Touchant plus de 50 millions de personnes dans le monde, l’épilepsie est un problème majeur de santé publique. Un tiers des patients souffrent d’épilepsie pharmaco-résistante. Une chirurgie visant à enlever la région cérébrale à l’origine des crises – la zone épileptogène – est considérée comme l’option de référence pour rendre libre de crises ces patients. Le taux d’échec chirurgical non négligeable a poussé la recherche d’autres marqueurs. Un marqueur potentiel est les oscillations à haute fréquence (HFOs). Une HFO est une brève oscillation entre 80-500 Hz qui dure au moins 4 périodes enregistrée en EEG intracérébrale. Par leur caractère très bref, le marquage visuel de ces petites oscillations est fastidieux et chronophage.. Il semble impératif de trouver un moyen de détecter automatiquement ces oscillations pour étudier les HFOs sur des cohortes de patients. Aucun détecteur automatique existant ne fait cependant l’unanimité. Durant cette thèse, nous avons développé un nouveau moyen de visualiser les HFOs grâce à une normalisation originale de la transformée en ondelettes pour ensuite mieux les détecter automatiquement. Puis, nous avons mise en place une stratégie pour caractériser et valider des détecteurs. Enfin, nous avons appliqué le nouveau détecteur à une cohorte de patients pour déterminer la fiabilité des HFOs et des pointes épileptiques - le marqueur standard - dans la prédiction de la zone épileptogène. La conclusion de cette thèse est que les HFOs ne sont pas meilleurs que les pointes épileptiques pour prédire la zone épileptogène mais que combiner ces deux marqueurs permettait d’obtenir un marqueur plus robuste. / Epilepsy is a major health problem as it affects 50 million people worldwide. One third of the patients are resistant to medication. Surgical removal of the brain areas generating the seizure – the epileptogenic zone – is considered as the standard option for these patients to be seizure free. The non-negligible rate of surgical failure has led to seek other electrophysiological criteria. One putative marker is the high-frequency oscillations (HFOs).An HFO is a brief oscillation between 80-500 Hz lasting at least 4 periods recorded in intracerebral EEG. Due to their short-lasting nature, visually marking of these small oscillations is tedious and time-consuming. Automatically detecting these oscillations seems an imperative stage to study HFOs on cohorts of patients. There is however no general agreement on existing detectors.In this thesis, we developed a new way of representing HFOs thanks to a novel normalisation of the wavelet transform and to use this representation as a base for detecting HFOs automatically. We secondly designed a strategy to properly characterise and validate automated detectors. Finally, we characterised, in a cohort of patients, the reliability of HFOs and epileptic spikes - the standard marker - as predictors of the epileptogenic zone using the validated detector. The conclusion of this thesis is that HFOs are not better than epileptic spikes in predicting the epileptogenic zone but combining the two leads to a more robust biomarker.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-04-18T19:02:52Z No. of bitstreams: 1 PRISCILA MARQUES SOSA.pdf: 4777732 bytes, checksum: 5e904d610fde40315a7aeacae32f9d55 (MD5) / Made available in DSpace on 2016-04-18T19:02:52Z (GMT). No. of bitstreams: 1 PRISCILA MARQUES SOSA.pdf: 4777732 bytes, checksum: 5e904d610fde40315a7aeacae32f9d55 (MD5) Previous issue date: 2016-03-15 / O AVE é uma das principais causas de morte e incapacidade funcional em todo mundo, sendo dividido em dois subtipos: isquêmico, causado pela diminuição do fluxo sanguíneo; e hemorrágico, caracterizado pelo extravasamento de sangue nos tecidos encefálicos. Considerando a alta taxa de mortalidade e a gravidade das sequelas pós AVE, torna-se de extrema importância a busca por alvos terapêuticos que visem diminuir as sequelas causadas pelos quadros isquêmico e hemorrágico. Sendo assim, este estudo investigou os efeitos neuroprotetores