L’un des aspects les plus critiques dans les planifications dosimétriques des traitements par radiothérapie est la délinéation des limites de la tumeur. Cette délinéation se fait généralement sur les images anatomiques de tomodensitométrie (TDM). Mais récemment, il est recommandé de faire cette délinéation pour les cancers broncho-pulmonaires non à petites cellules (CBNPC) sur les images fonctionnelles de Tomographie par Émission de Positon (TEP) pour prendre en compte les caractéristiques biologiques de la cible. Jusqu’à ce jour, aucune technique de segmentation ne s’est révélée satisfaisante pour les images TEP en application clinique. Une solution pour ce problème est proposée dans cette étude. Méthodes : Les optimisations de notre méthode ont consisté principalement à faire l’ajustement des seuils directement à partir des corps des patients au lieu de le faire à partir du fantôme. Résultats : Pour les lésions de grands axes supérieurs à 20 mm, notre technique de segmentation a montré une bonne estimation des mesures histologiques (la moyenne de différence de diamètre entre données mesurées et déterminées avec notre technique = +1,5 ± 8,4 %) et une estimation acceptable des mesures TDM. Pour les lésions de grands axes inférieurs ou égaux à 20 mm, cette méthode a montré un écart avec les mesures dérivées des données histologiques ou bien des données TDM. Conclusion : Cette nouvelle méthode d’ajustement montre une bonne précision pour la délimitation des lésions de grands axes compris entre 2 et 4,5 cm. Néanmoins, elle n’évalue pas correctement les lésions les plus petites, cela peut être dû à l’effet du volume partiel / Tumor delineation is a critical aspect in radiotherapy planning treatment and is usually performed on the anatomical images of a computed tomography (CT) scan. Recently, for non-small cell lung cancer, it has been recommended to use functional Positron Emission Tomography (PET) images to take into account the target biological characteristics. However, today, there is no satisfactory segmentation technique for PET images in clinical applications. In the present study, a solution of this problem is proposed. Methods: The optimizations of tumor delineation consisted primarily on the thresholds adjustment directly from patients, rather than phantoms. The development and the validation of this adjustment were done by comparing segmented lesions on PET images with two different gold standards: measurements performed on CT images of the selected lesions and histological measurements of surgically removed tumors. Results: For lesions greater than 20 mm, our segmentation technique showed very good estimation of histological measurements (mean difference diameter between measured and calculated data equal to +1.5 ± 8.4 %) and an acceptable estimation of CT measurements. For lesions smaller or equal to 20 mm, the method showed a large gap with the measurements derived from histological or CT data. Conclusion: This novel segmentation technique shows very high accuracy for the lesions of large axes between 2 and 4.5 cm. Nevertheless, it does not correctly evaluate smaller lesions probably because of the partial volume effect

Uma investigação experimental sobre a influência da estimulação elétrica direta na regeneração do nervo usando uma lesão por esmagamento do nervo ciático de ratos como modelo foi realizada. Quarenta e dois ratos foram utilizados e divididos em quatro grupos, de acordo com o procedimento: 1) Sem lesão e sem estimulação; 2) lesão por esmagamento, sem estimulação; 3) sem lesão, com estimulação; 4) lesão por esmagamento, com estimulação. O nervo ciático foi exposto através de uma incisão lateral na coxa direita e submetido à lesão por esmagamento numa máquina universal de testes com uma carga de 15.000 g concentrada em um segmento de 5 mm por 10 minutos, nos grupos 2 e 4. Um estimulador elétrico foi desenvolvido para liberar uma corrente elétrica contínua de baixa intensidade (1 &#956A). O mesmo foi implantado no espaço subcutâneo próximo a coluna lombar, o ânodo foi colocado proximalmente e o catôdo distalmente ao esmagamento. A recuperação funcional foi avaliada em intervalos semanais até o 21º dia pós-operatório, através do Índice Funcional do Ciático (IFC) e calculada por um programa específico, apresentando melhora progressiva em ambos os grupos com lesão por esmagamento, porém mais acentuada naqueles com estimulação elétrica. Os animais foram sacrificados no 21º dia pós-operatório para análise histológica e morfométrica dos nervos, onde os resultados mostraram aumento da densidade das fibras nervosas mas decréscimo do diâmetro das fibras nervosas, assim como um aumento no número e diâmetro dos vasos sangüíneos intra e extra~fasciculares no grupo estimulado. Similar, mas um menos evidente fenômeno foi observado no grupo sem lesão por esmagamento mas com estimulação elétrica. Concluiu-se