In modern medicine, the measurement of electrophysiological signals play a key role in health monitoring and diagnostics. Electrical activity originating from our nerve and muscle cells conveys real-time information about our current health state. The two most common and actively used techniques for measuring such signals are electrocardiography (ECG) and electroencephalography (EEG). These signals are very weak, reaching from a few millivolts down to tens of microvolts in amplitude, and have the majority of the power located at very low frequencies, from below 1 Hz up to 40 Hz. These characteristics sets very tough requirements on the electrical circuit designs used to measure them. Usually, measurement is performed by attaching electrodes with direct contact to the skin using an adhesive, conductive gel to fixate them. This method requires a clinical environment and is time consuming, tedious and may cause the patient discomfort. This thesis investigates another method for such measurements; by using a non-contact, capacitively coupled sensor, many of these shortcomings can be overcome. While this method relieves some problems, it also introduces several design difficulties such as: circuit noise, extremely high input impedance and interference. A capacitively coupled sensor was created using the bottom layer of a printed circuit board (PCB) as a capacitor plate and placing it against the signal source, that acts as the opposite capacitor plate. The PCB solder mask layer and any air in between the two acts as the insulator to create a full capacitor. The signal picked up by this sensor was then amplified by 60 dB with a high input impedance amplifier circuit and further conditioned through filtering. Two measurements were made of the same circuit, but with different input impedances; one with 10 MΩ and one with 10 GΩ input impedance. Additional filtering was designed to combat interference from the main power lines at 50 Hz and 150 Hz that was discovered during initial measurements. The circuits were characterized with their transfer functions, and the ability to amplify a very low-level, low frequency input signal. The results of these measurements show that high input impedance is of critical importance for the functionality of the sensor and that an input impedance of 10 GΩ is sufficient to produce a signal-to-noise ratio (SNR) of 9.7 dB after digital filtering with an input signal of 25 μV at 10 Hz.

O teste de potencial auditivo de tronco encefálico (PEATE) permite captar e registrar as atividades elétricas do sistema auditivo, desde a cóclea até o tronco encefálico. No Braisl ainda é pouco utilizado, e no Sul do país ainda não é realizado em animas.O objetivo deste trabalho foi identificar os valores absolutos de latência, interpicos, amplitudes, comparar as polaridades de compressão e rarefação e conhecer o limiar auditivo em onze cães hígidos da raça Beagle. Os cães passaram por exame físico e neurológico e após foram sedados e submetidos a otoscopia e ao exame de Potencial Auditivo de Tronco Encefálico (PEATE). Foram utilizados eletrodos de superfície e fones de inserção, o estimulo utilizado foi o clique com estimulação bilateral. O teste foi iniciado com a intensidade de 90 dB SPL com polaridade condensada. Realizava-se na sequência mais uma pesquisa em 90 dB SPL com polaridade rarefeita. Após, foi feito o exame com diminuição da intensidade de 10 dB SPL em 10 dB SPL, sendo todas as pesquisas feitas com polaridade condensada, para a pesquisa dos limiares auditivos. A interpretação do PEATE, foi realizada pela avaliação das ondas I, III e IV, pela identificação das latências absolutas e interpicos, pesquisa do limiar auditivo e comparação entre polaridades. Na latência da onda I com polaridade rarefeita em 90 dB SPL, os valores médios de latência absoluta da onda I foram significativamente maiores na orelha esquerda (p=0,037*). Dados relativos à latência absoluta da onda V evidenciou que na orelha direita a latência foi significativamente menor na intensidade de 70 dB SPL, e não houve presença de onda V na orelha esquerda em 40 dB SPL. Não houveram diferenças significativas nas latências dos interpicos entre as orelhas direita e esquerda, com polaridade condensada e rarefeita. Os valores das medianas das amplitudes I, III e V com 90 dB SPL em compressão e rarefação, não diferiram estatisticamente. Concluiu-se que o nível de resposta mínimo se encontrou entre 40 dB SPL e 