Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2015-01-19T14:06:17Z No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Dissertação - Flávia Moreno Duarte - 2014.pdf: 990547 bytes, checksum: 589026eb3ccc7e695e35abeb91deb9c4 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-01-19T14:06:33Z (GMT) No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Dissertação - Flávia Moreno Duarte - 2014.pdf: 990547 bytes, checksum: 589026eb3ccc7e695e35abeb91deb9c4 (MD5) / Made available in DSpace on 2015-01-19T14:06:33Z (GMT). No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Dissertação - Flávia Moreno Duarte - 2014.pdf: 990547 bytes, checksum: 589026eb3ccc7e695e35abeb91deb9c4 (MD5) Previous issue date: 2014-05-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Smell and taste are often impaired by neurodegenerative diseases, however, they have never been studied in association in individuals with cortical and subcortical neurodegenerative diseases in Brazil. This study aimed to evaluate the olfactory and gustative capacity of Parkinson’s disease (PD) individuals, comparing them to a group of subjects with cortical neurodegenerative diseases (CND) and to a control group. It was a cross-sectional study, with convenience sampling. PD individuals were recruited at the Reference Center of Movement Disorders of Clínicas Hospital at the Federal University of Goiás (Centro de Referência em Transtornos do Movimento do Hospital das Clínicas da Universidade Federal de Goiás) (n=80), CND patients were referred from a private clinic of Goiânia (n=20) and the control individuals, at the same age group of PD patients, neurodegenerative disease-free, came from several areas of Clínicas Hospital (n=40). Socio-demographic and clinical data were collected through direct interview and the use of a structured questionnaire including the following variables: gender, age, skin color, schooling, disease duration and stage and life habits. Olfactory capacity was assessed through Sniffin’ Sticks test (odor threshold, discrimination and identification) and gustative capacity through threshold and recognition test of the five basic tastes (sweet, savory, bitter, acid and umami). In order to test the association of olfactory and gustative capacity among the groups, Fisher’s exact test was used. For the comparison of detection and recognition thresholds’ means of basic tastes ANOVA and Kruskal-Wallis were used. PD and CND individuals presented, respectively, 93.8 % and 100 % olfactory compromising and only 15 % of control group individuals presented olfactory reduction, demonstrating statistically significant differences (p<0.001). There were also differences both in detection thresholds as in recognition thresholds of basic tastes among the groups (p<0.001), except for recognition threshold of acid taste (p= 0.088) and umami (p=0.153). Regarding gustative capacity, 53.8 % of PD patients, 50 % of CND individuals and 35 % of control group subjects presented no altered identification of basic tastes, however, there were no significant differences among the groups (p=0.150). It can be concluded that olfactory and gustative capacity in individuals with neurodegenerative diseases, both cortical and subcortical, is compromised and, consequently, presents itself as an important marker of these diseases. / Olfato e paladar estão frequentemente prejudicados nas doenças neurodegenerativas, contudo, nunca foram estudados conjuntamente em indivíduos com doenças neurodegenerativas corticais e subcorticais no Brasil. Este estudo teve como objetivo avaliar a capacidade olfatória e gustativa de indivíduos com doença de Parkinson (DP), comparando-os com um grupo de indivíduos com doenças neurodegenerativas corticais (DNC) e um grupo controle. O desenho do estudo foi transversal, com amostragem por conveniência. Os indivíduos com DP foram recrutados no Centro de Referência em Transtornos do Movimento do Hospital das Clínicas da Universidade Federal de Goiás (n=80), os pacientes com DNC encaminhados de uma clínica particular de Goiânia (n=20) e os controles, da mesma faixa etária do grupo DP, sem doenças neurodegenerativas foram oriundos das diversas áreas do Hospital das Clínicas (n=40). Dados sociodemográficos e clínicos foram coletados por meio de entrevista direta e uso de questionário estruturado abordando as variáveis: gênero, idade, cor da pele, escolaridade, duração e estágio da doença e hábitos de vida. Avaliou-se a capacidade olfatória por meio do teste Sniffin’ Sticks (limiar, discriminação e identificação de odores) e a capacidade gustativa por meio do teste de limiar e de reconhecimento dos cincos gostos básicos (doce, salgado, amargo, ácido e umami). Para testar a associação, da capacidade olfatória e gustativa entre os grupos, utilizou-se teste exato de Fisher. Para comparação de médias dos limites de detecção e de reconhecimento dos gostos básicos utilizou-se ANOVA e Kruskal-Wallis. Os indivíduos com DP e DNC apresentaram, respectivamente, 93,8 % e 100 %, de comprometimento no sentido do olfato e apenas 15 % dos indivíduos controles apresentaram redução no sentido do olfato, com diferenças significativas (p<0,001). Houve também diferenças tanto nos limites de detecção como nos limites de reconhecimento dos gostos básicos entre os grupos (p<0,001), exceto para o limite de reconhecimento do gosto ácido (p= 0,088) e do gosto umami (p=0,153). Em relação à capacidade gustativa, 53,8 % dos pacientes com DP, 50 % dos indivíduos do grupo DNC e 35 % dos indivíduos do grupo controle apresentaram alterações na identificação dos gostos básicos, porém não houve diferenças significativas entre os grupos (p=0,150). Conclui-se que a capacidade olfatória e gustativa em indivíduos com doenças neurodegenerativas, tanto corticais quanto subcorticais, estão comprometidas e, consequentemente, apresentam-se como um marcador importante dessas doenças.

