Changes in the Electrically Evoked Compound Action Potential over time After Implantation and Subsequent Deafening in Guinea Pigs

Abstract

The electrically evoked compound action potential (eCAP) is a direct measure of the responsiveness of the auditory nerve to electrical stimulation from a cochlear implant (CI). CIs offer a unique opportunity to study the auditory nerve’s electrophysiological behavior in individual human subjects over time. In order to understand exactly how the eCAP relates to the condition of the auditory nerve, it is crucial to compare changes in the eCAP over time in a controlled model of deafness-induced auditory nerve degeneration. In the present study, 10 normal-hearing young adult guinea pigs were implanted and deafened 4 weeks later, so that the effect of deafening could be monitored within-subject over time. Following implantation, but before deafening, most examined eCAP characteristics significantly changed, suggesting increasing excitation efficacy (e.g., higher maximum amplitude, lower threshold, shorter latency). Conversely, inter-phase gap (IPG) effects on these measures – within-subject difference measures that have been shown to correlate well with auditory nerve survival – did not vary for most eCAP characteristics. After deafening, we observed an initial increase in excitability (steeper slope of the eCAP amplitude growth function (AGF), lower threshold, shorter latency and peak width) which typically returned to normal-hearing levels within a week, after which a slower process, probably reflecting spiral ganglion cell loss, took place over the remaining 6 weeks (e.g., decrease in maximum amplitude, AGF slope, peak area, and IPG effect for AGF slope; increase in IPG effect for latency). Our results suggest that gradual changes in peak width and latency reflect the rate of neural degeneration, while peak area, maximum amplitude, and AGF slope reflect neural population size, which may be valuable for clinical diagnostics.

mTOR Signaling in BDNF-Treated Guinea Pigs after Ototoxic Deafening

“…Of particular interest was the peculiar localization of pAKT on the surface of pillar cells’ apical region. According to pillar cell structure, the apical region contains dense actin meshes [ 27 ], which could probably promote the localization of pAKT in the observed region. Moreover, we did not observe any differences in the PTEN protein levels between the three groups.…”

“…All experimental procedures were approved by the Dutch Central Authority for Scientific Procedures on Animals (CCD: 1150020174315). Only female guinea pigs were included in the study based on their easier handling compared to males (as reported previously [ 27 ]) and to exclude any sex-related mTOR differences [ 28 ].…”

Acute effects of cochleostomy and electrode-array insertion on compound action potentials in normal-hearing guinea pigs

“…Subsequently, a cochleostomy was manually performed with a 0.5 mm hand drill, just below (∼0.5 mm) the round window (POST1). This method has been previously performed without causing noticeable threshold shifts and/or hair cell loss ( Ramekers et al, 2015 , 2022 ). After the cochleostomy, a custom-made electrode array (Advanced Bionics; diameter 0.5 mm, length basal electrode to tip 3.5 mm, inter-electrode distance 1.0 mm) was inserted ∼4 mm into scala tympani (POST2) with all 4 electrodes of the array positioned intracochlearly.…”

A new method for removing artifacts from recordings of the electrically evoked compound action potential: Single-pulse stimulation

“…The eCAP has been shown to be useful for estimating the physiological status of the auditory nerve [3][4][5][6][7][8][9]. These estimates of the physiological status of the auditory nerve may have clinical benefits such as longitudinal monitoring of neural health [10,11], implant fitting [12][13][14] and explaining variance in speech perception performance among CI users [9,[15][16][17][18]. The primary challenge in recording eCAPs is the presence of unwanted voltages (i.e., electrical artifacts) that contaminate and obscure the neural response.…”

“…The eCAP has been shown to be useful for estimating the physiological status of the auditory nerve [3–9]. These estimates of the physiological status of the auditory nerve may have clinical benefits such as longitudinal monitoring of neural health [10, 11], implant fitting [12–14] and explaining variance in speech perception performance among CI users [9, 15–18].…”