Dissertations / Theses: 'Insular cortex'

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Rogers-Carter, Morgan M. "TheRole of the Insular Cortex in Rodent Social Affective Behavior:." Thesis, Boston College, 2019. http://hdl.handle.net/2345/bc-ir:108375.

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Thesis advisor: John P. Christianson In social species, animals must detect, evaluate and respond to the states of other individuals in their group. A constellation of gestures, vocalizations, and chemosignals enable animals to convey affect and arousal to others in nuanced, multisensory ways. Observers integrate such social information with environmental cues and internal physiology to general social behavioral responses via a process called social decision-making. The mechanisms and anatomical correlates of social decision-making, particularly those that allow behavioral responses to others’ emotional states, are not fully known. Therefore, the objective of this dissertation is to broaden the anatomical understanding of social decision-making by investigating the role of the insular cortex in social behaviors that depend upon others’ emotional state. Using a novel behavioral paradigm, I present causal evidence that implicates the insular cortex and its projections to the nucleus accumbens in social affective behavior. These findings are consistent with evidence from the literature that suggests insular cortex is positioned to convey sensory cues to social brain structures to produce flexible and appropriate behavioral responses to social affective cues Thesis (PhD) — Boston College, 2019 Submitted to: Boston College. Graduate School of Arts and Sciences Discipline: Psychology

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Tensaouti, Yacine. "Contribution of the rat insular cortex to stimulus-guided action." Electronic Thesis or Diss., Bordeaux, 2024. http://www.theses.fr/2024BORD0216.

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Chaque jour, nous sommes confrontés à de nombreuses décisions qui façonnent nos comportements. Les facteurs influençant ces choix sont multiples. Les besoins et désirs immédiats jouent souvent un rôle important dans la sélection des actions, guidés par la valeur du but. Cependant, il est essentiel de reconnaître l'impact des stimuli environnementaux. Par exemple, les stimuli alimentaires peuvent non seulement nous orienter vers la nourriture, mais aussi déclencher des envies, même en l'absence de faim. Afin d’identifier le rôle du cortex insulaire (CI) du rat dans les actions guidées par des stimuli et visant à obtenir des aliments, nous avons utilisé le paradigme du transfert Pavlovien-Instrumental (PIT). Étant donné le rôle bien établi du CI dans l'encodage et la surveillance des attentes générales et spécifiques, et sa contribution critique dans le choix guidé par la valeur spécifique d’un but, nous avons émis l'hypothèse d'un rôle du CI pendant le test de transfert PIT où les actions sont influencées par des stimuli prédictifs de récompense. Grâce à une approche chimiogénétique, nous avons démontré que l'inhibition du CI pendant les tests de transfert généraux et spécifiques abolissait la capacité des stimuli prédictifs de récompense pavloviens à stimuler la réponse instrumentale et à orienter spécifiquement le choix de l'action vers la même récompense que le stimulus prédictif présenté, respectivement. Ces résultats démontrent pour la première fois le rôle critique du CI dans le choix guidé par stimulus, englobant à la fois les propriétés motivationnelles générales acquises par les stimuli pavloviens et leur capacité à orienter spécifiquement la sélection de l'action vers des résultats spécifiques. De plus, nos résultats préliminaires suggèrent que cette dernière peut dépendre de façon critique d'une voie cortico-thalamique intacte impliquant la partie médiodorsale du thalamus Every day, individuals are faced with numerous decisions that shape their behavior. The factors influencing these choices are multifaceted and encompass a range of considerations. Immediate needs and desires often play a significant role in action selection, guided by the value of the outcome. However, it is crucial to recognize the impact of environmental stimuli. For instance, stimuli associated with food can not only direct us toward nourishment but also trigger cravings, even in the absence of hunger. To uncover the role of the rat insular cortex (IC) in stimulus-guided actions directed towards obtaining food outcomes, we used the Pavlovian-to-Instrumental Transfer (PIT) paradigm. Given the well-established role of IC in encoding and tracking general and specific outcome-expectancies, and its critical contribution in choice guided by specific-outcome values, we hypothesized a role of the IC during the PIT transfer test where actions are influenced by reward-predictive stimuli. Using chemogenetics, we demonstrated that IC inhibition during both general and specific transfer tests abolished the ability of Pavlovian reward-predictive stimuli to energize instrumental responding, and to specifically bias action selection towards the same outcome as the presented predictive stimulus, respectively. These results demonstrated for the first time the critical role of the IC in stimulus-guided choice, encompassing both the general motivational properties acquired by Pavlovian stimuli and their ability to specifically bias action selection towards specific outcomes. Moreover, preliminary results suggest that the latter may critically depend on an intact cortico-thalamic pathway involving the mediodorsal part of the thalamus. In conclusion, we provide the first evidence that the GC is required for both general and specific forms of PIT, with the latter depending on an intact cortico-thalamic pathway

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Jones, Catherine Louise. "The role of insular cortex in the integration of emotion, perception and cognition." Thesis, University of Brighton, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.590010.

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Influential models highlight that insular cortex integrates cognitive, affective, sensorimotor and autonomic signals to create unified perceptual experiences or "feeling states". One challenge in developing a satisfactory neuropsychological model of insula function is to account for its involvement across these different domains which require access across multiple functional circuits. This thesis combines behavioural, psychophysiological, functional neuroimaging and lesion methods to inform and extend current models of integration in the insula. In the first two experimental chapters, the integration of cognitive and emotional signals in risky decision making and autonomic regulation and feedback are investigated. In the final two experimental chapters the role of the insula in combining sensory information in the creation of perceptual illusions is explored. I find that the insula mediates urgent decision making, that damage to the insula can disrupt integrative processes in the context of multisensory integration and that the affective elements of synaesthetic illusions are associated with insula engagement. Together these findings shape our understanding of how the insula acts to integrate signals across different contexts and make an important and novel contribution in the development of a potentially unitary account of insula function.

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Couderc, Yoni. "Dopaminergic modulation of the insular cortex in anxiety-related behaviors and emotional valence." Electronic Thesis or Diss., Bordeaux, 2025. http://www.theses.fr/2025BORD0017.

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L'anxiété est une réponse adaptative des individus exposés à un contexte potentiellement menaçant. Cependant, des niveaux d'anxiété peuvent rester élevés de manière persistante, indépendamment de l'environnement, et devenir pathologiques. Bien que les troubles anxieux soient les affections psychiatriques les plus répandues – caractérisés par des niveaux chroniques élevés d'anxiété et un biais attentionnel envers les stimuli à valence négative – les mécanismes neurobiologiques sous-jacents restent encore mal compris. De nombreuses études, menées chez l'humain et dans des modèles précliniques, ont mis en évidence l'implication de différents neuromodulateurs, notamment la sérotonine, la noradrénaline, mais aussi la dopamine. Des études d'imagerie fonctionnelle ont montré que le cortex insulaire (ou insula), en particulier sa région antérieure, est hyperactivé chez les individus souffrant de troubles anxieux en réponse à des stimuli saillants ou négatifs. Bien que la neurotransmission dopaminergique soit connue pour réguler l'anxiété chez l'humain et dans les modèles animaux, ses effets spécifiques sur l'insula antérieure restent largement inexplorés.Cette thèse vise à explorer le rôle de la transmission dopaminergique dans le cortex insulaire dans la modulation de l'anxiété et de la valence émotionnelle chez la souris. À travers une approche multifactorielle, cette recherche a permis de révéler comment la dopamine module la fonction de l'insula antérieure dans les comportements liés à l’anxiété et à la valence émotionnelle, selon trois niveaux d’analyse clés. (1) Tout d’abord, nous avons cartographié le système dopaminergique insulaire et identifié une forte densité de neurones exprimant les récepteurs dopaminergiques de type 1 (D1), particulièrement marquée dans l’insula antérieure, et sept fois supérieure à celle des neurones exprimant les récepteurs de type 2 (D2). De plus, l’activation pharmacologique des récepteurs D1 dans l’insula antérieure s’est révélée anxiogène, établissant un lien direct entre la signalisation dopaminergique insulaire et les comportements associés à l’anxiété. (2) Par photométrie en fibre, nous avons montré que l’amplitude de la libération de dopamine sur les neurones D1-positifs de l’insula antérieure augmentait lorsque les souris étaient exposées à des espaces anxiogènes ou à des chocs électriques légers. Cette libération de dopamine était positivement corrélée avec le niveau d'anxiété intrinsèque des souris, renforçant l'idée que la dopamine joue un rôle central dans la modulation des réponses anxieuses. (3) Enfin, grâce à l’analyse par intelligence artificielle des dynamiques de population neuronale et des enregistrements de neurones unitaires dans l’insula antérieure, nous avons identifié des propriétés de codage neuronal distinctes pour les environnements anxiogènes et protégés, ainsi que pour les stimuli gustatifs à valence positive ou négative. De façon intéressante, l’activation systémique des récepteurs D1, qui augmente les comportements de type anxieux, perturbe cette dichotomie de codage en rendant le codage des espaces protégés plus variable et celui des espaces anxiogènes plus spécifique. De plus, le codage des espaces anxiogènes était corrélé positivement au niveau d’anxiété intrinsèque des souris. Nous avons également observé une tendance à une corrélation positive entre la spécificité du codage des stimuli gustatifs négatifs et le niveau d'anxiété des souris.En conclusion, ces résultats mettent en lumière un nouveau modèle de codage neuronal dans l’insula antérieure, en lien avec l’anxiété et la valence émotionnelle. Ils dévoilent également des mécanismes de codage dépendant des récepteurs D1 dans l’insula antérieure de la souris, ouvrant ainsi de nouvelles perspectives pour comprendre et traiter les troubles anxieux Anxiety is an adaptive response of individuals exposed to a potentially threatening context. However, anxiety levels can be persistently high independently of the environment and become pathological. Although anxiety disorders represent the most prevalent psychiatric conditions - characterized by chronic high levels of anxiety and an attentional bias towards negative valence - the underlying neurobiology remains poorly understood. Numerous studies in humans and in preclinical models revealed the implication of different neuromodulators including serotonin, norepinephrine, but also dopamine. Imaging studies have shown that the insular cortex (or insula), particularly its anterior region, is hyperactivated in individuals with anxiety disorders in response to salient or negative stimuli. Although dopamine neurotransmission is known to regulate anxiety in humans and animal models, its specific regulatory effects on the anterior insula have remained largely unexplored.This PhD dissertation aims to investigate the role of dopamine transmission in the insular cortex in shaping anxiety and emotional valence in mice. Through a multifaceted approach, this research uncovered how dopamine modulates anterior insula function in anxiety and valence processing at three key levels of analysis. (1) First, we mapped the dopaminergic system of the insular cortex and revealed a high density of neurons expressing type-1 dopamine receptors (D1) in the insula, particularly important in the anterior insula, and seven times greater than the density of neurons expressing type-2 dopamine receptors (D2). Then, we found that pharmacological activation of D1 in the anterior insula is anxiogenic, suggesting a direct link between insular dopamine signaling and anxiety-related behaviors. (2) Using fiber-photometry, we identified that the amplitude of dopamine release onto D1+ neurons in the anterior insula while mice were in anxiogenic spaces or receiving mild foot shocks was both positively correlated with mice level of trait anxiety. (3) Finally, population dynamics and deep-learning analyses of anterior insula single-unit recordings uncovered distinct coding patterns of anxiety-provoking and safe environments, as well as tastants of positive and negative valence. Remarkably, systemic D1 activation, which heightens anxiety-related behaviors, dampens this coding dichotomy by increasing coding variability for protected spaces while increasing the coding specificity for anxiogenic spaces. Interestingly, the coding reliability of anxiogenic areas was positively correlated with mice level of trait anxiety, and we observed a trend towards a positive correlation between the coding reliability of a negative tastants, and mice level of anxiety.Altogether, our findings provide a new model of neural population coding of anxiety and emotional valence and unravel D1-dependent coding mechanisms in the mouse anterior insula

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Gehrlach, Daniel [Verfasser], and Rüdiger [Akademischer Betreuer] Klein. "Anatomical and functional characterization of the mouse insular cortex / Daniel Gehrlach ; Betreuer: Rüdiger Klein." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1216039178/34.

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Dupin, Alice. "Insular Cortex neurons projecting to the vagal complex : characterization and roles in behavior and inflammation." Electronic Thesis or Diss., Sorbonne université, 2024. http://www.theses.fr/2024SORUS192.

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Les interactions entre le cerveau et le reste du corps sont cruciales pour la survie de l'organisme. Le cerveau reçoit et intègre une multitude d'informations externes et internes et régule diverses fonctions physiologiques en permanence. Notamment, le système nerveux interagit étroitement avec le système immunitaire. En cas d'infection, les caractéristiques uniques du cerveau permettent une régulation optimisée des réponses immunitaires. Cela inclut la capacité du cerveau à détecter les signaux environnementaux, à anticiper les situations à venir et à transmettre rapidement des signaux à travers un vaste réseau de neurones innervant l'ensemble du corps en quelques millisecondes. Le nerf vague, reliant le cerveau aux organes viscéraux, est un support important de cette communication bidirectionnelle. Il est composé de branches sensorielles et motrices. Les afférences relaient les informations périphériques au complexe vagal dans le cerveau, qui transmet les signaux aux structures cérébrales plus profondes, tandis que les efférences motrices transmettent les réponses générées vers les organes cibles. Dans le traitement des informations intéroceptives, le cortex insulaire émerge comme un hub multimodal essentiel. En tant que cortex sensoriel, il reçoit diverses entrées des systèmes de détection externes tels que les cortex somatosensoriels et olfactifs, tout en étant densément interconnecté avec les régions comme le complexe vagal, traitant les signaux internes tels que les stimuli inflammatoires. Cela permet au cortex insulaire d'intégrer les informations extéroceptives et intéroceptives et de jouer un rôle central dans le ‘salient network'. Au sein de l'organisme, il peut optimiser les réponses à des situations spécifiques en régulant l'activité cardiaque ou intestinale, ainsi que les réponses immunitaires, mais les circuits qui médient ces fonctions ne sont pas bien connus. Compte tenu de l'importance du nerf vague dans la transmission d'informations entre le cerveau et la périphérie, ainsi que l'existence de projections du cortex insulaire vers le complexe vagal (InsCtxVC), nous émettons l'hypothèse que certaines fonctions du cortex insulaire sont médiées par le nerf vague. Pour étudier le rôle de l'InsCtxVC, nous avons d'abord caractérisé ces neurones anatomiquement à l'aide d'un virus rétrograde permettant leur marquage. Nous avons constaté que les neurones InsCtxVC sont principalement situés dans le cortex insulaire postérieur-intermédiaire dans la couche V, et expriment CTIP, un effecteur en aval de la voie Fezf2. Ensuite, nous avons examiné les entrées et sorties de ces neurones en utilisant des marqueurs viraux. Nos expériences ont révélé qu'au sein du complexe vagal, les neurones InsCtxVC établissent préférentiellement des synapses avec le NTS médian (plutôt que le NTS caudal ou le DMN), ainsi qu'avec l'amygdale centrale et le noyau parasubthalamique. De plus, nous avons analysé leurs entrées présynaptiques, mettant en évidence une innervation prédominante des cortex sensoriels, y compris le cortex insulaire lui-même, et les cortex somatosensoriels et olfactifs. Sur la base de nos résultats anatomiques et de la littérature, nous avons examiné divers contextes susceptibles de recruter l'InsCtxVC. Grace à des manipulations chemogénétiques et optogénétiques spécifiques de ces neurones, nous avons constaté que l'InsCtxVC n'est pas impliqué dans les comportements anxieux ou l'aversion gustative conditionnée neuro-immunitaire. Cependant, l'activation chemogénétique des neurones InsCtxVC lors d'une inflammation induite par le LPS exacerbe le comportement de maladie, incluant une perte de poids accrue, une élévation des cytokines pro-inflammatoires et de la corticostérone dans le sang.En conclusion, nos résultats caractérisent une population neuronale non décrite précédemment reliant le cortex insulaire à un centre parasympathique majeur régulant les réponses immunitaires périphériques Brain-body interactions are crucial for organisms survival; the brain constantly receives external and internal information that it integrates to regulate various physiological function. Notably, the nervous system closely interacts with the immune system. In the case of inflammation, the brain's features enable an optimized regulation of immune responses. These features include the brain's ability to sense environmental cues, anticipate outcomes, and transmit signals rapidly through an extensive network of neurons innervating the entire body within milliseconds. The vagus nerve, linking the brain to visceral organs, is an important support of this bidirectional communication. It is composed of sensory and motor branches. Sensory afferences carry peripheral information to the vagal complex in the brain which transmits the signals to deeper brain structures, while motor efferences mediate the generated responses to targeted organs.In processing internal information, the insular cortex emerges as a critical multimodal hub. As a sensory cortex, it receives various inputs from external-sensing systems such as somatosensory, and olfactory cortices, while also being densely interconnected with regions processing internal cues such as inflammatory threats, such as the vagal complex. This allows the insular cortex to integrate exteroceptive and interoceptive information and play a pivotal role in the salience network. Within the organism, it can optimize responses to specific situations by regulating cardiac or intestinal activity, as well as immune responses, but the underlying circuits are poorly understood. Given the role played by the vagus nerve in transmitting information between the brain and the periphery, along with the presence of projections from the insular cortex to the vagal complex (InsCtxVC), we hypothesize that some of the insular cortex functions are mediated through the vagus nerve.To investigate the role of InsCtxVC, we first characterized these neurons anatomically using viral retrograde labeling. We found that InsCtxVC are predominantly located within the posterior-intermerdiate InsCtx, mainly in layer V, and express CTIP, a downstream effector of the Fezf2 pathway. Next, we examined the connectivity of these neurons using viral labeling of outputs and inputs. Our experiments revealed that within the vagal complex, InsCtxVC neurons preferentially synapse with the medial NTS (rather than caudal NTS or DMN), and the central amygdala and parasubthalamic nucleus. Additionally, we analyzed their presynaptic inputs, highlighting a predominant innervation from sensory cortices including the insula itself, the somatosensory and olfactory cortices. Based on our anatomical findings and existing litterature, we screened various contexts likely to recruit the InsCtxVC. Through specific chemogenetic and optogenetic manipulation of these neurons, we found that InsCtxVC are not involved in anxiety behaviors or neuroimmune conditionned taste aversion. However, chemogenetic activation of InsCtxVC neurons during early LPS-induced inflammation exacerbates sickness behavior, including increased weight loss, elevated blood proinflammatory cytokines and corticosterone response. Taken together, our results characterize a previsouly undefined neuronal population linking the insular cortex to a major parasympathetic center, which regulates immune responses in the periphery

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Cosme, Caitlin Victoria. "The role of the prefrontal cortex in cocaine and heroin seeking following extinction training." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5924.

