Frameless neuronavigational systems are a recent novelty for a precise approach to intracerebral tumours in open surgery. In this study 66 patients with a variety of intracranial tumours in various locations underwent surgical resection with neuronavigational guidance. Two different neuronavigational systems – the arm- and pointer-based ISG viewing wand and the miroscope-based MKM system – were compared for four different indications. Neuronavigation was used (a) in multiple tumours, e. g. brain metastases, (b) in solitary cortical or subcortical tumours located in eloquent brain areas, e. g. motor cortex or speech region, (c) in deep-situated brain tumours, including brain stem neoplasms, and (d) in infiltratively growing tumours to define the borders of the lesion. Using taped skin markers (MKM system) and a surface-fit algorithm (viewing wand) for registration, an accuracy of 1 to 2 mm deviation was achieved, which was sufficient for removal of all of the intracranial neoplasms investigated. Both systems proved to be safe and useful surgical tools regardless of the patient`s age, positioning of the patient during surgery or the location of the lesion. When these two systems were compared, the viewing wand was found to be preferable for resection of multiple brain tumours located in distant operative sides and solitary tumours in eloquent brain areas; this was because of the wide range of movement of the pointing device and the possibility of 3D reconstruction of the brain surface. As the MKM system provided the option of stereotactical guidance during the operative procedure, it was found to be superior in approaching small and deep-situated lesions. In certain cases brain shifting due to early drainage of the CSF led to minor underestimation of the real depth. For the precise definement of tumour borders of intraparenchymal neoplasms both system were equally suitable. However, intrusion of brain parenchyma into the resection cavity led to minor overestimation of the real tumour size in certain large intraparenchymal tumours. / Rahmenfreie Neuronavigationssysteme stellen eine Neuerung in der offenen operativen Behandlung intrazerebraler Tumoren dar. In dieser Studie wurden 66 Patienten mit verschiedenen intrakraniellen Tumoren in unterschiedlichen Lokalisationen mit Hilfe der Neuronavigation operiert. Hierbei wurden zwei verschiedene Navigationssysteme – ein Arm- und Pointer-basierendes System (ISG Viewing Wand) und ein Mikroskop-basierendes System (MKM) – für vier verschiedene Indikationen miteinander verglichen. Die Neuronavigation wurde verwendet (a) bei multiplen Tumoren, wie z.B. Hirnmetastasen, (b) bei solitären kortikalen oder subkortikalen Prozessen in eloquenten Hirnarealen, wie z.B. Motorkortex oder Sprachregion, (c) bei tiefgelegenen Hirntumoren einschließlich Hirnstammtumoren und (d) bei infiltrativ wachsenden Tumoren zur Bestimmung der Tumorgrenzen. Die Verwendung von Hautklebemarkern (MKM-System) und eines Oberflächen-Anpassungsalgorithmus (Viewing Wand) zur Registrierung war mit einer Genauigkeit von 1 bis 2 mm Abweichung für die operative Entfernung aller intrakraniellen Tumoren ausreichend. Beide Systeme bestätigten sich als sichere und geeignete chirurgische Hilfsmittel unabhängig vom Alter der Patienten, der Lagerung des Patienten unter dem chirurgischen Eingriff und der Lokalisation der Raumforderung. Im Systemvergleich zeigte die Viewing Wand durch einen weiten Bewegungsraum des Pointers und der Möglichkeit einer dreidimensionalen Rekonstruktion der Hirnoberfläche Vorteile in der Entfernung von multiplen, in entfernten Hirnregionen gelegenen Tumoren sowie von solitären Prozessen in eloquenter Lokalisation. Das MKM-System war durch die Bereitstellung einer stereotaktischen Führung während des operativen Eingriffes in der Ansteuerung kleiner tiefgelegener Prozesse zu bevorzugen. Eine frühzeitige Liquordrainage führte zu einem brain shifting mit einer diskreten Unterschätzung der wirklichen Tiefe. Für eine genaue Festlegung der Tumorgrenzen von intraparenchymalen Tumoren waren beide Systeme vergleichbar geeignet. Das Relabieren von Hirngewebe in die Resektionshöhle führte jedoch in einigen Fällen von großen intraparenchymalen Tumoren bei beiden Systemen zu einer geringen Überschätzung der wirklichen Tumorgrenzen. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

As principais incapacidades funcionais que se observam após o Acidente Vascular Encefálico (AVE), sob o ponto de vista clínico, decorrem da hemiparesia, da incoordenação, da hipertonia espástica dos membros superior e inferior contralaterais à lesão e da fraqueza ipsilateral e contralateral ao hemisfério lesado. Evidências sugerem que o aprendizado e a realização de tarefas motoras de habilidade podem induzir mudanças comportamentais e neurofisiológicas, o que ocorre tanto em animais intactos quanto naqueles submetidos às lesões do SNC. Nesse sentido, alguns trabalhos evidenciam a participação da atividade dendrítica, observada pelo aumento da imunorreatividade a MAP2, induzida por experiências comportamentais. Sendo assim, o objetivo do presente estudo foi avaliar o desempenho motor e a expressão da MAP2 no córtex motor primário, em ratos sham ou submetidos à HIC e aos treinamentos de habilidade do alcance (TH) ou ao treinamento de não-habilidade (TNH). Para tanto, ratos Wistar adultos foram inicialmente adaptados às diferentes tarefas motoras empregadas ao longo de três semanas, sendo, posteriormente, submetidos à cirurgia de indução da hemorragia intracerebral (HIC) por meio da administração intra-estriatal de colagenase tipo IV ou de veículo (animais Sham) (S). Em