Orientador: José de Anchieta de Castro e Horta Junior / Banca: Luiz Takase / Banca: Claudio Aparecido Casatti / Banca: Luciana Pinatto / Banca: Mirela Barros Dias / Resumo: O reflexo auditivo de sobressalto (RAS) é uma reação motora rápida e evidente frente a um estímulo acústico intenso e inesperado. Trata-se de um reflexo acústico-motor do tronco encefálico que está presente em muitas espécies de mamíferos, incluindo o homem. Possui caráter tanto defensivo frente a uma possível agressão quanto de alerta frente a aconteci-mentos não esperados. Além do RAS resultar em uma resposta sobre a musculatura esque-lética, possui ação sobre o sistema nervoso autônomo promovendo aumento da pressão arterial e da freqüência cardíaca. No rato o circuito neural elementar do RAS é constituído por: neurônios do gânglio espiral, neurônios da raiz coclear (CRN), neurônios reticuloespi-nais do núcleo reticular caudal da ponte (PnC) e motoneurônios da medula espinal. O RAS pode ser modulado pela habituação, sensibilização, inibição por estímulo prévio (PPI) e pela potenciação por um estímulo adverso. Estas modulações podem ocorrer mediante a influên-cia de diversas substâncias neuroativas sobre os componentes deste circuito. Neste traba-lho avaliamos a origem de aferências monoaminérgicas (serotonina e noradrenalina) e CART-érgicas para os CRN e PnC. Para isso foram utilizados 54 ratos Wistar, adultos fê-meas, que foram submetidos a injeções de traçadores neuronais anterógrados e retrógrados para mapeamento de vias nervosas e a identificação imuno-histoquímica de substâncias neuroativas. Todos os protocolos experimentais foram aprovados pela Comissão de Ética no Uso de Animais do Instituto de Biociências de Botucatu - UNESP (protocolo no 17/08). Nos-sos resultados demonstram que o grupamento noradrenérgico A5 é uma fonte de aferências noradrenérgicas e CART-érgicas para os CRN e PnC, enquanto que o núcleo dorsal da rafe (DR) é a origem de aferências serotoninérgicas para estas regiões. Existem conexões recí-procas entre o DR, o A5 e o PnC. Além disso,... / Abstract: The acoustic startle reflex (ASR) is a rapid motor reaction elicited by a sudden intense acoustic stimulus. This is an acoustic-motor reflex of brainstem conserved across mammal's species including man. Moreover the ASR is defensive behavior against both possible ag-gressive and alert to unexpected events. The ASR evokes responses of skeletal muscles as well as of autonomic nervous system with elevation of blood pressure and acceleration of the heart rate. In the rat, the elementary neural circuitry of ASR is mediated by ganglion cells of the organ of Corti, the cochlear root neurons (CRN), the pontine caudal reticular nucleus (PnC) and motoneurons of the spinal cord. The ASR could be modulated by habituation, sensitization, prepulse inhibition (PPI), and fear potentiation. These modulations were medi-ated by the influence of neuroactive substances on components of neuronal circuitry of ASR. In this work we evaluate the origin of monoaminergic (serotonin and noradrenaline) and CART-ergic afferents to CRN and PnC. Adult Female Wistar rats (n=54) were submitted to injections of retrograde and anterograde neuronal tracers in track-tracing experiments and identification of neuroactive substances in brain by immunohistochemistry technique. All ex-perimental protocols are according with Ethics Committee on Animal Use (protocol: 17/08). Our results demonstrate that noradrenergic area A5 (A5) is a source of noradrenergic and CART-ergic afferents to CRN and PnC, and dorsal raphe nucleus (DR) is origin of seroto-ninergic afferents to these regions. There are reciprocal connections between DR, A5 and PnC. Furthermore, after 14 and 21 days of lesion in A5, the percentage of PPI increased during intervals of 100 and 150 milliseconds without modification of ASR. This data suggest that A5 have direct action on elementary circuit of ASR evidenced his connections and modulation of PPI. Moreover, A5 and DR connections bring new insights about modulation ... / Doutor

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This study investigated the electromyogram eyeblink startle response in relationship to individual differences in dimensions of attention and arousability as assessed by the Cognitive Failures Questionnaire (Broadbent, Cooper, Fitzgerald & Parkes, 1982) and the Arousal Predisposition Scale (Coren, 1990). Individuals (n=48) fulfilling the cutoff criteria of the questionnaires compiled three groups: High Arousal/High Cognitive Failures, High Arousal/Low Cognitive Failures and Low Arousal/Low Cognitive Failures. The eyeblink startle response was examined in two conditions, one in which participants were instructed to attend to loud, startling acoustic stimuli and a second in which they were instructed to ignore the startling stimuli by mentally counting backwards by threes. It was hypothesized that groups would differ from each other in both amplitude and latency of their startle response. More specifically, if top-down controlled attentional processes mediated the startle response under such conditions, it was expected that those with less distractibility would exhibit less startle during the ignore task than those who were more distractible. If arousal level mediated the startle response, it was expected that those with high arousability would exhibit increased overall startle response. If the ignore condition was more arousing, it was expected that those with high arousability would exhibit more startle during the ignore