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Optical Stimulation of Neurons
Open accessAbstract
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.
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![Fig. (1) (a) 3D reconstruction of a guinea pig cochlea during stimulation. Black cylinder shows the position of the optical fibre, black dots indicates the spiral ganglion neurons, green dots are the inner pillar feet. (See online for colour) (b) The spatial tuning curve obtained from recordings of the ICC, showing stimulation at 10.8 kHz and 16.1 kHz. Fig. reproduced from [84], with permission from Elsevier.](/paper-figures/4a90f4f3adfe4bebb8c0cdac8cbe7139/optical-stimulation-of-neurons-figure-1.jpg)
![Fig. (2) Example of temperature measurement (left) and change in cell membrane potential (right) during and after exposure to INS. Adapted by permission from Macmillan Publishers Ltd: Nature Communications [56], copyright (2012).](/paper-figures/d4b80350b3a042f085753387c6b57e96/optical-stimulation-of-neurons-figure-2.jpg)
![Fig. (3) Absorption coefficient in water [140] and oxygenated blood (5% haematocrit) [141]. Reduced scattering coefficient in dermis [142] and white matter [142] over the wavelength range of 200 nm to 2500 nm. Wavelength ranges commonly used for Optogenetics (380 – 650 nm), INS (1400 – 2200 nm) and Nanoparticle Enhanced INS (700 – 900 nm) are highlighted. Vertical dashed grey lines show the therapeutic window where absorption and scattering is relatively low.](/paper-figures/e52a5e5db4d043dfb5e56287f9c7805a/optical-stimulation-of-neurons-figure-3.jpg)
![Fig. (4) SEM image of (a) silicon Utah slant optrode array and (b) glass optrode array reproduced from [153], with permission from SPIE.](/paper-figures/7feeb0d057594c338e109eaf0e3a9a6c/optical-stimulation-of-neurons-figure-4.jpg)
![Fig. (5) Heating from different stimulation rates with INS, when using a fibre with core diameter of 200 μm and NA = 0.22, with a wavelength of 1850 nm and pulse energy of 25 µJ. a) Over 1 second b) over 10 seconds. Reproduced from [160].](/paper-figures/e309f9bb1fe248e8b1a8d0a7e9f8a02b/optical-stimulation-of-neurons-figure-5.jpg)
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“ChR2 responds to blue (470 nm) lights to depolarise a neuron, and HR exhibits sensitivity toward green light (578 nm) that hyperpolarises the cell, thus inhibiting the propagation of action potentials [107].”
From Active Neural Interface Circuits and Systems for Selective Control of Peripheral Nerves: A Review (2024) · cites this paper as [107]
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“To date, a number of studies focusing on the safety in both acute and chronic usage of INS in the cochlea have been performed [66, 67, 97, 98, 90].”
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“This fabrication approach has been taken up by other researchers, including fabrication of 15 LED arrays suitable for implantation in a ChR2 sensitive cochlea [158] and vertical cavity surface emitting lasers to provide high intensity infrared light for INS [159].”
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“A range of photoactive materials are being developed with the aim of neural stimulation, including quantum dots [126, 127], photoconductive silicon [128], organic polymers [129, 130], and carbon nanotubes [125, 131].”
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“[149, 150] reported custom fabricated waveguides, capable of delivering light in a 3D pattern in tissue.”
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“The heart is another target of INS that has seen interest [63, 64, 76].”
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“Genes to express opsins are typically delivered with viral transfection [12], but electroporation transfection [26] and optical transfection [27] have also been demonstrated as a feasible techniques.”
MethodNew photochemical tools for controlling neuronal activity
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“photoswitchable ligands, which can regulate + K channels and glutamate receptors [17, 49].”
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Multiphoton stimulation of neurons
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“[6] demonstrated that neurons could be triggered through exposure to pulses of light from a femtosecond laser via a two-photon mechanism.”
BackgroundMethodOptogenetic Control of Targeted Peripheral Axons in Freely Moving Animals
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“[144] where an optical fibre and PDMS optical nerve cuff on the sciatic nerve was implanted in rats [144].”
BackgroundPulsed laser versus electrical energy for peripheral nerve stimulation
Wells, J. D., Konrad, P. E., Kao, C., Jansen, D., & Mahadevan-Jansen, A. M. (2007) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2007.03.016 · Cited by 156 · cited 3×
“[59] found a near linear relationship between the radiant exposure and the measured compound nerve action potential (CNAP) response, similar to that observed when using electrical stimulation.”
BackgroundResultSahel, J., & Roska, B. (2013) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062012-170304 · Cited by 150 · cited 1×
“Optogenetic techniques require transfection of genes into neuronal cells, which, besides technical challenges, will face significant regulatory hurdles for human use [40, 41].”
BackgroundNeural stimulation with optical radiation
Richter, C., Matic, A. I., Wells, J. D., Jansen, D., & Walsh, J. T. (2010) · Laser & Photonics Review · doi:10.1002/lpor.200900044 · Cited by 148 · cited 6×
“for genetic manipulation or other interventions [2, 15].”
BackgroundInfluentialIzzo, A. D., Walsh, J. T., Jansen, D., Bendett, M., Webb, J., Ralph, H., & Richter, C. (2007) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2007.892925 · Cited by 148 · cited 4×
“To date, a number of studies focusing on the safety in both acute and chronic usage of INS in the cochlea have been performed [66, 67, 97, 98, 90].”
BackgroundMethodInfluentialIntracellular calcium transients evoked by pulsed infrared radiation in neonatal cardiomyocytes
Dittami, G. M., Rajguru, S. M., Lasher, R. A., Hitchcock, R. W., & Rabbitt, R. D. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2010.198804 · Cited by 147 · cited 2×
“Initial work on cells cultured with gold nanorods demonstrated intracellular + 2 Ca transients in response to laser light at the plasmon resonance wavelength of the gold nanorods [124], similar to cells exposed to INS [114].”
