Orientador: Maria Aparecida Azevedo Pereira da Silva / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-19T19:30:51Z (GMT). No. of bitstreams: 1 Natalicio_MariaAngelica_D.pdf: 1137447 bytes, checksum: bf1a6d401d0100649213c09ece37f7f9 (MD5) Previous issue date: 2012 / Resumo: Testes sensoriais para a avaliação da função olfatória de indivíduos têm sido validados e utilizados em diagnósticos da população em geral, e em portadores de desordens cerebrais e pesquisas em neurociência em particular. No Brasil, testes para serem utilizados com segurança e eficiência para a avaliação da capacidade de identificação e discriminação de odores de indivíduos ainda não foram adequadamente desenvolvidos e validados. Assim, os objetivos da presente pesquisa foram: i) desenvolver, testar e validar testes de identificação e discriminação de odores para avaliar a função olfatória de indivíduos brasileiros, ii) avaliar a potencialidade das metodologias desenvolvidas para uso em pré-diagnóstico clínico de indivíduos da terceira idade e pacientes portadores de epilepsia, iii) verificar o desempenho, em portadores de epilepsia, de uma metodologia já validada e utilizada mundialmente para avaliar a capacidade de identificação de odores de indivíduos e, iv) avaliar em portadores de epilepsia, funções que são processadas por substratos neurais comuns à função olfatória, neste caso, a capacidade de reconhecimento de emoção facial e vocal. Para o teste de identificação de odores, foi desenvolvido um instrumento intitulado &quot;Pastilhas de Odor¿ contendo em pastilhas individuais, 36 odores familiares aos brasileiros. Os odores foram caracterizados quanto à intensidade, aceitação, pungência, refrescância e familiaridade, sendo considerados adequados para comporem um teste de avaliação da função olfatória. A identificação dos odores de &quot;Pastilhas de Odor¿ foi realizada através de um teste de múltipla escolha contendo quatro alternativas, das quais apenas uma é a correta. Para o desenvolvimento do teste de discriminação de odores, 24 voláteis odoríferos puros (P.A.), associados a 6 diferentes categorias de odor - doce, verde, frutal, cítrico, floral e desagradável - foram selecionados e diluídos em propilenoglicol. Com essas amostras, 36 testes de comparação pareada foram construídos, onde em cada categoria de odor, uma amostra alvo foi selecionada para ser comparada com as demais da mesma categoria. O desempenho de cada indivíduo neste teste é analisado utilizando-se a teoria &quot;signaldetection¿, através dos seguintes parâmetros: taxa de acertos (HR), taxa de falsos alarmes (FR), poder discriminativo (d¿L) e vício de resposta (CL). Os dois testes desenvolvidos - &quot;Pastilhas de Odor¿ e teste de discriminação - foram validados com a participação de três grupos de indivíduos: grupo controle, grupo da terceira idade e grupo de indivíduos portadores de epilepsia do lobo temporal (ELT). A capacidade de identificação de odores, de pacientes norte-americanos portadores de ELT foi também avaliada, utilizando-se com esse fim, o teste já validado, denominado &quot;University of Pennsylvania Smell Identification Test¿ (UPSIT), o qual consiste em um teste de múltipla escolha, composto por 40 estímulos odoríferos microencapsulados. Adicionalmente, avaliou-se nesses pacientes, a capacidade de reconhecimento de emoção facial e vocal, utilizando-se uma nova ferramenta intitulada &quot;Comprehensive Affect Testing System¿ (CATS). Com relação à capacidade de identificação de odores dos indivíduos brasileiros, os resultados obtidos através do teste &quot;Pastilhas de Odor¿ revelaram significância estatística tanto para o efeito &quot;sexo¿ (p=0,0003), como para o efeito &quot;idade¿ (p<0,001). O teste também permitiu identificar que os portadores de ELT, sem cirurgia e após ressecção do lobo temporal, apresentavam menor capacidade de identificação de odores comparativamente ao grupo controle (p= 0,05); este mesmo resultado foi observado ao aplicar o UPSIT em portadores de ELT norte-americanos, antes e após os mesmos terem sido submetidos à mencionada cirurgia. O teste &quot;Pastilhas de Odor¿ mostrou ser de fácil manuseio e aplicação em indivíduos adultos, apresentou alto coeficiente de confiabilidade no teste-reteste (r=0,87, p<0,001) e suas pastilhas apresentaram boa estabilidade ao armazenamento durante 3 meses. Por sua vez, os dados obtidos através do teste de discriminação de odores identificaram que tanto o grupo da terceira idade como o dos portadores de ELT apresentaram poder discriminativo e taxa de acertos inferiores (p=0.05) aos indivíduos do grupo controle. Os resultados obtidos pela aplicação do teste CATS em indivíduos norte-americanos, revelaram que pacientes ELT tanto pré- como póscirúrgicos apresentaram menor reconhecimento de emoção facial e vocal quando comparados com o grupo controle, principalmente para as emoções negativas. O fato dos testes &quot;Pastilhas de Odor¿ e de discriminação de odores desenvolvidos na presente pesquisa terem detectado deficiência olfatória nos indivíduos brasileiros da terceira idade e