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.

Objective Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow‐up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three‐dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image‐based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE. Methods This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively. Results Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic‐clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome. Significance LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.