Agnella Izzo Matic

Optical cochlear implants: evaluation of surgical approach and laser parameters in cats.

Previous research has shown that neural stimulation with infrared radiation (IR) is spatially selective and illustrated the potential of IR in stimulating auditory neurons. The present work demonstrates the application of a miniaturized pulsed IR stimulator for chronic implantation in cats, quantifies its efficacy, and short-term safety in stimulating auditory neurons. IR stimulation of the neurons was achieved using an optical fiber inserted through a cochleostomy drilled in the basal turn of the cat cochlea and was characterized by measuring compound action potentials (CAPs). Neurons were stimulated with IR at various pulse durations, radiant exposures, and pulse repetition rates. Pulse durations as short as 50 mus were successful in evoking CAPs in normal as well as deafened cochleae. Continual stimulation was provided at 200 pulses per second, at 200 mW per pulse, and 100 mus pulse duration. Stable CAP amplitudes were observed for up to 10 h of continual IR stimulation. Combined with histological data, the results suggest that pulsed IR stimulation does not lead to detectable acute tissue damage and validate the stimulation parameters that can be used in future chronic implants based on pulsed IR.

Infrared photostimulation of the crista ampullaris

Non‐technical summary  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.

Spread of cochlear excitation during stimulation with pulsed infrared radiation: Inferior colliculus measurements

Infrared neural stimulation (INS) has received considerable attention over the last few years. It provides an alternative method to artificially stimulate neurons without electrical current or the introduction of exogenous chromophores. One of the primary benefits of INS could be the improved spatial selectivity when compared with electrical stimulation. In the present study, we have evaluated the spatial selectivity of INS in the acutely damaged cochlea of guinea pigs and compared it to stimulation with acoustic tone pips in normal-hearing animals. The radiation was delivered via a 200 µm diameter optical fiber, which was inserted through a cochleostomy into the scala tympani of the basal cochlear turn. The stimulated section along the cochlear spiral ganglion was estimated from the neural responses recorded from the central nucleus of the inferior colliculus (ICC). ICC responses were recorded in response to cochlear INS using a multichannel penetrating electrode array. Spatial tuning curves (STCs) were constructed from the responses. For INS, approximately 55% of the activation profiles showed a single maximum, ∼22% had two maxima and ∼13% had multiple maxima. The remaining 10% of the profiles occurred at the limits of the electrode array and could not be classified. The majority of ICC STCs indicated that the spread of activation evoked by optical stimuli is comparable to that produced by acoustic tone pips.

Infrared neural stimulation: Beam path in the guinea pig cochlea

It has been demonstrated that INS can be utilized to stimulate spiral ganglion cells in the cochlea. Although neural stimulation can be achieved without direct contact of the radiation source and the tissue, the presence of fluids or bone between the target structure and the radiation source may lead to absorption or scattering of the radiation, which may limit the efficacy of INS. The present study demonstrates the neural structures in the radiation beam path that can be stimulated. Histological reconstructions and microCT of guinea pig cochleae stimulated with an infrared laser suggest that the orientation of the beam from the optical fiber determined the site of stimulation in the cochlea. Best frequencies of the INS-evoked neural responses obtained from the central nucleus of the inferior colliculus matched the histological sites in the spiral ganglion.

Laser stimulation of single auditory nerve fibers

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.

Behavioral and Electrophysiological Responses Evoked by Chronic Infrared Neural Stimulation of the Cochlea

Infrared neural stimulation (INS) has been proposed as a novel method for neural stimulation. In order for INS to translate to clinical use, which would involve the use of implanted devices over years or decades, the efficacy and safety of chronic INS needs to be determined. We examined a population of cats that were chronically implanted with an optical fiber to stimulate the cochlea with infrared radiation, the first known chronic application of INS. Through behavioral responses, the cats demonstrate that stimulation occurs and a perceptual event results. Long-term stimulation did not result in a change in the electrophysiological responses, either optically-evoked or acoustically-evoked. Spiral ganglion neuron counts and post implantation tissue growth, which was localized at the optical fiber, were similar in chronically stimulated and sham implanted cochleae. Results from chronic INS experiments in the cat cochlea support future work toward INS-based neuroprostheses for humans.

