calleux (AgCC) et un patient callosotomisé ont été comparés à des individus normaux dans une tâche de détection. Dans l’ensemble, les résultats suggèrent que le CC n’est pas nécessaire pour l’intégration interhémisphérique de stimulations multimodales. Sur la base d’études précédentes démontrant le rôle des collicules supérieurs (CS) dans l’intégration multimodale, nous concluons qu’en l’absence du CC, les bénéfices comportementaux résultants d’un traitement sous-cortical par les CS ne reflètent pas les règles d’intégration observées dans les études neurophysiologiques chez l’animal. / The integration of stimuli from the same or different modalities offers many benefits such as enhanced discrimination and accelerated reaction to objects. This thesis investigates the effects of stimuli’s spatial location on the redundancy gain (RG) obtained with cross-modal and within-modal stimulations. The RG is a decrease in reaction times (RT) when two or more stimuli are presented simultaneously rather than a single stimulation. The first study investigated cross-modal visuo-tactile integration in a single reaction time task and a choice reaction time task. Each unisensory stimulus was presented to either the left or right hemispace, and multisensory stimuli were presented in a unilateral (e.g. visual right/tactile right) or bilateral configuration (e.g. visual right/tactile left). The first task was a simple reaction time (SRT) paradigm where participants had to responded to all stimulations, irrespective of spatial position. Results showed that multisensory gain and coactivation were the same for spatially aligned and misaligned visuotactile stimulations. In the second task, a choice reaction time (CRT) paradigm where participants responded to rightsided stimuli only, bilateral stimuli yielded slower reaction times. No difference in multisensory gain was found between the SRT and CRT tasks for unilateral stimulations. Overall, the results suggest that when spatial information is task-irrelevant, multisensory integration of unilateral and bilateral stimuli is equivalent. However, manipulating task requirements can alter this effect. In the second study, we investigated if the behavioral enhancements resulting from within-modal and cross-modal integration depend on the spatial congruency of the redundant stimuli. Results show that the redundancy gains (RG) obtained from the cross-modal conditions were far greater than those obtained from combinations of two visual or two tactile targets. Moreover, we found that the spatial alignment of the targets did not influence the RG obtained in cross-modal conditions, whereas within-modal stimuli produced a greater RG when the targets where delivered in separate hemispaces. These results suggest that within-modal and cross-modal integration are not only distinguishable by the amount of facilitation they produce, but also by the spatial configuration under which this facilitation occurs. The third study examines the role of the corpus callosum (CC) in mediating the RG observed for unilateral and bilateral cross-modal integration. Using a simple detection task, we tested four congenitally acallosal and one callosotomized individuals. No significant difference between congenitally acallosal individuals and controls were found for unilateral within-modal conditions or for multisensory conditions. Overall, these results demonstrate that the CC in not required to integrate cross-modal information across hemispheres and that intrahemispheric processing is preserved in acallosal individuals. Based on previous studies demonstrating the role of the superior colliculus in multisensory integration, our results suggest that in the absence of the CC, the behavioral benefit resulting from subcortical processing by the superior colliculus does not reflect the neurophysiological constraints of multisensory integration.

Perceptual rivalry refers to visual phenomena that are characterised by alternations between different percepts, despite an unchanging sensory input. Two common types of perceptual rivalry are (i) reversible figures — two-dimensional stable images that when viewed, are perceived to switch between different interpretations, and (ii) binocular rivalry — the alternations in image dominance resulting from the presentation of conflicting stimuli, one to each eye. Several investigators have suggested that these rivalling phenomena are mediated by similar neural mechanisms. Such a view, however, has not only been inadequately substantiated, but has also yet to be assessed in the context of a directly testable neurophysiological model. Miller and Pettigrew have proposed a novel, high-level interhemispheric switch (IHS) explanatory model of binocular rivalry. This model conceptualises the perceptual alternations as being mediated by alternations between one hemisphere’s selected image and the other hemisphere’s selected (rival) image. To assess their hypothesis, caloric vestibular stimulation (CVS) was used. CVS is a simple, inexpensive, and non-invasive brain stimulation technique that unilaterally activates high-level attentional areas. In accordance with the IHS model, CVS was found to significantly affect predominance (the duration that one image is perceived relative to the other, within a given viewing period) during conventional binocular rivalry with horizontal/vertical gratings and with orthogonal oblique gratings. The present thesis therefore aims, through the use of CVS, to extend this IHS model of binocular rivalry to reversible-figure alternations and propose a general IHS model of perceptual rivalry. Chapter 1 provides a detailed literature review of the field within the context of comparing both perceptual rivalries. In Chapter 2, investigations are presented on two different reversible figures — the perspective-reversing Necker cube and the figure–ground reversing Rubin’s vase–faces illusion. In these experiments, CVS was found to significantly change observers’ predominance compared to their baseline predominance. These results demonstrate that interhemispheric switching also mediates the alternations of these visual phenomena, in addition to binocular rivalry, thereby extending the IHS model to one of perceptual rivalry in general. Moreover, the findings are interpreted in a cognitive neuroscience context, including a novel proposal of a forebrain framework for