Massachusetts Eye and Ear Infirmary
Regeneration of auditory neurons using stem cells

Hearing loss is usually permanent, and there are no effective interventions available to reverse symptoms by repair of damage. The overall goal of this research is to develop a cell-based therapy to replace auditory neurons. We have shown that neural progenitor cells derived from mouse embryonic stem (ES) cells transplanted into the auditory nerve send out fibers that grow to hair cells and to the cochlear nucleus. In this proposal, we will specifically address this issue through the use of a new mouse ES cell line for tracing the grafted cells and new procedures for detection of the synapses. We will connect the location of the new synapses with auditory function throughout the frequency range of the cochlea. Our study is composed of two related, specific aims. In the first aim we will assess auditory function after cell transplantation. In the second aim we will connect the synaptic counts to functional improvement in specific frequency regions.

Research areas: sensorineural hearing loss, stem cells and regeneration

Long-term goal of research: to find biological treatments for hearing loss. Hearing loss has lifelong consequences for individuals and their family. Hearing is mediated by hair cells, which convert sound vibrations into electric signals that are conveyed to the brain through the auditory nerve. Damage to hair cells and the auditory nerve result in hearing loss. Since mammals lack the regenerative capacity to replace hair cells and auditory nerve, hearing loss is usually permanent and there is no effective intervention to reverse the loss of these cells. Our previous work has demonstrated that neurons derived from stem cells can survive and re-innervate the cochlea. The proposed work will investigate a new approach to cell transplantation that will allow us to directly measure cell replacement and its effect on hearing.

East Carolina University
Place specificity of electrical stimulation with a cochlear implant and its relationship to neural survival and speech recognition

Modern cochlear implants code a speech signal by dividing it into spectral channels and modulating trains of biphasic electrical pulses with the low-frequency temporal envelope from each channel. Perception with a cochlear implant therefore is dependent on two factors: the acuity of processing the low frequency amplitude modulations and the place specificity of excitation. Cochlear implant users have demonstrated amplitude modulation detection similar to that found in normal hearing ears with larger individual variability, nonetheless the challenge of the prosthesis lies with the poor place specificity. Ideally, the output of an electrode should target a specific population of nerve fibers. However spread of excitation is often large, leading to neural interactions between channels. The first aim of the research is to investigate whether the underlying cause of channel interaction is the status of neural survival near the stimulation sites. The hypothesis is that excitation is more likely to spread further from a stimulation site in the cochlea when the density of surviving spiral ganglion cells is sparse. Neural status of a stimulation site will be estimated using a non-invasive psychophysical measure that correlates with the count of spiral ganglion cells in implanted animals. Place specificity of excitation will be measured by a psychophysical forward-masking procedure that is widely used to assess spatial tuning in electrical hearing. The second aim of the research is to examine the effects of place specificity on speech perception that requires mainly the spectral cues. The rationale is that poor place specificity would cause a reduction in spectral resolution or smearing of spectral speech cues. Proposed speech recognition tasks that demand good spatial tuning are perception of sine-wave speech, also known as the spectral skeleton of speech, and perception of speech presented in background noises.

Research area: Cochlear Implants

Long-term goal of research: If the proposed hypothesis is correct, that is, poor neural survival predicts poor spatial tuning, we will seek to ask the question whether the temporal processing acuity of the activated neurons at the site with low cell density would also be compromised. Once the relationship between temporal and spatial acuity is determined, we will examine the relative importance of the temporal and spatial acuity for speech recognition. The two acuities might not be equally important, or that they might be contributing to different aspects of speech recognition. With this information, the long term goal is to optimize implant user’s speech processing MAPs by strengthening the perception acuity that is the most important for speech recognition in the ear.