Mark P. Bendett

Optical Parameter Variability in Laser Nerve Stimulation: A Study of Pulse Duration, Repetition Rate, and Wavelength

Pulsed 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 laser stimulation of nerves and very little of the available optical parameter space has been studied. In this study, a pulsed diode laser, with wavelength between 1.844-1.873 mum, was used to elicit compound action potentials (CAPs) from the auditory system of the gerbil. We found that pulse durations as short as 35 mus elicit a CAP from the cochlea. In addition, repetition rates up to 13Hz can continually stimulate cochlear spiral ganglion cells for extended periods of time. Varying the wavelength and, therefore, the optical penetration depth, allowed different populations of neurons to be stimulated. The technology of optical stimulation could significantly improve cochlear implants, which are hampered by a lack of spatial selectivity

Laser Stimulation of Auditory Neurons: Effect of Shorter Pulse Duration and Penetration Depth

We have pioneered what we believe is a novel method of stimulating cochlear neurons, using pulsed infrared radiation, based on the hypothesis that optical radiation can provide more spatially selective stimulation of the cochlea than electric current. Very little of the available optical parameter space has been used for optical stimulation of neurons. Here, we use a pulsed diode laser (1.94 microm) to stimulate auditory neurons of the gerbil. Radiant exposures measured at CAP threshold are similar for pulse durations of 5, 10, 30, and 100 micros, but greater for 300-micros-long pulses. There is evidence that water absorption of optical radiation is a significant factor in optical stimulation. Heat-transfer-based analysis of the data indicates that potential structures involved in optical stimulation of cochlear neurons have a dimension on the order of approximately 10 microm. The implications of these data could direct further research and design of an optical cochlear implant.

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.

Laser stimulation of auditory neurons at high-repetition rate

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.

Characterization of single auditory nerve fibers in response to laser stimulation

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.

Laser stimulation of the auditory system at 1.94 μm and microsecond pulse durations

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 electrodes. 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.

Infrared neural stimulation in the cochlea.

The application of photonics to manipulate and stimulate neurons and to study neural networks has gained momentum over the last decade. Two general methods have been used: the genetic expression of light or temperature sensitive ion channels in the plasma membrane of neurons (Optogenetics and Thermogenetics) and the direct stimulation of neurons using infrared radiation (Infrared Neural Stimulation, INS). Both approaches have their strengths and challenges, which are well understood with a profound understanding of the light tissue interaction(s). This paper compares the opportunities of the methods for the use in cochlear prostheses. Ample data are already available on the stimulation of the cochlea with INS. The data show that the stimulation is selective, feasible at rates that would be sufficient to encode acoustic information and may be beneficial over conventional pulsed electrical stimulation. A third approach, using lasers in stress confinement to generate pressure waves and to stimulate the functional cochlea mechanically will also be discussed.

Frontiers in optical stimulation of neural tissues: past, present, and future

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.

Design, fabrication, and performance of an integrated optoelectronic cellular array

SUMMARY AND CONCLUSIONS An integrated optoelectronic chip has been designed and fabricated with a cellular architecture which providesoptical input and output, via LEDs and photoconducting detectors, from each cell in the array, and electricalinput and output to the array one row at a time. Each cell in the array can perform memory, thresholding and amplification functions.A fabrication process was developed for the integration of optoelectronic devices and GaAs enhancement-mode MESFET integrated circuits. The integrated process, which included the epitaxial deposition of layers for theLED, did not have any measurable effect on the performance of FETs and photodetectors fabricated on thesame substrate. LED efficiency and series resistance were degraded somewhat by the integrated process. Alloptical devices and electronic circuits functioned as designed when tested separately. However, a feedbackmechanism was observed between the LED and LED driver. The source of the problem was found to be

Development of VCSELs for optical nerve stimulation

Neural stimulation using infrared optical pulses has numerous potential advantages over traditional electrical stimulation, including improved spatial precision and no stimulation artifact. However, realization of optical stimulation in neural prostheses will require a compact and efficient optical source. One attractive candidate is the vertical cavity surface emitting laser. This paper presents the first report of VCSELs developed specifically for neurostimulation applications. The target emission wavelength is 1860 nm, a favorable wavelength for stimulating neural tissues. Continuous wave operation is achieved at room temperature, with maximum output power of 2.9 mW. The maximum lasing temperature observed is 60° C. Further development is underway to achieve power levels necessary to trigger activation thresholds.