the IHS model. Chapter 3 presents CVS experiments that address the issue of percept–to–hemisphere selection and the reproducibility of CVS effects, following Miller’s initial work on two types of conventional binocular rivalry. In planned analyses, significant predominance changes were not found in horizontal/vertical rivalry, oblique rivalry and Necker-cube rivalry. In post-hoc analyses that accounted for study-design differences between Miller’s original experiments and the present experiment, CVS was again not shown to induce significant predominance changes in any of the rivalry types. Assessment of directional predominance changes following CVS appeared to suggest an arbitrary selection of percept–to–hemisphere in all rivalry types, although no firm conclusions could be drawn from the obtained data on this issue. Nevertheless, the experiments further extend upon Miller’s earlier work by examining the inter- and intra-individual reproducibility of CVS-induced effects on predominance. Such reproducibility was found to be low and potential reasons for this are discussed. The experiments in Chapter 4 examine a type of binocular rivalry in which dichoptic presentation of Díaz-Caneja stimuli yields rivalry among four different stable images: half-field rivalry between the images presented to the eyes, and coherence rivalry in which aspects of each eye’s presented image are perceptually regrouped into rivalling coherent images. Each of these rivalries was found to occur for about half the given viewing time. Furthermore, CVS significantly shifted the predominance of perceived coherent images (coherence rivalry) but not half-field images (eye rivalry). This finding suggests that coherence rivalry (like conventional rivalry according to previous experiments) is mediated by interhemispheric switching at a high level, while eye rivalry is mediated by intrahemispheric mechanisms, most likely at a low level. In addition, it is proposed that Díaz-Caneja stimuli induce ‘meta-rivalry’ whereby these discrete high- and low-level competitive processes themselves rival for visual consciousness. The current thesis thus presents a novel meta-rivalry model of multistable binocular rivalry. It also presents the first direct evidence that interhemispheric switching mediates reversible-figure alternations, thereby supporting a generalised IHS model of perceptual rivalry. It is argued that both models provide a parsimonious exploratory framework within which specific predictions can be made and readily tested. Finally, the findings of all experiments in the current thesis are summarised.

Perceptual rivalry refers to visual phenomena that are characterised by alternations between different percepts, despite an unchanging sensory input. Two common types of perceptual rivalry are (i) reversible figures — two-dimensional stable images that when viewed, are perceived to switch between different interpretations, and (ii) binocular rivalry — the alternations in image dominance resulting from the presentation of conflicting stimuli, one to each eye. Several investigators have suggested that these rivalling phenomena are mediated by similar neural mechanisms. Such a view, however, has not only been inadequately substantiated, but has also yet to be assessed in the context of a directly testable neurophysiological model. Miller and Pettigrew have proposed a novel, high-level interhemispheric switch (IHS) explanatory model of binocular rivalry. This model conceptualises the perceptual alternations as being mediated by alternations between one hemisphere’s selected image and the other hemisphere’s selected (rival) image. To assess their hypothesis, caloric vestibular stimulation (CVS) was used. CVS is a simple, inexpensive, and non-invasive brain stimulation technique that unilaterally activates high-level attentional areas. In accordance with the IHS model, CVS was found to significantly affect predominance (the duration that one image is perceived relative to the other, within a given viewing period) during conventional binocular rivalry with horizontal/vertical gratings and with orthogonal oblique gratings. The present thesis therefore aims, through the use of CVS, to extend this IHS model of binocular rivalry to reversible-figure alternations and propose a general IHS model of perceptual rivalry. Chapter 1 provides a detailed literature review of the field within the context of comparing both perceptual rivalries. In Chapter 2, investigations are presented on two different reversible figures — the perspective-reversing Necker cube and the figure–ground reversing Rubin’s vase–faces illusion. In these experiments, CVS was found to significantly change observers’ predominance compared to their baseline predominance. These results demonstrate that interhemispheric switching also mediates the alternations of these visual phenomena, in addition to binocular rivalry, thereby extending the IHS model to one of perceptual rivalry in general. Moreover, the findings are interpreted in a cognitive neuroscience context, including a novel proposal of a forebrain framework for the IHS model. Chapter 3 presents CVS experiments that address the issue of percept–to–hemisphere selection and the reproducibility of CVS effects, following Miller’s initial work on two types of conventional binocular rivalry. In planned analyses, significant predominance changes were not found in horizontal/vertical rivalry, oblique rivalry and Necker-cube rivalry. In post-hoc analyses that accounted for study-design differences between Miller’s original experiments and the present experiment, CVS was again not shown to induce significant predominance changes in any of the rivalry types. Assessment of directional predominance changes following CVS appeared to suggest an arbitrary selection of percept–to–hemisphere in all rivalry types, although no firm conclusions could be drawn from the obtained data on this issue. Nevertheless, the experiments further extend upon Miller’s earlier work by examining the inter- and intra-individual reproducibility of CVS-induced effects on predominance. Such reproducibility was found to be low and potential reasons for this are discussed. The experiments in Chapter 4 examine a type of binocular rivalry in which dichoptic presentation of Díaz-Caneja stimuli yields rivalry among four different stable images: half-field rivalry between