BackgroundGold‐Nanorod‐Assisted Near‐Infrared Stimulation of Primary Auditory Neurons
Yong, J., Needham, K., Brown, W. G. A., Nayagam, B. A., McArthur, S. L., Yu, A., & Stoddart, P. R. (2014) · Advanced Healthcare Materials · doi:10.1002/adhm.201400027 · Cited by 146 · cited 3×
“The use of gold nanorods in cells as a selective absorber of near infrared light has also been investigated for in vitro neural stimulation [123, 124].”
BackgroundPulsed infrared light alters neural activity in rat somatosensory cortex in vivo
Cayce, J. M., Friedman, R. M., Jansen, D., Mahavaden-Jansen, A., & Roe, A. W. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.03.084 · Cited by 143 · cited 3×
“Cayce [65] Rat somatosensory cortex 1875 140(2) 0.”
BackgroundMethodResultTransient and selective suppression of neural activity with infrared light
Duke, A. R., Jenkins, M. W., Lu, H., McManus, J. M., Chiel, H. J., & Jansen, D. (2013) · Scientific Reports · doi:10.1038/srep02600 · Cited by 142 · cited 2×
“Hybrid electrical-optical stimulation has been used to show inhibition of electrical responses in vivo [72, 119] and spontaneous neural activity in vitro [100].”
MethodInfrared neural stimulation of primary visual cortex in non-human primates
Cayce, J. M., Friedman, R. M., Chen, G., Jansen, D., Mahadevan-Jansen, A. M., & Roe, A. W. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.08.040 · Cited by 142 · cited 2×
“Due to the improved spatial localisation of INS, it has attracted interest as a technique to stimulate the central nervous system [65, 79, 80, 81].”
ResultPhotovoltaic retinal prosthesis: implant fabrication and performance
Wang, L., Mathieson, K., Kamins, T. I., Loudin, J., Galambos, L., Goetz, G. A., Sher, A., Mandel, Y., Huie, P., Lavinsky, D., et al. (2012) · Journal of Neural Engineering · doi:10.1088/1741-2560/9/4/046014 · Cited by 142 · cited 1×
“Photoconductive silicon has been demonstrated as a substrate that can generate electric charge to stimulate neurons under exposure to light [128, 134].”
BackgroundRearrangements of Synaptic Connections in Visual Cortex Revealed by Laser Photostimulation
Dalva, M. B., & Katz, L. C. (1994) · Science · doi:10.1126/science.7912852 · Cited by 136 · cited 2×
“Caged molecules have emerged as a key technique for determining functional connectivity of neurons [44, 51].”
MethodMicro-LED arrays: a tool for two-dimensional neuron stimulation
Poher, V., Grossman, N., Kennedy, G., Nikolic, K., Zhang, H.-X., Gong, Z., Drakakis, E., Gu, E., Dawson, M. D., French, P., et al. (2008) · Journal of Physics D Applied Physics · doi:10.1088/0022-3727/41/9/094014 · Cited by 132 · cited 2×
“Another approach to deliver light to neurons is by developing microscale emitters and positioning or implanting them in close proximity to the target neurons [157-159].”
BackgroundMethodOPTICAL IMAGING AND CONTROL OF GENETICALLY DESIGNATED NEURONS IN FUNCTIONING CIRCUITS
Miesenböck, G., & Kevrekidis, I. G. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.051804.101610 · Cited by 131 · cited 2×
“In addition to control of neurons, techniques are emerging to read neural activity with light [50].”
MethodPerformance of conducting polymer electrodes for stimulating neuroprosthetics
Green, R. A., Matteucci, P. B., Hassarati, R. T., Giraud, B., Dodds, C. W. D., Chen, S., Byrnes-Preston, P., Suaning, G. J., Poole-Warren, L. A., & Lovell, N. H. (2013) · Journal of Neural Engineering · doi:10.1088/1741-2560/10/1/016009 · Cited by 127 · cited 1×
“Conductive polymers may overcome many of these limitations as an optoelectronic material [129, 130, 136, 137, 138, 139], although challenges in ensuring biocompatibility and stability of these polymers also remain to be resolved [125, 129].”
BackgroundA Polymer Optoelectronic Interface Provides Visual Cues to a Blind Retina
Gautam, V., Rand, D., Hanein, Y., & Narayan, K. S. (2013) · Advanced Materials · doi:10.1002/adma.201304368 · Cited by 127 · cited 1×
“Conductive polymers may overcome many of these limitations as an optoelectronic material [129, 130, 136, 137, 138, 139], although challenges in ensuring biocompatibility and stability of these polymers also remain to be resolved [125, 129].”
BackgroundOptical stimulation of auditory neurons: Effects of acute and chronic deafening
Richter, C., Bayon, R., Izzo, A. D., Otting, M., Suh, E., Goyal, S., Hotaling, J. M., & Walsh, J. T. (2008) · Hearing Research · doi:10.1016/j.heares.2008.01.011 · Cited by 125 · cited 9×
“Richter [69] Gerbil cochlea 1844 – 1873 3(3) 0.”
BackgroundMethodResultInfluentialHolographic optogenetic stimulation of patterned neuronal activity for vision restoration
Reutsky, I., Golan, L., Farah, N., Schejter, A., Tsur, L., Brosh, I., & Shoham, S. (2013) · Nature Communications · doi:10.1038/ncomms2500 · Cited by 119 · cited 1×
“Holographic patterning of light onto neural tissue was demonstrated by [122, 151].”