portadores de epilepsia, constrói validade para a utilização dos mesmos em diagnósticos clínicos associados a essas populações / Abstract: Sensory tests to evaluate olfactory function have been validated and used in the diagnosis of subjects, mainly in brain disorders patients, and in the neuroscience research. In Brazil, reliable tests of odor discrimination and identification have not been appropriately developed and validated. The aims of the present study were: i) to develop, test and validate odor discrimination and identification tests to assess olfactory function of Brazilian population; ii) to evaluate the methodologies performance in the diagnosis of elderly subjects and epilepsy patients. For odor identification test, the developed instrument was entitled &quot;Odor Tablets¿, with 36 different odors familiar to Brazilians; to verify the performance in patients with epilepsy, a methodology previously validated and used worldwide to evaluate the ability to identify odors of individuals, and iv) to evaluate in patients with epilepsy, functions that are processed by common neural substrates for olfactory function, in this case, the ability of recognition of voice and facial emotion. Odors were rated as to their intensity, pleasantness, pungency, coolness and familiarity and they were considered suitable for composing a test to assess olfactory function. &quot;Odor Tablets¿ proceeded through multiple-choice test with four alternatives which only one was correct. For the development of odor discrimination test, 24 pure odorants, associated with six different odor categories ¿ sweet, green, fruity, citric, floral and unpleasant - were selected and diluted in propylene glycol. With these samples, 36 paired comparison tests were constructed, where in each odor category, a target sample was selected to be compared with the others in the same category. The participant¿s performance in the odor discrimination test was analyzed using the &quot;signal-detection" theory through the following parameters: hit rate (HR), false-alarm rate (FR), discrimination measurement (d 'L) and bias response (CL). Both tests, &quot;Odor Tablets¿ and odor discrimination test, were validated with three groups of subjects: control group, elderly group and temporal lobe epilepsy patients group (TLE). The ability to identify odors from North American TLE patients was also measured, using for this purpose, the validated test "University of Pennsylvania Smell Identification Test" (UPSIT), a multiple choice test consisting of 40 microencapsulated odor stimuli. In addition, the ability of recognition of voice and facial emotion of TLE patients were evaluated using a new tool entitled "Comprehensive Affect Testing System" (CATS). For the subject¿s ability to identify odors, there were significant differences for gender (p=0.0003) and age (p<0.001). Also, for this test, the results showed that pre- and postsurgery epilepsy patients presented lower performance than the control group (p= 0.05); This same result was observed when applying the UPSIT in American TLE patients before and after surgery. &quot;Odor Tablets¿ proved to be easy to administer in adult subjects, showed a high coefficient of the test-retest reliability (r = 0.87, p<0.001), and the tablets presented a storage stability for 3 months. The discrimination test results showed that elderly and epilepsy patient groups presented lower performance in the discrimination measurement and hit rate parameters than the control group. The results obtained using the CATS test in American TLE patients revealed that both pre-and post-surgery showed deficits in the facial and vocal emotions when compared with the control group, especially for negative emotions. The fact that the &quot;Odor Tablets¿ and the discrimination odor test developed in the present study had detected olfactory dysfunction in elderly subjects and epilepsy patients, provides their validity for use in the diagnoses of these population / Doutorado / Consumo e Qualidade de Alimentos / Doutor em Alimentos e Nutrição

Loss of olfactory function can readily be overlooked in a clinical setting. In most cases, symptomatic patients recover the sense of smell without any treatment due to the intrinsic neuroregenerative capacity in adult olfactory epithelium. The substantial prevalence of olfactory dysfunction following viral infection of the respiratory system leads many clinicians to consider this physical dysfunction as a subjective symptom rather than a diagnostic and pathologic sign amenable to analysis. Better understanding of the mechanisms behind olfactory dysfunction is expected to increase its clinical importance. Through analyzation of human and mouse specimens, one is able to gain insight into viral-induced olfactory dysfunction on a pathophysiologic level. These murine and human models provide a better understanding of mechanisms and reveal potential therapeutic targets. This is becoming increasingly useful considering the high prevalence of olfactory loss among COVID-19 patients. Here, we discuss the process of