Penetrating electrode stimulation of the rabbit optic nerve: parameters and effects on evoked cortical potentials

  • Jingjing Sun
  • Yao Chen
  • Xinyu Chai
  • Qiushi RenEmail author
  • Liming LiEmail author
Basic Science



Stimulus parameters, in particular pulse shape, are an important consideration in the application of electrical stimulation when experimentally testing a visual prosthesis. We changed the biphasic pulse shape of several asymmetric charge-balanced pulses to investigate their effect on optic nerve (ON) stimulation and the recorded cortical response.


Monopolar platinum–iridium electrodes were implanted into the rabbit’s ON behind the eyeball. Electrical evoked potentials (EEPs) were recorded with silver ball electrodes placed on the cortex, and the results quantified.


Our results indicate that changing the shape of cathodic-first charge-balanced biphasic pulse (CA) while maintaining charge balance could reduce the current thresholds for stimulation. When stimulated at the same charge density, the stimulus having high-amplitude short-duration (HASD) cathodic phase produced a higher amplitude response, with a larger spatial spread but with a lower current threshold compared with other stimuli. Adding an inter-phase gap between the two phases of the stimulus increased the EEP amplitude, but was saturated at a gap of ∼0.2 ms; this was most obvious with CA stimulation, which was able to elicit a larger cortical response than that elicited by asymmetrical charge-balanced stimulus pulses with HASD cathodic phase, in contrast to CA without a gap. As the stimulating frequency increased, the amplitudes of the EEP components elicited by CA monotonically decreased. The fastest component (P0) was present with stimulating frequencies as high as 80 Hz, while the slower P1 and P2 disappeared with stimulating frequencies higher than 40 and 20 Hz, respectively.


A CA stimulus waveform with an inter-phase gap of 0.2 ms was more efficacious for ON stimulation than other stimulus combinations, and therefore should result in less tissue damage, minimal electrode etching, and lower power consumption if used in a visual prosthesis.


Electrical stimulation Monopolar Prosthesis Vision EEP Symmetrical/asymmetrical charge-balanced pulses Inter-phase gap 



This research is supported by The National Basic Research Program of China(973 Program, 2011CB707502/3); The National Natural Science Foundation of China (60971102, 31070981, 61171174, 91120304). The authors thank Dr. T. FitzGibbon for comments on earlier drafts of the manuscript.