INTRODUÇÃO: O diagnóstico da doença de Parkinson (DP) pode ser um desafio, principalmente nas fases precoces da doença. O diagnóstico acurado desta condição requer mais que a avaliação clínica isolada. A Tomografia computadorizada do crânio de fóton único (SPECT) e a ultrassonografia transcraniana (USTC) podem ser úteis na diferenciação entre a DP e as síndromes parkinsonianas atípicas ou entre a DP e o tremor essencial. O presente estudo objetivou investigar a acurácia da USTC combinada com o teste de olfação Sniffin\' Sticks (SST-16) para diferenciar pacientes com DP de controles saudáveis e comparar com a acurácia do SPECT com 99mTc- TRODAT-1 (TRODAT). MÉTODOS: Trata-se de um estudo transversal que incluiu pacientes com DP segundo critérios do United Kingdom Parkinson\'s disease Society e um grupo controle de indivíduos saudáveis pareados para idade e gênero. Os pacientes foram examinados por um especialista em distúrbios do movimento e submetidos a SPECT encefálico com TRODAT, USTC e SST-16. Curvas Receiver Operating Characteristic (ROC) foram obtidas para definir os pontos de corte dos métodos avaliados para detecção de DP. RESULTADOS: Vinte indivíduos com DP (13 homens e 7 mulheres) e 9 participantes saudáveis foram admitidos no estudo. A idade mediana de início dos sintomas foi de 56,5 anos e a mediana do tempo de duração da doença foi de 5 anos. Maior área de ecogênica da substância negra (SN) foi observada no grupo com DP (p=0,013). Área ecogênica da SN de 0,22 cm2 foi definida pela curva ROC para detecção de DP, com acurácia de 79%. O ponto de corte do potencial de ligação do TRODAT no striatum foi 0,90, com acurácia de 99% para o diagnóstico de DP. Escore do SST-16 maior ou igual a 10 pontos foi o ponto de corte para detecção de DP, com acurácia de 85,8%. A combinação da USTC com teste da olfação levou à acurácia de 95% para detecção de DP. CONCLUSÃO: A combinação da USTC com SST-16 eleva a capacidade de ! detecção da DP. A acurácia da USTC combinada ao SST-16 para identificar pacientes com DP idiopática aproximou-se da acurácia do SPECT com TRODAT / INTRODUCTION: Diagnosing Parkinson\'s disease (PD) can be challenging, especially in the early stages of the disease. An accurate diagnosis requires more than clinical findings alone. Brain single-photon emission computed tomography (SPECT) and transcranial sonography (TCS) are helpful for diagnosing PD and differentiating it from atypical parkinsonian syndromes as well as essential tremor. This study aimed to investigate the accuracy of TCS combined with the Sniffin\' sticks olfactory test (SST-16) for differentiation between idiopathic PD patients and healthy controls compared to that of 99mTc-TRODAT-1 SPECT (TRODAT). METHODS: A cross-sectional study included PD patients diagnosed in accordance with United Kingdom PD Society Brain Bank criteria and a control group of age and sex-matched healthy subjects. All patients were examined by a movement disorder specialist and underwent brain SPECT using TRODAT, TCS examination and SST-16 test. Receiver Operating Characteristic (ROC) curves were used to calculate cut-off points for TCS, Striatal TRODAT binding potentials and SST-16. The area under the ROC curve determined the accuracy of the method. RESULTS: Twenty patients with PD (13 males and 7 females) and nine healthy subjects were included. Median age of PD onset was 56.5 years with median disease duration of 5 years. A larger substantia nigra (SN) echogenic area was observed in the PD group (p=0.013). SN echogenic area cut-off point of 0.22 cm2 was obtained from a ROC curve for PD diagnosis. Considering this cut-off point, TCS accuracy was estimated at 79.2% for PD diagnosis. The cut-off value of 0.90 for striatal TRODAT binding was associated with 99% accuracy for the diagnosis of PD. SST-16 values equal or greater than 10 points showed a 85.8% accuracy for PD diagnosis. Combination of both SST-16 and TCS improved the accuracy to 95% for PD diagnosis. CONCLUSION: Combined assessment of SST-16 and TCS are reliable and highly accurate for distinguishing PD patients from healthy controls. The accuracy of TCS combined with SST-16 for differentiation between idiopathic PD patients and healthy controls is similar to that of SPECT TRODAT

