The characteristics of a cochlear implant (CI) filterbank determine the coding of spectral and temporal information in it. Hence, it is important to optimise the filterbank parameters to achieve optimal benefit in CI users. The present thesis aimed at modelling how the manipulation of the filterbank analysis length and the assignment of spectral channels may effect CI speech perception, using CI acoustical simulation techniques. Investigations were carried out to study the efficacy of providing additional spectral information in low and/or mid frequency channels using a longer filterbank analysis window, with respect to CI processed speech perception in various types of background noise. However, the increase of filterbank analysis length has an associated trade-off, which is a reduction in temporal information. Only a few CI acoustic simulations studies have modelled the characteristics of the FFT filterbank, the most commonly used filterbank in commercial CI processors. An initial experiment was carried out to validate the CI acoustical simulation technique used in the present thesis that implemented an FFT filterbank analysis. Next, the effect of a reduction in temporal information with the increase of the FFT analysis window length was studied. A filterbank with 16 ms analysis window, without the implementation of its finer spectral coding abilities, performed marginally poorer to that of a 4 ms analysis window in a sentence recognition test. The finer spectral coding abilities of the filterbank with 16 ms analysis window, when implemented, revealed that CI processed speech perception in noise could be significantly improved if additional spectral information is provided in the low and mid frequencies. The assignment of additional spectral channels to the low and mid frequencies led to a corresponding reduction in spectral channels assigned to high frequencies. However, no detrimental effect in speech perception was observed as long as at least two spectral channels represented information above 3 kHz. The assignment of additionallow and mid frequency spectral channels also led to significant levels of spectral shift. The significant benefits from additional low and mid frequency information, however, were lost when the effects of spectral shift were introduced in acute experiments, without any training or acclimatisation period. The findings of the present thesis highlight that a longer filterbank analysis, such as 16 ms, may be implemented in CI devices without the fear of any perceptual cost due to a reduction in temporal information, at least for tasks that do not require talker separation. Providing additional low and mid frequency spectral information with a longer filterbank analysis has the potential to improve CI speech perception. However, to obtain potential benefits, the effects of spectral shift should be overcome. The findings of this thesis, however, need to be interpreted considering the limitations of CI acoustical simulation experiments.

Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL) is a rapid loss of hearing caused by damage to the cochlea (inner ear) or auditory nerve. Spontaneous recovery has been seen in 32% - 81%. The incidence of the ISSNHL has been estimated to be between 5 and 20 per 100,000 per year. Different theories (infections, vascular catastrophes, immunologic damage or intracochlear membrane break) about the etiology have resulted in different treatment policies. The effect of therapy is difficult to evaluate for a single physician who sees just a few patients annually. The aim of the present thesis was to analyze the management and treatment of ISSNHL patients in Sweden with regard to outcome. A national database was developed for Sweden with half of all ENT clinics in Sweden participating by submitting a questionnaire for each patient with SSNHL. The questionnaire covered the patient’s background, current disorder, past and family history of different diseases, examinations and treatment. Audiograms at the onset of SSNHL and after three months were requested. All results were analyzed using ordinal logistic regression looking for interactions with hearing recovery and remaining hearing loss as dependent variables. Independent of treatment or no therapy heredity for hearing loss (I, II), older age (I, II) and presence of vertigo (II) was significantly associated with negative outcome. 40% of all patients had an MRI or CT, where 3 – 4% had acoustic neuroma. 24% of patients with ISSNHL who had hematological tests taken had one or more pathological findings. Blood screening varied from simple routine tests to a complete analysis with such tests as HSP70, Anti-Neutrophilic Cytoplasmic Antibodies (ANCA) and Borrelia tests. There was no association between any of these laboratory tests and either hearing improvement or remaining hearing loss evaluating the tests separately (I, II) or after categorization in comparison with those who had normal laboratory findings (II). Patients with hearing loss in the mid-frequency region had significantly better odds for hearing improvement compared to the other three frequency regions (low, high and “flat loss”). Almost 60% of patients with ISSNHL were medically treated, of which nearly 90% got corticosteroids. The medication had no association with either hearing improvement or remaining hearing loss. However, patients who were prescribed rest or sick leave had higher odds for hearing improvement regardless of other treatment. Those patients who did not receive any treatment at all also came significantly later to the ENT clinics than those treated medically and consequently had worse prognosis. Conclusion: There is no standard program for management or treatment of ISSNHL in Sweden. The diagnostic protocol varies. MRI is an underused resource to get specific diagnoses for the condition especially acoustic neuromas. Regardless of pathological findings, treatment is mainly limited to corticosteroids or no medication with no difference in outcome. A randomized placebo controlled study is necessary to evaluate whether there is an effect of corticosteroids on ISSNHL.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and yearly include 500 000 new cases worldwide. The outcomes for these patients have not been significantly improved over the last decades and the five year survival is still around 50 %. Establishing predictive markers of treatment response will have great impact on the clinical management of this disease. The aim of this thesis was to elucidate markers of intrinsic response to radiotherapy and cisplatin. Combining expression patterns of 14 proteins and identifying mutations in the p53 gene, we were able to incorporate both protein and genetic changes to create a predictive model termed Number of Negative Points (NNP). We used the NNP model to statistically calculate the combination of factors that had the best correlation to intrinsic radiosensitivity (IR). We established that a panel of three markers, epidermal growth factor receptor (EGFR), survivin and splice site/missence mutations of p53, had the best correlation to IR (R=0.990, p<0.0001). We also conducted gene expression analysis to investigate what genes and gene ontologies that are different between cell lines with varying IR. Furthermore, we wanted to identify key regulator genes with central positions of molecular networks, which were generated from the transcripts included in the deregulated gene ontologies. A transcriptional profile of 28 key regulator genes was generated. Immunoblot analysis supported deregulation at the protein level of three markers implicated from the transcriptional profile. We propose that these proteins, notch1, thrombospondin 1, and pai‐1 are predictive markers of IR. Finally, on a subset of cell lines with sensitivity or resistance to cisplatin, we performed gene expression analysis. Markers of intrinsic cisplatin sensitivity (ICS) such as gene ontologies and key regulators of molecular networks were proposed and five genes, APOE, CTNNB1, MMP7, MMP13, and THBS1 were selected for further analysis. Quantitative polymerase chain reaction (qPCR) analysis of these genes in 25 cell lines established that MMP7 (p=0.0013) and MMP13 (p=0.058) are possible predictive markers of ICS. The markers of IR and ICS presented here could, if confirmed in a clinical setting, guide clinicians in the choice of treatment and thus give a more individualized and effective therapy for patients with HNSCC.

