Focused electrical stimulation using a single current source.

OBJECTIVE: Cochlear implants, while providing significant benefits to recipients, remain limited due to broad neural activation. Focussed multipolar stimulation (FMP) is an advanced stimulation strategy that uses multiple current sources to produce highly focussed patterns of neural excitation in order to overcome these shortcomings. APPROACH: This report presents single-source multipolar stimulation (SSMPS), a novel form of stimulation based on a single current source and a passive current divider. Compared to conventional FMP with multiple current sources, SSMPS can be implemented as a modular addition to conventional (i.e. single) current source stimulation systems facilitating charge balance within the cochlea. As with FMP, SSMPS requires the determination of a transimpedance matrix to allow for focusing of the stimulation. The first part of this study therefore investigated the effects of varying the probe stimulus (e.g. current level and pulse width) on the measurement of the transimpedance matrix. SSMPS was then studied using in vitro based measurements of voltages at non-stimulated electrodes along an electrode array in normal saline. The voltage reduction with reference to monopolar stimulation was compared to tripolar and common ground stimulation, two clinically established stimulation modes. Finally, a proof of principle in vivo test of SSMPS in a feline model was performed. MAIN RESULTS: A probe stimulus of at least 40 nC is required to reliably measure the transimpedance matrix. In vitro stimulation using SSMPS resulted in a significantly greater voltage reduction compared to monopolar, tripolar and common ground stimulation. Interestingly, matching measurement and stimulation parameters did not lead to an improved focussing performance. Compared to monopolar stimulation, SSMPS resulted in reduced spread of neural activity in the inferior colliculus, albeit with increased thresholds. SIGNIFICANCE: The present study demonstrates that SSMPS successfully limits the broadening of the excitatory field along the electrode array and a subsequent reduction in the spread of neural excitation.

Gentamicin Applied to the Oval Window Suppresses Vestibular Function in Guinea Pigs.

Intratympanic gentamicin therapy is widely used clinically to treat the debilitating symptoms of Ménière's disease. Cochleotoxicity is an undesirable potential side effect of the treatment and the risk of hearing loss increases proportionately with gentamicin concentration in the cochlea. It has recently been shown that gentamicin is readily absorbed through the oval window in guinea pigs. The present study uses quantitative functional measures of vestibular and cochlea function to investigate the efficacy of treating the vestibule by applying a small volume of gentamicin onto the stapes footplate in guinea pigs. Vestibular and cochlea function were assessed by recording short latency vestibular evoked potentials in response to linear head acceleration and changes in hearing threshold, respectively, 1 and 2 weeks following treatment. Histopathology was analyzed in the crista ampullaris of the posterior semi-circular canal and utricular macula in the vestibule, and in the basal and second turns of the cochlea. In animals receiving gentamicin on the stapes footplate, vestibular responses were significantly suppressed by 72.7 % 2 weeks after treatment with no significant loss of hearing. This suggests that the vestibule can be treated directly by applying gentamicin onto the stapes footplate.

Electroacoustic stimulation: now and into the future.

Cochlear implants have provided hearing to hundreds of thousands of profoundly deaf people around the world. Recently, the eligibility criteria for cochlear implantation have been relaxed to include individuals who have some useful residual hearing. These recipients receive inputs from both electric and acoustic stimulation (EAS). Implant recipients who can combine these hearing modalities demonstrate pronounced benefit in speech perception, listening in background noise, and music appreciation over implant recipients that rely on electrical stimulation alone. The mechanisms bestowing this benefit are unknown, but it is likely that interaction of the electric and acoustic signals in the auditory pathway plays a role. Protection of residual hearing both during and following cochlear implantation is critical for EAS. A number of surgical refinements have been implemented to protect residual hearing, and the development of hearing-protective drug and gene therapies is promising for EAS recipients. This review outlines the current field of EAS, with a focus on interactions that are observed between these modalities in animal models. It also outlines current trends in EAS surgery and gives an overview of the drug and gene therapies that are clinically translatable and may one day provide protection of residual hearing for cochlear implant recipients.

A partial hearing animal model for chronic electro-acoustic stimulation.

OBJECTIVE: Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This paper outlines such a model that has been successfully used in our laboratory. APPROACH: This paper outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. MAIN RESULTS: Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. SIGNIFICANCE: This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain residual hearing following cochlear implantation. The ability to record CAPs via the CI has clinical direct relevance for obtaining objective measures of residual hearing.

Cochlear implantation for chronic electrical stimulation in the mouse.

The mouse is becoming an increasingly attractive model for auditory research due to the number of genetic deafness models available. These genetic models offer the researcher an array of congenital causes of hearing impairment, and are therefore of high clinical relevance. To date, the use of mice in cochlear implant research has not been possible due to the lack of an intracochlear electrode array and stimulator small enough for murine use, coupled with the difficulty of the surgery in this species. Here, we present a fully-implantable intracochlear electrode stimulator assembly designed for chronic implantation in the mouse. We describe the surgical approach for implantation, as well as presenting the first functional data obtained from intracochlear electrical stimulation in the mouse.

A fully implantable rodent neural stimulator.