80 dB SPL. / The Brainstem Auditory Evoked Potential (BAEP) capture and record the electrical activity of the auditory system, from the cochlea to the brainstem. The Brazil is still little used, and in the South of the country is not yet done in animals. The objective of this study was to identify the absolute values of latency, interpeaks, amplitudes, compare the polarities of compression and rarefaction and to know the auditory threshold in eleven healthy beagle dogs. The dogs underwent physical and neurological examination and were sedated and submitted to otoscopy and Brainstem Auditory Evoked Potential (BAEP). Surface electrodes and insertion headphones were used, the stimulus used was the click with bilateral stimulation. The test was started with 90 dB SPL intensity with condensed polarity. Further research was conducted on 90 dB SPL with rarefied polarity. After that, the test was performed with sequential reductions of 10 dB SPL intensity, and all the research for the auditory thresholds was done with condensed polarity. The interpretation of BAEP was performed by the evaluation of waves I, III and IV, by the identification of the absolute and interpeak latencies, auditory threshold research and comparison between polarities. In wave I latency with a rarefied polarity of 90 dB SPL, the mean absolute values of wave I latency were significantly higher in the left ear (p = 0.037*). Data on absolute V wave latency showed that, in the right ear, the latency was significantly lower in the intensity of 70 dB SPL, and there was no presence of V wave in the left ear in 40 dB SPL. There were no statistically significant differences in the interpeak latencies between the right and left ears, with condensed and rarefied polarity. The values of the medians of amplitudes I, III and V with 90 dB SPL in compression and rarefaction did not differ statistically. The minimum response level was found between 40 dB SPL and 80 dB SPL.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2014-05-22T17:10:14Z No. of bitstreams: 1 Icaro José Santos Ribeiro. Avaliação da... 2013.pdf: 880266 bytes, checksum: df7ddbb3ac2849200cda6a27447ba7f5 (MD5) / Made available in DSpace on 2014-05-22T17:10:14Z (GMT). No. of bitstreams: 1 Icaro José Santos Ribeiro. Avaliação da... 2013.pdf: 880266 bytes, checksum: df7ddbb3ac2849200cda6a27447ba7f5 (MD5) Previous issue date: 2013 / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / INTRODUÇÃO: O cenário de envelhecimento populacional e o aumento das Doenças Crônicas Não Transmissíveis (DCNT) requer o desenvolvimento e validação de métodos diagnóstico e de ferramentas não invasivas para identificação de fatores de risco e estadiamento destas doenças. Entre estes métodos evidencia-se a análise da modulação autonômica do coração por meio da Variabilidade da Frequência Cardíaca (VFC). OBJETIVO: Analisar a variabilidade da frequência cardíaca de idosos diabéticos (DM+) e não diabéticos (DM–) residentes em um município baiano; avaliar a resposta da variabilidade da frequência cardíaca na realização da manobra de levantar-se rapidamente. MÉTODOS: estudo epidemiológico transversal, de abordagem censitária. Desenvolvido com 205 idosos da zona urbana do munícipio de Aiquara-BA, após aplicação os critérios de inclusão e exclusão. Os dados da VFC foram coletados através do monitor Polar RS800CX, com registro inicial de 5 min em repouso, seguido por comando de levantar-se rapidamente para avaliação da razão 30:15. Para análise dos dados, as variáveis categóricas foram apresentadas em frequências (relativa e absoluta), enquanto variáveis contínuas, através de médias e medianas, desvio-padrão e intervalo interquartil. Foram realizados testes de comparação de proporções (chi quadrado ou exato de Fisher) e de mediana (Mann-Whitney). RESULTADOS: A média de idade foi de aproximadamente 71 anos (±7,32 dp). A população foi em sua maioria constituída por mulheres 59,1%, de baixa ou nenhuma escolaridade 60,0% e baixa renda 81,0%. A análise da VFC no domínio da frequência não evidenciou diferença quando comparados os grupos de DM+ e DM–. Doravante, no domínio do tempo, o rMSSD apresentou mediana de 16,09 [IQR 9,91-30,68]; e o pNN50 mediana de 0,79 [IQR 0,00-6,62], havendo diferença estatisticamente significante entre o grupo de DM+ e DM– (p<0,05). Como observado para os índices de atividade parassimpática em repouso, a razão 30:15, o índice de atividade parassimpática durante uma condição