Thesis (PhD) - Swinburne University of Technology, 2006. / Submitted for the degree of Doctor of Philosophy, Swinburne University of Technology - 2006. Typescript. Bibliography: p. 191-223.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 3 uppsatser.

Thesis (Doctoral)--Ludwig-Maximilians-Universität. / eContent provider-neutral record in process. Description based on print version record.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-06-17T12:34:24Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese_final_IlkaSoares.pdf: 9587167 bytes, checksum: 661e230d19d214ac34a110962a687ad0 (MD5) / Made available in DSpace on 2016-06-17T12:34:24Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese_final_IlkaSoares.pdf: 9587167 bytes, checksum: 661e230d19d214ac34a110962a687ad0 (MD5) Previous issue date: 2015-12-11 / Introdução: O diagnóstico precoce da perda auditiva causa um impacto na vida da família, mas por outro lado proporciona a intervenção rápida e uma melhor qualidade de vida, para isso as técnicas de diagnóstico devem ser aperfeiçoadas, trazendo mais precisão e um melhor prognóstico. Objetivo: Desenvolver uma técnica de estado estável para o registro do microfonismo coclear. Métodos: Foram analisados 26 voluntários, com limiares auditivos tonais até 25 dBNA. O estímulo foi gerado pelo sistema MASTER acoplado ao Audiômetro, com fone de inserção, dentro da cabine acústica. A seguinte derivação foi utilizada: Terra na clavícula direita, Referência G2 lóbulo contralateral e o Ativo G1 no CAE. No primeiro experimento usamos tons de 500, 1000, 2000 e 4000 Hz, modulados em 95 Hz e apresentados conjuntamente à orelha esquerda a intensidades de 60, 70 e 80 dBNPS. No segundo experimento, tons de 500, 1000, 2000 e 4000 Hz, modulados a 95 Hz, foram apresentados independentemente a orelha esquerda com uma intensidade de 80 dBNPS. Para o terceiro experimento tons de 500, 1000, 2000 e 4000 Hz foram modulados nas frequências de 95 Hz, 130, 160, 190 e 220 Hz e apresentados conjuntamente à orelha esquerda a uma intensidade de 80 dBNPS. Todos os experimentos foram obtidos registros na presença e ausência de mascaramento e ao menos um registro com fone clipado para cada participante. Resultados: No primeiro experimento as amplitudes das respostas foram maiores na condição sem mascaramento e crescem com o aumento da intensidade do estímulo (F(2,10)=11.686, p=0.002). No segundo experimento a amplitude da resposta foi maior ao estímulo combinado (F(4,4)= 7.284, p=0.0002). O terceiro experimento mostrou amplitudes significativamente maiores para os estímulos modulados em 95, 130 e 160 Hz. Conclusão: O registro do microfonismo coclear de estado estável pode ser realizado nas intensidades de 60 a 80 dB NPS. As frequências portadoras ideais para seu registro são 500, 1000, 2000 e 4000 Hz, combinadas. A frequência moduladora ideal para seu registro é de 95 Hz. / Introduction: Although early diagnosis of hearing loss has an impact on individuals and their families, it results in rapid intervention and enhanced quality of life. For this reason, diagnostic techniques should be perfected to provide a more accurate prognosis. Objective: Develop a steady-state technique for recording the cochlear microphonic. Methods: A total of 26 participants with puretone auditory thresholds up to 25 dBNA were analyzed. The stimulus was generated by the MASTER system coupled to the audiometer, using insert earphones, with subjects inside an audiometric sound booth. Electrodes were positioned as follows: ground on the right clavicle, electrode G2 (reference) on the contralateral lobe and G1 (active) in the external acoustic meatus. In the first experiment we used tones of 500, 1000, 2000 and 4000 Hz, modulated at 95 Hz and presented jointly to the left ear at intensities of 60, 70 and 80 dBNPS. In the second experiment, tones of 500, 1000, 2000 and 4000 Hz, modulated at 95 Hz, were presented separately to the left ear at an intensity of 80 dBNPS. For the third experiment tones of 500, 1000, 2000 and 4000 Hz were modulated at frequencies of 95 Hz, 130, 160, 190 and 220 Hz and presented jointly to the left ear at an intensity of 80 dBNPS. In all experiments recordings were obtained with and without masking and at least one using clip-on earphones for each participant. Results: In the first experiment response amplitudes were higher without masking and grew with an increase in stimulus intensity (F(2,10)=11.686, p=0.002). In the second experiment the response amplitude was greater than the combined stimulus (F(4,4)= 7.284, p=0.0002). The third experiment exhibited significantly higher amplitudes for stimuli modulated at 95, 130 and 160 Hz. Conclusion: The steady-state microphonic can be recorded at intensities between 60 and 80 dB NPS. The ideal carrier frequencies for recording are 500, 1000, 2000 and 4000 Hz, combined, and the ideal modulated frequency is 95 Hz.

