title: Chronic microstimulation in the feline ventral cochlear nucleus: physiologic and histologic effects.
abstract: This study was conducted to help to establish the feasibility of a multi-channel auditory prosthesis based on microstimulation within the human ventral cochlear nucleus, and to define the range of stimulus parameters that can be used safely with such a device. We chronically implanted activated iridium microelectrodes into the feline ventral cochlear nucleus and, beginning 80-250 days after implantation, they were pulsed for 7 h/day, on up to 21 successive days. The stimulus was charge-balanced pulses whose amplitude was modulated by a simulated human voice. The pulse rate (250 Hz/electrode) and the maximum pulse amplitude were selected as those that are likely to provide a patient with useful auditory percepts. The changes in neuronal responses during the multi-day stimulation regimens were partitioned into long-lasting, stimulation-induced depression of neuronal excitability (SIDNE), and short-acting neuronal refractivity (SANR). Both SIDNE and SANR were quantified from the changes in the growth functions of the evoked potentials recorded in the inferior colliculus. All of the stimulation regimens that we tested induced measurable SIDNE and SANR. The combined effect of SIDNE and the superimposed SANR is to depress the neuronal response near threshold, and thereby, to depress the population response over the entire amplitude range of the stimulus pulses. SIDNE and SANR may cause the greatest degradation of the performance of a clinical device at the low end of the amplitude range, and this may represent an inherent limitation of this type of spatially localized, high-rate neuronal stimulation. We determined sets of stimulus parameters which preserved most of the dynamic range of the neuronal response, when using either long (150 micros/phase) or short (40 micros/phase) stimulus pulses. Increasing the amplitude of the stimulus was relatively ineffective as a means of increasing the dynamic range of neuronal response, since the greater stimulus amplitude induced more SIDNE. All of the pulsed and unpulsed electrode sites were examined histologically, and no neuronal changes attributable to the stimulation were detected. There was some aggregation of glial cells immediately adjacent to some of the electrodes that were pulsed with the short-duration pulses, and at the highest current densities.
authors.affiliation: Huntington Medical Research Institutes, Neurological Research Laboratory, 734 Fairmount Avenue, Pasadena, CA 91105, USA. dougmc1@mindspring.com
authors.forename: D B
authors.initials: DB
authors.lastname: McCreery
authors.forename: T G
authors.initials: TG
authors.lastname: Yuen
authors.forename: L A
authors.initials: LA
authors.lastname: Bullara
mesh_terms: D000818:Animals; D002415:Cats; D017626:Cochlear Nucleus / Q000166:cytology* / Q000502:physiology*; D004558:Electric Stimulation / Q000295:instrumentation / Q000379:methods; D004567:Electrodes, Implanted; D005240:Feasibility Studies; D008839:Microelectrodes; D008855:Microscopy, Electron, Scanning; D009474:Neurons / Q000166:cytology / Q000502:physiology; D012032:Refractory Period, Electrophysiological; D013997:Time Factors