INTRODUÇÃO: O transtorno fonológico é uma alteração na fala que ocasiona um grau variável de inteligibilidade de fala. A gravidade deste transtorno pode ser medida por meio do Percentage of Consonants Correct-Revised, que verifica o número de consoantes corretas em uma amostra de fala em relação ao número total de consoantes desta amostra. A literatura relata sete subtipos do transtorno fonológico, dentre eles a relacionada à otite média com efusão. Os Potenciais Evocados Auditivos também são utilizados para avaliar indivíduos com alteração de linguagem, pois esta população pode apresentar um déficit na via auditiva central. OBJETIVO: caracterizar os resultados dos potenciais evocados auditivos de longa latência N1, P2, N2 e P300 obtidos em crianças com transtorno fonológico, e verificar a evolução dos resultados destes potenciais frente à terapia fonoaudiológica, correlacionando esta evolução ao histórico de otite e a gravidade deste transtorno. MÉTODOS: Participaram da pesquisa 66 crianças, 25 sem transtorno fonológico (grupo controle) e 41 com transtorno fonológico (grupo estudo). As crianças do grupo estudo foram divididas em dois subgrupos: 22 formaram o subgrupo estudo A e 19 formaram o subgrupo estudo B. Todas as crianças foram submetidas à avaliação audiológica básica e aos potencias evocados auditivos de longa latência. Após a avaliação audiológica completa, as crianças do subgrupo estudo A foram submetidas a 12 sessões de terapia fonoaudiológica e reavaliadas audiologicamente após este período e, as crianças do subgrupo estudo B, crianças que aguardavam terapia em fila de espera, foram reavaliadas após três meses da avaliação inicial. RESULTADOS: os resultados demonstraram, na análise dos dados quantitativos, que o grupo estudo, antes da terapia fonoaudiológica, apresentou diferença estatisticamente significante para as latências dos componentes P2 e P300 e para a amplitude do P300, quando comparado com o grupo controle. Na comparação das latências não foram observadas diferenças estatisticamente significantes entre a primeira e segunda avaliações audiológicas, tanto para o subgrupo estudo A como para o subgrupo estudo B. Verificou-se diferença estatisticamente significante para as amplitudes do P300 e do P2/N2 na comparação entre a primeira e segunda avaliações audiológicas para os subgrupos estudo A e B, respectivamente. Na análise dos dados qualitativos, verificou-se que o P300 apresentou maior porcentagem de resultados alterados no grupo estudo quando comparado ao grupo controle, sendo que o tipo de alteração mais freqüentemente encontrado foi o aumento de latência. Após terapia fonoaudiológica, observou-se maior ocorrência de melhora nos resultados para todos os componentes estudados. Os resultados demonstraram, também, que não existiu associação entre a evolução dos resultados dos potenciais evocados auditivos de longa latência e o histórico de otite, bem como correlação com o Percentage of Consonants Correct-Revised. CONCLUSÕES: crianças com transtorno fonológico apresentam alterações no P300, sugerindo comprometimento da via auditiva central, provavelmente decorrente de alteração no processamento auditivo, apresentando melhora nos resultados de todos os componentes dos potenciais evocados auditivos de longa latência frente à terapia fonoaudiológica. Não existe associação entre a evolução dos resultados e histórico de otite, bem como correlação entre a evolução dos resultados e Percentage of Consonants Correct-Revised. / INTRODUCTION: Phonological disorder is a speech disorder that causes a varying degree of speech intelligibility. The severity of this disorder may be measured by the Percentage of Consonants Corrects-Revised, which verifies the number of correct consonants in a speech sample in relation to the total number of consonants in the sample. Literature reports seven subtypes of phonological disorder, amongst them the one related to otitis media with effusion. Auditory evoked potentials are also used to assess individuals with language disorder since this population may present deficit in the central auditory pathway. AIM: to characterize the long latency auditory evoked potentials results N1, P2, N2 and P300 of children with phonological disorder and to verify the improvement of such potentials results with the speech therapy, correlating this improvement to the background of otitis and the severity of this disorder. METHODS: Sixty six children took part in this study, 25 without phonological disorder (control group) and 41 with phonological disorder (study group). Children of the study group were divided into two subgroups: study subgroup A, composed by 22 children and study subgroup B composed by 19 children. All children underwent a basic audiological evaluation and long latency auditory evoked potentials. After the complete audiological assessment, children from study subgroup A underwent 12 sessions of speech therapy and were audiologically re-assessed after this period; children from study subgroup B were re-assessed three months after the initial assessment. RESULTS: the analysis of quantitative data revealed that the study group presented significant statistical difference, before the speech therapy, for the latencies of components P2 and P300 and for the amplitude of P300 when compared to the control group. Comparing the latencies, no significant statistical differences were observed between the first and the second audiological evaluations, either for the study subgroup A or B. A significant statistical difference was verified for the amplitudes of P300 and P2/N2 in the comparison between the first and the second audiological evaluations for subgroups A and B respectively. The analysis of qualitative data revealed that the P300 presented higher percentage of altered results in the study group when compared to the control group, and the most frequent type of alteration found was increased latency. After the speech therapy, the results of all components analyzed improved. Results also showed that there was no association between the improvement of long latency auditory evoked potentials results with the background of otitis, as well as with the Percentage of Consonants Corrects-Revised. CONCLUSIONS: children with phonological disorder present altered P300 suggesting involvement of the central auditory pathway probably due to alterations in the auditory processing, presenting improvement in all components of long latency auditory evoked potentials results after speech therapy. There is no association between the improvement of results and the background of otitis, as well as no correlation between the improvement of results and the Percentage of Consonants Corrects-Revised.