que a estimulação elétrica direta de baixa intensidade provoca a regeneração nervosa após lesão por esmagamento em condições controladas e que o IFC é um método confiável para avaliar a recuperação nervosa uma vez que seus resultados aproximam-se do estudo morfométrico. / An experimental investigation of the influence of direct electrical stimulation on nerve regeneration using a crush injury of the sciatic nerve of rats as model was undertaken. Forty two rats were used and divided into four groups according to the procedure carried out: 1) no injury, no stimulation; 2) crush injury, no stimulation; 3) no injury, stimulation; 4) crush injury, stimulation. The sciatic nerve was exposed through a lateral incision on the Iight thigh and submitted to a crush injury in an universal testing machine with a 15000 g load concentrated on a 5 mm-long segment for 10 minutes, in groups 2 and 4. An electrical stimulator was developed to deliver a continuous direct low intensity electrical current (1 &#956A). The device was implanted into the subcutaneous space near the lumbar spine, the anode placed proximally and the cathode distally to the crush injury. Functional recovery was checked at weekly intervals up to the 21st postoperative day, by means of the Sciatic Functional Index (SFI) as calculated by a specific software and showed progressive improvement in both groups with crush injury but more marked in that with electrical stimulation (4). The animals were killed on the 21st post operative day for morphometric and histological examination of the nerves, whose results showed an increased nerve fiber density but decreased nerve fíber diameter, as well as increased number and diameter of intra and extrafascicular blood vessels in the stimulated group. Similar but less marked phenomena were observed in the group without crush injury but with electrical stimulation. It was concluded that low intensity direct electrical stimulation enhances nerve regeneration followíng a crush injury in controlled conditions and that the SFI is a reliable method to evaluate the nerve recovery since its results closely matched those of the morphometric study.

Diversos estudos sugerem que as células-tronco da medula óssea podem ser úteis no tratamento de lesões do tecido nervoso. O presente estudo investigou se a terapia com células medulares seria capaz de modificar os efeitos comportamentais de lesões no hipocampo. Células mononucleares da medula óssea marcadas com a proteína fluorescente verde (EGFP) foram transplantadas em camundongos C57BL/6 que tiveram o hipocampo dorsal danificado por lesão eletrolítica bilateral. Os resultados da avaliação comportamental no labirinto em cruz elevado mostraram que a lesão hipocampal produziu ansiólise, quadro que foi atenuado nos animais transplantados. Na análise imuno-histoquímica do tecido cerebral, foi observada presença limitada de células EGFP+ no cérebro dos animais lesionados. Dada a não recuperação da citoarquitetura tissular, acredita-se que os benefícios observados sobre o comportamento tenham resultado de um efeito parácrino das células mononucleares, que auxiliaram na ação de mecanismos endógenos para restituição parcial das funções do hipocampo. / Several studies suggest that stem cells from bone marrow may be useful in treating lesions of the nervous tissue. This study investigated if bone marrow cell therapy would be able to modify the behavioral effects of lesions in the hippocampus. Bone marrow mononuclear cells labeled with the enhanced green fluorescent protein (EGFP) were transplanted into C57BL/6 mice which had the dorsal hippocampus damaged by bilateral electrolytic lesion. The results of the behavioral assessment in the elevated plus-maze showed that the hippocampal lesion produced anxiolysis, an effect that was attenuated in transplanted animals. Immunohistochemical analysis of brain tissue revealed, however, a limited presence of EGFP+ cells into the brains of injured animals. Given the non-recovery of the tissue cytoarchitecture, it is believed that the observed benefits on the behavior resulted from a paracrine effect of the mononuclear cells, which possibly helped in the action of endogenous mechanisms for partial reimbursement of the hippocampal functions.