olfactory loss following viral infection, the possible mechanism of sudden olfactory dysfunction in COVID-19 infection, the possible benefits of clinical smell tests in COVID-19 patients, and a potentially overlooked consequence on olfactory function using dexamethasone in treating COVID-19 patients. We suggest that including smell tests in COVID-19 patients and studying the mechanism underlying olfactory dysfunction could provide potential strategy to prevent COVID-19 infection and spread and reveal potential therapeutic intervention to restore sense of smell. There are 18 sources used for this miniature literature review. All of our resources were chosen for up-to-date information regarding COVID-19 and it’s effect on the olfactory system. The sources were either found during a large PubMed search or recommendations sent from professors. This article just recently underwent a revision. After revision, our conclusions that smell tests would be beneficial in a clinical setting to prevent the spread and reveal therapeutic targets have been supported by the articles listed. This has been submitted and accepted by a peer-reviewed journal.

Purpose This study aimed to evaluate the course of olfactory dysfunction [OD] due to upper respiratory tract infections [URTI] especially for COVID-19 [C19] in a multicentric design and to investigate possible predictors for the outcome. Methods In a multicentric study, patients (n = 147, of which 96 were women) with OD due to URTI, including C19 and non-C19 were evaluated at two visits with a standardized medical history and “Sniffin’ Sticks” extended psychophysical testing to examine the course and possible predictors for improvement of olfactory function. Results C19 patients showed better overall olfactory function (p < 0.001) compared to non-C19. Olfactory function (p < 0.001) improved over 3.5 ± 1.2 months in a comparable fashion for C19 and non-C19 comparable over time (p = 0.20) except for a more pronounced improvement of odour threshold (p = 0.03) in C19. C19 patients with parosmia exhibited a higher probability of clinically relevant improvement of odour threshold, a better threshold in the second visit, and tended to have a better TDI-score at the second visit. Further possible predictors for an improving olfactory function were younger age, female gender, and had lower scores in olfactory tests at the first visit. Conclusions Patients with C19 and non-C19 URTI exhibit a similar improvement over 3–4 months except for the odour threshold, with a better TDI in both visits for C19. For C19 a better prognosis in terms of olfactory recovery was found for younger patients with parosmia and lower olfactory scores at the first visit. Still, for many patients with olfactory loss, an improvement that is experienced as complete may only occur over months and possibly years.

With covid-19 affecting people's ability to smell, it might be of interest to find multimodal solutions, where other senses could assist someone with an impaired sense of smell to identify an odor. This area of research lacks data since there has not been many studies on this. Moreover, there are studies that tried to find a connection between sound and smell in other contexts. The goal of this study was to find if it is possible to communicate an odor, with the help of foley sound, to someone with an impaired sense of smell. This required answers to questions regarding whether people, with and without a changed sense of smell, can improve their odor identification with the help of sound and if foley is an effective method for it. This was tested by first collecting sound associations to odors, as well as cultural associations. The data were analyzed to find common themes to choose the sounds that would be used. The participants in the study were asked to make free identifications after being presented with odor pens together with additional stimuli cues. The experiment included tests with an associated color, a matching foley sound, a matching soundscape, an incongruent color and an incongruent foley sound. The results showed that sound in general has a positive impact on someone's identification capabilities, which were measured by counting the amount of right answers on each test. The odors coffee, fish and leather had foley sound that greatly increased the amount of correct answers whilst the foley sound to lemon, rose and peppermint had less of an impact. People with an imparied sense of smell were affected similarly to the different stimuli as people without an impairment. Since identification of odors are dependent on prior experiences, some odors could be harder or easier to identify. In order to create an auditory icon for an odor there needs to be strong collective associations for it to be efficient in relaying information and not being distracting. / Covid-19 har haft en negativ effekt på människors förmåga att känna lukt, och därmed finns det ett intresse av att undersöka och hitta multimodala lösningar där andra sinnen kan hjälpa att identifiera en lukt. Det har inget större omfång av liknande