INTRODUÇÃO: A gagueira é um distúrbio da fluência multidimensional que resulta da interação de múltiplos processos fisiológicos, refletindo mais de um fator causal. Evidências científicas atuais sustentam a hipótese de que pessoas que gaguejam possuem conexões anômalas em regiões auditivas do hemisfério esquerdo, envolvidas no feedback sensorial dos sons da fala. Desta forma, é prudente pensar que déficits na sincronia neural, identificados por meio de alterações em testes comportamentais do processamento temporal e nos potenciais evocados auditivos (PEA), possam estar relacionados a este tipo de distúrbio. OBJETIVO: caracterizar os resultados do teste Gaps in Noise (GIN) e dos PEA com estímulos de diferentes complexidades em crianças gagas e em crianças em desenvolvimento típico. MÉTODOS: Dez crianças gagas com idades entre sete e 11 anos (grupo estudo - GE) e seus pares nãogagos (grupo controle - GC) foram submetidos a avaliações audiológicas e eletrofisiológicas da audição por meio dos seguintes testes: medidas de imitância acústica, audiometria tonal, logoaudiometria, teste GIN, potencial evocado auditivo de tronco encefálico (PEATE) com estímulos clique e de fala e potencial evocado auditivo de longa latência (PEALL) com estímulo tone burst e de fala. Os resultados obtidos no GC e GE foram comparados por meio de testes estatísticos. RESULTADOS: Ambos os grupos apresentaram resultados normais no teste GIN, de acordo com os critérios de normalidade adotados, contudo, observou-se melhor desempenho no GE. Não foram encontradas diferenças significantes entre os grupos para os resultados do teste GIN. No PEATE com estímulo clique, todos os sujeitos avaliados apresentaram resultados dentro dos padrões de normalidade. Observou-se no GE maior variabilidade nos tempos de latência, bem como tendência à diferença estatisticamente significante entre as orelhas direita e esquerda para o interpico I-III. No PEATE com estímulo de fala, verificaram-se valores de latência da onda C e de amplitude do complexo VA significantemente maiores no GE. No PEALL com estímulo tone burst não foi observada diferença estatisticamente significante entre os grupos. Contudo, observaram-se alterações (ausência de componentes do PEALL) em três sujeitos do GE e em um do GC. No PEALL com estímulo de fala, em ambos os grupos, verificou-se diferença estatisticamente significante entre as orelhas direita e esquerda no que tange a latência da onda N2 e amplitudes P2-N2 e da onda P300. Foram observadas alterações (ausência de componentes do PEALL) em um sujeito do GE. CONCLUSÃO: Embora não tenham sido verificadas alterações de resolução temporal no grupo de crianças gagas por meio do teste comportamental realizado, os resultados dos testes eletrofisiológicos sugerem a presença de diferenças nos processos neurais envolvidos no processamento da informação acústica, entre crianças em desenvolvimento típico e crianças gagas, principalmente em se tratando de elementos de maior complexidade, como a fala / INTRODUCTION: Stuttering is a multidimensional speech disorder that results from the interaction of multiple physiological processes, which means there is more than one causal factor. Current scientific evidence supports the hypothesis that people who stutter have anomalous connections in auditory regions of the left hemisphere, involved in the sensory feedback of speech sounds. Thus, it is reasonable to suppose that deficits in neural synchrony, showed by abnormal results in behavioral tests of temporal processing and auditory evoked potentials (AEP), may be related to this type of disorder. OBJECTIVE: to characterize the results of the Gaps in Noise Test (GIN) and the AEP using stimuli of different complexity, in children who stutter and in typically developing children. METHODS: Ten children who stutter aged between seven and 11 years (study group - SG) and their non-stuttering peers (control group - CG) underwent audiological and electrophysiological evaluation using the following tests: acoustic immittance measures, tonal audiometry, speech audiometry, GIN test, speech- and click-evoked Auditory Brainstem Response (ABR), and Long Latency Response (LLR) with tone burst and speech stimuli. Statistical tests were carried out for comparisons between CG and SG. RESULTS: Both groups presented normal results in the GIN test, according to the normality criteria. However, the SG showed better performance. No significant differences were found between groups for the GIN test results. In the click-evoked ABR, all subjects presented results within the normal range. The SG showed greater variability concerning the latency values, as well as a statistical trend toward significance regarding differences between the right and left ears for the interpeak I-III. In speech-evoked ABR, the latency values of wave C and the amplitude of VA complex were significantly higher in SG. No statistically significant difference between groups was observed in LLR with tone burst stimulus. However, abnormal results were observed (absence of LLR components) in three subjects from the SG and in one subject from the CG. In the LLR with speech stimuli, statistically significant differences were found for both groups, regarding the N2 latency, P2-N2, and P300 amplitudes, when the right and left ears were compared. Abnormal results were observed (absence of LLR components) in one subject from the SG. CONCLUSION: Although auditory temporal resolution deficits were not evidenced by the GIN test in the group of children who stutter, the results of the electrophysiological tests suggest the presence of differences in neural processes related to the acoustic information processing, when compared to typically developing children, especially when more complex elements, such as speech, are considered