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-06-26T19:30:57Z No. of bitstreams: 1 Stelmo.pdf: 9433038 bytes, checksum: 2b73bb4f0f32aec1145044fb676465e6 (MD5) / Made available in DSpace on 2017-06-26T19:30:57Z (GMT). No. of bitstreams: 1 Stelmo.pdf: 9433038 bytes, checksum: 2b73bb4f0f32aec1145044fb676465e6 (MD5) Previous issue date: 2016-10-17 / Lung cancer is one of the most common types of cancer around the world. Temporal evaluation has become a very useful tool when to whoever needs to analyze a lung lesion. The analysis occurs when a malignant lesion is under treatment or when there are indeterminate lesions, but they are probably benign. The objective from this work is to develop computational methods to detect, quantify and analyze local and global density changes of pulmonary lesions over time. Thus, it were developed four groups of methods to perform this task. The rst identi es local density changes and it has been denominated voxel-based. The second one is composed of the Jensen divergence and the hypothesis test with global and local approaches. Similarly, the third group has only one method, the principal component analysis. The last group has one method, it has been denominated modi ed quality threshold, and identi es the local density changes. In order to reach the objectives, it was proposed a methodology composed of ve steps: The rst step consists in image acquisition of the lesion at various instants. Two image databases were acquired and two models of lesions were created to evaluate the methods. The rst database has 24 lesions under treatment (public database) and the second has 13 benign nodules (private database) in monitoring. The second step refers to rigid registration of the lesion images. The next step is to apply the proposed four groups of methods. As a result, the second group of methods detected more density changes than the fourth group, which in turn, this latter detected more regions than the rst group and this more than the third group, for the public database. For the private database, the fourth group of density change methods detected more regions than the rst group. The third group detected few regions of changes when compared to the rst group and the second group had the lowest number of detected regions. In addition to the density changes found, the proposed classi cation model with texture features had accuracy above 98% in the diagnosis prediction. The results state that there are changes in both databases. However, the detected changes for each group of methods have di erent intensity and location to the databases. This conclusion is based from high accuracy that was obtained from the prediction of the lesion diagnosis from both databases. / O câncer de pulmão é um dos tipos de câncer de maior incidência no mundo. A avaliação temporal aparece como ferramenta bastante útil quando se deseja analisar uma lesão. A análise pode ocorrer quando uma lesão maligna está em tratamento ou quando surgem lesões indeterminadas, mas essas são provavelmente benignas. O objetivo deste trabalho é desenvolver métodos computacionais para detectar, quantifi car e analisar mudanças de densidade locais e globais das lesões pulmonares ao longo do tempo. Desta forma, foram desenvolvidos quatro conjuntos de métodos para realização da tarefa de detectar mudanças de densidade em lesões pulmonares. O primeiro conjunto identifi ca mudanças de densidade locais e foi denominado de métodos baseados em voxel. O segundo conjunto é composto da divergência de Jensen e do teste de hipótese com abordagens locais e globais. Com o mesmo propósito de detectar mudanças de densidade locais em lesões pulmonares, o terceiro conjunto possui um único método, a análise de componentes principais. O último conjunto também possui um único método, denominado de quality threshold modi ficado e identifi ca as mudanças locais de densidade. Para cumprir o objetivo deste trabalho, propõe-se uma metodologia composta de cinco etapas. A primeira etapa consiste na aquisição das imagens da lesão em diversos instantes. Duas bases de lesões foram utilizadas e dois modelos de lesões foram propostos para avaliação dos métodos. A primeira base possui 24 lesões em tratamento (base pública) e a segunda possui 13 nódulos benignos (base privada) em acompanhamento. A segunda etapa corresponde ao registro rígido das imagens da lesão. A próxima etapa é a aplicação dos quatro conjuntos de métodos propostos. Como resultado, o segundo conjunto de métodos detectou mais mudanças de densidade que o quarto conjunto, que por sua vez, este ultimo detectou mais regões que o primeiro conjunto e este mais que o terceiro conjunto, para a base pública de lesões. Em relação a base privada, o quarto conjunto de métodos detectou mais regiões de mudança de densidade que o primeiro conjunto. O terceiro conjunto detectou menos regiões de mudança quando comparado ao primeiro conjunto e o segundo conjunto teve o menor n úmero de regiões detectadas. Em adição às mudanças de densidade encontradas, o modelo de classi ficação proposto com medidas clássicas de textura para predição do diagnóstico da lesão teve acurácia acima de 98%. Os resultados encontrados indicam que existem mudanças de densidade em ambas as bases de lesões pulmonares. Entretanto, as mudanças detectadas por cada um dos métodos propostos possuem características de intensidade e localização diferentes em ambas as bases. Essa conclusão é motivada pela alta acurácia obtida em seu diagnóstico para as bases utilizadas.