seguida, os animais dos grupos S_TH e HIC_TH foram submetidos ao treinamento da tarefa de habilidade do alcance e preensão, os animais dos grupos S_TNH e HIC_TNH foram submetidos ao treinamento da tarefa de não-habilidade e os animais S_ST e HIC_ST não receberam nenhum tipo de treinamento durante 4 semanas. Ao longo desse período, os animais foram testados pelo teste do Staircase quanto ao desempenho motor ao final da 2° e 4° semana de treinamento. Encerrado o período de treinamento, os animais foram profundamente anestesiados, perfundidos e tiveram seus encéfalos processados para a análise imunoistoquímica. Os resultados mostram que a realização da tarefa de habilidade do alcance e preensão foi capaz de aumentar a imunorreatividade da MAP2 no córtex motor primário (M1) em ambos os hemisférios, tanto em animais lesados quanto em animais não-lesados. Além disso, os animais HIC e HIC_TNH apresentaram também aumento da imunorreatividade à MAP2 em ambos os hemisférios. Porém, apenas os animais HIC_TH apresentaram recuperação funcional dos movimentos do membro anterior afetado, avaliados pelo teste comportamental. Concluindo, o presente estudo demonstra que o treino de habilidade induz plasticidade dendrítica no M1 em condições normalidade e lesão e, como estratégia de reabilitação, mostra-se superior ao treino de não-habilidade, na recuperação funcional do membro anterior após a HIC experimental. / Under clinical view, the main functional impairment observed after stroke is resulting from the hemiparesis, incoordination, spastic hypertonia and from ipsilateral and contralateral weakness . Evidences suggest that learning and achievement of motor tasks ability may induce behavioral and neurophysiological changes, which occur in both intact and injured animals. Accordingly, some studies reveal the participation of dendritic activity, observed by increasing the immunoreactivity to MAP2, induced by behavioral experiences. Thus, the aim of this study was to evaluate the motor performance and the expression of MAP2 in primary motor cortex (M1), in rats submitted or not to the IHC and rehabilitation using skilled (SK) or unskilled (US) training. Animals were initially adapted to different motor tasks employed over three weeks, and, subsequently, submitted to surgery for the induction of intracerebral hemorrhage (IHC) by means of administration of bacterial collagenase type IV or vehicle (animals Sham) (S) into the striatum . Then, animals in groups S_SK and IHC_SK were submitted to the training skilled forelimb reaching, animals in groups S_US and IHC_US were submitted to the training unskilled and animals S and HIC received no type of training during 4 weeks. Throughout that period, the reaching ability was tested using the Staircase test at the end of 2nd and 4thweek of training. At the end of the rehabilitation period, animals were deeply anesthetized, perfused and the immunohistochemistry was processed. Results show that the achievement of the task skilled forelimb reaching was able to increase the MAP2 immunoreactivity in primary motor cortex (M1) in both hemispheres, both in injured animals as in intact animals. In addition, animals form IHC and IHC_US groups also presented increased immunoreactivity to MAP2 in both cerebral hemispheres. However, only IHC_SK animals presented functional recovery of movements of the forelimb, evaluated by test behavioral. In conclusion, this study shows that training of skills tasks can induce modifications in M1 under conditions of normality and lesion and, as a strategy of rehabilitation, induced higher plasticity than the unskilled training correlated with functional recovery of the forelimb after IHC experimental.

The diploma thesis deals with a problematic of management of the nursing care by a patient with intracranial hemorrhage. Most of the patients who survive intracranial hemorrhage stay permanently reliant on the care from others. That is why it is so important for this care to be as qualitative as possible and to have a fluent continuity. The aim of the thesis was to find out what is the role of a nurse by the patient with intracranial hemorrhage, then also find out, if the nurses know the warning signs of a worsening state of such patient, how do they cooperate with his/her family and what are the possibilities of the following care. In the empirical part of the diploma thesis, qualitative-quantitative research was used. For a complex view on a management of nursing care, the chosen technique of research was semi-structured questionnaire with patients with intracranial hemorrhage and non-standardized questionnaire with nurses who take care of these patients. For the quantitative part of the research, two hypotheses to two aims of the diploma thesis were set. Both hypotheses weren't proven by statistical methods. For qualitative research, four research questions were set. The respondents described the role of a nurse, especially in helping the patient, in rehabilitation and in also her role in educating the patient. Addressed respondents agreed on appropriate and swift reactions of the nurses in case the state of the patient starts to worsen. The cooperation of nurses and families is according to the patients without problems. It showed in the interviews with respondents, that there is a problem with insufficient awareness of the patients about the existing possibilities of following care. The outcome of the diploma thesis is a coherent educational material about nursing care by a patient with intracranial hemorrhage, which can serve to either the students or the nurses taking care of these patients.

