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.
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.
It has been demonstrated that spiral ganglion cells in the cochlea can be stimulated with infrared radiation (IR). The
potential benefits of infrared neural stimulation (INS) include the possibility of stimulating the neurons without direct
physical contact between the stimulation source and the neural tissue and the improved spatial selectivity. In order to
determine how INS can be best incorporated in both research and in neural interfaces, it is critical to identify the optimal
stimulation parameters for the laser. This study focuses on direct comparison of amplitudes of neural responses evoked
by various IR pulse shapes and durations. With the present experiments, the results indicate that the peak power is an
important variable for stimulating auditory neurons. While the radiant energy has little effect on amplitudes of
compound potentials (CAP) evoked by infrared pulses shorter than 70 μs, it impacts the amplitudes for pulses 80 μs and
longer. In addition, we show that the shape of the infrared pulse is important and varying the shape may allow an
expansion of response dynamic range while stimulating neurons. The results indicate that square pulses were the most
effective pulse shape to evoke CAPs.
It has been demonstrated previously that infrared neural stimulation (INS) can be used to stimulate spiral ganglion cells
in the cochlea. With INS, neural stimulation can be achieved without direct contact of the radiation source and the tissue
and is spatially well resolved. The presence of fluids or bone between the target structure and the radiation source may
lead to absorption or scattering of the radiation and limit the efficacy of INS. To develop INS based cochlear implants, it
is critical to determine the beam path of the radiation in the cochlea. In the present study, we utilized noninvasive X-ray
microtomography (microCT) to visualize the orientation and location of the optical fiber within the guinea pig and cat
cochlea. Overall, the results indicated that the optical fiber was directed towards the spiral ganglion cells in the cochlea
and not the nerve fibers in the center of the modiolus. The fiber was approximately 300 μm away from the target
structures. In future studies, results from the microCT will be correlated with physiology obtained from recordings in
A novel, spatially selective method to stimulate cranial nerves has been proposed: contact free stimulation with optical
radiation. The radiation source is an infrared pulsed laser. The Case Report is the first report ever that shows that optical
stimulation of the auditory nerve is possible in the human. The ethical approach to conduct any measurements or tests in
humans requires efficacy and safety studies in animals, which have been conducted in gerbils. This report represents the
first step in a translational research project to initiate a paradigm shift in neural interfaces. A patient was selected who
required surgical removal of a large meningioma angiomatum WHO I by a planned transcochlear approach. Prior to
cochlear ablation by drilling and subsequent tumor resection, the cochlear nerve was stimulated with a pulsed infrared
laser at low radiation energies. Stimulation with optical radiation evoked compound action potentials from the human
auditory nerve. Stimulation of the auditory nerve with infrared laser pulses is possible in the human inner ear. The
finding is an important step for translating results from animal experiments to human and furthers the development of a
novel interface that uses optical radiation to stimulate neurons. Additional measurements are required to optimize the
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.
Light can artificially stimulate nerve activity in vivo. A significant advantage of optical neural
stimulation is the potential for higher spatial selectivity when compared with electrical stimulation.
An increased spatial selectivity of stimulation could improve significantly the function of
neuroprosthetics, such as cochlear implants. Cochlear implants restore a sense of hearing and
communication to deaf individuals by directly electrically stimulating the remaining neural cells in
the cochlea. However, performance is limited by overlapping electric fields from neighboring
Here, we report on experiments with a new laser, offering a previously unavailable
wavelength, 1.94μm, and pulse durations down to 5μs, to stimulate cochlear neurons. Compound
action potentials (CAP) were evoked from the gerbil cochlea with pulse durations as short as 1μs.
Data show that water absorption of light is a significant factor in optical stimulation, as evidenced by
the required distance between the optical fiber and the neurons during stimulation. CAP threshold
measurements indicate that there is an optimal range of pulse durations over which to deposit the
laser energy, less than ~100μs. The implications of these data could direct further research and
design of an optical cochlear implant.
One sequela of skull base surgery is the iatrogenic damage to cranial nerves. Devices that stimulate nerves with electric
current can assist in the 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. Stimulation and screening
of the nerve is possible without making physical contact.
The gerbil facial nerve was irradiated with 250-μs-long pulses of 2.12 μm radiation delivered via a 600-μm-diameter
optical fiber at a repetition rate of 2 Hz. Muscle action potentials were recorded with intradermal electrodes. Nerve
samples were examined for possible tissue damage.
