Thesis (Ph. D.)--Florida State University, 2005. / Advisor: Dr. Richard Hyson, Florida State University, Program in Neuroscience. Title and description from dissertation home page (viewed Sept. 19, 2005). Document formatted into pages; contains ix, 64 pages. Includes bibliographical references.

published_or_final_version / abstract / Speech and Hearing Sciences / Master / Master of Science in Audiology

Introdução: A partir de sua descrição anatômica, o interesse sobre a ação das vias auditivas eferentes sobre a audição vem crescendo progressivamente, com estudos realizados em animais e humanos. A função do trato olivococlear medial em humanos pode ser avaliada por meio da supressão das emissões otoacústicas, exame clínico que se mostra promissor para a análise do estado coclear e dos mecanismos auditivos centrais, auxiliando no diagnóstico de lesões e disfunções retrococleares. O estudo sobre a supressão das emissões otoacústicas com apresentação de estímulo supressor contralateral ou bilateral torna-se útil para avaliar a interação entre as orelhas e contribuir para a investigação da ação do sistema eferente. Objetivo: Os objetivos do presente estudo foram: a) comparar o efeito da estimulação unilateral e bilateral na pesquisa dos níveis de resposta das emissões otoacústicas por estímulo transiente (EOAT) e por produto de distorção (EOAPD) em indivíduos com audição normal; b) comparar o efeito de supressão bilateral e contralateral das EOAT. Metodologia: Esta pesquisa foi realizada no Laboratório de Investigação Fonoaudiológica em Audição Humana do Departamento de Fisioterapia, Fonoaudiologia e Terapia Ocupacional da Faculdade de Medicina da Universidade de São Paulo. A casuística foi composta por 30 sujeitos com audição dentro dos parâmetros da normalidade, de acordo com a avaliação audiológica convencional, sendo 15 do gênero masculino e 15 do feminino, na faixa etária de 18 a 33 anos. Foi realizada a pesquisa das EOAT e EOAPD em ambas as orelhas, inicialmente com estimulação unilateral e posteriormente com estimulação bilateral (estímulo eliciador fornecido simultaneamente para ambas as orelhas). Em seguida realizou-se a pesquisa da supressão das EOAT com estímulo supressor contralateral. Foi utilizado o Analisador de Emissões cocleares Echoport ILO 292 USB II, versão 6, Otodynamics. Resultados: Observou-se que os valores de nível de resposta da coleta com estimulação unilateral foram significantemente maiores do que os valores da coleta com estimulação bilateral, tanto para EOAT como para EOAPD, evidenciando a redução do nível de resposta das emissões otoacústicas com a apresentação do estímulo eliciador bilateral. Não foi observado efeito de gênero e de lado de orelha tanto para as respostas de EOAT como de EOAPD. Para EOAT, comparando-se o valor da supressão bilateral com a supressão contralateral, observaram-se maiores valores de supressão com a estimulação acústica bilateral. Conclusão: A coleta das EOA com estimulação bilateral foi capaz de ativar mecanismos do sistema auditivo eferente e produziu um efeito supressor em relação à coleta unilateral. A supressão bilateral das EOAT observada apresentou maior magnitude em relação à supressão contralateral convencionalmente utilizada. / Introduction: Since the anatomical description of olivocochlear pathway, the interest on its action over the hearing has been growing progressively supported by studies performed in animals and humans. The function of medial olivocochlear pathway in humans can be assessed through the otoacoustic emissions suppression, a clinical examination which is useful for the analysis of cochlear state and central auditory mechanisms, aiding in the diagnosis of hearing injuries and disorders. The study about otoacoustic emissions suppression with presentation of contralateral or bilateral suppressor stimulus becomes useful to assess the interaction between the ears and contribute to research the auditory efferent system action. Aim: The main goal of this study was to compare the effect of unilateral and bilateral stimulation in response of transient evoked otoacoustic emissions (TEOAE) and distortion product evoked otoacoustic emissions (DPOAE) in individuals with normal hearing. The secondary purpose was to compare the effect of bilateral and contralateral transient evoked otoacoustic emissions suppression. Method: This study was developed in the Human Hearing Investigation Laboratory of the Physical Therapy, Speech and Hearing Science and Occupational Therapy Department of the Medicine College of São Paulo University, Brazil. Data were obtained from 30 adults (15 males and 15 females) with normal hearing, according to conventional audiological evaluation. Their age ranged from 18 to 33 years. The research of TEOAE and DPOAE was conducted in both ears, initially only with unilateral stimulation and later with bilateral stimulation (elicitor stimulus provided simultaneously to both ears). Then was performed the search of contralateral transient evoked otoacoustic suppression. It was used an Echoport ILO 292 USB II, version 6, Otodynamics. Results: The response levels of bilateral TEOAE and DPOAE were significantly larger than the response of unilateral search. So, it was observed a reduction in the response level of otoacoustic emissions with the presentation of bilateral elicitor stimulus. No significant differences in TEOAE and DPOAE responses were found among gender and ear side. For TEOAE, comparing the amount of bilateral and contralateral suppression, was found higher values in the first testing paradigm. Conclusion: The bilateral EOA search was capable of activating mechanisms of the auditory efferent system and produced a suppressive effect in comparison with unilateral EOA search. Bilateral TEOAE suppression showed a greater suppression effect than contralateral TEOAE suppression.