Um dos modelos experimentais mais utilizados para estudar a epilepsia do lobo temporal (ELT) é o abrasamento (kindling) por estimulação elétrica diária da amígdala, o abrasamento elétrico convencional. Uma alternativa rápida e eficaz a esse modelo é o abrasamento elétrico rápido, também capaz de gerar crises límbicas, porém com 10 estímulos elétricos aplicados ao dia, por 2 dias. No 3º dia é aplicado um estímulo elétrico adicional, o 21º estímulo, quando podem ser testadas drogas antiepilépticas ou estudados mecanismos de plasticidade ou memória. Entre as principais áreas ativadas nas crises límbicas encontram-se o complexo amigdalóide, a formação hipocampal, o córtex piriforme e neocórtices adjacentes. O envolvimento de estruturas olfatórias na ELT é antigo e estudos indicam que a exposição a um estímulo olfatório é capaz de suprimir, inibir ou induzir a ocorrência de crises. Todas as evidências clínicas e experimentais dão suporte científico para a hipótese de que a estimulação olfatória com o 2,5-Dihydro-2,4,5-trimethylthiazoline (TMT), uma potente substância química, derivada das fezes de raposa e que biologicamente representa o cheiro de predador pode influenciar no processo de crises evocadas por estimulação elétrica da amígdala. O objetivo geral do presente estudo foi avaliar a influência da apresentação do estímulo olfatório com TMT nas crises epilépticas de ratos Wistar, submetidos ao abrasamento elétrico rápido da amígdala. Para tanto, os parâmetros químicos do TMT foram avaliados, bem como as respostas comportamentais de ratos Wistar machos naives submetidos ao estímulo olfatório com diferentes doses de TMT. Na sequência, um novo grupo de ratos Wistar machos naives foi submetido ao protocolo de abrasamento elétrico rápido da amígdala com a aquisição dos registros eletrencefalográficos (EEGráficos) do córtex piriforme, formação hipocampal além do complexo amigdalóide. Após abrasados os animais foram expostos ao TMT ou água destilada, previamente ao 21º estímulo elétrico. Posteriormente o tecido cerebral foi processado (perfundido, crioprotegido, congelado e cortado) e então foram feitas as técnicas histoquímicas de: Nissl e Fluoro-Jade C (FJC, marcador de neurodegeneração). As respostas comportamentais foram analisadas mediante o uso do Índice de Gravidade para Crises Límbicas e da neuroetologia. Adicionalmente foi avaliada a expressão EEGráfica do 1º, 20º e 21º estímulos e verificada a presença/ausência de neurodegeneração em regiões do sistema límbico. Os resultados da análise comportamental obtidos nesse estudo foram comparados com os obtidos no protocolo de estimulação olfatória com TMT nas crises audiogênicas agudas de ratos da cepa WAR. O TMT desencadeou reações de medo e modificou as sequências comportamentais, reduziu a atividade motora e os comportamentos de autolimpeza. Dados qualitativos da cromatografia gasosa e algoritmos matemáticos possibilitaram estabelecer as concentrações na câmara para as diferentes doses de TMT. Além disso, a cromatografia gasosa identificou que 30 minutos é o tempo necessário para saturação e dessaturação da câmara ao TMT, e indicou uma saturação homogênea do interior dessa câmara. O TMT puro no abrasamento elétrico rápido em ratos Wistar foi capaz de reduzir significativamente o Índice de Gravidade para Crises Límbicas comparado à água, corroborando os dados neuroetológicos que indicam o efeito supressor do TMT nas crises, tanto para o modelo de abrasamento elétrico rápido quanto para as crises audiogênicas agudas. Os resultados da duração da pós-descarga EEGráfica primária no 21º estímulo foram inconclusivos, sendo necessárias outras análises empregando diferentes métodos analíticos. Com a técnica de FJC não foi possível verificar morte celular por necrose em qualquer região cerebral avaliada. / One of the most widely used experimental models to study temporal lobe epilepsy (TLE) is the kindling by electrical daily stimulation of the amygdala, the conventional kindling. A rapid and effective alternative to this model is rapid electrical kindling, also capable of generating limbic seizures, but with 10 electrical stimuli applied per day for 2 days. On the 3rd day an additional electrical stimulus is applied, the 21st stimulus, when antiepileptic drugs can be tested or mechanisms of plasticity and memory can be studied. Among the main areas activated in limbic seizures are the amygdaloid complex, the hippocampal formation, piriform cortex and adjacent neocortices. The involvement of the olfactory structures in TLE is old and studies indicate that exposure to an olfactory stimulus is capable to suppress or inhibit or induce the occurrence of seizures. All the clinical and experimental evidences provide scientific support for the hypothesis that the olfactory stimulation with 2,5-Dihydro-2,4,5-trimethylthiazoline (TMT), a powerful chemical substance derived from fox feces which biologically represents the \"predator smell can influence the seizures process evoked by electrical stimulation of the amygdala. The overall objective of this study was to evaluate the influence of olfactory stimulation with TMT in seizures of Wistar rats subjected to rapid electrical kindling of the amygdala. Therefore, the