forskning inom detta område. Däremot finns det studier som försökt hitta en koppling mellan ljud och lukt i andra kontexter. Målet med denna studie var att ta reda på ifall ljud kunde hjälpa att kommunicera en lukt för någon med försämrat luktsinne. Detta innebar att besvara frågor huruvida foleyljud kan förbättra människors luktidentifieringsförmåga, både för dem med nedsatt luktförmåga och oförändrat luktsinne. Det innebar också att testa ifall foleyljud är effektivare än andra typer av ljud. Forskningsfrågorna testades genom att först samla in ljud associationer till olika lukter, samt kulturella associationer. Datan analyserades för att hitta gemensamma teman att göra ljud av. Deltagarna i studien ombads skriva fria identifieringar efter att ha presenterats med doftpennor, samtidigt som de utsattes för ett annat stimulus. De stimulikombinationer som testades var doft med associerad färg, doft med ett tillhörande foleyljud, doft med en tillhörande ljudbild, samt versioner med inkongruent färg och inkongruent foleyljud. Resultatet visar att ljud har en positiv påverkan på personers identifieringsförmåga, vilket mättes med hur många som skrev rätt doft på varje test. Lukterna kaffe, fisk och läder hade foleyljud som ökade antalet rätta svar medan foleyljud till lukterna citron, ros och pepparmynta hade en mindre påverkan. Personer med nedsatt luktsinne påverkades på liknande sätt av de olika testerna som folk utan påverkan. Då luktperception påverkas av tidigare erfarenheter kan olika lukter vara svårare eller lättare att identifiera. För att lukt ska kunna sonifieras behövs starka kollektiva associationer som är tillräckligt kända för att lättare förmedla information och inte distrahera lyssnaren.

L’infection virale des voies respiratoires supérieures est la cause la plus fréquente des troubles de l’odorat. L’entraînement olfactif permet un rétablissement des fonctions olfactives chez une bonne proportion des patients avec une perte olfactive post-virale. Aussi, les fonctions olfactives sont corrélées avec différentes mesures neuroanatomiques du cortex olfactif. L’objectif de ce mémoire est donc de reproduire les résultats bénéfiques de l’entraînement olfactif chez des patients avec un trouble de l’odorat post-viral et d’observer si le rétablissement des performances olfactives modifie l’épaisseur corticale des régions olfactives. Trente-neuf patients ayant un trouble de l’odorat post-viral ont complété un entraînement olfactif d’une durée de 12 semaines. L’entraînement olfactif consistait à sentir des contenants avec une odeur de rose, de citron, d’eucalyptus et de clou de girofle, deux fois par jour. Les capacités olfactives ont été mesurées avec les tests Sniffin’Sticks au début et à la fin de l’étude. L’entraînement olfactif a permis l’amélioration clinique (≥6 points SDI) des fonctions olfactives chez 59% des patients. Ces patients avaient une épaisseur corticale plus importante au niveau du cortex orbitofrontal latéral gauche à p<0,0001 non corrigé. Les patients avec une amélioration du score SDI (≥0,25 points) ont une augmentation de l’épaisseur du cortex orbitofrontal médial gauche, du cortex entorhinal droit et du cortex cingulaire postérieur gauche (p<0,0001, non corrigé). Ces résultats démontrent l’efficacité de l’entraînement olfactif chez les patients avec un trouble de l’odorat post-viral et que la rémission des fonctions olfactives semble modifier l’épaisseur corticale de certaines régions du cortex olfactif. / Viral infection of the upper respiratory tract is the most common cause of disturbances in smell. Olfactory training allows a reestablishment of olfactory functions in a good proportion of patients with post-viral olfactory loss. Also, olfactory functions are correlated with different neuroanatomic measures of the olfactory cortex. The objective of this dissertation is therefore to reproduce the beneficial results of olfactory training in patients with post-viral olfactory dysfunction and to observe whether the restoration of olfactory performances changes the cortical thickness of the olfactory cortex. Thirty-nine patients with post-viral olfactory dysfunction completed a twelve-week olfactory training. The olfactory training consisted of smelling containers with the scent of roses, lemon, eucalyptus and cloves, twice a day. Olfactory functions were measured with the Sniffin'Sticks tests at the start and end of the study. Olfactory training resulted in clinical improvement (≥6 SDI points) of olfactory functions in 59% of patients. These patients had greater cortical thickness in the left lateral orbitofrontal cortex at p <0,0001 uncorrected. Patients with improved SDI score (≥0,25 points) had an increase in the thickness of the left medial orbitofrontal cortex, right entorhinal cortex and left posterior cingulate cortex (p <0,0001, uncorrected). These results demonstrate the effectiveness of olfactory training in patients with post-viral olfactory loss and that remission of olfactory functions appears to alter the cortical thickness of certain regions of the olfactory cortex.