INTRODUÇÃO: na tentativa de elucidar alguns aspectos relacionados ao zumbido, levantou-se a hipótese de alteração nas vias auditivas centrais. Diante disso, os potenciais evocados auditivos podem representar uma alternativa para detectar possíveis alterações auditivas centrais que possam estar presentes nesta população e que indiquem o provável sítio gerador desse sintoma. OBJETIVO: caracterizar os potenciais evocados auditivos de curta, média e longa latências em indivíduos com e sem queixa de zumbido e expostos a ruído ocupacional. MÉTODO: foram avaliados 60 sujeitos expostos a ruído de origem ocupacional com níveis de pressão sonora elevados (maior que 85 dBA), tanto do gênero masculino quanto feminino, na faixa etária entre 29 e 50 anos de idade, sendo 30 com queixa de zumbido (grupo pesquisa) e 30 sem queixa de zumbido (grupo controle). Foram realizados os potenciais evocados auditivos de curta, média e longa latências. RESULTADOS: na análise dos potenciais de curta latência, foi observado um aumento predominante das latências das ondas I e III, bem como, alteração de tronco encefálico baixo em 16 indivíduos do grupo pesquisa. Quanto aos potenciais de média latência, observou-se médias maiores para a latência da onda Na nas modalidades C4/A1 e C3/A2 no grupo pesquisa, evidenciando oito indivíduos com alteração. Por sua vez, para a latência da onda Pa e amplitude Na-Pa, tal aumento foi encontrado em todas as modalidades analisadas (C3/A1, C4/A1, C3/A2, C4/A2), sendo o efeito eletrodo o tipo de alteração mais frequentemente observado para a amplitude Na-Pa, e o aumento de latência para as ondas Na e Pa. Com relação aos potenciais de longa latência, constatou-se que o grupo pesquisa apresentou valores médios das latências das ondas N1, P2 e P300 e amplitude N1-P2 maiores que o grupo controle. Observou-se, também, um maior número de indivíduos alterados para o grupo pesquisa nos componentes N1(18 indivíduos) e P2 (20 indivíduos), sendo que o mesmo não pôde ser observado para o componente P300. Para esses potenciais, o aumento de latência foi tipo de alteração mais evidente. No estudo da associação entre lado da alteração nos potenciais evocados auditivos e localização do zumbido, verificou-se uma maior associação entre zumbido bilateral e alteração bilateral nos potenciais evocados auditivos de tronco encefálico e nos componentes N1, P2 e P300. CONCLUSAO: com base nos achados descritos, os resultados mostraram homogeneidade dos dois grupos quanto à faixa etária e tempo de exposição ao ruído. Apesar da inexistência de significância em algumas análises realizadas, as medidas dos potenciais de curta, média e longa latências mostraram que a maior parte dos indivíduos avaliados do grupo pesquisa apresentou alteração ao serem comparados com o grupo controle. Portanto, poder-se-ia supor a existência de uma possível disfunção no Sistema nervoso auditivo central desde o nervo auditivo até a região cortical em indivíduos com queixa de zumbido expostos a níveis de pressão sonora de origem ocupacional / INTRODUCTION: attempting to elucidate some aspects related to tinnitus, the hypothesis of alteration in the central auditory pathways was raised. Thus, auditory evoked potentials may represent an alternative to detect possible central auditory disorders that may be present in this population and that indicate the probable generator site of such symptom. AIM: to characterize short, middle and long latencies auditory evoked potentials in individuals with and without tinnitus complaint and exposed to occupational noise. METHOD: sixty subjects exposed to occupational noise with elevated sound pressure level (greater than 85 dBA), male and female, ranging in age from 29 to 50 years old took part in this study; 30 of them had tinnitus complaint (study group) and 30 did not have tinnitus complaint (control group). Short, middle and long latencies auditory evoked potentials were performed. RESULTS: analyzing the short latency potentials it was observed a predominant increase of the latency of waves I and III, as well as alteration in the lower brainstem in 16 individuals of the study group. Concerning the middle latency potentials it was observed higher averages for the latency of wave Na in the modalities C4/A1 and C3/A2 in the study group, evidencing eight individuals with altered results. Such increase was found in all modalities analyzed (C3/A1, C4/A1, C3/A2, C4/A2) for the latency of wave Pa and amplitude Na-Pa; the electrode effect was the most frequent type of alteration observed for the amplitude Na-Pa and the latency increase, for waves Na and Pa. Concerning the long latency potentials it was observed that the study group presented greater mean values of latencies of waves N1, P2 and P300, and amplitude N1-P2 than the control group. It was also observed in the study group a greater number of altered results concerning the components N1 (18 individuals) and P2 (20 individuals); the same was not observed for the component P300. For these potentials, the latency increase was the most evident type of alteration. Studying the association between the side of the altered auditory evoked potentials and the localization of the tinnitus it was verified a higher association between bilateral tinnitus and bilateral alteration in the brainstem auditory evoked potentials and in components N1, P2 and P300. CONCLUSION: based on the findings described, results showed homogeneity in both groups concerning the age and the time of noise exposure. Despite the inexistence of statistical significance in some of the analysis performed, measures of short, middle and long latencies potentials showed that most of the individuals analyzed in the study group presented alteration when compared to the control group. Therefore, the existence of a possible dysfunction in the central auditory nervous system from the auditory nerve until the cortical region in individuals with tinnitus complaint, exposed to sound pressure levels of occupational origin could be supposed