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The prefrontal cortex (PFC) is considered a critical node in the neural circuitry underlying drug-seeking behaviors. However, the mechanisms by which this region influences drug seeking and whether or not the lateral PFC mediates cocaine or heroin seeking are questions that have yet to be answered. To expand on the role of the PFC in drug seeking, rats were trained on either heroin or cocaine self-administration for a minimum of 12 days before undergoing extinction training and subsequent reinstatement tests (cued and drug-prime). All pharmacological manipulations were delivered immediately prior to reinstatement testing and were targeted at either the ventral region of the medial PFC, the infralimbic cortex (IL), the anterior portion of the medial PFC, the medial orbitofrontal cortex (mOFC), the anterior region of the insular cortex, the dorsal agranular insular cortex (AId), or the posterior region of the insular cortex, the posterior insular cortex (PIc). In chapter 1, D1 and D2 antagonists were administered into the IL and mOFC prior to cued and cocaine-prime reinstatement. Although previous studies found that the IL inhibits cocaine seeking, blocking D1 receptor activity in this region reduced cued reinstatement and had no effect on cocaine-prime reinstatement, indicating that the IL can promote cocaine seeking under certain circumstances. In contrast, blocking D1 receptors in the mOFC reduced all forms of reinstatement that were examined. Blocking D2 receptors in either region had no effect on cocaine seeking. Our data are the first to demonstrate a role for the mOFC in cocaine seeking and suggest that although the IL and mOFC lie immediately adjacent to one another, they play distinct roles in mediating cocaine seeking. In chapter 2, we pharmacologically inactivated the AId and PIc via a GABA agonist administered immediately prior to both cocaine and food seeking. Reversible inactivation of the AId reduced cued reinstatement but had no effect on cocaine-prime reinstatement. In contrast, inactivating the PIc had no effect on any form of cocaine seeking. Additionally, blocking the AId during cued and food-prime reinstatement had no effect on food seeking, indicating the role of the AId in reinstatement is specific to cocaine seeking and not general motivated behavior. Additionally, blocking CRF1 receptors in the AId blocked cued reinstatement, suggesting a possible mechanism whereby the AId is influencing cocaine seeking. These data are the first to establish a role for the AId in cocaine seeking and demonstrate that although the PIc influences alcohol and nicotine seeking, it does not mediate cocaine seeking. Chapter 3 further examined the role of the AId in cocaine seeking and expanded the influence of the insular cortex in drug seeking to heroin. AId D1 receptor blockade reduced both cued and cocaine-prime reinstatement following extinction training, whereas D2 receptor blockade had no effect on cocaine seeking. These results establish a role for the AId in cocaine-prime reinstatement, as pharmacological inactivation showed no role for the AId in cocaine-induced drug seeking. Additionally, blocking the AId during heroin seeking potentiated cued reinstatement whereas blocking the PIc during heroin seeking reduced cued reinstatement. These results demonstrate a role for the insular cortex in heroin seeking that has never been shown before and further explain how the AId may be influencing cocaine seeking.

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Almashaikhi, Talal. "Electrical brain stimulation and human insular connectivity." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10174/document.

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Le cortex insulaire est le cinquième lobe du cerveau en charge de l'intégration de nombreuses fonctions cognitives, sous-tendues par une organisation cytoarchitectonique etune connectivité aussi riche que complexe. Ce travail vise à évaluer la connectivité fonctionnelle insulaire du cerveau humain par le biais de stimulation électrique intra-cérébrale et de potentiels évoqués cortico-corticaux (PECC) réalisés chez des patients explorés en stéréoélectroencéphalographie (SEEG) pour une épilepsie partielle réfractaire. Nous avons développé un protocole automatisé permettant destimuler successivement l’ensemble des bipoles d’enregistrement intracérébraux (deux plots contigus d’une même électrode) disponibles chez les patients explorés en SEEG. Deux sériesde 20 stimulations monophasiques d’une durée unitaire de 1 ms et d’une intentisté de 1 mA, étaient délivrés à une fréquence de 0,2 Hz au niveau de chaque bipole (105 en moyenne,produisant un total d’environ 11.000 PECC par patient). Un premier travail a consisté dans lamise au point d’une méthode fiable d’analyse statistique objective des PECC significatifs, encomplement de l’analyse visuelle, sur un échantillon de 33017 enregistrements chez trois patients. L’analyse a porté sur les quatre fenêtres temporelles post-stimulation suivantes: 10-100 ms, 100-300 ms, 300-500 ms, 500-1000 ms. La seconde partie de notre thèse a appliquéces méthodes à l’étude des connections intra-insulaires sur un échantillon de10 patients présentant au moins deux éléctrodes intra-insulaires. La dernière partie de notre travail s’est intéressé aux efférences insulaires sur un échantillon de 11 patients. L’étude des PECC apporte des éléments de connectivité fonctionnelle derésolution spatiale et temporelle inégalée, complémentaires de ceux découlant des techniquesde neuroimagerie. La gestion complexe du volume de données à gérer pour chaque patientpeut être résolu par des procédures d’analyse statistiques automatisée de sensibilité etspécificité satisfaisante. Le pattern des connections intra- et extra-insulaires révélé par cetteapproche permet une meilleure compréhension de la physiologie de l’insula chez l’Homme etdes modalités de propagations des décharges épileptiques impliquant ce lobe The insular cortex is the fifth lobe of the brain and is in charge of the integration of many cognitive functions, underpinned by a rich cytoarchitectonic organization and a complex connectivity. Our work aims to evaluate the insular functional connectivity of the human brain using intracerebral electrical stimulation and recording of cortico-cortical evoked potentials (CCEPs) in patients investigated with stereoelectroencephalography (SEEG) for refractory partial epilepsy. We first developed an automated protocol to stimulate successively all intracerebral recorded bipoles (two contiguous leads of the same electrode) available in patients undergoing SEEG. Two sets of 20 monophasic stimulation of 1 ms duration and 1mA intensity were delivered at a frequency of 0.2 Hz at each bipole (105 on average, producing a total of about 11,000 recordings per patient). We then develop a reliable and objective statistical method to detect significant CCEPs as a complement to visual analysis, and validate this approach on a sample of 33017 recordings in three patients. The analysis was performed over four distinct post-stimulus epochs: 10-100 ms, 100-300 ms, 300-500 ms, 500-1000 ms. In the second part of our thesis, we applied these methods to the study of intrainsular connections on a sample of 10 patients with at least two intra-insular electrodes. The last part of our work used the same approach to investigate insular efferents in a sample of 11 patients. The study of CCEPs provides novel and important findings regarding the human brain functional connectivity, with unmatched spatial and temporal resolutions as compared to neuroimaging techniques. The complex management of large volume of data in each patient can be solved by automated statistical analysis procedures with satisfactory sensitivity and specificity. The pattern of connections within and outside the insula revealed by this approach provides a better understanding of the physiology of the Human insula as well as of the propagation of epileptic discharges involving this lobe

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Butti, Camilla. "Organization of the cetacean frontal and insular cortices: cytoarchitecture,chemoarchitecture, and neuronal specializations." Doctoral thesis, Università degli studi di Padova, 2009. http://hdl.handle.net/11577/3426496.

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The brain of cetaceans is very large in both absolute and relative size and possesses an extremely convoluted cortex. The understanding of how the brain of these mammals fully adapted to an aquatic life is organized is important to shed light on the processes that shaped the evolution of the mammalian brain in general, including humans. Three cortical regions, the anterior cingulate (ACC), anterior insular (AI), and frontopolar cortices (FPC) have been shown to be involved in high-level cognitive function in primates and thus, the understanding of their structural organization in cetaceans is particularly meaningful given the wide evidence of their cognitive abilities. Cytoarchitecture, chemoarchitecture based on the distribution of the calcium binding (CaBP) protein calretinin, glia/neuron ratio, and neuronal specializations were assessed in the ACC, AI, and FPC of a series of cetaceans representative of the main families such as the bottlenose dolphin (Tursiops truncatus, Odontoceti, Delphinidae), Risso’s dolphin (Grampus griseus, Odontoceti, Delphinidae), harbor porpoise (Phocoena phocoena, Odontoceti, Phocoenidae), killer whale, (Orcinus orca, Odontoceti, Delphinidae), beluga whale (Delphinapterus leucas, Odontoceti, Monodontidae), sperm whale (Physeter macrocephalus, Odontoceti, Physeteridae), pigmy sperm whale (Kogia simus, Odontoceti, Kogiidae), Amazon river dolphin (Inia geoffrensis, Odontoceti, Iniidae), minke whale (Balaenoptera acutorostrata, Mysticeti, Balaenopteridae), and humpback whale (Megaptera novaeangliae, Mysticeti, Balaenopteridae). Other species including the pigmy hippopotamus (Hexaprotodon liberiensis, Cetartiodactyla, Hippopotamidae), Florida manatee (Trichecus manatus latirostris, Sirenia, Trichechidae), Atlantic walrus (Odobenus rosmarus rosmarus, Carnivora, Odobenidae), African savannah elephant (Loxodonta africana, Proboscidea, Elephantidae), black rhinoceros (Diceros bicornis, Perissodactyla, Rhinocerotidae), rock hyrax (Procavia capensis, Hyracoidea, Procavidae), lowland streaked tenrec (Hemicentetes semispinosus, Afrosoricida, Tenrecidae), and black and rufous elephant shrew (Rhynchocyon petersi, Macroscelidea, Macroscelididae), were used for comparative purposes in different parts of this study. The results show that 1) Order-specific differences in the organization of the neocortex occur among cetaceans; 2) Cetaceans share structural features of the neocortex with the artiodactyls, both at a structural and neurochemical level; 3) The glia-neuron ratio of the cetacean neocortex corresponds to what is expected for their brain size; 4) The specific cortical regions investigated contain, in most of the available cetaceans species, a neuronal specialization observed with the same pattern of distribution only in great apes and humans, the Von Economo neurons. Overall these results are further evidence for an organization of the cetacean neocortex, which, although very different from that of primates, displays complexity, challenging the classical view of its homogeneous and simple structure. Specifically, the extended development of regions involved in high-level cognitive processes such as the ACC, AI, and FPC, their diverse cortical organization, and the presence of a specific neuronal specialization, all suggest that specific evolutionary selective pressures acted on these cortical regions and thus on their functions. Based on the evidence reported in the present thesis, the brain of cetaceans can be considered of a complexity comparable to that of primates, and an evolutionary alternative to the generation of complex behaviors. L’encefalo dei cetacei è caratterizzato dal notevole volume e dalla complessità ed estensione della superficie neocorticale. La conoscenza dell’organizzazione delle strutture cerebrali di questi mammiferi completamente adattati alla vita acquatica è di primaria importanza per comprendere i meccanismi che stanno alla base dell’evoluzione del sistema nervoso centrale dei mammiferi, incluso l’uomo. In particolare, le tre regioni corticali costitute dalla corteccia cingolata anteriore (ACC), dalla insula anteriore (AI) e dalla corteccia frontopolare (FPC) hanno un ruolo primario nei processi di alto livello cognitivo nei primati e, quindi, lo studio della loro organizzazione corticale nei cetacei assume una particolare importanza in ragione delle capacità cognitive ampiamente documentate in queste specie. La citoarchitettura, la chemoarchitettura basata sulla distribuzione della proteina legante il calcio (CaBP) calretinina (CR), il rapporto cellule della glia-neuroni (GNI) e le specializzazioni neuronali di ACC, AI e FPC sono state studiate in alcune specie, rappresentanti delle maggiori famiglie di cetacei, che includono il tursiope (Tursiops truncatus, Odontoceti, Delphinidae), il grampo (Grampus griseus, Odontoceti, Delphinidae), la focena (Phocoena phocoena, Odontoceti, Phocoenidae), l’orca (Orcinus orca, Odontoceti, Delphinidae), il beluga (Delphinapterus leucas, Odontoceti, Monodontidae), il capodoglio (Physeter macrocephalus , Odontoceti, Physeteridae), il capodoglio nano (Kogia simus, Odontoceti, Kogiidae), l’inia (Inia geoffrensis, Odontoceti, Iniidae), la balenottera minore (Balaenoptera acutorostrata, Mysticeti, Balaenopteridae) e la megattera (Megaptera novaeangliae, Mysticeti, Balaenopteridae). Specie selezionate che includono l’ippopotamo nano (Hexaprotodon liberiensis, Cetartiodactyla, Hippopotamidae), il lamantino della Florida (Trichecus manatus latirostris, Sirenia, Trichechidae), il tricheco (Odobenus rosmarus rosmarus Carnivora, Odobenidae), l’elefante africano (Loxodonta africana, Proboscidea, Elephantidae), il rinoceronte nero (Diceros bicornis, Perissodactyla, Rhinocerotidae), la procavia (Procavia capensis, Hyracoidea, Procavidae), il tenrec striato di pianura, (Hemicentetes semispinosus, Afrosoricida, Tenrecidae), e il toporagno elefante di Peters (Rhynchocyon petersi, Macroscelidea, Macroscelididae) sono state utilizzate, in una prospettiva comparata, in diverse parti della presente tesi. I risultati qui riportati dimostrano che 1) Esistono differenze ordine-specifiche nell’organizzazione corticale dei cetacei; 2) Esistono similitudini strutturali e chimiche nell’organizzazione corticale di cetacei e artiodattili; 3) Il rapporto cellule della glia-neuroni nella corteccia dei cetacei è conforme a quanto previsto sulla base delle dimensioni dell’encefalo; 4) Le specifiche regioni corticali esaminate nella presente tesi contengono, nella maggior parte delle specie di cetacei, una particolare specializzazione neuronale, osservata con la medesima distribuzione solo nell’elefante e nelle scimmie antropomorfe filogeneticamente più vicine all’uomo: i neuroni di Von Economo. In conclusione, i risultati qui riportati costituiscono una ulteriore evidenza del fatto che l’organizzazione corticale dei cetacei, anche se molto diversa da quella dei primati, è caratterizzata da una specifica complessità che sfida la visione di semplicità e monotonia classicamente associata alla struttura della corteccia cerebrale di questi mammiferi marini. In particolare, il notevole sviluppo di regioni corticali associate a complessi processi cognitivi, quali ACC, AI e FPC, l’ eterogeneità dell’organizzazione corticale, e la presenza di definite specializzazioni neuronali, suggeriscono che queste regioni corticali, e le loro funzioni, siano state plasmate da specifici processi evolutivi. Sulla base dei risultati riportati nella presente tesi, l’encefalo dei cetacei può essere considerato di complessità paragonabile a quella dei primati, ed una alternativa evoluzionistica per la produzione di comportamenti strutturati.

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Landron, Thelma. "Substrats cérébraux des choix basés sur les préférences : électrophysiologie et neuropsychologie." Electronic Thesis or Diss., Sorbonne université, 2024. http://www.theses.fr/2024SORUS063.

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Lorsque l'on fait face à plusieurs alternatives, la théorie de la décision postule que l'on choisit l'option qui présente la plus grande valeur attendue. Le choix comporte donc deux étapes : l'estimation pour chaque option de sa valeur attendue, qui intègre les potentiels coûts et bénéfices, et la sélection de la meilleure option, qui repose sur la comparaison des valeurs attendues. L'objectif de cette thèse est d'éclairer les mécanismes de la décision, au moyen de l'électrophysiologie intracérébrale, chez des patients souffrant d'épilepsie pharmacorésistante, et de la neuropsychologie, chez des patients souffrant de lésions vasculaires, dont on étudie le comportement. Les deux études expérimentales se concentrent sur le rôle de trois régions centrales pour la prise de décision et l'arbitrage entre coûts et bénéfices : le cortex orbitofrontal, le cortex préfrontal dorsomédian et le cortex insulaire antérieur. Selon le modèle dominant, le cortex orbitofrontal (OFC) implémente la comparaison des valeurs, formalisée par une compétition entre populations neuronales représentant les options au choix. Dans le cas d'un choix binaire, la simulation de ce réseau de neurones produit une activité globale qui signale d'abord la somme des valeurs puis la différence entre l'option choisie et l'option non choisie. Cette signature spécifique de la comparaison des valeurs a été identifiée dans les basses fréquences de l'activité en provenance de l'OFC recueillie par magnétoencéphalographie. Afin de mettre à l'épreuve cette conclusion, la première étude de cette thèse s'est focalisée sur l'analyse des données électrophysiologiques enregistrées dans l'OFC de 26 patients implantés pour repérage des foyers épileptogènes, pendant que ceux-ci choisissaient leurs préférées parmi des récompenses alimentaires présentées deux par deux. L'analyse des oscillations basses fréquences de l'OFC a reproduit les résultats antérieurs, mais a également identifié plusieurs propriétés du signal qui ne sont pas compatibles avec le modèle dominant. Les résultats sont en revanche compatibles avec la théorie selon laquelle l'OFC estime d'une part la valeur de chaque option et d'autre part la confiance dans le choix effectué.Si l'OFC signale les bénéfices (la valeur des récompenses), il a été suggéré que cortex insulaire antérieur signale les coûts, et que le cortex préfrontal dorsomédian intègre les coûts et les bénéfices. Afin de tester ces relations anatomo-fonctionnelles, la deuxième étude de cette thèse a testé le comportement de patients présentant des lésions vasculaires, soit dans le cortex préfrontal médian (mPFC, n = 18), soit dans le cortex insulaire (IC, n = 16). Les tests comportementaux comprenaient des items appartenant à trois catégories (récompense, punition et effort) et demandaient aux patients d'effectuer des évaluations, des choix binaires et des compromis coûts-bénéfices. Les résultats ont montré que les lésions du mPFC conduisent à sous-estimer la valeur des récompenses et à surestimer le coût des efforts, pouvant expliquer la réduction des comportements (l'apathie) observée chez ces patients. Les lésions du IC, au contraire, rendent les patients plus enclins à accepter les coûts (effort et punition) afin d'obtenir les bénéfices associés aux comportements. En conclusion, ce travail permet de préciser les rôles de l'OFC, du mPFC et de l'IC dans les choix basés sur les préférences, notamment dans l'estimation des valeurs et dans le compromis coût/bénéfice qui sous-tendent la motivation du comportement When faced with several alternatives, decision theory posits that the option with the highest expected value is chosen. Making a choice involves two stages: first, estimating the expected value of each option, by integrating prospective costs and benefits, and then second, selecting the best option, based on a comparison of the resulting expected values. The primary goal of this dissertation is to elucidate those mechanisms in two specific patient cohorts whose behavior is being studied: intracerebral electrophysiology is employed in patients with pharmaco-resistant epilepsy, while neuropsychology is utilized in individuals with vascular lesions. The presented experimental studies focus on the role of three central regions in decision-making and cost-benefit trade-offs: the orbitofrontal cortex, the dorsomedial prefrontal cortex and the anterior insular cortex.According to the prevailing model, the orbitofrontal cortex (OFC) implements value comparison as a competition between neuronal populations representing choice options. In the case of a binary choice, simulations of this neural network generate global activity that initially signals the sum of the option values, before signaling the difference between the chosen option value and the unchosen option value. This specific signature of value comparison was previously identified in the low frequencies of magnetoencephalographic activity recorded from the OFC. In order to test this prevailing model, the first study analyzed intracerebral electrophysiological data collected from the OFC of 26 patients, while choosing between food rewards presented in pairs. The analysis of the OFC low-frequency oscillations replicated previous findings, but also revealed several properties of the signal that conflicts with the dominant model. Nonetheless, the results align with the theory that the OFC estimates the value of each option on the one hand, and confidence in the choice that is being made on the other.While the OFC signals benefits (the expected value of rewards), it has been suggested that the anterior insular cortex signals costs, and that the dorsomedial prefrontal cortex integrates costs and benefits. To investigate these anatomical-functional relationships further, the second study tested the behavior of patients who had vascular lesions in either the medial prefrontal cortex (mPFC, n = 18) or the insular cortex (IC, n = 16). Behavioral tests included items from three categories (reward, punishment and effort) and required patients to perform ratings, binary choices and cost-benefit trade-offs. The results showed that lesions of the mPFC lead to an underestimation of the value of rewards and an overestimation of the cost of effort, which may explain the reduction in behavior (apathy) observed in these patients. Conversely, patients with IC lesions were more willing to endure costs (effort and punishment) in order to obtain the benefits associated with the options.In summary, this work clarifies the roles of the OFC, the mPFC, and the IC in value-based decision-making, particularly in the estimation of value and in the cost-benefit trade-off that drives the motivation of behavior

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Foilb, Allison R. "Sex Differences and the Neural Correlates of Safety Learning:." Thesis, Boston College, 2019. http://hdl.handle.net/2345/bc-ir:108467.

