INTRODUÇÃO: O Doppler Transcraniano funcional pode avaliar mudanças na velocidade do fluxo sanguíneo encefálico associadas a tarefas cognitivas e/ou sensitivo-motoras. Mede de maneira indireta a atividade metabólica de regiões cerebrais, segundo o princípio do acoplamento neurovascular. Os objetivos deste estudo foram: desenvolver um novo método de análise de Doppler transcraniano funcional para análise da lateralização hemisférica e verificar a capacidade deste novo método em diferenciar a lateralização hemisférica durante a execução de uma tarefa motora unimanual por indivíduos saudáveis. Adicionalmente, a lateralização hemisférica foi correlacionada com a preferência manual nestes indivíduos. MÉTODOS: Treze indivíduos saudáveis foram submetidos a um exame de Doppler transcraniano funcional durante uma prova de ativação motora manual (oposição de dedos). As sessões de Doppler transcraniano funcional foram realizadas com aparelho Doppler-Box Transcranial Doppler Unit. A prova manual compreendeu uma sequência de movimentos de oposição do primeiro e segundo dedos (thumb-tofinger opposition movement) realizado por uma mão e depois pela outra, em uma frequência de 1 movimento por segundo (1Hz) fornecida por um metrônomo digital. Durante a execução dos movimentos, foram insonadas simultaneamente as artérias cerebrais médias direita e esquerda. Para interpretação dos dados de Doppler transcraniano funcional desenvolvemos um novo programa de análise denominado FDAT, que tem vantagens de sofrer mínima influência de artefatos de ruído no sinal e de não assumir um formato pré-determinado da resposta hemodinâmica cerebral. Foi calculado um índice de lateralização (IL) como a diferença entre a velocidade relativa média da época de ativação e a velocidade relativa média da época de repouso para cada prova motora. Foi calculada a diferença dos valores de IL (ILe - ILd) provenientes da análise com cada método, obtendo-se um índice de ativação, próprio de cada sujeito. A comparação do índice de ativação durante a movimentação da mão direita, e durante a movimentação da mão esquerda, foi feita com o teste de Wilcoxon. A correlação entre o índice de ativação e a preferência manual avaliada pelo Inventário de Edimburgo foi avaliada pelo coeficiente rho de Spearman. RESULTADOS: Houve uma diferença estatisticamente significante entre o IA obtido durante a movimentação da mão direita ou da mão esquerda (p=0,02). Houve correlação estatisticamente significante entre a preferência manual e a assimetria na lateralização hemisférica identificada pelo Doppler Transcraniano funcional (rho = 0.85, p < 0.001). CONCLUSÕES: A análise do Doppler Transcraniano funcional mostrou-se viável pelo método proposto, capaz de avaliar o grau de lateralização hemisférica em uma prova de ativação motora, com boa correlação com a preferência manual. Trata-se de uma ferramenta prática, não invasiva e de baixo custo para a avaliação da lateralização hemisférica em determinadas provas funcionais / INTRODUCTION: Functional transcranial Doppler is a method for the assessment of changes in blood flow velocity of the middle cerebral artery. An asymmetric increase in blood flow velocity is a marker of hemispheric lateralization during unimanual motor task performance. The aims of this study were to propose a novel and efficient method for functional transcranial Doppler analysis based on cubic smoothing splines, and to verify the ability of this method to identify hemispheric lateralization during unimanual motor task performance in healthy subjects. In addition, hemispheric lateralization was correlated with handedness in these subjects. METHODS: Thirteen healthy subjects participated in the study. Blood flow velocities in the right and left middle cerebral arteries were recorded using functional transcranial Doppler during a finger-tapping task with either the right or left hand. Data were analyzed with a multi-step new method that included: baseline determination, raw data normalization, smoothing, lateralization Index calculation, definition of rest and motor task epochs and activation Index calculation. A positive activation Index reflects right-hemisphere lateralization and a negative activation index, left hemisphere lateralization. RESULTS: There was a statistically significant difference between the activation index obtained during right or left hand movements (p=0.02). Hand dominance was significantly correlated with asymmetry in hemispheric lateralization assessed with functional transcranial Doppler (rho = 0.85, p<0.001). CONCLUSIONS: This novel method for functional transcranial Doppler analysis was capable to assess the hemispheric lateralization during motor task performance, and correlated well with handedness. It is a practical, non-invasive and unexpensive tool for the assessment of hemispheric lateralization.