BackgroundOptical Stimulation of the Facial Nerve: A New Monitoring Technique?
Teudt, I. U., Nevel, A. E., Izzo, A. D., Walsh, J. T., & Richter, C. (2007) · The Laryngoscope · doi:10.1097/mlg.0b013e318074ec00 · Cited by 119 · cited 1×
“Teudt [60] Gerbil facial nerve 2120 710 0.”
BackgroundOptogenetic investigation of neural circuits in vivo
Carter, M. E., & de Lecea, L. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.12.005 · Cited by 117 · cited 1×
“Optogenetics have been utilised to further our understanding of neural disorders [36], understand neural systems and encoding [37] and there is interest in using optogenetics to treat blindness and Parkinson’s disease [17, 38, 39].”
BackgroundPhotochemical tools for remote control of ion channels in excitable cells
Krämer, R., Chambers, J. J., & Trauner, D. H. (2005) · Nature Chemical Biology · doi:10.1038/nchembio750 · Cited by 117 · cited 1×
“These techniques include genetically modifying the target neurons to introduce photosensitive receptors in the neurons [10, 12], or the introduction of photoswitchable molecules that bind to specific ion channels and modify their behaviour when exposed to light [11, 13, 14].”
BackgroundPhotorelease of GABA with visible light using an inorganic caging group
Verde, E. R. (2008) · Frontiers in Neural Circuits · doi:10.3389/neuro.04.002.2008 · Cited by 115 · cited 2×
“Caged molecules are also able to inhibit neural activity, through the release of GABA [46, 44].”
BackgroundOptically mediated nerve stimulation: Identification of injury thresholds
Wells, J. D., Thomsen, S., Whitaker, P., Jansen, D., Kao, C., Konrad, P. E., & Mahadevan-Jansen, A. M. (2007) · Lasers in Surgery and Medicine · doi:10.1002/lsm.20522 · Cited by 109 · cited 3×
“Studies on the safety margins [58] found that that the threshold to stimulate tissue and corresponding 95% confidence ranges did not overlap with the radiant exposures found to cause damage, when stimulation was performed at rates between 2 – 8 Hz.”
BackgroundTwo-photon uncaging: New prospects in neuroscience and cellular biology
Warther, D., Gug, S., Specht, A., Bolze, F., Nicoud, J., Mourot, A., & Goeldner, M. P. (2010) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2010.04.084 · Cited by 107 · cited 5×
“Caged molecules are also able to inhibit neural activity, through the release of GABA [46, 44].”
BackgroundInfluentialSelectivity of neural stimulation in the auditory system: a comparison of optic and electric stimuli
Izzo, A. D., Suh, E., Pathria, J., Walsh, J. T., Whitlon, D. S., & Richter, C. (2007) · Journal of Biomedical Optics · doi:10.1117/1.2714296 · Cited by 105 · cited 1×
“Spatial selectivity has been investigated with a range of techniques, including: fluorescent staining with c-FOS to identify excited neurons [82]; inferior colliculus (ICC) recordings which identify the localisation of signals to different neural pathways [83]; micro-CT reconstructions of the cochlea [84] (as shown in…”
MethodOptical cochlear implants: Evaluation of surgical approach and laser parameters in cats
Rajguru, S. M., Matic, A. I., Robinson, A. M., Fishman, A. J., Moreno, L. E., Bradley, A., Vujanovic, I., Breen, J., Wells, J. D., Bendett, M., et al. (2010) · Hearing Research · doi:10.1016/j.heares.2010.06.021 · Cited by 103
Richter, C.-P., Rajguru, S. M., Matic, A. I., Moreno, E. L., Fishman, A. J., Robinson, A. M., Suh, E., & Walsh, J. T. (2011) · Journal of Neural Engineering · doi:10.1088/1741-2560/8/5/056006 · Cited by 99 · cited 3×
“Overall, these results showed similar localisation of neural activity for both INS and acoustic tone pips, although some results point to stimulation on the far side of the cochlea rather than neurons directly in front of the optical fibre [83].”
BackgroundMethodResultInfrared photostimulation of the crista ampullaris
Rajguru, S. M., Richter, C., Matic, A. I., Holstein, G. R., Highstein, S. M., Dittami, G. M., & Rabbitt, R. D. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2010.198333 · Cited by 96 · cited 1×
“[102], who investigated INS of adult oyster toadfish crista ampullaris.”
BackgroundA comprehensive concept of optogenetics
Dugué, G. P., Akemann, W., & Knöpfel, T. (2012) · Progress in brain research · doi:10.1016/b978-0-444-59426-6.00001-x · Cited by 94
Acoustic Events and “Optophonic” Cochlear Responses Induced by Pulsed Near-Infrared LASER
Teudt, I. U., Maier, H., Richter, C., & Kral, A. (2011) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2011.2108297 · Cited by 88 · cited 1×
“As the rapid heating caused by INS laser pulses can generate an acoustic click [88], any results of INS in the cochlea require controls with deafened animals.”
BackgroundLugo, K., Miao, X., Rieke, F. M., & Lin, L. Y. (2012) · Biomedical Optics Express · doi:10.1364/boe.3.000447 · Cited by 83 · cited 1×
“A range of photoactive materials are being developed with the aim of neural stimulation, including quantum dots [126, 127], photoconductive silicon [128], organic polymers [129, 130], and carbon nanotubes [125, 131].”
BackgroundExciting Cell Membranes with a Blustering Heat Shock
Liu, Q., Frerck, M., Holman, H. A., Jørgensen, E. M., & Rabbitt, R. D. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2014.03.008 · Cited by 81 · cited 2×
“However, the authors argue that the magnitude of the voltage change due to capacitance is unlikely to act as an excitatory stimulus, except for the most voltage sensitive cells [115].”
