A computational model of electrical stimulation of the retinal ganglion cell

Greenberg, Robert J.; Velte, Toby J.; Humayun, Mark S.; Scarlatis, George N.; Juan, Eugene de

doi:10.1109/10.759051

Cited by 175 publications

(134 citation statements)

References 27 publications

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“…Several experimental measurements of the strength-duration relationship have been reported (Jankowska and Roberts 1972;Jensen et al 2005;Sekirnjak et al 2006;Yoemans et al 1988) and some computations have been performed (Greenberg et al 1999;Richardson et al 2000). However, all such calculations and many of the measurements have focused on simple monophasic or biphasic stimuli not much shorter than chronaxy.…”

Section: Introductionmentioning

confidence: 99%

Strength–Duration Relationship for Extracellular Neural Stimulation: Numerical and Analytical Models

Boinagrov¹,

Loudin²,

Palanker

2010

Journal of Neurophysiology

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Boinagrov D, Loudin J, Palanker D. Strength-duration relationship for extracellular neural stimulation: numerical and analytical models. J Neurophysiol 104: 2236 -2248, 2010. First published August 11, 2010 doi:10.1152/jn.00343.2010. The strength-duration relationship for extracellular stimulation is often assumed to be similar to the classical intracellular stimulation model, with a slope asymptotically approaching 1/ at pulse durations shorter than chronaxy. We modeled extracellular neural stimulation numerically and analytically for several cell shapes and types of active membrane properties. The strength-duration relationship was found to differ significantly from classical intracellular models. At pulse durations between 4 s and 5 ms stimulation is dominated by sodium channels, with a slope of Ϫ0.72 in log-log coordinates for the Hodgkin-Huxley ion channel model. At shorter durations potassium channels dominate and slope decreases to Ϫ0.13. Therefore the charge per phase is decreasing with decreasing stimulus duration. With pulses shorter than cell polarization time (ϳ0.1-1 s), stimulation is dominated by polarization dynamics with a classical Ϫ1 slope and the charge per phase becomes constant. It is demonstrated that extracellular stimulation can have not only lower but also upper thresholds and may be impossible below certain pulse durations. In some regimes the extracellular current can hyperpolarize cells, suppressing rather than stimulating spiking behavior. Thresholds for burst stimuli can be either higher or lower than that of a single pulse, depending on pulse duration. The modeled thresholds were found to be comparable to published experimental data. Electroporation thresholds, which limit the range of safe stimulation, were found to exceed stimulation thresholds by about two orders of magnitude. These results provide a biophysical basis for understanding stimulation dynamics and guidance for optimizing the neural stimulation efficacy and safety.

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Section: Introductionmentioning

confidence: 99%

Strength–Duration Relationship for Extracellular Neural Stimulation: Numerical and Analytical Models

Boinagrov¹,

Loudin²,

Palanker

2010

Journal of Neurophysiology

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“…In all of these applications, the characteristics of the stimulation waveform (principally the amplitude, polarity, and pulse width) play an important role in the design of a particular prosthetic device, making it critical to understand the relationship between stimulation threshold and pulse duration. Electrical stimulation of the retinal ganglion cells (RGC), used in epiretinal prostheses, was extensively studied by several research groups (Fried et al 2006;Jensen et al 2003Jensen et al , 2005Sekirnjak et al 2006Sekirnjak et al , 2008Stett et al 2000Stett et al , 2007Tsai et al 2009), and the strengthduration relationship has been experimentally measured (Jensen et al 2003(Jensen et al , 2005Sekirnjak et al 2006;Tsai et al 2009) and modeled computationally (Boinagrov et al 2010;Greenberg et al 1999). The strength-duration relationship defines for a given pulse duration the minimum stimulus strength, or stimulation threshold, above which an action potential (AP) is generated.…”

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confidence: 99%

Upper threshold of extracellular neural stimulation

Boinagrov

Pangratz-Fuehrer

Suh

et al. 2012

Journal of Neurophysiology

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It is well known that spiking neurons can produce action potentials in response to extracellular stimulation above certain threshold. It is widely assumed that there is no upper limit to somatic stimulation, except for cellular or electrode damage. Here we demonstrate that there is an upper stimulation threshold, above which no action potential can be elicited, and it is below the threshold of cellular damage. Existence of this upper stimulation threshold was confirmed in retinal ganglion cells (RGCs) at pulse durations ranging from 5 to 500 μs. The ratio of the upper to lower stimulation thresholds varied typically from 1.7 to 7.6, depending on pulse duration. Computational modeling of extracellular RGC stimulation explained the upper limit by sodium current reversal on the depolarized side of the cell membrane. This was further confirmed by experiments in the medium with a low concentration of sodium. The limited width of the stimulation window may have important implications in design of the electro-neural interfaces, including neural prosthetics

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“…Choosing that pulse duration, the amount of current needed to generate the response of a cell is much lower than that required to generate an axonal response. Greenberg et al, supported these observations by reporting that axonal threshold was 20% higher than that of the retinal ganglion cell [80]. Experimental findings by Jepson [63] exhibited single spike responses with sub-millisecond latency which is a characteristic of direct ganglion cell activation.…”

Section: Limitationsmentioning

confidence: 89%