The mechanisms underlying the generation and spread of seizure activity have remained elusive despite a considerable research effort over the last two decades. Most of this work has concentrated on the characteristics of neuronal excitability and burst discharge at the single cell level. These studies have provided some understanding of the possible abnormalities of neurons within an epileptic focus, but little direct insight into the factors responsible for the striking synchronization of action potentials during interictal discharge or in the spread of synchronous activity across apparently normal brain tissue. Although synaptic activation probably plays a role in the generation of seizure activity, recent evidence indicates that seizure-like discharge can occur during chemical blockade of synaptic transmission (Jefferys and Haas 1982; Taylor and Dudek 1982). This rather surprising result emphasizes the importance of considering non-synaptic mechanisms for both the synchronization and spread of abnormal neuronal activity in the central nervous system. One important non-synaptic mechanism to consider is ephaptic interactions. This term refers to the direct electrical influence of extracellular field potentials on neuronal excitability. It is possible that ephaptic interactions, generated during seizure activity, simultaneously depolarize an entire population of neurons leading to both recruitment and synchronization of action potential discharge. This thesis investigates ephaptic interactions during evoked potentials in the hippocampal formation. The hippocampus is one of the most seizure-prone regions of the brain and its anatomical structure is ideal for the generation of field effects. Evoked potentials were used as "models" of synchronous neuronal discharge since they are more reproducible, easier to control, and better understood than seizure activity. This initial investigation of ephaptic interactions lays the foundation for further studies involving the complexities of epileptic activity. The first phase of this project examined the spatial characteristics of field potentials evoked in the hippocampus and the dentate gyrus. Current source density (CSD) analysis and voltage gradient determinations obtained from these fields were used to characterize the pattern of current flow within the neuropil and to predict the polarity and relative intensity of ephaptic influences on neuronal excitability. The detailed characteristics of extracellular voltage gradients varied between CAl and the dentate gyrus, and also between anti- and orthodromic responses. In general, voltage gradients during the positive components of a somatic population spike predicted ephaptic hyperpolarization of the neuronal population, whereas gradients observed during the negative component predicted depolarization. They were often an order of magnitude greater than the smallest gradient known to influence granule cell activity. An exception to this rule was the minimal gradient observed during the negative component of the dentate response. In the second phase of the study, extracellular voltage gradients were experimentally applied to the dentate gyrus to determine the sensitivity of granule cells to ephaptic interactions. The magnitude of the applied gradients were in the range observed during the evoked potentials studied in the first phase. These experiments demonstrated a remarkable sensitivity of granule cells to the applied fields. The fields could alter the population spike from near minimal to near maximal. Surprisingly, even antidromic potentials were influenced by the gradients. On the other hand, the EPSP phase of the population spike was not influenced. These findings established that extracellular currents can influence the excitability within a neuronal population without altering synaptic drive. The final phase of the project investigated the transmembrane potential (TMP) of pyramidal and granule cells during applied fields and evoked potentials. The TMP was calculated by subtracting the extracellular from the intracellular response. This potential ultimately determines the voltage dependent behavior of a neuron and gives a direct measure of any ephaptic interactions. In order to measure the intracellular influences of applied fields, the TMP was