Made available in DSpace on 2016-03-15T19:40:17Z (GMT). No. of bitstreams: 1 Gabriel Gaudencio do Rego.pdf: 1139897 bytes, checksum: b56f45681ad1b3adb1fbebc620c7562a (MD5) Previous issue date: 2014-08-11 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Games are useful tools to simulate social interactions of cooperation or competition and can be applied in conjunction with behavioral and electrophysiological techniques, such as Event Related Potentials (ERP) analysis. The Ultimatum Game (UG) is a well-studied game which can be used to investigate how individuals react to injustice. An initial value is divided between a proponent, who suggests a division rate of this value, and a respondent, who may accept or reject it. If the respondent accepts, both players gain the proposed value, and if he or she rejects, they gain nothing. The behavioral and electrophysiological results have demonstrated typical reactions in the game. The Medial Frontal Negativity (MFN), a component associated with the automatic processing of negative social feedback, and the P300, associated with attention and memory process, are two components commonly observed during UG. While the interaction between volunteers and proponents with typical development is well described, the interaction between volunteers and proponents with Down syndrome is still unknown. This research aimed to investigate differences in the behavioral data, MFN and P300 in participants playing the UG with a typical proposer and Down proposer. 32 subjects participated in the experiment. Scales of social desirability, moral identity, self-esteem and an implicit association test about Down syndrome were applied. The results showed similar behavioral patterns among proponents and previous data described in the literature. Regarding ERPs, the MFN was not detected and there was greater amplitude of P200 component for proposals of the Down. There was also greater amplitude of P300 for fair proposals of the typical proponent compared to the fair proposals of the Down, and of these two compared to unfair proposals of both. The amplitude of the P300 for proposals of typical was negatively correlated with self-esteem scores. Together, the results suggest that the presence of a player with Down syndrome might influence the perception and expectation of the participants about the game, and this effect could be extended to the interaction with the typical proponent. The absence of MFN suggests that participants do not perceived the unfair proposals as a social negative outcome and P300 suggests that the interaction with the typical proposer was more relevant to the participants. Moreover, this relevance was modulated due to personal characteristics of self-esteem. Further studies are suggested in this area to confirm the hypotheses suggested in the present research. / Os jogos simulam situações sociais relativamente simples de cooperação ou competição e podem ser aplicados conjuntamente às técnicas de pesquisa comportamentais e eletrofisiológicas como a análise de potenciais relacionados a eventos (ERP). Um jogo muito estudado é o Ultimatum Game (UG), que pode ser utilizado para investigar como indivíduos reagem à injustiça. Um valor inicial é dividido entre um propositor, que sugere uma divisão do valor, e um respondente que pode aceitar ou rejeitar. Caso este aceite os dois ganham o valor proposto, caso rejeite ninguém ganha. Os resultados comportamentais e eletrofisiológicos têm demonstrado reações comuns no jogo. Os ERPs mais comuns é o MFN, associado ao processamento automático de feedbacks sociais negativos, e o P300, associado a processos atencionais e de memorização. Enquanto a interação entre sujeitos de pesquisa com propositores de desenvolvimento típico já é bem conhecida, o efeito desta interação com propositores com síndrome de Down ainda é desconhecido. O presente buscou investigar diferenças no padrão comportamental, de MFN e P300 em participantes jogando UG com propositor típico e com Down. 32 sujeitos participaram do experimento. Foram aplicadas escalas de desejabilidade social, identidade moral, de autoestima e um teste de atitudes implícitas frente às pessoas com Down. Os resultados demonstraram padrões comportamentais semelhantes entres os propositores e a literatura. Quanto aos ERPs, o MFN não foi detectado e houve presença de componente P200 para propostas de Down. Houve também maior amplitude de P300 para propostas justas do típico em comparação as justas do Down e destes dois em comparação às propostas injustas de ambos. A amplitude do P300 para propostas do típico apresentaram correlação negativa com escalas de autoestima. Os resultados sugerem que a presença de um jogador com síndrome de Down influenciou a percepção e expectativa dos participantes quanto ao jogo, e que este efeito pode ter se estendido para a interação com o propositor típico. A ausência de MFN sugere que não houve processamento das propostas injustas como respostas sociais negativas e o P300 sugere que a interação com o propositor foi de maior relevância para os participantes. Além disto, esta relevância foi modulada em razão de características pessoais de autoestima. São sugeridos novos estudos no tema para confirmar as hipóteses aqui apresentadas.