As principais incapacidades funcionais que se observam após o Acidente Vascular Encefálico (AVE), sob o ponto de vista clínico, decorrem da hemiparesia, da incoordenação, da hipertonia espástica dos membros superior e inferior contralaterais à lesão e da fraqueza ipsilateral e contralateral ao hemisfério lesado. Evidências sugerem que o aprendizado e a realização de tarefas motoras de habilidade podem induzir mudanças comportamentais e neurofisiológicas, o que ocorre tanto em animais intactos quanto naqueles submetidos às lesões do SNC. Nesse sentido, alguns trabalhos evidenciam a participação da atividade dendrítica, observada pelo aumento da imunorreatividade a MAP2, induzida por experiências comportamentais. Sendo assim, o objetivo do presente estudo foi avaliar o desempenho motor e a expressão da MAP2 no córtex motor primário, em ratos sham ou submetidos à HIC e aos treinamentos de habilidade do alcance (TH) ou ao treinamento de não-habilidade (TNH). Para tanto, ratos Wistar adultos foram inicialmente adaptados às diferentes tarefas motoras empregadas ao longo de três semanas, sendo, posteriormente, submetidos à cirurgia de indução da hemorragia intracerebral (HIC) por meio da administração intra-estriatal de colagenase tipo IV ou de veículo (animais Sham) (S). Em seguida, os animais dos grupos S_TH e HIC_TH foram submetidos ao treinamento da tarefa de habilidade do alcance e preensão, os animais dos grupos S_TNH e HIC_TNH foram submetidos ao treinamento da tarefa de não-habilidade e os animais S_ST e HIC_ST não receberam nenhum tipo de treinamento durante 4 semanas. Ao longo desse período, os animais foram testados pelo teste do Staircase quanto ao desempenho motor ao final da 2° e 4° semana de treinamento. Encerrado o período de treinamento, os animais foram profundamente anestesiados, perfundidos e tiveram seus encéfalos processados para a análise imunoistoquímica. Os resultados mostram que a realização da tarefa de habilidade do alcance e preensão foi capaz de aumentar a imunorreatividade da MAP2 no córtex motor primário (M1) em ambos os hemisférios, tanto em animais lesados quanto em animais não-lesados. Além disso, os animais HIC e HIC_TNH apresentaram também aumento da imunorreatividade à MAP2 em ambos os hemisférios. Porém, apenas os animais HIC_TH apresentaram recuperação funcional dos movimentos do membro anterior afetado, avaliados pelo teste comportamental. Concluindo, o presente estudo demonstra que o treino de habilidade induz plasticidade dendrítica no M1 em condições normalidade e lesão e, como estratégia de reabilitação, mostra-se superior ao treino de não-habilidade, na recuperação funcional do membro anterior após a HIC experimental. / Under clinical view, the main functional impairment observed after stroke is resulting from the hemiparesis, incoordination, spastic hypertonia and from ipsilateral and contralateral weakness . Evidences suggest that learning and achievement of motor tasks ability may induce behavioral and neurophysiological changes, which occur in both intact and injured animals. Accordingly, some studies reveal the participation of dendritic activity, observed by increasing the immunoreactivity to MAP2, induced by behavioral experiences. Thus, the aim of this study was to evaluate the motor performance and the expression of MAP2 in primary motor cortex (M1), in rats submitted or not to the IHC and rehabilitation using skilled (SK) or unskilled (US) training. Animals were initially adapted to different motor tasks employed over three weeks, and, subsequently, submitted to surgery for the induction of intracerebral hemorrhage (IHC) by means of administration of bacterial collagenase type IV or vehicle (animals Sham) (S) into the striatum . Then, animals in groups S_SK and IHC_SK were submitted to the training skilled forelimb reaching, animals in groups S_US and IHC_US were submitted to the training unskilled and animals S and HIC received no type of training during 4 weeks. Throughout that period, the reaching ability was tested using the Staircase test at the end of 2nd and 4thweek of training. At the end of the rehabilitation period, animals were deeply anesthetized, perfused and the immunohistochemistry was processed. Results show that the achievement of the task skilled forelimb reaching was able to increase the MAP2 immunoreactivity in primary motor cortex (M1) in both hemispheres, both in injured animals as in intact animals. In addition, animals form IHC and IHC_US groups also presented increased immunoreactivity to MAP2 in both cerebral hemispheres. However, only IHC_SK animals presented functional recovery of movements of the forelimb, evaluated by test behavioral. In conclusion, this study shows that training of skills tasks can induce modifications in M1 under conditions of normality and lesion and, as a strategy of rehabilitation, induced higher plasticity than the unskilled training correlated with functional recovery of the forelimb after IHC experimental.

