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The present thesis examines the effects of transcranial direct current stimulation and forelimb rehabilitation on motor recovery after stroke in rats. Post-stroke motor outcomes were quantified using an innovative battery of behavioural tests and high resolution, in vivo electrophysiology was employed to examine coherence of neural activity between hemispheres. It was shown that rats that received brain stimulation concurrently with forelimb rehabilitation displayed functional recovery, whereas rats that received rehabilitation alone partially regained motor function, but the improvements were not due to restitution of original movement patterns. Results from electrophysiological recordings showed that rats that received brain stimulation and rehabilitation regained pre-stroke levels of interhemispheric coherence, but rats that received rehabilitation alone did not. The present thesis suggests that transcranial direct current stimulation may be a viable adjunct therapy to increase the efficacy of physical rehabilitation with regard to post-stroke motor outcomes. Interhemishperic coherence between homotopic neuronal populations may represent a biomarker of genuine motor recovery after stroke. / ix, 75 leaves : col. ill. ; 29 cm

For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic ‘fashions’, and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients (www.IGSLI.org) and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health,lithium researchers from around the world have formed the Consortium on Lithium Genetics (www.ConLiGen.org) to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its efforts. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Made available in DSpace on 2014-08-20T13:49:09Z (GMT). No. of bitstreams: 1 Shadia Mussa Yussef.pdf: 1169456 bytes, checksum: 6d61b045046eb663e9959d6a88f3447e (MD5) Previous issue date: 2012-03-26 / Recent studies on motor learning have shown the effectiveness of the practice that incorporates some form of self-learning and performance of a motor task (JANELLE, 1997; CHIVIACOWSKY & WULF, 2002). In the present study aims to investigate whether the benefits generated by the typical practice self-control subjects are also found in individuals with motor impairment after stroke.The subjects, 26 adults of both sexes, with injury after stroke for at least 6 months, will be divided into two groups. A group of often self-controlled feedback (self) and a yoked group, which will receive feedback in a controlled externally, similar to a group subject to a self-controlled. The task of balance with demand, is to ride a pedal for some distance in the shortest possible time. All attempts to start with the foot contralateral to hemiparesis. A timer will be used to measure the movement time (MT), ie, the time needed to walk with the pedal to the starting line finish line. The research will consist of an acquisition phase, where participants will conduct 20 trials of practice, and a retention phase, 24 hours after the acquisition phase, in which four attempts to hold practice.The subjects of the group self, will be told they can use to support the upper limb support in attempts in which they find necessary.Yoked to subjects in the group, will be informed that in some trials should use the support and not others. The retention phase is performed without support in both groups. Before testing, subjects should be informed that the task at top speed / Estudos recentes sobre aprendizagem motora têm indicado a efetividade da prática que incorpora alguma forma de autocontrole na aprendizagem e na performance de uma tarefa motora (JANELLE, 1997; CHIVIACOWSKY & WULF, 2002). No presente estudo objetiva-se investigar se os benefícios gerados pela prática autocontrolada em sujeitos típicos também serão encontrados em sujeitos com comprometimento motor após acidente vascular encefálico (AVE). Os sujeitos, 26 adultos de ambos os sexos, com lesão pós AVE há pelo menos 6 meses, serão distribuídos em dois grupos. Um grupo com frequência de feedback autocontrolado (self) e um grupo que receberá feedback de forma externamente controlada (yoked), equiparados um a um aos sujeitos do grupo autocontrolado. A tarefa, com demanda de equilíbrio, consistirá em andar de pedalo