Introdução: A desnutrição energético-protéica é um dos maiores problemas de saúde pública no Brasil, ocorrendo mais frequentemente em pré-escolares e determinando o comprometimento do crescimento. A desnutrição pode provocar alterações no sistema nervoso central, dependendo da intensidade, da época de incidência e da duração da doença, comprometendo irreversivelmente as funções intelectuais. Levando-se em consideração a importância da integridade do Sistema Auditivo Periférico e Central na aquisição e desenvolvimento de fala, linguagem e aprendizado, torna-se imprescindível que anormalidades auditivas tanto periféricas como centrais sejam identificadas e tratadas precocemente nesta população. Objetivo: Caracterizar os achados das avaliações comportamentais, eletroacústicas e eletrofisiológicas da audição em crianças com desnutrição, bem como compará-los aos obtidos em crianças saudáveis da mesma faixa etária. Métodos: Foram realizados exames de audiometria tonal, logoaudiometria, teste dicótico de dígitos, imitanciometria, potencial evocado auditivo de tronco encefálico (PEATE) e potencial evocado auditivo de longa latência (PEALL) em 31 crianças desnutridas (grupo estudo) e 34 crianças saudáveis (grupo controle), com idade entre 7 e 12 anos, de ambos os gêneros. Resultados: Na análise dos dados quantitativos da audiometria tonal foi observada uma diferença estatisticamente significante entre os grupos para os limiares auditivos nas frequências de 250 e 8000 Hz, tendo o grupo estudo apresentado limiares auditivos mais elevados. Na análise qualitativa, não houve diferença estatisticamente significante entre os grupos, apesar de duas crianças do grupo estudo apresentarem perda auditiva discreta. Na análise dos dados qualitativos, não foram encontradas alterações na logoaudiometria para os dois grupos. No teste dicótico de dígitos, houve diferença estatisticamente significante entre os grupos, sendo observada uma maior proporção de crianças com alteração no grupo estudo. Ambos os grupos apresentaram resultados alterados na imitanciometria, não havendo diferença estatisticamente significante entre os grupos. Ambos os grupos apresentaram resultados normais do PEATE. Na análise dos dados quantitativos dos PEALL, verificou-se diferença estatisticamente significante entre os grupos para as latências dos componentes P1, N1 e P300, sendo que o grupo estudo apresentou latências maiores para todos os componentes. Na avaliação da amplitude do P300, houve diferença estatisticamente significante entre as orelhas direita e esquerda do grupo controle, sendo a amplitude do P300 maior na orelha direita. Por sua vez, no grupo estudo, não houve diferença significativa entre as orelhas direita e esquerda. Tanto o grupo controle quanto o grupo estudo apresentaram alterações nos resultados do PEALL, havendo diferença estatisticamente significante entre os grupos para os componentes P1, N1 e P300, sendo que o grupo estudo apresentou maior ocorrência de alterações. O tipo de alteração predominante nos componentes P1 e P300 foi o aumento de latência e, para o componente N1, foi a ausência de resposta no grupo estudo; para o grupo controle, o tipo de alteração predominante nos componentes P1, N1 e P300 foi o aumento de latência. Devido ao predomínio de crianças desnutridas de grau leve (58,1%), não foi possível estabelecer uma correlação entre o grau da desnutrição e a alteração dos PEALL. Conclusão: Crianças com desnutrição apresentaram mais alterações na avaliação comportamental da audição (audiometria tonal e teste dicótico de dígitos) e nos PEALL do que as crianças saudáveis, sugerindo déficit na via auditiva central e alteração no processamento da informação acústica. Há a necessidade de mais estudos para melhor caracterizar as alterações fonoaudiológicas e audiológicas desta população. / Introduction: Protein-energy malnutrition is a major public health problem in Brazil. It is more frequent among pre-school aged children and it compromises growth. Malnutrition may cause changes to the central nervous system depending on its intensity, time of incidence and duration, irreversibly compromising intellectual functions. Considering the importance of Peripheral and Central Auditory System integrity to the acquisition and development of speech, language and learning, it is crucial that both peripheral and central auditory abnormalities are identified and treated early in this population. Objective: To describe the findings of behavioral, electroacoustic and electrophysiological auditory assessments of malnourished children, as well as comparing them with findings from healthy children within the same age group. Methods: The following tests were performed in 31 malnourished children (study group) and 34 healthy children (control group), aged 7 to 12, from both genders: pure tone audiometry, speech audiometry, dichotic digit test, immittance measures, brainstem auditory evoked potential (BAEP) and long-latency auditory evoked potential (LLAEP). Results: While analyzing quantitative data from pure tone audiometry we observed statistically significant differences between groups for hearing thresholds at frequencies of 250 and 8000 Hz; the study group had higher hearing thresholds. As for quantitative analysis, there was no statistically significant difference between groups, although two children in the study group showed slight hearing loss. While analyzing qualitative data we did not find any changes in speech audiometry in any of the groups. As for the dichotic digit test, there was a statistically significant difference between groups, with a higher proportion of abnormal children in the study group. Both groups showed abnormal immittance measures results, although there was no statistically significant difference between the groups. Both showed normal BAEP results. When analyzing quantitative LLAEP data we observed a statistically significant difference between groups in terms of latency of components P1, N1 and P300; the study group had higher latencies for all components. When analyzing P300 amplitudes, there was a statistically significant difference between the right and left ears in the control group; P300 amplitudes was wider for the right ear. On the other hand, the study group did not show any statistically significant difference between the right and left ears. Both the control and study group shoed abnormal LLAEP results. There was a statistically significant difference between groups for components P1, N1 and P300; abnormalities were more frequent in the study group. The type of predominant abnormality in components P1 and P300 was increased latency and for component N1 it was lack of response in the study group; for the control group the type of predominant abnormality in components P1, N1 and P300 was increased latency. Because most children were only slightly malnourished (58.1%), it was not possible to establish a correlation between the level of malnutrition and LLAEP abnormalities. Conclusion: Malnourished children showed more abnormalities in auditory behavioral assessment (pure tone audiometry and dichotic digit test) and LLAEP than healthy children. This suggests a deficit in central auditory pathways and abnormalities in the processing of acoustic information. Further studies are necessary to better describe speech and language and hearing abnormalities in this population.

