Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients (n=7) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and 1.23 J/cm2. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at 1.09 J/cm2 and a 2∶1 safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans.
Infrared neural stimulation (INS) is becoming an important complementary tool to electrical stimulation. Since the mechanism of INS is photothermal, describing the laser-induced heat distribution is fundamental to determining the relationship between stimulation pulses and neural responses. This work developed both a framework describing the time evolution of the heat distribution induced by optical fluence and a new method to extract thermal criteria (e.g., temperature change and rate of change) for neural activation. To solve the general problem of describing the temperature distribution, a Green’s function solution to the heat diffusion equation was determined and convolved with the optical fluence. This provided a solution in the form of a single integral over time, from which closed-form solutions can be determined for special cases. This work also yielded an expression for thermal relaxation time, which provides a rigorous description of thermal confinement for INS. The developed framework was then applied to experimental data from the cochlea to extract the minimum temperature increase and rate of that increase to stimulate the cochlear spiral ganglion. This result, and similar analyses applied to other neural systems, can then shed light on the fundamental mechanism for INS and aid the development of optical neuroprostheses.
Here we present the first use of intraneural and intrafascicular infrared neural stimulation (INS) with early-generation
Utah Slanted Optrode Arrays (USOAs) to produce highly selective, artifact-free stimulation of peripheral nerves.
USOAs utilize technology previously developed for Utah Slanted Electrode Arrays, and contain 100 silicon optrodes of
0.5 to 1.5 mm length, spaced 400 μm apart in a 10 x 10 grid. The optrodes penetrate into the nerve and closely abut
nerve fibers, thus providing multiple, independent, focal sites of stimulation. We first demonstrated that intraneural (but
extrafascicular) infrared (IR) stimulation of cat sciatic nerve with conventional optical fibers coupled to a Lockheed
Martin Aculight Capella laser produced stronger and more selective neural and muscle compound action potentials
(CAPs) than did extraneural INS. We next tested INS through individual USOA optrodes (e.g., wavelength 1873 nm, 5-
ms stimulus pulse, < 1 mJ at optrode tip). In contrast to extraneural INS, intrafascicular INS evoked relatively strong and
highly selective, optrode-specific responses. Further, there were no observable stimulus artifacts, thereby allowing
adjacent electrical recordings. These initial results indicate that intrafascicular INS via USOAs may provide a more
efficient, more selective, high-optrode-count means of activating axons, plus greater access to interior nerve fibers.
Recently, thulium (Tm) fiber lasers have been investigated for use in surgical procedures, especially in urology, because
of their numerous advantages over existing laser systems. Lockheed Martin Aculight has recently developed the first
truly dual-mode Tm laser, which can be operated in either CW or in short-pulsed mode to produce high peak power. The
goal of this study was to assess both the soft tissue ablation performance of this laser in vitro and the feasibility of using
it for lithotripsy. Ablation tests were performed on liver tissue, chicken breast, and porcine skin, using a 100μm or
200μm delivery fiber, and operated in CW mode or pulsed (~350ns pulse widths) at 10kHz or 1kHz. Ablation
efficiencies for long (3 minutes) exposures and collateral damage zones for short (3-5 seconds) exposures were
determined for the different pulse modes and a range of pulse energies. In all tissues, the most energy-efficient ablation
occurred for the 10kHz pulsed mode operating just above ablation threshold, while the highest mass removal rate
occurred in 10kHz pulsed mode operating at max energy (2.1 mJ). In histological sections from short exposures, 10kHz
pulsed exposures created slightly smaller thermal coagulation zones than energy-matched CW exposures, while 1kHz
deliveries had substantially smaller thermal damage zones. In addition, using a 100μm fiber, the 10kHz mode was able
to fragment samples of uric acid stones.
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.
Infrared Nerve Stimulation (INS) offers several advantages over electrical stimulation, including more precise
spatial selectivity and improved surgical access. In this study, INS and electrical stimulation were compared
in their ability to activate the vestibular branch of the VIII<sup>th</sup> nerve, as a potential way to treat balance
disorders. The superior and lateral canals of the vestibular system of Guinea pigs were identified and
approached with the aid of precise 3-D reconstructions. A monopolar platinum stimulating electrode was
positioned near the ampullae of the canals, and biphasic current pulses were used to stimulate vestibular
evoked potentials and eye movements. Thresholds and input/output functions were measured for various
stimulus conditions. A short pulsed diode laser (Capella, Lockheed Martin-Aculight, Inc., Bothell WA) was
placed in the same anatomical position and various stimulus conditions were evaluated in their ability to
evoke similar potentials and eye movements.