BackgroundLaser exposure of gold nanorods can induce intracellular calcium transients
Paviolo, C., Haycock, J. W., Cadusch, P. J., McArthur, S. L., & Stoddart, P. R. (2013) · Journal of Biophotonics · doi:10.1002/jbio.201300043 · Cited by 77 · cited 2×
“Initial work on cells cultured with gold nanorods demonstrated intracellular + 2 Ca transients in response to laser light at the plasmon resonance wavelength of the gold nanorods [124], similar to cells exposed to INS [114].”
BackgroundCombined optical and electrical stimulation of neural tissue in vivo
Duke, A. R., Cayce, J. M., Malphrus, J. D., Konrad, P., Mahadevan-Jansen, A., & Jansen, E. D. (2009) · Journal of Biomedical Optics · doi:10.1117/1.3257230 · Cited by 76 · cited 3×
“[70] proposed using sub-threshold electrical depolarisation to reduce the optical energy required for stimulation.”
BackgroundMethodInfluentialNovel interfaces for light directed neuronal stimulation: advances and challenges
Bareket, L., & Hanein, Y. (2014) · International Journal of Nanomedicine · doi:10.2147/ijn.s51193 · Cited by 74 · cited 4×
“Current limitations include the challenges with biocompatibility [133] of these molecules and improving efficiency to reduce the optical power required [125].”
BackgroundMethodInfluentialProsthetic systems for therapeutic optical activation and silencing of genetically targeted neurons
Bernstein, J. G., Han, X., Henninger, M. A., Ko, E. Y., Qian, X., Franzesi, G. T., McConnell, J. P., Stern, P., Desimone, R., & Boyden, E. S. (2008) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.768798 · Cited by 74 · cited 1×
“Monte Carlo models have also been applied to understand light distributions in tissue during optogenetic stimulation [9, 33, 161].”
BackgroundNanosecond laser pulse stimulation of the inner ear—a wavelength study
Schultz, M., Baumhoff, P., Maier, H., Teudt, I. U., Krüger, A., Lenarz, T., & Kral, A. (2012) · Biomedical Optics Express · doi:10.1364/boe.3.003332 · Cited by 71 · cited 1×
“[94] showed that a range of wavelengths, from 400 nm to 2000 nm, can stimulate the cochlea with a nanosecond laser.”
BackgroundSpatial and temporal variability in response to hybrid electro-optical stimulation
Duke, A. R., Lu, H., Jenkins, M. W., Chiel, H. J., & Jansen, D. (2012) · Journal of Neural Engineering · doi:10.1088/1741-2560/9/3/036003 · Cited by 71 · cited 2×
“Duke [71] Aplysia buccal nerve 1875 8930 2 – 3 100”
BackgroundFried, N. M., Lagoda, G. A., Scott, N. J., Su, L.-M., & Burnett, A. L. “. (2008) · Journal of Endourology · doi:10.1089/end.2008.9996 · Cited by 71 · cited 3×
“[61] to establish the potential of INS for nerve mapping during nerve-sparing radical prostatectomy.”
BackgroundResultInfluentialDevelopment of bioactive conducting polymers for neural interfaces
Poole-Warren, L. A., Lovell, N. H., Baek, S., & Green, R. A. (2009) · Expert Review of Medical Devices · doi:10.1586/erd.09.58 · Cited by 71 · cited 1×
“However, silicon is limited by its rigidity and biocompatibility, thus potentially limiting its use as a prosthetic platform [135].”
BackgroundModeling of light absorption in tissue during infrared neural stimulation
Thompson, A., Wade, S. A., & Stoddart, P. R. (2012) · Journal of Biomedical Optics · doi:10.1117/1.jbo.17.7.075002 · Cited by 69 · cited 5×
“Recently, both analytical and numerical models have been developed to assist in understanding the flow of heat during INS, in the cochlea and in vitro models [55, 74, 101, 86, 100].”
BackgroundMethodInfluentialGautam, V., Bag, M., & Narayan, K. S. (2011) · Journal of the American Chemical Society · doi:10.1021/ja207853e · Cited by 63 · cited 1×
“Conductive polymers may overcome many of these limitations as an optoelectronic material [129, 130, 136, 137, 138, 139], although challenges in ensuring biocompatibility and stability of these polymers also remain to be resolved [125, 129].”
BackgroundHistological Assessment of Thermal Damage in the Brain Following Infrared Neural Stimulation
Chernov, M. M., Chen, G., & Roe, A. W. (2014) · Brain stimulation · doi:10.1016/j.brs.2014.01.006 · Cited by 62 · cited 1×
“Damage from higher stimulation rates of 200 Hz have been studied in rodents and squirrel monkeys [96].”
BackgroundChallenges in quantum dot-neuron active interfacing
Gomez, N. V., Winter, J. O., Shieh, F., Saunders, A. E., Korgel, B. A., & Schmidt, C. E. (2005) · Talanta · doi:10.1016/j.talanta.2005.06.041 · Cited by 62 · cited 1×
“Current limitations include the challenges with biocompatibility [133] of these molecules and improving efficiency to reduce the optical power required [125].”
BackgroundCalcium imaging of infrared-stimulated activity in rodent brain
Cayce, J. M., Bouchard, M. B., Chernov, M. M., Chen, B. R., Grosberg, L. E., Jansen, D., Hillman, E. M. C., & Mahadevan-Jansen, A. M. (2014) · Cell Calcium · doi:10.1016/j.ceca.2014.01.004 · Cited by 59 · cited 1×
“Due to the improved spatial localisation of INS, it has attracted interest as a technique to stimulate the central nervous system [65, 79, 80, 81].”