Acute Damage Threshold for Infrared Neural Stimulation of the Cochlea: Functional and Histological Evaluation

This article provides a mini review of the current state of infrared neural stimulation (INS), and new experimental results concerning INS damage thresholds. INS promises to be an attractive alternative for neural interfaces. With this method, one can attain spatially selective neural stimulation that is not possible with electrical stimulation. INS is based on the delivery of short laser pulses that result in a transient temperature increase in the tissue and depolarize the neurons. At a high stimulation rate and/or high pulse energy, the method bears the risk of thermal damage to the tissue from the instantaneous temperature increase or from potential accumulation of thermal energy. With the present study, we determined the injury thresholds in guinea pig cochleae for acute INS using functional measurements (compound action potentials) and histological evaluation. The selected laser parameters for INS were the wavelength (λ = 1,869 nm), the pulse duration (100 μs), the pulse repetition rate (250 Hz), and the radiant energy (0–127 μJ/pulse). For up to 5 hr of continuous irradiation at 250 Hz and at radiant energies up to 25 μJ/pulse, we did not observe any functional or histological damage in the cochlea. Functional loss was observed for energies above 25 μJ/pulse and the probability of injury to the target tissue resulting in functional loss increased with increasing radiant energy. Corresponding cochlear histology from control animals and animals exposed to 98 or 127 μJ/pulse at 250 Hz pulse repetition rate did not show a loss of spiral ganglion cells, hair cells, or other soft tissue structures of the organ of Corti. Light microscopy did not reveal any structural changes in the soft tissue either. Additionally, microcomputed tomography was used to visualize the placement of the optical fiber within the cochlea. Anat Rec, 2012.

Spatial extent of cochlear infrared neural stimulation determined by tone-on-light masking.

Artificial neural stimulation is widely used in clinic, rehabilitation, and research. One of the limitations of electrical stimulation is the current spread in tissue. Recently, pulsed mid-infrared laser stimulation of nerves has been investigated as an alternative stimulation method. The likely benefits of infrared neural stimulation (INS) include spatial selectivity of stimulation, noncontact mode of operation, and the lack of stimulation artifact in simultaneous electrical recordings. The hypothesis for this study is that INS of the cochlear spiral ganglion at low pulse energy is as spatially selective as low-level tonal stimulation of the cochlea. Spatial selectivity was measured using a masking method. An optical pulse with fixed optical parameters was delivered through a 200-μm diameter optical fiber. An acoustic tone, variable in frequency and level, was presented simultaneously with the optical pulse. Tone-on-light masking in gerbils revealed tuning curves with best frequencies between 5.3 and 11.4 kHz. The width of the tone-on-light tuning curves was similar to the width of tone-on-tone tuning curves. The results indicate that the spatial area of INS in the gerbil cochlea is similar to the cochlear area excited by a low level acoustic tone, showing promising results for future use of INS in implantable cochlear prostheses.

Optical stimulation in mice lacking the TRPV1 channel

Lasers can be used to stimulate neural tissue, including the sciatic nerve or auditory neurons. Wells and coworkers suggested that neural tissue is likely stimulated by heat.[1,2] Ion channels that can be activated by heat are the TRPV channels, a subfamily of the Transient Receptor Potential (TRP) ion channels. TRPV channels are nonselective cation channels found in sensory neurons involved in nociception. In addition to various chemicals, TRPV channels can also be thermally stimulated. The activation temperature for the different TRPV channels varies and is 43°C for TRPV1 and 39°C for TRPV3. By performing an immunohistochemical staining procedure on frozen 20 μm cochlear slices using a primary TRPV1 antibody, we observed specific immunostaining of the spiral ganglion cells. Here we show that in mice that lack the gene for the TRPV1 channel optical radiation cannot evoke action potentials on the auditory nerve.

Optical Stimulation of the Auditory Nerve

Improvements in cochlear implant devices during the last decade have mainly been achieved through novel coding strategies rather than through improvement of the neural interface. The neural interface, however, is a bottleneck for transferring information from the cochlear implant to the auditory nerve. Electric current spreads in the tissue and neighboring electrode contacts cannot be considered independent stimulation sources. Simultaneous transfer of information at adjacent electrodes may lead to deleterious interactions. Therefore, contemporary coding strategies use sequential stimulation paradigms that avoid simultaneous stimulation at neighboring electrode contacts. These coding strategies provide good speech recognition in quiet listening environments but fail in noisy backgrounds. It has been argued that an increase in the number of independent channels that transfer information to the auditory nerve could improve patient performance in noisy listening environments. Therefore, an important objective in implant electrode design is to maximize the spatial selectivity of stimulation.