As principais incapacidades funcionais que se observam após o Acidente Vascular Encefálico (AVE), sob o ponto de vista clínico, decorrem da hemiparesia, da incoordenação, da hipertonia espástica dos membros superior e inferior contralaterais à lesão e da fraqueza ipsilateral e contralateral ao hemisfério lesado. Evidências sugerem que o aprendizado e a realização de tarefas motoras de habilidade podem induzir mudanças comportamentais e neurofisiológicas, o que ocorre tanto em animais intactos quanto naqueles submetidos às lesões do SNC. Nesse sentido, alguns trabalhos evidenciam a participação da atividade dendrítica, observada pelo aumento da imunorreatividade a MAP2, induzida por experiências comportamentais. Sendo assim, o objetivo do presente estudo foi avaliar o desempenho motor e a expressão da MAP2 no córtex motor primário, em ratos sham ou submetidos à HIC e aos treinamentos de habilidade do alcance (TH) ou ao treinamento de não-habilidade (TNH). Para tanto, ratos Wistar adultos foram inicialmente adaptados às diferentes tarefas motoras empregadas ao longo de três semanas, sendo, posteriormente, submetidos à cirurgia de indução da hemorragia intracerebral (HIC) por meio da administração intra-estriatal de colagenase tipo IV ou de veículo (animais Sham) (S). Em seguida, os animais dos grupos S_TH e HIC_TH foram submetidos ao treinamento da tarefa de habilidade do alcance e preensão, os animais dos grupos S_TNH e HIC_TNH foram submetidos ao treinamento da tarefa de não-habilidade e os animais S_ST e HIC_ST não receberam nenhum tipo de treinamento durante 4 semanas. Ao longo desse período, os animais foram testados pelo teste do Staircase quanto ao desempenho motor ao final da 2° e 4° semana de treinamento. Encerrado o período de treinamento, os animais foram profundamente anestesiados, perfundidos e tiveram seus encéfalos processados para a análise imunoistoquímica. Os resultados mostram que a realização da tarefa de habilidade do alcance e preensão foi capaz de aumentar a imunorreatividade da MAP2 no córtex motor primário (M1) em ambos os hemisférios, tanto em animais lesados quanto em animais não-lesados. Além disso, os animais HIC e HIC_TNH apresentaram também aumento da imunorreatividade à MAP2 em ambos os hemisférios. Porém, apenas os animais HIC_TH apresentaram recuperação funcional dos movimentos do membro anterior afetado, avaliados pelo teste comportamental. Concluindo, o presente estudo demonstra que o treino de habilidade induz plasticidade dendrítica no M1 em condições normalidade e lesão e, como estratégia de reabilitação, mostra-se superior ao treino de não-habilidade, na recuperação funcional do membro anterior após a HIC experimental. / Under clinical view, the main functional impairment observed after stroke is resulting from the hemiparesis, incoordination, spastic hypertonia and from ipsilateral and contralateral weakness . Evidences suggest that learning and achievement of motor tasks ability may induce behavioral and neurophysiological changes, which occur in both intact and injured animals. Accordingly, some studies reveal the participation of dendritic activity, observed by increasing the immunoreactivity to MAP2, induced by behavioral experiences. Thus, the aim of this study was to evaluate the motor performance and the expression of MAP2 in primary motor cortex (M1), in rats submitted or not to the IHC and rehabilitation using skilled (SK) or unskilled (US) training. Animals were initially adapted to different motor tasks employed over three weeks, and, subsequently, submitted to surgery for the induction of intracerebral hemorrhage (IHC) by means of administration of bacterial collagenase type IV or vehicle (animals Sham) (S) into the striatum . Then, animals in groups S_SK and IHC_SK were submitted to the training skilled forelimb reaching, animals in groups S_US and IHC_US were submitted to the training unskilled and animals S and HIC received no type of training during 4 weeks. Throughout that period, the reaching ability was tested using the Staircase test at the end of 2nd and 4thweek of training. At the end of the rehabilitation period, animals were deeply anesthetized, perfused and the immunohistochemistry was processed. Results show that the achievement of the task skilled forelimb reaching was able to increase the MAP2 immunoreactivity in primary motor cortex (M1) in both hemispheres, both in injured animals as in intact animals. In addition, animals form IHC and IHC_US groups also presented increased immunoreactivity to MAP2 in both cerebral hemispheres. However, only IHC_SK animals presented functional recovery of movements of the forelimb, evaluated by test behavioral. In conclusion, this study shows that training of skills tasks can induce modifications in M1 under conditions of normality and lesion and, as a strategy of rehabilitation, induced higher plasticity than the unskilled training correlated with functional recovery of the forelimb after IHC experimental.

