The Impact of "Offset-Deafness" on Perception and Cortical Processing of Speech Sounds in Noise

Understanding speech in noisy environments is one of the most difficult --- and important --- tasks of human hearing. Accurate perception of speech in noise involves not only mechanisms of hearing within the ear, but also mechanisms of hearing within the brain. Many children with developmental disorders and elderly adults have abnormal difficulty perceiving speech in noisy environments, even when their hearing and their ability to perceive speech in quiet environments is normal. These difficulties with speech-in-noise perception are thought to arise, at least in part, from developmental and age-related abnormalities in the auditory brain rather than the ear. However, the nature of the auditory brain abnormalities affecting perception of speech in noisy environments remains poorly understood.

We have recently discovered, in a mouse model, that auditory brain sensitivity to sound offsets (disappearances) can be impaired while sensitivity to sound onsets (appearances) is not. This previously unrecognised form of hearing difficulty --- "offset-deafness" --- appears to arise in the brain rather than the ear. Standard clinical tests of human hearing focus almost exclusively on sensitivity to sound onsets, and would not even detect a specific deficit in auditory brain sensitivity to sound offsets like that observed in the mouse model. However, sensitivity to sound offsets is thought to be critical for speech-in-noise perception; therefore, it is possible that "offset-deafness" in humans could produce difficulties with speech-in-noise perception despite apparently normal hearing in clinical tests.

The main objective of this research is to test the hypothesis that "offset-deafness" can disrupt perception and cortical processing of speech-like sounds in noise. We propose to test this hypothesis using both our mouse model of naturally occurring "offset-deafness", and normal mice in which we will induce "offset-deafness" experimentally by suppressing activity of sound-offset-sensitive cells in the auditory brainstem. We will measure the ability of the mice to detect changes in speech-like sounds in noise, and simultaneously we will measure auditory cortical activity evoked by those sounds. In addition, we will collect similar behavioural and neural measures of brain sensitivity to simpler sounds such as brief gaps in noise and quiet tones in silence. By comparing results between mice with and without "offset-deafness", we will achieve our main objective: to determine whether reduced auditory brain sensitivity to sound offsets impairs perception and cortical processing of speech-like sounds in noise. Additional objectives will be to determine whether abnormalities in speech-in-noise sensitivity can be predicted from sensitivity to brief gaps in noise; and how sound-offset-sensitive cells in the auditory brainstem influence perception.

These experiments may help us to understand why some people with apparently normal hearing --- especially children with developmental disorders and elderly adults ---- have abnormal difficulty with perception of speech in noisy environments. If "offset-deafness" can indeed impair perception of speech in noisy environments, then the introduction of simple clinical tests for sound-offset sensitivity could help to identify patients likely to have to difficulty with speech-in-noise perception. Moreover, novel assisted-listening devices that enhance perception of sound offsets might improve the ability of young children to hear effectively in noisy classrooms, and of elderly adults to maintain healthy levels of social interaction into old age.

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.

This work has major potential for short-term and medium-term impact through advancement of scientific knowledge and provision of skilled people to the workforce; and further potential for long-term impact through advancement of health and well-being and economic competitiveness.

In the short term, this research will advance scientific knowledge of the novel phenomenon of "offset-deafness". Our recent discovery of naturally occurring "offset-deafness" in a mouse model proved that sound-onset-sensitive and sound-offset-sensitive auditory brain mechanisms are dissociable, and raised the possibility that "offset-deafness" might contribute to poorly understood difficulties with speech-in-noise perception in children with developmental disorders and elderly adults. The proposed experiments will reveal the perceptual implications of dissociation between sound-onset-sensitive and sound-offset-sensitive central auditory pathways, and clarify the potential relevance of "offset-deafness" to speech-in-noise perception. Thus, the work will advance understanding of both normal and abnormal central auditory processing.

Also in the short term, the research will contribute to provision of skilled people to the workforce, through career development of the postdoctoral fellow. The postdoctoral fellow will benefit from training in three different laboratories (PI, Co-I and Project Partner), and will learn essential methods of modern systems neuroscience such as multi-electrode electrophysiological recording in awake animals; behavioural testing in mice; optogenetic manipulation of neural circuitry; histological analysis; and mathematical modelling of neural data.

In the medium term, the work will contribute to advancement of science and technology education, through involvement of the PI and postdoctoral fellow in planned public engagement activities. Specifically, we will give guest lectures on brain mechanisms of sound perception to students at a comprehensive secondary school in London, and also we will offer one 8-week summer research internship per year to a student interested in science who is unlikely to have had any previous direct interactions with professional scientists. Through these planned yearly activities, we aim to increase awareness of professional scientists among economically and academically disadvantaged students; to provide role models to students interested in science; and ultimately to increase the number of students pursuing careers in science-related subjects.

In the longer term, our research could have a long-lasting impact on the health and wellbeing of children with developmental disorders and elderly adults --- and therefore an impact on the economic competitiveness of the UK. Our hypothesis is that "offset-deafness" affects cortical processing of speech sounds and can disrupt perception of speech in noise. Standard clinical assessments of hearing focus on sensitivity to sound onsets, but could easily be modified to include simple tests for sensitivity to sound offsets. Furthermore, it might be possible to develop novel assisted-listening devices that would increase the perceptual salience of sound offsets. Such advances in identification and treatment of "offset-deafness" might improve the ability of children with developmental disorders to hear in noisy classrooms, and might enable elderly adults to maintain healthy levels of social interaction into old age. We will work toward achieving such long-term impact in the period of the proposed basic-science project, by launching further research programmes to assess the value of testing sound-offset sensitivity in clinical settings, and to explore the feasibility of developing assisted-listening devices for increasing perceptual salience of sound offsets.