An emerging method in the field of neural stimulation is the use of photons to activate neurons. The possible advantage of optical stimulation over electrical is attributable to its spatially selective activation of small neuron populations, which is promising in generating superior spatial resolution in neural interfaces. Two principal methods are explored for cochlear prostheses: direct stimulation of nerves with infrared light and optogenetics. This paper discusses basic requirements for developing a light delivery system (LDS) for the cochlea and provides examples for building such devices. The proposed device relies on small optical sources, which are assembled in an array to be inserted into the cochlea. The mechanical properties, the biocompatibility, and the efficacy of optrodes have been tested in animal models. The force required to insert optrodes into a model of the human scala tympani was comparable to insertion forces obtained for contemporary cochlear implant electrodes. Side-emitting diodes are powerful enough to evoke auditory responses in guinea pigs. Chronic implantation of the LDS did not elevate auditory brainstem responses over 26 weeks.
Many diseases trigger morphological changes in affected tissue. Today, classical histology is still the “gold standard”
used to study and describe those changes. Classical histology, however, is time consuming and requires chemical tissue
manipulations that can result in significant tissue distortions. It is sometimes difficult to separate tissue-processing
artifacts from changes caused by the disease process. We show that synchrotron X-ray phase-contrast micro-computed
tomography (micro-CT) can be used to examine non-embedded, hydrated tissue at a resolution comparable to that
obtained with classical histology. The data analysis from stacks of reconstructed micro-CT images is more flexible and
faster than when using the classical, physically embedded sections that are by necessity fixed in a particular orientation.
We show that in a three-dimensional (3D) structure with meticulous structural details such as the cochlea and the kidney,
micro-CT is more flexible, faster and more convenient for morphological studies and disease diagnoses.
Infrared neural stimulation (INS) is a method to depolarize neurons with infrared light. While consensus exists that heating of the target structure is essential, subsequent steps that result in the generation of an action potential are controversially discussed in the literature. The question of whether cochlear INS is an acoustic event has not been clarified. Results have been published that could be explained solely by an acoustic event. However, data exist that do not support an acoustical stimulus as the dominant factor in cochlear INS. We review the different findings that have been suggested for the mechanism of INS. Furthermore, we present the data that clarify the role of an acoustical event in cochlear INS. Masking experiments have been performed in hearing, hearing impaired, and severely hearing impaired animals. In normal hearing animals, the laser response could be masked by the acoustic stimulus. Once thresholds to acoustic stimuli were elevated, the ability to acoustically mask the INS response gradually disappeared. Thresholds for acoustic stimuli were significantly elevated in animals with compromised cochlear function, while the thresholds for optical stimulation remained largely unchanged. The results suggest that the direct interaction between the radiation and the target structure dominates cochlear INS.
KEYWORDS: Electrodes, Neurons, Solar thermal energy, Acoustics, Tungsten, Fiber lasers, Infrared radiation, Action potentials, Infrared lasers, Signal to noise ratio
Auditory prostheses may benefit from Infrared Neural Stimulation (INS) because optical stimulation allows for spatially
selective activation of neuron populations. Selective activation of neurons in the cochlear spiral ganglion can be
determined in the central nucleus of the inferior colliculus (ICC) because the tonotopic organization of frequencies in the
cochlea is maintained throughout the auditory pathway. The activation profile of INS is well represented in the ICC by
multichannel electrodes (MCEs). To characterize single unit properties in response to INS, however, single tungsten
electrodes (STEs) should be used because of its better signal-to-noise ratio. In this study, we compared the temporal
properties of ICC single units recorded with MCEs and STEs in order to characterize the response properties of single
auditory neurons in response to INS in guinea pigs. The length along the cochlea stimulated with infrared radiation
corresponded to a frequency range of about 0.6 octaves, similar to that recorded with STEs. The temporal properties of
single units recorded with MCEs showed higher maximum rates, shorter latencies, and higher firing efficiencies
compared to those recorded with STEs. When the preset amplitude threshold for triggering MCE recordings was raised
to twice over the noise level, the temporal properties of the single units became similar to those obtained with STEs.
Undistinguishable neural activities from multiple sources in MCE recordings could be responsible for the response
property difference between MCEs and STEs. Thus, caution should be taken in single unit recordings with MCEs.