Abstract Primary intracerebral hemorrhage (pICH) is a severe, suddenly occurring disease involving high mortality and poor functional outcome. In the absence of curative treatment patient management is mainly supportive with the emphasis on preventing hematoma enlargement and complications. Better understanding of the factors predicting outcome are needed to define effective treatments. An unselected population-based registry study of 982 pICH patients admitted to Oulu University Hospital during the years 1993 to 2008 was conducted The study revealed that concomitant use of warfarin and serotonin-modulating antidepressants at the time of pICH increases the case fatality rate compared to patients with warfarin alone. An elevated C-reactive protein value on admission was an independent predictor of unfavorable outcome after pICH. This association was not explained by pre-existing heart disease, diabetes, severity of the bleeding, or infections. Patients undergoing surgical hematoma evacuation were observed to have improved 3-month survival compared to conservatively treated patients. Improved survival was noticed especially in patients with ≤70 years of age with ≥30ml supratentorial ICHs. Hematoma evacuation did not improve functional outcome. Earlier ischemic stroke was found to be an independent predictor of recurrent pICH. Diabetes seemed to increase and treated hypertension decrease the risk for fatal recurrence. Aspirin or serotonin-modulating antidepressants did not seem to increase the risk of recurrence. / Tiivistelmä Primääri aivoverenvuoto (pICH) on vakava, yhtäkkisesti alkava sairaus, johon liittyy korkea kuolleisuus ja vaikea vammautuminen. Parantavan hoidon puuttuessa on hoito lähinnä elintoimintoja tukevaa vuodon laajenemisen ja komplikaatioiden estämistä. Ennusteeseen vaikuttavien tekijöiden parempi tunteminen on ehto tehokkaiden hoitojen löytämiseksi. Väitöskirjatutkimustani varten kerättiin Oulun yliopistollisen sairaalan alueelta vuosien 1993-2008 aikana 982 aivoverenvuotoon sairastuneen potilaan väestöpohjainen aineisto. Tutkimus osoitti, että varfariinin ja selektiivisen serotoniinin takaisinoton estäjän (SSRI) yhteiskäyttö aivoverenvuodon aikana lisäsi kuolevuutta pelkkään varfariiniin nähden. Alkuvaiheen koholla oleva C-reaktiivinen proteiini oli itsenäinen aivoverenvuodon jälkeistä vammautuneisuutta ennustava tekijä. Yhteys ei selittynyt olemassa olevalla sydänsairaudella, diabeteksella, aivoverenvuodon vaikeudella tai infektioilla. Kirurginen aivoverenvuodon poistoleikkaus paransi kolmen kuukauden ennustetta verrattuna potilaisiin ilman leikkausta. Erityisesti leikkaus auttoi alle 70-vuotiaita potilaita, joilla oli yli 30 millilitran kokoinen pinnallisempi vuoto. Leikkaus ei parantanut fyysistä kuntoutumista. Aiempi sairastettu aivoinfarkti oli itsenäinen aivoverenvuodon uusiutumista ennustava tekijä. Diabetes saattaa lisätä ja hoidossa oleva verenpainetauti laskea riskiä tappavaan uusintavuotoon. Aspiriinin tai SSRI:n käyttö eivät lisänneet uusintavuodon riskiä.

Un des enjeux majeurs de la Psychologie Cognitive est de décrire les grandes fonctions mentales, notamment chez l’humain. Du point de vue neuroscientifique, il s’agit de modéliser l’activité cérébrale pour en extraire les éléments et mécanismes spatio-temporels susceptibles d’être mis en correspondance avec les opérations cognitives. Le travail de cette thèse a consisté à définir et mettre en œuvre des stratégies originales permettant de confronter les modèles cognitifs existants à des données issues d’enregistrements neurophysiologiques chez l’humain. Dans une première étude nous avons démontré que la distinction entre les organisations classiques de la dénomination de dessin sériel-parallèle, doit être adressée au niveau des essais uniques et non sur la moyenne des signaux. Nous avons conçu et mené l’analyse des signaux SEEG de 15 patients pour montrer que l’organisation temporelle de la dénomination de dessin n’est pas, au sens strict, parallèle. Dans une deuxième étude nous avons combiné trois techniques d’enregistrements : SEEG, EEG et MEG pour clarifier l’organisation spatiale des sources d’activité neuronales. Nous avons établi la faisabilité de l’enregistrement sur un patient qui exécute une tâche de perception visuelle. Au delà des corrélations entre les signaux moyens des trois techniques, cette analyse a révélé des corrélations au niveau des essais uniques. À travers deux approches expérimentales, cette thèse propose de nombreux développements méthodologiques et conceptuels originaux et pertinents. Ces contributions ouvrent de nouvelles perspectives à partir desquelles les signaux neurophysiologiques pourront informer les théories des Neurosciences Cognitives. / A major issue in Cognitive Psychology is to describe human cognitive functions. From the Neuroscientific perceptive, measurements of brain activity are collected and processed in order to grasp, at their best resolution, the relevant spatio-temporal features of the signal that can be linked with cognitive operations. The work of this thesis consisted in designing and implementing strategies in order to overcome spatial and temporal limitations of signal processing procedures used to address cognitive issues. In a first study we demonstrated that the distinction between picture naming classical temporal organizations serial-parallel, should be addressed at the level of single trials and not on the averaged signals. We designed and conducted the analysis of SEEG signals from 5 patients to show that the temporal organization of picture naming involves a parallel processing architecture to a limited degree only. In a second study, we combined SEEG, EEG and MEG into a simultaneous trimodal recording session. A patient was presented with a visual stimulation paradigm while the three types of signals were simultaneously recorded. Averaged activities at the sensor level were shown to be consistent across the three techniques. More importantly a fine-grained coupling between the amplitudes of the three recording techniques is detected at the level of single evoked responses. This thesis proposes various relevant methodological and conceptual developments. It opens up several perspectives in which neurophysiological signals shall better inform Cognitive Neuroscientific theories.