the images presented to the eyes, and coherence rivalry in which aspects of each eye’s presented image are perceptually regrouped into rivalling coherent images. Each of these rivalries was found to occur for about half the given viewing time. Furthermore, CVS significantly shifted the predominance of perceived coherent images (coherence rivalry) but not half-field images (eye rivalry). This finding suggests that coherence rivalry (like conventional rivalry according to previous experiments) is mediated by interhemispheric switching at a high level, while eye rivalry is mediated by intrahemispheric mechanisms, most likely at a low level. In addition, it is proposed that Díaz-Caneja stimuli induce ‘meta-rivalry’ whereby these discrete high- and low-level competitive processes themselves rival for visual consciousness. The current thesis thus presents a novel meta-rivalry model of multistable binocular rivalry. It also presents the first direct evidence that interhemispheric switching mediates reversible-figure alternations, thereby supporting a generalised IHS model of perceptual rivalry. It is argued that both models provide a parsimonious exploratory framework within which specific predictions can be made and readily tested. Finally, the findings of all experiments in the current thesis are summarised.

A esquizofrenia é um transtorno mental de alta complexidade e até o presente momento nenhuma teoria conseguiu explicar completamente sua etiologia. Uma dessas teorias acredita que a transferência de informações entre os hemisférios de pacientes com esquizofrenia, que ocorre através do corpo caloso, comissura anterior e posterior, pode estar comprometida. Os objetivos do nosso estudo foram avaliar se existem alterações de conectividade inter-hemisférica (IH) e se essas alterações sofrem influência do gênero, em pacientes portadores de esquizofrenia quando comparados com seus parentes em primeiro grau e controles saudáveis, utilizando-se da imagem de ressonância magnética por tensor de difusão (IRMTD). Participaram do estudo 30 pacientes portadores de esquizofrenia, diagnosticados pelos critérios do Manual diagnóstico e estatístico das doenças mentais em sua quarta edição, os quais foram selecionados entre os pacientes do grupo de medicações atípicas do ambulatório de esquizofrenia e da enfermaria psiquiátrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo; 30 parentes em primeiro grau desses pacientes; e 30 voluntários saudáveis. Todos os sujeitos do estudo foram submetidos a um exame de ressonância magnética, realizado no Centro de Ciências das Imagens e Física Médica de nossa instituição, onde foram adquiridas as sequências volumétricas e difusionais utilizadas em nosso estudo. Em posse das imagens de ressonância magnética dos 90 sujeitos do estudo, realizamos o pós-processamento dessas imagens, utilizando o software BrainVoyager QX® versão 2.4, com o intuito de obtermos, por meio dos dados provenientes da IRMTD, os mapas de anisotropia fracional (AF) e difusibilidade média (DM). Com esses mapas em mãos, procedemos à análise estatística do estudo, denominada de análise de covariância voxel a voxel (VANCOVA), no cérebro todo. Nessa análise, utilizamos a idade como covariável e verificamos a influência do gênero nos resultados encontrados. Nossos resultados 6 evidenciaram que os pacientes portadores de esquizofrenia apresentaram valores de AF e DM alterados em estruturas homólogas ao corpo caloso e áreas frontais adjacentes. Assim, podemos afirmar que descobrimos perda de conectividade IH nesses mesmos pacientes. Por meio de nosso estudo, descobrimos também a influência do gênero nos valores de AF e DM encontrados e então, consequentemente, podemos dizer que a conectividade IH de pacientes portadores de esquizofrenia sofreu influência do sexo. A idade também mostrou influenciar a conectividade IH de nossos pacientes. Com o atual conceito de que alterações de AF e DM podem ser encaradas como indicativos de comprometimento da mielina, e sabendo que a mielina participa diretamente das reações neuroquímicas do sistema glutamatérgico cerebral, também podemos dizer que o sistema glutamatérgico que participa da conectividade IH desses pacientes encontrava-se comprometido. / Schizophrenia is a highly complex mental disorder and no theory to date was able to fully explain the etiology of this disorder. One of the existing theories advocates that interhemispheric communication, which occurs through the corpus callosum and the anterior and posterior commissures, might be impaired in schizophrenia. Our study was designed to investigate whether there are interhemispheric connectivity (IC) alterations in schizophrenia and whether these alterations are influenced by gender through the comparison of schizophrenia patients with their first-degree relatives and healthy controls using diffusion tensor imaging (DTI). We enrolled 30 schizophrenia patients diagnosed according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and selected from the Group of Atypical Medications of the Schizophrenia Outpatient Clinic and the psychiatric ward of the Ribeirão Preto Medical School University Hospital, 30 first-degree relatives of these patients and 30 healthy volunteers. All subjects underwent magnetic resonance imaging (MRI) scans for the acquisition of volumetric and diffusion sequences. The images were post-processed using BrainVoyager QX® version 2.4 to create fractional anisotropy (FA) and mean diffusivity (MD) maps from DTI data. The resulting data were analyzed using voxel-to- voxel analysis of covariance (VANCOVA) for the whole brain. In this analysis, we used age as a co-variable and assessed the influence of gender. Our results showed that schizophrenia patients had altered FA and MD values in structures homologous to the corpus callosum and adjacent frontal areas, suggestive of IC loss in the patients. We also found that gender influenced FA and MD values and, therefore, that IC in schizophrenia patients is influenced by gender. Age was also found to influence IC in our patients. Based on the current conception that FA and MD alterations may indicate myelin impairment and knowing that myelin participates directly in neurochemical reactions of the glutamatergic system in the brain, we can infer that the glutamatergic system, which is implicated in IC, is affected in schizophrenia and is influenced by gender.

