Stimulus waveform design for decreasing charge and increasing stimulation selectivity in retinal prostheses

Abstract

Retinal degenerative diseases, such as retinitis pigmentosa, begin with damage to the photoreceptor layer of the retina. In the absence of presynaptic input from photoreceptors, networks of electrically coupled AII amacrine and cone bipolar cells have been observed to exhibit oscillatory behaviour and result in spontaneous firing of ganglion cells. This ganglion cell activity could interfere with external stimuli provided by retinal prosthetic devices and potentially degrade their performance. In this work, the authors computationally investigate stimulus waveform designs, which can improve the performance of retinal prostheses by suppressing undesired spontaneous firing of ganglion cells and generating precise temporal spiking patterns. They utilise a multi-scale computational model for electrical stimulation of degenerated retina based on the admittance method and NEURON simulation environments. They present a class of asymmetric biphasic pulses that can generate precise ganglion cell firing patterns with up to 55% lower current requirements compared to traditional symmetric biphasic pulses. This lower current results in activation of only proximal ganglion cells, provides more focused stimulation and lowers the risk of tissue damage.

Color and cellular selectivity of retinal ganglion cell subtypes through frequency modulation of electrical stimulation

“…Admittance method/NEURON computational framework. In this work, we utilized our threedimensional Admittance Method (AM)/NEURON multi-scale computational modeling platform 12,[61][62][63][64][65][66][67][68][69][70][71][72][73] to predict the electric fields generated inside retinal tissue, coupled to multi-compartmental models of neurons in order to determine the activation of realistic RGCs. The Admittance Method linked with NEURON has proven a powerful approach not only for studies of field distribution inside the tissue due to electrical stimulation, but also providing a platform to analyze realistic representations of various cell types 12,61-73 . Admittance method: constructing the retina tissue and electrodes.…”

“…However, slower rate of increase in Figure 1. A2 and D1 realistic morphologies as implemented and coded in our multiscale Admittance Method/ NEURON computational platform [61][62][63][64][65][66][67][68][69][70][71][72][73] . Left: A2-monostratified RGC ramified in the inner part of inner plexiform layer and has a larger soma and dendritic field diameters.…”

“…The voltage at the center of each voxel was estimated using a linear interpolation function. Since the Admittance Method and NEURON use the same coordinates, a computational code was developed to superimpose the potential computed in the tissue volume into the NEURON model and apply it as an extracellular voltage, using the "extracellular" mechanism built into NEURON software, to each compartment in the Hodgkin-Huxley circuit in series with the membrane 12,[61][62][63][64][65][66][67][68][69][70][71] .…”

Selective Activation of Retinal Ganglion Cell Subtypes Through Targeted Electrical Stimulation Parameters

“…Using our combined AM-NEURON multi-scale computational platform [39]- [47], we developed morphologically and biophysically realistic models of two classified RGCs, A2-monostratified and D1-bistratified [32]. This modeling framework has enabled us to have a more precise prediction of retinal neuron activities due to electrical stimulation [34], and particularly in this work the response of RGCs to epiretinal electrical stimulation of various stimulation parameters.…”

“…In this work, using our combined Admittance method (AM)/NEURON multiscale computational platform [ 17 ], [ 34 ], [ 39 ]–[ 47 ], we further characterized the impacts of pulse duration and interphase gap on the differential response of RGCs at 200 Hz. To better understand the sensitivity of RGCs to different stimulus parameters, we analyzed the firing rates of cells as a function of modulations in current amplitude.…”