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Objectives: We provide an appraisal of recent research on stimulation of the auditory system with light. In particular, we discuss direct infrared stimulation and ongoing controversies regarding the feasibility of this modality. We also discuss advancements and barriers to the development of an optical cochlear implant. Methods: This is a review article that covers relevant animal studies. Results: The auditory system has been stimulated with infrared light, and in a much more spatially selective manner than with electrical stimulation. However, there are experiments from other labs that have not been able to reproduce these results. This has resulted in an ongoing controversy regarding the feasibility of infrared stimulation, and the reasons for these experimental differences still require explanation. The neural response characteristics also appear to be much different than with electrical stimulation. The electrical stimulation paradigms used for modern cochlear implants do not apply well to optical stimulation and new coding strategies are under development. Stimulation with infrared light brings the risk of heat accumulation in the tissue at high pulse repetition rates, so optimal pulse shapes and combined optical/electrical stimulation are being investigated to mitigate this. Optogenetics is another promising technique, which makes neurons more sensitive to light stimulation by inserting light sensitive ion channels via viral vectors. Challenges of optogenetics include the expression of light sensitive channels in sufficient density in the target neurons, and the risk of damaging neurons by the expression of a foreign protein. Conclusion: Optical stimulation of the nervous system is a promising new field, and there has been progress toward the development of a cochlear implant that takes advantage of the benefits of optical stimulation. There are barriers, and controversies, but so far none that seem intractable. Level of evidence: NA (animal studies and basic research). [ABSTRACT FROM AUTHOR]

Infrared neural stimulation ( INS) may be beneficial in auditory prostheses because of its spatially selective activation of spiral ganglion neurons. However, the response properties of single auditory neurons to INS and the possible contributions of its optoacoustic effects are yet to be examined. In this study, the temporal properties of auditory neurons in the central nucleus of the inferior colliculus ( ICC) of guinea pigs in response to INS were characterized. Spatial selectivity of INS was observed along the tonotopically organized ICC. Trains of laser pulses and trains of acoustic clicks were used to evoke single unit responses in ICC of normal hearing animals. In response to INS, ICC neurons showed lower limiting rates, longer latencies, and lower firing efficiencies. In deaf animals, ICC neurons could still be stimulated by INS while unresponsive to acoustic stimulation. The site and spatial selectivity of INS both likely shaped the temporal properties of ICC neurons. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Nasal irrigations are commonly employed to promote nasal hygiene in the treatment of various sinonasal conditions. Few studies have evaluated how the ionic composition of irrigation solutions affects olfactory performance. The purpose of this study was to determine the dose responsiveness of human olfactory thresholds for each of the following ions: potassium, sodium, and calcium. Study Design Prospective translational study. Methods Irrigation solutions with variable potassium, sodium, and calcium were tested in 25 healthy human participants. Six potassium concentrations (range, 2-10 mM), six sodium concentrations (range, 73.7-113.7 mM), and three calcium concentrations (range, 0.44-0.64 mM) were used. Before and immediately following irrigations, olfactory thresholds were determined using the Sniffin' Sticks test. Differences in olfactory threshold scores before and after irrigations were compared to assess the effect of ionic composition on olfactory sensitivity. Results Physiologic concentrations of potassium, sodium, and calcium at 5.7, 89.5, and 0.54 mM, respectively, did not significantly change olfactory thresholds. Variations in both potassium and sodium concentrations demonstrated statistically significant dose-dependent elevations in olfactory thresholds ( P < .05). Only the calcium concentration that was lower than the physiologic level led to significant elevations in olfactory thresholds. Conclusions Different potassium and sodium concentrations in irrigation solutions provide distinctive dose-dependent shifts in olfactory thresholds. Calcium concentrations also elevate olfactory thresholds, but calcium plays a less significant role than potassium and sodium in modulating olfactory thresholds. These results highlight the importance of the intranasal ionic microenvironment in olfactory physiology and suggest that optimal ionic concentrations in irrigation solutions exist to preserve olfactory function. Level of Evidence NA Laryngoscope, 125:E50-E56, 2015 [ABSTRACT FROM AUTHOR]