MethodOptical pacing of the adult rabbit heart
Jenkins, M. W., Wang, Y. T., Doughman, Y. Q., Watanabe, M., Cheng, Y., & Rollins, A. M. (2013) · Biomedical Optics Express · doi:10.1364/boe.4.001626 · Cited by 59 · cited 3×
“Optical pacing of the heart was further explored in [64].”
BackgroundGoyal, V. K., Rajguru, S. M., Matic, A. I., Stock, S. R., & Richter, C. (2012) · The Anatomical Record · doi:10.1002/ar.22583 · Cited by 58 · cited 2×
“To date, a number of studies focusing on the safety in both acute and chronic usage of INS in the cochlea have been performed [66, 67, 97, 98, 90].”
BackgroundMatic, A. I., Robinson, A. M., Young, H. K., Badofsky, B., Rajguru, S. M., Stock, S. R., & Richter, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058189 · Cited by 57 · cited 5×
“[90], where an optical fibre was implanted in the cochlea of cats with miniaturised laser system mounted in a backpack.”
BackgroundInfluentialNanosecond pulsed electric field thresholds for nanopore formation in neural cells
Roth, C. C., Tolstykh, G. P., Payne, J. A., Kuipers, M. A., Thompson, G. L., DeSilva, M., & Ibey, B. L. (2013) · Journal of Biomedical Optics · doi:10.1117/1.jbo.18.3.035005 · Cited by 57 · cited 1×
“[117] found that cells exposed to nanosecond pulsed electric fields created nanopores in the cellular membrane, leading to an influx of + 2 Ca .”
BackgroundAuditory responses to electric and infrared neural stimulation of the rat cochlear nucleus
Verma, R. U., Guex, A., Hancock, K. E., Durakovic, N., McKay, C. M., Slama, M. C. C., Brown, M. C., & Lee, D. J. (2014) · Hearing Research · doi:10.1016/j.heares.2014.01.008 · Cited by 56 · cited 1×
“A follow up study found that after cutting the auditory nerve to deafen the animal, no response could be found from INS [92].”
BackgroundHeating during infrared neural stimulation
Liljemalm, R., Nyberg, T., & von Holst, H. (2013) · Lasers in Surgery and Medicine · doi:10.1002/lsm.22158 · Cited by 54 · cited 5×
“Recently, both analytical and numerical models have been developed to assist in understanding the flow of heat during INS, in the cochlea and in vitro models [55, 74, 101, 86, 100].”
BackgroundMethodInfluentialModeling of the temporal effects of heating during infrared neural stimulation
Thompson, A., Wade, S. A., Cadusch, P. J., Brown, W. G. A., & Stoddart, P. R. (2013) · Journal of Biomedical Optics · doi:10.1117/1.jbo.18.3.035004 · Cited by 54 · cited 6×
“Moreover, the long pulses (> 100 ms) used by the 1450 nm and 1540 nm sources are near the thermal diffusion time for the areas irradiated [74].”
BackgroundMethodInfluentialMotor neuron activation in peripheral nerves using infrared neural stimulation
Peterson, E. J., & Tyler, D. J. (2013) · Journal of Neural Engineering · doi:10.1088/1741-2560/11/1/016001 · Cited by 54 · cited 3×
“Hybrid electrical-optical stimulation has been used to show inhibition of electrical responses in vivo [72, 119] and spontaneous neural activity in vitro [100].”
BackgroundMethodHolographically patterned activation using photo-absorber induced neural–thermal stimulation
Farah, N., Zoubi, A., Matar, S., Golan, L., Marom, A., Butson, C. R., Brosh, I., & Shoham, S. (2013) · Journal of Neural Engineering · doi:10.1088/1741-2560/10/5/056004 · Cited by 54 · cited 3×
“Holographic patterning of light onto neural tissue was demonstrated by [122, 151].”
BackgroundInfrared neural stimulation: Beam path in the guinea pig cochlea
Moreno, L. E., Rajguru, S. M., Matic, A. I., Yerram, N. K., Robinson, A. M., Hwang, M., Stock, S. R., & Richter, C. (2011) · Hearing Research · doi:10.1016/j.heares.2011.06.006 · Cited by 53 · cited 2×
“reproduced from [84], with permission from Elsevier.”
MethodShimano, T., Fyk‐Kolodziej, B. E., Mirza, N., Asako, M., Tomoda, K., Bledsoe, S. C., Pan, Z., Molitor, S. C., & Holt, A. G. (2012) · Brain Research · doi:10.1016/j.brainres.2012.10.030 · Cited by 52 · cited 1×
“As there is interest in applying optogenetic techniques to neuroprothestic implants such as the cochlear implant [28-31], higher stimulation rates may be needed to match the electrical stimulation rates that are commonly used.”
BackgroundNovel wavelengths for laser nerve stimulation
McCaughey, R. G., Chlebicki, C. A., & Wong, B. J. F. (2009) · Lasers in Surgery and Medicine · doi:10.1002/lsm.20856 · Cited by 52 · cited 1×
“[73].”
Infrared Neural Stimulation: Influence of Stimulation Site Spacing and Repetition Rates on Heating
Thompson, A., Wade, S. A., Pawsey, N. C., & Stoddart, P. R. (2013) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2013.2272796 · Cited by 51 · cited 4×
“with a finite element model of heating, such as [101, 74, 100], may allow for predictions of damage with different pulse durations and stimulation frequencies.”