do exercício físico (8 semanas previamente à lesão) em um quadro de AVE isquêmico (através da oclusão bilateral das artérias carótidas comuns) e os efeitos neuroprotetores da apocinina (posteriormente à lesão – 2, 6 e 24h – na dose 0,5mg/kg) em um quadro de AVE hemorrágico (através da infusão de colagenase no corpo estriado) em ratos Wistar. Para avaliar a função motora dos animais, foram utilizados os testes de Campo Aberto (CA), Rotarod (RR) e Escala de Déficit Neurológico (NDS), e, para avaliar o balanço redox estriatal, avaliamos a presença de EROs, TBARS (espécies reativas ao ácido tiobarbitúrico) e capacidade antioxidante total (FRAP). Nossos resultados mostraram que o exercício físico é uma estratégia parcialmente eficaz de proteção em um modelo de AVE isquêmico. No entanto, a apocinina não se mostrou uma estratégia de neuroproteção eficaz em um modelo de AVE hemorrágico. Estes resultados revelam a possibilidade da utilização do exercício físico como estratégia de neuroproteção. A apocinina, por sua vez, precisa ser melhor estudada em casos de AVE hemorrágico, considerando a investigação do seu mecanismo, doses e tempos de administração. / The stroke is one of the leading causes of death and disability worldwide, and is divided into two subtypes: ischemic, caused by a decreased on blood flow; and hemorrhagic, characterized by leakage of blood in brain tissue. Considering the high mortality rate and severity of post stroke sequelae, it is extremely important to search for therapeutic targets aimed at reducing the consequences caused by ischemic and hemorrhagic frames. Thus, this study investigated the neuroprotective effects of physical exercise (8 weeks prior to injury) in an ischemic stroke modle (by bilateral occlusion of the common carotid arteries) and the neuroprotective effects of apocynin (after the injury - 2, 6 and 24 hours - at a dose 0.5 mg/kg) in a hemorrhagic stroke model (by collagenase infusion into the striatum) in Wistar rats. Open Field (OF), Rotarod (RR) and Neurologic Disabilities Scale (NDS) were used to evaluate the motor function of the animals. To the striatal redox balance evaluation we assessed the presence of ROS, TBARS (reactive species to thiobarbituric acid) and total antioxidant capacity (FRAP). Our results showed that physical exercise is a partially effective strategy to protect against ischemic stroke. However, apocynin was not an effective neuroprotective strategy in a experimental model of hemorrhagic stroke. These results show the possibility of using exercise as a neuroprotective strategy. The apocynin need to be better studied in cases of hemorrhagic stroke, whereas the investigation of its mechanism, dosages and times of administration.

Role of blood biomarkers in spontaneous intracerebral hemorrhage Background: The study of blood biomarkers can offer new possibilities in diagnostics, prognostication, determination of etiology, and management of spontaneous intracerebral hemorrhage. The aim of our study was to assess the relationship between a panel of selected blood biomarkers and clinical and radiodiagnostic parameters in patients with spontaneous intracerebral hemorrhage. Primarily, the aim was to find a prognostic biomarker which could help in deciding on the optimal categorization of treatment. Patients and methods: A total of 70 patients were prospectively included in this study. The following blood biomarkers were determined: glial fibrillary acidic protein, S100B protein, matrix metalloproteinase 9, interleukin 6, interleukin 10, 25-hydroxyvitamin D, 1,25- dihydroxyvitamin D, total cholesterol, leukocyte counts, blood glucose and C-reactive protein. These were then correlated with selected clinical and radiodiagnostic parameters. Results: Relative to hematoma volume a statistically significant positive correlation was found for S100B, interleukin 10, interleukin 6 and blood glucose (S100B: ρ= 0,54, p< 0,001, IL-10: ρ= 0,43, p< 0,001, IL-6: ρ= 0,26, p= 0,027, blood glucose: ρ= 0,24, p= 0,045). Using multivariate analysis, a...