It has been shown previously that application of short pulses of optical energy at infrared wavelengths can evoke action potentials in neurons and mechanical contraction in cardiac muscle cells. Optical stimuli are particularly attractive because of the ability to deliver focused energy through tissue without physical contact or electrical charge injection. Here we demonstrate efficacy of pulsed infrared radiation to stimulate balance organs of the inner ear, specifically to modulate the pattern of neural signals transmitted from the angular motion sensing semicircular canals to the brain. The ability to control action potentials demonstrates the potential of pulsed optical stimuli for basic science investigations and future therapeutic applications. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: One limitation with cochlear implants is the difficulty stimulating spatially discrete spiral ganglion cell groups because of electrode interactions. Multipolar electrodes have improved on this some, but also at the cost of much higher device power consumption. Recently, it has been shown that spatially selective stimulation of the auditory nerve is possible with a mid-infrared laser aimed at the spiral ganglion via the round window. However, these neurons must be driven at adequate rates for optical radiation to be useful in cochlear implants. We herein use single-fiber recordings to characterize the responses of auditory neurons to optical radiation. Study Design: In vivo study using normal-hearing adult gerbils. Methods: Two diode lasers were used for stimulation of the auditory nerve. They operated between 1.844 μm and 1.873 μm, with pulse durations of 35 μs to 1,000 μs, and at repetition rates up to 1,000 pulses per second (pps). The laser outputs were coupled to a 200-μm-diameter optical fiber placed against the round window membrane and oriented toward the spiral ganglion. The auditory nerve was exposed through a craniotomy, and recordings were taken from single fibers during acoustic and laser stimulation. Results: Action potentials occurred 2.5 ms to 4.0 ms after the laser pulse. The latency jitter was up to 3 ms. Maximum rates of discharge averaged 97 ± 52.5 action potentials per second. The neurons did not strictly respond to the laser at stimulation rates over 100 pps. Conclusions: Auditory neurons can be stimulated by a laser beam passing through the round window membrane and driven at rates sufficient for useful auditory information. Optical stimulation and electrical stimulation have different characteristics; which could be selectively exploited in future cochlear implants. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]

This article addresses an important current development in medical and biological imaging: the possibility of imaging soft tissue at resolutions in the micron range using hard X-rays. Challenging environments, including the cochlea, require the imaging of soft tissue structure surrounded by bone. We demonstrate that cochlear soft tissue structures can be imaged with hard X-ray phase contrast. Furthermore, we show that only a thin slice of the tissue is required to introduce a large phase shift. It is likely that the phase contrast image of the soft tissue structures is sufficient to image the structures even if surrounded by bone. For the present set of experiments, structures with low-absorption contrast have been visualized using in-line phase contrast imaging and a grating interferometer. The experiments have been performed at the Advanced Photon Source at Argonne National Laboratories, a third generation source of synchrotron radiation. The source provides highly coherent X-ray radiation with high-photon flux (>1012 photons/s) at high-photon energies (5-70 keV). Radiographic and light microscopy images of the gerbil cochlear slice samples were compared. It has been determined that a 20-μm thick tissue slice induces a phase shift between 1/3π and 2/3π. Microsc. Res. Tech., 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objectives/ Hypothesis: One sequela of skull base surgery is iatrogenic damage to cranial nerves, which can be prevented if the nerve is identified. Devices that stimulate nerves with electric current assist in nerve identification. Contemporary devices have two main limitations: 1) the physical contact of the stimulating electrode and (2) the spread of the current through the tissue. In contrast to electrical stimulation, pulsed infrared optical radiation can be used to safely and selectively stimulate neural tissue and might be valuable for screening.Methods: The gerbil facial nerve was exposed to 250 microsecond pulses of 2.12 microm radiation delivered via a 600-microm-diameter optical fiber at a repetition rate of 2 Hz. With use of 27 GA, 12-mm intradermal electrodes, muscle action potentials were recorded. Nerve samples were examined for possible tissue damage.Results: Eight facial nerves were stimulated with radiant exposures between 0.71 and 1.77 J/cm, resulting in compound muscle action potentials (CmAPs) that were simultaneously measured at the m. orbicularis oculi, m. levator nasolabialis, and m. orbicularis oris. Resulting CmAP amplitudes were 0.3 to 0.4 mV, 0.15 to 1.4 mV, and 0.3 to 2.3 mV, respectively, depending on the radial location of the optical fiber and the radiant exposure. Individual nerve branches were also stimulated, resulting in CmAP amplitudes between 0.2 and 1.6 mV. Histology revealed tissue damage at radiant exposures of 2.2 J/cm but no apparent damage at radiant exposures of 2.0 J/cm.Conclusions: The experiments showed that selective muscle action potentials can be evoked optically in the gerbil facial nerve without direct physical contact. [ABSTRACT FROM AUTHOR]