Apprendre de nouvelles habiletés motrices est fondamental à l'expérience humaine et à l'exécution des activités quotidiennes. L'apprentissage moteur peut être défini comme un ensemble de processus associés à la pratique ou à l'expérience menant à la capacité d'exécuter une nouvelle habileté motrice. À l'origine de ces mécanismes d'apprentissage, un contrôle moteur précis et une intégration sensorimotrice adéquate sont essentiels. De plus, la capacité d'identifier une séquence dans des évènements sériels et de reproduire avec précision la série de mouvements détectés est également importante en ce qui concerne l'apprentissage des séquences motrices présentes dans de nombreux comportements humains. Si l'un de ces processus élémentaires est compromis par une pathologie, on peut s'attendre à observer des difficultés à apprendre différentes habiletés motrices. Les études qui composent la présente thèse avaient pour objectif principal de caractériser les capacités d'apprentissage moteur dans deux populations cliniques présentant une anomalie sensorielle ou motrice avec la tâche de temps de réaction sérielle (TTRS). Dans l'article 1, les conséquences de la surdité sur l'apprentissage moteur ont été étudiées. Peu d'études ont examiné les capacités motrices chez les sourds profonds et ces quelques études ont suggéré la présence de déficits en dextérité manuelle et des retards dans la production de mouvements. Avant la publication de cet article, la capacité d'apprendre des séquences motrices complexes n'avait pas été explorée dans une population adulte sourde. L'apprentissage non-spécifique et spécifique à la séquence à la TTRS a été analysé en fonction des caractéristiques individuelles liées à la perte auditive. Les résultats ont révélé des différences significatives entre les groupes dans l'apprentissage spécifique à la séquence, les sujets sourds étant moins efficaces que les contrôles à acquérir les connaissances spécifiques à la séquence. Nous avons interprété les résultats à la lumière de la plasticité intermodale et de l'hypothèse d'échafaudage auditif. Dans l'article 2, l'apprentissage moteur, le transfert intermanuel d'une habileté motrice nouvellement acquise et la modulation du débordement moteur électrophysiologique (mouvements miroirs physiologiques; MMp) ont été évalués dans une grande famille de quatre générations avec des mutations du gène Deleted in Colorectal Cancer (DCC) et des mouvements miroirs congénitaux (MMC). Les MMC sont des contractions musculaires involontaires de l'autre côté du corps survenant lors d'un mouvement unilatéral volontaire. Ils ont été associés à une mutation dans le gène DCC, entraînant des voies cortico-spinales anormales et une inhibition interhémisphérique réduite (IIH). Comparativement aux membres de la famille sans MMC et aux contrôles sains non-apparentés, les MMp des individus avec MMC ont été significativement augmentés après l'exécution de la TTRS. L'apprentissage moteur et le transfert intermanuel ne différaient pas entre les groupes. Cependant, lorsque les participants avec la mutation DCC, avec ou sans MMC, étaient spécifiquement comparés aux participants sans la mutation DCC, l'apprentissage non-spécifique d'une séquence motrice était significativement réduit chez les personnes atteintes de la mutation DCC. Ces données suggèrent qu'une augmentation de l'activité miroir physiologique chez les patients atteints de MMC est associée à une réduction de l'IIH. De plus, les diminutions d'apprentissage moteur non-spécifique chez les porteurs de la mutation DCC pourraient être liés aux altérations de l'activité cérébelleuse et de la connectivité rapportées antérieurement. En résumé, les études comprises dans la présente thèse ont approfondi nos connaissances des capacités d'apprentissage moteur dans les contextes de déficits sensoriels ou moteurs. / Learning new motor skills is essential to the human experience and to the performance of everyday activities. Motor learning can be defined as a set of processes associated with practice or experience leading to the ability to skillfully perform a new motor skill. At the root of these learning mechanisms, precise motor control and adequate sensorimotor integration are critical. Additionally, the ability to identify a sequence in serial events and accurately reproduce the series of detected movements is also important with regards to learning motor sequences that are present in many human behaviors. If any of these fundamental processes are compromised by any pathology, one can expect to observe difficulties in learning different motor skills. The studies that compose the present thesis had as a main objective to characterize the motor learning abilities in two clinical populations presenting a sensory or motor abnormality with the serial reaction time task (SRTT). In article 1, the consequences of hearing impairment on motor learning were investigated. Few studies have examined motor capacities in the profoundly deaf and these studies have suggested the presence