La capacité à évaluer les résultats nos actions est fondamentale pour adapter et optimiser notre comportement et dépend d’un système superviseur chargé d’évaluer l’action, détecter les erreurs, déclencher des corrections.Le réseau neuronal sous-jacent la supervision de l’action n’a pas été complètement caractérisé chez l’homme.Dans une première étude nous avons enregistré dans l’Aire Motrice Supplémentaire (AMS) des LFP évoqués par les réponses et modulés par la performance. Des LFP évoqués exclusivement par les erreurs ont été enregistrés plus tardivement dans le cortex préfrontal médian.Dans la deuxième étude, nous avons observé que les activités de hautes-fréquences gamma sont, elles aussi, modulées par la performance des sujets, mais dans un vaste réseau frontal et extra-frontal.Dans une troisième étude, utilisant des enregistrements simultanés électroencéphalographiques (EEG) et magnétoencéphalographiques (MEG), nous observé une activité évoquée par un feedback interne sur l’EEG (mais pas en MEG), alors qu'une activité évoquée par le feedback externe était bien visible sur les enregistrements MEG, indiquant que les générateurs de ces deux activités cérébrales, sont différents. Nos résultats montrent une implication de l’AMSp dans la supervision de l’action chez l’homme, bien plus importante que ce que l’on soupçonnait auparavant. L’AMS évalue précocement, et de façon continue, l’action en cours et elle engage vraisemblablement des structures préfrontales en cas d’erreur seulement. Le traitement de l’erreur d’action, selon qu'il se fonde sur des informations internes ou externes est certainement sous-tendu par des réseaux corticaux différents. / The capacity to evaluate the outcome of our actions is fundamental for adapting and optimizing behaviour. This capability depends on an action monitoring system in charge of assessing ongoing actions, detecting errors, and evaluating outcomes.Electrical brain activity evoked by negative outcomes is thought to originate within the medial part of the frontal cortex. Nonetheless, the underlying neuronal network is incompletely characterised in humans.In the two first studies, we investigated the anatomical substrates of action monitoring in humans using intracerebral local field potential (LFP) recordings of cerebral cortex from epileptic patients. Response evoked LFPs sensitive to outcome were recorded from the Supplementary Motor Area proper (SMA), while LFPs evoked exclusively by errors were recorded later in the medial prefrontal cortex. High-gamma-frequency activity (60-180 Hz) was modulated as a function of action outcome in a vast frontal and extra-frontal network.In a third study using simultaneous recording of electroencephalography (EEG) and magnetoencephalography (MEG), we found that error related activity was detected by EEG (but not by MEG), while feedback-related activity was detected by MEG, indicating that the sources of these two forms of outcome-modulated brain activity are different.To conclude the SMA is much more involved in action monitoring than previously thought. SMA rapidly and continuously assesses ongoing actions and likely engages more rostral prefrontal structures in the case of error. Processing of action errors and of negative externally delivered feedback therefore appears to be supported by distinct cortical networks.