Cette étude a été divisée en 2 parties principales. Dans la première partie, nous examinons la relation entre l'activité des sources neuronales et les HFOs observés sur les électrodes intracérébrales. La deuxième partie traite de l'étude des conditions d'observabilité des HFO sur les électrodes du cuir chevelu. Les simulations ont montré que le modèle de champ neuronal proposé est capable de générer des HFOs montrant une forte ressemblance avec les signaux réels dans les deux cas EEG (cuir chevelu) et SEEG (intracérébral). De plus, nous avons pu relier les mécanismes physiopathologiques (GABA dépolarisant, inhibition directe, activité désynchronisée des populations neuronales) aux différentes caractéristiques morphologiques et spectrales des HFOs intracérébrales. Une hypothèse unifiée pour la production des HFOs et des pointes intercritiques est également formulée. Enfin, nous avons réussi à établir les conditions nécessaires sur l'activité temporelle et l'organisation spatiale des sources neuronales pour observer des HFOs sur les électrodes intracérébrales.En ce qui concerne la deuxième partie, la baisse inexpliquée de fréquence dans les HFOs collectées sur les électrodes du cuir chevelu a été abordée. Nous avons constaté que les mécanismes «non oscillatoires» de la génération de HFOs sont à l'origine de la faible fréquence (<200Hz) des HFOs du cuir chevelu et que le rapport signal / bruit (SNR) influe fortement sur la fréquence des oscillations. De plus, nous avons étudié la topographie des HFOs sur les électrodes du cuir chevelu et analysé comment cette topographie est affectée par différents paramètres (étendue spatiale épileptique, SNR, géométrie 3D). Enfin, nous avons montré que les HFOs du cuir chevelu peuvent être utilisés efficacement pour identifier la zone épileptique lorsque le rapport signal sur bruit des signaux enregistrés est suffisamment élevé. Une perspective de ce travail est l'identification non-invasive de la zone épileptique sans la nécessité d'enregistrements intracérébraux pré-chirurgicaux.Pour les deux études (HFO observés sur les électrodes intracérébrales et du cuir chevelu), un logiciel original et convivial a été développé. Ce logiciel a fortement facilité la simulation des signaux dans l'environnement cerveau/électrode virtuel, signaux obtenus en résolvant le problème direct de l’EEG (projection de la contribution électrique des sources neuronales sur les capteurs). / This study was divided into 2 main parts. In the first part, we address the relationship between the activity of neuronal sources and the HFOs observed on intracerebral electrodes. The second part deals with the investigation of observability conditions of HFOs on scalp electrodes. Simulations showed that the proposed neural field model is capable of generating HFOs showing strong resemblance with real signals in both cases EEG (scalp) and SEEG (intracerebral). Moreover, we were able to relate the pathophysiological mechanisms (depolarizing GABA, feedforward inhibition, desynchronized activity of neuronal populations) to different morphological and spectral features of intracerebral HFOs. A unified hypothesis for generation of HFOs and interictal spikes is also formulated. Finally, we managed to establish the necessary conditions about the temporal activity and the spatial organization of neuronal sources and about for HFOs to be observed on intracerebral electrodes. Regarding the second part, the unexplained drop in frequency in the collected HFOs on scalp electrodes was addressed. We found that the “non-oscillatory” mechanisms of the HFO generation is behind the low frequency (<200Hz) in scalp HFOs and that signal to noise ratio (SNR) heavily impacts the frequency of the oscillations. Moreover, we studied the topography of HFOS on scalp electrodes and analyzed how this topography is affected by different parameters (epileptic spatial extent, SNR, 3D geometry). Finally we showed that scalp HFOs can be effectively used to identify the epileptic zone when the SNR of the recorded signals is sufficiently high. A perspective to this work is the non-invasive identification of epileptic zone without the need for presurgical intracerebral recordings. For the purpose of both studies (HFOs observed on intracerebral & scalp electrodes) an original and user-friendly software package was developed. This software strongly facilitated the simulation of signals in the virtual brain/electrode environment obtained by solving the (S)EEG forward problem (projection of the electric contribution of neuronal sources onto electrode contacts).

