Evaluation of Possible Effects of a Potassium Channel Modulator on Temporal Processing by Cochlear Implant Listeners

• Published in: Journal of the Association for Research in Otolaryngology 2018-12, Vol.19 (6), p.669-680
• Main Authors: Carlyon, Robert P., Deeks, John M., Guérit, François, Lamping, Wiebke, Billig, Alexander J., Large, Charles H., Saeed, Shakeel R., Harris, Peter
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Auditory deprivation; Auditory discrimination; Auditory Perception - drug effects; Cochlea; Cochlear Implants; Cross-Over Studies; Deafness - therapy; Double-Blind Method; Frequency; Hearing Tests; Humans; Imidazoles - pharmacology; Imidazoles - therapeutic use; Information processing; Medicine; Medicine & Public Health; Middle Aged; Neurobiology; Neurosciences; Otorhinolaryngology; Potassium; Potassium channels (voltage-gated); Psychophysics; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Research Article; Shaw Potassium Channels
• ISSN: 1525-3961; 1438-7573; 1438-7573
• DOI: 10.1007/s10162-018-00694-z

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.