Late electrically-evoked compound action potentials as markers for acute micro-lesions of spiral ganglion neurons

Abstract

Cochlear implants (CIs) are the treatment of choice for profoundly hearing impaired people. It has been proposed that speech perception in CI users is influenced by the neural health (deafferentation, demyelination and degeneration) of the cochlea, which may be heterogeneous along an individual cochlea. Several options have been put forward to account for these local differences in neural health when fitting the speech processor settings, however with mixed results. The interpretation of the results is hampered by the fact that reliable markers of locally restricted changes in spiral ganglion neuron (SGN) health are lacking. The aim of the study was (i) to establish mechanical micro-lesions in the guinea pig as a model of heterogeneous SGN deafferentation and degeneration and (ii) to assess potential electrophysiological markers that can also be used in human subjects. First, we defined the extent of micro-lesions in normal hearing animals using acoustically-evoked compound action potentials (aCAPs); second, we measured electrically-evoked CAPs (eCAPs) before and after focal lesioning in neomycin-deafened and implanted animals. Therefore, we inserted guinea pig adjusted 6-contact CIs through a cochleostomy in the scala tympani. The eCAP was recorded from a ball electrode at the round window niche in response to monopolar or bipolar, 50 µs/phase biphasic pulses of alternating anodic- and cathodic-leading polarity. To exclude the large electrical artifact from the analysis, we focused on the late eCAP component. We systematically isolated the eCAP parameter that showed local pre- versus post-lesion changes and lesion-target specificity. Histological evaluation of the cleared cochleae revealed focal damage of an average size of 0.0036 mm³ with an apical-basal span of maximal 440 µm. We found that the threshold of the late N2P2 eCAP component was significantly elevated after lesioning when stimulating at basal (near the lesion), but not apical (distant to the lesion) CI contacts. To circumvent the potentially conflicting influence of the apical-basal gradient in eCAP thresholds, we used the polarity effect (PE=cathodic-anodic) as a relative measure. During monopolar stimulation, but not bipolar stimulation, the PE was sensitive to the lesion target and showed significantly better cathodic than anodic thresholds after soma lesions. We conclude that the difference in N2P2 thresholds in response to cathodic versus anodic-leading monopolar stimulation corresponds to the presence of SGN soma damage, and may therefore be a marker for SGN loss. We consider this electrophysiological estimate of local neural health a potentially relevant tool for human applications because of the temporal separation from the stimulation artifact and possible implementation into common eCAP measurements.

Keywords: Cochlear implant; Electrically-evoked compound action potential; Mechanical micro-lesion; Neural health; Polarity effect; Spiral ganglion neuron.