Neuronavigation and transcranial magnetic stimulation (TMS) are valuable tools in clinical and research environment. Neuronavigation provides visual guidance of a given instrument during procedures of neurological interventions, relative to anatomic images. In turn, TMS allows the non-invasive study of cortical brain function and to treat several neurological disorders. Despite the well-accepted importance of both techniques, high-cost of neuronavigation systems and limited spatial accuracy of TMS in targeting brain structures, limit their applications. Therefore, the aim of this thesis was to i) develop an open-source, free neuronavigation software, ii) study a possible combination of neuronavigation and 3D printing for surgical planning, and iii) construct a multi-channel TMS coil with electronic control of electric field (E-field) orientation. In the first part, we developed and characterized a neuronavigation software compatible with multiple spatial tracking devices, the InVesalius Navigator. The created co-registration algorithm enabled tracking position and orientation of instruments with an intuitive graphical interface. Measured accuracy was similar to that of commercial systems. In the second part, we created 3D printed models from patients with neurological disorders and assessed the errors of localizing anatomical landmarks during neuronavigation. Localization errors were below 3 mm, considered acceptable for clinical applications. Finally, in the last part, we combined a set of two thin, overlapping coils to allow electronic control of the E-field orientation and investigated how the motor evoked responses depend on the stimulus orientation. The developed coil enabled the stimulation of the motor cortex with high angular resolution. Motor responses showed the highest amplitude and lowest latency with E-field approximately perpendicular to the central sulcus. In summary, this thesis provides new methods to improve spatial accuracy of techniques to brain interventions. / A neuronavegação e a estimulação magnética transcraniana (EMT ou TMS, do termo em inglês transcranial magnetic stimulation) têm sido apresentadas como ferramentas valiosas em aplicações clínicas e de pesquisa. A neuronavegação possibilita a localização de instrumentos em relação a imagens anatômicas durante procedimentos de intervenção neurológica. Por sua vez, a EMT permite o estudo não invasivo da função cerebral e o tratamento de doenças neurológicas. Apesar da importância de ambas as técnicas, o alto custo dos sistemas de neuronavegação e a reduzida precisão espacial da EMT em ativar estruturas cerebrais limitam suas aplicações. Sendo assim, o objetivo desta tese foi: i) desenvolver um software de neuronavegação gratuito e de código aberto, ii) estudar a combinação entre neuronavegação e impressão 3D para planejamento cirúrgico, e iii) construir uma bobina de EMT multicanal com controle eletrônico da orientação do campo elétrico (CE). Na primeira parte, desenvolvemos e caracterizamos um software de neuronavegação compatível com vários rastreadores espaciais, o InVesalius Navigator. O algoritmo criado possibilitou o rastreamento de instrumentos por uma interface gráfica intuitiva. A precisão medida foi semelhante à de sistemas comerciais. Na segunda parte, imprimimos modelos 3D de pacientes com patologias neurológicas e avaliamos os erros de localização de marcos anatômicos durante a neuronavegação. Os erros de localização foram inferiores a 3 mm, considerados aceitáveis para aplicações clínicas. Por fim, na última parte, combinamos duas bobinas sobrepostas para controlar eletronicamente a orientação do CE, e investigamos como as respostas motoras evocadas dependem da orientação da corrente. A bobina desenvolvida possibilitou estimular o córtex motor com alta resolução angular. As respostas motoras apresentaram maior amplitude e menor latência para orientação do CE aproximadamente perpendicular ao sulco central. Em suma, esta tese fornece novos métodos para melhorar a precisão espacial de técnicas de intervenção com o cérebro.