Program Description: Current prosthetic auditory implants have achieved a high level of success, however, it would be fair to say that performance gains over the past decade have reached a stable plateau. The latest phase of development has centered primarily on increasing stimulus resolution, preserving residual auditory ultrastructure and function, and implanting higher order neural pathways. To serve these objectives, electrodes have been designed to more closely approximate the spiral ganglion and be inserted virtually atraumatically. Implantation of the higher order pathways has already been performed with combinations of penetrating needles or electrode paddles at the brainstem. Prototypes even exist for stimulation as high up as the auditory cortex. We are now also witnessing the development of highly focused fiberoptic delivery systems for infrared laser energy as the stimulus source. A panel of surgeons and scientists, all of whom have been involved in both clinical and basic science of auditory implants, will debate the strategies being developed to foster the next leap in performance gains. The seminar will begin with a candid appraisal of the successes of currently marketed achievements including modiolar hugging electrodes, hearing preservation hybrid implants, compressed and split arrays for severely malformed and obstructed cochleae, and bilateral implantation. Minimally invasive surgical techniques will be examined with the questions posed: What truly constitutes a minimally invasive procedure? What technical features need to be retained in order to maintain necessary safeguards and precautions? The variable successes of auditory brainstem implantation will be reviewed with an eye toward future improvement. The panelists will then present their collective experience with emerging technologies aiming to push the envelope of performance higher into the future. The constant gains in microprocessor speeds will offer opportunities for development of novel processing strategies including current steering. The emerging concept of integrated drug delivery systems will require a careful re‐exploration of the well‐known design problems of hermeticity, durability, and ultrastructural trauma induction. Changes in stimulus energy source (eg, infrared laser) will undoubtedly require radical changes in device designs and coding strategies. It is the hope of the organizers that this miniseminar will benefit both the attendees and the panelists through the process of evaluative debate and exploration of new ideas. Educational Objectives: 1) Understand the current status and future direction of hybrid "hearing preservation" cochlear implantation. 2) Understand the newest device and coding strategies including infrared laser optical based devices. 3) Be familiar with the current systems under development including vestibular prostheses, DACS and ABI. [ABSTRACT FROM AUTHOR]