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Thesis advisor: John P. Christianson Accurate discrimination between safety and danger is necessary for survival, but is aberrant in individuals with post-traumatic stress disorder (PTSD). Despite its clinical relevance, very little is known about the cognitive and neural processes that underlie safety learning. Understanding how cues become safety signals is critical to understanding the impairments in fear modulation observed in individuals with PTSD. PTSD is more prevalent in women than men, and while research on sex differences in safety learning is limited, there is substantial evidence that males and females acquire and utilize safety signals differently. The aim of this dissertation is to describe behavioral sex differences in learning and recall of fear discrimination and explore the neural circuitry that allows this discrimination to occur Thesis (PhD) — Boston College, 2019 Submitted to: Boston College. Graduate School of Arts and Sciences Discipline: Psychology

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Bradley, Claire. "The first steps of cortical somatosensory and nociceptive processing in humans : anatomical generators, functional plasticity, contribution to sensory memory and modulation by cortical stimulation." Thesis, Lyon 1, 2015. http://www.theses.fr/2015LYO10213.

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Les sensations en provenance de notre corps se combinent pour donner lieu à des perceptions extrêmement variées, pouvant aller de la brûlure douloureuse au toucher agréable. Ces deux types d'informations dites nociceptives et non nociceptive sont traitées au sein du système nerveux somatosensoriel. Dans ce travail de thèse, nous avons modélisé et caractérisé l'activité électrique du cortex operculo-insulaire au sein des réseaux somatosensoriels non-douloureux et nociceptif, grâce à des enregistrements non-invasifs chez l'Homme. La validité du modèle en réponse à un stimulus nociceptif a été évaluée par comparaison avec des enregistrements intra-corticaux réalisés chez des patients épileptiques. Nous avons ensuite utilisé ce modèle pour déterminer si la stimulation corticale non invasive classiquement utilisée pour soulager les douleurs neuropathiques (stimulation magnétique du cortex moteur) permettait de modifier les réponses nociceptives chez des participants sains. Nous avons montré que cette intervention n'est pas plus efficace qu'une stimulation factice (placebo) sur le plan du blocage nociceptif. Finalement, nous avons tenté de stimuler directement le cortex operculo-insulaire, par trois méthodes différentes : par stimulation électrique locale, intracrânienne et par stimulations non-invasives magnétique (rTMS) et électrique (tDCS). Dans l'ensemble, les travaux présentés ici montrent comment une approche non-invasive chez l'Homme permet de caractériser et de moduler l'activité du cortex operculo-insulaire, qui pourrait être une cible intéressante pour le traitement des douleurs réfractaires The somatosensory system participates in both non-nociceptive and nociceptive information Processing. In this thesis work, we model and characterize the electrical activity of the operculo-insular cortex within non-painful and nociceptive networks, using non-invasive electrophysiological recordings in humans. Validity of the modeled response to a nociceptive stimulus was evaluated by comparing it to intra-cranial recordings in epileptic patients, revealing excellent concordance. We went on to use this model to determine whether a technique of non-invasive cortical stimulation currently used to relieve neuropathic pain (motor cortex magnetic stimulation) was able to modulate acute nociceptive processing in healthy participants. We show that this intervention is not more efficacious than placebo stimulation in blocking nociception. This raises questions regarding the mechanisms of action of this technique in patients, which might implicate a modulation of pain perception at a higher level of processing. Finally, we attempted to stimulate the operculo-insular cortex directly, using three different methods. Low-frequency intra-cortical stimulation in epileptic, transcranial magnetic stimulation (TMS) of the same region in healthy participants and multipolar transcranial electrical stimulation (tDCS).Altogether, the studies presented here show how a non-invasive approach in humans allows characterising and modulating the activity of the operculo-insular cortex. While this region might be an interesting target for future treatment of drug-resistant pain, its stimulation in patients would require further investigation of parameters and procedures

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Bouchatta, Otmane. "Sensibilisation à la douleur chez un modèle murin de troubles du déficit de l'attention et de l'hyperactivité." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0356/document.

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L’ADHD (Attention-deficit/hyperactivity disorder) est une maladie du développement caractérisée par l’impulsivité, l’hyperactivité, et l’inattention. Les voies neuronales impliquées dans ces déficits indiquent des dysfonctionnements dans les réseaux catécholaminergiques frontal-sous-corticaux, impliquant l'innervation dopaminergique et noradrénergique. Des études récentes ont mis en évidence une hypersensibilité à la douleur chez les patients ADHD et soulignent une possible comorbidité entre l’ADHD et la douleur. Cependant, les mécanismes et les circuits neuraux impliqués dans ces interactions sont inconnus. Afin de décrypter cette relation, nous avons généré un modèle ADHD de souris à P5 par une lésion néonatale des voies dopaminergiques centrales avec la 6-Hydroxydopamine (6-OHDA) et nous avons démontré la validité du modèle pour mimer le syndrome ADHD. Ensuite, nous avons analysé les comportements douloureux dans le modèle de souris 6-OHDA. Ces derniers présentent un abaissement des seuils de la douleur, ce qui suggère que l’ADHD induit une sensibilisation à la douleur (comorbidité ADHD-Douleur). Nous avons confirmé à l’aide d’enregistrements extracellulaires unitaires, que les modifications de la sensibilité à la douleur des souris 6-OHDA sont dues à une augmentation de l’excitabilité des neurones nociceptifs de la moelle épinière. Cette sensibilisation passe donc par une altération de l’intégration sensorielle dans la moelle épinière via la mise en jeu de contrôles descendants. La connectivité "cortex cingulaire antérieur (ACC) – insula postérieur (PI)" est la clé dans cette comorbidité ADHD-douleur, impliquée dans les fonctions exécutives, les émotions et elle envoie aussi des projections vers la corne dorsale de la moelle épinière. En effet, en combinant les analyses électrophysiologiques, optogénétiques et comportementales, nous avons démontré que les effets de l’ADHD sur la sensibilisation douloureuse passent par la mise en jeu de l’ACC et de la voie ACC – PI. En conclusion, nous montrons que les conditions ADHD induisent une hyperactivation des neurones nociceptifs de la moelle épinière et une hypersensibilité à la douleur. Nous suggérons également que le circuit ACC – PI pourrait déclencher un dysfonctionnement des neurones de la moelle épinière sur la douleur dans les conditions ADHD Attention deficit hyperactivity disorder (ADHD) is characterized by the core symptoms of inattention, hyperactivity and impulsivity. Neural pathways underlying these deficits point to deficits within frontal-subcortical catecholaminergic networks, involving dopaminergic and noradrenergic innervation. Hence, impairment of the dopaminergic neurotransmission is a frequent target of ADHD medication. Low-dose psychostimulants, including methylphenidate (MpH) and amphetamines (AMP) are the most widely used treatments of ADHD. Recent evidence pointed to pain hypersensitivity in subjects with ADHD history, and suggests possible comorbidity of ADHD with pain. However, the mechanisms and neural circuits involved in these interactions are unknown. In order to understand this comorbidity, the first objective was to create a good animal model of ADHD. We generated a mouse model at P5 by neonatal disruption of central dopaminergic pathways with 6-Hydroxydopamine (6-OHDA) and we demonstrated the validity of the model to mimic ADHD syndrome. Next, we analyzed nociceptive responses in the 6-OHDA mouse model of ADHD. We found that 6-OHDA mice exhibited a marked decrease of withdrawal thresholds, suggesting that ADHD increase nociceptive sensitivity. Interestingly, by using in vivo electrophysiological recordings, we demonstrated that allodynia and hyperalgesia may be caused by neuronal hyperexcitability in the dorsal spinal cord. Moreover, we found that both lowered wihdrawal threshold and increased activity of nociceptive neurons in ADHD-like mice was not normalized by MpH. We tested the hypothesis that descending controls are responsible for pain alterations through the modulation of spinal circuits. The ‘anterior cingulate cortex (ACC) – posterior insular (PI)’ connectivity is at the cross-road of ADHD and pain, being involved in executive functions and emotions, as well as sending projections to the dorsal horn of the spinal cord. By combining electrophysiological, optogenetic and behavioral analyzes, we have shown that the effects of ADHD on painful sensitization involve the implication of ACC and the ACC - PI pathway. In conclusion, we showed that ADHD conditions induce spinal cord nociceptive neurons hyperactivation and pain hypersensitivity. We also suggest that the ACC - PI circuit may trigger dysfunction of spinal cord neurons in ADHD conditions

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Ferrier, Jeremy. "Douleurs neuropathiques induites par l'oxaliplatine. Physiopathologie et approches thérapeutiques." Thesis, Clermont-Ferrand 1, 2013. http://www.theses.fr/2013CLF1PP06/document.

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L’oxaliplatine, anticancéreux utilisé pour le traitement du cancer colorectal, est responsable d’une neurotoxicité périphérique dose-limitante affectant une grande majorité de patients. La neurotoxicité de l’oxaliplatine se présente sous deux formes : une forme immédiate, se traduisant par des paresthésies transitoires, et une forme retardée et cumulative, caractérisée par l’apparition d’une neuropathie périphérique douloureuse fortement invalidante. A l’heure actuelle, la prise en charge des douleurs neuropathiques est souvent incomplète, principalement à cause du manque de traitements efficaces et bien tolérés. Dans ce contexte, il existe un réel besoin d’innovation thérapeutique pour améliorer le traitement de ces neuropathies, nécessitant au préalable une meilleure compréhension de leur physiopathologie. La première partie de ce travail porte sur l’évaluation de l’effet d’une alimentation sans polyamines sur l’apparition et la chronicisation de la neurotoxicité de l’oxaliplatine chez le rat. En effet, en modulant positivement la sous-unité NR2B des récepteurs NMDA, les polyamines alimentaires pourraient faciliter la sensibilisation douloureuse. Un régime sans polyamines a permis de prévenir l’hypersensibilité thermique et mécanique induite par l’oxaliplatine. Bien que ces symptômes nociceptifs ne soient pas associés à une augmentation de l’expression de la sous-unité NR2B au niveau spinal, l’ifenprodil (antagoniste NR2B spécifique) permet d’en diminuer l’intensité de manière dose-dépendante. Enfin, une étude métabolomique réalisée par spectroscopie RMN du proton a montré que le régime sans polyamines permettait de réguler la neurotransmission excitatrice (glutamate) au niveau de la corne dorsale de la moelle épinière des animaux, expliquant ainsi son effet antalgique. Dans un deuxième temps, nous nous sommes intéressés aux mécanismes supraspinaux impliqués dans la neuropathie chronique induite par l’oxaliplatine, à l’aide d’une approche métabolomique par 1 H-RMN HRMAS. Cette étude a révélé d’importantes modifications métaboliques cérébrales chez les animaux traités par oxaliplatine, notamment une augmentation de la choline dans le cortex insulaire postérieur corrélée de manière significative aux seuils douloureux. Une analyse transcriptomique et pharmacologique a permis de mettre en évidence une implication de la neurotransmission cholinergique dans cette structure. Le ciblage pharmacologique de cette neurotransmission pourrait représenter une stratégie potentiellement intéressante pour le développement de nouveaux traitements antalgiques. L’ensemble de ces résultats expérimentaux a permis l’identification de nouvelles pistes pour la compréhension et le traitement des douleurs neuropathiques chimio-induites. Dans une perspective de recherche translationnelle, ces deux approches précliniques sont en cours de transposition dans des protocoles de recherche clinique. Un essai clinique de phase II (NEUROXAPOL, NCT01775449) a débuté afin de confirmer l’intérêt d’un régime appauvri en polyamines chez des patients recevant une chimiothérapie à base d’oxaliplatine. Une seconde étude clinique (INSULOX) est actuellement en cours de préparation au CHU de Clermont-Ferrand afin de mesurer par IRM les concentrations en choline dans l’insula de patients souffrant de douleurs neuropathiques induites par oxaliplatine Oxaliplatin, an anticancer drug used for the treatment of colorectal cancer, is responsible for a dose-limiting peripheral neurotoxicity in the majority of treated patients. This neurotoxicity appears with two components: a rapid-onset acute neurotoxicity manifesting as transient paresthesias and cold-induced dysesthesias; and a late-onset cumulative neurotoxicity characterized by the development of a painful chronic neuropathy. To date, the management of chemotherapy- induced neuropathic pain is still challenging because of the lack of effective treatments. In this context, a better understanding of the pathophysiological mechanisms underlying this neurotoxicity could lead to the identification of new therapeutic targets. Firstly, we aimed to assess the preventive effect of a polyamine deficient diet on the development of oxaliplatin-induced acute neurotoxicity. Exogenous polyamines, by positively modulating spinal NR2B-containing NMDA receptors, could facilitate pain sensitization. This study has shown that a polyamine deficient diet for 7 days totally prevented oxaliplatin-induced acute cold and mechanical hypersensitivity in rats. Although we observed no change in spinal NR2B expression or phosphorylation, intrathecal ifenprodil (a specific NR2B antagonist) reduced oxaliplatin-induced allodynia in a dose-dependent manner. Finally, proton NMR spectroscopy- based metabolomic analysis has revealed a regulation of spinal glutamate neurotransmission as the most likely mechanism underlying the preventive effect of the diet. Secondly, the metabolic variations associated with oxaliplatin-induced chronic neuropathy were assessed at the supraspinal level using a 1 H-NMR HRMAS-based metabolomic approach. Among the neurochemical changes evidenced in this study, we observed a significant increase in choline within the posterior insular cortex, significantly correlated with the mechanical pain thresholds. A transcriptomic and pharmacological approach have revealed an implication of cholinergic neurotransmission in this brain area. Targeting the cholinergic system using centrally active muscarinic agents could represent an interesting strategy for the treatment of oxaliplatin- induced neuropathic pain. These experimental results led to the identification of new molecular targets for the comprehension and the treatment of chemotherapy-associated painful neuropathy. In a translational approach, these preclinical data will be extended to the clinical setting. A phase II clinical trial (NEUROXAPOL, NCT01775449) is undergoing to confirm the therapeutic interest of a polyamine free diet in patients receiving oxaliplatin. A second clinical project (INSULOX) aiming at assessing the choline concentrations in the insula of patients suffering from oxaliplatin-induced neuropathy is in preparation

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Brooks, Samantha J., Jonathan Cedernaes, and Helgi B. Schiöth. "Increased prefrontal and parahippocampal activation with reduced dorsolateral prefrontal and insular cortex activation to food images in obesity : a meta-analysis of fMRI studies." Uppsala universitet, Funktionell farmakologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-199757.

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BACKGROUND AND OBJECTIVES: Obesity is emerging as the most significant health concern of the twenty-first century. A wealth of neuroimaging data suggest that weight gain might be related to aberrant brain function, particularly in prefrontal cortical regions modulating mesolimbic addictive responses to food. Nevertheless, food addiction is currently a model hotly debated. Here, we conduct a meta-analysis of neuroimaging data, examining the most common functional differences between normal-weight and obese participants in response to food stimuli. DATA SOURCE: We conducted a search using several journal databases and adhered to the 'Preferred Reporting Items for Systematic Reviews and Meta-analyses' (PRISMA) method. To this aim, 10 studies were found with a total of 126 obese participants, 129 healthy controls, equaling 184 foci (146 increased, 38 decreased activation) using the Activation Likelihood Estimation (ALE) technique. Out of the 10 studies, 7 investigated neural responses to food versus non-food images. RESULTS: In response to food images, obese in comparison to healthy weight subjects had increased activation in the left dorsomedial prefrontal cortex, right parahippocampal gyrus, right precentral gyrus and right anterior cingulate cortex, and reduced activation in the left dorsolateral prefrontal cortex and left insular cortex. CONCLUSIONS: Prefrontal cortex areas linked to cognitive evaluation processes, such as evaluation of rewarding stimuli, as well as explicit memory regions, appear most consistently activated in response to images of food in those who are obese. Conversely, a reduced activation in brain regions associated with cognitive control and interoceptive awareness of sensations in the body might indicate a weakened control system, combined with hypo-sensitivity to satiety and discomfort signals after eating in those who are prone to overeat.