dinâmica, mostrou uma diferença significativa entre DM + e DM - idosos (p <0,05). CONCLUSÕES: A análise da VFC entre os grupos evidenciam a possibilidade de degeneração do ramo parassimpático no grupo DM+ pela diminuição nos parâmetros do tempo e a razão 30:15. Isso pode representar repercussões graves no sistema cardiovascular, uma vez que os índices reduzidos nestes indivíduos indicam uma menor cardioproteção. / INTRODUCTION: The scenario of population aging and the increase of Chronic Noncommunicable Diseases (NCDs) requires the development and validation of diagnostic methods and non-invasive tools for identification of risk factors and staging of these diseases.Among these methods, the analysis of autonomic modulation of the heart using the Heart Rate Variability (HRV) becomes evident. OBJECTIVE: To analyze the heart rate variability in diabetic (DM+) and nondiabetic (DM–) elderlies residents in a municipality of Bahia, and also to know the response of heart rate variability in performance of the quickly stand up maneuver. METHODS: cross-sectional study of censitary approach. Carried out with 205 elderlies in the urban area of the municipality of Aiquara-BA, after had applied the inclusion and exclusion criteria. HRV data were collected through the Polar RS800CX monitor with 5 min initial record at rest, followed by the command to quickly stand up. For data analysis, categorical variables were presented as frequencies (relative and absolute), while continuous variables as median, standard deviation and interquartile range (IQR). Tests were conducted to compare proportions (chi square or Fisher's exact test) and median (Mann-Whitney). RESULTS: The mean age was approximately 71 years (± 7.32 sd). The population was mostly made up of women 59.1%, with low or no schooling 60% and low income 81.0%. HRV analysis in the frequency domain showed no difference when comparing the two groups of DM+ and DM–. Henceforth in the time domain the rMSSD showed median of 16.09 [IQR 9.91-30.68]; the pNN50 median of 0.79 [IQR 0.00-6.62], with statistical significance between the group of DM+ and DM–. As observed for parasympathetic activity indexes at rest, the 30:15 ratio, an parasympathetic activity index during a dynamic condition, showed a significant difference between DM + and DM – elderlies (p < 0.05). CONCLUSIONS: HRV analysis between groups showed the possibility of deterioration of the parasympathetic branch of the DM + group, by decreasing the parameters of time and the 30:15 ratio. This can have serious repercussions on the cardiovascular system, since the reduced rates in those individuals indicate less cardioprotection.

O teste de potencial auditivo de tronco encefálico (PEATE) permite captar e registrar as atividades elétricas do sistema auditivo, desde a cóclea até o tronco encefálico. No Braisl ainda é pouco utilizado, e no Sul do país ainda não é realizado em animas.O objetivo deste trabalho foi identificar os valores absolutos de latência, interpicos, amplitudes, comparar as polaridades de compressão e rarefação e conhecer o limiar auditivo em onze cães hígidos da raça Beagle. Os cães passaram por exame físico e neurológico e após foram sedados e submetidos a otoscopia e ao exame de Potencial Auditivo de Tronco Encefálico (PEATE). Foram utilizados eletrodos de superfície e fones de inserção, o estimulo utilizado foi o clique com estimulação bilateral. O teste foi iniciado com a intensidade de 90 dB SPL com polaridade condensada. Realizava-se na sequência mais uma pesquisa em 90 dB SPL com polaridade rarefeita. Após, foi feito o exame com diminuição da intensidade de 10 dB SPL em 10 dB SPL, sendo todas as pesquisas feitas com polaridade condensada, para a pesquisa dos limiares auditivos. A interpretação do PEATE, foi realizada pela avaliação das ondas I, III e IV, pela identificação das latências absolutas e interpicos, pesquisa do limiar auditivo e comparação entre polaridades. Na latência da onda I com polaridade rarefeita em 90 dB SPL, os valores médios de latência absoluta da onda I foram significativamente maiores na orelha esquerda (p=0,037*). Dados relativos à latência absoluta da onda V evidenciou que na orelha direita a latência foi significativamente menor na intensidade de 70 dB SPL, e não houve presença de onda V na orelha esquerda em 40 dB SPL. Não houveram diferenças significativas nas latências dos interpicos entre as orelhas direita e esquerda, com polaridade