Foram analisados os efeitos da manobra de preensão manual (PM) na autorregulação encefálica (AE) dinâmica, através de um método não estacionário que utiliza o modelo de autorregressão de médias móveis. Doze indivíduos saudáveis foram orientados a realizar a manobra de PM durante 11 minutos com contração muscular constante e carga de 30% da força máxima. Registraram-se continuamente as medidas da velocidade do fluxo sanguíneo nas artérias cerebrais médias, pressão parcial de CO2 (PCO2) no ar expirado e pressão arterial (PA) não invasiva, durante o repouso (5 min), PM (3 min) e recuperação (3 min). A pressão crítica de fechamento (PCrF) e o produto área-resistência (PAR) foram obtidos empregando-se o método do primeiro harmônico. O índice de autorregulação encefálica (IAE) variável no tempo foi calculado através do modelo da autorregressão de médias móveis. As variáveis foram expressas em porcentagem de variação em relação aos valores obtidos no repouso (30 s previamente ao início da manobra de PM). Não houve alteração significativa da PCO2 do ar expirado durante MP. A PA aumentou continuamente durante a manobra (27% dos valores basais), enquanto que a velocidade do fluxo sanguíneo encefálico elevou-se inicialmente e alcançou um platô (15% dos valores basais). A elevação da PA aumentou o PAR, possivelmente devido à vasoconstricção arteriolar encefálica, o que refletiria a atuação do componente miogênico na regulação do fluxo sanguíneo encefálico; por outro lado, a PCrF reduziu-se, o que representa a ação do mecanismo metabólico. O IAE apresentou diminuição tanto no início quanto ao fim da manobra de PM; este achado pode estar relacionado à reação de alerta e/ou à diferença no tempo de resposta dos mecanismos envolvidos na adaptação neurovascular (mecanismos miogênico, metabólico e neurogênico). Conclui-se que o estudo da AE dinâmica com o modelo da autorregressão de médias móveis, durante a manobra de PM, pode ampliar os conhecimentos acerca das modificações hemodinâmicas encefálicas durante o exercício e elucidar aspectos ainda pouco conhecidos da resposta fisiológica do organismo / We investigated the effect of handgrip (HG) maneuver on time-varying estimates of dynamic cerebral autoregulation (CA), using the autoregressive moving average (ARMA) technique. Twelve healthy subjects were recruited to perform HG maneuver during 3 minutes with 30% of maximum contraction force. Cerebral blood flow velocity, end-tidal CO2 pressure (PETCO2), and noninvasive arterial blood pressure (ABP) were continuously recorded during baseline, HG and recovery. Critical closing pressure (CrCP), resistance areaproduct (RAP), and time-varying autoregulation index (ARI) were obtained. PETCO2 did not show significant changes during HG maneuver. Whilst ABP increased continuously during the maneuver, to reach 27% of its baseline value, CBFV raised to a plateau approximately 15% above baseline. This was sustained by a parallel increase in RAP, suggestive of myogenic vasoconstriction, and a reduction in CrCP that could be associated with metabolic vasodilation. The time-varying ARI index dropped at the beginning and end of the maneuver (p<0.005), which could be related to corresponding alert reactions or to different time constants of the myogenic, metabolic and/or neurogenic mechanisms. Changes in dynamic CA during HG suggest a complex interplay of regulatory mechanisms during static exercise that should be considered when assessing the determinants of cerebral blood flow and metabolism

Potenciais evocados somatossensitivos e motores são modalidades de testes neurofisiológicos com capacidade para avaliar funcionalmente a integridade das vias sensoriais e motoras, respectivamente, podendo ser utilizados na avaliação neurológica, no estabelecimento de prognóstico e na monitoração da evolução de uma lesão na medula espinhal. Este trabalho visa descrever as técnicas de obtenção de potenciais evocados com estimulação elétrica em cães portadores de doença de disco intervertebral toracolombar, e verificar se há associação com os sinais clínicos e com os achados da tomografia computadorizada (TC). Cinco cães hígidos (grupo controle) e dez cães condrodistróficos com paralisia de membros pélvicos (grupo afetado) devido à extrusão de disco intervertebral toracolombar foram avaliados com relação à classificação neurológica, imagens por TC e potenciais evocados somatossensitivos e motores sob anestesia geral. Presença ou ausência de registros caudais à lesão, mensuração de latências e amplitudes foram efetuadas. Foram captados registros cranianos em todos os cães após estimulação dos membros