Introdução: Indivíduos com Transtorno do Espectro do Autismo (TEA) apresentam prejuízos nas interações sociais, comunicação e comportamento, além de poderem apresentar alterações cognitivas e de linguagem. Tendo em vista que o desenvolvimento da linguagem depende do funcionamento adequado da via auditiva periférica e central, ressalta-se a importância da avaliação audiológica completa, em especial, da avaliação do Sistema Nervoso Auditivo Central nessa população, tanto no diagnóstico como durante o processo terapêutico. Objetivos: caracterizar o Potencial Evocado Auditivo de Tronco Encefálico (PEATE) com estímulos clique e fala e o Potencial Evocado Auditivo de Longa Latência (PEALL) com estímulos tone burst e de fala, em indivíduos com TEA. Metodologia: participaram deste estudo 30 indivíduos na faixa etária de sete a 12 anos, de ambos os sexos, sendo 15 do grupo estudo (GE - crianças com diagnóstico de TEA) e 15 do grupo controle (GC - crianças com desenvolvimento típico - DT), pareados por sexo e idade. Foram realizados os seguintes procedimentos: anamnese, meatoscopia, avaliação audiológica básica (audiometria tonal, logoaudiometria e imitanciometria), e avaliação eletrofisiológica da audição (PEATE com estímulos clique e fala, e PEALL com estímulos tone burst e fala). Todos os exames foram realizados no Centro de Docência e Pesquisa do Departamento de Fisioterapia, Fonoaudiologia e Terapia Ocupacional da Faculdade de Medicina da Universidade de São Paulo. Resultados: No PEATE com estímulo clique, o valor médio de latência da onda I apresentou-se maior para orelha direita em ambos os grupos (valor-p = 0,037), ocorrendo assim o efeito orelha. Observou-se, também, que o interpico III - V no grupo com TEA foi maior do que o obtido no grupo com DT (valor-p = 0,046). No PEATE com estímulo de fala, a latência absoluta da onda V foi menor no grupo com TEA quando comparado ao grupo com DT (valor-p = 0,011). No PEALL, tanto para o estímulo tone burst quanto para o estímulo de fala, a latência do componente N1 foi maior na orelha direita (valor-p = 0,050), não sendo observada diferença significante entre os grupos tanto para os valores de latência quanto para os de amplitude dos componentes estudados. Conclusão: No que diz respeito ao PEATE clique, indivíduos com TEA apresentaram resultados sugestivos de alteração na via auditiva em tronco encefálico alto, indicando possíveis lesões ou disfunções do Sistema Nervoso Auditivo Central (SNAC). Com relação ao PEATE com estímulo de fala, pode-se concluir que a população de estudo apresentou codificação neural mais rápida da parte inicial do estímulo acústico (onset) quando comparada ao grupo com DT. Os resultados do PEALL não demonstraram alteração a nível cortical em indivíduos com TEA. Frente aos resultados obtidos, sugere-se novos estudos que realizem os exames eletrofisiológicos de curta e longa latência com um número maior de participantes / Introduction: Individuals with Autism Spectrum Disorder (ASD), showed issues in social interactions, communication and behavior, and it is also possible to present impaired cognitive and language skills. Taking into account the knowledge about the peripheral and central hearing, it highlights importance of the complete audiological evaluation, in particular, the evaluation of the Central Auditory Nervous System in this population, in diagnosis and during the therapeutic process. Aim: To characterize Brainstem Evoked Response Auditory (BERA) with click and speech stimuli and Long-Latency Auditory Evoked Potential (LLAEP) with tone burst and speech stimuli, in individuals with ASD. Methods: 30 children aged between seven and 12 years, of both sexes participated in this study, 15 of the study group (SG - children diagnosed with ASD) and 15 of the control group (CG - children with typical development - TD), matched by sex and age. The following tests were accomplished: anamnesis, meatoscopy, basic audiological evaluation (tonal audiometry, logoaudiometry and imitanciometry), and electrophysiological evaluation of hearing (BERA with click and speech stimulus and LLAEP with tone burst and speech stimulus). All the exams were done at the Teaching and Research Center of the Department of Physical Therapy, Speech and Hearing Therapy and Occupational Therapy, Faculty of Medicine, University of São Paulo. Results: In BERA with click stimulus, the average latency value of the wave I was higher for the right ear in all groups (p-value = 0.037), this occurring the ear effect. It was also observed that the III-V interpeak is higher in the TEA group than TD group (p-value = 0.046). In BERA with speech stimulus, an absolute latency of wave V was smaller than the ASD group when compared to the group with TD (p-value = 0.011). In the LLAEP, for the tone burst stimulus as well as for the speech stimulus, the latency of the N1 component was higher in the right ear (p-value = 0.050), between the groups were not being observed meaning differences for the latency values as for the amplitude values of the studied components. Conclusion: In relation to the BERA click, TEA group presented suggestive results of impairment in the auditory pathway, upper brainstem part, indicating possible lesions or dysfunctions of the Central Auditory Nervous System (CANS). With regard to BERA speech, can be concluded that the study population presented faster neural encoding of the initial part in the acoustic stimulus (onset) when compared with the TD group. The results of the LLAEP didn\'t show any changes in a cortical level of TEA group. From the results, we suggest new studies with BERA and LLAEP with a larger number of participants