O presente estudo teve como objetivo avaliar o impacto de um modelo 3D, sobre a formação e progressão de lesões de cárie como objeto de aprendizagem, no desempenho teórico/prático e grau de satisfação de alunos de graduação em odontologia de diferentes contextos, na detecção de lesões de cárie utilizando o ICDAS. Foi conduzido um estudo multicêntrico controlado randomizado envolvendo uma amostra por conveniência de alunos de graduação em odontologia de cinco instituições (1 nacional e 4 internacionais). Inicialmente, os alunos receberam uma aula teórica tradicional e responderam uma primeira avaliação teórica. Posteriormente, foram aleatoriamente alocados em dois grupos: 1) grupo teste: que recebeu uma aula teórica tradicional expositiva mais acesso ao modelo 3D e 2) grupo controle: que recebeu unicamente a aula teórica tradicional expositiva. Depois, os alunos do grupo controle saíram da sala e um vídeo de 6 minutos (modelo 3D) foi projetado. Após o vídeo os alunos do grupo controle regressaram à sala e ambos os grupos foram submetidos a uma avaliação teórico/prática com o propósito de avaliar o desempenho após a intervenção e grau de satisfação da atividade. Análises de regressão linear e de Poisson multinível foram realizadas para analisar o impacto do objeto de aprendizagem no desempenho teórico-prático do aluno. Análises descritivas foram realizadas para avaliar o grau de satisfação do aluno. Um total de 307 alunos participou do estudo. Alunos que tiveram melhor desempenho na avaliação teórica inicial obtiveram melhores notas na média teórica final (OR=1,11; 95%IC=1,02-1,21). Alunos do grupo teste tiveram um melhor desempenho teórico em comparação com os do grupo controle (p=0,04), principalmente para questões relacionadas à correlação histológica do ICDAS com características clínicas dos diferentes estágios de progressão. Não houve diferença estatisticamente significante na avaliação prática entre grupos e, um alto nível de satisfação da atividade foi observado na amostra. Conclui-se que, a atividade avaliada teve um impacto satisfatório no desenvolvimento de competências teóricas relacionadas à detecção de lesões de cárie utilizando o ICDAS. / This study aimed at evaluating the impact of a 3D model as a learning object in the training/teaching and satisfaction degree of undergraduate dental students from different contexts for the detection of caries lesions using the ICDAS. A multicenter controlled randomized trial was conducted, involving a convenience sample of undergraduate dental students from five institutions (1 national and 4 international). Firstly, students attended a traditional theoretical lecture and answered a first theoretical test. Then, they were randomly allocated into two groups as follows: 1) test group: receiving the theoretical lecture and accessing the 3D model, and 2) control group: receiving the theoretical lecture only. Afterwards, control group students left the room and a 6-minute video was projected (3D model). Once the video had finished, control group students returned to the room and both groups were submitted to a theoretical/practical test to evaluate their performance after intervention as well as their satisfaction degree. Multilevel linear and Poisson regression analyses were done, to analyze the learning object impact in the students´ theoretical/practical performance. Descriptive analyses were conducted to assess the students´ satisfaction degree. Three hundred and seven students participated. Those having a better performance in the initial theoretical test also had better grades in the final theoretical assessment (OR=1,11; 95%IC=1,02-1,21). Test group students had a better theoretical performance in comparison to control group ones (p=0,04), mainly in relation to questions regarding the ICDAS histological correlation with clinical features on each severity caries stage. There were no statistically significant differences regarding practical assessment between groups, and a high level of activity satisfaction was observed. In conclusion, the assessed activity had a satisfactory impact in the developing of theoretical skills in relation to the detection of caries lesions using the ICDAS.