According to the World Health Organization (WHO), in 2010 hearing loss affected more than 278 million people
worldwide. The loss of hearing and communication has significant consequences on the emotional well-being of each
affected individual. The estimated socio-economic impact is about $100 billion in unrealized household income per year.
Despite this impact on society, no Food and Drug Administration (FDA) approved drug intervention is available today
that would either protect or reverse the effects of hearing loss. A limiting factor for all efforts to validate drugs for
treatment relates to the time consuming animal experiments and subsequent histology. Here, we present an imaging
method that is superior to current gold standard methods in flexibility and time for evaluation of histology. Tissue
processing times are reduced from weeks to hours. As an example, we show that Brain Derived Neurotrophic Factor
(BDNF) reduces the effect of noise induced hearing loss.
Spatial selective infrared neural stimulation has potential to improve neural prostheses, including cochlear implants.
The heating of a confined target volume depolarizes the cell membrane and results in an action potential. Tissue
heating may also result in the generation of a stress relaxation wave causing mechanical stimulation of hair cells in
the cochlea, creating an optoacoustic response. Data are presented that quantify the effect of an acoustical stimulus
(noise masker) on the response obtained with INS in normal hearing, and chronic deaf animals. While in normal
hearing animals an acoustic masker can reduce the response to INS, in chronic deaf animals this effect has not been
detected. The responses to INS remain stable following the different degrees of cochlear damage.
Infrared neural stimulation (INS) has been used in the past to evoke neural activity from hearing and partially deaf
animals. All the responses were excitatory. In Aplysia californica, Duke and coworkers demonstrated that INS also
inhibits neural responses [1], which similar observations were made in the vestibular system [2, 3]. In deaf white cats
that have cochleae with largely reduced spiral ganglion neuron counts and a significant degeneration of the organ of
Corti, no cochlear compound action potentials could be observed during INS alone. However, the combined electrical
and optical stimulation demonstrated inhibitory responses during irradiation with infrared light.
Responses of units in the central nucleus of the inferior colliculus of the guinea pig were recorded with tungsten electrodes. The set of data presented here is limited to high stimulus levels. The effect of changing the modulation frequency and the modulation depth was explored for acoustic and laser stimuli. The selected units responded to sinusoidal amplitude modulated (AM) tones, AM trains of clicks, and AM trains of laser pulses with a modulation of their spike discharge. At modulation frequencies of 20 Hz, some units tended to respond with 40 Hz to the acoustic stimuli, but only at 20 Hz for the trains of laser pulses. For all modes of stimulation the responses revealed a dominant response to the first cycle of the modulation, with decreasing number of action potential during successive cycles. While amplitude modulated tone bursts and amplitude modulated trains of acoustic clicks showed similar patterns, the response to trains of laser pulses was different.
Spatial selective infrared neural stimulation has potential to improve neural prostheses, including cochlear implants. The heating of a confined target volume depolarizes the cell membrane and results in an action potential. Tissue heating may also results in thermal damage or the generation of a stress relaxation wave. Stress relaxation waves may result in a direct mechanical stimulation of remaining hair cells in the cochlea, so called optophony. Data are presented that quantify the effect of an acoustical stimulus (noise masker) on the response obtained with INS in normal hearing, acutely deafened, and chronic deaf animals. While in normal hearing animals an acoustic masker can reduce the response to INS, in acutely deafened animals the masking effect is reduced, and in chronic deaf animals this effect has not been detected. The responses to INS remain stable following the different degrees of cochlear damage.
Among neural prostheses cochlear implants (CIs) are considered the most successful devices. They restore some hearing to ~210,000 severe-to-profound hearing impaired people. Despite the devices’ success, the performance of the implanted individuals in noisy environments is poor and music perception is rudimentary. It has been argued that increasing the number of independent channels for stimulation can improve the performance of a CI user in challenging hearing environments. An optical method, stimulating neurons with infrared radiation, has been suggested as a novel approach to increase the number of independent channels. Infrared neural stimulation (INS) works through the deposition of heat into the tissue. Thermal damage is therefore a potential risk, particularly for longterm exposure. To verify the efficacy and safety of INS, cats were implanted for about 4 weeks and were continuously stimulated daily for 6-8 hours. Cochlear function did not change during the stimulation, and histology did not reveal signs of damage. Tissue growth following the implantation was largely localized at the cochleostomy.
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