No description available.

Background Swallowing problems are common in Parkinson’s disease, and these affect morbidity and mortality largely due to aspiration-induced pneumonia. Even mild dysphagia affects patient Quality of Life. Deep Brain Stimulation (DBS), a surgical treatment for Parkinson’s disease, improves overall motor function, though the effect of DBS on swallowing function is not clear. The aim of the studies in this thesis was to improve our understanding of the effect from DBS of caudal zona incerta and subthalamic nucleus on pharyngeal swallowing function. Specific aims were to compare DBS effects over time postoperatively (6 & 12 months) for swallowing function, on and off stimulation, with a preoperative baseline assessment in order to identify possible negative swallowing effects of DBS. Methods Eight patients with DBS in caudal zona incerta and eleven patients with DBS in subthalamic nucleus were included in the two studies. The effect of DBS on swallowing function was evaluated by self-estimation on a visual analogue scale and fiberoptic endoscopic evaluation of swallowing function with a predefined swallowing protocol including Rosenbek’s Penetration/Aspiration Scale, Secretion Severity Scale,preswallow spillage, pharyngeal residue and pharyngeal clearance. The patients with caudal zona incerta DBS also answered questions regarding swallowing-related Quality of Life. All patients received L-dopa treatment during postoperative assessments. Results There was no clear effect of DBS on swallowing function in the two samples. The occurrence of aspiration, secretions, pharyngeal residue or clearance was not affected by the surgery or the stimulation. In the subthalamic nucleus DBS sample, self-estimations revealed an improvement with stimulation turned on. For the caudal zona incerta DBS patients, no effect of DBS was seen on the results from the swallowing-related QOL questions. Conclusion Subthalamic nucleus DBS and caudal zona incerta DBS did not appear to have a negative effect on swallowing function in this cohort. Patients with subthalamic nucleus DBS reported a self-perceived improvement in swallowing function after DBS. There appears to be no increased risk for aspiration or penetration due to surgery or stimulation regardless of stimulation site. Since the sample sizes in these cohorts are small, the findings need to be confirmed in larger studies.