At any given time, 3-9% of the general population experiences a voice problem. The incidence of voice disorders in children can vary anywhere between 6 and 23%, yet, only 2-4% of the population are seen by speech-language pathologists for further assessment and treatment. Voice disorders have negative effects on the social, emotional, and physical functioning of the child. Unfortunately, there is little known about the appropriate management of children with voice disorders. Depending on the nature of the voice disorder, different approaches, including behavioral voice therapy, vocal hygiene management, or medical intervention, are available. However, a concern with behavioral voice therapy is the ability of the child to transfer skills learned in clinic to an outside setting - limiting generalization and adaptation of the new behavioral approach. Biofeedback has been successfully used in adults with voice disorders to help generalize new vocal behaviors. Such data is lacking in the treatment of voice problems in the pediatric population. The current case study aimed to understand the use of biofeedback in an eight-year-old male who was diagnosed with a unilateral vocal fold lesion, who exhibited difficulty maintaining and generalizing his new vocal behaviors. It was hypothesized that the child would benefit from biofeedback and would maintain new vocal behaviors including the use of a safe and efficient voice pattern outside the clinic setting. Longitudinal data on vocal parameters including the pitch, loudness, and vocal fold vibration were obtained over a period of five weeks using an ambulation phonation monitor (APM). The APM uses an accelerometer attached to the sternal notch and measures pitch, loudness, and vocal fold vibration, which helps determine an individual’s daily voice use pattern and thereby determines the appropriate biofeedback setting. The five week period included (a) a week of pretesting, (b) two weeks of biofeedback, (c) a week of post-testing immediately following the week of biofeedback, and (d) a generalization testing two months post-study. During the five-week period, vocal parameters were monitored for an average of 7- 10 hours for 2-3 days each week. On weeks two and three, the child was provided with biofeedback on loudness levels based on his data from the pretesting week. Results indicated change in vocal parameters including loudness and vocal fold vibration patterns during the weeks of biofeedback. However, such generalization was not observed neither during immediate post feedback monitoring nor two months following the study protocol. Such data provide immediate effects from biofeedback on vocal behavior, however, motor learning principles, dose, and frequency of biofeedback will be discussed to further understand the long-term effects of biofeedback in children with voice problems.

Cette thèse porte sur la segmentation des tumeurs du foie sur des images tomodensitométriques. Ce sujet présente un intérêt certain pour le domaine médical puisque les médecins pourraient ainsi bénéficier d'une méthode reproductible et fiable pour segmenter de telles lésions. Une segmentation précise des tumeurs du foie permettrait en effet d'aider les médecins lors de l'évaluation des lésions (détection, localisation, quantification), du choix d'un traitement, et de sa planification. Les méthodes développées dans ce cadre doivent faire face à trois principales difficultés scientifiques: (i) la grande variabilité de l'apparence et de la forme des structures recherchées, (ii) leur ressemblance avec les régions environnantes et finalement (iii) la faiblesse du rapport signal sur bruit observé dans les images dans lesquelles on travaille. Ce problème est abordé dans une optique d'application clinique et est résolu en suivant une approche en deux temps commençant par le calcul d'une enveloppe du foie, avant de segmenter les tumeurs présentes à l'intérieur de cette enveloppe. Nous commençons par proposer une approche basée sur des atlas pour le calcul d'une enveloppe des foies pathologiques. Tout d'abord, un outil de traitement d'image a été développé pour calculer une enveloppe autour d'un masque binaire, afin d'essayer d'obtenir une enveloppe du foie à partir d'une estimation du parenchyme sain. Un nouvel atlas statistique a ensuite été introduit, puis utilise pour la segmentation à travers son recalage difféomorphique avec une image. La segmentation est finalement réalisée en combinant les coûts d'appariement des images avec des a priori spatiaux et d'apparence, le tout en suivant une approche multi échelle basée sur des MRFs. La deuxième étape de notre approche porte sur la segmentation des lésions continues dans ces enveloppes en combinant des techniques d'apprentissage par ordinateur avec de méthodes basées sur des graphes. Un espace d'attributs approprié est tout d'abord défini en considérant des descripteurs de textures déterminés à travers des filtres de diverses tailles et orientations. Des méthodes avancées d'apprentissage automatique sont ensuite utilisées pour déterminer les attributs pertinents, ainsi que l'hyperplan qui sépare les voxels tumoraux des voxels correspondant à des tissus sains dans cet espace d'attributs. Pour finir, la segmentation est réalisée en minimisant une énergie sous forme de MRF, laquelle combine les probabilités d'appartenance de chaque voxel à une classe, avec celles de ses voisins. Des résultats prometteurs montrent les potentiels de notre méthode.

