Abstract
Temporal processing by cochlear implant listeners is degraded and is affected by auditory deprivation. The fast-acting Kv3.1 potassium channel is important for sustained temporally accurate firing and is also susceptible to deprivation, the effects of which can be partially restored in animals by the molecule AUT00063. We report the results of a randomised placebo-controlled double-blind study on psychophysical tests of the effects of AUT00063 on temporal processing by CI listeners. The study measured the upper limit of temporal pitch, gap detection, and discrimination of low rates (centred on 120 pps) for monopolar pulse trains presented to an apical electrode. The upper limit was measured using the optimally efficient midpoint comparison (MPC) pitch-ranking procedure; thresholds were obtained for the other two measures using an adaptive procedure. Twelve CI users (MedEl and Cochlear) were tested before and after two periods of AUT00063 or placebo in a within-subject crossover study. No significant differences occurred between post-drug and post-placebo conditions. This absence of effect occurred despite high test-retest reliability for all three measures, obtained by comparing performance on the two baseline visits, and despite the demonstrated sensitivity of the measures to modest changes in temporal processing obtained in other studies from our laboratory. Hence, we have no evidence that AUT00063 improves temporal processing for the doses and patient population employed.
Highlights
Despite the success of cochlear implants (CIs) in restoring hearing to more than half a million people worldwide, auditory perception by CI listeners suffers from fundamental limitations in spatial selectivity and in temporal processing compared to normal hearing (NH)
The fact that the rate discrimination ratio (RDR) and gap detection threshold (GDT) improved from sessions 1 to 3 whereas the upper limit did not may be related to the fact that correct answer feedback was provided only for the RDR and GDT tests
The mean GDT of 2.9 ms reported here was slightly lower than the average value of 5.1 ms obtained from Advanced Bionics users by Bierer et al (2015), who used very similar methods to those used here, and falls within the range of GDTs obtained by Garadat and Pfingst (2011) for pulse trains presented at a level corresponding to 90 % of the dynamic range
Summary
Despite the success of cochlear implants (CIs) in restoring hearing to more than half a million people worldwide, auditory perception by CI listeners suffers from fundamental limitations in spatial selectivity and in temporal processing compared to normal hearing (NH). A possible neural correlate of the upper limit has been observed in single-neuron recordings in the inferior colliculus (IC) of anaesthetized cats, which phase lock to electrical pulse trains up to a certain rate beyond which they exhibit only an onset response (Snyder et al 1995; Vollmer et al 2005; Middlebrooks 2008; Middlebrooks and Snyder 2010; Hancock et al 2013; Vollmer et al 2017) It is not known whether the limitation arises at or before the IC, there is evidence from humans that the limitations on TFS processing arise centrally to the auditory nerve (AN). If—as turned out to be the case—no significant benefits were found, one could exclude the explanations that either the CI processor removed the appropriate (TFS) information, and/or that the tests were not sufficiently sensitive to reveal a significant effect
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