Malgré le développement de nouvelles générations d’antipsychotiques, certains symptômes schizophréniques ne répondent pas à ces traitements. S’appuyant sur des hypothèses physiopathologiques sous tendant ces symptômes, de nouvelles thérapeutiques comme la thérapie de remédiation cognitive et les techniques de neurostimulation externe ont été développées. Cette approche était restée essentiellement clinique. Dans ce travail, l’étude en imagerie des mécanismes biologiques sous tendant les effets bénéfiques de ces thérapeutiques non pharmacologiques nous a permis de tester des hypothèses physiopathologiques. L’IRM fonctionnelle (IRMf) et la spectroscopie par résonance magnétique (SRM) ont été utilisées pour rechercher les effets d’une thérapie de remédiation cognitive (TRC), de la stimulation magnétique transcrânienne (TMS) et de la stimulation électrique transcrânienne en courant continu (tDCS). Nous avons mis en évidence (1) que la TRC modifie les activations cérébrales durant une tâche de mémoire de travail chez des patients schizophrènes (2) que la TMS modifie la biochimie cérébrale de la zone stimulée et de régions cérébrales profondes chez un patient schizophrène, (3) que la tDCS modifie les réseaux de connectivité fonctionnelle d’une tâche de repos chez des volontaires sains / Despite the development of new generation antipsychotic drugs, some symptoms of schizophrenia do not respond to these treatments. Based on the pathophysiological hypothesis underlying these symptoms, new therapies such as cognitive remediation therapy and neurostimulation techniques have been developed. This approach remained essentially clinical. In this work, the study of biological mechanisms tending benefits of these non-pharmacological treatment has allowed us to test these pathophysiological hypotheses. Functional MRI (fMRI) and magnetic resonance spectroscopy (MRS) were used to investigate the effects of cognitive remediation therapy (CRT), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We demonstrated (1) that CRT modifies cerebral activations during a working memory task in patients with schizophrenia, (2) that TMS modifies brain biochemistry of the stimulated area and of deep brain regions in a patient with schizophrenia and (3) that tDCS modifies the functional connectivity in resting state networks of healthy volunteers

Recentes evidências sugerem que a dor lombar crônica está associada a alterações plásticas no cérebro, que podem ser modificadas por estratégias de neuromodulação. Neste ensaio clínico investigamos a eficácia analgésica de 12 sessões não consecutivas de estimulação transcraniana por corrente contínua (ETCC), estimulação elétrica periférica (EEP), ETCC+EEP e estimulação simulada (sham) em 92 pacientes com dor lombar crônica inespecífica. A intensidade, aspecto sensorial e afetivo da dor, incapacidade e percepção global de recuperação foram avaliadas antes do tratamento e quatro semanas, três e seis meses pós-randomização. Efeitos adversos, satisfação do paciente com o tratamento e fatores de confusão como ansiedade e depressão também foram avaliados. Os resultados demonstraram efeitos analgésicos clinicamente importantes da ETCC+EEP (MD = -2,6 IC95% = -4,4 a -0,9) e EEP isolada (MD = -2,2 IC95% = -3,9 a -0,4) comparada ao grupo sham, mas não da ETCC isolada (MD = -1,7 IC95% = -3,4 a -0,0). Além da manutenção do efeito analgésico por até três meses a ETCC+EEP obteve maior proporção de respondedores em diferentes pontos de corte. Os resultados sugerem que tanto a ETCC+EEP quanto EEP isolada são eficazes em curto prazo para o alívio da dor lombar crônica inespecífica. No entanto o efeito analgésico mais duradouro aliado a maior proporção de respondedores indicam um possível efeito aditivo e sinérgico da ETCC+EEP no alívio da dor em pacientes com dor lombar crônica não específica. Os nossos resultados não apoiam o uso da ETCC no regime de tratamento utilizado / Recent evidence suggests that chronic low back pain is associated with plastic changes in the brain that can be modified by neuromodulation strategies. In this clinical trial we have investigated the analgesic efficacy of 12 non-consecutive sessions of transcranial direct current stimulation (tDCS), peripheral electrical stimulation (PES), tDCS+PES and sham stimulation in 92 patients with chronic nonspecific low back pain. Intensity, the sensory and affective aspect of pain, disability, and overall perception of recovery were assessed before treatment and four weeks, three and six months post-randomization. Adverse