Η αθηροσκλήρυνση είναι μια παθολογική διαδικασία η οποία λαμβάνει χώρα στις μεγάλες αρτηρίες και αποτελεί την υποκείμενη αιτία καρδιαγγειακών συμβαμάτων, εγκεφαλικών επεισοδίων και περιφερικής αρτηριακής νόσου. Η τυπική αθηροσκληρυντική βλάβη αποτελείται από έναν λιπιδικό πυρήνα που καλύπτεται από ινώδες περίβλημα. Ορισμένοι «ευάλωτοι» ασθενείς εμφανίζουν σε μεγάλο ποσοστό τις λεγόμενες «ασταθείς» βλάβες. Αυτές είναι αλλοιώσεις που έχουν την τάση να ρήγνυνται με αποτέλεσμα το σχηματισμό θρόμβου ο οποίος μερικά ή ολικά αποφράσσει την κυκλοφορία. Στην εργασία αυτή μελετώνται η παθοφυσιολογία του φαινομένου και οι παράγοντες που σχετίζονται με την τοπική και συστηματική βιολογία και συμμετέχουν στην αστάθεια και ρήξη της πλάκας. / Atherosclerosis is a pathological process that takes place in the large arteries and constitutes the amenable cause of cardiovascular events, cerebrovascular accidents and peripheral arterial disease. The typical atherosclerotic lesion is constituted by ljpid core that is covered by fibrous cap. Certain \"sensitive\" patients have the predisposition to develop the so - called \"unstable\" lesions. These are alterations that have the tendency to rupture resulting to the formation of clot which occludes the vessel partially or totally. This work studies the pathophysiology of phenomenon and the factors that are related with the local and systematic biology and participate in the instability and rupture of plaque.

No description available.

L’habenula, un noyau épithalamique, est située au centre de la voie dorsale diencéphalique. Cette voie relie les structures limbiques et les ganglions de la base aux cellules monoaminergiques du mésencéphale. En particulier, l’habenula latérale (HbL) projette directement aux cellules dopaminergiques et GABAergiques de l’aire tegmentale ventrale (ATV). L’ATV est le site d’origine de la voie mésolimbique dopaminergique, une voie impliquée de façon cruciale dans la manifestation des comportements dirigés. L’importance de cette projection habenulaire pour le comportement demeure encore méconnue. Ainsi, l’objectif de cette étude est d’approfondir notre compréhension du rôle de régulation de l’HbL sur les comportements dépendants de la neurotransmission dopaminergique. MATÉRIEL ET MÉTHODES: Des rats adultes mâles Sprague-Dawley ont été anesthésiés avec de l’isofluorane et installés sur un appareil stéréotaxique. L’acide iboténique, une neurotoxine agoniste des récepteurs glutamatergiques, était infusée bilatéralement dans l’HbL (0,25 μg/0,25 μl/côté). Les rats du groupe contrôle recevaient des infusions NaCl 0,9%. Les rats de l’expérience d’autostimulation intracérébrale (ASIC) étaient aussi implantés d’une électrode monopolaire dans le mésencéphale postérieur. Un groupe de rats était testé pour leur réponse de locomotion à l’amphétamine (0; 0,5 ou 1 mg/kg, intrapéritonéal), dix jours suivant la lésion de l’HbL. La locomotion était mesurée dans des chambres d’activité, chacune équipée de deux faisceaux parallèles infrarouges. Le jour du test, les rats étaient pesés et placés dans la chambre d’activité puis leur activité locomotrice de base était mesurée pendant une heure. Les rats recevaient ensuite une dose d’amphétamine ou le véhicule (NaCl 0,9%) par voie intrapéritonéale et l’activité locomotrice était mesurée pendant deux heures supplémentaires. Un groupe de rats distinct a été utilisé dans l’expérience d’ASIC. Commençant sept jours suivant la lésion, les rats étaient entraînés à appuyer sur un levier afin de s’autoadministrer des stimulations électriques, au cours de sessions quotidiennes. Nous avons ensuite mesuré chacun des taux de réponses d’une série de stimulations aux fréquences décroissantes. À partir d’une courbe réponses-fréquences, le seuil de récompense était inféré par la fréquence de la stimulation nécessaire pour produire une réponse semi-maximale. Les seuils de récompense étaient stabilisés à un niveau similaire pour l’ensemble des rats. Enfin, l’effet sur la récompense de l’amphétamine était testé aux mêmes doses employées pour l’expérience de locomotion. RÉSULTATS: Une lésion neurotoxique de l’HbL n’a pas altéré les niveaux de base de l’activité locomotrice dans chaque groupe. Cependant, une telle lésion