of deficits in manual dexterity and delays in movement production. Before the publication of this article, the ability to learn complex sequential motor patterns had not been explored in a deaf adult population. Non-specific and sequence-specific learning on the SRTT were analyzed in relation to individual features related to the hearing loss. The results revealed significant differences between groups in sequence-specific learning, with deaf subjects being less efficient than controls in acquiring sequence-specific knowledge. We interpreted the results in light of cross-modal plasticity and the auditory scaffolding hypothesis. In article 2, motor learning, intermanual transfer of a newly acquired motor skill and activity-dependent modulation of electrophysiological motor overflow (physiological mirror movements; pMM) were assessed in a large, four-generational family with a Deleted in Colorectal Cancer (DCC) gene mutation and congenital mirror movements (CMM). CMM are involuntary muscle contractions in the opposite side of the body occurring during voluntary unilateral movement. They have been associated with a frameshift mutation in the DCC gene, resulting in abnormal corticospinal tracts and reduced interhemispheric inhibition (IHI). Compared with family members without CMM and unrelated healthy controls, pMM were significantly increased in CMM individuals following execution of the SRTT. Motor learning and intermanual transfer did not differ between groups. However, when participants with the DCC mutation, with or without CMM, were compared with participants without the DCC mutation, non-specific learning of a motor sequence was significantly reduced in individuals with the DCC mutation. These data suggest that increased physiological mirroring in CMM patients is associated with reduced IHI. Furthermore, impairments in non-specific motor learning in DCC mutation carriers may be related to the reported alterations in cerebellar activity and connectivity. In summary, the studies comprised in the present thesis significantly increase our knowledge of motor learning abilities in the contexts of sensory or motor deficits.

Thèse de doctorat présentée en vue de l'obtention du doctorat en psychologie - recherche intervention, option neuropsychologie clinique (Ph.D) / Les oscillations endogènes cérébrales sont associées à des fonctions cognitives spécifiques et jouent un rôle important dans la communication entre les différentes régions corticales et sous-corticales. Les rythmes alpha (8-12 Hz) et bêta (13-30 Hz) ont été observés de façon dominante dans les aires sensorimotrices, avec des moyennes de fréquence autour de 10 et 20 Hz, et jouent un rôle dans les fonctions motrices. Ces oscillations cérébrales peuvent être entrainées par une stimulation externe, notamment par la stimulation électrique transcrânienne par courant alternatif (SEtCA). Ainsi, la SEtCA de 10 et 20 Hz a un effet sur certaines mesures physiologiques comme l’excitabilité corticospinale et la puissance des oscillations via la stimulation magnétique transcrânienne (SMT) et l’électroencéphalogramme (EEG), respectivement. Toutefois, les effets post-stimulation sont variables et parfois incohérents. De plus, à ce jour, aucune étude n’a mesuré les effets physiologiques d’une stimulation bilatérale sensorimotrice tant sur l’activité locale que sur l’interaction entre les deux aires sensorimotrices. Les articles composant le présent ouvrage visent à explorer les effets post-stimulation de deux fréquences de stimulation, soit 10 Hz et 20 Hz, sur les régions sensorimotrices à l’aide d’un montage SEtCA bilatéral. Ce travail de recherche s’est effectué à travers une revue de la littérature ainsi que deux études avec des paramètres méthodologiques relativement similaires, mais avec des mesures différentes et complémentaires de SMT et d’EEG. L’article 1 sert d’assise à la pertinence de l’évaluation de la connectivité entre le cortex moteur et les différentes aires du cerveau. Cet excursus recense et décrit les différents protocoles de stimulation magnétique pairée qui ont été développés au cours des dernières années afin d’évaluer la connectivité effective entre les aires sensorimotrices du cerveau. L’article 2 montre que la SEtCA bilatérale à 10 Hz a permis de réduire l’excitabilité corticospinale via la SMT après la stimulation. La fréquence bêta de 20 Hz n’a cependant mené à aucun changement. De plus, la SEtCA n’a pas modulé de façon significative les mesures d’interaction entre les régions sensorimotrices, telles l’inhibition interhémisphérique et les mouvements miroirs physiologiques. Dans l’article 3, les résultats démontrent que la SEtCA bilatérale à 10 et 20 Hz appliquée sur les aires sensorimotrices peut modifier la puissance des oscillations alpha et bêta après la stimulation. Notons que les résultats étaient associés à une variabilité interindividuelle qui est également rapportée dans la littérature. Ces résultats peuvent avoir des implications dans la conception de protocoles visant