Le trouble de l’odorat est un symptôme fréquent bien connu de la Maladie de Parkinson (MP). Il apparaît plusieurs années avant la possibilité d’un diagnostic de la maladie et son étude est ainsi d’intérêt particulier pour aider au développement d’outils de dépistage précoces et la sélection de candidats pouvant participer à des essais cliniques visant le développement de traitements potentiellement curateurs. Pour ce faire, il est important de différencier un trouble de l’odorat associé à la MP d’autres troubles de l’odorat non reliés à une maladie neurodégénérative (trouble de l’odorat non-parkinsonien : TONP), tels que des troubles de l’odorat liés à une infection virale, à un traumatisme craniocérébral ou des troubles sinu-nasaux. Le système olfactif est plus complexe qu’il ne le semble et est intimement lié au système trigéminal, un système moins bien connu, qui permet, entre autres, la perception de sensations de fraicheur, chaleur et picotement des odeurs. L’interaction entre les systèmes olfactif et trigéminal est complexe et peu connue. La sensibilité trigéminale est typiquement réduite dans le cas d’un système olfactif altéré dans les TONP, mais il n’est pas bien compris comment les deux systèmes interagissent ensemble dans le cas d’un trouble de l’odorat associé à la MP. L’objectif principal de cette thèse visait donc la caractérisation du trouble de l’odorat associé à la MP lorsque spécifiquement comparé à des patients atteints de TONP. Par conséquent, cette thèse avait aussi pour objectif d’apporter une meilleure compréhension de l’interaction entre les systèmes olfactif et trigéminal dans le cas d’un système olfactif fonctionnel et d’un système olfactif altéré dans la MP et d’autres TONP. Nous avons donc d’abord évalué la sensibilité olfactive et trigéminale, sur le plan comportemental (étude 1). Cette première étude a permis d’identifier un patron de réponse spécifique dans la MP avec un système olfactif altéré et un système trigéminal intact,en comparaison à des contrôles, en contraste à une sensibilité trigéminale réduite dans les TONP. Dans le même ordre d’idée, nous avons ensuite évalué la perception des dimensions trigéminales et olfactives de différentes odeurs (étude 2). Nos résultats suggèrent que la perception de sensations trigéminales est intacte chez les patients avec la MP en contraste à la perception de dimensions olfactives qui est réduite, comparativement à des contrôles. Pour mieux comprendre l’interaction entre le système olfactif et trigéminal dans le cas d’un système olfactif fonctionnel, nous avons ensuite évalué l’impact d’un stimulus olfactif sur la capacité à latéraliser un stimulus trigéminal chez des participants contrôles (étude 3). Cette étude a démontré un effet d’amplification de la réponse trigéminale lors d’une co-stimulation olfactive ipsilatérale suggérant ainsi une interaction au niveau de l’épithélium nasal. Afin de mieux comprendre la réponse trigéminale dans la MP, nous avons évalué la sensibilité trigéminale périphérique et centrale en réponse à un stimulus trigéminal pur via des mesures électrophysiologiques (étude 4). Nous avons ainsi démontré une altération spécifique de la réponse trigéminale dans la MP comparativement à d’autres TONP et à des contrôles. Puisque le bulbe olfactif est l’une des premières régions affectées dans la MP, nous avons ensuite mesuré le volume du bulbe olfactif sur des images IRM (étude 5). Nos résultats ont démontré un volume réduit dans la MP et les TONP comparativement à des contrôles, mais aucune différence entre les patients atteints de la MP et de TONP. Néanmoins, l’utilisation de techniques d’apprentissage profond sur les images IRM du bulbe olfactif a permis de différencier les patients avec la MP des TONP avec une exactitude considérable. Enfin, nous avons étudié la connectivité fonctionnelle au sein du réseau chimiosensoriel (étude 6). Nous avons ainsi identifié des altérations spécifiques de la connectivité et la modularité des réseaux entre des régions de traitement olfactif et trigéminal au repos et lors de la réalisation d’une tâche olfactive et d’une tâche trigéminale chez des patients atteints de la MP en comparaison avec des TONP et des contrôles. En conclusion, la série d’études présentée dans cette thèse contribue à une meilleure compréhension du trouble de l’odorat associé à la MP et propose de potentielles pistes pour le différencier d’autres TONP, notamment par la mesure du système trigéminal. Cette thèse apporte une meilleure compréhension de l’interaction entre le système olfactif et trigéminal dans un système olfactif fonctionnel et de son altération dans les troubles olfactifs associés à la MP ou à