condition than those with low arousability. It was expected that the startle response between men and women would differ significantly. Furthermore, it was hypothesized that those participants reporting high distractibility would demonstrate a larger Stroop Effect than those reporting low distractibility. Results indicated that for mean startle response amplitude there was a significant Attention Group X Condition interaction but not an Arousal Group X Condition interaction. Post hoc tests did not reveal one condition to be greater in mean amplitude than another. When including sex as a factor, for mean onset latency there was a significant Attention X Gender interaction and a significant Arousal X Gender interaction. High arousal and high distractible men also showed significantly more significantly more startling than low distractible men and low distractible women. There were no significant differences of the Stroop Effect found between high and low distractible participants. Taken together, it appears that controlled top-down processing can influence the startle response when manipulations of the direction of attention are given. It also appears that men are more extreme in their responsivity than women. Implications for future research are discussed. / Master of Science

<p>Bilder av potentiella hot upptäcks snabbt och leder till en snabbare reaktionstid än bilder av icke-potentiella hot. Potentiella hot stjäl också fokus och kognitiva resurser, med en långsammare reaktionstid som följd. Rädsla, som kan mätas genom startlereflexen, leder till antingen ökad handlingsberedskap (snabbare reaktionstid) eller kognitiv distraktion (långsammare reaktionstid). Fem försöksdeltagare fick reagera på en visuell probe som lades ovanpå djurbilder, både potentiella hot och icke-potentiella hot i ett kombinerat reaktionstids- och startleprobeexperiment, där ljudstötar utdelades i hörlurar. Startlereaktion, hjärtfrekvens och reaktionstid mättes, varefter korrelationskoefficienter räknades ut. Resultatet visade på en svag negativ korrelation mellan reaktionstid och startlepotentiering på gruppnivå, men inga signifikanta samband påvisades på individnivå. Resultatet på gruppnivå kan bero på att de individuella resultaten tenderar samlas i kluster och därför skapar ett skensamband. Även en positiv korrelation mellan hjärtfrekvensförändring och startlereaktion påvisades, men ingen korrelation mellan hjärtfrekvens och reaktionstid.</p> / <p>Pictures of fear relevant animals are detected fast and lead to shorter reaction time, compared to pictures of fear irrelevant animals. Fear relevant animals also capture attention and steals focus, which leads to slower reaction time. Fear leads to either preparedness for action (faster reaction time) or cognitive distraction (slower reaction time). In a combined startle probe and reaction time experiment, five participants were requested to react to a visual probe, superimposed on pictures of animals, both relevant and irrelevant to fear. Startle probes were given as noise bursts in headphones. Startle reaction, heart rate and reaction time were measured. A negative correlation between reaction time and startle potentiation was found on group level, whereas no significant correlations were found on the individual level. However, the individual results tend to gather in clusters, which might give a significant result on group level even if there is none.</p>

Bilder av potentiella hot upptäcks snabbt och leder till en snabbare reaktionstid än bilder av icke-potentiella hot. Potentiella hot stjäl också fokus och kognitiva resurser, med en långsammare reaktionstid som följd. Rädsla, som kan mätas genom startlereflexen, leder till antingen ökad handlingsberedskap (snabbare reaktionstid) eller kognitiv distraktion (långsammare reaktionstid). Fem försöksdeltagare fick reagera på en visuell probe som lades ovanpå djurbilder, både potentiella hot och icke-potentiella hot i ett kombinerat reaktionstids- och startleprobeexperiment, där ljudstötar utdelades i hörlurar. Startlereaktion, hjärtfrekvens och reaktionstid mättes, varefter korrelationskoefficienter räknades ut. Resultatet visade på en svag negativ korrelation mellan reaktionstid och startlepotentiering på gruppnivå, men inga signifikanta samband påvisades på individnivå. Resultatet på gruppnivå kan bero på att de individuella resultaten tenderar samlas i kluster och därför skapar ett skensamband. Även en positiv korrelation mellan hjärtfrekvensförändring och startlereaktion påvisades, men ingen korrelation mellan hjärtfrekvens och reaktionstid. / Pictures of fear relevant animals are detected fast and lead to shorter reaction time, compared to pictures of fear irrelevant animals. Fear relevant animals also capture attention and steals focus, which leads to slower reaction time. Fear leads to either preparedness for action (faster reaction time) or cognitive distraction (slower reaction time). In a combined startle probe and reaction time experiment, five participants were requested to react to a visual probe, superimposed on pictures of animals, both relevant and irrelevant to fear. Startle probes were given as noise bursts in headphones. Startle reaction, heart rate and reaction time were measured. A negative correlation between reaction time and startle potentiation was found on group level, whereas no significant correlations were found on the individual level. However, the individual results tend to gather in clusters, which might give a significant result on group level even if there is none.

