Measurements of Cochlear Synaptopathy Using Electrocochleography

Hearing loss is typically defined as an increase in the threshold sound levels required for detection of different frequencies. Hidden hearing loss is defined as impairment of complex auditory function, such as understanding speech in noise, with little or no change in detection thresholds. A major hypothesis recently developed based on animal studies is that hidden hearing loss may be due to prolonged overstimulation, which causes loss of auditory nerve connections to the hair cells that detect sound vibrations. In this view, detection thresholds can be maintained with a limited number of connected auditory nerve fibers, but complex processing is impaired without the complete complement of connected fibers. This mechanism of cochlear synaptopathy is difficult to observe in humans, but anatomical evidence in the form of loss of auditory nerve synapses and fibers seen post-mortem indicates that it occurs. Physiological tests to demonstrate it in living subjects are lacking. For this project, we will use the technique of electrocochleography (ECochG) to study and describe cochlear function in detail in living subjects. ECochG involves recording the electrical responses from the cochlea in response to sounds. The two sources of these electric potentials are the hair cell receptors that detect vibrations and the auditory nerve that transmits the information to the brain. Consequently, the technique is ideal to study the relative proportions of connections between hair cells and the auditory nerve, with any imbalance toward hair cells being an indication of cochlear synaptopathy.

Our project has three aims: The first aim is to develop metrics of cochlear synaptopathy using data from animal models and apply them to human subjects recorded under similar conditions. Using animals, ototoxins or neurotoxins can be applied to selectively eliminate hair cells or neural contributions, respectively. These experiments have allowed us to identify unique signatures of responses from each source, and to develop models based on biophysical properties that generate the responses that report the magnitudes of each component. The working models are relatively early versions not specifically designed for detecting cochlear synaptopathy, and so development for this purpose is a main activity of this aim. In addition, new animal work is needed to characterize synaptopathy in the noise-exposure model that has been used in previous studies and to separate the hair cell and neural responses into their constituent components, which are not incorporated in the current models. Finally, recordings in human subjects recorded under comparable signal-to-noise conditions are available only for subjects undergoing cochlear implant surgeries. To better characterize the distribution of cochlear synaptopathy we need subjects with less compromised hearing. Consequently, recordings will be done intraoperatively in other subjects where access to the inner ear is available.

The second aim is to develop the techniques for use with non-invasive recordings from the ear canal. These are needed so that they can be used routinely in the clinic. We can compare intraoperative and ear canal measurements directly by recording both at the same time. In addition, we can examine ear canal measurements in a cohort of young, normal hearing subjects, which are a good representation of many currently deployed service members.

The third aim is to compare ECochG measures of cochlear synaptopathy to audiometric and speech-in-noise measurements. A link between the suspected synaptopathy and behavioral outcomes has been difficult to make. The ECochG can provide a scale of synaptopathy based on objective measurements, to better test correlations between synaptopathy and the expected deficits. These subjects will also be young adults and will have audiometric hearing within the normal range. The overall product expected from this endeavor is an advanced system for evaluating cochlear function using ECochG that can be applied to synaptopathy and hidden hearing loss or to assess cochlear function in general. This system should be scalable to the needs both of advanced diagnostics and for local measurements by clinical users at various levels of training. It is intended to provide a reliable, objective measure of hair cell and neural function on an individual level.