Objetivo: Avaliar e comparar os achados dos Potenciais Evocados Auditivos de Tronco Encefálico em indivíduos com holoprosencefalia (HPE) e holoprosencefalia-like (HPE-like). Modelo: Análise prospectiva comparando os achados dos PEATE entre três grupos: indivíduos com HPE clássica (GH), indivíduos com HPE-like (GHL) e grupo controle (GC), a um nível de significância de 5%. Local de Execução: Setor de Genética, HRAC-USP. Participantes: 57 pacientes, com idades entre 1 ano e 6 meses e 22 anos, sendo 13 com HPE clássica, 22 com HPE-like, e um grupo controle de 22 indivíduos normais. Variáveis: Latências absolutas das ondas I, III e V; latências interpicos I-V, III-V e I-III e diferença interaural da onda V do PEATE, em milissegundos, para cada orelha. Resultados: Os valores médios em milissegundos das latências absolutas e interpicos nas orelhas direita e esquerda respectivamente foram os seguintes. ara a onda I: 2,21 e 2,19 (GH); 1,99 e 2,01 (GHL); 1,92 e 1,91 (GC). Para a onda III: 4,35 e 4,52 (GH); 4,04 e 4,04 (GHL); 3,97 e 3,94 (GC). Para a onda V: 6,47 e 6,51 (GH); 5,95 e 5,94 (GHL); 5,90 e 5,90 (GC). Para o interpicos I-V: 4,20 e 4,24 (GH); 3,94 e 3,92 (GHL); 3,97 e 3,97 (GC). Para o interpicos III-V: 2,27 e 2,07 (GH); 1,91 e 1,90 (GHL); 1,92 e 1,95 (GC). Para o interpicos I-III: 2,14 e 2,33 (GH); 1,03 e 2,01 (GHL); 2,04 e 2,01 (GC). Os valores de diferença interaural da onda V foram: 0,13 (GH); 0,06 (GHL) e 0,03 (GC). Conclusões: Os dados sugerem que grande parte dos indivíduos com HPE clássica apresentam alterações de PEATE compatíveis com o grau de comprometimento neurológico, enquanto aqueles com HPE-like apresentam poucas alterações, sendo estas justificadas pelas patologias de orelha média decorrentes da fissura de palato. / Objective: To evaluate and compare Auditory Brainstem Response (ABR) findings in patients with holoprosencephaly (HPE) and the “HPE-like" phenotype. Model: A prospective analysis comparing ABR results among three different groups: patients with classic HPE (GH), patients with HPE-like (GHL) and control group (GC), at a 5% significance level. Setting: Genetics Department, HRAC-USP. Participants: 57 patients, aged from 18 months to 22 years. Thirteen of them had classic HPE, 22 had HPE-like, and 22 were audiologically normal individuals, who joined the GC. Variables: Waves I, III and V absolute latencies; interpeak intervals I-V, III-V and I-III and wave V interear difference of ABR, in milisseconds, considering both right and left ears. Results: Mean values, in milisseconds, of absolute latencies and interpeaks recorded from right and left ears, respectivelly, were: Wave I: 2,21 and 2,19 (GH); 1,99 and 2,01 (GHL); 1,92 and 1,91 (GC). Wave III: 4,35 and 4,52 (GH); 4,04 and 4,04 (GHL); 3,97 and 3,94 (GC). Wave V: 6,47 and 6,51 (GH); 5,95 and 5,94 (GHL); 5,90 and 5,90 (GC). Interpeak I-V: 4,20 and 4,24 (GH); 3,94 and 3,92 (GHL); 3,97 and 3,97 (GC). Interpeak III-V: 2,27 and 2,07 (GH); 1,91 and 1,90 (GHL); 1,92 and 1,95 (GC). Interpeak I-III: 2,14 and 2,33 (GH); 1,03 and 2,01 (GHL); 2,04 and 2,01 (GC). Wave V interear difference were: 0,13 (GH); 0,06 (GHL) and 0,03 (GC). Conclusions: Results suggest that most patients with classic HPE have abnormalities detected by ABR testing, which are related to the severity of neurologic impairment. Otherwise, those with the HPE-like phenotype have few alterations, most likely resulting from middle ear pathologies that occur in presence of cleft palate.