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Horn, Felicitas Marietta [Verfasser], and Henry [Akademischer Betreuer] Evrard. "Elemental localization of the von Economo neuron and fork neuron in the insular cortex in humans and macaque monkeys / Felicitas Marietta Horn ; Betreuer: Henry Evrard." Tübingen : Universitätsbibliothek Tübingen, 2020. http://d-nb.info/1205313443/34.

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Lee, Woogul. "Neural substrates of intrinsic motivation: fMRI studies." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/2738.

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Numerous social and educational psychologists propose that intrinsic motivation generated by personal interests and spontaneous satisfactions is qualitatively different from extrinsic types of motivation generated by external compensations and also that intrinsic motivation is more beneficial to learning than extrinsic types of motivation. However, in the field of neuroscience, intrinsic motivation has been little studied while extrinsic types of motivation (e.g., incentive motivation) have been thoroughly studied. The purpose of the present studies was to expand the neural understanding of motivation to include intrinsic motivational processes. To do so, a series of three event-related functional magnetic resonance imaging (fMRI) studies were conducted. Study 1 and Study 2 compared the neural activities when participants decided to act for intrinsic reasons (i.e., self-determined volitional and agentic behavior) versus when they decided to act for extrinsic reasons (i.e., non-self-determined volitional and agentic behavior). Both studies showed that the anterior insular cortex, known to be related to a sense of agency, was more activated during self-determined behavior associated with intrinsic reasons for acting while the posterior parietal regions (e.g., posterior cingulate cortex, angular gyrus), known to be related to a sense of a loss of agency, were more activated during non-self-determined behavior associated with extrinsic reasons for acting. These findings confirm the existence of neural-based intrinsic motivational processes, differentiate intrinsic motivation from incentive motivation, and document the important neural activities which function for generating self-determined agentic action. Study 3 examined these same neural activities as participants engaged in interesting and uninteresting versions of two experimental tasks. Results confirmed the results of the earlier two studies, as the anterior insular cortex was more recruited when participants performed the interesting, but not the uninteresting, version of the tasks. Results also extended the findings from Studies 1 and 2 in an important way in that the ventral striatum, a well-known brain region for reward processing, was more activated when participants performed the interesting, but not the uninteresting, version of the experimental tasks. These findings suggest that intrinsic motivation is generated based on the feeling of intrinsic need satisfaction (from anterior insular cortex activations) and the feeling of reward (from ventral striatum activations). Overall, the present research established three new findings: (1) the neural bases of intrinsic motivation lies largely in increased anterior insular cortical activities; (2) when people made decisions about self-determined intrinsically-motivated behavior, they show enhanced insular cortical activities and suppressed posterior parietal cortical activities; and (3) when people engaged in actual self-determined intrinsically-motivated behavior, they show enhanced insular cortical and ventral striatal activities. In establishing these new findings, the paper introduces a new area of study for motivational neuroscience--namely, intrinsic motivation.

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Zhao, Zhe. "Le rôle du récepteur des cannabinoïde de type 1 dans la consommation d'eau." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0319.

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L’apport hydrique est crucial pour le maintien homéostatique des fluides corporels et pour la survie de l’animal. Des processus cérébraux complexes déclenchent la soif, qui survient suite à une perte de volume sanguin (déshydratation extracellulaire) ou une augmentation de l’osmolalité sanguine (déshydratation intracellulaire), afin d’apporter de l’eau pour l’équilibre des fluides. Cependant, les mécanismes centraux favorisant la prise hydrique sont encore peu caractérisés. Les récepteurs aux cannabinoïdes de type 1 (CB1) sont exprimés de manière large et abondante dans le système nerveux central où ils modulent une variété de fonctions telles que la mémoire, l’anxiété et les comportements alimentaires. Cependant, le rôle des récepteurs CB1 dans le contrôle de l’apport hydrique est encore matière à débat du fait de résultats contradictoires d’expériences d’activation ou de blocage pharmacologique de ces récepteurs sur les comportements de consommation d’eau.Mon travail de thèse s’est concentré sur le rôle des récepteurs CB1 dans le contrôle de l’apport hydrique. Par l’utilisation d’approches génétiques, pharmacologiques, comportementales et de traçage neuronal, j’ai examiné l’implication des récepteurs CB1 dans le contrôle de l’apport hydrique induit par différentes conditions physiologiques de déshydratation extra- et intracellulaire. Les résultats montrent que la signalisation du récepteur CB1 est requise pour promouvoir l’apport hydrique. En particulier, la délétion globale du récepteur CB1 ne change pas l’osmolalité plasmatique ni la composition corporelle en eau, mais elle diminue l’apport hydrique induit par une privation d’eau, une administration systémique ou intracérébroventriculaire (ICV) de chlorure de sodium ou une injection ICV de l’hormone peptidergique angiotensine II. Dans le but de mieux décrire les mécanismes neuronaux de cette fonction, j’ai découvert que la présence des récepteurs CB1 dans les neurones glutamatergiques corticaux, en particulier ceux présents dans le cortex cingulaire antérieur (CCA) favorisent le comportement de consommation d’eau. En effet, les récepteurs CB1 sont exprimés abondamment dans les terminaisons axonales des neurones glutamatergiques du CCA projetant sur l’amygdale basolatérale (ABL) et une réexpression sélective des récepteurs CB1 dans ce circuit est suffisante pour garantir un comportement de consommation d’eau normal chez la souris. Dans l’ensemble, ces données révèlent que les récepteurs CB1 sont nécessaires pour promouvoir l’apport hydrique, et que leur présence dans le circuit CCA-ABL est suffisant pour le contrôle descendant des comportements de consommation d’eau.De plus, j’ai également montré que les récepteurs CB1 contrôlaient l’apport hydrique dans différentes conditions à d’autres niveaux comme au niveau du cortex insulaire, des cellules cholinergiques et des mitochondries.En résumé, mon travail de thèse a analysé le rôle des récepteurs CB1 dans des populations cellulaires / circuits neuronaux distincts dans le contrôle de l’apport hydrique. Ces résultats apportent de plus amples preuves permettant la compréhension des fonctions du système endocannabinoïde et de la régulation cérébrale de la soif Water intake is crucial for maintaining body fluid homeostasis and animals’ survival. Complex brain processes trigger thirst, which arises upon losing blood volume (i.e. extracellular dehydration) or increasing blood osmolality (i.e. intracellular dehydration), to replenish water for fluid balance. The brain plays a key role in modulating these processes, but the central mechanisms regulating water intake are not fully understood. Type-1 cannabinoid receptors (CB1) are widely and abundantly expressed in the central nervous system where they modulate a variety of functions, such as memory, anxiety and feeding behavior. However, the role of CB1 receptors in the control of water intake is still a matter of debate, since pharmacological activation or blockade of CB1 receptors produced contradictory results in drinking behavior experiments.My thesis work focuses on the role of CB1 receptors in the control of water intake. By using genetic, pharmacological, anatomical, imaging, and behavioral approaches, I examined the involvement of CB1 receptors in the control of water intake induced by different physiological conditions of extracellular or intracellular dehydration. The results showed that CB1 receptor signaling is required to promote water intake. In particular, global deletion of CB1 receptors does not change plasma osmolality and body water composition, but it decreases water intake induced by water deprivation, systemic or intracerebroventricular (ICV) administration of sodium chloride, or ICV injection of the peptide hormone angiotensin II. In the attempt to better detail the neuronal mechanisms of this function, I discovered that the presence of CB1 receptors in cortical glutamatergic neurons, particularly the ones located in the anterior cingulate cortex (ACC) glutamatergic neurons promote drinking behavior. CB1 receptors are abundantly expressed in axon terminal of ACC glutamatergic neurons projecting to the basolateral amygdala (BLA) and selective expression of CB1 receptors in this circuit is sufficient to guarantee proper drinking behavior in mice. Altogether, these data reveal that CB1 receptors are necessary to promote water intake, and that their presence in the ACC-BLA circuit is sufficient for the top-down control of drinking behavior.Furthermore, I also provided evidence that CB1 controls water intake in different conditions at other levels, e.g. insular cortex, cholinergic cells, and mitochondria.In summary, my thesis work analyzed the role of CB1 receptors in distinct cell populations/neuronal circuits for the control of water intake. These results will help further understanding the functions of the ECS and the brain regulation of thirst

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19

Chapuis, Julie. "Les circuits neuronaux de l'aversion olfactive conditionnée : approche électrophysiologique chez le rat vigile." Phd thesis, Université Claude Bernard - Lyon I, 2009. http://tel.archives-ouvertes.fr/tel-00603782.

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L'objectif de cette thèse est de décrire le réseau cérébral et la dynamique neuronale qui pourraient servir de support aux aversions alimentaires de type olfactives. Nous avons réalisé des enregistrements multisites de potentiel de champ locaux chez le rat vigile engagé dans cet apprentissage, en proposant deux modes de présentation de l'indice olfactif : à proximité de l'eau de boisson (distal) ou ingéré (distal-proximal). Après apprentissage, la présentation du seul indice distal induit l'émergence d'une activité oscillatoire de forte amplitude dans la bande de fréquence beta (15-40 Hz). Finement corrélée au comportement d'aversion de l'animal, cette activité est proposée comme la signature du réseau de structures fonctionnellement impliquées dans la reconnaissance de l'odeur en tant que signal. Nous montrons que ce réseau peut être plus ou moins étendu selon la façon dont le stimulus a été perçu lors du conditionnement: dans certaines aires (bulbe olfactif, cortex piriforme, amygdale basolatérale, cortex orbitofrontal) la modulation en puissance de l'activité beta se fait indépendamment du mode de conditionnement; dans d'autres aires (cortex insulaire, cortex infralimbique) ces changements ont lieu si et seulement si l'odeur a été ingérée. Complétés par l'étude des interactions fonctionnelles entre ces différentes structures dans la bande de fréquence considérée, ces résultats nous permettent de mieux comprendre comment un stimulus peut être représenté en mémoire dans un réseau cérébral en fonction de l'expérience que l'animal en a fait.

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20

Smith, Mark Allan. "An investigation into the gating properties of rat cortex neuronal BK channels." Thesis, University of Aberdeen, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322636.

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In this thesis it is demonstrated that leptin and insulin hyperpolarise hypothalamic glucose responsive neurones via the activation of the large conductance ATP-sensitive (KAPT) channel. This channel was potassium selective, had a single channel conductance of 150 pS and channel activity was inhibited by micromolar tolbutamide and millimolar internal ATP. Brain cortical cell bodies and nerve terminals possess a large-conductance calcium-activated potassium (BK) channel. The nerve terminal BK channel switched from high to low activity modes, whereas cell body BK channel activity inactivates during depolarisation. Furthermore, BK channel inactivation was abolished by internal trypsin treatment, suggesting an inactivating particle was associated with the channel. Internal application of alkaline phosphatase irreversibly removed mode switching and inactivation of cortical BK channels. Blocking the cell body BK channel pore with 100 mM intracellular tetraethylammonium (TEA) prevented alkaline phosphatase removal of inactivation, indicating that the phosphatase site of action was located close to the pore. Finally, protein kinase A (PKA) increased the occurrence of the high BK channel activity mode whereas PKA retarded the full recovery of BK inactivation induced by hyperpolarisation. In a separate study it was demonstrated that stably expressed human brain BK (hSlo) channels inactivate in a trypsin-insensitive manner. This inactivation was not due to barium contamination, since 5 μM internal barium blocked hSlo channels only during strong depolarisations, yet inactivation was observed at less positive potentials. Furthermore co-expression of either hSloβ-1, or voltage-gated potassium (Kv) β1.1 or β2.1 subunits with the hSlo α-subunit did not affect the extent or rate of channel inactivation. Finally, the Kvβ-subunits moved the calcium and voltage curves of hSlo to more negative voltages and altered the activation and deactivation kinetics in a manner almost identical to that observed on co-expression of hSloβ-1 subunit with hSlo or by increasing the internal calcium concentration.

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21

Mazzola, Laure. "ROLE DU CORTEX OPERCULO-INSULAIRE DANS LA SOMESTHESIE ET LA DOULEUR CHEZ L'HOMME." Phd thesis, Université Claude Bernard - Lyon I, 2011. http://tel.archives-ouvertes.fr/tel-00793586.

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Ce travail de thèse a pour objectif de préciser le rôle du cortex operculo-insulaire dans la somesthésie et la douleur chez l'Homme à l'aide d'études réalisées par stimulations électriques intracérébrales et en IRM fonctionnelle (IRMf). Deux secteurs fonctionnels distincts ont été mis en évidence; d'une part l'insula dont 60% des stimulations induisent des réponses somato-sensitives dont 10% sont douloureuses, où il existe une localisation préférentiellement postérieure des sites de stimulation donnant lieu à une réponse douloureuse et un décrément antéro-postérieur du seuil de déclenchement d'une réponse douloureuse, dont les champs récepteurs couvrent de larges surfaces cutanées, et où les réponses douloureuses ont une organisation somatotopique grossière ; d'autre part l'aire SII dont la stimulation induit quasi exclusivement des réponses somato-sensitives dont 10% sont douloureuses, sur des surfaces cutanées plus restreintes. SII et l'insula postérieure sont les deux seules régions corticales dont la stimulation est capable d'induire une sensation douloureuse. Une ségrégation fonctionnelle au sein de SII et de l'insula a été montrée en IRMf, par l'existence de patterns spécifiques d'activation pour chaque modalité sensitive, comprenant des sous- régions dont l'activation semble spécifique de la sensation douloureuse. Ceci confère à ces régions une originalité toute particulière au sein de la matrice douleur, puisqu'il semble qu'elles seules puissent activer le réseau fonctionnel des aires impliquées dans la sensation douloureuse et ainsi permettre 'l'expérience' de la douleur.

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22

ATTIA, ALY SAAD MOHAMED AHDY. "Consequences d'une ischemie du cortex insulaire sur la fonction baroreflexe cardiaque du rat." Paris 6, 1989. http://www.theses.fr/1989PA066016.

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Cette etude precise la fonction cardiaque du baroreflexe apres une ischemie sylvienne gauche provoquant une lesion insulaire chez le rat. L'analyse est realisee pharmacologiquement selon la technique du steady state et sur une echelle large de variations tensionnelles chez le rat conscient

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Mazzola, Laure. "Rôle du cortex operculo-insulaire dans la somesthésie et la douleur chez l'homme." Thesis, Lyon 1, 2011. http://www.theses.fr/2011LYO10208/document.

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

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Frot, Maud Gaëlle. "Réponses nociceptives et somesthésiques des cortex operculaire supra-sylvien et insulaire chez l'homme : étude électrophysiologique par enregistrements intra-cérébraux." Lyon 1, 2001. http://www.theses.fr/2001LYO1T028.

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25

LIAVA, ALEXANDRA. "Interactions between emotions and decision making: a SEEG study with focus on the role of the cingulate cortex." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2015. http://hdl.handle.net/10281/94409.

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Introduction Depending on their content, negative or positive, emotions can promote or slow down the cognitive functions. The inhibiting influence of negative affects on the cognitive control has been attributed to the reciprocal inhibition of the neuronal systems implicated in emotion and cognitive functions, but the mechanisms and the temporal process are not well established. The anterior cingulate cortex has been classically subdivided in two major regions with distinct functions: a dorsal-cognitive division and a rostral–ventral affective division. Recent evidence, however, do not support this traditional differentiation but indicate that both subdivisions of the anterior cingulate make important contributions to emotional processing. Aim of the study The project consisted on performing an analysis of the cerebral activity (mainly in the gamma band: > 30Hz) during a protocol of alternating tasks which necessitated the taking of simples decisions, either within an emotionally neutral and within an emotionally negative context, with the aim (i) to compare the performance in an emotionally-negative condition with the performance in an emotionally-neutral condition, (ii) to search the electrophysiological responses of the cerebral areas implanted, implicated in the cognitive and in the emotional control in the different conditions, (iii) to compare the frequency modulations of the different subregions of the cingulate cortex implanted in the different conditions. Patients and methods The study was realized with 6 adult patients (female/male: 3/3) undergoing invasive presurgical evaluation for epilepsy surgery by stereo-electroencephalography (SEEG) in the Claudio Munari Epilepsy Surgery Center, Niguarda Hospital. Monopolar SEEG data were converted to the format of the software Elpho-SEEG developed in LabView, in the Besta Institute. A total of 1365 contacts were analysed. Contacts exploring lesional areas and those showing ictal paroxystic abnormalities were excluded. Frequency changes between the range 1-150 Hz were included in the study. Results In 3 patients reaction time was not associated with the emotional content of the pictures but rather with the complexity of the Raven matrices; furthermore the mean reaction time, as well as the total number of erroneous responses, progressively decreased from the first to the last task, indicating learning mechanisms/adaptability, independently of the emotional valence of the associated pictures. On the other hand, 3 patients did more errors and showed a slightly faster or slower reaction time in the Raven trial in the negative condition compared with the other two ones. Analysis of frequency modulations during the exposure (300msec) to the negative images compared with the affectively neutral conditions, showed a power increase in the anterior aspect of midcingulate cortex, the pregenual aspect of anterior cingulated cortex, the short gyri of insula, the supplementary motor area, the frontal antero-mesial cortex as well as the temporal pole. Interestingly, only the short gyri of insula (anterior insular cortex), but not the long gyri, were activated during the exposure to the negative pictures. Our results are in line with the existing human imaging studies focusing on empathy for other's aversive events that have highlighted the role of these regions involved in the direct pain experience. Furthermore, we provide evidence that dorsal cingulate codes emotional processing. Moreover, our results support the suggestion that "second-hand" experience of pain follows only an anterior activation pattern of the insular cortex.

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Shaw, Lynda Joan. "Emotional processing of natural visual images in brief exposures and compound stimuli : fMRI and behavioural studies." Thesis, Brunel University, 2009. http://bura.brunel.ac.uk/handle/2438/3203.