Tinnitus, often defined as the perception of sound in the absence of an external stimulus, affects millions of people worldwide and, in extreme cases, can be severely debilitating. While certain changes within the auditory system have been linked to tinnitus, the exact underlying causes of the phenomenon have not, as yet, been elucidated. Animal models of tinnitus have considerably furthered understanding of the some of the changes associated with the condition, allowing researchers to examine changes following noise exposure, the most common trigger for tinnitus. This thesis documents the development of an animal model of tinnitus, using the guinea pig to examine neural changes following induction of tinnitus. In the first study, a novel adaptation of a behavioural test was developed, in order to be able to determine whether guinea pigs were experiencing tinnitus following the administration of sodium salicylate, a common inducer of tinnitus in humans. This test relies on a phenomenon known as prepulse inhibition, whereby a startle response can be reduced in amplitude by placing a gap in a low-level, continuous background noise immediately prior to the startling stimulus. The hypothesis for this test is that if the background sound is adjusted to be similar to an animal’s tinnitus (induced artificially following noise exposure or drug administration), the tinnitus percept will fill in the gap and the startle response will not be reduced. The results from this first study indicated that using the Preyer reflex (a flexion of the pinnae in response to a startling stimulus) as this startle measure was more robust in guinea pigs than the commonly-used whole-body startle. Furthermore, transient tinnitus was reliably identified following salicylate administration. Following the development and validation of this test, a study was conducted to determine whether guinea pigs experienced tinnitus following unilateral noise exposure. Neural changes commonly associated with the condition (increases in spontaneous firing rates and changes in auditory brainstem responses) were examined, to determine whether there were any differences between animals that did develop tinnitus following noise exposure and those that did not. Two different methods were applied to the behavioural data to determine which animals were experiencing tinnitus. Regardless of the behavioural criteria used, increased spontaneous firing rates were observed in the inferior colliculus of noise-exposed guinea pigs, in comparison to control animals, but there were no differences between tinnitus and no-tinnitus animals. Conversely, significant reductions in the latency of components of the auditory brainstem response were present only in the tinnitus animals. The final study examined whether the original hypothesis for the behavioural test (that tinnitus is filling in the gap) was valid, or whether there was an alternative explanation for the deficits in behavioural gap detection observed previously, such as changes in the temporal acuity of the auditory system preventing detection of the gap. Recordings were made in the inferior colliculus of noise-exposed animals, separated into tinnitus and no-tinnitus groups according to the behavioural test, as well as unexposed control animals, to determine whether there were changes in the responses of single-units in detecting gaps of varying duration embedded in background noise. While some minor changes were present in no-tinnitus animals, tinnitus animals showed no significant changes in neural gap detection thresholds, demonstrating that changes in temporal acuity cannot account for behavioural gap detection deficits observed following noise exposure. Interestingly, significant shifts in the response types of cells were observed which did appear to relate to tinnitus. The present data indicate that the Preyer reflex gap detection test is appropriate for examining tinnitus in guinea pigs. It also suggests that increases in spontaneous firing rates at the level of the inferior colliculus cannot solely account for tinnitus. Changes in auditory brainstem responses, as well as shifts in response types, do appear to relate to tinnitus and warrant further investigation.

The main purpose of this work is to explore whether and how much multichannel signal processing strategies can be beneficial for improving the detection procedure for auditory late response (ALR) in clinical applications in comparison with single channel recording. To achieve this target, four multichannel noise reduction methods based on independent component analysis (ICA) were proposed for noise reduction for multichannel recording of ALR. The four alternative component selection strategies introduced in this work are: Magnitude Squared Coherence (MSC) [based on coherency of the ICs with an evoking stimulus], the maximum Signal to Noise Ratio (Max-SNR) of ICs over a particular interval, the kurtosis (maximum non-Gaussianity of the ICs), and minimum entropy of the ICs. The proposed methods are applied for the noise reduction of auditory late response (ALR) data captured using 63 channel EEG from 10 normal hearing participants. The performances of the proposed methods for improving signal quality were compared with each other and also with the single channel alternatives. All automated component selection approaches produced high SNR for multichannel ALR data. MSC-ICs produced significantly higher SNR than Max-Kurt-ICs or Min-Entropy-ICs. However the performance of MSC-ICs and Max-Fmp-ICs were not significantly different. Therefore, the MSC-ICs approach was selected for further work. MSC-ICs were used for three different clinical applications: Finding hearing threshold level, exploring the effect of attention and exploring inter- and intra- subject variability. The results for MSC-ICs were compared to the single channel signal processing alternative of weighted averaging. The results confirm that the multichannel signal processing can significantly improve the detection procedure for threshold measurement and for measuring the effects of attention. However, no significant enhancement was found for detecting inter- and intra- subject variability with multichannel processing over single channel alternative. The MSC-ICs method was also used in an application for removing cardiac artifact from the ALR recordings and the results was compared with an existing artifact rejection platform based on constraint ICA (cICA). The results of this comparison show that the proposed method can significantly improve the quality of cardiac artifact rejection from ALR data. Finally, the use of MSC-ICs was explored for reducing the required time for recording ALR. Time reduction was investigated in two senses: 1. reducing the number of stimulus repetitions. 2. Optimizing the position and the number of the recording electrodes in multichannel recordings (potentially saving the time required to place many electrodes on the scalp). The results show that using multichannel processing can significantly reduce the number of stimulus repetitions and consequently the time of recording in comparison with the single channel alternative. Minimum required number of stimulus repetition (average over10 subjects) for having SNR equal to single channel processing at Cz was found to be 74 for un-weighted averaging and 85 for weighted averaging. Moreover, the results of optimal electrode placement procedure confirm that, the ALR can be recorded form the vertex (with the same SNR as when ALR is recorded using 63 channels) by using fewer numbers of electrodes. For the data set of this study (10 normal hearing adults) the same SNR as with 63 channels was achieved by using 40 channels. Placing 40 electrodes (instead of 63) on the scalp decreases the required time for recording ALR considerably, i.e. 53% improved.