  1. 1.
    Schmidt EM, Bak MJ, Hambrecht FT, Kufta CV, O'Rourke DK, Vallabhanath P (1996) Feasibility of a visual prosthesis for the blind based on intracortical micro stimulation of the visual cortex. Brain 119:507–522PubMedCrossRefGoogle Scholar
  2. 2.
    Humayun MS, Weiland JD, Fujii GY, Greenberg R, Williamson R, Little J, Mech B, Cimmarusti V, Van Boemel G, Dagnelie G (2003) Visual perception in a blind subject with a chronic microelectronic retinal prosthesis. Vision Res 43:2573–2581PubMedCrossRefGoogle Scholar
  3. 3.
    Rizzo JF 3rd, Wyatt J, Loewenstein J, Kelly S, Shire D (2003) Methods and perceptual thresholds for short-term electrical stimulation of human retina with microelectrode arrays. Invest Ophthalmol Vis Sci 44:5355–5361PubMedCrossRefGoogle Scholar
  4. 4.
    Kanda H, Morimoto T, Fujikado T, Tano Y, Fukuda Y, Sawai H (2004) Electrophysiological studies of the feasibility of suprachoroidal–transretinal stimulation for artificial vision in normal and RCS rats. Invest Ophthalmol Vis Sci 45:560–566PubMedCrossRefGoogle Scholar
  5. 5.
    Kim ET, Kim C, Lee SW, Seo JM, Chung H, Kim SJ (2009) Feasibility of microelectrode array (MEA) based on silicone–polyimide hybrid for retina prosthesis. Invest Ophthalmol Vis Sci 50:4337–4341PubMedCrossRefGoogle Scholar
  6. 6.
    Yamauchi Y, Franco LM, Jackson DJ, Naber JF, Ziv RO, Rizzo JF, Kaplan HJ, Enzmann V (2005) Comparison of electrically evoked cortical potential thresholds generated with subretinal or suprachoroidal placement of a microelectrode array in the rabbit. J Neural Eng 2:S48–S56PubMedCrossRefGoogle Scholar
  7. 7.
    Zrenner E, Bartz-Schmidt KU, Benav H, Besch D, Bruckmann A, Gabel VP, Gekeler F, Greppmaier U, Harscher A, Kibbel S (2011) Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc Biol Sci 278:1489–1497PubMedCrossRefGoogle Scholar
  8. 8.
    da Cruz L, Coley B, Christopher P, Merlini F, Wuyyuru V, Sahel JA, Stanga P, Filley E, Dagnelie G (2010) Patients blinded by outer retinal dystrophies are able to identify letters using the ArgusTM II retinal prosthesis system. Invest Ophthalmol Visual Sci 51: ARVO E-Abstract #2023Google Scholar
  9. 9.
    Brelén ME, De Potter P, Gersdorff M, Gersdorff M, Cosnard G, Veraart C, Delbeke J (2006) Intraorbital implantation of a stimulating electrode for an optic nerve visual prosthesis. J Neurosurg 104:593–597PubMedCrossRefGoogle Scholar
  10. 10.
    Veraart C, Raftopoulos C, Mortimer JT, Delbeke J, Pins D, Michaux G, Vanlierde A, Parrini S, Wanet-Defalque MC (1998) Visual sensations produced by optic nerve stimulation using an implanted self-sizing spiral cuff electrode. Brain Res 813:181–186PubMedCrossRefGoogle Scholar
  11. 11.
    Duret F, Brelén ME, Lambert V, Gérard B, Delbeke J, Veraart C (2006) Object localization, discrimination, and grasping with the optic nerve visual prosthesis. Restor Neurol Neurosci 24:31–40PubMedGoogle Scholar
  12. 12.
    Veraart C, Wanet-Defalque MC, Gérard B, Vanlierde A, Delbeke J (2003) Pattern recognition with the optic nerve visual prosthesis. Artif Organs 27:996–1004PubMedCrossRefGoogle Scholar
  13. 13.
    Li L, Cao P, Sun M, Chai X, Wu K, Xu X, Li X, Ren Q (2009) Intraorbital optic nerve stimulation with penetrating electrodes: in vivo electrophysiology study in rabbits. Graefes Arch Clin Exp Ophthalmol 247:349–361PubMedCrossRefGoogle Scholar
  14. 14.
    Sun J, Lu Y, Cao P, Li X, Cai C, Chai X, Ren Q, Li L (2010) Spatiotemporal properties of multipeaked electrically evoked potentials elicited by penetrative optic nerve stimulation in rabbits. Invest Ophthalmol Vis Sci 52:146–154CrossRefGoogle Scholar
  15. 15.
    Rosahl SK, Mark G, Herzog M, Pantazis C, Gharabaghi F, Matthies C, Brinker T, Samii M (2001) Far-field responses to stimulation of the cochlear nucleus by microsurgically placed penetrating and surface electrodes in the cat. J Neurosurg 95:845–852PubMedCrossRefGoogle Scholar
  16. 16.
    Brummer SB, Turner MJ (1977) Electrochemical considerations for safe electrical stimulation of the nervous system with platinum electrodes. IEEE Trans Biomed Eng 24:59–63PubMedCrossRefGoogle Scholar
  17. 17.
    Rowland V, MacIntyre WJ, Bidder TG (1960) The production of brain lesions with electric currents. II. Bidirectional currents. J Neurosurg 17:55–69PubMedCrossRefGoogle Scholar
