A new method for in vivo neural activation using low-intensity, pulsed infrared light exhibits advantages over standard electrical means by providing contact-free, spatially selective, artifact-free stimulation. Here we investigate the biophysical mechanism underlying this phenomenon by careful examination of possible photobiological effects after absorption-driven light-tissue interaction. The rat sciatic nerve preparation was stimulated in vivo with a Holmium:yttrium aluminum garnet laser (2.12 microm), free electron laser (2.1 microm), alexandrite laser (750 nm), and prototype solid-state laser nerve stimulator (1.87 microm). We systematically determined relative contributions from a list of plausible interaction types resulting in optical stimulation, including thermal, pressure, electric field, and photochemical effects. Collectively, the results support our hypothesis that direct neural activation with pulsed laser light is induced by a thermal transient. We then present data that characterize and quantify the spatial and temporal nature of this required temperature rise, including a measured surface temperature change required for stimulation of the peripheral nerve (6 degrees C-10 degrees C). This interaction is a photothermal effect from moderate, transient tissue heating, a temporally and spatially mediated temperature gradient at the axon level (3.8 degrees C-6.4 degrees C), resulting in direct or indirect activation of transmembrane ion channels causing action potential generation.
For more than a century, the traditional method of stimulating neural activity has been based on electrical methods, and it remains the gold standard to date. We report a technological breakthrough in neural activation in which low-level, pulsed infrared laser light is used to elicit compound nerve and muscle potentials in mammalian peripheral nerve in vivo. Optically induced neural action potentials are spatially precise, artifact free, and damage free and are generated by use of energies well below tissue ablation threshold. Thus optical stimulation presents a simple yet novel approach to contact-free in vivo neural activation that has major implications for clinical neurosurgery, basic neurophysiology, and neuroscience.
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 (lambda = 2 to 10 microm) and a solid state holmium:YAG laser (lambda = 2.12 microm). Threshold radiant exposure required for stimulation varies with wavelength from 0.312 Jcm2 (lambda = 3 microm) to 1.22 Jcm2 (lambda = 2.1 microm). 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 microm). 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.
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.
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