Background: Cerebral small vessel disease (SVD) causes substantial cognitive, psychiatric and physical disabilities. Despite its common nature, SVD pathogenesis and molecular mechanisms remain poorly understood, and prevention and treatment are probably suboptimal. Identifying the genetic determinants of SVD will improve understanding and may help identify novel treatment targets. The aim of this thesis is to better understand genetic associations with SVD through investigating its pathological, radiological and clinical phenotypes. Methods: To unravel the genetic associations with SVD, I used three complementary approaches. First, I performed a systematic review looking at existing intracerebral haemorrhage (ICH) classification systems and their reliability, to help inform future studies of ICH genetics. Second, I performed a series of systematic reviews and meta-analyses, investigating associations between genetic polymorphisms and histopathologically confirmed cerebral amyloid angiopathy (CAA). Third, I performed meta-analyses of existing genome-wide datasets to determine associations of >1000 common single nucleotide polymorphisms (SNP) in the COL4A1/COL4A2 genomic region with clinico-radiological SVD phenotypes: ICH and its subtypes, ischaemic stroke and its subtypes, and white matter hyperintensities. Results: The reliability of existing ICH classification systems appeared excellent in eight studies conducted in specialist centres with experienced raters, although these existing systems have several limitations. In my systematic evaluation of CAA genetics, meta-analyses of 24 studies including 3520 participants showed robust evidence for a dose-dependent association between APOE ɛ4 and histopathological CAA. There was, however, no convincing association between APOE ɛ2 and presence of CAA in a meta-analysis of 11 studies including 1640 participants. Meta-analyses of five studies including 497 participants showed, contrary to an existing popular hypothesis, that while APOE 4 may increase the risk of developing severe CAA vasculopathy, there is no clear evidence to support a role of ɛ2. There were few data about the role of APOE in hereditary CAA, but in the three studies that had looked at this, there was no evidence for an association between APOE ɛ4 and CAA severity. There were too few studies and participants to draw firm conclusions about the effect of non-APOE ε2/ε3/ε4 genetic polymorphisms on CAA, but there were positive associations with TGF-β1, TOMM40 and CR1 genes in four studies. Finally, in my meta-analyses of the COL4A1/COL4A2 genomic region, three intronic SNPs in COL4A2 were associated with SVD phenotypes: significantly with deep ICH, and suggestively with lacunar ischaemic stroke and WMH. Conclusions: I have shown that while existing ICH classification systems appear to have very good reliability, further research is needed to determine their performance in different settings. For large population-based prospective studies of ICH genetics, anatomical systems are likely to be more feasible, scalable and appropriate, although they have limitations and will need to be further developed. Using systematic reviews and meta-analyses, I have confirmed a dose-related association between APOE ɛ4 and histopathological CAA, but also demonstrated that, despite popular acceptance, there is insufficient data to draw firm conclusions about the association with APOE ɛ2. I found some positive associations with CAA in other genes, which merit replication in further larger studies, and showed that there is currently insufficient data about the role of APOE in hereditary CAA. Finally, I identified a novel association between a locus in a known hereditary SVD gene – COL4A2 – and sporadic SVD. This highlights a new and successful approach for selecting candidate genes and can be expanded in future studies to include other known hereditary SVD genes.