à induire des changements persistants dans l'activité cérébrale. / Endogenous brain oscillations are associated with specific cognitive functions and are known to have an important role in regimenting communication between cortical and subcortical areas. Alpha (8-12 Hz) and beta (13-30 Hz) rhythms have been observed predominantly in sensorimotor areas, with averages around 10 and 20 Hz, and are believed to play a role in motor functions. These cerebral oscillations can be entrained by external stimulation, in particular by transcranial alternating current stimulation (tACS). Thus, tACS has shown an impact on certain physiological measures such as corticospinal excitability and the power of oscillations via transcranial magnetic stimulation (TMS) and electroencephalogram (EEG), respectively. However, the after-effects are variable and incoherent. In addition, to date no study has measured the physiological effects of a bilateral sensorimotor stimulation montage on both local activity and the interaction between the two sensorimotor areas. Thus, the studies included in the present thesis aim to explore the after-effects of two stimulation frequencies, 10 Hz and 20 Hz, on sensorimotor regions using a bilateral montage. This research was carried out through a review of the literature as well as two methodological studies with relatively similar parameters, but using different and complementary measures of TMS and EEG. Article 1 provides a basis for the relevance of assessing the connectivity between the motor cortex and different areas of the brain. This excursus identifies and describes the different paired magnetic stimulation protocols that have been developed in recent years to assess the effective connectivity between sensorimotor areas of the brain. Study 2 shows that bilateral 10 Hz tACS significantly reduced corticospinal excitability via TMS after stimulation. However, the 20 Hz frequency did not lead to any change. In addition, tACS did not significantly modulate measures of interaction between sensorimotor regions, such as interhemispheric inhibition and physiological mirror movements. In study 3, the results failed to demonstrate reliably that bilateral tACS at 10 and 20 Hz administered over sensorimotor areas could modulate offline alpha and beta oscillations power at the stimulation site. Note that the results were associated with inter-individual variability, which is also reported in the literature. These findings may have implications for the design and implementation of future protocols aiming to induce sustained changes in brain activity.

En plus de la triade de symptômes caractérisant l’autisme, ce trouble neurodévelopmental est associé à des particularités perceptives et motrices et, au niveau cérébral, par une connectivité atypique entre les différentes régions du cerveau. Au niveau anatomique, un des résultats les plus communs est la réduction du corps calleux. Toutefois, des effets directs de cette altération anatomique sur l’intégrité et l’efficacité du transfert interhémisphérique restent à être démontrés. Pour la présente thèse, trois différentes études investiguent différents aspects du traitement de l’information visuomotrice : le transfert interhémisphérique entre les régions bilatérales motrices et visuelles, la vitesse de traitement perceptif, et les habiletés motrices visuellement guidées. Dans la première étude, le paradigme visuomoteur de Poffenberger a été utilisé pour mesurer le temps de transfert interhémisphérique (TTIH). L’imagerie par résonnance magnétique fonctionnelle (IRMf) et structurale ainsi que l’imagerie de diffusion ont aussi été utilisées pour étudier les réseaux cérébraux impliqués dans la tâche de Poffenberger. Les autistes ont été comparés à un groupe d’individus à développement typique. La deuxième étude avait pour but d’investiguer la vitesse de traitement perceptif en autisme. Dans la troisième étude, deux tâches motrices (Purdue et Annett) ont été utilisées pour examiner la nature et l’importance des déficits moteurs. La tâche de Purdue inclut deux conditions bimanuelles utilisées comme indice additionnel d’intégration interhémisphérique. Dans les études 2 et 3, le groupe d’autistes a aussi été comparé à un groupe d’individus Asperger afin de voir si, et comment, les deux sous-groupes peuvent être distingués en ce qui concerne le traitement visuel et les déficits moteurs. Aucune différence entre les groupes n’a été observée en termes de TTIH. Les résultats de l’étude IRMf révèlent des différences d’activations corticales en lien avec la tâche de Poffenberger. Dans les groupes d’autistes et de typiques, l’efficacité de la communication interhémisphérique était associée à différentes portions du corps calleux (frontales/motrices chez les typiques, postérieures/visuelles chez les autistes). De façon globale, les résultats de cette étude démontrent un patron atypique de transfert interhémisphérique de l’information visuomotrice en autisme, reflétant un rôle plus important des mécanismes visuels