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Can the brain register the emotional valence of brief exposures of complex natural stimuli under conditions of forward and backward masking, and under conditions of attentional competition between foveal and peripheral stimuli? To address this question, three experiments were conducted. The first, a behavioural experiment, measured subjective valence of response (pleasant vs unpleasant) to test the perception of the valence of natural images in brief, masked exposures in a forward and backward masking paradigm. Images were chosen from the International Affective Picture System (IAPS) series. After correction for response bias, responses to the majority of target stimuli were concordant with the IAPS ratings at better than chance, even when the presence of the target was undetected. Using functional magnetic resonance imaging (fMRI), the effects of IAPS valence and stimulus category were objectively measured on nine regions of interest (ROIs) using the same strict temporal restrictions in a similar masking design. Evidence of affective processing close to or below conscious threshold was apparent in some of the ROIs. To further this line of enquiry, a second fMRI experiment mapping the same ROIs and using the same stimuli were presented in a foveal (‘attended’) peripheral (‘to-be-ignored’) paradigm (small image superimposed in the centre of a large image of the same category, but opposite valence) to investigate spatial parameters and limitations of attention. Results are interpreted as showing both valence and category specific effects of ‘to-be-ignored’ images in the periphery. These results are discussed in light of theories of the limitations of attentional capacity and the speed in which we process natural images, providing new evidence of the breadth of variety in the types of affective visual stimuli we are able to process close to the threshold of conscious perception.

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Chaddad, Neto Feres Eduardo Aparecido. "Estudo das caracteristicas morfologicas do lobo da insula em pacientes portadores de epilepsia do lobo temporal medial." [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309216.

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Orientador: Evandro Pinto da Luz de Oliveira Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas Made available in DSpace on 2018-08-06T17:08:11Z (GMT). No. of bitstreams: 1 ChaddadNeto_FeresEduardoAparecido_M.pdf: 5740692 bytes, checksum: 41706f7c50d8c3c6567a1c592112c6e0 (MD5) Previous issue date: 2006 Resumo: A epilepsia do lobo temporal medial é o subtipo mais freqüente de epilepsia do lobo temporal e é causada, principalmente, pela esclerose medial temporal (EMT). A EMT é caracterizada pela esclerose hipocampal e diferentes graus de acometimento das estruturas vizinhas como amídala, giro parahipocampal e córtex entorrinal. O lobo da ínsula é uma estrutura neocortical e se constitui no envoltório externo da região dos núcleos da base, apresentando várias conexões com o lobo temporal e com o sistema límbico. O estudo apresenta como objetivo analisar o lobo da ínsula, descrevendo se há alteração do mesmo pelo método Neuroline e E-Film. O estudo avaliou 40 indivíduos com EMT e 40 do grupo controle. Pelo método Neuroline 45% eram homens e 55% eram mulheres com EMT- Pelo método E-Fim a distribuição foi de 50% entre os sexos do grupo esclerose. Os casos foram avaliados por um método para as medidas da insula (E-Film) e outro método para o cálculo do volume (Neuroline). Não houve diferença estatística de alteração de volume e das medidas do lobo da ínsula nos pacientes portadores de EMT. O estudo não demonstrou alteração morfológica da ínsula quando comparado os dois grupos Abstract: The temporal medial epilepsy is the most common type of temporal lobe epilepsy caused, specially, by temporal medial sclerosis (TMS). The TMS is characterized by hippocampal sclerosis and by distinghished grades of injury near to other neurological structures such as: amygdaloid nucleus, parahippocampal girus and entorhinal region. The insula's lobe is neocortical structure which is formed by an external wrapped of the basal ganglion, it's usually presenting some connections with temporal lobe and with limbic system. The aim's study was analyzing the insula's lobe if there are alteration with patient's carriers of TMS by Neuroline's and E-Film's methods. The study analyzed 40 patients with TMS and 40 people from the control cluster. All cases were evaluated by two methods: measurement of insula's cortex (E-Film) and evaluation of the insula's volume (Neuroline). By Neuroline's method 45 per cent were male and 55 per cent were female. By E-Film's method there are distribution with half of the percentage for both genders. There was no statistical difference between the insula's volume and insula's measurement for the two groups. This study did not show the insula's morphological variation when these two groups were compared Mestrado Neurologia Mestre em Ciências Médicas

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Desgranges, Bertrand. "Etude des apprentissages olfactifs alimentaires : importance de l'amygdale basolatérale et du cortex insulaire chez le rat." Thesis, Tours, 2009. http://www.theses.fr/2009TOUR4004/document.

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Dans la perspective de mieux comprendre les mécanismes impliqués dans les apprentissages olfactifs alimentaires, nous avons investigué les bases neurobiologiques de l’aversion olfactive conditionnée (AOC) et de la préférence olfactive conditionnée (POC). Nous nous sommes intéressés au rôle joué par deux structures de convergence des informations olfactives, gustatives et viscérales, le noyau basolatéral de l’amygdale (NBL) et le cortex insulaire (CI). Une approche pharmacologique nous permet de montrer que le NBL est indispensable à l’acquisition, la consolidation et le rappel de l’AOC. A contrario, le CI n’est nécessaire à aucune de ces étapes mnésiques. Grâce à une technique d’imagerie cellulaire (catFISH), nous observons que l’apprentissage de la POC s’accompagne d’une augmentation de la convergence des informations odeur-goût au sein des neurones du NBL mais pas du CI, due à un recrutement d’une nouvelle population neuronale. Que l’approche soit systémique ou cellulaire, qu’elle intéresse un apprentissage aversif ou appétitif, nos études soulignent l’importance du NBL dans la mémoire olfactive alimentaire To better understand the mechanisms involved in food olfactory learning, the neurobiological basis of conditioned odor aversion (COA) and the conditioned odor preference (COP) were investigated. We study the basolateral amygdala (BLA) and the insular cortex (IC), which receive olfactory, gustatory and visceral information. Using a pharmacological approach, we show that the BLA is involved in acquisition, consolidation and both recent and remote memory retrieval of COA. By contrast, the IC is not necessary to any of these memory phases. Using a cellular imaging technique (catFISH), we find that COP leads to an increase of odor-taste convergence onto individual neurons in the BLA, but not the IC, by means of the recruitment of a new population. Whether the approach is systemic or cellular and the learning is aversive or appetitive, our study highlights the importance of the BLA in food olfactory learning

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Gueguen, Maëlle. "Dynamique intracérébrale de l'apprentissage par renforcement chez l'humain." Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAS042/document.

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Chaque jour, nous prenons des décisions impliquant de choisir les options qui nous semblent les plus avantageuses, en nous basant sur nos expériences passées. Toutefois, les mécanismes et les bases neurales de l’apprentissage par renforcement restent débattus. D’une part, certains travaux suggèrent l’existence de deux systèmes opposés impliquant des aires cérébrales corticales et sous-corticales distinctes lorsque l’on apprend par la carotte ou par le bâton. D’autres part, des études ont montré une ségrégation au sein même de ces régions cérébrales ou entre des neurones traitant l’apprentissage par récompenses et celui par évitement des punitions. Le but de cette thèse était d’étudier la dynamique cérébrale de l’apprentissage par renforcement chez l’homme. Pour ce faire, nous avons utilisé des enregistrements intracérébraux réalisés chez des patients épileptiques pharmaco-résistants pendant qu’ils réalisaient une tâche d’apprentissage probabiliste. Dans les deux premières études, nous avons d’investigué la dynamique de l’encodage des signaux de renforcement, et en particulier à celui des erreurs de prédiction des récompenses et des punitions. L’enregistrement de potentiels de champs locaux dans le cortex a mis en évidence le rôle central de l’activité à haute-fréquence gamma (50-150Hz). Les résultats suggèrent que le cortex préfrontal ventro-médian est impliqué dans l’encodage des erreurs de prédiction des récompenses alors que pour l’insula antérieure, le cortex préfrontal dorsolatéral sont impliqués dans l’encodage des erreurs de prédiction des punitions. De plus, l’activité neurale de l’insula antérieure permet de prédire la performance des patients lors de l’apprentissage. Ces résultats sont cohérents avec l’existence d’une dissociation au niveau cortical pour le traitement des renforcements appétitifs et aversifs lors de la prise de décision. La seconde étude a permis d’étudier l’implication de deux noyaux limbiques du thalamus au cours du même protocole cognitif. L’enregistrement de potentiels de champs locaux a mis en évidence le rôle des activités basse fréquence thêta dans la détection des renforcements, en particulier dans leur dimension aversive. Dans une troisième étude, nous avons testé l’influence du risque sur l’apprentissage par renforcement. Nous rapportons une aversion spécifique au risque lors de l’apprentissage par évitement des punitions ainsi qu’une diminution du temps de réaction lors de choix risqués permettant l’obtention de récompenses. Cela laisse supposer un comportement global tendant vers une aversion au risque lors de l’apprentissage par évitement des punitions et au contraire une attirance pour le risque lors de l’apprentissage par récompenses, suggérant que les mécanismes d’encodage du risque et de la valence pourraient être indépendants. L’amélioration de la compréhension des mécanismes cérébraux sous-tendant la prise de décision est importante, à la fois pour mieux comprendre les déficits motivationnels caractérisant plusieurs pathologies neuropsychiatriques, mais aussi pour mieux comprendre les biais décisionnels que nous pouvons exhiber We make decisions every waking day of our life. Facing our options, we tend to pick the most likely to get our expected outcome. Taking into account our past experiences and their outcome is mandatory to identify the best option. This cognitive process is called reinforcement learning. To date, the underlying neural mechanisms are debated. Despite a consensus on the role of dopaminergic neurons in reward processing, several hypotheses on the neural bases of reinforcement learning coexist: either two distinct opposite systems covering cortical and subcortical areas, or a segregation of neurons within brain regions to process reward-based and punishment-avoidance learning.This PhD work aimed to identify the brain dynamics of human reinforcement learning. To unravel the neural mechanisms involved, we used intracerebral recordings in refractory epileptic patients during a probabilistic learning task. In the first study, we used a computational model to tackle the brain dynamics of reinforcement signal encoding, especially the encoding of reward and punishment prediction errors. Local field potentials exhibited the central role of high frequency gamma activity (50-150Hz) in these encodings. We report a role of the ventromedial prefrontal cortex in reward prediction error encoding while the anterior insula and the dorsolateral prefrontal cortex encoded punishment prediction errors. In addition, the magnitude of the neural response in the insula predicted behavioral learning and trial-to-trial behavioral adaptations. These results are consistent with the existence of two distinct opposite cortical systems processing reward and punishments during reinforcement learning. In a second study, we recorded the neural activity of the anterior and dorsomedial nuclei of the thalamus during the same cognitive task. Local field potentials recordings highlighted the role of low frequency theta activity in punishment processing, supporting an implication of these nuclei during punishment-avoidance learning. In a third behavioral study, we investigated the influence of risk on reinforcement learning. We observed a risk-aversion during punishment-avoidance, affecting the performance, as well as a risk-seeking behavior during reward-seeking, revealed by an increased reaction time towards appetitive risky choices. Taken together, these results suggest we are risk-seeking when we have something to gain and risk-averse when we have something to lose, in contrast to the prediction of the prospect theory.Improving our common knowledge of the brain dynamics of human reinforcement learning could improve the understanding of cognitive deficits of neurological patients, but also the decision bias all human beings can exhibit

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30

Smith, Ryan, Richard D. Lane, Anna Alkozei, et al. "Maintaining the feelings of others in working memory is associated with activation of the left anterior insula and left frontal-parietal control network." OXFORD UNIV PRESS, 2017. http://hdl.handle.net/10150/625065.

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The maintenance of social/emotional information in working memory (SWM/EWM) has recently been the topic of multiple neuroimaging studies. However, some studies find that SWM/EWM involves a medial frontal-parietal network while others instead find lateral frontal-parietal activations similar to studies of verbal and visuospatial WM. In this study, we asked 26 healthy volunteers to complete an EWM task designed to examine whether different cognitive strategies- maintaining emotional images, words, or feelings- might account for these discrepant results. We also examined whether differences in EWM performance were related to general intelligence (IQ), emotional intelligence (EI), and emotional awareness (EA). We found that maintaining emotional feelings, even when accounting for neural activation attributable to maintaining emotional images/words, still activated a left lateral frontal-parietal network (including the anterior insula and posterior dorsomedial frontal cortex). We also found that individual differences in the ability to maintain feelings were positively associated with IQ and EA, but not with EI. These results suggest that maintaining the feelings of others (at least when perceived exteroceptively) involves similar frontal-parietal control networks to exteroceptive WM, and that it is similarly linked to IQ, but that it also may be an important component of EA.

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31

Bou, Sader Nehme Sarah. "Cortical mechanisms of comorbidity between pain sensitization and attention-deficit/hyperactivity disorder (ADHD) in a mouse model." Electronic Thesis or Diss., Bordeaux, 2024. http://www.theses.fr/2024BORD0488.

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Le trouble du déficit de l'attention avec ou sans hyperactivité (TDAH) et la douleur chronique sont deux syndromes complexes d’origine multifactorielle. Des études confirment une comorbidité entre ces deux pathologies. Cependant, les mécanismes ne sont toujours pas élucidés. Une hyperactivité des neurones de l’ACC et une dérégulation de la voie ACC-insula postérieure (PI) ont été démontrées dans un modèle de souris TDAH. La neuroinflammation serait impliquée dans cette concomitance. Notre hypothèse suggère que la neuroinflammation déclencherait une amplification de l’activité neuronale dans l’ACC, sensibilisant ainsi les voies impliquées dans les symptômes du TDAH et la perception douloureuse. Ce travail de thèse vise donc à identifier les mécanismes inflammatoires à l’origine du TDAH et de la sensibilisation douloureuse qui lui est associée, avec un intérêt porté sur le rôle du récepteur purinergique P2X4 dans cette comorbidité.Afin de répondre à cette question, nous avons généré un modèle de souris TDAH par injection unilatérale et intracérébroventriculaire de 6-hydroxydopamine (6-OHDA), à P5. D’une part, des souris sauvages mâles et femelles âgées de deux mois ont été sacrifiées, leurs cerveaux ont été extraits et leurs ACC et PI ont été disséqués. Des tissus fixés ont été utilisés pour des études morphologiques tandis que des tissus frais ont été utilisés pour des études transcriptomique, protéomique et phosphoprotéomique. D’autre part, des souris avec un knock-out total du récepteur P2X4 ont été soumises à des tests de sensibilisation à la douleur (thermique et mécanique) et d'hyperactivité. Les tissus provenant d’ACC fixés ont été utilisés afin d’étudier les changements morphologiques microgliaux tandis que des tissus provenant d’ACC et de PI fraîchement extraits ont été utilisés pour des analyses transcriptomiques.En ce qui concerne les marqueurs identifiés chez les souris modèles de TDAH, nos résultats démontrent (i) des changements dans la morphologie des cellules microgliale et astrocytaire, associés à une réactivité cellulaire, dans l'ACC des souris 6-OHDA, (ii) la présence d’un environnement pro-inflammatoire dans l'ACC et la PI des souris 6-OHDA, (iii) des modifications dans l'expression de multiples protéines et l’activité de plusieurs kinases (sérine-thréonine et tyrosine) dans l'ACC et la PI des souris 6-OHDA, associées à des altérations du guidage axonal, de l’apoptose, de la dynamique du cytosquelette, de cascades de signalisation, de neurotrophines et de neurotransmetteurs, et (iv) des variations des interactions neurones-glie, et en particulier de la communication entre les neurones et les astrocytes dans l'ACC des souris 6-OHDA. L'intégration des données a permis d'identifier quatre processus altérés dans l'ACC et la PI des souris mâles et femelles 6-OHDA : l'apoptose, le guidage axonal, la plasticité synaptique (potentialisation à long terme) et la croissance des prolongements neuronaux ; des processus précédemment associés au TDAH et aux douleurs chroniques. De plus, nos résultats suggèrent un effet délétère du récepteur P2X4 sur l’activité locomotrice des souris et la réactivité microgliale. Il exercerait néanmoins un effet protecteur en limitant l'expression de molécules pro-inflammatoires, probablement sécrétées par des cellules non-microgliales.En conclusion, nos travaux fournissent des pistes sur les mécanismes inflammatoires qui sous-tendent la comorbidité entre le TDAH et la sensibilisation à la douleur. Ces pistes devront ultérieurement être validées individuellement. Le maintien d’un environnement pro-inflammatoire dans l'ACC et la PI entraîne des changements dans certains processus synaptiques (potentialisation à long-terme, guidage axonal, croissance des composants neuronaux) et apoptotiques. Ces altérations modifieraient la connectivité cellulaire et l'activité neuronale, participant ainsi à la pathogenèse du TDAH et de la douleur chronique Attention deficit/hyperactivity disorder (ADHD) and chronic pain are two complex conditions of multifactorial origins. Clinical and preclinical studies support an association between these two syndromes. However, the mechanisms underlying their comorbidity are not well understood. Previous findings from our team demonstrated a hyperactivity of the neurons of the anterior cingulate cortex (ACC) and a deregulation of the ACC-posterior insula (PI) pathway in ADHD-like conditions. Growing evidence also suggests a role for neuroinflammation in this concomitance. Our hypothesis thus suggests that neuroinflammation triggers an enhanced neuronal activity in the ACC that sensitizes pathways involved in ADHD symptoms and pain perception. Therefore, this Ph.D. work aims to elucidate the inflammatory mechanisms that may underlie ADHD and its associated pain sensitization, with an interest in the role of the purinergic P2X4 receptor.To address this question, we generated an ADHD-like mouse model through the unilateral intracerebroventricular injection of 6-hydroxydopamine (6-OHDA) at P5. Two-month-old wild-type male and female mice were sacrificed, their brains were extracted, and their ACC and PI were dissected. Fixed tissues were used to study microglial and astrocytic morphology while fresh tissues were utilized for transcriptomic, proteomic, and phosphoproteomic investigations. Moreover, mice with a total knock-out of the P2X4 receptor were tested for thermal and mechanical pain sensitization, in addition to hyperactivity. Fixed tissues of the ACC were used to study changes in microglial morphology while fresh tissues of the ACC and PI were utilized for transcriptomic analyses.Regarding the identification of inflammatory mechanisms in our ADHD-like mouse model, our results report (i) changes in microglial and astrocytic morphology, associated with cellular reactivity, in the ACC of 6-OHDA mice, (ii) the presence of a pro-inflammatory environment in the ACC and PI of 6-OHDA mice, (iii) modifications in protein expression and kinase (serine-threonine and tyrosine) activity in the ACC and PI of 6-OHDA mice, and correlated with impairments in axon guidance, apoptosis, cytoskeleton dynamics, signaling cascades, neurotrophins, and neurotransmitter systems, and (iv) alterations in protein interactions and, therefore, neuronal-astrocytic communication in the ACC of 6-OHDA mice. Finally, data integration identified four processes impaired in the ACC and PI of 6-OHDA males and females: apoptosis, axon guidance, synaptic plasticity (long-term potentiation), and growth of neuronal components. Interestingly, alterations in these processes were not only linked to ADHD and chronic pain conditions but also associated with Eph/ephrin bidirectional signaling cascades. Our findings also indicate a role for the P2X4 receptor in the worsening of ADHD hyperactivity symptom and the induction of morphological changes in microglial cells that correlate with cellular reactivity. However, it exerts a protective effect by limiting the expression of pro-inflammatory molecules, possibly from non-microglial cells.In conclusion, our work provides interesting insights into the inflammatory mechanisms that may underpin the comorbidity between ADHD and pain sensitization. A mild and sustained pro-inflammatory environment in the ACC and PI drives changes in synaptic-related (long-term potentiation, axon guidance, outgrowth of neuronal components) and apoptotic processes. These impairments alter cell-cell connectivity and neuronal activity, thus participating in ADHD and chronic pain pathogenesis

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32

Naqvi, Nasir Hasnain. "The effects of lesions in the ventromedial prefrontal cortex and related areas on emotional responses to cigarette smoking." Diss., University of Iowa, 2007. http://ir.uiowa.edu/etd/173.