Purpose: Traumatic brain injury (TBI) leads to important and deleterious neuroinflammation, as evidenced by edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. Strategies that block inflammatory and oxidative mediators have been shown to induce neuroprotective and anti-inflammatory effects after brain injury. After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation. In this study, we hypothesized that cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation after TBI and, in conjunction with leukocytes, represent a key cellular target for statin therapy. We investigated the effect of acute and continuous treatment of simvastatin on behavior and inflammation in adult rats following experimental TBI. Materials and Methods: Cortical contusions were induced using a device adapted from the impact method. There were 3 groups: (1) sham group, craniotomy only; (2) control group, TBI without treatment; and (3) treatment group, TBI with simvastatin administration. The treatment group received 15 mg/kg of simvastatin daily for 3 days. Neurological function was assessed with the grip test (Grip strength meter, Singa). Results: Non-treatment control group had a significantly greater increase in ICAM-1 expression from pre-injury to the post-injury 72 h time point, compared to the simvastatin treatment group. The treatment group had a significantly smaller amount of reduction in successful trials in grip test than the control group did from baseline to 72 h. The analysis of western blot and pathological study also demonstrated similar results. Conclusion: Our findings indicate that continuous administration of simvastatin after injury attenuates the cerebral vascular endothelial inflammatory response and improves functional and histological outcomes in a rat model of TBI. This improvement is associated with a reduction in expression of ICAM-1 in the blood and brain after rat TBI when compared with the untreated control group. Hence, we recommend simvastatin administration in the first 72 h following TBI.

Thesis (Ph.D.)--Ohio University, November, 2007. / Abstract only has been uploaded to OhioLINK. Includes bibliographical references (leaves 155-178)

Thesis (M.Sc.)--Memorial University of Newfoundland, 2004. / Bibliography: leaves 45-56.

L’augmentation de la prévalence des hémorragies cérébrales (HC) sous traitement antithrombotique constitue un problème de Santé Publique à cause du mauvais pronostic vital et fonctionnel et du risque compétitif de récidive hémorragique ou ischémique chez les survivants, qui pose le problème d’une prévention secondaire adaptée._x000D_L’objectif de la thèse était d’étudier l’impact des traitements antithrombotiques sur le pronostic des HC. Le terme d’HC, entendu au sens large, regroupe les HC spontanées et les microhémorragies cérébrales.La première partie avait comme objectif de comparer les caractéristiques des HC survenant avec ou sans traitement par antagonistes de la vitamine K (AVK), stratifiant l’analyse selon la localisation de l’HC. L’analyse a porté sur 545 patients de la cohorte Lilloise (PITCH), parmi lesquels 83 (15%) étaient sous AVK. La prise d’un traitement par AVK n’influençait pas la localisation de l’HC, mais était prédictive d’HC plus volumineuses (25 ml vs 12 ; p=0.002) chez les victimes d’HC non lobaire, alors que aucune différence existait en cas d’HC lobaire (26 ml vs 30; p=0.507). Ces résultats suggèrent que l’impact des AVK diffère en fonction de la localisation de l’HC et de la vasculopathie sous-jacente.La deuxième partie avait comme objectif d’analyser l’impact du traitement antithrombotique sur l’apparition de nouvelles microhémorragies cérébrales stratifiant l’analyse selon la localisation de l’HC. L’étude a porté sur 168 survivants à 6 mois d’une HC (cohorte PITCH) ayant bénéficié d’une IRM cérébrale 1.5T lors de l’HC et durant le suivi. Lors de l’HC, 89 (53%) patients présentaient des microhémorragies, et 80 (48%) ont développé des microhémorragies durant le suivi. La présence sur la première IRM de microhémorragies (aOR 2,3; IC 95%1,2-4,3), leur position mixte, lobaire et profonde (aOR 3.7; IC95% 1,7-8,3), et la présence de séquelles de macrohémorragies (aOR 6,8; IC95% 2,8-16,7), étaient