BackgroundInfluentialInfrared Neural Stimulation of Thalamocortical Brain Slices
Cayce, J. M., Kao, C., Malphrus, J. D., Konrad, P. E., Mahadevan-Jansen, A. M., & Jansen, D. (2009) · IEEE Journal of Selected Topics in Quantum Electronics · doi:10.1109/jstqe.2009.2032424 · Cited by 51 · cited 2×
“Due to the improved spatial localisation of INS, it has attracted interest as a technique to stimulate the central nervous system [65, 79, 80, 81].”
BackgroundCharacterization of a 3D optrode array for infrared neural stimulation
Abaya, T. V. F., Diwekar, M., Blair, S., Tathireddy, P., Rieth, L. W., Clark, G. A., & Solzbacher, F. (2012) · Biomedical Optics Express · doi:10.1364/boe.3.002200 · Cited by 48 · cited 1×
“[154] developed a Utah slanted optrode array (USOA), similar to the Utah slanted electrode array, which has allowed for more specific electrical stimulation of neurons in nerve trunks than was achievable with traditional electrodes [155].”
BackgroundDuke, A. R., Peterson, E., Mackanos, M. A., Atkinson, J., Tyler, D., & Jansen, E. D. (2012) · Journal of Neural Engineering · doi:10.1088/1741-2560/9/6/066006 · Cited by 45 · cited 2×
“A variety of standard silica core fibres have been used with a range of diameters, including for example, 600 μm [54, 57], 400 μm [56, 77], 200 μm [69] and”
BackgroundSpatial extent of cochlear infrared neural stimulation determined by tone-on-light masking
Matic, A. I., Richter, C., & Walsh, J. T. (2011) · Journal of Biomedical Optics · doi:10.1117/1.3655590 · Cited by 43 · cited 1×
“1) and acoustic tone masking [85].”
Green laser light activates the inner ear
Wenzel, G. I., Balster, S., Zhang, K., Lim, H. H., Reich, U., Massow, O., Lubatschowski, H., Ertmer, W. A., Lenarz, T., & Reuter, G. (2009) · Journal of Biomedical Optics · doi:10.1117/1.3174389 · Cited by 42 · cited 1×
“[93].”
Optical control of neuronal excitation and inhibition using a single opsin protein, ChR2
Liske, H., Qian, X., Anikeeva, P., Deisseroth, K., & Delp, S. (2013) · Scientific Reports · doi:10.1038/srep03110 · Cited by 42 · cited 1×
“Hirase et al. [6] demonstrated that neurons could be triggered through exposure to pulses of light from a femtosecond laser via a two-photon mechanism.”
BackgroundDavis, F. A., Schauf, C. L., Reed, B. J., & Kesler, R. L. (1976) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.39.5.442 · Cited by 40
Normann, R. A., Dowden, B. R., Frankel, M. A., Wilder, A. M., Hiatt, S. D., Ledbetter, N. M., Warren, D. A., & Clark, G. A. (2012) · Journal of Neural Engineering · doi:10.1088/1741-2560/9/2/026019 · Cited by 37
Excitation of primary afferent neurons by near-infrared light in vitro
Katz, E. J., Ilev, I. K., Krauthamer, V., Kim, D. H., & Weinreich, D. M. (2010) · Neuroreport · doi:10.1097/wnr.0b013e32833add3a · Cited by 37 · cited 1×
“[54] that heatsensitive ion channels may be a mechanism behind INS, the heat-sensitive vanilloid subfamily of TRP channels (TRPV) [103, 104] have been the subject of some research in the literature [105-107].”
BackgroundOptogenetics: Tools for Controlling and Monitoring Neuronal Activity
(2012) · Progress in brain research · doi:10.1016/c2011-0-05056-1 · Cited by 35
Photostimulation of sensory neurons of the rat vagus nerve
Rhee, A. Y., Li, G., Wells, J. D., & Kao, J. P. Y. (2008) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.772037 · Cited by 35 · cited 1×
“[112] exposed dissociated neurons from the vagus nerve of rats to laser stimulation and measured the change in intracellular Ca concentrations.”
BackgroundAntkowiak, M. K., Torres‐Mapa, M. L., Witts, E. C., Miles, G. B., Dholakia, K., & Gunn‐Moore, F. J. (2013) · Scientific Reports · doi:10.1038/srep03281 · Cited by 34 · cited 1×
“Genes to express opsins are typically delivered with viral transfection [12], but electroporation transfection [26] and optical transfection [27] have also been demonstrated as a feasible techniques.”
MethodHe‐Ne laser irradiation of single identified neurons
Balaban, P. M., Esenaliev, R. O., Кару, Т. Й., Kutomkina, E., Letokhov, V. S., Oraevsky, A. A., & Ovcharenko, N. (1992) · Lasers in Surgery and Medicine · doi:10.1002/lsm.1900120315 · Cited by 34 · cited 1×
“[8] found that He-Ne laser irradiation ( 632.”
BackgroundPulsed 808-nm infrared laser stimulation of the auditory nerve in guinea pig cochlea
Xia, N., Wu, X. Y., Wang, X., Mou, Z. X., Wang, M. Q., Gu, X., Zheng, X. L., & Hou, W. (2013) · Lasers in Medical Science · doi:10.1007/s10103-013-1348-8 · Cited by 34 · cited 1×
“range of laser parameters have been used for INS in the cochlea and a number of studies have been performed on the effect of varying the pulse length [67-69, 74, 86] and wavelength [55, 67, 68, 74, 87] used to stimulate the neurons.”
MethodFried, N. M., Lagoda, G. A., Scott, N. J., Su, L., & Burnett, A. L. “. (2008) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/iembs.2008.4649778 · Cited by 31 · cited 2×
“Fried [62] Rat cavernous nerve 1850 – 1880 350 2.”
