How does auditory experience shape neural sensitivity to acoustic events? Non-invasive investigations in animal models.

The ability to detect and respond quickly to changes in the environment, for example, the appearance, disappearance or movement of an object, impacts significantly on survival. Detecting changes in the acoustic environment is critical to this process; we often rely on our hearing in the dark or in visually-cluttered environments, and for events that occur beyond the field of vision. Because detecting acoustic changes is such a basic and vital ability, and since modern environments are characterized by 'noise pollution' or competing sources of acoustic information - the need to detect important events within a mixture of sounds, is increasingly important. The present proposal seeks to understand how the auditory brain's sensitivity to the unfolding acoustic environment is shaped by previous long-term exposure changes, and the degree to which this sensitivity is mutable during adulthood. Inherent difficulties in assessing the nature of brain mechanisms underlying sensitivity to acoustic changes means that the questions posed in the current proposal have never been, to the best of our knowledge, addressed experimentally. One reason for this deficit lies in the need to control carefully developmental experience and exposure to sound patterns, a requirement that renders investigations in human subjects almost impossible. So too, addressing such questions in animal models is limited by the difficulties that arise in evaluating the results of exposure/training, coupled with a lack of basic knowledge concerning the sites (i.e. which brain areas) to which electrophysiological recordings might be directed (or indeed how detecting acoustic changes relates to activity at the level of single neurons). Here, we propose a method of assessing the long term plasticity of mechanisms underlying detection of acoustic changes by means of non-invasive, gross brain activity - measurements in animal models (mice and guinea pigs), for which behavioral relevance and developmental experience can be carefully controlled. To measure gross brain activity we will employ a small animal MEG (magneto-encephalography) device. Relative to other means of measuring brain responses from small animals, such as EEG (electro-encephalography), this emerging technology is entirely non-invasive, increasing the efficiency of measuring event-related responses, and facilitating repeated measurements from individual animals. In the first experiment proposed, we will examine the effects of training in adulthood on subsequent neural sensitivity to change. Two groups of animals will be exposed to an identical auditory stimulus, containing changes in two sound features (pitch and timbre). One group will be trained to respond to pitch changes, while ignoring timbre changes, and vice versa for the other group. A control group will be exposed to the same stimuli but without a training element. Change-evoked brain responses (measured using MEG) will then be recorded from non-behaving anesthetized animals to determine whether, and in which manner, such training alters change-detection mechanisms in auditory cortex, A second experiment will investigate the extent to which passive exposure to sound during development, shapes neural representations of change detection in adulthood. Different groups of animals will be raised in specifically controlled sound environments such that the statistics of sound features across groups will be identical, but the statistics of changes (the frequency of changes encountered) different. Following exposure, MEG responses to acoustic changes will be measured. Differences in response patterns between groups will be specifically attributable to the differential exposure of the groups to patterns of changes. The outcome of this experiment will reveal the means by which statistics of acoustic changes shape cortical responses, and which changes (rare or commonly-occurring) are dominant in this process.

This project is focused on understanding how the brain's sensitivity to the unfolding acoustic environment is shaped by exposure to specific change statistics during development, and the degree to which this sensitivity is mutable during adulthood. Whilst prior research exists examining the effects of prolonged exposure to sound on the neural representation of simple acoustic features, to the best of our knowledge, no study has ever investigated the long-term plasticity of change-detection mechanisms. To assess such long term plasticity, we will measure MEG (magneto-encephalography) gross brain activity in animal models (mice and guinea pigs), for whom behavioral relevance and developmental experience can be carefully controlled. In the first experiment, we will study the effects of training in adulthood on subsequent sensitivity to acoustic changes. Two groups of animals will be exposed to identical auditory stimuli, containing changes in two sound features (pitch and timbre). One group will be trained to respond to pitch changes, while ignoring timbre changes, and the other vice versa. A control group will be exposed to the same stimuli, but without training. To assess effects of training, MEG responses to acoustic changes will be recorded from non-behaving anesthetized animals. A second experiment will investigate how passive exposure during development shapes change sensitivity. Different groups of animals will be raised in specifically controlled sound environments such that only the statistics of changes (the frequency of changes encountered) differ between groups. Post-exposure, MEG responses to acoustic changes will be measured. The outcome of this experiment will reveal the means by which statistics of acoustic changes shape cortical responses, and which changes (rare or commonly-occurring) dominate this process.

The ability to detect and respond quickly to a change in the environment, such as the appearance, disappearance or movement of an object, is of great importance to survival and auditory change detection, the topic of this grant proposal, plays a pivotal role in this process. We rely on auditory change detection in visually cluttered environments, in the darkness, and for events outside of the field of vision. Because auditory change detection is such a basic and vital ability, and because modern environments are characterized by 'acoustic pollution' and an increased need to detect important events out of a mixture of many ongoing sources, understanding the factors that affect auditory change sensitivity will have wide-ranging implications for the public: 1.Understanding how exposure to acoustic change shapes the developing brain, and how prolong periods of hearing loss (where such 'reshaping' does not occur or is compromised) affect this process, would be particularly important for therapies that seek to reverse hearing loss. 2.Beyond the field of audiology, understanding the processes that govern change detection plasticity may provide insight into diseases such as dyslexia and schizophrenia, which are often characterized by abnormal change detection (e.g. Naatanen, R. International Journal of Audiology 2008; 47 (Suppl. 2):S16-S20). 3.Understanding how training affects the brain's sensitivity to change would significantly benefit the design of training programs for professionals (e.g. air traffic controllers, pilots, operating room monitors) who must cope with hectic auditory environments where the detection of certain auditory events is crucial. Understanding the underlying brain processes may be of use for technological applications involving audio signal process, brain-machine interfaces, etc. To insure that these beneficiaries indeed benefit from this research we will: 1.The UCL Ear Institute is allied with the Royal National Throat Nose and Ear Hospital (the only specialist ENT hospital in the UK), and is thus in a unique position to explore clinical applications of our results. Our partner in France (LPP, Laboratoire de Psychologie de la Perception, Paris, of which our collaborator Dr de Cheveigne is a member) animates an extensive clinical research network (entitled GRAEC, groupement de recherche en audiologie expérimentale et clinique) that is supported by public, industrial and private partners. The UCL Ear Institute and the LPP/GRAEC are deeply involved in training programs in audiology, insuring rapid dissemination of any useful results. 2.The wider implications of this research will be monitored by the three Principal Investigators, the Researcher Co-Investigator, and the Project Collaborator, and communicated to the public through public lectures and communications with the media. UCL has an established media relations team, designed to facilitate, encourage and promote the dissemination of original research to the public and we plan to take full advantage of these tools. 3.The UCL Ear Institute has strong connections with UK institutions involved in raising public awareness of issues related to hearing. For example, the three Principal Investigators participated in the recent 'Hear Here!' program sponsored by the Royal Philharmonic Society in association with Classic FM radio and Deafness Research UK. If appropriate, we will seek a formal partnership with such institutions