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33

Lueken, Ulrike, Johann Daniel Kruschwitz, Markus Muehlhan, Jens Siegert, Jürgen Hoyer, and Hans-Ulrich Wittchen. "How specific is specific phobia? Different neural response patterns in two subtypes of specific phobia." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-112819.

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Specific phobia of the animal subtype has been employed as a model disorder exploring the neurocircuitry of anxiety disorders, but evidence is lacking whether the detected neural response pattern accounts for all animal subtypes, nor across other phobia subtypes. The present study aimed at directly comparing two subtypes of specific phobia: snake phobia (SP) representing the animal, and dental phobia (DP) representing the blood-injection-injury subtype. Using functional magnetic resonance imaging (fMRI), brain activation and skin conductance was measured during phobogenic video stimulation in 12 DP, 12 SP, and 17 healthy controls. For SP, the previously described activation of fear circuitry structures encompassing the insula, anterior cingulate cortex and thalamus could be replicated and was furthermore associated with autonomic arousal. In contrast, DP showed circumscribed activation of the prefrontal and orbitofrontal cortex (PFC/OFC) when directly compared to SP, being dissociated from autonomic arousal. Results provide preliminary evidence for the idea that snake and dental phobia are characterized by distinct underlying neural systems during sustained emotional processing with evaluation processes in DP being controlled by orbitofrontal areas, whereas phobogenic reactions in SP are primarily guided by limbic and paralimbic structures. Findings support the current diagnostic classification conventions, separating distinct subtypes in DSM-IV-TR. They highlight that caution might be warranted though for generalizing findings derived from animal phobia to other phobic and anxiety disorders. If replicated, results could contribute to a better understanding of underlying neurobiological mechanisms of specific phobia and their respective classification.

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34

Costa, Vinícius Pelarin do Nascimento. "Empatia em camundongos: avaliação do papel da amídala, insula e córtex cingulado anterior na nocicepção em camundongos expostos ao teste de contorções abdominais." Universidade Federal de São Carlos, 2014. https://repositorio.ufscar.br/handle/ufscar/1376.

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Made available in DSpace on 2016-06-02T19:23:02Z (GMT). No. of bitstreams: 1 6369.pdf: 1124310 bytes, checksum: 0ca17967bc2f98ad5efcffdb78af91d5 (MD5) Previous issue date: 2014-05-09 Universidade Federal de Minas Gerais Empathy can be defined as the capacity for perceive emotional signals from others. Among these signals, the ability to perceive pain has clear adaptive and evolutionary value. Pain can be defined as a subjective experience that includes sensorial, emotional and cognitive components. Evidence has emphasized the role of amygdala, anterior cingulate cortex (ACC) and insula in modulation of pain and empathy. Research indicates the capacity of rodents to express empathy to a conspecific in pain or suffering. Works from literature and finds from our laboratory demonstrated that living together with a cagemate is able to alter the nociceptive behavior in mice. However, there are no works evidencing if occur alterations in nociception by living together with a cagemate with chronic pain and which encephalic structures would be involved in this modulation. To overcome this, male Swiss-albino mice were housed in groups or in pairs. The role of amygdala, ACC and insula are accessed by non-selective inactivation with cobalt chloride (CoCl2). Mice housed in groups (Experiment 1), aging 6-8 weeks, underwent a stereotaxic surgery. 4 to 5 days after surgery, these animals received saline or CoCl2 microinjection, and, after 10 minutes, they were submitted to the writhing test during 5 minutes (acetic acid 0.6%, i.p., nociceptive stimulus). On the dyads (Experiment 2), animals lived together for 28 days since weaning. On the 14th day, one animal of each pair were submitted to a sciatic nerve constriction (SNC animal) or not (sham animal). On the 24th day, the cagemate underwent a stereotaxic surgery, and, on the 28th day, they were submitted to the writhing test after microinjection of saline or CoCl2, like the procedure described to Experiment 1. To Experiment 1 were utilized Student s t test to independent samples; to Experiment 2 were utilized two-way analysis of variance (ANOVA; living together x treatment). Duncan s multiple range tests were utilized as post hoc. A p value of 0.05 or less was required for significance in both experiments. In Experiment 1, inactivation of the amygdala increased the number of writhing, while inactivation of ACC and insula did not alter this measure, suggesting a distinct modulatory role of these structures on the sensorial compound of pain. Our results demonstrated that for the mice that lived in groups, while inactivation of the ACC and insula did not change writhing, inactivation of amygdala increased it, suggesting a distinct modulatory role of these structures on sensory component of pain in the writhing test. In Experiment 2, living together with a SNC-cagemate increased writhing on the pair, suggesting that this experience activates the circuitry of neural representation of pain on the observer mouse (state of priming ). Thus, when this animal experienced nociception, its response was exacerbated. In this condition, inactivation of insula and amygdala produces opposite results, i.e., decreased and increased in contortions in those animals that lived together with a SNC animal, respectively. ACC inactivation did not alter writhing behavior. In this sense, our results suggest a different modulatory role of these structures on cognitive, affective-emotional and sensorial components of pain, and on empathy for pain. Sob uma perspectiva evolucionista, a empatia é expressa pela capacidade de captar sinais emocionais nos outros. Neste sentido, a habilidade em perceber a dor também possui valor claramente adaptativo e evolutivo. A dor pode ser definida como uma experiência subjetiva que inclui componentes sensoriais, afetivo-emocionais e cognitivos. Evidencias apontam para o papel da amídala, córtex cingulado anterior (CCA) e insula na modulação da dor e da empatia. Estudos indicam para a capacidade de roedores em apresentarem empatia frente à dor ou ao sofrimento de seus coespecíficos. Trabalhos da literatura e do nosso grupo demonstram que a convivência em pares é capaz de alterar bidirecionalmente a resposta nociceptiva em camundongos. Entretanto, nenhum estudo havia ainda evidenciado se ocorrem alterações nociceptivas devido à convivência com um coespecífico em quadro de dor crônica, e quais estruturas encefálicas estariam envolvidas nessa modulação. Neste sentido, camundongos machos Suiço-albinos foram alojados em grupos ou em duplas para avaliação do papel da amídala, insula e córtex cingulado anterior por meio de inativação com cloreto de cobalto (CoCl2). Os animais alojados em grupo (Experimento 1), ao atingirem idade entre 6-8 semanas, passaram por cirurgia estereotáxica. De 4 à 5 dias após a cirurgia, esses animais receberam microinjeção de salina ou CoCl2 e, após 10 minutos, foram submetidos ao teste de contorções abdominais (ácido acético 0,6%, i.p., estímulo nociceptivo) durante 5 minutos. Nas duplas (Experimento 2), os animais conviveram por um período de 28 dias após o desmame. No 14º dia, um animal de cada par foi submetido à cirurgia de constrição do nervo ciático (animal CNC) ou não (animal sham). No 24º dia, o camundongo que conviveu com o animal CNC ou animal sham passou por uma cirurgia estereotáxica, e, no 28º dia, foi submetido ao teste de contorções abdominais, após microinjeção de salina ou CoCl2, conforme Experimento 1. Para o Experimento 1 foi utilizado o teste t de Student para amostras independentes; no Experimento 2 foi utilizada a análise de variância (ANOVA) de dois fatores (convívio x tratamento). O post hoc utilizado foi o teste de comparações múltiplas de Duncan. Os valores de p menores ou iguais a 0,05 foram considerados como significativos nos dois experimentos. No Experimento 1, a inativação da amídala aumentou o número de contorções, enquanto a inativação do CCA e da insula não alterou esse parâmetro, sugerindo um papel modulatório distinto dessas estruturas no componente sensorial da dor para o teste de contorções. No experimento 2, o convívio com um animal CNC aumentou o número de contorções no parceiro, sugerindo que essa convivência causou ativação dos circuitos de representatividade neural da dor no camundongo observador (state of priming ). Dessa forma, quando esse animal experiencia nocicepção, sua resposta é exacerbada. Nessa condição, a inativação da insula e amídala produziu resultados opostos, ou seja, diminuição e aumento das contorções naqueles animais que conviveram com o animal CNC, respectivamente. A inativação do CCA não alterou o número de contorções. Nesse sentido, nossos resultados sugerem um papel modulatório distinto dessas estruturas nos componentes cognitivo, afetivo-emocional e sensorial da dor, e na empatia para a dor.

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35

Zheng, Qi. "Performance Characterization of Silicon-On-Insulator (SOI) Corner Turning and Multimode Interference Devices." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23234.

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Silicon-on-insulator (SOI) technology has become increasingly attractive because of the strong light confinement, which significantly reduces the footprint of the photonic components, and the possibility of monolithically integrating advanced photonic waveguide circuits with complex electronic circuits, which may reduce the cost of photonic integrated circuits by mass production. This thesis is dedicated to numerical simulation and experimental performance measurement of passive SOI waveguide devices. The thesis consists of two main parts. In the first part, SOI curved waveguide and corner turning mirror are studied. Propagation losses of the SOI waveguide devices are accurately measured using a Fabry-Perot interference method. Our measurements verify that the SOI corner turning mirror structures can not only significantly reduce the footprint size, but also reduce the access loss by replacing the curved sections in any SOI planar lightwave circuit systems. In the second part, an optical 90o hybrid based on 4 × 4 multimode interference (MMI) coupler is studied. Its quadrature phase behavior is verified by both numerical simulations and experimental measurements.

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36

Lueken, Ulrike, Johann Daniel Kruschwitz, Markus Muehlhan, Jens Siegert, Jürgen Hoyer, and Hans-Ulrich Wittchen. "How specific is specific phobia? Different neural response patterns in two subtypes of specific phobia." Technische Universität Dresden, 2011. https://tud.qucosa.de/id/qucosa%3A26867.

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Specific phobia of the animal subtype has been employed as a model disorder exploring the neurocircuitry of anxiety disorders, but evidence is lacking whether the detected neural response pattern accounts for all animal subtypes, nor across other phobia subtypes. The present study aimed at directly comparing two subtypes of specific phobia: snake phobia (SP) representing the animal, and dental phobia (DP) representing the blood-injection-injury subtype. Using functional magnetic resonance imaging (fMRI), brain activation and skin conductance was measured during phobogenic video stimulation in 12 DP, 12 SP, and 17 healthy controls. For SP, the previously described activation of fear circuitry structures encompassing the insula, anterior cingulate cortex and thalamus could be replicated and was furthermore associated with autonomic arousal. In contrast, DP showed circumscribed activation of the prefrontal and orbitofrontal cortex (PFC/OFC) when directly compared to SP, being dissociated from autonomic arousal. Results provide preliminary evidence for the idea that snake and dental phobia are characterized by distinct underlying neural systems during sustained emotional processing with evaluation processes in DP being controlled by orbitofrontal areas, whereas phobogenic reactions in SP are primarily guided by limbic and paralimbic structures. Findings support the current diagnostic classification conventions, separating distinct subtypes in DSM-IV-TR. They highlight that caution might be warranted though for generalizing findings derived from animal phobia to other phobic and anxiety disorders. If replicated, results could contribute to a better understanding of underlying neurobiological mechanisms of specific phobia and their respective classification.

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37

Chiarovano, Elodie. "Instabilité posturale chez les séniors : dysfonction vestibulaire périphérique ou centrale ?" Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCB006.

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L’instabilité posturale est fréquente chez les séniors et peut entrainer la chute. La chute chez les séniors est un problème majeur de santé publique. Les chiffres épidémiologiques sont éloquents : une personne sur trois âgées de plus de 70 ans fera une chute dans l’année. Les causes sont multifactorielles : ostéo-articulaire, visuelle, cognitive, vestibulaire…. Dans cette étude, nous nous sommes intéressés à l’évolution de la fonction des récepteurs vestibulaires périphériques avec l’âge et à la perception de rotation à partir des entrées canalaires horizontales (système vestibulaire central et projections vestibulaires corticales). Notre but est d’essayer de comprendre l’implication du vieillissement du système vestibulaire dans l’instabilité posturale des séniors. Au niveau périphérique, nous avons quantifié la fonction des canaux semi-circulaires horizontaux par le test calorique et le vidéo-head impulse test. La fonction des récepteurs otolithiques (utriculaire et sacculaire) a été évaluée par les potentiels évoqués myogéniques recueillis au niveau cervical (voies sacculo-spinales) et oculaire (voies utriculo-oculaires). Au niveau central, la perception de l’entrée vestibulaire canalaire horizontale a été appréciée après irrigation à l’eau chaude du conduit auditif externe en appliquant un score de perception (présence ou absence de sensation rotatoire). Finalement, l’équilibre a été quantifié grâce au test d’organisation sensorielle sur l’Equitest et grâce à un système que nous avons récemment mis au point en collaboration avec le Professeur Curthoys à Sydney, comprenant une Wii Balance Board, un tapis mousse et un masque de réalité virtuelle (Oculus Rift). Les résultats ont montré une diminution des réponses oculaires au test calorique après 70 ans mais une absence de baisse du gain du réflexe vestibulo-oculaire horizontal au vidéo-head impulse test. La fonction otolithique, sacculaire et utriculaire, est altérée avec l’âge quelle que soit la stimulation utilisée (aérienne ou osseuse). La perception de l’entrée vestibulaire canalaire horizontale induite par une stimulation calorique nous a permis de montrer pour la première fois que certains séniors ne percevaient pas la sensation de rotation malgré une réponse oculaire normale (vitesse maximale de la phase lente du nystagmus oculaire supérieure à 15°/s). Dans notre population, nous avons pu ainsi définir deux types de séniors : un groupe présentant une perception de vertige rotatoire et un groupe « négligeant » ne pouvant pas reconstruire une sensation rotatoire à partir des entrées vestibulaires canalaires horizontales. La comparaison de ces deux groupes de séniors appariés sur l’âge ne montre aucune différence de la fonction canalaire horizontale ni de la fonction otolithique sacculaire et utriculaire. Néanmoins, les séniors négligents présentent en majorité des performances anormales (chute ou score diminué) à l’Equitest notamment en conditions 5 et 6. De plus, leur score au DHI est plus élevé relevant ainsi le handicape ressenti par ces séniors à cause de leur instabilité. En conclusion, les troubles de l’équilibre chez certains seniors pourraient résulter en partie d’une dysfonction vestibulaire centrale. Des études ultérieures permettront de déterminer si l’augmentation du seuil de perception rotatoire est un bon facteur prédictif du risque de chute Postural instability is common in seniors and can lead to falls which seniors are a major problem for Public Health. Epidemiological studies clearly show the magnitude of this problem: one in three people aged than more 70 years will fall in a year. This is caused by multiple factors including: musculoskeletal, visual, cognition, vestibular… The present study concerns the effect of age on the vestibular peripheral receptors function and on the perception of rotation from horizontal canal inputs (central vestibular processing and vestibular cortical projection). The aim is to try to understand the vestibular mechanisms involved in postural instability and mobility with age. At the peripheral level, the horizontal canal function was assessed using caloric test and video-Head Impulse Test. Otolith function (saccular and utricular) was assessed using vestibular evoked myogenic potentials recorded at cervical level (sacculo-spinal pathways) and at ocular level (utriculo-ocular pathways). At the central level, perception of motion from vestibular horizontal canal inputs was studied after caloric stimulation with warm water using a subjective perceptual score (presence or absence of rotatory vertigo). Finally, postural equilibrium was assessed with the Sensory Organization Test on the Equitest machine and also with a new system developed in collaboration with Prof. Curthoys (Sydney) using a Wii Balance Board, a foam rubber pad and a virtual reality headset (Oculus Rift DK2). Results showed decreased ocular responses induced by caloric stimulation after 70 years of age but healthy horizontal gain of the vestibulo-ocular reflex assessed by video-head impulse testing. The otolithic (saccular and utricular) function is impaired with age for all the stimuli used (air or bone conducted). Perception of motion induced by caloric stimulation (vestibular horizontal canal inputs) allowed us to show for the first time that some seniors are unable to feel the induced rotatory vertigo even with normal ocular responses (peak of the slow phase eye velocity higher than 15°/s). We defined two types of seniors: one senior group having a normal feeling of vertigo and one senior ‘neglect’ group who did not feel any sensation of rotation from horizontal canal inputs. The comparison of these two age-matched groups showed no difference in horizontal canal function, or otolithic function. The majority of the ‘neglect’ seniors with an absence of perception exhibited falls or a decreased score in conditions 5 and 6 during the Equitest. Moreover, their DHI scores were higher, showing the handicap induced by postural instability in these seniors. In conclusion, postural instability and falls in seniors may result from central vestibular impairment (inadequate central processing). A prospective study is needed to determine whether the increase perceptual threshold of rotation could be a good predictor of fall risk in seniors

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Sawamoto, Nobukatsu. "Expectation of pain enhances responses to nonpainful somatosensory stimulation in the anterior cingulate cortex and parietal operculum/posterior insula : an event-related functional magnetic resonance imaging study." Kyoto University, 2001. http://hdl.handle.net/2433/150507.