dans le comportement sensorimoteur possiblement en lien avec une réorganisation cérébrale. Les résultats des études comportementales 2 et 3 indiquent que les autistes excellent dans la tâche mesurant la vitesse de traitement perceptif alors que les Asperger accomplissent la tâche à des niveaux similaires à ceux des typiques. La nature des déficits moteurs diffère aussi entre les deux sous-groupes; la dextérité et la coordination bimanuelle est affectée chez les individus Asperger mais pas chez les autistes, qui eux sont plus atteints au niveau de la rapidité unimanuelle. Les sous-groupes d’autistes et de syndrome d’Asperger sont caractérisés par des profils cognitifs différents dont les particularités perceptives et motrices font partie intégrante. / In addition to the triad of symptoms characterizing autism, this neurodevelopmental condition is characterized by visual and motor atypicalities and, at the cerebral level, by atypical connectivity between the different brain areas. Anatomically, one of the most replicated finding is a reduction of the corpus callosum. However, evidence of a direct effect of the corpus callosum reductions on integrity and efficiency of interhemispheric transfer is lacking. Three different studies were designed to investigate different aspect of visuo-motor processing: interhemispheric transfer between bilateral motor and visual brain areas, perceptual processing speed, visually guided motor performance. In the first study, the visuo-motor Poffenberger paradigm was used to measure interhemispheric transfer time (IHTT). Structural and functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were also used to study the brain networks involved in the Poffenberger task. Autistics were compared to typically developing individuals. The second study investigates whether perceptual processing speed (Inspection Time task) is atypical in autism. In the third study, two visually-guided motor tasks (the Purdue pegboard and Annett peg moving task) were used to verify the nature and magnitude of motor deficits. The Purdue task includes two bimanual conditions used as additional measures of interhemispheric communication integrity. Moreover, in studies 2 and 3, behavioral differences between autistic and Asperger individuals were investigated in order to see if and how the two subgroups can be distinguished in terms of perceptual processing and motor deficits. No group difference was observed in terms of IHTT. The fMRI results reveal a different pattern of cortical activations associated to the Poffenberger task. In the autism and typical groups, the efficiency of interhemispheric communication was associated with different portions of the corpus callosum (frontal/premotor in typicals, posterior/visual in autistics). These results demonstrate an atypical pattern of interhemispheric visuo-motor information transfer, possibly reflecting a more prominent role of visual mechanisms guiding sensorimotor behavior in autism, related to cerebral reorganizations. Results of the behavioral studies indicate that autistics have an excellent visual processing speed while Asperger individuals performed like typicals. Motor impairments also differed between the two subgroups; dexterity and bimanual coordination was impaired in Asperger individuals but not in autistics, who presented more difficulties in unimanual conditions. Autism and Asperger subgroups are characterized by different cognitive profiles in which visual processing and motor deficits are important factors.

Spike timing-dependent plasticity (STDP) has been suggested as one of the key mechanism underlying learning and memory. Due to its importance, timing-dependent plasticity studies have been approached in the living human brain by means of non-invasive brain stimulation (NIBS) protocols such as paired associative stimulation (PAS). However, contrary to STDP studies at a cellular level, functional plasticity induction in the human brain implies the interaction among target cortical networks and investigates plasticity mechanisms at a systems level. This thesis comprises of two independent studies that aim at understanding the importance of considering broad cortical networks when predicting the outcome of timing-dependent associative plasticity induction in the human brain. In the first study we developed a new protocol (ipsilateral PAS (ipsiPAS)) that required timing- and regional-specific information transfer across hemispheres for the induction of timing-dependent plasticity within M1 (see chapter 3). In the second study, we tested the influence of individual brain structure, as measured with voxel-based cortical thickness, on a standard PAS protocol (see chapter 4). In summary, we observed that the near-synchronous associativity taking place within M1 is not the only determinant influencing the outcome of PAS protocols. Rather, the online interaction of the cortical networks integrating information during a PAS intervention determines the outcome of the pairing of inputs in M1.