torácicos, mas apenas em seis cães após estimulação dos membros pélvicos. Da mesma forma, todos os cães apresentaram registros em membros torácicos após estimulação transcraniana, mas apenas em seis cães nos membros pélvicos e esfíncter anal. Houve diferença significativa quanto à presença ou ausência de registros entre os grupos afetado e controle para os membros pélvicos. Os valores mensurados de latência e amplitudes entre os grupos também são discutidos. Potenciais evocados e motores são factíveis de serem produzidos em cães com e sem paralisia de membros pélvicos sob anestesia geral, e foram correlacionados aos sinais clínicos. / Somatosensory and motor evoked potentials are neurophysiologic tests that assesse the integrity of sensory and motor pathways, and may be used in the neurological assessment, prognosis establishment and spinal cord injury monitoration. This study aims to describe the technique for evoked potentials recording with electrical stimulation in healthy dogs and in dogs with thoracolumbar intervertebral disc disease, and determine whether there is any association with clinical signs and computed tomography (CT) findings. Five clinically normal dachshunds (control group) and ten chondrodystrophic dogs with hind limb paralysis (affected group) due to thoracolumbar intervertebral disc extrusions were evaluated according to their neurological status, CT scans and somatosensory and motor evoked potentials under general anesthesia. Recordings presence or absence caudal to lesion, onset latencies and peak-to-peak amplitudes were measured. Records were captured in the scalp in all dogs after front limb stimulation, but only in six dogs after hind limb stimulation. Likewise, in all dogs records were obtained in forelimbs after transcranial stimulation, but only in six dogs on pelvic limbs and on external anal sphincter muscle. There were significant differences in presence or absent recordings between affected and control groups related to pelvic limbs PESS and PEM. Latencies and amplitudes measured between groups are discussed. Somatosensory and motor evoked potentials are feasible to produce in dogs with or without hind limb paralysis under general anesthesia, and correlated with clinical signs.

Background: While pain is essential for physiological functioning, chronic or pathologic pain is responsible for a major burden of disease in society. Novel approaches to treating acute and chronic pain have employed neuromodulatory tools to target the central and peripheral neural structures that mediate pain. Transcranial direct current stimulation (tDCS), for example, is a safe, non-invasive brain stimulation technique that has been shown in preliminary studies to reduce chronic pain when applied to the primary motor cortex. In contrast to this exogenous neuromodulatory approach, diffuse noxious inhibitory controls (DNIC) refers to endogenous pain regulatory mechanisms that decrease pain following introduction of heterotopic noxious stimuli. This thesis explores whether combining these exogenous and endogenous pain modulation approaches synergistically increases the threshold at which pain is perceived. Methods: We conducted a double-blinded, randomized, placebo-controlled trial with a crossover design to investigate the effects of tDCS and DNIC on pain thresholds in 15 healthy human subjects. Pain thresholds were assessed prior to and following administration of active tDCS, sham tDCS, cold-water-induced DNIC, and combined active tDCS and DNIC. Using magnetic resonance spectroscopy, we examined whether baseline concentrations of brain metabolites such as N-acetylaspartate in pain-related regions of interest were associated with responses to the varying neuromodulatory conditions. Results: Pain thresholds significantly increased following both active tDCS and the DNIC paradigm. These modulatory approaches appeared to have additive effects when combined. Pain threshold increases after active tDCS were positively correlated with baseline levels of N-acetylaspartate, a marker of good neural function, in the anterior cingulate cortex and negatively correlated with baseline levels of glutamine in the thalamus. Conclusions: Combining endogenous pain regulatory mechanisms with exogenous stimulation of the motor cortex can more effectively increase pain thresholds in healthy humans. Future studies should examine whether existing pain therapies may be enhanced with noninvasive brain stimulation and activation of DNIC. They should also assess whether brain metabolite levels can be utilized to predict clinical response to therapeutic interventions.