condensada e rarefeita. Os valores das medianas das amplitudes I, III e V com 90 dB SPL em compressão e rarefação, não diferiram estatisticamente. Concluiu-se que o nível de resposta mínimo se encontrou entre 40 dB SPL e 80 dB SPL. / The Brainstem Auditory Evoked Potential (BAEP) capture and record the electrical activity of the auditory system, from the cochlea to the brainstem. The Brazil is still little used, and in the South of the country is not yet done in animals. The objective of this study was to identify the absolute values of latency, interpeaks, amplitudes, compare the polarities of compression and rarefaction and to know the auditory threshold in eleven healthy beagle dogs. The dogs underwent physical and neurological examination and were sedated and submitted to otoscopy and Brainstem Auditory Evoked Potential (BAEP). Surface electrodes and insertion headphones were used, the stimulus used was the click with bilateral stimulation. The test was started with 90 dB SPL intensity with condensed polarity. Further research was conducted on 90 dB SPL with rarefied polarity. After that, the test was performed with sequential reductions of 10 dB SPL intensity, and all the research for the auditory thresholds was done with condensed polarity. The interpretation of BAEP was performed by the evaluation of waves I, III and IV, by the identification of the absolute and interpeak latencies, auditory threshold research and comparison between polarities. In wave I latency with a rarefied polarity of 90 dB SPL, the mean absolute values of wave I latency were significantly higher in the left ear (p = 0.037*). Data on absolute V wave latency showed that, in the right ear, the latency was significantly lower in the intensity of 70 dB SPL, and there was no presence of V wave in the left ear in 40 dB SPL. There were no statistically significant differences in the interpeak latencies between the right and left ears, with condensed and rarefied polarity. The values of the medians of amplitudes I, III and V with 90 dB SPL in compression and rarefaction did not differ statistically. The minimum response level was found between 40 dB SPL and 80 dB SPL.

La nicotine est considérée comme étant la « molécule » addictogène de la cigarette et du tabac. Mais différentes études cliniques, utilisant notamment des substituts nicotiniques, débouchent pratiquement toutes sur une même conclusion : efficacité ne dépassant que de peu celle d’un placebo, et très limitée dans le temps, contrastant avec le pouvoir hautement addictif du tabac, qu'il soit chiqué, prisé ou fumé. Dans ce travail de thèse, nous avons essayé de mettre en évidence le rôle que pourraient avoir certains des autres composés présents dans le tabac ou produits par pyrolyse. Nous avons d’abord utilisé des extraits aqueux de fumée et de tabac pour approcher un aspect global de ce que les fumeurs absorbent chaque fois qu’ils fument une cigarette, nous rapprochant ainsi des conditions physiologiques du fumeur. Puis nous avons choisi un certain nombre de substances. La cotinine, métabolite de la nicotine. L’harmane, une ß-carboline, synthétisée au cours de la combustion et dans l’organisme des fumeurs. La norharmane, une ß-carboline, présente en partie dans le tabac et synthétisée dans la fumée par pyrolyse. La technique utilisée tout au long de ce travail est l’enregistrement électrophysiologique. Cette technique s’applique très bien à l’étude in vivo de différents systèmes neuronaux y compris le système dopaminergique. Nous l’avons utilisée chez le rat, la souris WT et la souris Knockout ß2 (ß2KO). Nous nous sommes intéressés à deux aspects de l’activité cellulaire des neurones dopaminergiques de l’aire tegmentale ventrale : la fréquence de décharge (le firing) et les bouffées (bursts). En parallèle, nous avons conduit des expériences de liaison (binding) sur des cultures de cellules exprimant le récepteur nicotinique α4ß2. Nos résultats les plus significatifs ont montré que : Les bursts sont le plus souvent absents après les injections d’extraits de tabac et de fumée. Cela pourrait, entre autres, impliquer qu’il existe dans le tabac et la fumée des composés autres que la nicotine qui bloquent les effets de la nicotine sur les bursts. Les effets des extraits de tabac et de fumée sur le firing et les bursts ne sont plus présents chez les souris ß2 KO, ce qui implique que l’ensemble des composés du tabac agit essentiellement sur les récepteurs