Objective: To determine whether treating pneumococcal meningitis with a combined antibiotic and steroid regime will prevent cochlear damage, a common pneumococcal meningitis side effect., Study Design: Prospective animal study., Methods: Gerbils were randomly assigned to three experimental groups. Animals in group 1 received intrathecal saline injections. Animals in groups 2 and 3 received intrathecal injections of Streptococcus pneumoniae to induce meningitis. Group 2 was treated for 7 days with intraperitoneal penicillin injections (48,000 units). Animals from group 3 received intraperitoneal dexamethasone (0.5 mg/kg) injections for 4 days in addition to 7 days of intraperitoneal penicillin. Three months after the meningitis was induced, the animals' cochlear functions were determined using auditory brainstem responses (ABRs). After measuring cochlear function, the animals were sacrificed for cochlear histopathology. Spiral ganglion cell densities at Rosenthal's canal were determined., Results: ABR thresholds were significantly elevated in animals from group 2 when compared with the animals in groups 1 and 3 (P < .05). ABR thresholds for animals from group 3 and group 1 were similar (P > .05). Damage of cochlear structures was detected in animals from group 2. The degree of the damage varied: one animal in group 2 had no identifiable hair cells and pillar cells and showed damage of the tectorial membrane. Spiral ganglion density in the basal turn was significantly less in animals from group 2 when compared with controls (P < .05). Although spiral ganglion cell density was less in the dexamethasone-treated group (group 3) when compared with group 1 (control group), but greater than observed in animals treated with antibiotics only (group 2), the differences were statistically not significant (P > .5). Nuclear diameters of the spiral ganglion cells decreased on average from 7.24 +/- 0.48 microm (group 1) to 6.28 +/- 0.76 microm (group 3, animals that received dexamethasone) to 5.57 +/- 0.82 microm (group 2, animals that received antibiotics only). Differences were significant (P < .05). Differences in stria vascularis thickness were not significant among the animals., Conclusion: Dexamethasone has a protective effect on the cochlea when given together with antibiotics in the treatment of pneumococcal meningitis.

Objectives/hypothesis: In the present series of experiments, the effect of neural degeneration on the cochlear structure electrical resistivities was evaluated to test if it alters the current flow in the cochlea and if increased current levels are needed to stimulate the impaired cochlea. In cochlear implants, frequency information is encoded in part by stimulating discrete populations of spiral ganglion cells along the cochlea. However, electrical properties of the cochlear structures result in shunting of the current away from the auditory neurons. This consumes energy, makes cochlear implants less efficient, and drastically reduces battery life. Models of the electrically stimulated cochlea serve to make predictions on current paths using modified and improved cochlear implant electrodes. However, one of the model's shortcomings is that most of the values for tissue impedances are not direct measurements. They are derived from bulk impedance measurements, which are fitted to lumped-element models., Study Design: The four-electrode reflection-coefficient technique was used to measure resistivities in the gerbil cochlea. In vivo and in vitro (the hemicochlea) models were used. Measurements were made in normal and in deafened animals. Cochlear damage was induced by neomycin injection into the animals' middle ears. Neural degeneration was allowed to occur over 2 months before performing the measurements in the deafened animals., Results: The resistivity values in deafened animals were smaller than in the normal-hearing animals, thus altering the current flow within the cochlea., Conclusions: Resistivity changes and subsequent changes in current path should be considered in future designs of cochlear implants.

Objective/hypothesis: The objective of the present study was to determine whether treating pneumococcal meningitis with a combined antibiotic and steroid regime will prevent cochlear damage, a common pneumococcal meningitis side effect., Study Design: This was a prospective animal study., Methods: Gerbils were randomly assigned to three experimental groups. Animals in group 1, the control animals, received intrathecal saline injections. Animals in groups 2 and 3 received intrathecal injections of Streptococcus pneumoniae to induce meningitis. Although group 2 solely was treated for 7 days with intraperitoneal penicillin injections (48,0000 units), group 3 received, in addition to the antibiotic for 4 days, 0.5 mg/kg intraperitoneal dexamethasone injections. Three months after the meningitis was induced, the animals' cochlear function was determined using auditory brainstem responses (ABRs). Fifteen frequencies were tested, five octaves at three steps per octave between 2 and 50 kHz., Results: ABR thresholds were significantly elevated only in group 2. When compared with group 1, ABR thresholds were 19 dB higher (P<.05). Frequencies at the low-frequency end of the hearing range were affected more than the midfrequencies. Animals that received dexamethasone had 2-dB higher thresholds than the control group (P>.05)., Conclusions: Dexamethasone therapy in conjunction with antibiotic therapy preserves cochlear function in cases of S. pneumoniae meningitis in the Mongolian gerbil model.