Temporal Processing In The Superior Olivary Complex: Impact Of Deafness And Peripheral Electrical Stimulation Strategies
Funder
National Health and Medical Research Council
Funding Amount
$225,500.00
Summary
The brain can use timing or temporal information to extract the frequency and location of sound. Timing information is coded by the pattern of responses of brain cells that match the period of the sound wave. These responses can be measured as small voltage spikes or action potentials. Integration of these responses from one brain-processing site to another relies on precise (temporally matched) firing among a population of cells that are activated in response to sound. Sound localisation relies ....The brain can use timing or temporal information to extract the frequency and location of sound. Timing information is coded by the pattern of responses of brain cells that match the period of the sound wave. These responses can be measured as small voltage spikes or action potentials. Integration of these responses from one brain-processing site to another relies on precise (temporally matched) firing among a population of cells that are activated in response to sound. Sound localisation relies on this temporal integration from information coming from both ears. Specifically, the integration of this information relies on the balance of incoming inputs from both ears, which maintains an appropriate time window depending on the location of sound in space. Recent evidence suggests that in deafness this process of integration is disrupted which may be possibly due to an inability to regulate the coherent activation of cells. This has implications for cochlear implant users whose ability to process temporal information is compromised by a loss of temporal coding ability resulting from prior deafness. In this project we will measure voltage changes occurring inside cells of the superior olivary complex, which contains a group of structures that integrate input from both ears. We will examine the ability of these cells to process temporal information in normal and deafened conditions. This study will lead not only to an understanding of basic mechanisms for auditory coding but also to improved electrical stimulation strategies for patients with cochlear implants.Read moreRead less
Extraction Of Key Features Of Natural Speech By Ventral Cochlear Nucleus Neurons
Funder
National Health and Medical Research Council
Funding Amount
$225,330.00
Summary
Little is known about how speech is processed and transformed by the central auditory pathway, and how the critical temporal and spectral features that identify a speech sound segment (a phoneme) are extracted. To date, most studies have approached this issue by using synthetic speech and examined the responses of the peripheral auditory nerve only. The aim of this study is to examine how important features of naturally-spoken speech are encoded by the cochlear nucleus (CN) - the first station i ....Little is known about how speech is processed and transformed by the central auditory pathway, and how the critical temporal and spectral features that identify a speech sound segment (a phoneme) are extracted. To date, most studies have approached this issue by using synthetic speech and examined the responses of the peripheral auditory nerve only. The aim of this study is to examine how important features of naturally-spoken speech are encoded by the cochlear nucleus (CN) - the first station in the auditory pathway located in the brainstem. The CN is a complex of different cell types that have the capacity to transmit, transform, and encode complex acoustic information in different ways. The proposed experiments involve recording the bioelectrical signal from single CN cells in anaesthetised rats while presenting naturally-spoken syllables, both in quiet and in the presence of noise. It is important to examine what happens to the neural responses in the latter condition, because all animals must cope with the problem of extracting important signals from background noise. While noise clearly interferes with the perception of another sound, the auditory system is in fact quite good at extracting signals in the presence of noise. This is well demonstrated by our ability to understand speech in the presence of quite high noise levels. This ability is severely degraded in the hearing impaired. Thus, one of the aims of this study is to examine the mechanisms and limits of the CN's ability to encode speech in a noisy background. A greater understanding of the mechanisms the nervous system uses to extract critical features of speech will not only build on our knowledge of auditory brainstem processes, but may also provide clues to improving processing strategies for cochlear implants.Read moreRead less
Improved Perception Of Temporal Information In Electrical Signals For Profoundly Deaf Users Of Cochlear Implants
Funder
National Health and Medical Research Council
Funding Amount
$170,440.00
Summary
The ultimate goal of this project is to improve the ability of cochlear implant users to understand speech. The way in which a speech signal varies in amplitude over time provides useful information to the listener about the content of the speech signal. Currently, the way that the acoustic signal amplitude is converted to electrical signal amplitude for cochlear implantees does not take into consideration the very significant loudness summation present in multiple-electrode electrical stimulati ....The ultimate goal of this project is to improve the ability of cochlear implant users to understand speech. The way in which a speech signal varies in amplitude over time provides useful information to the listener about the content of the speech signal. Currently, the way that the acoustic signal amplitude is converted to electrical signal amplitude for cochlear implantees does not take into consideration the very significant loudness summation present in multiple-electrode electrical stimulation. That is, when there are multiple sequential current pulses on different electrodes over a short time, the resultant loudness is greater than the loudness due to individual current pulses. The lack of consideration of loudness summation effects has led to the amplitude variations in the acoustic signal not being accurately represented in the loudness variation perceived by the cochlear implantee. This project aims to develop a practical way of more accurately representing speech signal amplitude fluctuations for cochlear implantees by studying the effects of loudness summation. A second aim of the project is to study the effects on perception of using differently-shaped current pulses from those currently used. There is evidence from physiology experiments that using different shapes might cause the electrical stimulation to activate a more narrowly-spaced set of auditory neurons for each electrode. The application of results of both these studies will lead directly to improved perception of speech and other sounds by cochlear implantees, thus improving their communication ability and quality of life.Read moreRead less