We studied the effect of infrared (IR) stimulation on rat sensory neurons. Primary sensory neurons were prepared by
enzymatic dissociation of the inferior (or "nodose") ganglia from the vagus nerves of rats. The 1.85-μm output of a
diode laser, delivered through a 200-μm silica fiber, was used for photostimulation. Nodose neurons express the
vanilloid receptor, TRPV1, which is a non-selective cation channel that opens in response to significant temperature
jumps above 37 C. Opening TRPV1 channels allows entry of cations, including calcium (Ca<sup>2+</sup>), into the cell to cause
membrane depolarization. Therefore, to monitor TRPV1 activation consequent to photostimulation, we used fura-2, a
fluorescent Ca<sup>2+</sup> indicator, to monitor the rise in intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]i). Brief trains of 2-msec IR pulses activated TRPV1 rapidly and reversibly, as evidenced by transient rises in [Ca<sup>2+</sup>]i (referred to as Ca<sup>2+</sup> transients). Consistent with the Ca<sup>2+</sup> transients arising from influx of Ca<sup>2+</sup>, identical photostimulation failed to evoke Ca<sup>2+</sup> responses in the absence of extracellular Ca<sup>2+</sup>. Furthermore, the photo-induced Ca<sup>2+</sup> signals were abolished by capsazepine, a specific blocker of TRPV1, indicating that the responses were indeed mediated by TRPV1. We discuss the feasibility of using focal IR stimulation to probe neuronal circuit properties in intact neural tissue, and compare IR stimulation with another photostimulation technique-focal photolytic release of "caged" molecules.
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.
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.
<b>Background/Objective:</b> The traditional method of stimulating neural activity has been based on electrical methods and remains the gold standard to date despite inherent limitations. We have previously shown a new paradigm to in vivo neural activation based on pulsed infrared light, which provides a contact-free, spatially selective, artifact-free method without incurring tissue damage that may have significant advantages over electrical stimulation in a variety of diagnostic and therapeutic applications. The goal of this study was to investigate the physical mechanism of this phenomenon, which we propose is a photo-thermal effect from transient tissue temperature changes resulting in direct or indirect activation of transmembrane ion channels causing propagation of the action potential.
<b>Methods:</b> Rat sciatic nerve preparation was stimulated in vivo with the Holmium:YAG laser (2.12μm), Free Electron Laser (2.1μm), Alexandrite laser (690nm), and the prototype for a solid state commercial laser nerve stimulator built by Aculight (1.87μm) to determine contributions of photobiological responses from laser tissue interactions, including temperature, pressure, electric field, and photochemistry, underlying the biophysical mechanism of stimulation. Single point temperature measurements were made with a microthermocouple adjacent to the excitation site, while an infrared camera was used for 2-D radiometry of the irradiated surface. Displacement from laser-induced pressure waves or thermoelastic expansion was measured using a PS-OCT system.
<b>Results:</b> Results exclude a direct photochemical, electric field, or pressure wave effect as the mechanism of optical stimulation. Measurements show relative small contributions from thermoelastic expansion (300 nm) with the laser parameters used for nerve stimulation. The maximum change in tissue temperature is about 9°C (average increase of 3.66 °C) at stimulation threshold radiant exposures.
<b>Conclusion:</b> Neural activation with pulsed laser-light occurs by a transient thermally induced mechanism. Future experiments will reveal if this effect is through direct membrane interaction or facilitated through an indirect effect leading to membrane depolarization.
A novel method for damage-free, artifact-free stimulation of neural tissue using pulsed, low-energy infrared laser light is presented. Optical stimulation elicits compound nerve and muscle potentials similar to responses obtained with conventional electrical neural stimulation in a rat sciatic nerve model. Stimulation and damage thresholds were determined as a function of wavelength using a tunable free electron laser source (=2 to 10 µm) and a solid state holmium:YAG laser (=2.12 µm). Threshold radiant exposure required for stimulation varies with wavelength from 0.312 J/cm2 (=3 µm) to 1.22 J/cm2 (=2.1 µm). Histological analysis indicates no discernable thermal damage with suprathreshold stimulation. The largest damage/stimulation threshold ratios (>6) were at wavelengths corresponding to valleys in the IR spectrum of soft tissue absorption (4 and 2.1 µm). Furthermore, optical stimulation can be used to generate a spatially selective response in small fascicles of the sciatic nerve that has significant advantages (e.g., noncontact, spatial resolution, lack of stimulation artifact) over conventional electrical methods in diagnostic and therapeutic procedures in neuroscience, neurology, and neurosurgery.