MethodOptical stimulation in mice lacking the TRPV1 channel
Suh, E., Matic, A. I., Otting, M., Walsh, J. T., & Richter, C. (2009) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.816891 · Cited by 30 · cited 1×
“[54] that heatsensitive ion channels may be a mechanism behind INS, the heat-sensitive vanilloid subfamily of TRP channels (TRPV) [103, 104] have been the subject of some research in the literature [105-107].”
BackgroundSuzurikawa, J., Takahashi, H., Kanzaki, R., Nakao, M., Takayama, Y., & Jimbo, Y. (2007) · Applied Physics Letters · doi:10.1063/1.2709627 · Cited by 29 · cited 2×
“Photoconductive silicon has been demonstrated as a substrate that can generate electric charge to stimulate neurons under exposure to light [128, 134].”
BackgroundBalster, S., Wenzel, G. I., Warnecke, A., Steffens, M., Rettenmaier, A., Zhang, K., Lenarz, T., & Reuter, G. (2013) · Biomedizinische Technik/Biomedical Engineering · doi:10.1515/bmt-2013-0038 · Cited by 28 · cited 1×
“To enable an optically based implant to stimulate the cochlea, work has been performed to develop a waveguidebased optical delivery system [147].”
MethodNanosecond laser pulse stimulation of spiral ganglion neurons and model cells
Rettenmaier, A., Lenarz, T., & Reuter, G. (2014) · Biomedical Optics Express · doi:10.1364/boe.5.001014 · Cited by 25 · cited 1×
“When the cochlea was deafened with neomycin no response to the laser was observed and no strong response has been observed in spiral ganglion neurons in vitro [95].”
Liljemalm, R., & Nyberg, T. (2013) · Annals of Biomedical Engineering · doi:10.1007/s10439-013-0940-1 · Cited by 23 · cited 1×
“An Arrhenius model for describing the kinetics of cellular damage from INS due to heat shocks to neurons and neuroglia was developed [99].”
MethodOptical stimulation enables paced electrophysiological studies in embryonic hearts
Wang, Y. T., Gu, S., Ma, P., Watanabe, M., Rollins, A. M., & Jenkins, M. W. (2014) · Biomedical Optics Express · doi:10.1364/boe.5.001000 · Cited by 22 · cited 1×
“The heart is another target of INS that has seen interest [63, 64, 76].”
BackgroundDeep-tissue light delivery via optrode arrays
Abaya, T. V. F., Diwekar, M., Blair, S., Tathireddy, P., Rieth, L. W., & Solzbacher, F. (2014) · Journal of Biomedical Optics · doi:10.1117/1.jbo.19.1.015006 · Cited by 22 · cited 2×
“SEM image of (a) silicon Utah slant optrode array and (b) glass optrode array reproduced from [153], with permission from SPIE.”
BackgroundMethodOptical Stimulation of Zebrafish Hair Cells Expressing Channelrhodopsin-2
Monesson-Olson, B. D., Sugai, J. A., Aziz‐Bose, R., Kreines, F. M., & Trapani, J. G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096641 · Cited by 19 · cited 1×
“Optogenetics have been utilised to further our understanding of neural disorders [36], understand neural systems and encoding [37] and there is interest in using optogenetics to treat blindness and Parkinson’s disease [17, 38, 39].”
BackgroundNorton, B. J., Bowler, M. A., Wells, J. D., & Keller, M. D. (2013) · Journal of Biomedical Optics · doi:10.1117/1.jbo.18.9.098001 · Cited by 18
Temperature-controlled optical stimulation of the rat prostate cavernous nerves
Tozburun, S., Hutchens, T. C., McClain, M. A., Lagoda, G. A., Burnett, A. L. “., & Fried, N. M. (2013) · Journal of Biomedical Optics · doi:10.1117/1.jbo.18.6.067001 · Cited by 18 · cited 2×
“This probe was adapted [146] to provide temperature monitoring and feedback with the continuous wave stimulation technique [75].”
MethodA Compact Laparoscopic Probe for Optical Stimulation of the Prostate Nerves
Tozburun, S., Mayeh, M., Lagoda, G. A., Farahi, F., Burnett, A. L. “., & Fried, N. M. (2010) · IEEE Journal of Selected Topics in Quantum Electronics · doi:10.1109/jstqe.2009.2035432 · Cited by 17 · cited 1×
“A laparoscopic probe designed to deliver a collimated top hat beam profile to allow uniform illumination of the cavernous nerves was developed in [145].”
MethodTozburun, S., Stahl, C. S. D., Hutchens, T. C., Lagoda, G. A., Burnett, A. L. “., & Fried, N. M. (2013) · Urology · doi:10.1016/j.urology.2013.06.031 · Cited by 16 · cited 2×
“This probe was adapted [146] to provide temperature monitoring and feedback with the continuous wave stimulation technique [75].”
BackgroundMethodOrigins of Spectral Changes in Fiber Bragg Gratings Due to Macrobending
Thompson, A., Cadusch, P. J., Robertson, D., Stoddart, P. R., & Wade, S. A. (2012) · Journal of Lightwave Technology · doi:10.1109/jlt.2012.2222016 · Cited by 15 · cited 1×
“Regardless of the application, there are fundamental limitations of using fibre optics in terms of mechanical stiffness and the ability to sustain sharp bends [148], in particular when compared to coiled wire electrodes.”
BackgroundActivation using infrared light in a mammalian axon model
Peterson, E. J., & Tyler, D. J. (2012) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc.2012.6346323 · Cited by 11 · cited 1×
“[116] applied the changes in membrane capacitance observed by Shapiro et al.”