  18. 18.
    Loucks RB, Weinberg H, Smith M (1959) The erosion of electrodes by small currents. Electroencephalogr Clin Neurophysiol 11:823–826PubMedCrossRefGoogle Scholar
  19. 19.
    Shepherd RK (1999) Chronic electrical stimulation of the auditory nerve using non-charge-balanced stimuli. Acta Otolaryngol 119:674–684PubMedCrossRefGoogle Scholar
  20. 20.
    Lilly JC, Hughes JR, Alvord EC Jr, Galkin TW (1955) Brief, noninjurious electric waveform for stimulation of the brain. Science 121:468–469PubMedCrossRefGoogle Scholar
  21. 21.
    Lilly JC, Cherry RB (1955) Surface movements of figures in spontaneous activity of anesthetized cerebral cortex: leading and trailing edges. J Neurophysiol 18:18–32PubMedGoogle Scholar
  22. 22.
    Lilly JC (1961) Injury and excitation by electric currents. In: Electrical stimulation of the brain. University of Texas Press, Austin, pp 60–66Google Scholar
  23. 23.
    Van Wieringen A, Macherey O, Carlyon RP, Deeks JM, Wouters J (2008) Alternative pulse shapes in electrical hearing. Hear Res 242:154–163PubMedCrossRefGoogle Scholar
  24. 24.
    Macherey O, Van Wieringen A, Carlyon RP, Deeks JM, Wouters J (2006) Asymmetric pulses in cochlear implants: Effects of pulse shape, polarity, and rate. J Assoc Res Otolaryngol 7:253–266PubMedCrossRefGoogle Scholar
  25. 25.
    Choudhury BP (1987) Visual cortex in the albino rabbit. Exp Brain Res 66:565–571PubMedCrossRefGoogle Scholar
  26. 26.
    Burke W, Cottee LJ, Garvey J, Kumarasinghe R, Kyriacou C (1986) Selective degeneration of optic nerve fibres in the cat produced by a pressure block. J Physiol 376:461–476PubMedGoogle Scholar
  27. 27.
    Burke W, Burne JA, Martin PR (1985) Selective block of Y optic nerve fibres in the cat and the occurrence of inhibition in the lateral geniculate nucleus. J Physiol 364:81–92PubMedGoogle Scholar
  28. 28.
    Rizzo JF 3rd, Goldbaum S, Shahin M, Denison TJ, Wyatt J (2004) In vivo electrical stimulation of rabbit retina with a microfabricated array: strategies to maximize responses for prospective assessment of stimulus efficacy and biocompatibility. Restor Neurol Neurosci 22:429–443PubMedGoogle Scholar
  29. 29.
    Miller CA, Abbas PJ, Robinson BK, Rubinstein JT, Matsuoka AJ (1999) Electrically evoked single-fiber action potentials from cat: responses to monopolar, monophasic stimulation. Hear Res 130:197–218PubMedCrossRefGoogle Scholar
  30. 30.
    Ranck JB (1975) Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res 98:417–440PubMedCrossRefGoogle Scholar
  31. 31.
    Miller CA, Robinson BK, Rubinstein JT, Abbas PJ, Runge-Samuelson CL (2001) Auditory nerve responses to monophasic and biphasic electric stimuli. Hear Res 151:79–94PubMedCrossRefGoogle Scholar
  32. 32.
    van den Honert C, Mortimer JT (1979) The response of the myelinated nerve fiber to short duration biphasic stimulating currents. Ann Biomed Eng 7:117–125PubMedCrossRefGoogle Scholar
  33. 33.
    Grill WM, Mortimer JT (1995) Stimulus waveforms for selective neural stimulation. IEEE Eng Med Biol Mag 14:375–385CrossRefGoogle Scholar
  34. 34.
    Van Wieringen A, Carlyon RP, Laneau J, Wouters J (2005) Effects of waveform shape on human sensitivity to electrical stimulation of the inner ear. Hear Res 200:73–86PubMedCrossRefGoogle Scholar
  35. 35.
    Grill WM, Mortimer JT (1996) The effect of stimulus pulse duration on selectivity of neural stimulation. IEEE Trans Biomed Eng 43:161–166PubMedCrossRefGoogle Scholar
  36. 36.
    Shepherd RK, Javel E (1999) Electrical stimulation of the auditory nerve: II. Effect of stimulus waveshape on single fibre response properties. Hear Res 130:171–188PubMedCrossRefGoogle Scholar
  37. 37.
    Prado-guitierrez P, Fewster LM, Heasman JM, Mckay CM, Shepherd RK (2006) Effect of interphase gap and pulse duration on electrically evoked potentials is correlated with auditory nerve survival. Hear Res 215:47–55PubMedCrossRefGoogle Scholar
  38. 38.
    Delbeke J, Oozeer M, Veraart C (2003) Position, size and luminosity of phosphenes generated by direct optic nerve stimulation. Vision Res 43:1091–1102PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Department of Biomedical Engineering, College of EngineeringPeking UniversityBeijingChina

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