Auditory-Nerve Responses to Varied Inter-Phase Gap and Phase Duration of the Electric Pulse Stimulus as Predictors for Neuronal Degeneration

Abstract

After severe hair cell loss, secondary degeneration of spiral ganglion cells (SGCs) is observed-a gradual process that spans years in humans but only takes weeks in guinea pigs. Being the target for cochlear implants (CIs), the physiological state of the SGCs is important for the effectiveness of a CI. For assessment of the nerve's state, focus has generally been on its response threshold. Our goal was to add a more detailed characterization of SGC functionality. To this end, the electrically evoked compound action potential (eCAP) was recorded in normal-hearing guinea pigs and guinea pigs that were deafened 2 or 6 weeks prior to the experiments. We evaluated changes in eCAP characteristics when the phase duration (PD) and inter-phase gap (IPG) of a biphasic current pulse were varied. We correlated the magnitude of these changes to quantified histological measures of neurodegeneration (SGC packing density and SGC size). The maximum eCAP amplitude, derived from the input-output function, decreased after deafening, and increased with both PD and IPG. The eCAP threshold did not change after deafening, and decreased with increasing PD and IPG. The dynamic range was wider for the 6-weeks-deaf animals than for the other two groups. Excitability increased with IPG (steeper slope of the input-output function and lower stimulation level at the half-maximum eCAP amplitude), but to a lesser extent for the deafened animals than for normal-hearing controls. The latency was shorter for the 6-weeks-deaf animals than for the other two groups. For several of these eCAP characteristics, the effect size of IPG correlated well with histological measures of degeneration, whereas effect size of PD did not. These correlations depend on the use of high current levels, which could limit clinical application. Nevertheless, their potential of these correlations towards assessment of the condition of the auditory nerve may be of great benefit to clinical diagnostics and prognosis in cochlear implant recipients.

Integration of Pulse Trains in Humans and Guinea Pigs with Cochlear Implants

“…A number of studies have reported the effects of neural survival on electrophysiological measures in implanted guinea pigs (e.g., Prado-Guitierrez et al 2006;Ramekers et al 2014). Here, we report the effects of various aspects of cochlear health of the implanted ears on psychophysical integration of electrical pulses.…”

Assessing the Firing Properties of the Electrically Stimulated Auditory Nerve Using a Convolution Model

“…In this study, we perform a deconvolution of eCAPs to examine CDLDs, presuming that they could provide information about the neural status of the auditory periphery. It has been shown that the eCAP in a guinea pig exhibits differences in its morphology depending on the neural health of the auditory nerve (Ramekers et al 2014(Ramekers et al , 2015. Therefore, eCAPs from deafened guinea pigs are analysed to assess effects of the status of the auditory nerve on its firing probability.…”

“…Data were acquired from 18 guinea pigs (Ramekers et al 2014(Ramekers et al , 2015, which were divided into 3 groups of 6 animals: normal-hearing (NH), 2 weeks deaf (2WD) and 6 weeks deaf (6WD). Methods of deafening and eCAP recordings are described in detail in Ramekers et al (2014).…”

“…Methods of deafening and eCAP recordings are described in detail in Ramekers et al (2014). Briefly, profound cochlear hair cell loss was induced by co-treatment of kanamycin and furosemide.…”

Relationship between multipulse integration and speech recognition with cochlear implants

“…Several psychophysical and electrophysiological measures have been developed to probe sensory and neural health in implanted animals. These measures include psychophysical threshold functions such as temporal integration of electrical pulse trains (threshold-versus-stimulus-duration functions) as well as electrophysiological measures such as electrically evoked compound action potentials and auditory brainstem responses (Hall, 1990;Prado-Guitierrez et al, 2006;Smith and Simmons, 1983;Kang et al, 2010;Pfingst et al, 2011a;Pfingst et al, 2011b;Ramekers et al, 2014). Advantages of an animal model include that histological analysis can be conducted a short time after these functional measurements are made and that the conditions of the inner ear of the animals can be systematically manipulated.…”