chemical parameters of TMT were evaluated, as well as behavioral responses of naive male Wistar rats exposed to the olfactory stimulus with different concentrations of TMT. Other group of rats was electrically stimulated in the amygdaloid complex, following the protocol of rapid electrical kindling and the electroencephalographic recordings (EEGraphic) obtained from the piriform cortex, hippocampal formation in addition to the amygdaloid complex. After scorched the animals were exposed to TMT or distilled water, prior to the 21st electrical stimulation. Subsequently the cerebral tissue was processed (perfused, cryoprotected, frozen and sliced) and then processed for Nissl and Fluoro-Jade C histochemistry (FJC, a marker of neurodegeneration). The behavioral responses were analyzed by using the Severity Index for Limbic Seizures and neuroethology. In addition to EEG, reviewed after the 1st, 20th and 21th stimuli we also examined the presence/absence of neurodegeneration in regions of the limbic system. The results obtained in this study were compared with those obtained in the protocol of olfactory stimulation with TMT on acute audiogenic seizures of rats from the WAR strain. The TMT triggered fear reactions and modified the behavioral sequences, reduced motor activity and grooming behavior. Qualitative data from gas chromatography and mathematical algorithms made possible to establish the concentrations in the camera for the different doses of TMT. In addition, the gas chromatography helped to identify that 30 minutes is the time required for saturation and desaturation of the camera to TMT and indicated a homogeneous saturation of the interior of such camera. The pure TMT in rapid electrical kindling in Wistar rats was able to significantly reduce the Severity Index for Limbic Seizures, compared to water, corroborating the data of the neuroethology method indicating the suppressive effect of TMT in seizures, in both, the model of rapid electrical kindling as well as the acute audiogenic seizures. However, the results of the duration of the EEGraphic primary after-discharge at the 21th stimulus were inconclusive, requiring further analysis using different analytical methods. With the technique of FJC it was not observed necrotic cell death in any studied brain region.

Orientadores: Simone Appenzeller, Lilian Tereza Lavras Costallat / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T13:51:27Z (GMT). No. of bitstreams: 1 Peres_FernandoAugusto_M.pdf: 1437476 bytes, checksum: a879071e9da761defaf00fb710eaf9b4 (MD5) Previous issue date: 2014 / Resumo: Lúpus Eritematoso Sistêmico (LES) é uma doença autoimune, crônica e mutissistêmica, caracterizada por períodos de atividade e remissão. Manifestações neuropsiquiátricas ocorrem em 12-95% dos pacientes, dependendo dos critérios diagnósticos aplicados e estão associadas a uma elevada morbi-mortalidade. Vários anticorpos têm sido relacionados com manifestações neuropsiquiátricas no LES, os mais frequentemente associados são anticorpo antifosfolípides, um subtipo de dupla-fita DNA e anticorpo anti-P ribossomal. Estudos recentes têm demonstrado a alta especificidade do anti-P ribossomal para o LES podendo ser também um marcador para atividade de doença. Anti-P ribossomal são capazes de se ligar em células neuronais em áreas relacionadas com o sistema límbico que são associadas ao olfato. Os objetivos deste trabalho foram analisar a prevalência de distúrbio olfatório no LES, correlacionar essas alterações olfatórias a alterações de humor, ansiedade, presença de manifestações neuropsiquiátricas e atividade e dano da doença e associar os níveis de anti-P ribossomal com distúrbios olfatórios, presença de manifestações neuropsiquiátricas e atividade da doença. Foram selecionados pacientes com diagnóstico de LES, seguidos no ambulatório de reumatologia do HC-UNICAMP, no período de março de 2011 a dezembro de 2013. O grupo controle foi constituído por voluntários sadios com idade e gênero semelhantes aos do grupo de pacientes com LES, que não apresentavam histórico de doenças autoimunes ou alérgicas, sem alterações de vias aéreas superiores e sem histórico de uso de drogas inalantes. Foram incluídos 120 pacientes com LES, e 135 voluntários sadios. Ansiedade foi encontrada em 67,5% dos pacientes e em 39,2% dos controles e depressão foi identificada em 46,6% dos pacientes e em 28,8% dos controles. Alteração olfatória foi observada em 51,6% dos pacientes e em 29,6% dos controles. O anti-P ribossomal foi identificado exclusivamente em pacientes e estava presente em 13 (10,8%) deles. Alteração olfatória foi associada com LES; pacientes tiveram médias significativamente menores nas três fases da avaliação olfatória e, consequentemente, no somatório total do teste (LDI). A alteração olfatória ainda se associou inversamente com ansiedade (p=0,004; R= -0,18), depressão (p=0,01; R= -0,232), dano da doença (p=0,002; R=-0,282) e maior idade (p<0,001; R= -0.353). Não encontramos associação entre alteração olfatória, sexo ou atividade da doença (p=0,891 e p=0,914, respectivamente). O LDI se correlacionou com histórico de manifestações NP, sendo que pacientes com manifestações NP tinham média de LDI de 28,35 (DP±5,30) pontos, enquanto que pacientes sem manifestações NP tinham média de LDI de 30,8 (DP±4,51) pontos (p<0,05). O Anti-P ribossomal não foi associado com a presença de manifestações NP (p=0,730), porém quando analisamos os subitens classificatórios de manifestações NP separadamente, observamos associação entre anti-P ribossomal positivo e psicose (p<0,05). Observamos ainda associação do anti-P ribossomal com atividade da doença. Não observamos outras associações com anti-P ribossomal. Concluímos que pacientes apresentam uma significativa diminuição do olfato quando comparados a controles sadios, que se associa com histórico de manifestações neuropsiquiátricas, ansiedade, depressão, dano da doença e maior idade. Os anticorpos anti-P ribossomais estavam presentes exclusivamente em pacientes e se associou com psicose e atividade da doença / Abstract: Systemic lupus erythematosus (SLE) is an autoimmune, chronic, multisystemic disorder characterized by periods of activity and remission. Neuropsychiatric manifestations occur in 12-95 % of SLE patients, depending on the diagnostic criteria applied and are associated with a high morbidity and mortality. Several antibodies have been associated with neuropsychiatric manifestations in SLE. These antibodies are more often associated with antiphospholipid antibody, a subtype of double-stranded DNA and antiribosomal P antibodies. Recent studies have demonstrated the high specificity of antiribosomal P antibodies for SLE, suggesting that antiribosomal P antibodies may be a biomarker for disease activity. Antiribosomal P antibodies are able to bind to neuronal cells in areas of the limbic system which are responsible to the olfactory. The objectives of this study were to analyze the prevalence of olfactory disorder in SLE, to correlate olfactory changes to mood disorders, anxiety, presence of neuropsychiatric manifestations, disease activity and damage, and also to associate of the presence of antiribosomal P antibodies with olfactory disorders, presence of neuropsychiatric manifestations and disease activity. One hundred and twenty SLE patients included in the study were followed at the outpatient rheumatology UNICAMP, from March 2011 to December 2013. The control group was consisted of 135 healthy volunteers matched by age and sex. They had no history of autoimmune or allergic diseases, with no changes in upper airway and no history of use of inhalant drugs. Anxiety was observed in 67.5 % SLE patients and in 39.2% controls. Depression was identified in 46.6 % SLE patients and in 28.8% controls. Olfactory changes were observed in 51.6 % SLE patients and in 29.6 % controls. Anti-ribosomal P antibodies were identified exclusively in SLE patients and were present in 13 (10.8%) of them. Olfactory changes had significantly lower averages in all three phases of the olfactory evaluation and, consequently, in the total sum test (LDI). The olfactory also inversely associated with anxiety (p = 0.004, R = -0.18), depression (p = 0.01, R = -0.232), cumulative damage (p = 0.002 R = -0.282) and age (p <0.001 , R = -0.353). We did not observe an association between olfactory changes and gender or disease activity (p = 0.891 and p = 0,914), respectively. The TDI was correlated with a CNS involvement, and patients with NPC [mean of 28.35 (SD ± 5.30] points, whereas patients without CNS involvement had a mean TDI of 30.8 (SD ± 4.51) points (p < 0.05). Antiribosomal P antibodies were not associated with the presence of CNS involvemnt (p = 0.730), but when we analyzed each subitem of CNS involvement separately, we observed an association between the presence of antiribosomal P antibodies and psychosis (p < 0.05). We also observed an association between antiribosomal P antibodies and disease activity (p < 0.05). We concluded that SLE patients show a significant decrease of smell when compared to healthy controls. Olfactory changes are associated with a history of neuropsychiatric symptoms, anxiety, depression, cumulative damage, and older age. Antiribosomal P antibodies were exclusively observed in SLE patients compared to healthy controls and were associated with psychosis and disease activity / Mestrado / Clinica Medica / Mestre em Clinica Medica

No description available.