a potentialisé l’effet de locomotion de l’amphétamine (1 mg/kg) pendant la première heure suivant son administration, et une tendance similaire était observable pendant la seconde heure. À l’inverse, nous n’avons observé aucune interaction entre une lésion à l’HbL et l’effet amplificateur sur la récompense de l’amphétamine. CONCLUSION: Nos résultats révèlent une importante contribution fonctionnelle de l’HbL à la locomotion induite par l’activation de la voie mésolimbique dopaminergique avec une dose de 1 mg/kg d’amphétamine. À l’opposé, aucun effet sur la récompense n’a été observé. Ces résultats suggèrent que l’activation psychomotrice et l’amplifiation de la récompense produite par l’amphétamine dépendent de substrats dissociables, chacun étant différentiellement sensible à la modulation provenant de l’HbL. / The habenula, an epithalamic nucleus, is centrally located within the dorsal diencephalic conduction system. This dorsal pathway connects the limbic forebrain and basal ganglia to midbrain monoaminergic cell groups intricately involved in the control of behavior. In particular, the lateral habenula (LHb) projects to, among other sites, the ventral tegmental area (VTA). Indeed, recent work has revealed direct LHb innervation of VTA dopamine as well as GABA cells. Little is known, however, about the behavioral relevance of this innervation but this knowledge is of potential importance, since the VTA gives rise to the mesolimbic dopamine pathway, a system critically involved in goal-directed behavior. Our aim here was to begin to understand the contribution of the LHb to dopamine-dependent behaviors. To do this, we produced neurotoxic lesions of the LHb and measured amphetamine-enhanced locomotion and intracranial self-stimulation (ICSS), two behaviors highly sensitive to mesolimbic dopamine neurotransmission. METRIALS AND METHODS: Adult male Sprague-Dawley rats were anesthetised with isoflurane and mounted onto a stereotaxic apparatus. Ibotenic acid, an excitatory neurotoxin at glutamatergic receptors, was infused bilaterally into the LHb (0.25 μg/0.25 μl/side). Sham-lesioned rats received infusions of 0.9% sterile saline. Rats in the ICSS experiment were additionally implanted with a monopolar stimulation electrode in the posterior mesencephalon. One group of rats was tested for their locomotor response to amphetamine (0, 0.5 or 1 mg/kg, i.p.), ten days after LHb lesion. Locomotion was measured in rectangular activity chambers, each equipped with two parallel infrared photobeams. On test day, rats were weighed, placed in the activity chamber and baseline locomotor activity was measured for 1 hour. Rats then received amphetamine or vehicle (0.9% saline) and locomotor activity was measured for 2 more hours. A separate group of rats was used in the ICSS experiment. Beginning seven days post-lesion, rats were trained to press a lever in order to self-administer trains of stimulation pulses. We then measured response rates at each of a series of pulse frequencies during daily sessions. From these response-frequency curves, we obtained estimates of reward thresholds, defined as the pulse frequency necessary for half-maximal responding. Baseline reward thresholds were matched across all rats and once stable, we tested the reward-enhancing effect of amphetamine, at the same doses tested in the locomotion experiment. RESULTS: Neurotoxic lesions of the LHb did not alter baseline locomotor activity in either group. Amphetamine enhanced locomotor activity throughout the entire 2 hour test. Importantly, the locomotor stimulant effect of amphetamine (1 mg/kg) was significantly greater in lesioned rats during the first hour, and a similar tendency was observed during the second hour. On the other hand, we did not observe any difference in amphetamine-induced enhancement of reward between lesioned and sham rats, at any dose or any time post-injection. CONCLUSION: Our findings reveal an important functional contribution of the LHb to dopamine-mediated locomotion. On the other hand, the clear dissociation between the locomotor-stimulant and rewarding effects of amphetamine suggests that the neural substrates mediating these two are dissociable and differentially sensitive to LHb modulation.