effects, patient satisfaction with treatment and confounding factors such as anxiety and depression were also evaluated. The results showed clinically significant analgesic effects of tDCS+PES (Mean Reduction (MR) = -2.6; CI95% = -4.4 to - 0.9) and PES alone (MD = -2.2, CI95% = -3.9 to -0.4) compared to sham group, but not tDCS alone (MD = -1.7, CI95% = -3.4 to -0.0). In addition to maintaining the analgesic effect for up to three months, tDCS+PES treatment had a higher proportion of responders in different cutoff points. The results suggest that both tDCS+PES and PES alone are effective in relieving chronic nonspecific low back pain in the short term. However the most lasting analgesic effect, combined with a higher proportion of responders, indicates a possible additive and synergistic effect of tDCS+PES in relieving low back pain. Our findings do not support the use of tDCS alone in this condition

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Le traitement visuel répété d’un visage inconnu entraîne une suppression de l’activité neuronale dans les régions préférentielles aux visages du cortex occipito-temporal. Cette «suppression neuronale» (SN) est un mécanisme primitif hautement impliqué dans l’apprentissage de visages, pouvant être détecté par une réduction de l’amplitude de la composante N170, un potentiel relié à l’événement (PRE), au-dessus du cortex occipito-temporal. Le cortex préfrontal dorsolatéral (CPDL) influence le traitement et l’encodage visuel, mais sa contribution à la SN de la N170 demeure inconnue. Nous avons utilisé la stimulation électrique transcrânienne à courant direct (SETCD) pour moduler l’excitabilité corticale du CPDL de 14 adultes sains lors de l’apprentissage de visages inconnus. Trois conditions de stimulation étaient utilisées: inhibition à droite, excitation à droite et placebo. Pendant l’apprentissage, l’EEG était enregistré afin d’évaluer la SN de la P100, la N170 et la P300. Trois jours suivant l’apprentissage, une tâche de reconnaissance était administrée où les performances en pourcentage de bonnes réponses et temps de réaction (TR) étaient enregistrées. Les résultats indiquent que la condition d’excitation à droite a facilité la SN de la N170 et a augmentée l’amplitude de la P300, entraînant une reconnaissance des visages plus rapide à long-terme. À l’inverse, la condition d’inhibition à droite a causé une augmentation de l’amplitude de la N170 et des TR plus lents, sans affecter la P300. Ces résultats sont les premiers à démontrer que la modulation d’excitabilité du CPDL puisse influencer l’encodage visuel de visages inconnus, soulignant l’importance du CPDL dans les mécanismes d’apprentissage de base. / Repeated visual processing of an unfamiliar face suppresses neural activity in face-specific areas of the occipito-temporal cortex. This "repetition suppression" (RS) is a primitive mechanism involved in learning of unfamiliar faces, which can be detected through amplitude reduction of the N170 event-related potential (ERP). The dorsolateral prefrontal cortex (DLPFC) exerts top-down influence on early visual processing. However, its contribution to N170 RS and learning of unfamiliar faces remains unclear. Transcranial direct current stimulation (tDCS) transiently increases or decreases cortical excitability, as a function of polarity. We hypothesized that DLPFC excitability modulation by tDCS would cause polarity-dependent modulations of N170 RS during encoding of unfamiliar faces. tDCS-induced N170 RS enhancement would improve long-term recognition reaction time (RT) and/or accuracy rates, whereas N170 RS impairment would compromise recognition ability. Participants underwent three tDCS conditions in random order at ~72 hour intervals: right anodal/left cathodal, right cathodal/left anodal and sham. Immediately following tDCS conditions, an EEG was recorded during encoding of unfamiliar faces for assessment of P100 and N170 visual ERPs. P300 was analyzed to detect prefrontal function modulation. Recognition tasks were administered ~72 hours following encoding. Results indicate the right anodal/left cathodal condition facilitated N170 RS and induced larger P300 amplitudes, leading to faster recognition RT. Conversely, the right cathodal/left anodal condition caused increases in N170 amplitudes and RT, but did not affect P300. These data are the first to demonstrate that DLPFC excitability modulation can influence early visual encoding of unfamiliar faces, highlighting the importance of DLPFC in basic learning mechanisms.