L’imagerie fonctionnelle cérébrale détecte les changements hémodynamiques induits par un stimulus pour déterminer les zones d’activation neuronale. Plus particulièrement, l’imagerie BOLD en IRMf détecte les changements d’oxygénation du sang grâce aux propriétés paramagnétiques de la déoxyhémoglobine. L’oxygène n’est donc pas uniquement un substrat énergétique pour le tissu neuronal, il joue également un rôle majeur dans l’imagerie noninvasive du cerveau humain. Au cours de ma thèse, j’ai tout d’abord participé à la mise au point d’une nouvelle technique non-invasive d’imagerie de l’oxygène dans le cerveau d’animaux anesthésiés. Couplant un nouveau senseur phosphorescent de l’oxygène (Finikova et al., 2008) et la microscopie biphotonique, cette approche permet à la fois de cartographier l’oxygène en 3D avec une résolution spatiale et temporelle jusqu’alors inégalée, mais aussi de suivre simultanément l’oxygène et le flux sanguin dans les capillaires cérébraux au repos ou lors d’une activation neuronale (Lecoq et al., 2011). Tirant profit des nouvelles possibilités de cette technique, nous avons alors démontré: • la présence d’un shunt artério-veineux uniquement basé sur la diffusion de l’oxygène. Ce résultat, obtenu chez le rat dans la couche la plus superficielle du bulbe olfactif: la couche du nerf (ONL), confirme que l’oxygène ne diffuse pas uniquement à partir des capillaires et démontre que les artérioles contribuent significativement à l’oxygénation du tissu cérébral. Il démontre également qu’il n’est pas possible de déterminer ni la Po2 capillaire ni la Po2 tissulaire à partir de la Po2 veineuse. • l’existence de transitoires de Po2 associés à chaque globule rouge dans le compartiment capillaire, appelés EATs (erythrocyte-associated transients) (Hellums, 1977; Cabrales and Intaglietta, 2007). En bref, de part leur diamètre supérieur à celui de la lumière d’un capillaire, les globules rouges passent un à un dans la lumière des capillaires, laissant entre eux un espace de plasma. Cependant, la faible solubilité de l’oxygène dans le plasma crée une barrière à la diffusion, ce qui se traduit par une inhomogénéité de la Po2 capillaire: celle-ci est élevée au bord du globule rouge et décroit avec la distance pour atteindre un minimum à mi-distance entre deux globule rouges. Poursuivant l’étude des EATs (Parpaleix et al., 2013), nous avons observé les points suivants: • La Po2 tissulaire dans l’environnement immédiat d’un capillaire peut être déterminée à partir de la Po2 vasculaire à mi-distance entre deux érythrocytes. Ce résultat est intéressant en ce qu’il permettra d’effectuer des mesures non invasives de Po2 tissulaire, utile notamment chez l’animal éveillé. • L’amplitude des EATs est si large (35 mmHg en moyenne) que la Po2 capillaire moyenne ne reflète en rien la saturation en oxygène de l’hémoglobine. • Une empreinte filtrée des EATs vasculaires est détectable dans le tissu (_5 mmHg d’amplitude). • Au cours d’une stimulation neuronale, une diminution de la Po2 capillaire moyenne peut être détectée avant l’hyperémie fonctionnelle, un résultat jusqu’à présent controversé dans le domaine de l’imagerie BOLD en IRMf, mais important en ce que ce dip pourrait être un rapporteur très résolutif de l’activation neuronale. Parmi les questions restant en suspens et pouvant être étudiées finement avec notre approche, j’en citerai une principale: quel est le poids des différents facteurs (métaboliques, présynaptiques ou post-synaptiques) et du flux sanguin dans l’établissement de la Po2 cérébrale au repos? / In humans, functional mapping of brain activity mainly relies on the increase of cerebral blood flow (CBF) triggered by neuronal activation. This neurovascular coupling provides energy substrates such as oxygen and glucose to the activated area. The steady state concentration of oxygen, as well as its dynamics upon neuronal activation, have been investigated with numerous methods, however, none of them provided highly resolute measurements in depth. During my PhD, we combined a phosphorescence quenching approach with two-photon microscopy to detect, in depth and with a micrometer spatial resolution scale, the emission of phosphorescence by PtP-C343, a new oxygen nano-sensor designed for two-photon excitation. We first characterized the technique and then reported two biological results, using the olfactory bulb (OB) glomerulus as a model to study oxygen concentration, at rest and upon odor stimulation. We found an arterio-venous shunt, purely based on diffusion, in the superficial nerve layer of the OB, confirming the role of arterioles in brain oxygenation. Simultaneous measurements of Po2 and blood flow allowed us to reveal the presence of erythrocyte-associated transients (EATs), i.e. Po2 fluctuations that are associated with individual erythrocytes. Pursuing the investigation of EAT characteristics, we found that in capillaries, Po2 at mid-distance between two erythrocytes is at equilibrium with, and thus reports Po2 in the nearby neuropil. Finally, we could observe that even in capillaries, a small oxygen initial dip can be detected prior to functional hyperemia, upon odor activation.