Le but de cette thèse était d'étudier l'organisation anatomo-fonctionnelle du système sensorimoteur humain et la façon dont les mouvements volontaires sont produits et contrôlés. Avec le développement de l’imagerie cérébrale, des méthodes de corrélation anatomo-clinique et de stimulation électrique directe cérébrale, de nombreuses avancées scientifiques ont pu être réalisée. Ces trois approches complémentaires ont été utilisé dans cette thèse afin d’améliorer la compréhension de l’organisation sensorimotrice cérébrale. Dans la première étude (soumise à publication), nous avons montré que la chirurgie cérébrale éveillée utilisant la stimulation électrique directe est une procédure sûre et efficace chez les enfants afin de réduire le déficit neurologique postopératoire. L'approche améliore la précision de la détection des zones éloquentes, avec une bonne tolérance neuropsychologique et psychologique. Une évaluation psychologique et neuropsychologique est essentielle. Dans une deuxième série de deux études, nous avons montré que la partie dorso-postérieure dorsal du cortex pariétal (DPPr) est une structure clé dans l'organisation complexe du mouvement manuel fin chez l'homme à travers la mise en oeuvre d'une boucle sensori-parieto-motrice.La première étude (publiée, Current Biology 2018) montre que la stimulation électrique directe d’une region corticale focale dans la partie dorso-postérieure du cortex pariétal entraine l’inhibition de la production du mouvement manuel, c’est-à-dire bloque l'initiation et la réalisation de ce dernier, sans produire de contraction musculaire ni de sensation consciente de mouvement. Dans la seconde étude (en cours de soumission), nous avions pour objectif d'identifier précisément les bases anatomiques du circuit parietal inhibiteur précédemment décrit. Grâce à la tractographie de diffusion (DTI), nous avons réussi à isoler des projections ipsilatérales spécifiques reliant les sites d’inhibition du DPPr, retrouvés dans la première étude, avec la zones dévolues au contrôle distal fin dans les cortex primaires moteur (M1) et sensoriel (S1). Ces données montrent que la boucle pariétale inhibitrice est directe depuis S1 vers DPPr vers M1 (même s'il n'est pas possible d'exclure l'existence d'échanges bidirectionnels entre ces aires). Dans la dernière étude (en cours de soumission), nous nous sommes intéressé à une structure motrice fondamentale, qui supporte 50 % des invasions tumorales chez l'enfant : le cervelet. Il s'agissait de déterminer si les lésions précoces étaient oui ou non prédictives d'une récupération déficitaire à long terme après prise en compte des covariables les plus critiques. Nous avons mesuré la récupération fonctionnelle à long terme chez 3 groupes survivants de lésion de la fosse postérieure. Les 3 groupes étaient comparables en ce qui concerne leurs caractéristiques tumorales mais opérés à différents âges : jeune (≤ 7 ans), moyen (> 7 ans et ≤ 13 ans) et tardif (> 13 ans). La qualité de vie (échelles cliniques : Health-related Quality of Life -hrQol- et Performance Status -PS-), les performances motrices (ataxie -ICARS- et motricité fine -Pegboard-) et cognitif (quotient intellectuel -FSIQ-) furent mesurés. L'âge précoce lors de la chirurgie, une lésion des noyaux profonds cérébelleux et la nécessité d'une radiothérapie postopératoire révélèrent une influence significativement négative et indépendante sur la récupération à long terme des participants. Ces résultats confirment l'existence d'une période critique de développement au cours de laquelle la "machine à apprendre" cérébelleuse revêt une importance cruciale / The aim of the thesis was to investigate the mapping of the anatomofunctional organization of the human sensorimotor system and how volutional movements of human are produced and controlled. Neuroimaging and especially DTI, fine anatomo-functional observation in patient and direct electrical stimulation were considered. This multi-modal approach permitted to improve our understanding of sensorimotor organization in humans. In the first study, we showed that awake brain surgery with the use of direct electrical stimulation is a safe and efficient procedure in children in order to decrease post-operative neurological deficit. It improves the accuracy of detecting eloquent area, with a good tolerance from a neuropsychological and psychological aspect. Age-adapted neuropsychologic preparation may enable offering ABS even to younger children on an individual basis. In a second series of two studies, we showed that the dorso-posterior part of the parietal cortex is a key structure in the complex organization of movement in human with a S1-DPPr-M1 loop. In the first study, direct electrical stimulation of focal cortical site in the dorso-posterior part of the parietal cortex triggered inhibition of movement production and blocked ongoing movement without producing muscle contraction or conscious movement sensation. In the second study, we aimed to find a direct projection from the PRR, defined in the first study (Desmurget et al., 2018), to the primary motor cortex and the primary somatosensory cortex. Thanks to the DTI state-of-the-art tractography, we succeeded in finding such major ipsilateral streamlines projecting in the well-known hand knob region giving new insights of the white matter structures involved in the inhibition of volitional hand movements. These observations confirm clinical per-operative data showing that stimulating the counterpart of PRR in humans can disrupt hand movements ipsilaterally, irrespective of the hemisphere. Moreover, our results shed light on the implication of the PRR for the volitional hand sensorimotor operating behavior. In the last study, we investigate the impact of early cerebellar damage on long-term functional recovery in 3 groups of posterior fossa survivors, comparable with respect to their tumoural characteristics but operated at different ages: young (≤ 7 years), middle (> 7 years and ≤ 13 years) and old (> 13 years). Daily (Health-related Quality of Life -hrQol-, Performance Status -PS-), motor (International Cooperative Ataxia Rating Scale -ICARS-, Pegboard Purdue Test -PegBoard-) and cognitive (Full Scale Intelligence Quotient -FSIQ-) functioning were measured. Early age at surgery, lesion of deep cerebellar nuclei and post-operative radiotherapy had a significant, independent negative influence on long term recovery. These results support the existence of an early critical period of development during which the cerebellar "learning machine" is of critical importance