A utilização das emissões otoacústicas (EOs) têm contribuído na avaliação do sistema auditivo eferente por meio do estudo do efeito da estimulação acústica simultânea à pesquisa das EOs, descrito na literatura como supressão das EOs. Este trabalho teve por objetivo comparar o efeito da estimulação contralateral do ruído na amplitude das emissões otoacústicas evocadas por clique (EOE-c), em crianças que apresentam audição normal e em crianças com Neuropatia Auditiva/Dessincronia Auditiva. A casuística foi constituída de 16 crianças com audição normal e 11 crianças com o diagnóstico audiológico de Neuropatia Auditiva/Dessincronia Auditiva. As EOE-c foram pesquisadas, utilizando-se o clique linear na intensidade de 60 dB NPS e, para a estimulação contralateral do ruído, foi utilizado o ruído branco na intensidade de 65 dB NPS, com monitoramento do nível de pressão sonora, gerado no conduto auditivo externo, por meio do microfone sonda. Os resultados demonstraram que, nas crianças com audição normal, além da redução da amplitude das EOE-c, foi observada supressão das EOE-c, ou seja, a ausência do registro das EOE-c com a estimulação contralateral do ruído. Nas crianças com Neuropatia Auditiva/Dessincronia Auditiva, foi observado que a estimulação contralateral do ruído não provocou mudanças significativas na amplitude das EOE-c. Este trabalho permitiu concluir que a amplitude das EOE-c do grupo de crianças com audição normal se comportou de maneira estatisticamente diferente do grupo de crianças com Neuropatia Auditiva/Dessincronia Auditiva na presença da estimulação contralateral do ruído, e que a média da redução da amplitude das EOE-c frente à estimulação contralateral do ruído nas crianças com audição normal é estatisticamente maior que a redução da amplitude das EOEc nas crianças com Neuropatia Auditiva/Dessincronia Auditiva. / The use of otoacoustic emissions (EOs) has contributed to the evaluation of the efferent auditory system through the effect of the acoustic stimulation simultaneous to the EOs, described in the literature as EOs suppression. This study had the objective of comparing the effect of the contralateral stimulation of the noise in the amplitude of the click-evoked otoacoustic emissions (EOE-c), in children having normal hearing and in children with Auditory Neuropathy/ Auditory Dsy-synchrony. The casuistry was constituted by 16 children having normal hearing and 11 children diagnosed audiologically as having Auditory Neuropathy/ Auditory Dsy-synchrony. The EOE-c were scrutinized by using the linear click in the intensity of 60 dB SPL, and to the contralateral noise stimulation, the white noise was employed in the intensity of 65 dB SPL, with the monitoring of the level of sound pressure generated in the external auditory conduit, by using the microphone probe. The results have shown that in children with normal hearing, besides the reduction of amplitude of the EOE-c, it was noticed their suppression, that is, the absence of the record of the EOE-c with the contralateral noise stimulation. It was observed that the contralateral noise stimulation havent provoked significative change in the amplitude of the EOE-c in children with Auditory Neuropathy/ Auditory Dsy-synchrony. This study allowed us to conclude that the amplitude of EOE-c in children with normal hearing presented a different statistical result in the group of children with Auditory Neuropathy/ Auditory Dsy-synchrony in the presence of the contralateral noise stimulation and the average of the amplitude reduction of the EOE-c in the face of children with normal hearing is statistically higher than the amplitude reduction of the EOE-c in the children with Auditory Neuropathy/Auditory Dsy-synchrony.