associées à l’apparition de microhémorragies. Chez les patients avec HC non lobaire, l’apparition de microhémorragies était associée à l’utilisation d’un traitement antithrombotique durant le suivi (aOR 2,9 ; IC95% 1,1-7,3) et avec l’apparition de lacunes (aOR: 2,9; 95%CI 1,0-7,8). Chez les patients avec HC lobaire, l’apparition de microhémorragies était associée à l’apparition de macrohémorragie (aOR 9.8 ; IC95% 1,1-88,8). Ces résultats suggèrent que l’impact des traitements antithrombotiques diffère en fonction de la vasculopathie sous-jacente.La troisième partie avait comme objectif de : (i) comparer les proportions de survivants d’une HC ayant une indication formelle au traitement antithrombotique chez lesquels ce traitement était repris à la sorite ; (ii) identifier les caractéristiques associées à la reprise du traitement antithrombotique, au sein de 5 cohortes européennes (Lille, n=542; Utrecht, n=389 ; Amsterdam, n= 403 ; Londres, n=667 ; Lothian, n=137). Un traitement antithrombotique était recommencé chez 96 (20%) des 469 survivants ayant une indication formelle, mais en proportions différentes dans les 5 cohortes (Lille 18%, Utrecht 45%, Amsterdam 30% ; Londres 11% ; Lothian 15%; p<0.001). Nous n’avons retrouvé aucun autre facteur prédictif de reprise du traitement antithrombotique en dehors de la cohorte d’origine. Ces résultats montrent que la décision de reprise du traitement antithrombotique ne repose pas sur des critères reproductibles, et soulignent la nécessité de réaliser des essais randomisés.La quatrième partie, actuellement en cours, prévoit d’évaluer chez ces mêmes patients (survivants d’une HC ayant une indication formelle au traitement antithrombotique) le risque de récidive hémorragique ou ischémique en fonction de la reprise ou de l’arrêt du traitement antithrombotique. Il s’agit d’une étude observationnelle portant sur 274 patients de 4 cohortes Européennes, avec un suivi d’environ 2.5 ans. L’analyse statistique est en cours. / The proportion of patients who are taking antithrombotic drugs at the time they suffer a spontaneous intracerebral hemorrhage (ICH) is increasing over time, and this is a major issue in public health because of the poor prognosis of patients. Also, the decision to restart or not antithrombotic drugs in survivors is still a clinical dilemma. _x000D_The aim of this work was to evaluate the impact of antithrombotic drugs on ICH prognosis. The term ICH regroups (i) spontaneous ICH and (ii) cerebral microbleeds (CMBs).As a first step, we compared baseline characteristics of 545 consecutive patients with ICH included in the PITCH cohort (Lille, France), receiving or not Vitamin K Antagonists (VKAs) at the time of ICH, stratifying the analysis according to the ICH location (lobar vs non lobar). VKAs-ICH accounted for 83 patients (15%). The use of VKAs did not influence ICH location, but influenced ICH volume: in non lobar ICH, VKAs use was associated with larger ICH volumes (25 ml versus 12 ml, p=0.002). In lobar ICH, no difference was observed (26ml versus 30ml; p=0.507). The different impact of VKAs on ICH volumes according to location suggests a different susceptibility of the underlying vasculopathies to VKAs.As a second step, we aimed to evaluate the impact of antithrombotic drugs on the incidence of CMBs in 168 ICH survivors from the PITCH cohort who underwent 1.5T Magnetic resonance imaging (MRI) at ICH onset and during follow-up, stratifying the analysis according to the index ICH location. At the time of ICH, 89 (53%) patients had CMBs at ICH onset, and 80 (48%) showed new CMBs during follow-up. Predictors of incident CMBs were the presence on the first MRI of: at least 1 CMB (aOR 2.3; 95% CI: 1.2-4.3), old macro-hemorrhage (aOR 6.8; 95%CI 2.8-16.7), and CMBs in mixed location (aOR 3.7; 95%CI 1.7-8.3). In non lobar ICH, incident CMBs were associated with incident lacunes (aOR: 2.9; 95%CI 1.0-7.8) and with the use of antiplatelet agents (aOR 2.9; 95%CI 1.1-7.3). In lobar ICH, incident CMBs were associated with incident macro-hemorrhage (aOR 9.8; 95%CI 1.1-88.8). These results suggest that the impact of antithrombotic drugs differs according to the index ICH location, and therefore according