monitored while the impaled cell was exposed to extracellular voltage gradients spanning the same range as used in phase two of the project. The TMP shifted by as much as plus or minus 5 mV, depending on the amplitude and polarity of the gradient. This large shift in TMP accounts for the observed influence of the applied field potentials, and suggests that the voltage gradients associated with evoked potentials should also have a marked effect on the TMP. A depolarizing wave of the TMP occurred during the negative component of anti- and orthodromic CA1 responses. This depolarization was capable of initiating action potentials, and decreased the latency to discharge during orthodromic responses. During epileptiform discharge, a similar depolarizing wave was associated with each negative component of the burst. These depolarizations recruit and synchronize neuronal discharge by simultaneously increasing the excitability within an entire population of cells. These data support the hypothesis that ephaptic interactions in the hippocampal formation influence the pattern of cell discharge during evoked potentials. It is postulated that similar ephaptic interactions may contribute to recruitment and synchronization during seizure activity. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

The electrophysiological properties of somatic and dendritic membranes of CA1 pyramidal neurons were investigated using the rat in vitro hippocampal slice preparation. A comprehensive analysis of extracellular field potentials, current-source density (CSD) and intracellular activity has served to identify the site of origin of action potential (AP) discharge in CA1 pyramidal neurons. 1) Action potential discharge of CA1 pyramidal cells was evoked by suprathreshold stimulation of the alveus (antidromic) or afferent synaptic inputs in stratum oriens (SO) or stratum radiatum (SR). Laminar profiles of the "stimulus evoked" extracellular field potentials were recorded at 25µm intervals along the dendro-somatic axis of the pyramidal cell and a 1-dimensional CSD analysis applied. 2) The shortest latency population spike response and current sink was recorded in stratum pyramidale or the proximal stratum oriens, a region corresponding to somata and axon hillocks of CA1 pyramidal neurons. A biphasic positive/negative spike potential (current source/sink) was recorded in dendritic regions, with both components increasing in peak latency through the dendritic field with distance from the border of stratum pyramidale. 3) A comparative intracellular analysis of evoked activity in somatic and dendritic membranes revealed a basic similarity in the pattern of AP discharge at all levels of the dendro-somatic axis. Stimulation of the alveus, SO, or SR evoked a single spike while injection of depolarizing current evoked a repetitive train of spikes grouped for comparative purposes into three basic patterns of AP discharge. 4) Both current and stimulus evoked intracellular spikes displayed a progressive decline in amplitude and increase in halfwidth with distance from the border of stratum pyramidale. 5) The only consistent voltage threshold for intracellular spike discharge was found in the region of the cell body, with no apparent threshold for spike activation in dendritic locations. 6) Stimulus evoked intradendritic spikes were evoked beyond the peak of the population spike recorded in stratum pyramidale, and aligned with the biphasic extradendritic field potential shown through laminar profile analysis to conduct with increasing latency from the cell body layer. The evoked characteristics of action potential discharge in CA1 pyramidal cells are interpreted to indicate the initial generation of a spike in the region of the soma-axon hillock and a subsequent retrograde spike invasion of dendritic arborizations. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18180号 / 医博第3900号 / 新制||医||1004(附属図書館) / 31038 / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 金子 武嗣, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