nicotiniques porteurs de la chaine ß2, même si des hypothèses alternatives existent. L’harmane a des effets activateurs très puissants sur le firing des neurones dopaminergiques, et ces effets sont bloqués à 80% par la mécamylamine, ce qui démontre qu’un des principaux composés du tabac et de la fumée autre que la nicotine agit par un mécanisme essentiellement nicotinique. Les expériences de binding confirment que les effets du tabac et de la fumée impliquent les récepteurs nicotiniques d’une façon majeure, mais d’une façon qui diffère légèrement de celle de la nicotine.Les résultats que nous avons obtenus montrent que les effets pharmacologiques du tabac ne se résument pas à ceux de la seule nicotine. Ils peuvent constituer un point de départ pour d’autres travaux, notamment pour étudier de plus près les effets des ß-carbolines. Il est nécessaire d’identifier les types de récepteurs sur lesquels elles se fixent, en utilisant des agonistes et antagonistes de récepteurs aux neurotransmetteurs contrôlant l’activité des neurones dopaminergiques. Des expériences sur des souris transgéniques chez lesquelles différents types de sous-unités de récepteurs nicotiniques ont été supprimés doivent également être envisagées, pour déterminer les mécanismes d’action des composants autres que la nicotine contenus dans le tabac et sa fumée sur les neurones dopaminergiques / Nicotine is generally considered as the sole tobacco addictive compound. However, nicotine replacement therapy studies almost all end with the same conclusion: the effectiveness of nicotine replacement is very limited on the short-term, and hardly exceeds that of placebo on the long-term. In addition, studies dealing with the effects of denicotinized cigarettes have provided evidence that these cigarettes have an addictive potential. In the present work, we tried to determine the behavioral role of some tobacco or smoke compounds other than nicotine at the neuronal level. We first compared the effects of nicotine with those of whole tobacco and smoke extracts, given that these preparations closer mimic the smoking situation than nicotine alone. We then examined the effects of a number of selected tobacco or smoke compounds. Cotinine, a major nicotine metabolite. Harmane and norharmane, two ß-carbolines synthesized in smoke as well as in the body of smokers. The technique used consists in the in vivo recording of the firing rate and bursts of dopamine neurons in the ventral tegmental area after intravenous injections of compounds in rats and mice. This electrophysiological technique is known to be a useful way to investigate the properties of selected compounds. In the case of mice, we used wild type and ß2 KO mice. We also made a series of in vitro experiments investigating the binding properties of the compounds on cells expressing high densities of α4ß2 nicotinic receptors. The main results of our studies are the following: Bursts are absent most of the times after the injection of the extracts. These results suggest that tobacco and smoke extracts contain compounds that inhibit the burst-promoting effects of nicotine. Increased firing is no longer present in ß2 KO mice treated with tobacco or smoke extracts, indicating that tobacco and smoke components, as a whole, primarily acts on nicotinic receptors that carry the ß2 chain, although alternative hypotheses may exist. Harmane very strongly activates the firing of dopaminergic neurons. Up to 80% of this effect is blocked by mecamylamine, demonstrating that that a major component of tobacco and smoke other than nicotine acts primarily through a nicotinic mechanism. The binding experiments confirm that the effects of tobacco and smoke involve nicotinic receptors in a major way, but in a way that slightly differs from that of nicotine. Our results may constitute a new starting point for further work, especially for a closer look at the effects of ß-carbolines. Attempts to identify the types of receptors involved in these effects are needed, using agonists and antagonists of neurotransmitter receptors that control the activity of dopamine neurons. Experiments on transgenic mice with deletion of different types of subunits of nicotinic receptors should also be made, to determine the different mechanisms of action of tobacco and smoke compounds other than nicotine on dopaminergic neurons