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Endres, Ralph Julian Verfasser], Ulrike [Gutachter] Lüken, and Marcel [Gutachter] [Romanos. "Networks of fear: Functional connectivity of the amygdala, the insula and the anterior cingulate cortex in two subtypes of specific phobia / Ralph Julian Endres ; Gutachter: Ulrike Lüken, Marcel Romanos." Würzburg : Universität Würzburg, 2019. http://d-nb.info/1187140546/34.

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Fall, Anna. "Rôles différentiels du cortex cingulaire antérieur sous-génual et de l'insula antérieure dans la régulation des conséquences socio-affectives de l'exclusion sociale chez le rat." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS097.

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Les humains sont motivés par un besoin fondamental de maintenir des relations stables et durables. De nombreuses études comportementales ont démontré que l’exclusion sociale menace ce besoin fondamental d’appartenance. Au niveau neuronal, il a été mis en évidence l’implication du cortex cingulaire antérieur sous génual (CCAsg) et de l’insula antérieure (AI), deux régions aussi impliquées dans la dépression majeure, où le rejet social constitue un facteur de risque établi. A ce jour, le rôle du CCAsg et de l’AI dans les processus d’intégration et de régulation de l’exclusion sociale reste cependant inconnu. Afin d’étudier les conséquences comportementales de l’exclusion sociale ainsi que les rôles différentiels du CCAsg et de l’AI, nous avons dans un premier temps développé une nouvelle tâche d’exclusion sociale chez le rat. Cette tâche nous a permis, dans un second temps, d’étudier i) les conséquence socio-affectives de l’exposition à un stress social, ii) l’effet de lésions discrètes au niveau de l’homologue murin du CCAsg (cortex infralimbique, A25) et de l’AI (insula agranulaire) sur la réponse affective et iii) l’impact de l’administration d’ocytocine (OT), un neuropeptide impliqué dans les processus affiliatifs, sur les interactions sociales. Nous avons pu montrer que l’exclusion sociale impactait négativement les interactions sociales ainsi que les comportements de type dépressifs. Les lésions au niveau de A25 et l’administration d’OT ont réduit cet effet négatif et modulé l’activation neuronale au niveau du CCAsg et de l’AI. Nos données permettent de proposer un modèle d’intégration et de régulation des signaux d’exclusion sociale impliquant le CCAsg et l’AI Humans are motivated by a fundamental need to create and maintain strong and stable relationships. Numerous behavioral studies showed that social exclusion negatively affect this fundamental need. At the neuronal level, imaging studies highlighted the involvement of the subgenual anterior cingulate cortex (sgACC) and anterior insula (AI). Interestingly, these regions are also involved in the physiopathology of major depressive disorder, where social rejection constitutes a risk factor. To this day, the role of the sgACC and AI in the integration and regulation of social exclusion signals remains relatively unknown. To investigate the behavioral consequences of social exclusion, and the differential roles of the sgACC and AI, we first developed a new behavioral task of social exclusion in rats. This tasks allowed us to investigate i) the socio-affective consequences of being exposed to a social stress, ii) the consequences of excitotoxic lesion in the rodent homologous of the sgACC (infralimbic cortex or A25) and the AI (agranular insula) on affective behavior, iii) the impact of oxytocin (OT) administration, a neuropeptide involved in affiliative behaviors, on social interactions. Our results showed that exposure to social exclusion affected social interactions and increased depressive-like behaviors. The administration of OT and lesions of the infralimbic cortex reduced this negative impact and modulated neuronal activation. In conclusion, our work highlighted a differential role of the sgACC and the AI, and allowed us to propose a framework for the mechanisms of detection and processing of social exclusion signals

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Musselmann, Kurt. "Developing culture conditions to study keratocyte phenotypes in vitro." [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001726.

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Ciucci, Francesca. "Insulin-like Growth Factor 1 (IGF-1) mediates the effects of enriched environments on visual system development." Doctoral thesis, Scuola Normale Superiore, 2007. http://hdl.handle.net/11384/85967.

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Penin, Lucie. "Maintien des populations de coraux Scléractiniaires en milieu insulaire fragmenté (archipel de la Société, Polynésie française) : influence du recrutement et de la mortalité post-fixation." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2007. http://tel.archives-ouvertes.fr/tel-00743644.

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De façon à améliorer la compréhension des mécanismes de maintien des populations de Scléractiniaires en milieu insulaire fragmenté, l'influence des variations du recrutement, d'une part, et de la mortalité post-recrutement, d'autre part, sur la structure des peuplements juvéniles et adultes a été explorée. Pour cela, dans un premier temps, la variabilité spatio-temporelle du recrutement a été caractérisée à l'échelle insulaire sur 5 ans autour de Moorea et à l'échelle régionale sur 1 an dans l'archipel de la Société (Polynésie française) de façon à mener des analyses spatio-temporelles à multi-échelles. Dans un deuxième temps, la mortalité benthique des stades recrue et juvénile a été quantifiée autour de Moorea, et les principaux facteurs de mortalité identifiés. Nos résultats montrent l'importance des événements post-recrutement dans la structuration et le maintien des peuplements de Scléractiniaires, quelles que soient les échelles spatio-temporelles considérées. Cependant, pour certains taxons, la structure spatiale des populations adultes à Moorea semble majoritairement gouvernée par la variabilité spatiale du recrutement sur plusieurs années, illustrant l'implication des différences de traits d'histoire de vie dans les mécanismes de maintien des populations. Autour de Moorea, la mortalité des recrues est particulièrement élevée (50 % en 7 jours), et notamment liée à la prédation par les poissons des familles Scaridae et Balistidae (en particulier les espèces Scarus psittacus, Chlorurus sordidus et Melichthys vidua), et à la compétition avec les autres organismes encroûtants. En outre, la variabilité spatiale de cette mortalité post-fixation précoce explique de façon convaincante les différences observées entre la structure spatiale des recrues et celle des juvéniles, pour deux des trois sites étudiés. La mortalité des juvéniles est de moindre intensité (40 % en 14 mois), mais présente également une variabilité spatiale marquée, notamment en lien avec les variations de l'abondance des poissons de la famille Chaetodontidae (Chaetodon pelewensis) et avec le recouvrement en coraux vivants. Cette étude souligne ainsi la prépondérance des événements post-recrutement dans la structuration des populations et des peuplements adultes, et l'importance des événements ayant lieu au cours des premières semaines de la vie benthique (stade recrue), parmi lesquels la mortalité liée aux interactions biotiques (prédation et compétition) semble particulièrement importante.

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Della, Corte Karen Aimee [Verfasser]. "Dietary sugar intake: International time trends in intake levels among children and adolescents and aspects of its relevance for subclinical inflammation and insulin sensitivity among adults / Karen Aimee Della Corte." Paderborn : Universitätsbibliothek, 2021. http://d-nb.info/1230468323/34.

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Duarte, Marcio de Souza. "Desempenho e qualidade de carne em novilhas de corte alimentados com dois níveis de concentrado e proteína não degradável no rúmen e influência da maturidade fisiológica sobre parâmetros qualitativos da carcaça e da carne bovina." Universidade Federal de Viçosa, 2010. http://locus.ufv.br/handle/123456789/5659.

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Made available in DSpace on 2015-03-26T13:54:58Z (GMT). No. of bitstreams: 1 texto completo.pdf: 847490 bytes, checksum: 96b19b5b36a4040238163990d01928e6 (MD5) Previous issue date: 2010-02-22 Conselho Nacional de Desenvolvimento Científico e Tecnológico The present work was developed based on two experiments. The first experiment was conducted aiming to evaluate the effects of ruminal energy-protein synchronization on feed intake, nutrients digestibility, feed conversion, animal performance, carcass yields and composition, composition of the carcass gain, percentage of commercial cuts and meat quality of feedlot heifers. In this trial, twenty crossbreed heifers (240+6kg) were used, all of them coming from the same contemporary group. At the beginning, four animals were slaughtered as reference group and the sixteen animals remaining were assigned to a completely randomized design in 2x2 factorial schemes, two levels of concentrate (40 and 80%, based on dry matter) and two levels of ruminally undegradable protein (RUP). These animals were individually fed during 112 days and slaughtered at the end of the trial. There was no interaction (P>0.05) between the level of concentrate and RUP. The dry matter intake (DMI), feed intake and nutrients digestibility were not affected (P>0.05) by RUP level. However, the animals fed higher level of RUP diets had higher (P<0.05) average daily gain (ADG) compared with the animals fed lower level of RUP diets. The level of concentrate did not affect (P>0.05) the DMI, feed conversion and ADG, but the intakes of TDN, NDFcp and EE, were superior (P<0.05) in the animals fed higher concentrate diets. The digestibilities of all nutrients, except the NDFcp, were greater (P<0.05) for the 80% concentrate diets. There was no affect (P>0.05) of RUP level on carcass yields. Similarly, the percentage of commercial cuts, the composition of the carcass and the composition of the carcass gain were not affected (P>0.05) by the level of RUP and concentrate. However, the animals fed 80% concentrate diets had a larger (P<0.05) rib eye area (REA) compared with the animals fed 40% concentrate diets. No differences (P>0.05) in Warner-Bratzler shear force, myofibrillar fragmentation index, percentage of total cooking loss, and chemical composition of the Longissimus dorsi, were found among the levels of concentrate and RUP. It can be concluded that the level of RUP did not affect the feed intake and nutrients digestibilities, but improved the feed conversion and increased the ADG. Neither level of RUP nor level of concentrate affected the carcass composition, composition of carcass gain, percentage of commercial cuts and the meat quality of the feedlot heifers. The second experiment was conducted to evaluate the beef carcass traits and meat quality of cattle differing in numbers of permanent incisors. Sixty-three Nellore bulls, non-castrated, all from the same farm and grown on pasture, were used. The animals were selected at a large commercial beef plant. Immediately after the slaughter, the numbers of incisors were recorded after a visual examination by looking directly at the teeth and the carcasses were grouped in four categories according to teeth maturity (two, four, six or eight). After 24-h chill, data of carcass weight, pH, rib eye area (REA) and 12th rib fat thickness were collected. After carcass data collection, a boneless Longissimus section between the 9th and 11th rib was removed, vacuum packaged, frozen and held at -200C. The REA and the 12th rib fat thickness increased (P<0.05) as the number of permanent incisors increased. However, no differences (P>0.05) in carcass ultimate pH were found among the four dental classes. There was no effect (P>0.05) of dental maturity on percentage of evaporative and total cooking losses, but differences in percentage of thawing and drip losses were found (P<0.05) among the four dental classes. The Longissimus intramuscular fat and water content were affected (P<0.05) by the dental maturity. However, there was no difference (P>0.05) in percentage of protein and ashes among the dental classes. With the exception of b* values, the dental maturity did not affect (P>0.05) the instrumental color of the Longissimus. The Warner-Bratzler shear force (WBSF), the myofibrillar fragmentation index (MFI) and collagen solubility were affected (P<0.05) by dental maturity, whereas the WBSF has increased while the MFI and collagen solubility decreased as the number of permanent incisors increased. An increase of WBSF was associated (P<0.01) with decreased MFI (r = -0,36) and collagen solubility (r = - 0,14). It can be concluded that the physiological maturity, based on dental classification, affects the carcass traits and meat quality of Nellore cattle. It can also be concluded that meat from non-castrated Zebu cattle up to four permanent incisors has a desirable tenderness. O presente trabalho foi desenvolvido a partir de dois experimentos. O primeiro foi conduzido para de avaliar o efeito da adequação de energia e proteína na dieta sobre o consumo, digestibilidade dos nutrientes, conversão alimentar, desempenho, características e composição físico-química da carcaça, composição do ganho de carcaça, rendimento de cortes comerciais e características qualitativas da carne de novilhas confinadas. Nesse experimento, foram utilizadas 20 novilhas mestiças, provenientes de um mesmo grupo contemporâneo e com peso corporal médio inicial de 240 kg. Quatro animais foram abatidos no inicio do experimento para constituir o grupo referência e os 16 animais restantes foram distribuído em quatro tratamentos em delineamento experimental inteiramente casualizado, em esquema fatorial 2x2, 40 e 80 % de concentrado, e dois níveis de proteína não degradável no rúmen (PNDR). Os animais permaneceram em média 112 dias em confinamento, sendo alimentados individualmente e foram abatidos ao final do período experimental. Não foi verificada interação (P>0,05) entre o nível de concentrado na dieta e a degradabilidade da proteína. Não houve efeito da PNDR (P>0,05) sobre o consumo e digestibilidade dos nutrientes. Entretanto, PNDR influenciou (P>0,05) o ganho de peso médio diário (GMD) dos animais. O nível de concentrado na dieta não influenciou (P>0,05) o consumo de matéria seca (CMS), a conversão alimentar e o GMD dos animais. Entretanto, o consumo de nutrientes digestíveis totais (NDT), fibra em detergenteneutro corrigido para cinzas e proteína (FDNcp) e extrato etéreo (EE) dos animais alimentados com dietas contendo 80% de concentrado mostrou-se superior (P<0,05) em relação aos animais alimentados com a dieta contendo 40% de concentrado. A dieta contendo 80% de concentrado propiciou maiores coeficientes de digestibilidade (P<0,05) de todos os nutrientes, comparado-se a dieta contendo 40% de concentrado, exceto para a FDNcp. As novilhas alimentadas com os diferentes níveis de concentrado apresentaram composição físico-química da carcaça e do ganho de carcaça similar (P>0,05). O nível de concentrado na dieta influenciou (P<0,05) a área de olho de lombo (AOL), e as novilhas alimentadas com dietas contendo 80% de concentrado apresentaram maior AOL em relação às novilhas alimentadas com dietas contendo 40% de concentrado. O rendimento dos cortes comerciais e as características qualitativas da carne não foram influenciadas (P>0,05) pela quantidade de PNDR presente na dieta nem pelo nível de fornecimento de concentrado. O nível de PNDR na dieta não alterou o consumo e digestibilidade dos nutrientes; melhorou a conversão alimentar e o desempenho de novilhas confinadas; não alterou a composição físico-química da carcaça, do ganho de carcaça e as características qualitativas da carne. As novilhas alimentadas com 80% de concentrado apresentam composição físico-química da carcaça, composição do ganho de carcaça e características qualitativas da carne semelhantes às novilhas alimentadas com dietas contendo 40% de concentrado. Conclui-se o maior fornecimento de PNDR na dieta de novilhas confinadas não implica em melhorias nas principais características de carcaça e qualidade da carne. Conclui-se ainda que novilhas confinadas alimentadas níveis moderados de concentrado na dieta (40% na matéria seca total) apresentam características de carcaça e da carne semelhantes às novilhas alimentadas com altos níveis de concentrado (80% na matéria seca total). No segundo experimento objetivou-se avaliar as características de carcaça e a qualidade da carne de bovinos em diferentes estádios de maturidade fisiológica, avaliada através da contagem do número de dentes incisivos permanentes (d.i.p.) na arcada dentária. Foram utilizados 63 animais da raça Nelore, todos machos não castrados e criados a pasto. Os animais foram selecionados em frigorífico comercial previamente ao abate. As carcaças dos animais selecionados foram agrupadas em quatro categorias de acordo com o número de d.i.p presentes na arcada dentária (2, 4, 6 e 8 d.i.p.). Após o período de resfriamento, as carcaças foram pesadas e realizou-se a mensuração do pH, área de olho de lombo (AOL) e espessura de gordura subcutânea (EGS). Em seguida foram coletadas amostras do músculo Longissimus entre a 9a e a 11a costela para realização das análises de qualidade de carne. A maturidade alterou (P<0,05) o peso da carcaça fria, AOL e a espessura de gordura subcutânea (EGS) da carcaça sendo observado aumento dessas características com o aumento do número de d.i.p na arcada dentária dos animais. Entretanto, a maturidade não alterou (P>0,05) o pH final da carcaça sendo o valor médio encontrado para essa característica igual a 6,4. Em relação as perdas das carne, à exceção das perdas por descongelamento e gotejamento, não foram detectadas diferenças (P>0,05) entre os grupos de dentição. Não houve diferença (P>0,05) entre os grupos de dentição para o teor de proteína e cinzas do músculo Longissimus. Entretanto, foram verificadas diferenças (P<0,05) entre os grupos de dentição quanto ao teor de água e extrato etéreo presentes no Longissimus. Os valores de luminosidade (L*) e intensidade de vermelho (a*) da carne não diferiram (P>0,05) entre os grupos de dentição. Entretanto, verificou-se que a maturidade alterou (P<0,05) a intensidade de amarelo (b*). A força de cisalhamento (FC), o índice de fragmentação miofibrilar (IFM) e o teor de colágeno solúvel foram influenciados (P<0,05) pela maturidade sendo observado o aumento da FC e redução dos valores de IFM e colágeno solúvel com o aumento no número de d.i.p. A FC apresentou-se negativamente correlacionada (P<0,01) com o IFM (r = -0,36) e com o teor de colágeno solúvel (r = -0,14). Conclui-se que a maturidade fisiológica avaliada pela análise da arcada dentária, influencia as características de carcaça e os principais parâmetros qualitativos da carne de bovinos Nelore. Conclui-se ainda que para animais zebuínos inteiros abatidos em frigorífico comercial, a carne pode ser considerada com maciez aceitável nos animais com até 4 dentes incisivos permanentes, ou seja, animais de até 36 meses, aproximadamente.

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Mishura, Daria [Verfasser], Cornelius [Akademischer Betreuer] Bollheimer, and Cornel [Gutachter] Sieber. "Untersuchungen zum Einfluss der Stoffwechselhormone Adiponektin, Insulin und Leptin auf die ernährungsabhängige Entwicklung von Sarkopenie im präklinischen Modell der alternden Hochfettratte / Daria Mishura ; Gutachter: Cornel Sieber ; Betreuer: Cornelius Bollheimer." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2019. http://d-nb.info/1184023832/34.

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Almeida, Madson Queiroz de. "Expressão dos genes IGF-II, IGF-IR, SF-1 e DAX-1 em tumores adrenocorticais de crianças e adultos." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-31102008-153148/.