MethodTemporal Modulation of Sodium Current Kinetics in Neuron Cells by Near-Infrared Laser
Li, X., Liu, J., Liang, S., Guan, K., An, L., Wu, X., Shao, L., & Sun, C. (2013) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-013-9674-9 · Cited by 10 · cited 1×
“Recently, heating of hippocampal neurons with 808 nm light has been shown to accelerate Na current kinetics [113].”
BackgroundLaser stimulation of the auditory system at 1.94 μm and microsecond pulse durations
Izzo, A. D., Walsh, J. T., Ralph, H., Webb, J., Wells, J. D., Bendett, M., & Richter, C. (2008) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.761315 · Cited by 8
Masking of infrared neural stimulation (INS) in hearing and deaf guinea pigs
Kadakia, S., Young, H. K., & Richter, C. (2013) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.2013848 · Cited by 6 · cited 4×
“Results have shown that the laser interaction with the target neurons is not primarily acoustic [89].”
BackgroundInfluentialOptical stimulation of excised murine sciatic nerve using 1.8-μm wavelength laser
Cargill, R. S., Baumann, T., & Jacques, S. L. (2008) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.776992 · Cited by 6
Suzurikawa, J., Takahashi, H., Takayama, Y., Warisawa, S., Mitsuishi, M., Nakao, M., & Jimbo, Y. (2006) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society · doi:10.1109/iembs.2006.259828 · Cited by 5
Material considerations for optical interfacing to the nervous system
Chernov, M. M., Duke, A. R., Cayce, J. M., Crowder, S. W., Sung, H., & Jansen, D. (2012) · MRS Bulletin · doi:10.1557/mrs.2012.121 · Cited by 5 · cited 1×
“While fibres have been able to deliver light to a localised area and are able to display a significant improvement over electrical stimulation for some applications [83], there is interest in alternative delivery techniques that are able to deliver light closer to the nerves or to multiple nerves from a single implant…”
BackgroundLaser source development for infrared neural stimulation
Keller, M. D., Stafford, J. W., Stafford, R. C., Norton, B. J., Wells, J. D., Bendett, M., Dummer, M. M., & Hibbs-Brenner, M. K. (2013) · Saudi International Electronics, Communications and Photonics Conference · doi:10.1109/siecpc.2013.6550979 · Cited by 4 · cited 2×
“This fabrication approach has been taken up by other researchers, including fabrication of 15 LED arrays suitable for implantation in a ChR2 sensitive cochlea [158] and vertical cavity surface emitting lasers to provide high intensity infrared light for INS [159].”
BackgroundMethodInvestigation of infrared neural stimulation in the cochlea
Thompson, A. C. (2014) · Swinburne figshare (Swinburne University of Technology) · doi:10.25916/sut.26269414 · Cited by 4
3D waveguide penetrating arrays for optical neural stimulation
Abaya, T. V. F., Diwekar, M., Blair, S., Tathireddy, P., Rieth, L. W., & Solzbacher, F. (2012) · International Conference on Optical MEMS and Nanophotonics · doi:10.1109/omems.2012.6318880 · Cited by 3 · cited 1×
“The Utah slanted optrode array was improved upon in [156], which reported a 3D silica optrode array with non-tapering tips.”
Method
Research works printed but not linked: 1
- [142]Vo-Dinh T Biomedical photonics 2003 handbook CRC Press
Cited by
Sorted by citations
Next-generation probes, particles, and proteins for neural interfacing
Rivnay, J., Wang, H., Fenno, L., Deisseroth, K., & Malliaras, G. G. (2017) · Science Advances · doi:10.1126/sciadv.1601649 · Cited by 514
“For example, short-pulse IR light has been demonstrated for photothermal stimulation as a result of thermally sensitive ion channels or due to a change in cell capacitance (159).”
BackgroundBiological effects and medical applications of infrared radiation
Tsai, S.-R., & Hamblin, M. R. (2017) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2017.04.014 · Cited by 497
Optically Stimulated Artificial Synapse Based on Layered Black Phosphorus
Ahmed, T., Kuriakose, S., Mayes, E. L. H., Ramanathan, R., Bansal, V., Bhaskaran, M. C., Sriram, S., & Walia, S. (2019) · Small · doi:10.1002/smll.201900966 · Cited by 335
Multifunctional Optoelectronics via Harnessing Defects in Layered Black Phosphorus
Ahmed, T., Kuriakose, S., Tawfik, S. A., Spencer, M. J. S., Rahman, M. A., Tahir, M., Lu, Y., Sonar, P. M., Bansal, V., Bhaskaran, M. C., et al. (2019) · Advanced Functional Materials · doi:10.1002/adfm.201901991 · Cited by 161
Gold nanoparticles for regulation of cell function and behavior
Bodelón, G., Costas, C., Pérez‐Juste, J., Pastoriza‐Santos, I., & Liz‐Marzán, L. M. (2017) · Nano Today · doi:10.1016/j.nantod.2016.12.014 · Cited by 107
Metadata
- Authors
- C. Thompson, A., R. Stoddart, P., & Jansen, E. D.
- Venue
- Current Molecular Imaging
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2015-02-04
- Volume
- 3
- Issue
- 2
- Pages
- 162-177
- ISSN
- 2211-5544 (ISSN-L)
- 2211-5552
- PMC
- PMC4541079
- OpenAlex
- W1967609781
- Cited by
- 105
- References
- 161
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 7 · 2023: 12 · 2022: 4 · 2021: 12 · 2020: 11 · 2019: 18 · 2018: 10 · 2017: 12 · 2016: 7 · 2015: 1
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc
- Locations
- Current molecular imaging (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS052407)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- optical neural stimulation, optogenetics, photoactive molecules, infrared neural stimulation, neural interfaces, light delivery, implant-induced inflammation
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