Les traumatismes crâniens peuvent provoquer des troubles de la perception de molécules odorantes chez l’homme. Les causes de ces troubles post-traumatiques peuvent être : une altération mécanique dans la cavité nasale, des cisaillements des filets nerveux olfactifs et des lésions des régions cérébrales impliquées dans le traitement de l’information olfactive.Il est crucial en clinique ORL de pouvoir déterminer objectivement la fonctionnalité de l’odorat.Pour cela, nous avons conçu une méthode d’enregistrement électrophysiologique des potentiels évoqués olfactifs incluant, en plus de la composante classique P2/P3, une composante cognitive reflétant la perception du stimulus odorant : la variation de contingence négative (CNV).Cette méthode a été tout d’abord validée avec 24 sujets normosmiques et 8 sujets totalement anosmiques (absence congénitale des bulbes olfactifs). La CNV était présente chez tous les normosmiques contrairement à l’onde P2/P3 présente dans seulement 82% (28/34 cavités nasales stimulées) des observations. Les signaux sont tous absents chez les anosmiques.Nous avons aussi examiné 41 patients se plaignant d’anosmie ou d’une hyposmie associée à une perception déformée des odeurs. Dans la plupart des cas ces troubles étaient consécutifs à un choc occipital et/ou temporal. Les enregistrements ont été confrontés aux observations IRM focalisées sur la région des bulbes olfactifs : aspect des bulbes olfactifs et lésions dans le gyrus rectus et le gyrus orbitaire médian.Dans la grande majorité des cas, les deux bulbes présentaient un aspect anormal et les enregistrements électrophysiologiques montraient une absence totale de fonctionnalité.Cependant pour quelques patients, l’anormalité de l’aspect des bulbes n’empêchait pas la transmission de l’information au cerveau, comme indiqué par l’enregistrement des potentiels évoqués. Dans ce cas, la lésion bulbaire était associée à une parosmie (perception déformée des odeurs) et à une incapacité d’identification de celles-ci.Au bilan, notre méthode d’enregistrement permet, au niveau de chaque individu, d’obtenir de façon objective des informations essentielles permettant le diagnostic objectif de l’existence d’un trouble de l’odorat. Notre étude des traumatisés crâniens montre que la région des bulbes olfactifs est fragile et susceptible d’être endommagée partiellement ou totalement, même en cas de traumatisme crânien de relativement faible importance. / Head traumas can cause trouble of odor perception in humans. The causes of these post-traumatic troubles can be either mechanical damage to the nasal cavity, shearing of olfactory nerve fibers or lesions of the brain regions involved in processing olfactory information.In clinical ENT, it is crucial to objectively determine olfaction functionality.We developed electrophysiological recording of olfactory evoked potentials including, in addition to the classic P2/P3 component, a cognitive component reflecting the perception of odorants i.e.: the contingent negative variation (CNV).This method was first validated with 24 normosmic subjects and 8 completely anosmic subjects (congenital anosmia without olfactory bulb). The CNV was present in all normosmic subjects whereas P2/P3 was present in only 82 % (28/34 nasal cavities stimulated) of the observations. No signal was observed in any anosmic subjects.We also examined 41 patients complaining of anosmia or hyposmia associated with a distorted perception of odorants. In most cases, these troubles were consecutive to an occipital and / or temporal impact. The recordings were compared to MRI observations focusing on the region of the olfactory bulbs which exhibited olfactory bulbs lesions and lesions in the gyrus rectus and in the medial orbital gyrus. In most cases, the two bulbs had an abnormal appearance and electrophysiological recordings showed a complete lack of functionality. However, for some patients, the abnormal aspect of the bulb did not prevent the transmission of information to the brain, as indicated by the electrophysiological responses. In this case, the bulbar lesion was associated with parosmia (distorted perception of smell) and an inability to identify odors.In conclusion, our recording method allows obtaining, for each subject, the essential information for an objective diagnosis of the existence of a smell disorder. Our study of patients with head trauma shows that the region of the olfactory bulbs is fragile and can be damaged either partially or completely, even for light head trauma.

No description available.