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Introdução: A patogênese molecular dos tumores adrenocorticais é heterogênea e ainda pouco compreendida. A hiperexpressão do gene do fator de crescimento semelhante à insulina II (IGF-II) tem sido demonstrada na maioria dos carcinomas adrenocorticais em adultos. Os efeitos mitogênicos do IGF-II são mediados pela interação com o receptor de IGF-I (IGF-IR). Adicionalmente, o fator esteroidogênico 1 (SF-1) e o fator codificado por uma região crítica do cromossomo X associada ao sexo reverso e à hipoplasia adrenal congênita (DAX-1), ambos envolvidos no desenvolvimento e na esteroidogênese adrenal, também têm sido implicados na tumorigênese adrenocortical. Objetivos: Analisar a expressão gênica e a imunorreatividade dos fatores IGF-II, IGF-IR, SF-1 e DAX-1 em tumores adrenocorticais de crianças e adultos. Avaliamos ainda os efeitos de um inibidor seletivo do IGF-IR (NVP-AEW541) na proliferação celular e apoptose de linhagens celulares de tumores adrenocorticais. Métodos: Neste estudo, a expressão gênica foi determinada por PCR quantitativa em tempo real em 57 tumores adrenocorticais (37 adenomas e 20 carcinomas). Vinte e três pacientes tinham idade inferior ou igual a 15 anos. A análise de imunohistoquímica foi realizada em 109 tumores adrenocorticais (71 adenomas e 38 carcinomas). Os efeitos do tratamento com NVP-AEW541 (0,3 a 30 M) na proliferação celular e apoptose foram avaliados nas células NCI H295 de carcinoma adrenocortical humano e em uma nova linhagem celular estabelecida a partir de um adenoma adrenocortical pediátrico da nossa casuística. Resultados: A hiperexpressão do gene IGF-II foi evidenciada nos tumores adrenocorticais benignos e malignos de crianças (média ± EPM, 50,8 ± 18,5 vs. 31,2 ± 3,7, respectivamente; p= 0,23). Em adultos, a expressão do gene IGF-II foi significativamente mais elevada nos carcinomas adrenocorticais quando comparada com os adenomas (270,5 ± 130,2 vs. 16,1 ± 13,3; p= 0,0001). O percentual das células neoplásicas imunorreativas para o IGF-II não foi significativamente diferente entre os adenomas e carcinomas adrenocorticais pediátricos (14,1 ± 2,8% vs. 31,1 ± 13,1%, respectivamente; p= 0,32). Em adultos, o percentual das células neoplásicas positivas para o IGF-II foi significativamente maior nos carcinomas adrenocorticais em relação aos adenomas (34,4 ± 5,8% vs. 14,2 ± 3,2, respectivamente; p= 0,03). Os valores de RNAm do IGF-IR foram significativamente mais elevados nos carcinomas adrenocorticais pediátricos em relação aos adenomas (9,1 ± 1,2 vs. 2,6 ± 0,3; p= 0,0001), enquanto a expressão deste receptor foi similar nos tumores adrenocorticais benignos e malignos de adultos (1,6 ± 0,3 vs. 1,8 ± 0,5, respectivamente; p= 0,75). Os valores de RNAm do IGF-IR [risco relativo (RR) 2,0, intervalo de confiança (IC) de 95% 1,2 a 3,1; p= 0,004] e os critérios histopatológicos de Weiss (RR 1,8, IC de 95% 1,2 a 2,7; p= 0,003) foram marcadores independentes de metástases em crianças e adultos, respectivamente. O NVP-AEW541 inibiu a proliferação celular estimulada por IGF-II de forma dose e tempo dependentes nas 2 linhagens celulares de tumores adrenocorticais através de uma significativa indução da apoptose. Adicionalmente, a hiperexpressão do gene SF-1 foi identificada em 13% e 15% dos tumores adrenocorticais diagnosticados em crianças e adultos, respectivamente. O percentual das células neoplásicas com imunorreatividade nuclear para SF-1 foi significativamente maior nos tumores adrenocorticais pediátricos em relação aos tumores diagnosticados em adultos (29,1 ± 5,4% vs. 8,3 ± 2,3%, respectivamente; p= 0,0001). Estes dados indicam que o aumento da expressão do SF-1 nos tumores adrenocorticais pediátricos ocorre em nível pós-traducional. A hiperexpressão do gene DAX-1 foi identificada em 39% dos tumores adrenocorticais, com uma prevalência semelhante em crianças e adultos. De forma similar, o aumento da expressão da proteína DAX-1 foi identificado em 36% e 27% dos tumores adrenocorticais diagnosticados em crianças e adultos, respectivamente. A imunorreatividade nuclear para DAX- 1 foi semelhante nos adenomas e carcinomas adrenocorticais (29,2 ± 3,8% vs. 21,4 ± 5,8% das células neoplásicas, respectivamente; p= 0,12). Conclusões: A hiperexpressão do IGF-II tem um papel relevante na tumorigênese adrenocortical. A hiperexpressão do gene IGF-IR foi um marcador biológico independente do carcinoma adrenocortical metastático em crianças. Os efeitos anti-tumorais in vitro do NVP-AEW541 sugerem que o IGF-IR constitui um potencial alvo terapêutico para o carcinoma adrenocortical humano. Adicionalmente, o aumento da expressão do SF-1 foi evidenciado predominantemente nos tumores adrenocorticais pediátricos. A hiperexpressão do DAX-1 constitui um evento importante na patogênese molecular dos tumores adrenocorticais benignos e malignos Introduction: The molecular pathogenesis of adrenocortical tumors is heterogeneous and incompletely understood. Insulin-like growth factor II (IGF-II) overexpression has been demonstrated in adult adrenocortical carcinomas. IGF-II exerts its mitogenic effects through interaction with IGF-I receptor (IGF-IR). In addition, steroidogenic factor 1 gene (SF-1) and dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome gene (DAX-1), which regulate adrenal development and steroidogenesis, have been also involved in adrenocortical tumorigenesis. Objectives: To analyze gene and protein expression of IGF-II, IGF-IR, SF-1 and DAX-1 in pediatric and adult adrenocortical tumors. We also evaluated the effects of a selective IGF-IR kinase inhibitor (NVP-AEW541) on adrenocortical tumor cell lines. Methods: Gene expression was determined by quantitative real-time PCR in 57 adrenocortical tumors (37 adenomas and 20 carcinomas) from 23 children and 34 adults. Twenty and three patients were younger than 15 years. A tissue microarray analysis was performed on a large cohort of 109 ACT (71 adenomas and 38 carcinomas; 39 children and 70 adults) In addition, the effects of NVP-AEW541 treatment (0.3 to 30M) on proliferation and apoptosis were investigated in the NCI H295 cell line and in a new cell line established from a pediatric adrenocortical adenoma of our cohort. Results: IGF-II transcripts were overexpressed in pediatric adrenocortical carcinomas and adenomas (mean ± SE, 50.8 ± 18.5 vs. 31.2 ± 3.7, respectively; p= 0.23). IGF-II gene expression was significantly higher in adult adrenocortical carcinomas than in adenomas (270.5 ± 130.2 vs. 16.1 ± 13.3; p= 0.0001). The percentual of neoplastic cells immunostaining for IGF-II was not statistically different between pediatric adrenocortical adenomas and carcinomas (14.1 ± 2.8% vs. 31.1 ± 13.1%, respectively; p= 0.32). Otherwise, the percentual of positive neoplastic cells for IGF-II was significantly higher in adult adrenocortical carcinomas than in adenomas (34.4 ± 5.8% vs. 14.2 ± 3.2, respectively; p= 0.03). IGF-IR mRNA levels were significantly higher in pediatric adrenocortical carcinomas than in adenomas (9.1 ± 1.2 vs. 2.6 ± 0.3; p= 0.0001), whereas similar IGF-IR expression levels were identified in adult adrenocortical carcinomas and adenomas (1.6 ± 0.3 vs. 1.8 ± 0.5, respectively; p= 0.75). In a Cox multivariate analysis, IGF-IR gene expression [hazard ratio (HR) 2.0, 95% confidence interval (CI) 1.2 to 3.1; p= 0.004] and Weiss score (HR 1.7, 95% CI 1.2 to 2.7; p= 0.003) were independent biomarkers of metastasis in pediatric and adult adrenocortical tumors, respectively. Furthermore, NVP-AEW541 blocked cell proliferation in a dose- and time-dependent manner in both NCI H295 and pediatric adrenocortical cell lines through a significant increase of apoptosis. Additionally, SF-1 gene overexpression was identified in 13% and 15% of pediatric and adult adrenocortical tumors, respectively. The percentual of neoplastic cells with nuclear immunoreactivity for SF-1 was significantly higher in pediatric than in adult adrenocortical tumors (29.1 ± 5.4% vs. 8.3 ± 2.3%, respectively; p= 0.0001). These findings suggest that SF-1 overexpression occurs at the translational level in pediatric adrenocortical tumors. DAX-1 gene overexpression was identified in 39% of adrenocortical tumors with a similar frequency in children and adults. Similarly, DAX-1 protein overexpression was identified in 36% and 27% of pediatric and adult adrenocortical tumors, respectively. DAX-1 immunostaining on nuclei was not statistically different in benign and malignant adrenocortical tumors (29.2 ± 3.8% vs. 21.4 ± 5.8% of neoplastic cells, respectively; p= 0.12). Conclusion: IGF-II overexpression has a pivotal role to adrenocortical tumorigenesis. IGFIR overexpression was a potential biomarker of metastases in children with adrenocortical carcinoma. We demonstrated that a selective IGF-IR kinase inhibitor had anti-tumor effects in adult and pediatric ACT cell lines, suggesting that IGF-IR inhibitors represent a promising therapy for human adrenocortical carcinoma. In addition, SF-1 overexpression might be mainly involved in pediatric adrenocortical tumorigenesis. DAX-1 overexpression has an important role to molecular pathogenesis of benign and malignant adrenocortical tumors

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48

Cabral, Diogo da Cunha. "Neurosurgical anatomy of the insular cortex." Master's thesis, 2019. https://hdl.handle.net/10216/128912.

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OBJETIVOS: Com este estudo procurámos clarificar e aprofundar o conhecimento existente sobre a morfologia do córtex insular, focando-nos não só na forma da ínsula, como também na organização dos seus sulcos e circunvoluções. MATERIAIS E MÉTODOS: Após a devida exposição, as ínsulas de sessenta hemisférios humanos adultos previamente fixados em formaldeído foram fotografadas. As dimensões de cada circunvolução e de cada sulco foram medidas com recurso a um software de análise de imagem. Os dados morfométricos obtidos foram depois analisados estatisticamente. RESULTADOS: A forma do córtex insular alterna entre triangular e trapezoide, sendo a primeira mais frequente (75%). O ângulo formado pelos sulcos peri-insulares posterior e inferior nas ínsulas trapezoides apresentava uma amplitude média de 131.17 (DP = 12.277). Um número mínimo de 3 e um número máximo de 6 circunvoluções por ínsula foram observadas, sendo que 5 era o número mais frequentemente observado. A circunvolução acessória estava presente em 66% das ínsulas, encontrando-se bem desenvolvida em 38% dos casos. Foi encontrada uma associação estatística entre o número de circunvoluções do lobo posterior e a presença de uma nova circunvolução no lobo anterior ou de uma circunvolução acessória mais desenvolvida (p = 0.006). A circunvolução posterior curta era a mais longa do lobo anterior (p < 0.001), sendo seguida pela circunvolução anterior curta (p < 0.001). No lobo posterior, a circunvolução anterior longa demonstrou ser mais larga que a circunvolução posterior longa (p = 0.003). A contribuição de cada circunvolução para a formação do ápex insular revelou-se muito inconsistente. O padrão mais frequentemente observado foi a combinação da circunvolução anterior curta com a circunvolução média curta. CONCLUSÕES: O presente estudo faz uma contribuição robusta e relevante para o conhecimento da anatomia do córtex insular, auxiliando os neurocirurgiões na decisão sobre as melhores formas de abordar esta área cortical. OBJECTIVE: The purpose of this study was to clarify the morphology of the insular cortex focusing not only on the shape of the insula, but also on sulcal and gyral organization. PATIENTS AND METHODS: Sixty formalin-fixed adult brain hemispheres had their insula exposed and photographed. The dimensions of each gyrus and sulcus were measured using an image analysis software. The morphometric data obtained was statistically analysed. RESULTS: The insular cortex shape alternates between triangular and trapezoid, being the triangular shape the most common (75%). The angle between the posterior and inferior peri-insular sulcus in the trapezoid insulae had a mean range of 131.17 (SD = 12.277). A minimum of 3 and a maximum of 6 insular gyri were observed, being 5 the most common total number of gyri observed. The accessory gyrus was present in 66% of the insulae and well-developed in 38% of the cases. A statistical association between the number of gyri in the posterior lobe and the presence of a novel gyrus or a more developed accessory gyrus in the anterior lobe was found (P = 0.006). The posterior short gyrus was the longest of the short gyri (P < 0.001), followed by the anterior short gyrus (P < 0.001). The anterior long gyrus was the largest of the long gyri (P = 0.003). The contribution of each of the short gyri to the formation of the insular apex was inconstant. The most common observed apex arrangement was the combination of the anterior and of the middle short gyri. CONCLUSIONS: This study makes a strong contribution to the understanding of the insular cortex anatomy, allowing neurosurgeons to be more capable to decide the best approach to this cortical area.

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49

Cabral, Diogo da Cunha. "Neurosurgical anatomy of the insular cortex." Dissertação, 2019. https://hdl.handle.net/10216/128912.

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OBJETIVOS: Com este estudo procurámos clarificar e aprofundar o conhecimento existente sobre a morfologia do córtex insular, focando-nos não só na forma da ínsula, como também na organização dos seus sulcos e circunvoluções. MATERIAIS E MÉTODOS: Após a devida exposição, as ínsulas de sessenta hemisférios humanos adultos previamente fixados em formaldeído foram fotografadas. As dimensões de cada circunvolução e de cada sulco foram medidas com recurso a um software de análise de imagem. Os dados morfométricos obtidos foram depois analisados estatisticamente. RESULTADOS: A forma do córtex insular alterna entre triangular e trapezoide, sendo a primeira mais frequente (75%). O ângulo formado pelos sulcos peri-insulares posterior e inferior nas ínsulas trapezoides apresentava uma amplitude média de 131.17 (DP = 12.277). Um número mínimo de 3 e um número máximo de 6 circunvoluções por ínsula foram observadas, sendo que 5 era o número mais frequentemente observado. A circunvolução acessória estava presente em 66% das ínsulas, encontrando-se bem desenvolvida em 38% dos casos. Foi encontrada uma associação estatística entre o número de circunvoluções do lobo posterior e a presença de uma nova circunvolução no lobo anterior ou de uma circunvolução acessória mais desenvolvida (p = 0.006). A circunvolução posterior curta era a mais longa do lobo anterior (p < 0.001), sendo seguida pela circunvolução anterior curta (p < 0.001). No lobo posterior, a circunvolução anterior longa demonstrou ser mais larga que a circunvolução posterior longa (p = 0.003). A contribuição de cada circunvolução para a formação do ápex insular revelou-se muito inconsistente. O padrão mais frequentemente observado foi a combinação da circunvolução anterior curta com a circunvolução média curta. CONCLUSÕES: O presente estudo faz uma contribuição robusta e relevante para o conhecimento da anatomia do córtex insular, auxiliando os neurocirurgiões na decisão sobre as melhores formas de abordar esta área cortical. OBJECTIVE: The purpose of this study was to clarify the morphology of the insular cortex focusing not only on the shape of the insula, but also on sulcal and gyral organization. PATIENTS AND METHODS: Sixty formalin-fixed adult brain hemispheres had their insula exposed and photographed. The dimensions of each gyrus and sulcus were measured using an image analysis software. The morphometric data obtained was statistically analysed. RESULTS: The insular cortex shape alternates between triangular and trapezoid, being the triangular shape the most common (75%). The angle between the posterior and inferior peri-insular sulcus in the trapezoid insulae had a mean range of 131.17 (SD = 12.277). A minimum of 3 and a maximum of 6 insular gyri were observed, being 5 the most common total number of gyri observed. The accessory gyrus was present in 66% of the insulae and well-developed in 38% of the cases. A statistical association between the number of gyri in the posterior lobe and the presence of a novel gyrus or a more developed accessory gyrus in the anterior lobe was found (P = 0.006). The posterior short gyrus was the longest of the short gyri (P < 0.001), followed by the anterior short gyrus (P < 0.001). The anterior long gyrus was the largest of the long gyri (P = 0.003). The contribution of each of the short gyri to the formation of the insular apex was inconstant. The most common observed apex arrangement was the combination of the anterior and of the middle short gyri. CONCLUSIONS: This study makes a strong contribution to the understanding of the insular cortex anatomy, allowing neurosurgeons to be more capable to decide the best approach to this cortical area.

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50

Vignovich, Martin Nicholas. "Integration of Taste and Odor in Agranular Insular Cortex." Thesis, 2019. https://doi.org/10.7916/d8-qdv7-q834.

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Our perception of the world is limited by the senses we are endowed with. In the case of taste, its functional fidelity is so critical for our survival that we come into the world with innate preference for sweet and disgust for bitter. These stereotyped behaviors are hardwired at the lowest levels of taste processing and they support the view that taste serves as an arbiter of the chemical world, passing judgement before permitting ingestion. Yet our experience of foods is manifold. This complexity results from distinct contributions from the sights, sounds and smells of the foods we consume. Of these, odors are a co-equal component of flavor and the impairment of olfaction can disrupt enjoyment of eating and alter patterns of consumption. The goal of this thesis is to identify the neural basis of odor-taste perception and to characterize how neural activity is affected by odor-taste integration. In contrast to the discrete and innate categorization performed by the taste system, the sense of smell enables discrimination of thousands of unique odor percepts which have no innate value. At the level of olfactory cortex, odor representations are randomly distributed and have been shown to be conditioned through association with other stimuli. The act of eating produces near simultaneous taste and odor transduction originating from the same source. Yet despite ultimately projecting to neighboring cortical regions, taste and odor pathways are anatomically segregated prior to reaching the cortex. Using viral tracing strategies, we identified Agranular Insular cortex (AIc) as a putative site of odor-taste integration. We then used in vivo two-photon Ca2+ Imaging to characterize odor and taste responsive neurons and identify changes in population activity when these stimuli were simultaneously presented. We next asked whether specific flavor experiences altered activity in AIc compared to naive animals. Finally, we developed a behavioral task to test whether silencing AIc disrupted perception of a flavor compound.

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