Effects of Early-Onset Deafness in the Developing Auditory System

Abstract

Estimates of the incidence of congenital hearing loss in the United States range from one to six in every 1000 births. When undetected, early hearing loss results in significant developmental delay in language acquisition and substantial lifetime costs to society. Cochlear implants (CIs) have radically changed the rehabilitation of individuals with severe to profound sensorineural hearing loss. However, there is great variability in outcomes with the CI, at least some of which is due to the condition of the auditory nerve and cochlear spiral ganglion (SG) neurons that are the targets of CI stimulation. This has focused attention on maintaining better SG survival after deafness, an issue that is particularly important for pediatric CIs owing to the profound effects of early-onset hearing loss and expected long duration of CI use.In this chapter, we review histopathological studies in human temporal bones and studies in animal models for evidence of the importance of SG neuronal survival for CI function and the factors that may contribute to or ameliorate neural degeneration. Animal studies have demonstrated that electrical stimulation from CI may help prevent degeneration of the SG degeneration after early deafness, and intracochlear delivery of pharmacologic agents and neurotrophic factors may further improve neuronal survival. Although many studies utilizing intracochlear drug delivery provide convincing evidence for several potential therapeutic agents to promote improved auditory nerve survival for optimum CI efficacy, there are many critically important questions that must be addressed before clinical application can be considered.Another important issue for studies of neurotrophic effects in the developing auditory system is the potential role of critical periods. Studies examining animals deafened at 30 days of age have explored whether a brief initial period of normal auditory experience affects the vulnerability of the SG or cochlear nucleus (CN) to auditory deprivation. Interestingly, the total volume of the CN was significantly closer to normal in the animals deafened at 30 days as compared to animals deafened as neonates. However, no difference was observed in either deafened group between the CN ipsi- and contralateral to a CI that restored auditory input by delivering chronic electrical stimulation. Spherical cells in the anteroventral CN also were significantly closer to normal size after later onset of deafness than in the neonatally deafened group. Further, electrical stimulation elicited a significant increase in spherical cell size in the CN ipsilateral to the CI as compared to the contralateral CN in both deafened groups.Neuronal tracer studies examining the primary afferent projections from the SG to the CN in neonatally deafened cats have demonstrated a clear cochleotopic organization despite severe auditory deprivation from birth. However, when normalized for the smaller CN size after deafness, projections were 30% to 50% broader than normal. Moreover, after unilateral CI stimulation there was no difference between projections from the stimulated and nonstimulated ears. These findings suggest that early normal auditory experience may be essential for the normal development (or subsequent maintenance) of the topographic precision of the cochlear SG projections to the CN. After early deafness, the CN volume is markedly smaller than normal, and the spatial precision of SG projections that underlie frequency resolution in the central auditory system may be reduced. Electrical stimulation over several months did not either ameliorate or exaggerate these degenerative changes. If similar principles pertain in the human auditory system, then findings in animal models suggest that the fundamental tonotopic organization of the central auditory pathways seems to be relatively “hardwired” at least at the level of the CN and should be intact even in congenitally deaf individuals. On the other hand, the precision of that organization can be significantly modified by early-onset deafness. This reduced spatial resolution of the primary afferent projections in animal studies suggests that there may be inherent limitations for CI stimulation in congenitally deaf subjects. Specifically, spatial (spectral) selectivity of stimulation delivered on adjacent CI channels may be poorer owing to the greater overlap of SG central axons representing nearby frequencies. Such CI users may be more dependent on temporal features of electrical stimuli, and it may be advantageous to enhance the salience of such cues, for example, by removing some electrodes from the processor “map” to reduce channel interaction.