La fibrilación auricular es una de las arritmias cardíacas más comunes observadas en la práctica clínica. Por lo tanto, es de vital importancia desarrollar nuevas tecnologías destinadas a diagnosticar y acabar con este tipo de arritmia, para mejorar la calidad de vida de los pacientes y reducir los costes de los sistemas nacionales de salud. En los últimos años ha aumentado el uso de las nuevas técnicas de mapeo auricular, basadas en sistemas multi-electrodo para mapear la actividad eléctrica en humanos. Dichas técnicas permiten localizar y ablacionar los impulsores de la fibrilación auricular, como son las fuentes focales o los rotores. Sin embargo, todavía existe incertidumbre sobre su precisión y los procedimientos experimentales para su análisis están limitados debido a su carácter invasivo. Por lo tanto, las simulaciones computacionales son una herramienta muy útil para superar estas limitaciones, al permitir reproducir con fidelidad las observaciones experimentales, dividir el problema bajo estudio en sub-estudios más simples, y realizar investigaciones preliminares imposibles de llevar a cabo en el práctica clínica. Esta tesis doctoral se centra en el análisis de la precisión de los sistemas de mapeo multi-electrodo a través de modelos y simulaciones computacionales. Para ello, desarrollamos modelos realistas multi-escala con el objetivo de simular actividad eléctrica auricular reentrante, en primer lugar en una lámina de tejido auricular, y en segundo lugar en las aurículas completas. Posteriormente, analizamos los efectos de las configuraciones geométricas multi-electrodo en la precisión de la localización de los rotores, mediante el uso de agrupaciones multi-electrodo con distancias inter-electrodo equidistantes, así como a través de catéteres de tipo basket con distancias inter-electrodo no equidistantes. Después de calcular los electrogramas unipolares intracavitarios, realizamos mapas de fase, detecciones de singularidad de fase para rastrear los rotores, y mapas de frecuencia dominantes. Finalmente, descubrimos que la precisión de los sistemas de mapeo multi-electrodo depende de su posición dentro de la cavidad auricular, de la distancia entre los electrodos y el tejido, de la distancia inter-electrodo, y de la contribución de las fuentes de campo lejano. Además, como consecuencia de estos factores que pueden afectar a la precisión de los sistemas de mapeo multi-electrodo, observamos la aparición de rotores falsos que podrían contribuir al fracaso de los procesos de ablación de la fibrilación auricular. / Atrial fibrillation is one of the most common cardiac arrhythmias seen in clinical practice. Therefore, it is of vital importance to develop new technologies aimed at diagnosing and terminating this kind of arrhythmia, to improve the quality of life of patients and to reduce costs to national health systems. In the last years, new atrial mapping techniques based on multi-electrode systems are increasingly being used to map the atrial electrical activity in humans and localise and target atrial fibrillation drivers in the form of focal sources or rotors. However, significant concerns remain about their accuracy and experimental approaches to analyse them are limited due to their invasive character. Therefore, computer simulations are a helpful tool to overcome these limitations since they can reproduce with fidelity experimental observations, permit to split the problem to treat into more simple substudies, and allow the possibility of performing preliminary investigations impossible to carry out in the clinical practice. This PhD thesis is focused on the analysis for accuracy of the multielectrode mapping systems through computational models and simulations. For this purpose, we developed realistic multiscale models in order to simulate atrial electrical reentrant activity, first in a sheet of atrial tissue and, then, in the whole atria. Then, we analysed the effects of the multi-electrode geometrical configurations on the accuracy of localizing rotors, by using multi-electrode arrays with equidistant inter-electrode distances, as well as multi-electrode basket catheters with non-equidistant inter-electrode distances. After computing the intracavitary unipolar electrograms, we performed phase maps, phase singularity detections to track rotors, and dominant frequency maps. We finally found out that the accuracy of multi-electrode mapping systems depends on their position inside the atrial cavity, the electrode-to-tissue distance, the inter-electrode distance, and the contribution of far field sources. Furthermore, as a consequence of these factors, false rotors might appear and could contribute to failure of atrial fibrillation ablation procedures. / La fibril·lació auricular és una de les arítmies cardíaques més comuns observades en la pràctica clínica. Per tant, és de vital importància desenvolupar noves tecnologies destinades a diagnosticar i acabar amb aquest tipus d'arítmia, per tal de millorar