Au cours des 20 dernières années, de nombreux modèles animaux ont émergé, permettant le développement de nouvelles approches pour l'étude préclinique du cerveau sain et pathologique. Les rongeurs sont ainsi devenus des acteurs incontournables des avancées thérapeutiques. Dans ce contexte, l'imagerie radioisotopique, qui permet de quantifier des traceurs radioactifs avec une sensibilité excellente, constitue un outil de choix l'étude des processus cérébraux in vivo. Mais, jusqu'à présent, les techniques de radioimagerie les plus courantes imposent l'anesthésie ou l'immobilisation de l'animal. Or, les anesthésiants affectent les processus biologiques étudiés. De plus, il existe un vif intérêt pour l'étude simultanée du comportement de l'animal. L'acquisition d'une image dynamique des processus cérébraux concomitante à la mesure du comportement de l'animal éveillé et libre de ses mouvements est une information précieuse pour l'étude de l'addiction, de la mémoire, etc.À IMNC, nous avons abordé la neuroimagerie comportementale par une approche originale basée sur des sondes intracérébrales qui mesurent la concentration du traceur radioactif par détection directe des positons in situ. La sonde PIXSIC, basée sur un capteur pixelisé à diodes de silicium, a démontré leur pertinence dans le cadre d'études pharmacologiques chez l'animal totalement libre de ses mouvements. Toutefois, PIXSIC a montré quelques limitations pour son utilisation longitudinale : un niveau de bruit élevé dû aux perturbations électromagnétiques, une forte sensibilité au rayonnement gamma d'annihilation et une grande fragilité mécanique de l'implant aminci à 200 micromètres. En nous appuyant sur l'avènement des technologies CMOS pour la détection des particules chargées en physique des hautes énergies, nous avons pour ambition de concevoir MAPSSIC, une sonde qui réponde aux difficultés mises en avant par PIXSIC. Les capteurs CMOS permettent d'inclure l'amplification au niveau des pixels, limitant ainsi le bruit d'origine électromagnétique. Le volume sensible peut être réduit à une épaisseur de quelques dizaines de micromètres, réduisant ainsi fortement la sensibilité aux gammas et autorisant l'augmentation de son épaisseur totale pour assurer sa robustesse mécanique. Enfin, les capteurs CMOS nous permettent de concevoir un détecteur fortement pixelisé pour accéder à de nouvelles capacités d'imagerie. Cette thèse a eu pour objectif de développer une version optimisé de la sonde. Pour cela, nous avons imaginé un premier prototype de capteur CMOS et nous avons développé un modèle Monte Carlo pour estimer ses propriétés de détection. Nous avons pu démontrer que ses performances le qualifiait pour l'usage prévu. Notamment en terme de sensibilité, de volume d’isoefficacité et d’énergie déposée. Nous avons également pu explorer plusieurs paramètres d’optimisation, les dimensions des pixels et l’épaisseur de la zone sensible, qui nous permettent de considérer MAPSSIC au delà du premier prototype. Fort de ces bases théoriques nous avons conçu plusieurs exemplaires du capteur. Les développements qui ont été établis durant la thèse se sont ensuite focalisés sur un ensemble d'outils méthodologiques, logiciels et matériels afin de permettre la caractérisation physique du capteur à l'aide de sources radioactives. Nous avons pu établir l'uniformité de la réponse des pixels et la plage de taux d’évènements assurant la linéarité du taux de comptage. Ces éléments nous ont permis de conclure sur la pertinence de ce capteur pour la conception d'un dispositif autonome d'imagerie. Celui-ci est constitué d'un implant fait de deux capteurs dos-à-dos, d'un système électronique assurant le contrôle des capteurs, la lecture du signal et la communication sans fil et d'une station d'acquisition. Dans le cadre de la thèse, nous avons montré son adéquation pour l'évaluation des variations de l'activité d'une source radioactive bêta+ liquide dans laquelle l'implant a été plongé. / Over the last 20 years, many animal models have emerged, allowing the development of new approaches for the preclinical study of the healthy and pathological brain. Rodents have become key players in therapeutic advances. In this context, radioisotope imaging, which quantifies radioactive tracers with excellent sensitivity, is a prime tool for the study of brain processes in vivo. But so far, the most common radioimaging techniques require anesthesia or immobilization of the animal. However, anesthetics affect the biological processes studied. In addition, there is a keen interest in the simultaneous study of the behavior of the animal. The acquisition of a dynamic image of brain processes concomitant with the behavior of the awake and freely moving animal is valuable information for the study of addiction, memory, etc.At IMNC lab, we have approached behavioral neuroimaging with an original method based on intracerebral probes that measure the concentration of the radioactive tracer by direct detection of positrons in situ. The PIXSIC probe, based on a pixelized sensor with silicon diodes, demonstrated their relevance in the context of pharmacological studies with completely freely moving animals. However, PIXSIC has shown some limitations for its longitudinal use: a high level of noise due to electromagnetic perturbations, a high sensitivity to annihilation gamma radiation and a high mechanical fragility of the implant thinned to 200 microns.Based on the advent of CMOS technologies for the detection of charged particles in high energy physics, our ambition is to design MAPSSIC, a probe that responds to the difficulties highlighted by PIXSIC. CMOS sensors allows amplification at the pixel level, thus limiting electromagnetic noise. The sensitive volume can be reduced to a thickness of a few tens of microns, thus greatly reducing the sensitivity to gammas and allowing the increase of its total thickness to ensure its mechanical robustness. Finally, CMOS sensors allows us to design a highly pixelated detector to reach new imaging capabilities. This thesis aims to develop an optimized version of the probe. We imagined a first prototype CMOS sensor and we developed a Monte Carlo model to estimate its detection properties. We were able to show that his performances qualified it for the intended use, in terms of sensitivity, isoefficiency volume and deposited energy. We have also been able to explore several optimization parameters, the pixel dimensions and the thickness of the sensitive area, which allow us to consider MAPSSIC beyond the first prototype. With these theoretical bases we have produced several copies of the sensor. The developments that were established during the thesis then focused on a set of methodological tools, software and hardware to allow the physical characterization of the sensor using radioactive sources. We have been able to establish the uniformity of the pixel response and the event rate range ensuring the linearity of the count rate.These elements allowed us to conclude on the relevance of this sensor for the design of an autonomous imaging device. This consists of an implant made of two back-to-back sensors, an electronic system providing sensor control, signal reading and wireless communication and an acquisition station. In the context of the thesis, we have shown its suitability for the evaluation of the variations of the activity of a liquid beta+ radioactive source in which the implant has been immersed.