This thesis addresses the problem of gas distribution modelling for gas monitoring and gas detection. The presented research is particularly focused on the methods that are suitable for uncontrolled environments. In such environments, gas source locations and the physical properties of the environment, such as humidity and temperature may be unknown or only sparse noisy local measurements are available. Example applications include air pollution monitoring, leakage detection, and search and rescue operations. This thesis addresses how to efficiently obtain and compute predictive models that accurately represent spatio-temporal gas distribution. Most statistical gas distribution modelling methods assume that gas dispersion can be modelled as a time-constant random process. While this assumption may hold in some situations, it is necessary to model variations over time in order to enable applications of gas distribution modelling for a wider range of realistic scenarios. This thesis proposes two time-dependent gas distribution modelling methods. In the first method, a temporal (sub-)sampling strategy is introduced. In the second method, a time-dependent gas distribution modelling approach is presented, which introduces a recency weight that relates measurement to prediction time. These contributions are presented and evaluated as an extension of a previously proposed method called Kernel DM+V using several simulation and real-world experiments. The results of comparing the proposed time-dependent gas distribution modelling approaches to the time-independent version Kernel DM+V indicate a consistent improvement in the prediction of unseen measurements, particularly in dynamic scenarios under the condition that there is a sufficient spatial coverage. Dynamic scenarios are often defined as environments where strong fluctuations and gas plume development are present. For mobile robot olfaction, we are interested in sampling strategies that provide accurate gas distribution models given a small number of samples in a limited time span. Correspondingly, this thesis addresses the problem of selecting the most informative locations to acquire the next samples. As a further contribution, this thesis proposes a novel adaptive sensor planning method. This method is based on a modified artificial potential field, which selects the next sampling location based on the currently predicted gas distribution and the spatial distribution of previously collected samples. In particular, three objectives are used that direct the sensor towards areas of (1) high predictive mean and (2) high predictive variance, while (3) maximising the coverage area. The relative weight of these objectives corresponds to a trade-off between exploration and exploitation in the sampling strategy. This thesis discusses the weights or importance factors and evaluates the performance of the proposed sampling strategy. The results of the simulation experiments indicate an improved quality of the gas distribution models when using the proposed sensor planning method compared to commonly used methods, such as random sampling and sampling along a predefined sweeping trajectory. In this thesis, we show that applying a locality constraint on the proposed sampling method decreases the travelling distance, which makes the proposed sensor planning approach suitable for real-world applications where limited resources and time are available. As a real-world use-case, we applied the proposed sensor planning approach on a micro-drone in outdoor experiments. Finally, this thesis discusses the potential of using gas distribution modelling and sensor planning in large-scale outdoor real-world applications. We integrated the proposed methods in a framework for decision-making in hazardous inncidents where gas leakage is involved and applied the gas distribution modelling in two real-world use-cases. Our investigation indicates that the proposed sensor planning and gas distribution modelling approaches can be used to inform experts both about the gas plume and the distribution of gas in order to improve the assessment of an incident.

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No description available.

Cette thèse s’intéresse à la capacité du cerveau à s’adapter à un environnement changeant. Plus spécifiquement, elle s’intéresse à la plasticité cérébrale dans le système olfactif. Les sommeliers, experts dans le domaine de l’olfaction, ont constitué notre modèle. Une première étude nous a permis d’établir un protocole afin de tester la performance olfactive des sommeliers. Dans une deuxième étude, nous avons testé des étudiants en sommellerie au début de leur formation d’un an et demi qui mène à la profession de sommelier. Nous avons observé que ces futurs experts de l’olfaction présentaient déjà, au cours des deux premiers mois, des capacités olfactives supérieures. Dans une troisième étude, nous avons de nouveau testé les étudiants à la fin de leur formation, afin d’examiner les effets d’un entraînement olfactif à long terme sur la performance olfactive et sur le cerveau : en plus de mesurer les capacités olfactives avec le test des Sniffin’ Sticks, nous avons utilisé l’imagerie par résonance magnétique (IRM) pour évaluer l’évolution du cerveau au cours de la formation en sommellerie. Nos principales observations concernent des changements au niveau de la structure cérébrale. Premièrement, le volume du bulbe olfactif a augmenté au cours de la formation, ce qui est en accord avec la littérature disponible à propos de cette structure. Deuxièmement, nous avons observé un épaississement au niveau du cortex entorhinal mais aussi un amincissement au niveau d’autres régions du cortex. Mises en relation avec les résultats d’études antérieures, ces observations soutiennent le récent modèle de surproduction-élagage selon lequel les changements dus à la plasticité liée à l’entraînement ne sont pas linéaires mais font intervenir différents processus en plusieurs phases. Ce modèle constitue une avancée importante dans la compréhension des mécanismes impliqués dans la plasticité cérébrale et devrait être pris en compte dans les futures études sur la plasticité. Bien que les résultats sur le plan neuroimagerie soient intéressants, les résultats de l’étude longitudinale relatifs à la performance olfactive n’étaient pas concluants sur le plan comportemental. Nous avons donc mis en place dans une quatrième étude une tâche d’identification d’odorants au sein de mélanges plus complexe et plus adaptée aux sommeliers qui a confirmé la supériorité de leurs capacités olfactives. Nous avons aussi entraîné des novices sur cette tâche pendant cinq jours pour tester les effets d’un court entraînement olfactif. Cette thèse est organisée sous forme de thèse par articles. Le premier chapitre correspond à l’introduction générale, qui est elle-même organisée en plusieurs grandes parties. Ces différentes parties définissent les concepts-clés de cette thèse : l’olfaction, les corrélations neuroanatomiques dans le système olfactif, la plasticité cérébrale, la plasticité liée à l’entraînement dans le système olfactif, la neuroimagerie. La dernière partie conclut l’introduction en présentant les objectifs et hypothèses de recherche. Les chapitres suivants correspondent aux articles rédigés au cours du doctorat et présentant les résultats des recherches. Le dernier chapitre constitue une discussion générale. Enfin, en annexes se trouvent deux articles publiés lors du doctorat, un chapitre à paraître dans un livre ainsi que des résultats non publiés. / This thesis is about the brain’s ability to adapt to an ever-changing environment. More specifically, it is about brain plasticity in the olfactory system. We used sommeliers, who are experts in olfaction, as our model. A first study allowed us to instate a protocol to assess sommeliers’ olfactory function. In a second study, we tested sommelier students at the start of their year-and-a-half-long training which is the prerequisite to become a professional sommelier. We observed that these future experts in olfaction already had, during the first two months of training, superior olfactory abilities. In a third study, we tested sommelier students again at the end of their training to examine the effects of a long-term olfactory training on olfactory performance and on the brain: beside assessing olfactory performance with the Sniffin’ Sticks test, we used magnetic resonance imaging (MRI) to examine the evolution of brain structure and function during sommelier training. Changes in brain structure constituted our main results. Firstly, olfactory bulb volume increased during sommelier training, which is in line with previous reports about this structure. Secondly, we observed a cortical thickness increase in the entorhinal cortex but also cortical thinning in other brain areas. Put together with findings from previous studies, these results support the recent overproduction-pruning model of plasticity according to which changes due to training-related brain plasticity are nonlinear but involve different processes and different phases. This model constitutes a great advance in the understanding of brain plasticity and its underlying mechanisms and should be considered in future studies about plasticity. Though neuroimaging results were interesting, results from olfactory tests in our longitudinal study were not conclusive so we conducted a fourth study to test the ability to identify odorants within mixtures, a task which is more complex and suitable for sommeliers than the Sniffin’ Sticks test. Sommeliers performed better. We also tested novices that we had trained on this task for five days to evaluate the effects of a short-term olfactory training. This thesis is organized by articles. The first chapter is a general introduction, itself organized in several parts. These different parts define the major concepts of this thesis: olfaction, neuroanatomical correlations in the olfactory system, brain plasticity, plasticity in the olfactory system, neuroimaging. The last part concludes the introduction with aims and hypotheses. The following chapters are articles written during PhD that present the results of our research. The last chapter is a general discussion of all the results. Finally, two articles published during PhD, a chapter that is to be published in a book and unpublished results are presented as appendices.