to the underlying vasculpathy.The third step consisted in comparing the characteristics and proportions of patients taking antithrombotic drugs at ICH discharge in five European cohorts (Lille, France, n=542; Utrecht, The Netherlands, n=389; Amsterdam, The Netherlands, n=403; multicenter UK cohort, n=667; Lothian, Scotland, n=137). We then identified characteristics associated with restarting. Antithrombotic drugs were restarted in 96 (20%) of the 469 survivors who had an indication for antithrombotic drugs (secondary prevention or atrial fibrillation), but in different proportions according to the cohort of origin (Lille 18%, Utrecht 45%, Amsterdam 30%, CROMIS-2 ICH 11%, Lothian 15%; p<0.001). We did not find other consistent associations with restarting antithrombotic drugs. The variation in clinical practice in restarting antithrombotic drugs after ICH supports the need for randomized controlled trials.In the fourth step, we aim to analyse the risk of ICH recurrences or ischemic events in the same population of patients (ICH survivors who suffered from ICH while on antithrombotic drugs because of secondary prevention or atrial fibrillation) according to the antithrombotic drug status during follow-up. We included 274 patients from 4 European cohorts, with a median follow-up of 2.5 years. Statistical analysis is ongoing.

Ce travail de thèse a pour objectif de préciser le rôle du cortex operculo-insulaire dans la somesthésie et la douleur chez l'Homme à l'aide d'études réalisées par stimulations électriques intracérébrales et en IRM fonctionnelle (IRMf). Deux secteurs fonctionnels distincts ont été mis en évidence; d'une part l'insula dont 60% des stimulations induisent des réponses somato-sensitives dont 10% sont douloureuses, où il existe une localisation préférentiellement postérieure des sites de stimulation donnant lieu à une réponse douloureuse et un décrément antéro-postérieur du seuil de déclenchement d'une réponse douloureuse, dont les champs récepteurs couvrent de larges surfaces cutanées, et où les réponses douloureuses ont une organisation somatotopique grossière ; d'autre part l'aire SII dont la stimulation induit quasi exclusivement des réponses somato-sensitives dont 10% sont douloureuses, sur des surfaces cutanées plus restreintes. SII et l'insula postérieure sont les deux seules régions corticales dont la stimulation est capable d'induire une sensation douloureuse. Une ségrégation fonctionnelle au sein de SII et de l'insula a été montrée en IRMf, par l'existence de patterns spécifiques d'activation pour chaque modalité sensitive, comprenant des sous- régions dont l'activation semble spécifique de la sensation douloureuse. Ceci confère à ces régions une originalité toute particulière au sein de la matrice douleur, puisqu'il semble qu'elles seules puissent activer le réseau fonctionnel des aires impliquées dans la sensation douloureuse et ainsi permettre 'l'expérience' de la douleur / This work aims at assessing the role of operculo-insular cortex in somesthesia and pain in Humans, using intracerebral electrical stimulations and fMRI. Two distinct functional zones were highlighted; the insular cortex on one hand, in which 60% of stimulations induced somato-sensory responses (10% painful), with a clear antero-posterior gradient in terms of localization and pain stimulation threshold, and where receptive fields were large and pain evoked sensations showed a rough somatotopic organization. The inner part of the parietal operculum (second somatosensory area SII) on the other hand, where electrical stimulation induced almost exclusively somato-sensory sensations, of which 10% were painful, in more restricted cutaneous territories. SII and posterior insula are the only cortical regions where electrical stimulation can elicit painful sensation. Functional segregation in SII and insula was found using fMRI, showing that specific patterns of activation do exist, depending on the type of somato-sensory stimulations, including sub-regions specifically activated during pain stimulation. These characteristics confer to these regions a crucial and special role, which consists in triggering the building of pain 'experience' by the pain matrix