Hair cell trauma from aminoglycosides, which may lead to permanent loss of hair cells in mammals, was studied physiologically in frogs by measuring an auditory evoked potential (AEP) in Rana pipiens. The AEP was evaluated in order to measure threshold shift (TS) and recovery from TS after the administration of the aminoglycoside antibiotic, gentamicin. To obtain an AEP, chronic electrodes were implanted into the cranium near the cochlear nucleus. The frogs were then exposed to frequency-specific narrow band ~clicks" which included a single period 1 kHz sinewave, and a computer synthesized high frequency and low frequency click. Amphibians have two hearing organs, the amphibian and basilar papillae, sensitive to low (150-1500) and high (1500-2000) frequencies, respectively. The low (AP) and high (BP) frequency clicks were created to stimulate specifically the corresponding papillae. After normal thresholds were recorded for each frog, gentamicin sulfate, 200 μM, 300 μM, or 400 μM, was injected bilaterally into the otic capsules. Thresholds were recorded until the TS had disappeared, allowing the threshold recovery period to be measured. The injections of 200 μM yielded a 10 dB change in one animal and no change in two others. The injection of 300 μM into 10 frogs and 400 μM into 20 frogs yielded at least a 10 dB change in 60% and 93% of the frogs, respectively, with the concentration of 400 μM producing threshold shifts of 20 dB. Thus, the threshold shifts were dose-dependent. Recovery times varied between six and fourteen days. No apparent differences between thresholds for the high frequency click, low frequency click and sinewave clicks were observed.

This thesis presents data which support cochlear involvement in attentional listening. It has been previously proposed that the descending auditory pathways, in particular the medial olivocochlear system, play a role in reducing the cochlea's response to noise in a process known as antimasking. This hypothesis was investigated in human subjects for its potential impact on the detection of signals in noise following auditory cues. Three experimental chapters (Chapters 3, 4 and 5) are described in this thesis. Experiments in the first chapter measured the effect of acoustic cues on the detection of subsequent tones of equal or different frequency. Results show that changes in the ability to detect signals following auditory cues are the result of both enhanced detection for tones at the cued frequency, and suppressed detection for tones at non-cue frequencies. Both effects were measured to be in the order of ~3 dB. This thesis has argued that the enhancement of a cued tone is the implicit result of an auditory cue, while suppression of a probe tone results from the expectation of a specific frequency based on accumulated experience of a listening task. The properties of enhancement support the antimasking hypothesis, however, the physiological mechanism for suppression is uncertain. In the second experimental chapter, auditory cues were replaced with visual cues (representing musical notes) whose pitch corresponded to the target frequency, and were presented to musician subjects who possessed absolute or relative pitch. Results from these experiments showed that a visual cue produces the same magnitude of enhancement as that produced by an acoustic cue. This finding demonstrates a cognitive influence on the detection of tones in noise, and implicates the role of higher centres such as those involved in template-matching or top-down control of the efferent pathways. The final experimental chapter repeated several of the experiments from the first chapter on subjects with various forms of hearing loss. The results indicate that subjects with an outer hair cell deficit (concomitant with a sensorineural hearing loss) do not exhibit an enhancement of cued frequencies or a suppression of unexpected frequencies to the same extent as the normal-hearing subjects. In addition, one subject with a long-standing conductive hearing loss (with normal cochlear function) produced an enhancement equivalent to that of the normalhearing subjects. These findings also support the role of the medial olivocochlear system and the outer hair cells in antimasking. It is the conclusion of this thesis that enhancement most likely results from a combination of changes in receptive field characteristics, at various levels of the auditory system. The medial olivocochlear system is likely to be involved in unmasking a portion of the signal at the cochlear level, which may be influenced by both acoustic reflex pathways or higher centres of the brain.