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L’exécution d’un mouvement purement unilatéral nécessite le recrutement d’un vaste réseau de régions corticales et sous-corticales, qu’il est possible de regrouper sous le terme de réseau de transformation non-miroir. Ce réseau doit contrer la tendance naturelle du cerveau à exécuter des mouvements de manière bilatérale et synchronisée, en miroir. Malgré l’efficacité de ce réseau, une activité miroir subtile est observée au niveau de la main qui doit demeurer inactive lors de mouvements unilatéraux chez l'humain en santé. Ce débordement moteur doit être inhibé grâce aux interactions interhémisphériques transitant par le corps calleux (CC), la plus grande commissure du cerveau servant de pont entre les hémisphères. Ainsi, la commande motrice peut être acheminée efficacement du cortex moteur primaire (M1) controlatéral à la main devant exécuter une l’action par l’entremise de la voie corticospianle (VCS). En plus du CC, le cortex prémoteur (CPM) joue un rôle important dans ce réseau puisque son interférence via la stimulation magnétique transcrânienne (SMT) entraîne une augmentation de l’activité miroir dans la main devant normalement demeurer inactive lors d’un mouvement unilatéral. Ainsi, toute modification dans ce réseau ou dans les processus interhémisphériques peut provoquer l’augmentation des mouvements miroirs (MM). À ce jour, aucune étude n’a tenté de moduler ces interactions pour réduire la présence de MM. Ainsi, les études cliniques et méthodologiques qui composent la présente thèse comportent deux objectifs principaux : (1) déterminer si la stimulation électrique transcrânienne à courant direct (SÉTcd) permet l'étude du réseau de transformation non-miroir, et si cette technique est en mesure de diminuer l’intensité des MM chez des individus en santé; (2) caractériser l'anatomie et le fonctionnement du cerveau dans deux populations d’individus porteurs de mutations génétiques affectant le développement de structures impliquées dans la latéralisation du mouvement, le CC et la VCS. L’article 1 décrit les assisses théoriques de la présente thèse grâce à une revue de la littérature portant sur les interactions interhémisphériques dans le mouvement unilatéral. L’article 2 suggère que la SÉTcd est un outil efficace dans l'étude du réseau de transformation non-miroir puisque le protocole de stimulation bilatérale a permis d’augmenter la présence et l’intensité des MM physiologiques (MMp) chez des individus en santé. Cependant, il n’a pas été possible de moduler à la baisse les MMp malgré différents protocoles de stimulation. Dans l’article 3, l'étude d’individus nés sans CC a mis en lumière une augmentation de l’épaisseur corticale au niveau des aires somatosensorielles (S1) et visuelles (V1) primaires, de même qu’au niveau de la représentation de la main dans M1. Ces différences demeurent toutefois légères considérant l’importance du CC. L’article 4 a démontré que les individus porteurs d’une mutation sur le gène DCC présentent un phénotype similaire à celui de porteurs d'une mutation sur le gène RAD51. Ces mutations affectent la migration de la VCS au niveau des pyramides. La VCS projette ainsi aux deux mains, causant des mouvements miroirs congénitaux (MMC). Cette pathologie est également accompagnée d’anomalies neurophysiologiques, telle qu’une inhibition interhémisphérique (IIH) réduite. En somme, les études composant cette thèse ont permis d’approfondir notre connaissance de certaines structures responsables de la latéralisation adéquate du mouvement, tout en décrivant de nouvelles méthodes pour en étudier le fonctionnement. / The execution of purely unilateral hand movements requires the recruitment of vast cortical and subcortical brain areas known as the non-mirroring network. This network counteracts the natural tendency of the brain, which tends to execute movements in a bilateral and synchronized manner. Despite the efficacy of the non-mirroring network in restricting motor output to contralateral limbs, subtle mirroring can be observed in the inactive hand of healthy individuals when performing a unilateral task. This motor overflow needs to be inhibited through interhemispheric projections coursing through the corpus callosum (CC), the biggest white matter tract of the brain. This mechanism makes it possible for motor commands originating from the primary motor cortex (M1) to reach the contralateral hand performing an action via the corticospinal tract (CST). It has been suggested that the premotor cortex (PMC) is an important component of the non-mirroring network since its interference with transcranial magnetic stimulation (TMS) enhances mirror activity in the inactive, mirror hand when a unilateral hand movement is performed. Indeed, modulation of parts of the non-mirroring network and interhemispheric projections can result in enhanced mirror movements (MM). It is not known whether specific interventions can decrease MM. The clinical and methodological studies that compose the present thesis have two main objectives: (1) Determine whether transcranial direct-current stimulation (tDCS) can be used to assess non-mirroring network function and reduce MM intensity in healthy individuals; (2) Characterize brain function and anatomy in two clinical populations presenting specific genetic mutations that affect the development of structures involved in the lateralization of movement (the CC and CST). Article 1 provides a theoretical basis for the present essay through a review of the literature pertaining to interhemispheric interactions in the production of unilateral movements. Article 2 shows that tDCS can be used to study the non-mirroring network since a bilateral stimulation protocol significantly increased the intensity of physiological MM (pMM) in healthy individuals. However, despite different stimulation protocols, it was not possible to reduce pMM. In article 3, anatomical MRIs performed in individuals born without a CC revealed increases in cortical thickness in primary somatosensory (S1) and visual (V1) cortex, as well as in the hand representation of M1. Taken together, however, the data suggest that anatomical differences between acallosal patients and healthy participants are relatively subtle considering the size and function of the CC. Article 4 showed that individuals presenting a mutation on the DCC gene display a phenotype similar to that of individuals presenting a mutation on the RAD51 gene. DCC mutations affect the crossing of the CST at the pyramidal level, resulting in a CST that projects to both hands simultaneously, causing congenital mirror movements (CMM). This pathological condition is accompanied by neurophysiological anomalies that include reduced interhemispheric inhibition (IHI). In summary, the studies comprised in the present thesis significantly increase our knowledge of the specific brain structures that enable the proper lateralization of movements. It also describes novel methods that can be used to investigate the non-mirroring network.