Alexander C. Thompson

Modeling of light absorption in tissue during infrared neural stimulation

A Monte Carlo model has been developed to simulate light transport and absorption in neural tissue during infrared neural stimulation (INS). A range of fiber core sizes and numerical apertures are compared illustrating the advantages of using simulations when designing a light delivery system. A range of wavelengths, commonly used for INS, are also compared for stimulation of nerves in the cochlea, in terms of both the energy absorbed and the change in temperature due to a laser pulse. Modeling suggests that a fiber with core diameter of 200 μm and NA=0.22 is optimal for optical stimulation in the geometry used and that temperature rises in the spiral ganglion neurons are as low as 0.1°C. The results show a need for more careful experimentation to allow different proposed mechanisms of INS to be distinguished.

Teraflop per second gravitational lensing ray-shooting using graphics processing units

Abstract Gravitational lensing calculation using a direct inverse ray-shooting approach is a computationally expensive way to determine magnification maps, caustic patterns, and light-curves (e.g. as a function of source profile and size). However, as an easily parallelisable calculation, gravitational ray-shooting can be accelerated using programmable graphics processing units (GPUs). We present our implementation of inverse ray-shooting for the NVIDIA G80 generation of graphics processors using the NVIDIA Compute Unified Device Architecture (CUDA) software development kit. We also extend our code to multiple GPU systems, including a 4-GPU NVIDIA S1070 Tesla unit. We achieve sustained processing performance of 182 Gflop/s on a single GPU, and 1.28 Tflop/s using the Tesla unit. We demonstrate that billion-lens microlensing simulations can be run on a single computer with a Tesla unit in timescales of order a day without the use of a hierarchical tree-code.

Optical Stimulation of Neurons

Our capacity to interface with the nervous system remains overwhelmingly reliant on electrical stimulation devices, such as electrode arrays and cuff electrodes that can stimulate both central and peripheral nervous systems. However, electrical stimulation has to deal with multiple challenges, including selectivity, spatial resolution, mechanical stability, implant-induced injury and the subsequent inflammatory response. Optical stimulation techniques may avoid some of these challenges by providing more selective stimulation, higher spatial resolution and reduced invasiveness of the device, while also avoiding the electrical artefacts that complicate recordings of electrically stimulated neuronal activity. This review explores the current status of optical stimulation techniques, including optogenetic methods, photoactive molecule approaches and infrared neural stimulation, together with emerging techniques such as hybrid optical-electrical stimulation, nanoparticle enhanced stimulation and optoelectric methods. Infrared neural stimulation is particularly emphasised, due to the potential for direct activation of neural tissue by infrared light, as opposed to techniques that rely on the introduction of exogenous light responsive materials. However, infrared neural stimulation remains imperfectly understood, and techniques for accurately delivering light are still under development. While the various techniques reviewed here confirm the overall feasibility of optical stimulation, a number of challenges remain to be overcome before they can deliver their full potential.

Modeling of the temporal effects of heating during infrared neural stimulation.

Abstract. A model of infrared neural stimulation (INS) has been developed to allow the temporal characteristics of different stimulation parameters and geometries to be better understood. The model uses a finite element approach to solve the heat equation and allow detailed analysis of heat during INS with both microsecond and millisecond laser pulses. When compared with experimental data, the model provides insight into the mechanisms behind INS. In particular, the analysis suggests that there may be two broad regimes of INS: the process tends to be limited by the total pulse energy for pulse lengths below 100 μs, while the temperature gradient with respect to time becomes more important above 100 μs.

Infrared neural stimulation fails to evoke neural activity in the deaf guinea pig cochlea

At present there is some debate as to the processes by which infrared neural stimulation (INS) activates neurons in the cochlea, as the lasers used for INS can potentially generate a range of secondary stimuli e.g. an acoustic stimulus is produced when the light is absorbed by water. To clarify whether INS in the cochlea requires functioning hair cells and to explore the potential relevance to cochlear implants, experiments using INS were performed in the cochleae of both normal hearing and profoundly deaf guinea pigs. A response to laser stimulation was readily evoked in normal hearing cochlea. However, no response was evoked in any profoundly deaf cochleae, for either acute or chronic deafening, contrary to previous work where a response was observed after acute deafening with ototoxic drugs. A neural response to electrical stimulation was readily evoked in all cochleae after deafening. The absence of a response from optical stimuli in profoundly deaf cochleae suggests that the response from INS in the cochlea is hair cell mediated.

Infrared Neural Stimulation: Influence of Stimulation Site Spacing and Repetition Rates on Heating

A model to simulate heating as a result of pulse repetitions during infrared neural stimulation (INS), with both single- and multiple-emitters is presented. This model allows the temperature increases from pulse trains rather than single pulses to be considered. The model predicts that using a stimulation rate of 250 Hz with typical laser parameters at a single stimulation site results in a temperature increase of 2.3°C. When multiple stimulation sites are used in analogy to cochlear implants, the temperature increases further depending upon the spacing between emitters. However, when the light is more localized at multiple stimulation sites the temperature increase is reduced.