INTRODUÇÃO: A Esclerose Múltipla é uma doença desmielinizante e autoimune, na qual ocorre a destruição da bainha de mielina por autoanticorpos. Esta destruição causa uma diminuição na velocidade de condução do impulso nervoso alterando, assim, as funções cerebral e neural. Para ocorrer o funcionamento adequado do sistema auditivo, tanto na sua porção periférica quanto na central há necessidade que o mesmo esteja íntegro. OBJETIVO: Este estudo tem como objetivo verificar a ocorrência de alterações nos potenciais evocados auditivos de curta (PEATE), média (PEAML) e longa (P300) latências em adultos audiologicamente normais com diagnóstico de Esclerose Múltipla do tipo remitente recorrente ou surto remissivo. MÉTODO: Para o grupo controle foram avaliados 25 indivíduos com histórico de desenvolvimento neurológico normal e sem queixa de zumbido, sendo 19 do gênero feminino e seis do masculino, com idade variando entre 25 e 55 anos (média de 35,16 anos de idade). Para o grupo pesquisa foram avaliados 25 indivíduos com Esclerose Múltipla do tipo remitente-recorrente ou surto-remissivo, seis do gênero masculino e 19 do feminino, com idades entre 25 e 53 anos (média de 34,88 anos de idade). Todos os indivíduos participantes da pesquisa realizaram audiometria tonal e vocal, medidas de imitância acústica e os potenciais evocados auditivos de curta, média e longa latências. RESULTADOS: Os resultados demonstraram ocorrência de alterações nos potenciais evocados auditivos de tronco encefálico e de média latência e no potencial cognitivo, em indivíduos com Esclerose Múltipla. Com relação ao potencial evocado auditivo de tronco encefálico, verificou-se aumento de latência das ondas III e V e dos interpicos I-III e I-V, sugerindo alteração de tronco encefálico baixo. No que diz respeito ao potencial evocado auditivo de média latência observou-se atraso nas latências das ondas Na e Pa e, para o potencial cognitivo, evidenciou-se aumento da latência do P300. Conclusão: Indivíduos com Esclerose Múltipla do tipo remitente recorrente apresentam alterações eletrofisiológicas observadas nos resultados dos potenciais evocados auditivos de curta e média latências e no potencial cognitivo, sugerindo comprometimento em diferentes locais do sistema nervoso auditivo central / INTRODUCTION: The Multiple Sclerosis is a demyelinating disease and autoimmune, which is the destruction of the myelin sheath of a selfantibodies. This destruction causes a decrease in impulse driving speed of nervous changing thus the brain and neural functions. To place the proper functioning of the auditory system, both in its peripheral portion as the central need that it is full. PURPOSE: This study aims to determine the occurrency of changes in auditory evoked potentials of short (PEATE), middle (PEAML) and long (P300) latencies in adults audiologically normal diagnosed with Multiple Sclerosis remitting type of applicant or remissive outbreak. METHOD: For the control group were evaluated 25 individuals with a history of normal neurological development and without complaint from tinnitus, and 19 females and six males, with ages ranging between 25 and 55 years (average of 35.16 years of age) . To search the group were evaluated 25 individuals with Multiple Sclerosis-remitting type of applicant or flareremissive, six males and 19 females, aged between 25 and 53 years (average of 34.88 years of age). All individuals participating in the search conducted tone audiometry and speech, acoustic immitance measures brainstem auditory evoked potential, middle latency response and cognitive potential RESULTS: The results showed occurrencies of changes in brainstem auditory evoked potential and middle latency and cognitive potential in individuals with Multiple Sclerosis. Regarding the potential of brain stem auditory evoked, there was an increase in latency wave III and V and interpeaks I-III and IV, suggesting change in brainstem down. Regarding the auditory evoked potential of average latency there was delay in latencies of Na and Pa waves, and the potential for cognitive, showed an increase of latency of P300. Conclusion: Individuals with multiple sclerosis relapsing remitting type of applicant presents electrophysiological changes seen in the results of sound evoked short and middle latency and the potential cognitive suggesting impairment from different parts of the central auditory nervous system