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De tout temps, les humains ont cherché différents moyens pour améliorer leur quotidien. Avec les avancées technologiques actuelles, cette quête s’en trouve facilitée, notamment dans la volonté d’accroître leurs capacités cognitives et/ou motrices. La neuro imagerie permet dorénavant de renseigner les aires cérébrales activées lors de différentes tâches fonctionnelles. Il est aussi possible de moduler l’activité cérébrale en stimulant localement le cerveau avec de faibles courants électriques. Une des techniques les plus répandues à cet effet est appelée tDCS pour transcranial direct current stimulation. Il s’agit en fonction de la polarité du courant induit de moduler à la hausse (stimulation anodale) ou à la baisse (stimulation cathodale) l’excitabilité cortico-spinale en dépolarisant ou en hyperpolarisant la membrane des neurones, respectivement. Malgré une démocratisation grandissante de la neuromodulation via tDCS, les résultats rapportés par la communauté scientifique sont relativement hétérogènes. Les travaux initiés au début des années 2000 sont remis en cause par des résultats actuels faisant état d’une variabilité inter et intra individuelle assez importante. Cette pierre d’achoppement nécessite de développer de nouveaux protocoles d’application de la tDCS. Dans cette thèse, nous avons étudié plusieurs modalités d’application de la tDCS afin d’accroître la persistance des effets neuroplastiques induits et d’augmenter les performances comportementales. Deux études ont été menées afin de révéler dans un premier temps les apports induits par le couplage tâche motrice-tDCS pour ensuite mettre en avant les effets cumulatifs de la répétition de sessions de tâche motrice-tDCS avec pré conditionnement sur la performance motrice. La première étude à travers l’utilisation de la spectroscopie dans le proche infrarouge a permis de rapporter des changements hémodynamiques distincts subséquents au couplage tâche motrice-tDCS par rapport à des protocoles tDCS plus conventionnels. La primauté de l’utilisation concomitante de la tDCS à la tâche motrice a été révélée par la moindre activation du cortex sensorimoteur durant la stimulation ainsi que par une activation cérébrale retardée accrue qui pourrait représenter une réorganisation neuroplastique. La seconde étude s’est intéressée aux effets de la polarité du conditionnement lors de sessions répétées avec comme objectif d’améliorer l’apprentissage et la rétention du système sensorimoteur. Le conditionnement par tDCS était plus propice lors de sessions répétées à engendrer des performances motrices supérieures contrairement à la condition sham. La polarité cathodale engendrait une persistance prolongée. Les premiers résultats de ces travaux de thèse ont permis de défendre l’usage concomitant de la tDCS avec la tâche motrice. De futures recherches sont nécessaires afin d’étudier le transfert de ces résultats dans le monde de l’entraînement ainsi que celui de la réhabilitation. / Historically, humans have sought various ways to improve their daily lives. With the current technological advances, this quest is facilitated, especially in the desire to increase their cognitive and / or motor skills. Neuro imagery now makes it possible to inform the areas activated during different functional tasks. Today, it is now possible to modulate brain activity by stimulating the brain locally with weak electrical currents. One of the most common techniques for this purpose is called tDCS for transcranial direct current stimulation. The polarity of the induced current (anodal or cathodal stimulation) allows to modulate upward or downward cortico-spinal excitability by depolarizing or hyperpolarizing the membrane of the neurons, respectively. Despite a growing interest of neuromodulation techniques via tDCS, the results reported by the scientific community are relatively heterogeneous. The work initiated at the beginning of the 2000s is called into question by current results showing a rather large inter and intra variability. This stumbling block requires the development of new protocols for the application of anodal tDCS (atDCS). In this thesis, we were interested in optimizing atDCS protocols in order to increase the persistence of the induced-neuroplastic effects and to increase the behavioral performances. Two studies were carried out in order to first reveal the impact from the motor task/atDCS coupling and then to highlight the cumulative effects of multiple motor-tDCS task sessions with priming atDCS on motor performance. The first study through the use of near infrared spectroscopy allowed to report various hemodynamic changes subsequent to the motor task/atDCS coupling with respect to independent and controlled stimulation protocols. The primacy of the concomitant use of tDCS with the motor task was revealed by the slightest activation of the sensorimotor cortex during stimulation and by an increased delayed cerebral activation which could represent a neuroplastic reorganization. The second study examined the effects of repeated atDCS sessions with anoadal or cathodal tDCS priming in order to improve the learning and retention gains of the sensorimotor system. TDCS priming was more favorable for repeated atDCS sessions to generate higher motor performances contrary to sham. The cathodal polarity produced prolonged persistence. The major findings of this work allow to support the concomitant use of atDCS with the motor task. Future research is needed to study the transfer of these results into the fields of coaching and rehabilitation.

Background: Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types. Methods: We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. PROSPERO ID: CRD42016042055. Results: We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upperextremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events. Conclusion: Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.