por certa distância no menor espaço de tempo possível. Todas as tentativas iniciarão com o pé contralateral à hemiparesia. Um cronômetro será utilizado para medir o tempo de movimento (TM), ou seja, o tempo necessário para andar com o pedalo da linha de partida até a linha de chegada. A pesquisa constará de uma fase de aquisição, onde os participantes realizarão 20 tentativas de prática, e uma fase de retenção, 24 horas após a fase de aquisição, em que realizarão quatro tentativas de prática. Aos sujeitos do grupo self, será informado que poderão utilizar o suporte para apoio dos membros superiores nas tentativas em que acharem necessário. Aos sujeitos do grupo yoked, será informado que em algumas tentativas deverão utilizar o suporte e em outras não. A fase de retenção será realizada sem auxílio do suporte em ambos os grupos. Antes da realização do teste, os sujeitos serão informados que deverão realizar a tarefa na maior velocidade possível

L’accident vasculaire cérébral (AVC) est un problème majeur de santé publique car les troubles fonctionnels associés ont des répercussions délétères sur la qualité de vie des patients. Deux axes de recherche portant sur l’ischémie cérébrale chez le rat sont abordés. Pour le premier, il s’agira d’étudier les modifications de la régulation des réflexes somatiques qui peuvent contribuer à expliquer en partie les déficits fonctionnels. Nos résultats montrent une fatigue précoce au cours d’un exercice isométrique du triceps brachial et une perturbation de l’inhibition du réflexe-H post-exercice. Nous avons précisé que la perturbation de l’activité des voies réflexes est associée à une modification de l’action inhibitrice des afférences musculaires des groupes III et IV pouvant expliquer la fatigue précoce observée. L’axe 2 concerne l’optimisation de l’entrainement d’endurance, stratégie prometteuse pour traiter les déficits. L’objectif est de définir la stratégie d’endurance la plus appropriée en nous focalisant sur l’intensité de l’exercice. Pour cela, les effets des exercices d’intensité modérée (classiquement recommandés) ont été confrontés avec ceux des exercices intermittents de haute intensité (HIT) en analysant la récupération fonctionnelle et la neuroplasticité cérébrale. Nos résultats montrent que l’intensité de travail, déterminée à partir du seuil lactique, est un paramètre crucial car les HIT se révèlent être plus efficaces en termes de récupération de la force, d’aptitude aérobie et de neuroplasticité. Ces travaux ouvrent de nombreuses perspectives où ces 2 axes pourraient se rejoindre en approfondissant les effets des HIT au niveau cérébral et spinal. / Stroke is a major public health issue because associated functional disorders have detrimental impacts on life quality and independence of patients as well as on economic state. This thesis work is focused on 2-research axis concerning cerebral ischemia in rat. The aim of the first axis is to study plasticity at spinal level by investigating the alteration of somatic reflex regulation that could contribute to partially explain functional deficits. Ours results show early fatigue of triceps brachii during an isometric contraction and H-reflex inhibition perturbation post-exercise. We also observed that the disturbance of reflex pathway activity is associated with a decrease of the inhibitory effect induced by muscular metabosensitive afferents that might explain early fatigue and observed functional deficits. The second axis treats about endurance training that is a promising strategy to reduce stroke-induced disorders but remains to improve. In that way, the purpose is to determine which endurance strategy is the most suitable by focusing on exercise intensity. In order to ensure this, the effects of moderate intensity exercise (classically recommended) have been compared to high intensity interval training (HIT) by analysing the functional recovery and cerebral neuroplasticity. Our data show that work intensity, based on lactic threshold, is a critical parameter. Indeed, HIT is more effective for increasing grip strength recovery, aerobic capacity as well as promoting neuroplasticity. The results of these 2 lines of research could be now associated by deepening the HIT effects at cerebral and spinal level that lead to numerous perspectives.

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L'objectif de la présente thèse de doctorat était d'étudier la relation entre le bilinguisme et le contrôle exécutif général. Les recherches sur le bilinguisme en psycholinguistique ont montré que la co-activation permanente des langues ainsi que la nécessité de s'adapter à l'environnement linguistique peuvent produire un renforcement des capacités de contrôle chez les bilingues. Toutefois, la nature des processus de contrôle impliqués reste controversée. Trois études ont examiné cette question au niveau neuronal chez des bilingues tardifs français-allemand. Différentes tâches expérimentales mettant en jeu un conflit cognitif ont été utilisées, les unes impliquant une composante linguistique (Stroop et amorçage négatif), et une autre impliquant une composante motrice (antisaccades). Les principaux résultats sont les suivants : (1) Renforcement des processus de gestion de conflits et d'inhibition chez les bilingues, (2) Interaction entre le cortex cingulaire antérieur et le cortex préfrontal dans le contrôle cognitif plus efficace chez les bilingues que chez les monolingues et (3) Modulation du contrôle exécutif par divers facteurs linguistiques individuels inhérents au bilinguisme. Prises dans leur ensemble, ces observations corroborent l'hypothèse d'une implication de processus de contrôle général dans le bilinguisme et révèlent des capacités d'adaptation neuroplastique en fonction des contraintes linguistiques. / The present doctoral thesis aimed to study the relation between bilingualism and domain-general executive control. Psycholinguistic research on bilingualism has shown that the sustained co-activation of languages and the need to adapt to the linguistic environment lead to a reinforcement of control abilities in bilinguals. However, the nature of domain-general executive control involvement in multiple language use is a matter of debate. Three studies were conducted in order to investigate this issue at the neuronal level in French-German late bilinguals. Different experimental tasks involving a cognitive conflict were used, certain of them involving a linguistic component (Stroop and negative priming) and the other one involving a motoric component (antisaccade). The main findings collected in the present doctoral thesis showed (1) the behavioral and neurophysiological evidence of enhanced conflict monitoring and inhibition in bilinguals, (2) the more efficient dynamic interplay between the anterior cingulate cortex and the prefrontal cortex in executive control in bilinguals in comparison with monolinguals, and (3) a modulation of executive control by the individual linguistic factors inherent to bilingualism. Taken together, the present findings support psycholinguistic theories postulating domain-general control involvement in bilingualism and reveal the capacity of neuroplastic adaptation as a function of linguistic constraints.

L'aphasie est un trouble acquis du langage qui cause des difficultés de communication pouvant affecter la compréhension et l'expression. Lorsque l'aphasie survient par suite d’un accident vasculaire cérébral, des difficultés importantes de communication sont initialement constatées, puis une amélioration graduelle dans les semaines et les mois qui suivent. Toutefois, pour certaines personnes, l’aphasie peut rester sévère un an, l’aphasie est alors considérée comme chronique. L'une des manifestations les plus courantes de l'aphasie est l'anomie - un manque de mots. Un nombre croissant d'études se penchent sur l'impact de la thérapie sur l'aphasie chronique et ont montré une amélioration du langage après plusieurs années. Des thérapies sont développées et étudiées en anglais, mais peu d’écrits scientifiques décrivent les effets des thérapies spécifiques et formalisées en français. Le but du présent travail doctoral est d'examiner les effets comportementaux et d’explorer les substrats neurologies du protocole Analyse des Composantes Phonologiques (ACP) ainsi que l’influence des facteurs individuels sur les gains chez dix-huit personnes vivant avec une aphasie chronique. Ainsi, la thèse comporte trois articles qui abordent, chacun, des facettes différentes des effets de l’ACP. Dans le premier article, les effets comportementaux de l’ACP sont explorés ainsi que le rôle des facteurs individuels sur la réponse à l’intervention. Le deuxième considère l’effet de l’ACP sur la connectivité fonctionnelle du cerveau, tout en considérant l’effet des facteurs individuels. Enfin, le troisième article s’intéresse à la réponse par suite de l’intervention ACP en considérant les facteurs individuels du bilinguisme et des caractéristiques neuroanatomiques comme la localisation des lésions et l’épaisseur corticale. L'ensemble de résultats démontre une amélioration significative de la dénomination des noms parmi les dix-huit participant·e·s inclus·e·s. Par ailleurs, cette amélioration a été mesurée sur des mots non-traités, ce qui reflète un effet de généralisation. Par surcroit, cette amélioration se maintient à trois mois et six mois après la fin de l’intervention. L’âge, la sévérité de l’anomie et la présence d’une apraxie de la parole sévère influencent les gains mesurés. Les analyses neurofonctionnelles de connectivité fonctionnelle au repos auprès de dix participant·e·s montrent une meilleure intégration des réseaux visuels et langagiers, associés lors d’une tâche de dénomination des noms. Les changements de connectivité observés dépendent de la sévérité de l'aphasie. Plus spécifiquement, l’intégration interhémisphérique et au sein de l’hémisphère droit est plus importante chez les personnes ayant une aphasie plus légère. Finalement, être bilingue influence aussi les gains observés par suite du protocole Analyse des Composantes Phonologiques. Les personnes bilingues s’améliorent davantage, cet avantage est associé une épaisseur corticale supérieure dans l’hémisphère droit comparativement aux personnes monolingues. Ces données préliminaires suggèrent que les changements comportementaux observés résultent de la combinaison des composantes phonologiques et orthographiques de l'intervention, et que l’intervention requiert et entraîne les fonctions exécutives. Les données cueillies dans le cadre de cette thèse sont prometteuses en ce qui concerne les effets bénéfiques de l’Analyse des Composantes Phonologiques en français. Plus précisément, les gains mesurés auprès d’un échantillon présentant des symptômes variés, la généralisation et le maintien supportent l’utilisation de ce protocole d’intervention auprès de personnes francophones. Il est à noter que la taille du groupe étudié est modeste, mais les méthodologies complémentaires et la convergence des résultats avec les données existantes dans les écrits scientifiques et à travers les méthodes d'étude de cette thèse (niveaux comportemental et neurofonctionnel) justifient des études subséquentes pour mieux comprendre les mécanismes d'action et l’influence des facteurs individuels sur les gains. / Aphasia is an acquired language disorder that causes communication difficulties that can affect understanding and expression. When aphasia occurs following a stroke, significant communication difficulties are initially noted, followed by gradual improvement over the following weeks and months. However, for some people, the aphasia may remain severe after a year even when recovery has been seen, in which case the aphasia is considered chronic. One of the most common symptoms in aphasia is anomia - a difficulty finding and saying words. A growing number of studies are looking at the impact of speech and language therapy on chronic aphasia and have shown improvement in language after several years. Therapies are developed and studied in English, but little scientific literature describes the effects of specific, formalized therapies in French. The purpose of the present doctoral work is to examine the behavioural effects and to explore the neurological substrates of the Phonological Component Analysis (PCA) protocol as well as the influence of individual factors on gains in 18 adults living with chronic aphasia. Thus, the dissertation consists of three articles, each of which addresses different facets of the effects of PCA. In the first article, the behavioural effects of PCA are explored as well as the role of individual factors on the response to the intervention. The second considers the effect of PCA on resting-state functional brain connectivity, while considering the effect of individual factors. Finally, the third paper looks at the response to the PCA intervention by considering the individual factors of bilingualism and neuroanatomical characteristics associated such as cortical thickness, and also lesion location. The overall results show a significant improvement in naming among the eighteen participants included in the thesis. Moreover, this improvement was measured on untreated words, which reflects a generalization effect and was maintained at three and six months after the end of the intervention. Age, severity of impairment and the presence of severe apraxia of speech influenced the measured gains. Neurofunctional analyses of resting-state functional connectivity in ten participants showed improved integration of the visual and language networks, associated during a naming task. The connectivity changes observed depend on the severity of the aphasia. More specifically, interhemispheric and right hemisphere integration is greater in individuals with milder aphasia. Finally, being bilingual also influences the gains observed following the Phonological Component Analysis protocol. Bilinguals improved more, and this advantage was associated with greater cortical thickness in frontal regions of the right hemisphere compared to monolinguals. These preliminary data suggest that the observed behavioural changes result from the combination of the phonological and orthographic components of the intervention, and that the intervention requires and trains executive functions. The data collected in this thesis show promise for the beneficial effects of Phonological Component Analysis in French. Specifically, the gains, generalization, and maintenance measured in a sample of adults living with aphasia displaying varied symptoms support the use of this intervention protocol with French speakers. It should be noted that the size of the study group is modest, but the complementary methodologies and the convergence of the results with existing data in the scientific literature and through the study methods of this thesis (behavioural and neurofunctional levels) justify subsequent studies to better understand the mechanisms of action and the influence of individual factors on gains.