Title from PDF of title page. / Document formatted into pages; contains 18 pages. / Thesis (Au.D.)--University of South Florida, 2003. / Includes bibliographical references. / Text (Electronic thesis) in PDF format. / ABSTRACT: This study examined the effects of genetic background on the acoustic startle response (ASR) and its modulation by prepulse inhibition (PPI) by comparing nine inbred strains of mice. The ASR, a jerk-like motor reflex, is elicited by bursts of noise or tones with sound pressure levels of 80-90 dB and greater. PPI is a type of modulation of the ASR, requires no training, and results in observable response in both mice and humans. Data were obtained from nine inbred mouse strains, sixteen per strain, which were shipped at approximately 3-5 weeks old from The Jackson Laboratory. In general, ASRs were generally smaller when the startle stimulus was less intense. PPI was relatively weak for the 4 kHz prepulse, and stronger with prepulses of 12 kHz and 20 kHz. However, means varied widely across strains for both ASR and PPI, suggesting a strong influence of genetic background on these behaviors. / ABSTRACT: In addition to genetic influences, peripheral hearing loss and central auditory processing factors must be taken into consideration. / System requirements: World Wide Web browser and PDF reader. / Mode of access: World Wide Web.

Objectif: Cette thèse avait pour objectif principal la mise en oeuvre et la validation de la faisabilité, chez l'humain, du paradigme de modulation du réflexe acoustique de sursaut par un court silence (GPIAS) afin de l'utiliser comme mesure objective de l'acouphène. Pour ce faire, trois expériences ont été réalisées. L'expérience 1 avait pour objectif de valider l'inhibition du réflexe de sursaut par un court silence chez des participants humains normo-entendants (sans acouphène) lors de la présentation d'un bruit de fond centré en hautes et en basses fréquences afin de déterminer les paramètres optimaux du paradigme. L'expérience 2 avait pour objectif de valider la précision et la fidélité d'une méthode de caractérisation psychoacoustique de l'acouphène (appariement en intensité et en fréquence). Finalement, l'expérience 3 avait pour objectif d'appliquer le paradigme d'objectivation de l'acouphène par le réflexe de sursaut à des participants atteints d'acouphènes chroniques en utilisant les techniques développées lors des expériences 1 et 2. Méthodologie : L'expérience 1 incluait 157 participants testés dans l'une des conditions de durée du court silence (5, 25, 50, 100, 200 ms) et dans l'un des deux paradigmes (court silence à l'intérieur du bruit de fond ou suivant celui-ci) à l'aide de bruits de fond en hautes et en basses fréquences. L'expérience 2 incluait deux groupes de participants avec acouphène, l'un musicien (n=16) et l'autre sans expérience musicale (n=16) ainsi qu'un groupe de simulateur sans acouphène (n=18). Ils tous ont été évalués sur leur capacité d'appariement en fréquence et en intensité de leur acouphène. Les mesures ont été reprises chez un sous-groupe de participants plusieurs semaines plus tard. L'expérience 3 incluait 15 participants avec acouphène et 17 contrôles évalués à l'aide du paradigme d'inhibition du réflexe de sursaut à l'aide d'un court silence (GPIAS). Les paramètres psychoacoustiques de l'acouphène ont également été mesurés. Toutes les mesures ont été reprises plusieurs mois plus tard chez un sous-groupe de participants. Résultats : Expérience 1 : le paradigme d'inhibition du réflexe acoustique de sursaut par un court silence est applicable chez l'humain normo-entendant. Expérience 2 : les mesures psychoacoustiques informatisées de l'acouphène incluant l'appariement en fréquence et en intensité sont des mesures précises et fidèles du percept de l'acouphène. Expérience 3 : un déficit d'inhibition au paradigme du GPIAS a été retrouvé chez le groupe de participants avec acouphène pour les bruits de fond en hautes et en basses fréquences au test et au retest. Les mesures d'appariement en fréquence ont révélé un acouphène dont la fréquence prédominante était d'environ 16 000 Hz chez la plupart des participants. Discussion : Il est possible d'appliquer le paradigme d'inhibition du réflexe acoustique de sursaut par un court silence à des participants humains atteints d'acouphène, tel qu'il est utilisé en recherche animale pour « objectiver » la présence d'acouphène. Toutefois, le déficit d'inhibition mesuré n'est pas spécifique à la fréquence de l'acouphène lorsque validé à partir des données