[Truncated abstract] The mammalian cochlea receives an efferent innervation which originates in the superior olive. Known collectively as the olivocochlear system, this efferent innervation can be divided into lateral and medial systems. While the function of the lateral efferent system in the cochlea is still unknown, previous studies have identified both excitatory and inhibitory changes in sound-evoked and spontaneous cochlear responses attributable to the lateral efferent system. One of the neurotransmitters in the lateral efferents is the catecholamine dopamine, which in the central nervous system is known to exert inhibitory and excitatory effects by activating different receptor subtypes. The first experiments in this thesis were designed to determine if activation or blockade of different dopamine receptor subtypes in the cochlea could lead to both excitatory and inhibitory changes in sound-evoked and spontaneous cochlear responses. Adult guinea pigs were anaesthetised (Nembutal and Hypnorm) and highly specific D1/5 (SKF 38393, SKF 81297, SCH 23390), D2 ((+) PHNO, L 741, 626) and D3 (PD 128907, U 99194A) receptor agonists and antagonists were perfused through the cochlea for 15 minutes. Sound-evoked (compound action potential, summating potential, cochlear microphonic) and spontaneous cochlear responses were recorded before and after perfusion. Remarkably, activating or blocking D1/5 or D2 receptor subtypes resulted in the suppression of CAP amplitudes. These findings are paradoxical as the agonist data suggest that the D1/5 and D2 receptor subtypes are inhibitory, but the antagonist perfusions suggest that these receptors are excitatory. We propose that the presence of an agonist induces a process of receptor desensitisation which would elicit changes akin to receptor antagonism. If this is indeed the case then our agonist findings are spurious and require further interpretation. ... The suppression of the cochlear microphonic suggests that dopamine receptor influence is not confined to the primary afferent dendrite may also include the active process of the outer hair cells. The D1/5 and D2 antagonist data also suggests that dopamine receptors are activated by intrinsic dopamine. Therefore, we attempted to investigate the effects of putative dopamine depletion of the cochlea and found that application of the dopaminergic neurotoxin MPTP causes changes in both neural and hair cell responses which have not been reported before. However, we also demonstrated that tyrosine hydroxylase positive nerve fibres are still present in MPTP treated cochleae which suggests that dopamine is still present in these cochleae. Furthermore, we observed significant electrophysiological changes in these same cochleae when these were exposed to a D2 receptor antagonist which again supports the presence of intrinsic dopamine in these 'depleted cochleae'. These data suggest that the currently accepted method of acute dopamine depletion using MPTP is insufficient and different methods must be developed in the future.

[Truncated abstract] The mammalian inner ear is innervated by the efferent olivocochlear system which is divided into medial and lateral systems. In anaesthetised animals, medial olivocochlear (MOC) axons can be electrically stimulated at the floor of the IVth ventricle. MOC stimulation suppresses the spontaneous activity and sound-evoked responses of primary afferents by its actions on outer hair cells. Effects of MOC stimulation have been also reported on responses of neurons in the cochlear nucleus, the first central auditory center receiving cochlear input. However, very little is known about the net results of MOC effects in higher order neurons. This issue was investigated by electrically stimulating MOC axons at the IVth ventricle and recording extracellular single unit activities in the central nucleus of the inferior colliculus (CNIC) of anaesthetised guinea pigs. For the first part of the study, anatomical and neurophysiological studies were carried out to establish that the focal midline MOC stimulation can selectively stimulate MOC axons without any current spread to adjacent ascending fibers. The MOC stimulation and CNIC recordings were then carried out in a series of experiments that included normal hearing animals, animals treated acutely with gentamicin (in which the acetylcholine-mediated peripheral suppression of the olivocochlear efferents is selectively eliminated) and partially deafened animals. ... However, in other CNIC neurons, effects could not be so explained, showing either additional suppression or even marked excitatory effects. (4) MOC stimulation also suppressed the spontaneous activity of CNIC neurons in normal hearing animals. When similar efferent stimulation was carried out in partially deafened animals, the abnormally high spontaneous activity of some CNIC neurons in the deafened frequency regions was also transiently suppressed by MOC shocks. The results from this study clearly demonstrate that the MOC system can modulate the responses of midbrain neurons in a more complex manner compared to the effects seen in the periphery. The more complex effects seen for responses to tones in quiet and in noisy background are likely to result from a complex interplay between altered afferent input in the cochlea and central circuitry. In addition, the ability of MOC efferents in suppressing the normal and abnormal spontaneous activity in the midbrain also could have implications for the role of the descending system in the pathophysiology and treatment of tinnitus.

Thesis (Ph.D.)--University of Western Australia, 2007.