Eight facial nerves were stimulated with radiant exposures between 0.71-1.77 J/cm2, 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 0.3-0.4 mV, 0.15-1.4 mV and 0.3-2.3 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/cm2, but no apparent damage at radiant exposures of 2.0 J/cm2.
One drawback with traditional cochlear implants, which use electrical currents to stimulate spiral ganglion cells, is the ability to stimulate spatially discrete cells without overlap and electric current spread. We have recently demonstrated that spatially selective stimulation of the cochlea is possible with optical stimulation. However, for light to be a useful stimulation paradigm for stimulation of neurons, including cochlear implants, the neurons must be stimulated at high stimulus repetition rates. In this paper we utilize single fiber recordings from the auditory nerve to demonstrate that stimulation is possible at high repetition rates of the light pulses. Results showed that action potentials occurred 2.5-4. ms after the laser pulse. Maximum rates of discharge were up to 300 Hz. The action potentials did not respond strictly after the light pulse with high stimulation rates, i.e. >300 pulses per second. The correlation between the action potentials and the laser pulses decreased drastically for laser pulse repetition rate larger than 300 pulses per second.
Since lasers were first used in medicine and biomedical related research there have been a variety of
documented effects following the irradiation of neural tissues. The first systematic studies to report
the direct stimulatory effect of infrared light on neural tissues were performed by researchers at
Vanderbilt University in the rat sciatic nerve. These initial studies demonstrated a set of associated
advantages of standard stimulation methods, which lead to much excitement and anticipation from
the neuroscience community and industry. The inception of this new field included a partnership
between industry and academia to foster the development, not only of the applications but also a
series of devices to support the research and ultimate commercialization of technology.
Currently several institutions are actively utilizing this technique in various applications including in
the cochlear and vestibular systems. As more researchers enter the field and new devices are
developed we anticipate the number of applications will continue to grow. Some of the next steps
will include the establishment of the safety and efficacy data to move this technique to clinical trials
and human use.
Pulsed, mid-infrared lasers were recently investigated as a method to stimulate neural activity. There are significant benefits of optically stimulating nerves over electrically stimulating, in particular the application of more spatially confined neural stimulation. We report results from experiments in which the gerbil auditory system was stimulated by optical radiation, acoustic tones, or electric current. Immunohistochemical staining for the protein c-FOS revealed the spread of excitation. We demonstrate a spatially selective activation of neurons using a laser; only neurons in the direct optical path are stimulated. This pattern of c-FOS labeling is in contrast to that after electrical stimulation. Electrical stimulation leads to a large, more spatially extended population of labeled, activated neurons. In the auditory system, optical stimulation of nerves could have a significant impact on the performance of cochlear implants, which can be limited by the electric current spread.
Pulsed, mid-infrared lasers can evoke neural activity from motor as well as sensory neurons in vivo. Lasers allow more selective spatial resolution of stimulation than the conventional electrical stimulation. To date, few studies have examined pulsed, mid-infrared neural stimulation and very little of the available optical parameter
space has been studied. We found that pulse durations as short as 20 ?s elicit a compound action potential from the gerbil cochlea. Moreover, stimulation thresholds are not a function of absolute energy or absolute power deposited. Compound action potential peak-to-peak amplitude remained constant over extended periods
of stimulation. Stimulation occurred up six hours continuously and up to 50 Hz in repetition rate. Single fiber experiments were made using repetition rates of up to 1 kHz. Action potentials occurred 2.5-4 ms after the laser pulse. Maximum rates of discharge were up to 250 action potentials per second. With increasing stimulation rate
(300 Hz), the action potentials did not respond strictly after the light pulse. The results from these experiments
are important for designing the next generation of neuroprostheses, specifically cochlear implants.
It is known that electrical current injected from cochlear implant contacts spreads within the cochlea, causing overlapping stimulation fields and possibly limiting the performance of cochlear implant users. We have investigated an alternative mechanism to stimulate auditory neurons in the gerbil cochlea using a laser, rather than electrical current. With the laser, it is possible to direct the light to a selected, known volume of tissue that is smaller than the electrically stimulated population of cells. In the present experiments, a transiently expressed transcription factor, c-FOS, was used to stain activated nerve cells. Immunohistochemical staining for c-FOS in the cochlea shows a small area of optical stimulation, which occurs directly opposite to the optical fiber. Additionally, masking data indicate that the laser can stimulate a small population of cells similar to an acoustic toneburst. Smaller populations of stimulated cells could reduce the amount of overlap in stimulation fields and allow more stimulation contacts in a neuroprothesis.