INTRODUÇÃO: A Esclerose Múltipla é uma doença desmielinizante e autoimune, na qual ocorre a destruição da bainha de mielina por autoanticorpos. Esta destruição causa uma diminuição na velocidade de condução do impulso nervoso alterando, assim, as funções cerebral e neural. Para ocorrer o funcionamento adequado do sistema auditivo, tanto na sua porção periférica quanto na central há necessidade que o mesmo esteja íntegro. OBJETIVO: Este estudo tem como objetivo verificar a ocorrência de alterações nos potenciais evocados auditivos de curta (PEATE), média (PEAML) e longa (P300) latências em adultos audiologicamente normais com diagnóstico de Esclerose Múltipla do tipo remitente recorrente ou surto remissivo. MÉTODO: Para o grupo controle foram avaliados 25 indivíduos com histórico de desenvolvimento neurológico normal e sem queixa de zumbido, sendo 19 do gênero feminino e seis do masculino, com idade variando entre 25 e 55 anos (média de 35,16 anos de idade). Para o grupo pesquisa foram avaliados 25 indivíduos com Esclerose Múltipla do tipo remitente-recorrente ou surto-remissivo, seis do gênero masculino e 19 do feminino, com idades entre 25 e 53 anos (média de 34,88 anos de idade). Todos os indivíduos participantes da pesquisa realizaram audiometria tonal e vocal, medidas de imitância acústica e os potenciais evocados auditivos de curta, média e longa latências. RESULTADOS: Os resultados demonstraram ocorrência de alterações nos potenciais evocados auditivos de tronco encefálico e de média latência e no potencial cognitivo, em indivíduos com Esclerose Múltipla. Com relação ao potencial evocado auditivo de tronco encefálico, verificou-se aumento de latência das ondas III e V e dos interpicos I-III e I-V, sugerindo alteração de tronco encefálico baixo. No que diz respeito ao potencial evocado auditivo de média latência observou-se atraso nas latências das ondas Na e Pa e, para o potencial cognitivo, evidenciou-se aumento da latência do P300. Conclusão: Indivíduos com Esclerose Múltipla do tipo remitente recorrente apresentam alterações eletrofisiológicas observadas nos resultados dos potenciais evocados auditivos de curta e média latências e no potencial cognitivo, sugerindo comprometimento em diferentes locais do sistema nervoso auditivo central / INTRODUCTION: The Multiple Sclerosis is a demyelinating disease and autoimmune, which is the destruction of the myelin sheath of a selfantibodies. This destruction causes a decrease in impulse driving speed of nervous changing thus the brain and neural functions. To place the proper functioning of the auditory system, both in its peripheral portion as the central need that it is full. PURPOSE: This study aims to determine the occurrency of changes in auditory evoked potentials of short (PEATE), middle (PEAML) and long (P300) latencies in adults audiologically normal diagnosed with Multiple Sclerosis remitting type of applicant or remissive outbreak. METHOD: For the control group were evaluated 25 individuals with a history of normal neurological development and without complaint from tinnitus, and 19 females and six males, with ages ranging between 25 and 55 years (average of 35.16 years of age) . To search the group were evaluated 25 individuals with Multiple Sclerosis-remitting type of applicant or flareremissive, six males and 19 females, aged between 25 and 53 years (average of 34.88 years of age). All individuals participating in the search conducted tone audiometry and speech, acoustic immitance measures brainstem auditory evoked potential, middle latency response and cognitive potential RESULTS: The results showed occurrencies of changes in brainstem auditory evoked potential and middle latency and cognitive potential in individuals with Multiple Sclerosis. Regarding the potential of brain stem auditory evoked, there was an increase in latency wave III and V and interpeaks I-III and IV, suggesting change in brainstem down. Regarding the auditory evoked potential of average latency there was delay in latencies of Na and Pa waves, and the potential for cognitive, showed an increase of latency of P300. Conclusion: Individuals with multiple sclerosis relapsing remitting type of applicant presents electrophysiological changes seen in the results of sound evoked short and middle latency and the potential cognitive suggesting impairment from different parts of the central auditory nervous system

published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy