NIHRDataInsights/HRCSData huggingface dataset:
Title: The neural basis of perceptual sensitivity to sound in auditory cortex of the mouse.
Funder: Medical Research Council

Abstract: The natural world consists of many separate and interfering sound sources. In animals, these sounds converge at the cochlea, which reports sound frequency to the brain. Somehow, the brain is able to separate and group frequency information into distinct auditory objects in order to build accurate perceptions of the world. The ability to detect salient sounds in the environment is critically important to the survival of many animal species, and is a key factor in human communication. Such sounds are often embedded within noisy backgrounds, reducing the signal-to-noise ratio at which the auditory system must operate, and making detection more difficult. The brain is known to exploit certain features of natural sounds in order to improve signal detection, but the mechanisms by which it performs these tasks remain largely unknown. Therefore, the overall aim of this project is to understand how activity in auditory cortex influences signal perception in the presence of background noise. By modulating the amplitude of background noise coherently, it is possible to improve signal detection. This is a well-characterised psychoacoustic phenomenon called co-modulation masking release, the mechanism of which I shall investigate using electrophysiological recordings in the auditory cortex of anaesthetised and awake-behaving mice. My key goals are: 1. To determine how modulations in background noise influence the representation of acoustic signals in auditory cortex. 2. To determine how the perceptual interpretation of a stimulus is influenced by auditory cortical activity. First, using extracellular population recordings, I will establish how patterns of firing within populations of auditory cortical neurons are affected by noise modulations. Second, using whole cell recordings from single cells, I will determine the mechanisms that underlie these changes. Subsequently, mice will be trained to detect pure tones embedded in modulated background noise in a behavioural task. I will then record neuronal activity in auditory cortex whilst they perform this task, and therefore directly relate neuronal activity to perceptual outcome. Finally, I will determine whether single neuron stimulation in auditory cortex can influence task outcome. Having characterised the mechanisms underlying signal detection in the brain, they may then be applied to improve synthetic listening devices: both cochlear implant technology for the hearing impaired, and other machine listening systems (e.g. for accurate speech recognition in noisy environments). Furthermore, by studying how complex sound information is processed in the auditory cortex, we may uncover fundamental principles about how neural networks perform sensory discriminations.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: EAR;NEUROLOGICAL
Title: Brain Mechanisms underlying Performance in ITD Processing: Biophysics to Behaviour
Funder: Medical Research Council

Abstract: Binaural hearing, particularly the ability to detect small differences in the timing of sound at the two ears (interaural time differences, ITDs) underpins the ability to localize sound sources, and is important for decoding complex spatial listening environments into separate objects ? a critical factor in ?cocktail-party listening?. The current proposal will address critical questions as to how the brain generates sensitivity to ITDs, assesses performance limits in ITD processing for a range of relevant listening conditions, including the use of ITDs carried in the ?envelope? structure of modulated sounds (critical to cochlear implantation) and demonstrates how a general principal of neural coding ? that of efficiency ? is evident in the biophysical properties of binaural neurons. The programme of worll will exploit in vivo and in vitro physiological recordings in small animals to examine basic mechanisms of binaural hearing, including biophysical and physiological limits to binaural hearing that potentially impact on the development of future hearing technologies. Human psychophysics, brain imaging (magneto-encephalography ? MEG ? and functional MRI) and electrophysiology (EEG) studies will seek to establish mechanisms and performance limits in processing binaural cues for spatial processing. Experiments are also proposed employing non-invasive techniques (MEG) to test more directly the relevance of physiological findings in small animals to the human brain. Theoretical and modeling studies will seek to establish how current models of ITD processing based on psychophysical and neural sensitivity to low-level acoustic cues can be used to inform perceptual and cognitive models of auditory spatial processing. Building on outcomes of my previous research, the proposed programme will establish a coherent and integrated view of binaural hearing in the mammalian brain, one that can be exploited in the development of hearing devices and audio technologies.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: EAR;NEUROLOGICAL
Title: Development and validation of a model of the electrocochlear responses in auditory neuropathy patients.
Funder: Action on Hearing Loss

Abstract: The first aim of the project is to build on existing models of cochlear electromechanics and develop them to the point where the cochlear microphonic and summating potential measured by extratympanic electrodes can be predicted. A second aim is to validate the model against both previously reported findings, and against novel measurements in normally hearing and auditory neuropathy participants. The methods for the modelling phase involves incorporating additional elements into the models to capture the nonlinear characteristics of the inner hair cell receptor potentials for cells arrayed along the basilar membrane, and a model of the propagation of the potentials from the cells through the temporal bone. Simulations will then be carried out to predict the nonlinear responses in otoacoustic emissions, cochlear microphonics and summating potentials for click, pure-tone, and tone-burst stimulation. Simulations of different aetiologies will be performed by changes to the inner hair cell receptor potential characteristics. In the validation phase, electrocochlear responses will be measured in normal hearing and auditory neuropathy participants using extra-tympanic electrodes under various stimulus conditions to allow the non-linearity to be characterised.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.3 MEDICAL DEVICES
Health categories: EAR;NEUROLOGICAL
Title: µLED-based optogenetic auditory midbrain implant
Funder: Action on Hearing Loss

Abstract: Over the last decade the auditory midbrain implant (AMI) has been developed, but the capability is still limited compared to the cochlear implant. Therefore, further improvement and alternative approaches are required. Here we will demonstrate the feasibility of a novel AMI utilising µLED and optogenetic technologies. This project will consist of three phases: (1) Functional mapping of the central nucleus of the inferior colliculus (ICC) and the primary auditory cortex (A1). Using high-density electrode arrays in mice, we will characterise population activity in ICC and A1 simultaneously. Specifically, we will confirm the tonotopic organisation in both structures to guide the following projects. (2) Validation of µLED-based AMI. Controlling ICC activity optogenetically with a µLED array and monitoring A1 activity, we will test the hypothesis that our µLED-based approach can achieve depth-dependent activation in ICC and elicit A1 activity in a topographically organised fashion. (3) Application of µLED-based AMI for presbycusis model. Taking the same approach in a mouse model of age-related hearing loss (presbycusis), we will test the hypothesis that optical stimulation of ICC can restore A1 responses resembling auditory-evoked responses. Thereby we will demonstrate the feasibility of µLED-based optogenetic AMI to benefit patients who cannot receive the cochlear implant.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.3 MEDICAL DEVICES
Health categories: EAR;NEUROLOGICAL
Title: The life course of neuronal microdomains regulating excitability of the auditory nerve
Funder: Dunhill Medical Trust

Abstract: Sensory hair cells in the inner ear transform sound energy into electrical signals which are carried by the auditory nerve to the brain. The individual auditory nerve fibres are wrapped by specialised cells called glia, which form an insulating layer around the fibres. The insulating layer is interspersed by regularly-spaced short gaps, in which reside the proteins responsible for transmitting the electrical signals, and others which anchor them in position. These highly organised regions are known as ‘neuronal microdomains’, and they enable the auditory nerve to transmit fast and precise electrical signals, a requirement for accurate representation of the complex timing cues within sound. Recently, changes to the organisation of the microdomains have been observed to occur during noise-induced hearing loss, confirming the importance of their fine structure for normal hearing. However, very little is known about the processes involved in the formation and maintenance of neuronal microdomains in the inner ear. This project has two main aims. Firstly, I will identify when individual proteins first arrive within different regions of the microdomains in the mouse auditory nerve. The research would use high-resolution microscopy and electrical recordings to study how glia influence the development of nerve fibres, and in turn, how the functional properties of those glia change during nerve maturation. Secondly, I will measure how the fine structure of microdomains change during ageing, and determine whether there are specific losses of protein components that could contribute to age-related hearing loss (ARHL) in mice. ARHL is the most common form of progressive sensory deficit, and is predicted to almost double in the next decade. Recently, studies have demonstrated that connections between hair cells and auditory nerve fibres are disrupted during ageing in both humans and mice. This is proposed to contribute to difficulties in hearing speech in a noisy environment, an early sign of ARHL. It is therefore important to determine whether changes to the nerve fibre microdomains may also contribute to the hearing deficits associated with age. Understanding the molecular components involved in the formation of microdomains is a first step towards identifying potential targets for therapies which could restore function to the auditory nerve in ARHL, or other types of hearing loss where the nerve has been damaged. New procedures developed during the research will help future studies of auditory nerve development and maintenance, and provide new models for testing drug treatments.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: EAR;NEUROLOGICAL
Title: MICA: Novel applications of microphone technologies to hearing aids.
Funder: Engineering and Physical Sciences Research Council

Abstract: Four preliminary ideas will be explored:- A small, sensitive, low-noise microphone could be created using MEMS technology. MEMS microphones with a low-noise characteristic could be made at some cost in terms of distortion, but existing techniques can be used to remove this with digital signal processing, and that processing could be built into an integrated low-noise digital microphone chip. Insertion gain could optimised by placing additional microphones within the ear canal, perhaps using MEMS technology once again, to provide in-situ real-time measurement of ear-canal sound levels. This approach could also save time in the fitting process. The technique could be verified using laser vibrometry. Alternatively laser vibrometry of the tympanic membrane could itself act as the internal microphone. Intra-canal microphones could also support more sophisticated approaches to feedback suppression. The time delay between signals detected from internal and external mikes could be used to discriminate between genuine external sounds and feedback (whose delay would match the acoustic transmission time from the loudspeaker to the external mikes). Existing hearing aids generally use just two microphones and adaptive beam-forming to suppress a single interfering noise in different directions at different frequencies (they produce one "null"). Such systems are programmed to null out the most prominent sound in the rear hemifield and thus improve the SNR of speech sources in front of the listener, but they ultimately have quite low directional sensitivity. Only a small number of commercial systems have attempted alternative approaches (Siemens triano and Phonak's stereoZoom). The key to stronger beam-forming is the use of larger numbers of mikes, perhaps distributed over a pair of glasses. For instance, in principle, an N-microphone systems are capable of directing N nulls in each frequency channel. They can also be used in conjunction with sparse coding.


Research activity codes: 5.3 MEDICAL DEVICES;5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: EAR;NEUROLOGICAL
Title: Peripheral and central mechanisms of hearing impairment, tinnitus and auditory aging: non-invasive studies in humans
Funder: Medical Research Council

Abstract: Auditory signal processing consists of two stages. At the first stage, which is presumed to occur mainly at sub-cortical levels, the auditory system has to extract the informational components of the incoming signal to process perceptual features, such as pitch, sound location or phonological identity. At the second stage, which occurs at the level of auditory cortex, this pre-processed information has to be represented in a way that makes it accessible to higher-order cognitive processes, such as attentional selection or memory storage. In the auditory system, both the information-extraction and the representational stage of the processing can be influenced by top-down, or efferent information. Understanding afferent auditory signal processing and encoding mechanisms and their interplay with efferent modulatory influences is a crucial prerequisite for gaining a better understanding of auditory disability of both peripheral and central origin. The aim of this research strand is, in the first instance, to investigate afferent and efferent mechanisms of auditory signal processing in normal human listeners using both behavioural and non-invasive neuroimaging methods (EEG and fMRI). In the second part of the project, we will then explore, how these mechanisms change with aging, whether or how they can be influenced by non-invasive neuro-stimulation techniques, and how they are affected by cognitive processes such as attention or learning.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: EAR;NEUROLOGICAL
Title: Investigation of low-sound-level auditory processing deficits after chronic exposure to very high noise levels.
Funder: Medical Research Council

Abstract: Noise exposure produced by nightclubs and rock concerts, where sound levels exceed 95 to 100 dB(A), has been shown to produce deficits in processing of signal envelopes by humans. These deficits typically appear with signals presented at low sensation levels (SL) (Stone et al., 2008; Stone and Moore, in revision 2014). Since they have only been identified so far in younger listeners, the intention is to recruit an older group of hearing impaired (HI) listeners, in order to characterise a more mature manifestation of the deficit. This older group will be sub-divided according to self-report into those with a history of high or low exposure to these recreational noises. The project aims to improve diagnosis of the extent of the deficit previously identified in the processing of low-SL modulations. We propose to measure auditory processing at low SLs in narrow frequency regions in subjects with different aetiologies to their hearing loss. Specifically we will use psychophysical and electro-physiological measures to characterize frequency-specific auditory abilities as well as a signal processing technique to selectively degrade only low-level portions of target speech. We will also investigate the effects of varying the speed of dynamic range compression to modify the extent of hearing-aid-induced distortions to the temporal envelopes of signals. Apart from remediation, the work has the potential to identify early signs of hearing damage so as to advise on behavioural changes.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: EAR;NEUROLOGICAL
Title: The Impact of "Offset-Deafness" on Perception and Cortical Processing of Speech Sounds in Noise
Funder: Medical Research Council

Abstract: The objective of this research is to test the hypothesis that "offset-deafness" --- selective impairment of auditory brain sensitivity to sound offsets --- can disrupt perception and cortical processing of speech-like sounds in noise. We will test this hypothesis using both a mouse model of naturally occurring "offset-deafness", and normal mice in which we will induce "offset-deafness" experimentally through optogenetic suppression of activity in sound-offset-sensitive neurons of the auditory brainstem. We will measure the ability of the mice to detect changes in speech-like sounds in noise in a go/no-go behavioural task, while simultaneously recording sound-evoked activity of neurons in the auditory cortex using extracellular multi-electrodes. Similar behavioural and cortical measures will also be collected for tasks involving simpler sounds such as brief gaps in noise and quiet tones in silence. Behavioural and neural data will be compared between mice with and without naturally occurring or experimentally induced "offset-deafness", to determine whether reduced auditory brain sensitivity to sound offsets impairs perception and cortical processing of speech-like sounds in noise. Additionally, we will determine whether abnormalities in speech-in-noise sensitivity can be predicted from gap-in-noise detection thresholds; and how manipulations of activity in sound-offset-sensitive brainstem neurons influence cortical activity and auditory perception. These experiments may help us to understand why some people with clinically normal hearing nevertheless have abnormal difficulty with perception of speech in noisy environments. If "offset-deafness" can indeed impair perception of speech in noisy environments, then simple clinical tests for sound-offset sensitivity could improve diagnosis of speech-in-noise processing difficulties in children with developmental disorders and elderly adults, opening up new possibilities for intervention and treatment.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: EAR;NEUROLOGICAL
Title: Fundamentals of human hearing: from basic cochlear processing to cortical representations
Funder: Medical Research Council

Abstract: Neurophysiological research has suggested that, in animals, peripheral hearing loss can lead to profound changes in cortical auditory processing, causing large-scale reorganization in primary cortical tonotopic maps and down-regulating contextual and time-dependent suppression of cortical responses through lateral inhibition and neuronal adaptation. Such changes, if they also occur in humans, might explain common, but as yet untreatable consequences of hearing loss, such as hearing difficulty in noisy environments, hyperacusis and tinnitus. This research programme is aimed at testing the extent to which these changes occur in humans, and developing efficient and unbiased tools for measuring them in individual patients. In order to measure cortical tonotopic reorganization, we will first formulate an integrated model of human auditory cortex organization based on functional and structural MRI data measured at ultra-high field strengths (7T). Based on this model, we will develop a set of operational tools for delineating auditory areal borders in individual living brains (in-vivo parcellation). Hearing loss-related changes in contextual and time-dependent suppression will be measured with EEG. For that, we will develop a new method of estimating EEG sources from different cortical areas defined by tonotopic fMRI mapping, which will reduce inter-individual variability and establish a direct relationship between EEG and MRI results.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: EAR;NEUROLOGICAL
Title: 3D functional changes in the gap junctional signaling during the age related neurodegeneration in the mammalian inner ear Organ of Corti
Funder: Medical Research Council

Abstract: Hearing loss is a major health issue worldwide, especially in the aging population, majority of which suffers from some form of hearing loss. Several pathophysiological changes in the auditory inner ear have been associated with the process of cochlear degeneration, including the alterations in the function of supporting cells, stria vascularis and spiral ligament. These cells are coupled via gap junctions, which are known to play a critical role in hearing function. While the signaling conferred through the gap junctions is of instrumental important for proper development and maintenance of the auditory function, their functions in the inner ear are still not fully understood. It is plausible that the functional changes in gap junction intercellular communication (GJIC) contribute to age related hearing loss, similar to what has been observed in other systems. The proposed pilot work is the first to investigate the effects of aging on GJIC in the Organ of Corti (OC).We propose to utilize appropriate optical techniques developed by NIH High Resolution Optical Imaging group to non-invasively study in-vitro GJIC dynamics in a population of cells in the aging mouse OC. New technologies provide high resolution 'optical sectioning' in transparent samples while producing minimal damage to the sample, in contract to confocal or two photon microscopes. It is also enabled to study fast intracellular dynamics. Thus, the main idea is to use novel cell permeable light activated dyes which can defuse through gap junctions to monitor coupling while using local pharmacological manipulations to alter GJIC.The results of this project will shed light on the functional alterations in the GJIC that may contribute to the hearing loss and unravel the complexities of GJIC in the aging OC. The research outcomes may provide new directions and fresh opportunities to understand the process of hearing, and may contribute to development of future treatments of hearing loss.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EAR;NEUROLOGICAL