p53, known as the “guardian of the genome”, is the most well-characterized tumor suppressor gene. The central role of p53 is to prevent genome instability. p53 is the central node in an incredibly elaborate genome defense network for receiving various input stress signals and controlling diverse cellular responses. The final output of this network is determined not only by the p53 protein itself, but also by other p53 cooperating proteins. p300 and CBP (CREB-Binding Protein) act as multifunctional regulators of p53 via acetylase and ubiquitin ligase activities. Prior work in vitro has shown that the N-terminal 595 aa of p300 encode both generic ubiquitin ligase (E3) and p53-directed E4 functions. Analysis of p300 or CBP-deficient cells revealed that both coactivators were required for endogenous p53 polyubiquitination and the normally rapid turnover of p53 in unstressed cells. Unexpectedly, p300/CBP ubiquitin ligase activities were absent in nuclear extracts and exclusively cytoplasmic. In the nucleus, CBP and p300 exhibited differential regulation of p53 gene target expression, C-terminal acetylation, and biologic response after DNA damage. p300 activated, and CBP repressed, PUMA expression, correlating with activating acetylation of p53 C-terminal lysines by p300, and a repressive acetylation of p53 lysine-320 induced by CBP. Consistent with their gene expression effects, CBP deficiency augmented, and p300 deficiency blocked, apoptosis after doxorubicin treatment. Subcellular compartmentalization of p300/CBP’s ubiquitination and transcription activities reconciles seemingly opposed functions—cytoplasmic p300/CBP E4 activities ubiquitinate and destabilize p53, while nuclear p300/CBP direct p53 acetylation, target gene activation, and biological outcome after genotoxic stress. p53 is a prominent tumor suppressor gene and it is mutated in more than 50% of human tumors. Reactivation of endogenous p53 is one therapeutic avenue to stop cancer cell growth. In this thesis, we have identified S5as a critical regulator of p53 degradation and activity. S5a is a non-ATPase subunit in the 19S regulatory particle of the 26S proteasome. Our preliminary data indicates that S5a is required for p53 instability and is a negative regulator of p53 tranactivation. As a negative regulator of p53, S5a may therefore also represent a new target for cancer drug development against tumors that specifically maintain wild type p53.

Posttranslational modifications are of great importance in the mediation of transcriptional effects, necessary for signalling in cancer. A characteristic example of such modifications is acetylation of the p53 tumour suppressor, a transcription factor involved in several crucial cellular functions including cell-cycle arrest and apoptosis. p53 is stabilised under hypoxic and DNA damaging-conditions. However, only in the latter scenario is p53 fully capable of inducing the expression of its proapoptotic targets through acetylation. The hypoxia inducible factor 1 (HIF-1) transcription factor is stabilised at low oxygen levels to mediate a cellular adaptive response under these conditions, promoting cell survival. As these two opposing transcription factors share a common transcriptional regulator, p300/CBP, this study focused on deciphering the p300/CBP complex components under differential stress to determine its composition required for cellular responses elicited in response to DNA damage or hypoxia, in an effort to investigate a possible link between differential posttranslational modifications and the resulting cell fate. Hence, the aim of this study was to investigate the roles of p300/CBP components in dictating transcriptional regulation of both HIF-1 and p53 in hypoxic conditions. To carry out this study, the proapoptotic BID gene was the system used, as its promoter contains a p53 response element and a HIF-1 response element (HRE). The p300/CBP associated factors PCAF and Strap were appointed as potent candidates for posttranslational modifications under differential conditions, as they are stress-responsive cofactors. Under DNA damage, PCAF acetylates p53 at K320 and Strap augments p300 binding to p53, both of which amplify the p53 response. Evidence from this study demonstrates that under hypoxia-mimicking conditions PCAF-mediated p53 acetylation at K320 is reduced to a greater extent compared to p300/CBP acetylation at K382. The limited amounts of acetylated p53 at K320 are preferentially recruited to the promoter of the cell cycle arrest p21WAF-1/CIP-1 gene that appears to be unaffected by hypoxia, but fail to be recruited to the BID promoter, rendering p53 incapable of upregulating proapoptotic BID in hypoxic conditions. In addition, under the same conditions, PCAF was found to acetylate, and direct HIF-1 to a particular subset of its targets, leading to alterations in the net physiological effect. Moreover, the intrinsic acetyl transferase activity of PCAF was shown to increase the stability of HIF-1. An additional role was attributed to PCAF in relation to apoptosis, albeit from another angle. BID protein translocation to the cytoplasm in hypoxic conditions was facilitated by ectopically expressed PCAF.Strap was found to be preferentially recruited to the HRE of the BID promoter in hypoxic conditions, and to exert a transrepression effect that appeared to be p53-dependent. Strap also interacted with specific PCAF isoforms depending on the type of cellular stress. Contrary to PCAF, ectopically expressed Strap did not have any effect on BID subcellular distribution. This study has provided additional insight in the mechanisms by which cofactors are involved in cell fate, either by affecting activity and stability of HIF-1 and p53, or having a direct effect on Bcl-2 member subcellular distribution.