No description available.

Over a four month period from 1 st November 1998 to 28th February 1999 a randomised prospective study was undertaken in 75 patients with peritonsiller abscess (PTA) to determine the treatment modality that is most effective in alleviating the excruiating pain and discomfort associated with the condition. The patients were divided into three treatment groups. There were 25 patients in each group. Group A patients were treated with intravenous antibiotics and intra muscular opiates, Group B aspiration and oral antibiotics and Group C incision and drainage and oral antibiotics. Pain relief was objectively assessed with each treatment modality by measuring the upper to lower incisor distance, 15 mins, 24 hours and 48 hours and oral intake at 2 hours, 24 hours and 48 hours after the initial treatment. The improvement of the mean upper to lower incisor distance 15 minutes after the initial treatment was 5% in Group A, 38% in Group B and 100% in Group C. Twenty four hours later the improvement was 30% in Group A, 111 % in Group B and 125% in Group C. None of the patients in Group A were able to take fluid orally at 2 hours. Only 2 patients (8%) could in Group B and 23 patients (92%) in Group C. 24 hours later, 15 patients (60%) could take fluid orally in group A, 19 (76%) in group B and 25 (100%) in group C. Treatment failures were those patients in whom the trismus, odynophagia and pyrexia failed to subside after 48 hours. There were 8 patients (30 per cent) in group A, 6 (24%) in group B and none in Group C. The 14 failures were successfully treated with incision and drainage. The conclusion derived from this study is that incision and drainage is superior to intravenous antibiotic and aspiration in alleviating the pain and discomfort associated with peritonsillar abscess. / Thesis (M.Med.)-University of Natal, 1999.

The performance of our hearing system degrades with age, causing a reduction in our ability to understand speech. This thesis describes the design of a personal audio system, aimed at enhancing the audio signal from a TV, for hard of hearing listeners. Such system generates a zone of high acoustic pressure in a specific area of a room, whilst minimising the sound radiated to other zones. In order to obtain a very narrow sound radiation, superdirective techniques are used. Such techniques improve the performance of an array of small dimensions at mid and low frequencies, but they can require the use of a large amount of power and can be very sensitive to errors in the source transfer functions. A practical balance between performance and array effort is achieved in a design that uses phase-shift sources. Two arrays have been built. The first array uses 8 phase-shift sources and provides a high directionality in the free field. The second array uses 4 phase-shift sources vertically plus 8 horizontally and is more directional in a 3D sense, hence reducing the reverberant field excitation. The design of superdirective filters has been considered in both time and frequency domains. The effect of the reverberant field in the performance of superdirective radiators has also been investigated, by first examining how the radiation pattern is modified, and then by observing how the reverberant field affects the robustness of the control. The performance has been assessed by means of off-line simulations with point source Green functions and measured transfer responses, and by real time measurements in free-field and reverberant environments. The later chapters of the thesis consider the subjective assessment of arrays as an aid for speech intelligibility. The assessment has first been performed using an objective metric, in particular the speech transmission index (STI). The performance has also been assessed in a subjective study, in which 30 participants have judged the increase in intelligibility. A cochlear model has also been utilised to investigate equalisation methods that minimise masking and provide a better speech intelligibility, particularly for the hearing impaired. Although this has not been tested with behavioural experiments, STI simulations have predicted that it can lead to an intelligibility improvement.