d’autres TONP. La caractérisation de ce symptôme non-moteur pourra éventuellement aider au développement d’outils de dépistage précoce de la MP. / Olfactory dysfunction is a highly reliable non-motor symptom of Parkinson’s disease (PD) that appears several years before the possibility of a diagnosis of the disease. Hence, its study is of particular interest to help the development of early diagnosis tools and the selection of ideal candidates to participate in clinical trials that aims to test potential neuroprotective treatments. To do so, it is important to differentiate PD-related olfactory dysfunction from other non-neurodegenerative forms of olfactory dysfunctions that can be related to infections, head trauma or sinonasal disease (non-parkinsonian olfactory dysfunction: NPOD). The olfactory system is more complex than it seems and is intimately connected to the trigeminal system, a less well-known system, that allows, amongst others, the perception of sensation of freshness, warmth, and piquancy of odors. The interaction between the olfactory and trigeminal system is complex and not well understood. Trigeminal sensitivity is typically reduced in cases of an impaired olfactory system related to NPOD; however, this is not clear how both systems interact together in PD-related olfactory dysfunction. The main objective of this thesis was to principally characterize PD-related olfactory dysfunction when specifically compared to patients with NPOD. Consequently, this thesis also aimed to bring a better understanding of the interaction between the olfactory and trigeminal system in a fully functional olfactory system as well as in alterations of the olfactory system associated with PD and other NPOD. We have thus first assessed the olfactory and trigeminal sensitivity using behavioral measures (study 1). This study allowed the identification of a specific response pattern in PD patients with an altered olfactory system and an intact trigeminal system, when compared to controls, in contrast to the reduced trigeminal sensitivity observed in NPOD. We then evaluated the perception of trigeminal and olfactory dimensions of different odors (study 2). Our results suggest that the perception of trigeminal sensations is intact in patients with PD in contrast to the perception of olfactory dimensions which is reduced when compared to control participants. To better understand the interaction between the olfactory and trigeminal systems in a functioning olfactory system, we evaluated the impact of an olfactory stimulus on the capacity to lateralize a trigeminal stimulus in healthy participants (study 3). This study has demonstrated an amplification effect of the olfactory system on the trigeminal system particularly during ipsilateral co-stimulation, suggesting an interaction at the level of the olfactory mucosa. To better understand the trigeminal response in PD patients, we further investigated the peripheral and central trigeminal sensitivity in response to a pure trigeminal stimulus by means of electrophysiological measurements (study 4). We thus demonstrated a specific alteration of the trigeminal response in PD patients when specifically compared to patients with NPOD and healthy control participants. As the olfactory bulb is one of the first regions to be affected in PD, we then measured the olfactory bulb volume on MRI scans (study 5). Our results showed reduced olfactory bulb volume in PD patients as well as in NPOD, when compared to controls, but no difference between PD and NPOD patients. Interestingly, the use of deep learning techniques on MRI scans of the olfactory bulb allowed the discrimination between PD patients and NPOD patients with considerable accuracy. Finally, we investigated the functional connectivity within the chemosensory network (study 6). We identified a specific pattern of functional connectivity and chemosensory network modularity in PD patients at resting-state and while performing an olfactory or a trigeminal task, when specifically compared to patients with NPOD and controls. In conclusion, all taken together, the studies presented in this thesis contributes to a better understanding of the PD-related olfactory dysfunction and suggest potential avenues to differentiate it from NPOD, notably through the measurement of the trigeminal system. This thesis brings further knowledge regarding the interaction between the olfactory and trigeminal systems in a functional olfactory system and its alteration in cases of an impaired olfactory system related to PD or NPOD. The characterization of this non-motor symptom of the disease will eventually help the development of early diagnostic tools for PD.