<p>Brain-computer interfaces (BCI) have the potential to restore communication or control abilities in individuals with severe neuromuscular limitations, such as those with amyotrophic lateral sclerosis (ALS). The role of a BCI is to extract and decode relevant information that conveys a user's intent directly from brain electro-physiological signals and translate this information into executable commands to control external devices. However, the BCI decision-making process is error-prone due to noisy electro-physiological data, representing the classic problem of efficiently transmitting and receiving information via a noisy communication channel. </p><p>This research focuses on P300-based BCIs which rely predominantly on event-related potentials (ERP) that are elicited as a function of a user's uncertainty regarding stimulus events, in either an acoustic or a visual oddball recognition task. The P300-based BCI system enables users to communicate messages from a set of choices by selecting a target character or icon that conveys a desired intent or action. P300-based BCIs have been widely researched as a communication alternative, especially in individuals with ALS who represent a target BCI user population. For the P300-based BCI, repeated data measurements are required to enhance the low signal-to-noise ratio of the elicited ERPs embedded in electroencephalography (EEG) data, in order to improve the accuracy of the target character estimation process. As a result, BCIs have relatively slower speeds when compared to other commercial assistive communication devices, and this limits BCI adoption by their target user population. The goal of this research is to develop algorithms that take into account the physical limitations of the target BCI population to improve the efficiency of ERP-based spellers for real-world communication. </p><p>In this work, it is hypothesised that building adaptive capabilities into the BCI framework can potentially give the BCI system the flexibility to improve performance by adjusting system parameters in response to changing user inputs. The research in this work addresses three potential areas for improvement within the P300 speller framework: information optimisation, target character estimation and error correction. The visual interface and its operation control the method by which the ERPs are elicited through the presentation of stimulus events. The parameters of the stimulus presentation paradigm can be modified to modulate and enhance the elicited ERPs. A new stimulus presentation paradigm is developed in order to maximise the information content that is presented to the user by tuning stimulus paradigm parameters to positively affect performance. Internally, the BCI system determines the amount of data to collect and the method by which these data are processed to estimate the user's target character. Algorithms that exploit language information are developed to enhance the target character estimation process and to correct erroneous BCI selections. In addition, a new model-based method to predict BCI performance is developed, an approach which is independent of stimulus presentation paradigm and accounts for dynamic data collection. The studies presented in this work provide evidence that the proposed methods for incorporating adaptive strategies in the three areas have the potential to significantly improve BCI communication rates, and the proposed method for predicting BCI performance provides a reliable means to pre-assess BCI performance without extensive online testing.</p> / Dissertation

During cell specification, temporal and spatially restricted gene expression programs are set up, forming different cell types and ultimately a multicellular organism. In this thesis, we have studied the molecular mechanisms by which sequence specific transcription factors and coactivators regulate RNA polymerase II (Pol II) transcription to establish specific gene expression programs and what epigenetic patterns that follows. We found that the transcription factor Dorsal is responsible for establishing discrete epigenetic patterns in the presumptive mesoderm, neuroectoderm and dorsal ectoderm, during early Drosophila embryo development. In addition, these different chromatin states can be linked to distinct modes of Pol II regulation. Our results provide novel insights into how gene regulatory networks form an epigenetic landscape and how their coordinated actions specify cell identity. CBP/p300 is a widely used co-activator and histone acetyltransferase (HAT) involved in transcriptional activation. We discovered that CBP occupies the genome preferentially together with Dorsal, and has a specific role during development in coordinating the dorsal-ventral axis of the Drosophila embryo. While CBP generally correlates with gene activation we also found CBP in H3K27me3 repressed chromatin. Previous studies have shown that CBP has an important role at transcriptional enhancers. We provide evidence that the regulatory role of CBP does not stop at enhancers, but is extended to many genomic regions. CBP binds to insulators and regulates their activity by acetylating histones to prevent spreading of H3K27me3. We further discovered that CBP has a direct regulatory role at promoters. Using a highly potent CBP inhibitor in combination with ChIP and PRO-seq we found that CBP regulates promoter proximal pausing of Pol II. CBP promotes Pol II recruitment to promoters via a direct interaction with TFIIB, and promotes transcriptional elongation by acetylating the first nucleosome. CBP is regulating Pol II activity of nearly all expressed genes, however, either recruitment or release of Pol II is the rate-limiting step affected by CBP. Taken together, these results reveal mechanistic insights into cell specification and transcriptional control during development. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.</p><p> </p>