The process of movement execution can be separated into two sections; the foreperiod and the response time. The foreperiod represents the time between the warning signal (WS) and the presentation of the imperative “go” signal, and the response time incorporates both the reaction time (RT) and the movement time (Schmidt & Lee, 2011). Transcranial magnetic stimulation (TMS) was used to probe corticospinal excitability (CE) which has been measured in a variety of RT tasks during both the foreperiod and the response time periods. The purpose of the two studies in this thesis was to measure when and at what rate changes in CE occur in both simple and complex tasks. The results of the first experiment indicated that CE levels quickly increased from baseline with the presentation of the WS. This was followed by a holding period in which CE was held constant until a decline in CE occurred prior to the presentation of the IS. This decline was followed by a rapid increase in CE as the movement was initiated and released. Importantly, even though levels of CE were decreasing relative to the start of the decline, participants were still in a heightened state as they prepared to release their movements. Furthermore, it is suggested that selective inhibitory control mechanisms were at least partly responsible for the decline prior to the IS. The results of the second experiment indicated that MEP amplitudes in a simple task were significantly larger compared to those in a complex task relative to both the IS and the onset of electromyography. These findings suggest that simple and complex tasks achieve differing levels of corticospinal excitability, and it is suggested that the complex requires the use of the cerebellum, which suppresses excitatory projections to the thalamus, and consequently to the motor cortex.

The corpus callosum provides a physical and functional connection between the two hemispheres of the brain allowing interactions between homologous cognitive, sensory and motor areas. In humans, the integrity of transcallosal connections between motor cortices can be evaluated quickly and non-invasively using transcranial magnetic stimulation (TMS) via the ipsilateral silent period (iSP). While the technique has been known for 20 years, many issues remain unsolved regarding which methods are best to elicit the iSP as an index of transcallosal inhibition. In addition, there is still limited information regarding the influence of individualized factors such as age on iSP measurements. This thesis investigates how common physiological and methodological factors influence the iSP in order to establish this method as a reliable index to assess the integrity of the transcallosal pathway linking primary motor cortices. In the first series of experiments, we used a previously described TMS protocol to elicit iSPs [1] to investigate changes in motor transcallosal inhibition in relation to individual factors linked to age, hand preference and history of concussions. A second series of methodological experiments examined the effects of stimulation intensity on the iSP and to determine its inter-session reliability. Our first series of experiments provided evidence that advancing age and history of concussions in young athletes were each independently associated with alterations in transcallosal inhibition. This was evidenced by changes in the duration of transcallosal inhibition (DTI) and in the latency of transcallosal inhibition (LTI) derived from iSP measurements. These experiments also revealed that the degree of hand preference in young adults was reflected in measures of transcallosal inhibition, so that mixed-handed individuals (i.e., ambidextrous) exhibited evidence of more efficient transcallosal transmission than either strong right or left handed individuals. The second series of experiments focusing on methodological aspects showed that the iSP duration (though not its onset) was influenced by stimulation intensity, increasing linearly with intensity up to 140% of the resting motor threshold (RMT). Our analysis further revealed that the probability of eliciting detectable iSP also increased with increasing intensity up to 130% RMT before reaching a plateau. A stimulation intensity of 130% of RMT appears to be optimal to elicit iSPs in healthy participants. In a subsequent study, we showed that iSP elicited at this stimulation intensity (i.e., 130% RMT) had good inter-session reliability. In light of these investigations, we recommend for future studies that, in addition to contraction of the homologous muscles of the opposite hand as proposed by Giovannelli et al 2009, that an intensity of 130% RMT should be used to elicit the iSP when assessing transcallosal inhibition between motor cortices.

Observing others performing actions is a common way to learn new motor skills. Such ability appears to be linked with one’s ability to imagine actions (motor imagery) (Wang et al. 2014). While motor imagery has been widely used in the context of athletic performance, the same approach has also been advocated in rehabilitation settings, where they often target populations with chronic pain using mobile health applications (de la Vega and Miro 2014). However, we still have very limited information as to how the ability to perform motor imagery addresses this rehabilitation application (Johnson et al. 2012). In the present study, we examined this question by looking at modulation in corticospinal excitability in the context of a motor imagery task. The imagery task itself consisted of judging whether images depicting hands in different postures represented either right or left hands. Based on prior neuroimaging and chronometric studies, such laterality judgments about hand postures are thought to involve mental rotations of one’s own hand (i.e., a form of implicit motor imagery) and thus provided an ideal context to evaluate if advocating such strategy is a valid approach to elicit motor activation in rehabilitation patients (Butson et al. 2014; Goble and Brown 2008; Parsons 1987). To this end, we used non-invasive transcranial magnetic stimulation (TMS) to probe the excitability of the motor system while young healthy participants performed mental rotations in the hand judgment task. Corticospinal excitability was tested in both hemispheres separately (target muscle: first dorsal interosseous) with participants (n=18) seated in front of a computer screen while they performed hand laterality judgments using a commercial set of pictures depicting bare hands in different postures. Excitability was tested also under two other conditions to contrast with variations measured during the hand laterality task, i.e. a mental counting task and a control task (looking at the image of a static foot). In all conditions, TMS (110% resting motor threshold) was set to trigger at ~half of the mean response time in the hand laterality task measured prior to testing with TMS. Comparison of task-related variations in MEP amplitude revealed no significant hemispheric main effect or interaction, although MEPs tended to be larger in general in response to left TMS. A “task condition” effect was observed owing to the large MEP facilitation elicited during the mental counting task, which was significantly different (p<0.001) from either the control “Foot” task or the hand rotation task. In fact, the latter task tended to be associated with MEP depression. A secondary experiment involving a subset of participants (n=6) to examine the influence of image contents (i.e. hand performing actions instead of bare hands) and probing more proximal muscles produced similar results as the main experiment. These results indicate that the general assumption that laterality tasks involving body parts will lead to internal mental rotation and motor activation and enhanced excitability is not necessarily true. In fact, our observations suggest that participants may rely on non-motor strategies based on visual cues when making laterality judgments about body parts. As well, no evidence for hemispheric asymmetry was found with the hand laterality task which is in line with other recent reports. Collectively, these results highlight the need to exert caution when using laterality tasks for rehabilitation purposes. One cannot simply assume that such tasks will translate into motor simulation and facilitation of the motor system. More research should be undertaken before recommending the hand mental rotation task as a viable rehabilitation option for chronic pain.

Abstract Light acts as the most important regulating and entraining factor of the mammalian circadian rhythm. This rhythm has evolved to set phases, in which different physiological and behavioral events occur at the right time of the day to synchronize the organism. The mechanism of light transduction via eyes to the brain and its effects on circadian rhythmicity is well known. Yet, it has also been shown that light is able to penetrate the skull bone directly, but it is still unknown, whether transcranial light is able to affect molecules regulating circadian rhythmicity. Monoamines and especially opsins have been shown to act as important regulators in circadian rhythmicity. Both group of molecules can mediate the effects of light on regulation and entrainment. In this thesis, mice and hamsters have been illuminated transcranially and the expression of three different opsins and the concentrations of several monoamines have been measured. The animals were illuminated under anesthesia either just after the onset of the light period or just after the beginning of the dark period. The opsin expression in rodent brain were measured by western blot and the monoamine concentrations from mouse brain, plasma and adrenal gland were measured by HPLC. It was observed that both opsin expression and monoamine concentrations can be influenced by transcranial illumination. The effect varied depending on the studied molecule, tissue and time of illumination. The findings of this study demonstrate that opsins, which are considered to be the most important molecules regulating circadian rhythmicity, can be directly and specifically affected not only via the eyes but also by light illuminated through the skull. Furthermore, monoamine production can be altered in both the central nervous system and the peripheral tissues by transcranial illumination. This thesis demonstrates an alternate pathway for circadian entrainment and regulation by light involving specific molecular mediators such as opsins and monoamines. / Tiivistelmä Valo on tärkein yksittäinen tekijä nisäkkäiden vuorokausirytmiikassa. Tämä rytmi on kehittynyt ajoittamaan fysiologiset ja käyttäytymiseen perustuvat ilmiöt tapahtumaan oikeaan aikaan vuorokaudesta. Valosignaalin välittyminen silmien kautta aivoihin ja sen vaikutukset vuorokausirytmiikkaan ovat hyvin tunnetut ja paljon tutkitut, mutta vielä on epäselvää, pystyykö kallon läpi annettava valo samaan, vaikka valon on osoitettu pystyvän läpäisemään nisäkkäiden kallon. Monoamiinit ja opsiinit ovat molekyylejä, jotka ovat tärkeässä roolissa vuorokausirytmiikan säätelyssä, ja molempien ilmeneminen on riippuvainen valon määrästä. Tässä väitöskirjassa valotettiin hiirien ja hamstereiden aivoja korvan kautta annettavalla valolla ja mitattiin kolmen eri opsiinin ekspressiota sekä monoamiinien määrää. Eläimiä valotettiin nukutuksessa joko valojakson alussa aamulla tai valojakson päätyttyä illalla. Opsiinien ekspressio aivoissa mitattiin western blot -menetelmällä ja monoamiinien HPLC-menetelmällä. Tuloksista huomattiin, että sekä opsiinien ekspressioon että monoamiinien pitoisuuksiin voidaan vaikuttaa suoraan kallon läpi annettavalla valolla. Valohoidon vaikutus riippui tutkittavasta molekyylistä, kudoksesta ja valohoidon ajankohdasta. Näiden tulosten avulla pystyttiin osoittamaan, että opsiinien, jotka ovat tärkeimpiä molekyylejä vuorokausirytmiikan säätelyssä, määrää voidaan manipuloida myös kallon läpi annettavan valon vaikutuksesta. Lisäksi kallon läpi annettavalla valolla voidaan vaikuttaa monoamiinien pitoisuuksiin sekä keskushermostossa että muissa kudoksissa. Tämä väitöskirja antaa tärkeää tietoa vuorokausirytmiikkaa säätelevistä molekyyleistä ja osoittaa, että niihin pystytään vaikuttamaan myös muuten kuin silmien kautta annettavalla valolla.

In addition to low mood, major depressive disorder (MDD) is characterized by persistent cognitive deficits that impair daily functioning and resist improvement with conventional pharmacotherapies. Repetitive transcranial magnetic stimulation (rTMS) holds promise as an efficacious alternative, offering better outcomes than medication for patients with treatment-resistant depression (TRD). Yet, current rTMS protocols that administer sinusoidal biphasic pulses achieve remission in less than the majority. However, monophasic pulses may yield higher success rates based on greater cortical excitation/neuromodulation strength. MDD is associated with altered P300 event-related potentials (ERPs), indexing decreased attentional resource allocation and slower cortical processing speed. Using a cohort of 20 TRD patients who received high-frequency rTMS, this study aimed to assess the impact of monophasic and biphasic stimulation on attention-related P300 measures and their utility as correlates of clinical/cognitive response. Based on baseline and post-treatment change in P300 components, rTMS-induced increases in automatic attention/passive information processing differed by pulse type and predicted greater clinical improvement in depressed individuals. This study represents an important step towards identifying cognitive changes and underlying cortical mechanisms associated with rTMS response and targeted MDD treatment.

La compréhension des effets cérébraux sous-tendant l’impact de la stimulation magnétique transcrânienne répétée (rTMS) est un a priori nécessaire à la connaissance de la prise en charge thérapeutique des patients bénéficiant de ces traitements. A posteriori, elle permet en plus de comprendre les processus physiopathologiques responsables des symptômes cliniques propres aux troubles mentaux. Nous nous sommes ici intéressés aux effets de la rTMS sur le cerveau des patients souffrant de schizophrénie (SZ), au travers des deux principes fondamentaux du fonctionnement cérébral que sont la ségrégation et l’intégration fonctionnelle. En premier lieu, nous avons analysé l’effet de la rTMS visant le cortex préfrontal médian (CPM) sur le principe de ségrégation fonctionnelle chez des SZ avec trouble de la cognition sociale. Pour ce faire nous avons développé un paradigme d’imagerie par résonance magnétique fonctionnelle (IRMf) écologique et novateur de cognition sociale. Un prérequis aux études longitudinales en IRMf est la reproductibilité du signal d’activation. Nous avons alors démontré la fiabilité de notre paradigme entre deux sessions, puis à l’aide de ce paradigme, nous avons étudié l’effet de la rTMS sur la ségrégation à partir de la variation du signal BOLD et des taux de N-AcetylAspartate et de glutamate. Puis nous avons étudié l’impact de la rTMS ciblant le sillon temporal supérieur gauche (STSg) sur les hallucinations auditivo-verbales (AVH) en termes de connectivité fonctionnelle statique (intégration fonctionnelle). Nous avons ainsi mis en évidence l’effet bénéfique de la rTMS sur le trouble de cognition sociale et sur les AVH. En outre, quand la rTMS cible le STSg, il ne semble pas avoir d’effet sur la connectivité fonctionnelle statique du réseau cérébral du langage observé. Cependant, focalisé au niveau du CPM, elle permettrait d’augmenter la concentration de N-acétylaspartate des SZ. L’absence d’effet de la rTMS illustrerait plutôt des profils d’organisation cérébrale différents des SZ, et ce par des variabilités interindividuelles, suggérant qu’il serait à l’avenir bénéfique de déterminer les caractéristiques optimales de la stimulation sur une base individuelle afin de mieux moduler les processus anormaux du cerveau dans les schizophrénies. / The understanding of the brain effects underlying the impact of repeated transcranial magnetic stimulation (rTMS) is a necessary a priori necessary concerning patients treatments. A posteriori, it also helps to understand the pathophysiological processes responsible for the clinical symptoms of mental disorders. Hither, we are interested in the effects of rTMS on the brain of patients with schizophrenia (SZ), through the two fundamental principles of cerebral functioning: segregation and functional integration. First, we have analyzed the effect of rTMS on the medial prefrontal cortex (MPFC) according to functional segregation in SZ with social cognition disorder. To do this we have developed an ecological and innovative social cognition paradigm for functional magnetic resonance imaging (fMRI). A prerequisite for longitudinal studies in fMRI is the reproducibility of the activation signal, we have then demonstrated the reliability of our paradigm between two sessions. Using this paradigm, we have studied the effect of rTMS on segregation from the variation of the BOLD signal and the levels of N-Acetyl Aspartate and glutamate. Then, we studied the impact of rTMS targeting the left temporal sulcus (STS) on auditory-verbal hallucinations (AVH) in terms of functional connectivity (functional integration). We have thus demonstrated the beneficial effect of rTMS on social cognition disorder and on AVH. Moreover, when the rTMS targets the STS, it does not seem to have an effect on the static functional connectivity within the listening language network. However, focused on the MPFC, it would increase the N-acetylaspartate concentration of SZ. The absence of the effect of the rTMS would rather illustrate different brain organization patterns of the SZ, due to inter-individual variability, suggesting that it would be in the future beneficial to determine optimal characteristics of stimulation on an individual basis in order to best modulate abnormal processes of the brain in schizophrenias.