Molecular Basis Of Asymptomatic Colonization Of The Human Urinary Tract
Funder
National Health and Medical Research Council
Funding Amount
$461,894.00
Summary
Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for >$1.6 billion in medical expenses each year. It is estimated that 50% of women will develop a UTI in their lifetime. This research aims to understand the processes by which bacteria colonize the human bladder and the surface of urinary catheters. The work has implications for the development of new approaches to prevent and treat UTI ....Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for >$1.6 billion in medical expenses each year. It is estimated that 50% of women will develop a UTI in their lifetime. This research aims to understand the processes by which bacteria colonize the human bladder and the surface of urinary catheters. The work has implications for the development of new approaches to prevent and treat UTI.Read moreRead less
Urinary Tract E. Coli: The Good Guys Versus The Bad Guys
Funder
National Health and Medical Research Council
Funding Amount
$296,150.00
Summary
Escherichia coli is the primary cause of urinary tract infection (UTI) in the developed world. In Australia alone, E. coli affects more than 250,000 yearly to the extent where they require medical intervention. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime and in the USA UTIs result in $1.6 billion in medical expenses each year. Uropathogenic E. coli (UPEC) strains readily form biofilms on indwelling catheters and recent evidence suggests that ....Escherichia coli is the primary cause of urinary tract infection (UTI) in the developed world. In Australia alone, E. coli affects more than 250,000 yearly to the extent where they require medical intervention. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime and in the USA UTIs result in $1.6 billion in medical expenses each year. Uropathogenic E. coli (UPEC) strains readily form biofilms on indwelling catheters and recent evidence suggests that they also form biofilm-like aggregates in the bladder. No treatment other than antibiotics (often inefficient due to resistance) is currently available. E. coli is also the most frequent cause of asymptomatic bacteriuria (ABU). ABU occurs in up to 6% of healthy individuals and affects high risk groups such as the elderly and diabetics. In general, most patients with ABU do not need treatment and in many cases the colonizing organism actually helps to prevent infection by other more virulent bacteria. The aim of this project is to compare UPEC and ABU E. coli for differences associated with virulence and biofilm growth. The project will generate a comprehensive and defined strain bank relative to E. coli that cause UTI. Understanding biofilm growth by this organism may lead to the development of improved and-or novel treatments. Furthermore, increased knowledge of ABU E. coli is essential if we are to fully explore the possibility of employing these organisms as probiotic agents to prevent infection by other pathogens in specific high risk patient groups.Read moreRead less
Coordinate Expression Of Virulence Factors In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Escherichia coli is a versatile pathogen capable of causing a range of disease types including diarrhoea, dysentery, haemolytic uremic syndrome, bladder and kidney infections, septicaemia, pneumoniae and meningitis. Infections due to pathogenic E. coli may be limited to mucosal surfaces or can disseminate throughout the body. Amongst the different classes of pathogenic E. coli, diarrheagenic strains (namely enterotoxigenic and enteroinvasive E. coli) are responsible for the death of an estimated ....Escherichia coli is a versatile pathogen capable of causing a range of disease types including diarrhoea, dysentery, haemolytic uremic syndrome, bladder and kidney infections, septicaemia, pneumoniae and meningitis. Infections due to pathogenic E. coli may be limited to mucosal surfaces or can disseminate throughout the body. Amongst the different classes of pathogenic E. coli, diarrheagenic strains (namely enterotoxigenic and enteroinvasive E. coli) are responsible for the death of an estimated one million humans per year, mainly in third world countries. The majority (80%) of urinary tract infections (UTIs) in humans are caused by E. coli and in Australia alone there are about 250,000 cases per year. It is estimated that one in four women and one in twenty men will develop a urinary tract infection in their lifetime. Pathogenic E. coli strains are normally equipped with multiple virulence factors and there is mounting evidence that the expression of such factors is finely orchestrated by mutual regulatory cross-talk. For example, expression of flagella (which provide motility) and adhesins (which provide attachment) are fundamentally counteracting phenotypes, yet the molecular and genetic mechanisms that coordinate their expression are unknown. I plan to examine inter-system cross-regulation of bacterial surface structures (namely adhesins, autoaggregaters, capsules and flagella). The aim is to understand on the molecular level how microorganisms orchestrate expression of virulence factors and will have consequences for our understanding of microbial pathogenicity. The strategy outlined may lead to new routes for strain attenuation and perhaps a method for vaccine strain construction. The research will be performed in collaboration with international high profile partners.Read moreRead less
Nanostructured Porous Silicon For Ophthalmic Implants
Funder
National Health and Medical Research Council
Funding Amount
$536,657.00
Summary
Blindness exerts major physical, emotional and economic constraints upon the sufferer. Our goal is to develop novel nanostructured porous silicon-based implants to improve outcomes for patients prone to recurrent episodes of inflammation in the eye, or with visual loss following ocular trauma or infection. Treatments are available, but are not always effective. Porous silicon is a non-toxic, non-inflammatory, biodegradable material that can be loaded with drugs or cells for transfer to the eye.