d'appariement psychoacoustique. Nos résultats soulèvent des questions quant à l'interprétation originale du paradigme pour détecter la présence d'un acouphène chez les animaux. / Objective: The main objective of this thesis was the implementation and validation of applying the gap prepulse inhibition of the acoustic startle reflex (GPIAS) paradigm in humans, in order to objectively measure tinnitus. To do this, three experiments were carried out. Experiment 1 was designed to validate the inhibition of the acoustic startle reflex by using a short gap within high and low frequency narrowband noise in normal hearing humans (without tinnitus) to determine the optimal paradigm parameters. Experiment 2 was designed to validate the accuracy and the test-retest fidelity of a tinnitus psychoacoustic characterization method (intensity and frequency matching). Finally, Experiment 3 applied the GPIAS paradigm to participants with chronic tinnitus using the techniques developed in experiments 1 and 2. Methods: Experiment 1 included 157 participants tested with only one gap duration (5, 25, 50, 100, 200 ms) and with one of the two paradigms (gap imbedded in the background noise or following it) including high and low frequencies background noise. Experiment 2 included two groups of participants with tinnitus, one group consisting of musicians (n=16) and one group without musical experience (n=16). A third group consisted of adults who were instructed to simulate having tinnitus (n = 18). Tinnitus pitch and intensity matching abilities were assessed for all participants. A subgroup of participants was retested several weeks later. Experiment 3 included 15 participants with tinnitus and 17 controls assessed with the GPIAS. The psychoacoustic parameters of tinnitus were also measured. A subgroup of participants was retested several weeks later. Results: Experiment 1: the GPIAS is applicable in humans with normal hearing. Experiment 2: psychoacoustic measurements of tinnitus frequency and intensity using a computerized matching procedure produced precise and accurate measurements of the tinnitus percept. Experiment 3: an inhibition deficit was found using the GPIAS paradigm in the tinnitus group for background noise of high and low frequency compared to the control group, at test and retest. The frequency matching measurements revealed a 16,000 Hz tinnitus predominant frequency for most tinnitus participants. Discussion: It is possible to apply the gap prepulse inhibition of the startle reflex paradigm on human participants with tinnitus, as used in animal research to "objectify" the presence of tinnitus. However, the inhibition deficit found in the tinnitus group was not specific to their tinnitus frequency. This was validated by psychoacoustic tinnitus pitch matching. Our results question the original interpretation of the GPIAS paradigm for objectifying the presence of tinnitus.

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N-methyl-D-asparate (NMDA) receptors located within the basolateral complex of the amygdala are required for the consolidation and expression of Pavlovian conditioned fear. The events downstream of receptor activation that mediate these processes are not well defined. An intermediate step that may be of significance is the synthesis of the gas nitric oxide (NO). Nitric oxide is synthesised as a result of NMDA receptor activation and acts as an unconventional neurotransmitter freely diffusing across cell membranes interacting with its targets in a non-synaptic manner. The targets of NO include cellular components that play significant roles during the consolidation of conditioned fear and the neurotransmission associated with its expression. This implies that NO may be an important intermediary of NMDA receptor activation and both these processes. The current study sought to examine this possibility using fear potentiated startle to examine the expression of learned fear. Three experiments were conducted, fifty rats received intra-BSC microinfusions of the global nitric oxide synthase inhibitor L-NAME either prior to fear conditioning, fear testing, or examination of the shock sensitization of the acoustic startle affect. The results indicated that NO was indeed required for both the consolidation and expression of learned fear, whereas it was not required for shock enhanced startle responding. This study provides new information about the sub-cellular basis of conditioned fear, and highlights the pivotal role played by NO in processes associated with conditioned fear.