Nanoparticle-enhanced infrared neural stimulation.

OBJECTIVE Recent research has demonstrated that nerves can be stimulated by transient heating associated with the absorption of infrared light by water in the tissue. There is a great deal of interest in using this technique in neural prostheses, due to the potential for increased localization of the stimulus and minimization of contact with the tissue. However, thermal modelling suggests that the full benefits of increased localization may be reduced by cumulative heating effects when multiple stimulus sites and/or high repetition rates are used. APPROACH Here we review recent in vitro and in vivo results suggesting that the transient heating associated with plasmon absorption in gold nanorods can also be used to stimulate nerves. MAIN RESULTS Patch clamp experiments on cultured spiral ganglion neurons exhibited action potentials when exposed to 780 nm light at the plasmon absorption peak, while the amplitude of compound action potentials in the rat sciatic nerve were increased by laser irradiation of gold nanorods in the vicinity of the plasma membrane. Similarly, calcium imaging studies of NG108-15 neuronal cells incubated with Au nanorods revealed an increased level of intracellular calcium activity synchronized with laser exposure. SIGNIFICANCE Given that the plasmon absorption peak of gold nanorods can be matched with the transparency window of biological tissues, these results demonstrate that nanorod absorbers hold great promise to enhance the process of infrared neural stimulation for future applications in neural prostheses and fundamental studies in neuroscience.

Origins of Spectral Changes in Fiber Bragg Gratings Due to Macrobending

The effect of macrobending on fiber Bragg gratings (FBGs) in standard and specialist use single-mode fibers has been investigated for bend diameters down to 6 mm. The bend dependence of various spectral properties of FBGs, including center wavelength, were found to depend upon fiber type. A maximum centre wavelength shift of 0.39 nm was measured for a FBG written in low bend loss fiber bent to a 6 mm diameter. To investigate the cause of the observed wavelength shift, and the dependence on fiber design, a number of theoretical models have been applied to the problem. The results of modeling suggest that bend-induced changes in mode structure may explain the observed differences between fiber types, while wavefront distortion might be the cause of the general shift to shorter FBG center wavelengths when the bend diameter decreases.

Challenges for the application of optical stimulation in the cochlea for the study and treatment of hearing loss.

ABSTRACT Introduction: Electrical stimulation has long been the most effective strategy for evoking neural activity from bionic devices and has been used with great success in the cochlear implant to allow deaf people to hear speech and sound. Despite its success, the spread of electrical current stimulates a broad region of neural tissue meaning that contemporary devices have limited precision. Optical stimulation as an alternative has attracted much recent interest for its capacity to provide highly focused stimuli, and therefore, potentially improved sensory perception. Given its specificity of activation, optical stimulation may also provide a useful tool in the study of fundamental neuroanatomy and neurophysiological processes. Areas covered: This review examines the advances in optical stimulation – infrared, nanoparticle-enhanced, and optogenetic-based – and its application in the inner ear for the restoration of auditory function following hearing loss. Expert opinion: Initial outcomes suggest that optogenetic-based approaches hold the greatest potential and viability amongst optical techniques for application in the cochlea. The future success of this approach will be governed by advances in the targeted delivery of opsins to auditory neurons, improvements in channel kinetics, development of optical arrays, and innovation of opsins that activate within the optimal near-infrared therapeutic window.

The role of membrane capacitance and ion channels in the response of primary auditory neurons to infrared light (Conference Presentation)

Infrared light can be used to modulate the activity of neuronal cells with broad generality and without any need for exogenous materials. The action potential response has been shown to be associated with heating due to the absorption of light by water in and around the illuminated tissues, which gives rise to at least two distinct processes: namely, the temperature pulses cause depolarizing capacitive currents due to an intramembrane thermo-mechanical effect, and in addition, temperature-sensitive TRPV ion channels (and likely, voltage-gated channels) drive additional membrane depolarization. However, substantial differences between the activation threshold of primary auditory neurons ( 300 mJ/cm^2) in vivo have generated some controversy in the field. A temperature-dependent Hodgkin-Huxley type model, which combines capacitive currents and the experimentally-derived characteristics of voltage-gated potassium and sodium ion channels in primary auditory neurons, was used to accurately explain the in vitro response to 1870 nm infrared illumination. TRPV channels do not make a significant contribution in this case, suggesting that the detailed mechanism of the neuronal response to infrared light is dependent on the specific cell type. Furthermore, based on this detailed understanding of the cell behaviour, it is shown that action potentials cannot be generated at safe laser power levels. This suggests that the previously reported response of the auditory system to infrared stimulation in vivo might arise from a different mechanism, and calls into question the potential usefulness of the effect for auditory prostheses.