la qualitat de vida dels pacients i reduir els costos dels sistemes nacionals de salut. En els últims anys, ha augmentat l'ús de les noves tècniques de mapeig auricular, basades en sistemes multielèctrode per a mapejar l'activitat elèctrica auricular en humans. Aquestes tècniques permeten localitzar i ablacionar els impulsors de la fibril·lació auricular, com són les fonts focals o els rotors. No obstant això, encara hi ha incertesa sobre la seua precisió i els procediments experimentals per al seu anàlisi estan limitats a causa del seu caràcter invasiu. Per tant, les simulacions computacionals són una eina molt útil per a superar aquestes limitacions, en permetre reproduir amb fidelitat les observacions experimentals, dividir el problema sota estudi en subestudis més simples, i realitzar investigacions preliminars impossibles de dur a terme en el pràctica clínica. Aquesta tesi doctoral es centra en l'anàlisi de la precisió del sistemes de mapeig multielèctrode mitjançant els models i les simulacions computacionals. Per a això, desenvolupàrem models realistes multiescala per tal de simular activitat elèctrica auricular reentrant, en primer lloc en una làmina de teixit auricular, i en segon lloc a les aurícules completes. Posteriorment, analitzàrem els efectes de les configuracions geomètriques multielèctrode en la precisió de la localització dels rotors, mitjançant l'ús d'agrupacions multielèctrode amb distàncies interelèctrode equidistants, així com catèters de tipus basket amb distàncies interelèctrode no equidistants. Després de calcular els electrogrames unipolars intracavitaris, vam realitzar mapes de fase, deteccions de singularitat de fase per a rastrejar els rotors, i mapes de freqüència dominants. Finalment, vam descobrir que la precisió dels sistemes de mapeig multielèctrode depèn de la seua posició dins de la cavitat auricular, de la distància entre els elèctrodes i el teixit, de la distància interelèctrode, i de la contribució de les fonts de camp llunyà. A més, com a conseqüència d'aquests factors, es va observar l'aparició de rotors falsos que podrien contribuir al fracàs de l'ablació de la fibril·lació auricular. / Martínez Mateu, L. (2018). Mapping of the electrical activity of human atria. Multiscale modelling and simulations [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/104604 / TESIS

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<p>Persistent and maladaptive fear in the absence of a threat can be disruptive because it decreases an organism’s opportunity to seek life-sustaining substances. Learned safety signaling can suppress fear and encourage reward-seeking behavior, thus freeing the organism from fear induced immobilization. The infralimbic (IL) region of the prefrontal cortex is important for recalling fear extinction memories and for suppressing fear via learned safety signals. Neurons in the IL show an excitatory response to an extinguished fear cue. We thus hypothesized that neurons in the IL would encode safety by showing an excitatory response during active fear suppression to a learned safety signal. </p> <p>To assess global changes in IL activity, we monitored IL multi-unit activity to different cues while training animals in a fear-reward-safety discrimination task (Sangha, Chadick, & Janak, 2013). During the discrimination task, male rats learned that the reward cue predicted liquid sucrose, the fear cue predicted footshock and the joint presentation of both the fear and safety cues resulted in no footshock. We also counterbalanced the modality of fear and safety cues (auditory vs visual) with two separate groups of animals to control for potential sensory modality effects. Male rats showed high levels of freezing to the fear cue, and significantly reduced levels of freezing to the combined fear+safety cue. Male rats also showed high levels of port activity to the reward cue. There was no significant difference in the learning rate between the two counterbalanced conditions. </p> <p>Our multi-unit-data showed an increase in IL neuronal firing to the fear+safety cue across training sessions. This effect was consistent between the two counterbalanced conditions. We also examined single-unit activity from all animals that received light as the safety cue (n=8). This allowed us to examine the population response profile with a subset of the total animals. Although not statistically significant, our preliminary single-unit data demonstrated a decrease in the percentage of neurons that showed an inhibitory response to the fear+safety cue, but no change in the percentage of neurons that showed an excitatory response to the fear+safety cue. There was also no change in the magnitude of averaged firing rate in fear+safety excitatory or inhibitory neurons across training. Taken together, the decreased inhibition of single-unit activity in the IL may drive the increased excitation in multi-unit activity in the IL during behavioral fear suppression to a safety signal. </p>