Frameless neuronavigational systems are a recent novelty for a precise approach to intracerebral tumours in open surgery. In this study 66 patients with a variety of intracranial tumours in various locations underwent surgical resection with neuronavigational guidance. Two different neuronavigational systems – the arm- and pointer-based ISG viewing wand and the miroscope-based MKM system – were compared for four different indications. Neuronavigation was used (a) in multiple tumours, e. g. brain metastases, (b) in solitary cortical or subcortical tumours located in eloquent brain areas, e. g. motor cortex or speech region, (c) in deep-situated brain tumours, including brain stem neoplasms, and (d) in infiltratively growing tumours to define the borders of the lesion. Using taped skin markers (MKM system) and a surface-fit algorithm (viewing wand) for registration, an accuracy of 1 to 2 mm deviation was achieved, which was sufficient for removal of all of the intracranial neoplasms investigated. Both systems proved to be safe and useful surgical tools regardless of the patient`s age, positioning of the patient during surgery or the location of the lesion. When these two systems were compared, the viewing wand was found to be preferable for resection of multiple brain tumours located in distant operative sides and solitary tumours in eloquent brain areas; this was because of the wide range of movement of the pointing device and the possibility of 3D reconstruction of the brain surface. As the MKM system provided the option of stereotactical guidance during the operative procedure, it was found to be superior in approaching small and deep-situated lesions. In certain cases brain shifting due to early drainage of the CSF led to minor underestimation of the real depth. For the precise definement of tumour borders of intraparenchymal neoplasms both system were equally suitable. However, intrusion of brain parenchyma into the resection cavity led to minor overestimation of the real tumour size in certain large intraparenchymal tumours. / Rahmenfreie Neuronavigationssysteme stellen eine Neuerung in der offenen operativen Behandlung intrazerebraler Tumoren dar. In dieser Studie wurden 66 Patienten mit verschiedenen intrakraniellen Tumoren in unterschiedlichen Lokalisationen mit Hilfe der Neuronavigation operiert. Hierbei wurden zwei verschiedene Navigationssysteme – ein Arm- und Pointer-basierendes System (ISG Viewing Wand) und ein Mikroskop-basierendes System (MKM) – für vier verschiedene Indikationen miteinander verglichen. Die Neuronavigation wurde verwendet (a) bei multiplen Tumoren, wie z.B. Hirnmetastasen, (b) bei solitären kortikalen oder subkortikalen Prozessen in eloquenten Hirnarealen, wie z.B. Motorkortex oder Sprachregion, (c) bei tiefgelegenen Hirntumoren einschließlich Hirnstammtumoren und (d) bei infiltrativ wachsenden Tumoren zur Bestimmung der Tumorgrenzen. Die Verwendung von Hautklebemarkern (MKM-System) und eines Oberflächen-Anpassungsalgorithmus (Viewing Wand) zur Registrierung war mit einer Genauigkeit von 1 bis 2 mm Abweichung für die operative Entfernung aller intrakraniellen Tumoren ausreichend. Beide Systeme bestätigten sich als sichere und geeignete chirurgische Hilfsmittel unabhängig vom Alter der Patienten, der Lagerung des Patienten unter dem chirurgischen Eingriff und der Lokalisation der Raumforderung. Im Systemvergleich zeigte die Viewing Wand durch einen weiten Bewegungsraum des Pointers und der Möglichkeit einer dreidimensionalen Rekonstruktion der Hirnoberfläche Vorteile in der Entfernung von multiplen, in entfernten Hirnregionen gelegenen Tumoren sowie von solitären Prozessen in eloquenter Lokalisation. Das MKM-System war durch die Bereitstellung einer stereotaktischen Führung während des operativen Eingriffes in der Ansteuerung kleiner tiefgelegener Prozesse zu bevorzugen. Eine frühzeitige Liquordrainage führte zu einem brain shifting mit einer diskreten Unterschätzung der wirklichen Tiefe. Für eine genaue Festlegung der Tumorgrenzen von intraparenchymalen Tumoren waren beide Systeme vergleichbar geeignet. Das Relabieren von Hirngewebe in die Resektionshöhle führte jedoch in einigen Fällen von großen intraparenchymalen Tumoren bei beiden Systemen zu einer geringen Überschätzung der wirklichen Tumorgrenzen. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.