The ability to electrically stimulate neural and other excitable tissues in behaving experimental animals is invaluable for both the development of neural prostheses and basic neurological research. We developed a fully implantable neural stimulator that is able to deliver two channels of intra-cochlear electrical stimulation in the rat. It is powered via a novel omni-directional inductive link and includes an on-board microcontroller with integrated radio link, programmable current sources and switching circuitry to generate charge-balanced biphasic stimulation. We tested the implant in vivo and were able to elicit both neural and behavioural responses. The implants continued to function for up to five months in vivo. While targeted to cochlear stimulation, with appropriate electrode arrays the stimulator is well suited to stimulating other neurons within the peripheral or central nervous systems. Moreover, it includes significant on-board data acquisition and processing capabilities, which could potentially make it a useful platform for telemetry applications, where there is a need to chronically monitor physiological variables in unrestrained animals.

Synaptic plasticity after chemical deafening and electrical stimulation of the auditory nerve in cats.

The effects of deafness on brain structure and function have been studied using animal models of congenital deafness that include surgical ablation of the organ of Corti, acoustic trauma, ototoxic drugs, and hereditary deafness. This report describes the morphologic plasticity of auditory nerve synapses in response to ototoxic deafening and chronic electrical stimulation of the auditory nerve. Normal kittens were deafened by neonatal administration of neomycin that eliminated auditory receptor cells. Some of these cats were raised deaf, whereas others were chronically implanted with cochlear electrodes at 2 months of age and electrically stimulated for up to 12 months. The large endings of the auditory nerve, endbulbs of Held, were studied because they hold a key position in the timing pathway for sound localization, are readily identifiable, and exhibit deafness-associated abnormalities. Compared with those of normal hearing cats, synapses of ototoxically deafened cats displayed expanded postsynaptic densities, a 35.4% decrease in synaptic vesicle (SV) density, and a reduction in the somatic size of spherical bushy cells (SBCs). In comparison with normal hearing cats, ototoxically deafened cats that received cochlear stimulation had endbulbs that expressed postsynaptic densities (PSDs) that were statistically identical in size, showed a 48.1% reduction in SV density, and whose target SBCs had a 25.5% reduction in soma area. These results demonstrate that electrical stimulation via a cochlear implant in chemically deafened cats preserves PSD size but not other aspects of synapse morphology. This determination further suggests that the effects of ototoxic deafness are not identical to those of hereditary deafness.

Auditory hair cell explant co-cultures promote the differentiation of stem cells into bipolar neurons.

Auditory neurons, the target neurons of the cochlear implant, degenerate following a sensorineural hearing loss. The goal of this research is to direct the differentiation of embryonic stem cells (SCs) into bipolar auditory neurons that can be used to replace degenerating neurons in the deafened mammalian cochlea. Successful replacement of auditory neurons is likely to result in improved clinical outcomes for cochlear implant recipients. We examined two post-natal auditory co-culture models with and without neurotrophic support, for their potential to direct the differentiation of mouse embryonic SCs into characteristic, bipolar, auditory neurons. The differentiation of SCs into neuron-like cells was facilitated by co-culture with auditory neurons or hair cell explants, isolated from post-natal day five rats. The most successful combination was the co-culture of hair cell explants with whole embryoid bodies, which resulted in significantly greater numbers of neurofilament-positive, neuron-like cells. While further characterization of these differentiated cells will be essential before transplantation studies commence, these data illustrate the effectiveness of post-natal hair cell explant co-culture, at providing valuable molecular cues for directed differentiation of SCs towards an auditory neuron lineage.

Summing responses of cat soleus muscle spindles to combined static and dynamic fusimotor stimulation(1).

This is a study of the summation of responses of primary endings of muscle spindles to combined static and dynamic fusimotor stimulation in the soleus muscle of the anaesthetised cat. Summation, expressed as a summation coefficient, K, was measured under a variety of conditions including (1) at several, fixed muscle lengths using steady rates of stimulation, (2) using ramp-shaped increases in stimulation rates, (3) during passive stretches after muscle conditioning, and (4) during combined stretch plus stimulation. The predominant effect observed was occlusion, that is, the combined response was less than the sum of the two individual responses. The calculated mean K value for responses at fixed length was 0.156 (+/-0.005 S.E.M.). It was hypothesised that summation arose from electrotonic spread of generator current between the afferent terminals, either directly, or as a result of mechanical interactions between the contracting intrafusal fibres. Summation for responses from pairs of static fusimotor fibres gave a larger mean K value, 0.340 (+/-0.020 S.E.M.). These findings were interpreted in terms of a model of the muscle spindle where responses to dynamic fusimotor stimulation arise at one impulse generating site, and static fusimotor responses arise at another.

Occupational medicine. The science of accounting.

Accounting is inextricably linked to professional practice, industry and commerce. Having knowledge of some fundamental concepts may ease the burdens imposed by the need to maintain accounting records and help occupational health professionals to operate better within the corporate realm. The material in this chapter is intended to provide a bare-bones introduction to accounting for the novice and a brief review for those with more experience. More advanced material is contained in Chapter 4.

Occupational medicine. The essentials of finance.

Finance is concerned with the generation and use of funds to support organizational objectives whereas accounting records transactions and summarizes how funds are expended. Money has costs associated with its procurement and use. There are costs associated with maintaining equipment and inventory. Financial analysts have developed methods to evaluate a company's efficiency in using money. While the occupational physician may not be directly involved in financial activities, knowledge of the techniques used should improve an understanding of organizational limitations.